Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bajenova, Olga, E-mail: o.bazhenova@spbu.ru; Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034; Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178

2014-06-10

Oncomarkers play important roles in the detection and management of human malignancies. Carcinoembryonic antigen (CEA, CEACAM5) and epithelial cadherin (E-cadherin) are considered as independent tumor markers in monitoring metastatic colorectal cancer. They are both expressed by cancer cells and can be detected in the blood serum. We investigated the effect of CEA production by MIP101 colorectal carcinoma cell lines on E-cadherin adherens junction (AJ) protein complexes. No direct interaction between E-cadherin and CEA was detected; however, the functional relationships between E-cadherin and its AJ partners: α-, β- and p120 catenins were impaired. We discovered a novel interaction between CEA andmore » beta-catenin protein in the CEA producing cells. It is shown in the current study that CEA overexpression alters the splicing of p120 catenin and triggers the release of soluble E-cadherin. The influence of CEA production by colorectal cancer cells on the function of E-cadherin junction complexes may explain the link between the elevated levels of CEA and the increase in soluble E-cadherin during the progression of colorectal cancer. - Highlights: • Elevated level of CEA increases the release of soluble E-cadherin during the progression of colorectal cancer. • CEA over-expression alters the binding preferences between E-cadherin and its partners: α-, β- and p120 catenins in adherens junction complexes. • CEA produced by colorectal cancer cells interacts with beta-catenin protein. • CEA over-expression triggers the increase in nuclear beta-catenin. • CEA over-expression alters the splicing of p120 catenin protein.« less

A novel lable-free electrochemical immunosensor for carcinoembryonic antigen based on gold nanoparticles-thionine-reduced graphene oxide nanocomposite film modified glassy carbon electrode.

PubMed

Kong, Fen-Ying; Xu, Mao-Tian; Xu, Jing-Juan; Chen, Hong-Yuan

2011-10-15

In this paper, gold nanoparticle-thionine-reduced graphene oxide (GNP-THi-GR) nanocomposites were prepared to design a label-free immunosensor for the sensitive detection of carcinoembryonic antigen (CEA). The nanocomposites with good biocompatibility, excellent redox electrochemical activity and large surface area were coated onto the glassy carbon electrode (GCE) surface and then CEA antibody (anti-CEA) was immobilized on the electrode to construct the immunosensor. The morphologies and electrochemistry of the formed nanocomposites were investigated by using scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectrometry, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). CV and differential pulse voltammetry (DPV) studies demonstrated that the formation of antibody-antigen complexes decreased the peak current of THi in the GNP-THi-GR nanocomposites. The decreased currents were proportional to the CEA concentration in the range of 10-500 pg/mL with a detection limit of 4 pg/mL. The proposed method was simple, fast and inexpensive for the determination of CEA at very low levels. Copyright © 2011 Elsevier B.V. All rights reserved.

Relapsed prostate cancer with neuroendocrine differentiation and high serum levels of carcinoembryonic antigen without elevation of prostrate-specific antigen: a case report.

PubMed

Kinebuchi, Yoshiaki; Noguchi, Wataru; Irie, Kyoko; Nakayama, Tsuyoshi; Kato, Haruaki; Nishizawa, Osamu

2007-02-01

A 62-year-old man had been treated with combined androgen blockade due to cT2bN1M0 prostate cancer, and his serum prostate-specific antigen (PSA) levels decreased and remained under the level of 0.5 ng/mL during therapy. Approximately 40 months after the initial therapy, difficulty on urination and constipation developed gradually, and serum carcinoembryonic antigen (CEA) and pro-gastrin-releasing peptide (ProGRP) levels were high at this point. He underwent transrectal and transurethral biopsy of the prostate, which revealed adenocarcinoma positive for CEA and chromogranin A. He received palliative pelvic irradiation, and oral estramustine phosphate and etoposide combined therapy. Tumor markers decreased and clinical symptoms improved for several months. The patient died of encephalopathy of unknown etiology approximately 11 months after the relapse.

The predictive value of preoperative carcinoembryonic antigen level in the prognosis of colon cancer.

PubMed

Kirat, Hasan T; Ozturk, Ersin; Lavery, Ian C; Kiran, Ravi P

2012-10-01

We evaluated factors associated with an increased preoperative carcinoembryonic antigen (CEA) level for colon cancer patients undergoing elective curative surgery and assessed whether this was associated with prognosis when accounting for other potential confounders. Prospectively accrued data of patients with stage I, II, and III colon cancer undergoing surgery (1980-2008) were retrieved retrospectively. Patients with a preoperative CEA level greater than 5 ng/mL (group B) were compared with those with a CEA level of 5 ng/mL or less (group A). There were 651 patients (379 men) with a median age of 67 years (range, 21-94 y) and a median follow-up period of 5.9 years. Groups A (n = 451) and B (n = 200) had similar ages and tumor locations. Group B had larger tumors; more patients with T3 and N1/N2; and more patients with stage II/III tumors, and hence greater use of chemotherapy (P = .04). On multivariate analysis, patient age, tumor stage, and differentiation were associated with oncologic outcomes. A CEA level greater than 5 ng/mL was not associated independently with recurrence, recurrence-free survival (P = .47), or overall survival (P = .3). An increased preoperative CEA level is a marker for a more advanced tumor stage. For adequately staged patients, a high preoperative CEA level is not associated independently with oncologic outcomes. Copyright © 2012 Elsevier Inc. All rights reserved.

CEA, CA 15-3, and TPS as Prognostic Factors in the Follow-up Monitoring of Patients After Radical Surgery for Breast Cancer.

PubMed

Svobodova, Sarka; Kucera, Radek; Fiala, Ondrej; Marie, Karlikova; Narsanska, Andrea; Zedníková, Ilona; Treska, Vladislav; Slouka, David; Milena, Rousarova; Topolcan, Ondrej; Finek, Jindrich

2018-01-01

The aim of this study was to evaluate the ability of tissue polypeptide-specific antigen (TPS), carcinoembryonic antigen (CEA), and cancer antigen 15-3 (CA 15-3) to predict relapse in breast cancer patients, when the measurement of biomarkers is performed within 6 months after surgery. Four hundred and seventy-two patients with breast cancer were evaluated. TPS, CEA, and CA 15-3 were measured in months 1, 3, and 6, after surgery. Disease recurrence was recorded between 7-12 months after surgery. Disease recurrence occurred in 60 patients, while 412 patients remained in recurrence-free status. TPS levels of the recurrence group differed statistically significantly in the first and sixth month after surgery compared to recurrence-free group (p=0.0339, AUC=0.6056; p<0.0001, AUC=0.7196). CEA and CA 15-3 measurements did not achieve a statistically significant difference for any month examined. TPS level in the sixth month after surgery is the best candidate biomarker to predict disease recurrence. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Keratin, luminal epithelial antigen and carcinoembryonic antigen in human urinary bladder carcinomas. An immunohistochemical study.

PubMed

Nathrath, W B; Arnholdt, H; Wilson, P D

1982-01-01

14 urinary bladder carcinomas of all main types were investigated with antisera to "broad spectrum keratin" (aK), "luminal epithelial antigen" (aLEA) and carcinoembryonic antigen (aCEA), using an indirect immunoperoxidase method on formalin fixed paraffin embedded sections. Keratin and LEA were both present in normal transitional epithelium, papilloma and carcinoma in situ whereas CEA was absent. Transitional cell carcinomas reacted with both aK and aLEA whereas CEA was seen only in a few foci. In squamous metaplasia and squamous carcinoma reaction with aK was particularly strong, while LEA was almost lacking and CEA was present in necrotic centres. In adenocarcinomas aK and aLEA reacted equally while aCEA reacted only on the surface.

Value of combining serum carcinoembryonic antigen and PET/CT in predicting EGFR mutation in non-small cell lung cancer.

PubMed

Gu, Jincui; Xu, Siqi; Huang, Lixia; Li, Shaoli; Wu, Jian; Xu, Junwen; Feng, Jinlun; Liu, Baomo; Zhou, Yanbin

2018-02-01

We sought to investigate the associations between pretreatment serum Carcinoembryonic antigen (CEA) level, 18 F-Fluoro-2-deoxyglucose ( 18 F-FDG) uptake value of primary tumor and epidermal growth factor receptor ( EGFR ) mutation status in non-small cell lung cancer (NSCLC). We retrospectively reviewed medical records of 210 NSCLC patients who underwent EGFR mutation test and 18 F-FDG positron emission tomography/computed tomography (PET/CT) scan before anti-tumor therapy. The associations between EGFR mutations and patients' characteristics, serum CEA, PET/CT imaging characteristics maximal standard uptake value (SUVmax) of the primary tumor were analyzed. Receiver-operating characteristic (ROC) curve was used to assess the predictive value of these factors. EGFR mutations were found in 70 patients (33.3%). EGFR mutations were more common in high CEA group (CEA ≥7.0 ng/mL) than in low CEA group (CEA <7.0 ng/mL) (40.4% vs . 27.6%; P=0.05). Females (P<0.001), non-smokers (P<0.001), patients with adenocarcinoma (P<0.001) and SUVmax <9.0 (P=0.001) were more likely to be EGFR mutation-positive. Multivariate analysis revealed that gender, tumor histology, pretreatment serum CEA level, and SUVmax were the most significant predictors for EGFR mutations. The ROC curve revealed that combining these four factors yielded a higher calculated AUC (0.80). Gender, histology, pretreatment serum CEA level and SUVmax are significant predictors for EGFR mutations in NSCLC. Combining these factors in predicting EGFR mutations has a moderate diagnostic accuracy, and is helpful in guiding anti-tumor treatment.

Serum CEA levels in patients with gastric carcinoma correlate with the tumorigenicity of their xenografts in nude mice.

PubMed

Kiyama, T; Onda, M; Tokunaga, A; Okuda, T; Mizutani, T; Yoshiyuki, T; Shimizu, Y; Nishi, K; Matsukura, N; Tanaka, N

1991-01-01

We examined the correlation among preoperative serum carcinoembryonic antigen (CEA) levels, staining properties of the tumors by CEA immunohistochemistry and the tumorigenicity of their xenografts in nude mice, in 28 patients with gastric cancer. Eleven (40 per cent) of them were positive for serum CEA (greater than or equal to 2.5 ng/ml) and seven (25 per cent) of the xenografts were tumorigenic in nude mice. All the tumorigenic cases were positive for serum CEA (p less than 0.001) and the mean value of the serum CEA level in the patients with tumorigenic neoplasms was 20.8 ng/ml, being significantly higher than that (1.4 ng/ml) in the patients with non-tumorigenic neoplasms (p less than 0.001). Twenty-five of the 28 carcinomas (89 per cent) were positive for CEA staining in their cancer cells by the ABC method and CEA localization correlated with tumorigenicity (p less than 0.05). These results suggest that the serum CEA level in patients is correlated with the tumorigenicity of their gastric carcinoma xenografts in nude mice and may account for the poor prognosis of patients with high serum CEA.

[Diagnostic values of type III Procollagen N-terminal peptide and combination assay of type III procollagen N-terminal peptide with CEA and CA 19-9 in gastric cancer].

PubMed

Akazawa, S; Harada, A; Futatsuki, K

1984-07-01

It is known that interstitial collagens are initially synthesized as precursors (procollagen), which possess extra peptide segments at both ends of the molecules. The authors attempted to detect the aminoterminal peptide of type III procollagen (type III-N-peptide) and also to measure the carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) together in sera of patients with gastric cancer. The results showed that: (1) mean serum levels and positive ratios of the type III-N-peptide increased as the clinical stage of the patients with gastric cancer advanced; (2) serum levels of the type III-N-peptide were not correlated either with those of CEA or CA 19-9; (3) positive ratios of type III-N-peptide, CEA and CA 19-9 were 51.7%, 44.8% and 48.3%, respectively: (4) positive ratio in combination of the type III-N-peptide with CEA was 69.3% and that in combination of the type III-N-peptide with CEA and CA 19-9 was 72.4%. These results suggest that type III-N-peptide is available for diagnosis of gastric cancer and, that the combination assay of type III-N-peptide with CEA and CA 19-9 is more effective than a single assay for diagnosis.

Carcinoembryonic antigen (CEA) levels in hookah smokers, cigarette smokers and non-smokers.

PubMed

Sajid, Khan Mohammad; Parveen, Riffat; Durr-e-Sabih; Chaouachi, Kamal; Naeem, Ayisha; Mahmood, Rubaida; Shamim, Rahat

2007-12-01

To find CEA levels in smokers of different categories (hookah smokers, cigarette smokers smoking different brands of cigarettes and different number of cigarettes per day) and to correlate CEA levels with type and rate of smoking. A total of 122 cigarette smokers (115 men and 7 women) and 14 hookah smokers (all men) with age ranging from 16-80 years were studied. CEA levels were also measured in 36 non-smokers who served as controls. Enhanced chemilumiscent immunometeric technique was applied to measure CEA levels in our subjects. The mean CEA levels of cigarette smokers were compared with the mean CEA levels observed in hookah smokers (7.16 +/- 10.4 ng/ml) and non-smokers (2.15 +/- 0.68 ng/ml). The mean value of CEA level observed in cigarette smokers, 9.19 +/- 14.9 ng/ml (n=122) was significantly higher than the levels in non-smokers and hookah smokers (p < 0.0067). It was also observed that CEA levels increased with the number of cigarettes smoked per day. The highest levels were observed in smokers who smoke more than 31 cigarettes per day. The smokers that use relatively cheaper brands of cigarettes had higher levels of CEA compared to those who use high quality brands. It was concluded that the brands of cigarettes (which were ranked on the basis of price) and the rate of smoking both play an important role in raising the CEA levels. Further the common belief that hookah also called narghile or shisha is a relatively safe mode of smoking is not completely correct; a significant proportion of hookah smokers have high levels of CEA although mean levels of hookah smokers were low compared to cigarette smokers.

Detection of carcinoembryonic antigen messenger RNA in blood using quantitative real-time reverse transcriptase-polymerase chain reaction to predict recurrence of gastric adenocarcinoma

PubMed Central

2010-01-01

Background The existence of circulating tumor cells (CTCs) in peripheral blood as an indicator of tumor recurrence has not been clearly established, particularly for gastric cancer patients. We conducted a retrospective analysis of the relationship between CTCs in peripheral blood at initial diagnosis and clinicopathologic findings in patients with gastric carcinoma. Methods Blood samples were obtained from 123 gastric carcinoma patients at initial diagnosis. mRNA was extracted and amplified for carcinoembryonic antigen (CEA) mRNA detection using real-time RT-PCR. Periodic 3-month follow-up examinations included serum CEA measurements and imaging. Results The minimum threshold for corrected CEA mRNA score [(CEA mRNA/GAPDH mRNA) × 106] was set at 100. Forty-five of 123 patients (36.6%) were positive for CEA mRNA expression. CEA mRNA expression significantly correlated with T stage and postoperative recurrence status (P = 0.001). Recurrent disease was found in 44 of 123 cases (35.8%), and 25 of these (56.8%) were positive for CEA mRNA. Of these patients, CEA mRNA was more sensitive than serum CEA in indicating recurrence. Three-year disease-free survival of patients positive for CEA mRNA was significantly poorer than of patients negative for CEA mRNA (P < 0.001). Only histological grade and CEA mRNA positivity were independent factors for disease-free survival using multivariate analysis. Conclusions CEA mRNA copy number in peripheral blood at initial diagnosis was significantly associated with disease recurrence in gastric adenocarcinoma patients. Real-time RT-PCR detection of CEA mRNA levels at initial diagnosis appears to be a promising predictor for disease recurrence in gastric adenocarcinoma patients. PMID:21040522

Detection of carcinoembryonic antigen messenger RNA in blood using quantitative real-time reverse transcriptase-polymerase chain reaction to predict recurrence of gastric adenocarcinoma.

PubMed

Qiu, Miao-Zhen; Li, Zhuang-Hua; Zhou, Zhi-Wei; Li, Yu-Hong; Wang, Zhi-Qiang; Wang, Feng-Hua; Huang, Peng; Aziz, Fahad; Wang, Dao-Yuan; Xu, Rui-Hua

2010-10-31

The existence of circulating tumor cells (CTCs) in peripheral blood as an indicator of tumor recurrence has not been clearly established, particularly for gastric cancer patients. We conducted a retrospective analysis of the relationship between CTCs in peripheral blood at initial diagnosis and clinicopathologic findings in patients with gastric carcinoma. Blood samples were obtained from 123 gastric carcinoma patients at initial diagnosis. mRNA was extracted and amplified for carcinoembryonic antigen (CEA) mRNA detection using real-time RT-PCR. Periodic 3-month follow-up examinations included serum CEA measurements and imaging. The minimum threshold for corrected CEA mRNA score [(CEA mRNA/GAPDH mRNA) × 106] was set at 100. Forty-five of 123 patients (36.6%) were positive for CEA mRNA expression. CEA mRNA expression significantly correlated with T stage and postoperative recurrence status (P = 0.001). Recurrent disease was found in 44 of 123 cases (35.8%), and 25 of these (56.8%) were positive for CEA mRNA. Of these patients, CEA mRNA was more sensitive than serum CEA in indicating recurrence. Three-year disease-free survival of patients positive for CEA mRNA was significantly poorer than of patients negative for CEA mRNA (P < 0.001). Only histological grade and CEA mRNA positivity were independent factors for disease-free survival using multivariate analysis. CEA mRNA copy number in peripheral blood at initial diagnosis was significantly associated with disease recurrence in gastric adenocarcinoma patients. Real-time RT-PCR detection of CEA mRNA levels at initial diagnosis appears to be a promising predictor for disease recurrence in gastric adenocarcinoma patients.

[Clinical value of serum TPS, CEA, Pro-GRP and CYFRA21-1 in patients with lung cancer].

PubMed

Wang, Jinghui; Shi, Guangli; Zhang, Shucai; Wang, Qunhui; Yang, Xinjie; Li, Xi; Wang, Haiyong; Zhang, Hui; Song, Changxing

2010-05-01

Serum tumor markers play important roles in diagnosis, response and prognosis monitoring for lung cancer. The clinical significance of serum level of tissue polypeptide specific antigen (TPS) was investigated in diagnosis, response monitoring and prognosis in patients with lung cancer, compared with carcinoembryonic antigen (CEA), precursor of gastrin-releasing peptide (Pro-GRP) and cytokeratin-19-fragments (CYFRA21-1). Blood samples of eighty-two patients with lung cancer before treatment and some after chemotherapy were measured by ELISA for four tumor markers. Compared with lung benign diseases group and health control group, the positive rates and levels of TPS, CEA and Pro-GRP in patients with lung cancer were higher, with statistically significant difference. TPS in extensive-small cell lung cancer was significant higher than that in limited-small cell lung cancer. The positive rates and levels of TPS, CEA and Pro-GRP in patients after treatment had significant decreases compared with before treatment. TPS was an independent prognostic factor of non-small cell lung cancer. TPS is valuable to diagnosis, response monitoring for patients with lung cancer, moreover, it maybe a useful factor of prognosis of non-small cell lung cancer.

Significance of CEA and VEGF as Diagnostic Markers of Colorectal Cancer in Lebanese Patients.

PubMed

Dbouk, Hashem A; Tawil, Ayman; Nasr, Fahd; Kandakarjian, Loucine; Abou-Merhi, Raghida

2007-11-08

Carcinoembryonic antigen and vascular endothelial growth factors are among the most important prognostic markers of colorectal cancer. Testing for these markers independently has been of limited value in screening for this tumor. The aim of this study is to determine the importance of simultaneous blood CEA and VEGF level determinations in diagnosis of colorectal cancer. Thirty-six patients diagnosed with colorectal cancer along with eight healthy controls were tested by ELISA for CEA and VEGF levels in serum and plasma, respectively. The positive predictive value of these markers was 95.4% for CEA and 89.5% for VEGF, and for combined CEA and VEGF was also high at 88%. Combined CEA and VEGF blood level assay constitutes a useful panel in detecting patients with colorectal cancer. Positive results allow selection of a subgroup of patients with a high tumor risk; therefore, such tests comprise valuable tumor diagnostic tests to add to current detection methods.

Kinetics of anti-carcinoembryonic antigen antibody internalization: effects of affinity, bivalency, and stability

PubMed Central

Schmidt, Michael M.; Thurber, Greg M.

2010-01-01

Theoretical analyses suggest that the cellular internalization and catabolism of bound antibodies contribute significantly to poor penetration into tumors. Here we quantitatively assess the internalization of antibodies and antibody fragments against the commonly targeted antigen carcinoembryonic antigen (CEA). Although CEA is often referred to as a non-internalizing or shed antigen, anti-CEA antibodies and antibody fragments are shown to be slowly endocytosed by LS174T cells with a half-time of 10–16 h, a time scale consistent with the metabolic turnover rate of CEA in the absence of antibody. Anti-CEA single chain variable fragments (scFvs) with significant differences in affinity, stability against protease digestion, and valency exhibit similar uptake rates of bound antibody. In contrast, one anti-CEA IgG exhibits unique binding and trafficking properties with twice as many molecules bound per cell at saturation and significantly faster cellular internalization after binding. The internalization rates measured herein can be used in simple computational models to predict the microdistribution of these antibodies in tumor spheroids. PMID:18408925

Combination of a poxvirus-based vaccine with a cyclooxygenase-2 inhibitor (celecoxib) elicits antitumor immunity and long-term survival in CEA.Tg/MIN mice.

PubMed

Zeytin, Hasan E; Patel, Arti C; Rogers, Connie J; Canter, Daniel; Hursting, Stephen D; Schlom, Jeffrey; Greiner, John W

2004-05-15

The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli. Naive mice fed the celecoxib-supplemented diets developed eosinophilia with lowered plasma prostaglandin E(2) levels and reduced COX-2 mRNA expression levels in their splenic T cells. Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN-gamma production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib. When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the Apc(Delta850) gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2. Beginning at 30 days of age, the administration of a diversified prime/boost recombinant CEA-poxvirus-based vaccine regimen or celecoxib (1000 ppm)-supplemented diet reduced the number of intestinal neoplasms by 54% and 65%, respectively. Combining the CEA-based vaccine with the celecoxib-supplemented diet reduced tumor burden by 95% and significantly improved overall long-term survival. Both tumor reduction and improved overall survival were achieved without any evidence of autoimmunity directed at CEA-expressing or other normal tissues. Celecoxib is prescribed for the treatment of familial adenomatous polyposis in humans, and the CEA-based vaccines have been well tolerated and capable of eliciting anti-CEA host immune responses in early clinical studies. The results suggest that the administration of a recombinant poxvirus-based vaccine is compatible with celecoxib, and this combined chemoimmuno-based approach might lead to an additive therapeutic antitumor benefit not only in patients diagnosed with familial adenomatous polyposis but, perhaps, in other preventive settings in which COX-2 overexpression is associated with progression from premalignancy to neoplasia.

Amplification of the antigen-antibody interaction from quartz crystal microbalance immunosensors via back-filling immobilization of nanogold on biorecognition surface.

PubMed

Tang, Dian-Quan; Zhang, Da-Jun; Tang, Dian-Yong; Ai, Hua

2006-10-20

A new quartz crystal microbalance immunoassay method based on a novel transparent immunoaffinity reactor was developed for clinical immunoassay. To construct such an affinity reactor, resonators with a frequency of 10 MHz were fabricated by affinity binding of functionalized gold nanoparticles (nanogold) to quartz crystal with immobilized specific ligand for the label-free analysis of the affinity reaction between a ligand and its receptor. [Recombinant human tumor markers, carcinoembryonic antigen (CEA) was chosen as a model ligand.] The binding of target molecules onto the immobilized antibodies decreased the sensor's resonant frequency, and the frequency shift was proportional to the CEA concentration in the range of 3.0-50 ng/ml with a detection limit of 1.5 ng/ml at a signal/noise ration of 3. A glycine-HCl solution (pH 2.3) was used to release antigen-antibody complexes from the biorecognition surface. Good reusability was exhibited. Moreover, spiking various levels of CEA into normal human sera was diagnosed using the proposed immunoassay. Analytical results show the precision of the developed immunoassay is acceptable, implying a promising alternative approach for detecting CEA in clinical immunoassay. Compared with the conventional enzyme-linked immunosorbent assay, the proposed immunoassay system was simple and rapid without multiple labeling and separation steps. Importantly, the proposed immunoassay system could be further developed for the immobilization of other antigens or biocompounds.

Increased mortality associated with elevated carcinoembryonic antigen in insurance applicants.

PubMed

Stout, Robert L; Fulks, Michael; Dolan, Vera F; Magee, Mark E; Suarez, Luis

2007-01-01

Determine the relationship between the carcinoembryonic antigen (CEA) value and all-cause mortality in life insurance applicants aged 50 years and over. By use of the Social Security Master Death Index, mortality was examined in 115,590 insurance applicants aged 50 and up for whom blood samples for CEA were submitted to the Clinical Reference Laboratory. Results were stratified by CEA value (<5 ng/mL, 5 to 9.9 ng/mL, 10+ ng/mL), smoking status, and age groups (50-59 years, 60-69 years, and 70 years and up). Relative mortality is increased at CEA values between 5 and 9.9 ng/mL and further increased at 10+ ng/mL for all age groups, with the most dramatic increase at the youngest ages. Excess mortality appears to last at least 3 to 4 years after the elevated result. Five-year all-cause mortality in applicants with CEA values of 10+ ng/mL is 25.2% with a mortality ratio relative to those with a CEA <5 ng/mL of 1156%. This study shows that CEA can detect the risk of early excess mortality in life insurance applicants; CEA levels of 5 ng/mL and over may be of concern. CEA testing beginning at age 50 years for life insurance applicants could capture 4.6% of early mortality if the threshold for further evaluation was set at 10 ng/mL. Only 0.4% of all applicants aged 50 and over have CEA values at or above this threshold.

Degranulation and shrinkage of dark cells in eccrine glands and elevated serum carcinoembryonic antigen in patients with acquired idiopathic generalized anhidrosis.

PubMed

Sano, K; Asahina, M; Uehara, T; Matsumoto, K; Araki, N; Okuyama, R

2017-12-01

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by anhidrosis/hypohidrosis without other autonomic and neurological dysfunctions. Pathologically, AIGA is considered to usually present no significant morphological alterations in eccrine glands, the secretory portion which consists of clear cells, dark cells, and myoepithelial cells. AIGA patients recently have been reported to show high serum concentrations of carcinoembryonic antigen (CEA). Our aim is to reveal morphological abnormalities of dark cells and investigate their relationship with serum CEA. We performed comparative analysis of eccrine glands between sweat-preserved and non-sweating skin in four AIGA patients. Serum CEA concentrations in 22 cases with AIGA were measured with healthy volunteers. Furthermore, we semiquantitatively investigated dermcidin, FoxA1 and CEA expression in eccrine glands of 12 cases with AIGA and 5 cases with non-AIGA. Marked degranulation and shrinkage of dark cells consistently occurred in AIGA. Furthermore, high serum CEA concentrations were found in 14 of 22 AIGA patients (over 60%), but serum CEA levels were not correlated with CEA expression in eccrine glands. Dermcidin expression in dark cells apparently decreased in AIGA patients, severely in those with high serum CEA and moderately in those with low serum CEA, while well-preserved expression was found in non-AIGA subjects. Our study suggests morphological damage and molecular dysregulation of dark cells, leading to impairment of their functions in AIGA patients. Severely damaged dark cells correspond to high serum CEA. Accordingly, these pathological changes in eccrine dark cells may be involved in anhidrosis/hypohidrosis of AIGA. © 2017 European Academy of Dermatology and Venereology.

Neem leaf glycoprotein enhances carcinoembryonic antigen presentation of dendritic cells to T and B cells for induction of anti-tumor immunity by allowing generation of immune effector/memory response.

PubMed

Sarkar, Koustav; Goswami, Shyamal; Roy, Soumyabrata; Mallick, Atanu; Chakraborty, Krishnendu; Bose, Anamika; Baral, Rathindranath

2010-08-01

Vaccination with neem leaf glycoprotein matured carcinoembryonic antigen (CEA) pulsed dendritic cells (DCs) enhances antigen-specific humoral and cellular immunity against CEA and restricts the growth of CEA(+) murine tumors. NLGP helps better CEA uptake, processing and presentation to T/B cells. This vaccination (DCNLGPCEA) elicits mitogen induced and CEA specific T cell proliferation, IFN gamma secretion and induces specific cytotoxic reactions to CEA(+) colon tumor cells. In addition to T cell response, DCNLGPCEA vaccine generates anti-CEA antibody response, which is principally IgG2a in nature. This antibody participates in cytotoxicity of CEA(+) cells in antibody-dependent manner. This strong anti-CEA cellular and humoral immunity protects mice from tumor development and these mice remained tumor free following second tumor inoculation, indicating generation of effector memory response. Evaluation of underlying mechanism suggests vaccination generates strong CEA specific CTL and antibody response that can completely prevent the tumor growth following adoptive transfer. In support, significant upregulation of CD44 on the surface of lymphocytes from DCNLGPCEA immunized mice was noticed with a substantial reduction in L-selectin (CD62L). (c) 2010 Elsevier B.V. All rights reserved.

Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance.

PubMed

Peng, Shaoyong; Huang, Pinzhu; Yu, Huichuan; Wen, Yanlin; Luo, Yanxin; Wang, Xiaolin; Zhou, Jiaming; Qin, Si; Li, Tuoyang; Chen, Yao; Liu, Guangjian; Huang, Meijin

2018-03-01

Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA.Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis.Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131-3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247-3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257-3.555; P = .005), 2.450 (95% CI: 1.420-4.226; P = .001), and 2.265 (95% CI: 1.304-3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS.CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression.

Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance

PubMed Central

Peng, Shaoyong; Huang, Pinzhu; Yu, Huichuan; Wen, Yanlin; Luo, Yanxin; Wang, Xiaolin; Zhou, Jiaming; Qin, Si; Li, Tuoyang; Chen, Yao; Liu, Guangjian; Huang, Meijin

2018-01-01

Abstract Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA. Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis. Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131–3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247–3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257–3.555; P = .005), 2.450 (95% CI: 1.420–4.226; P = .001), and 2.265 (95% CI: 1.304–3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS. CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression. PMID:29517661

[A study of growth and malignancy grading of stomach and colorectal cancers by serial serum carcinoembryonic antigen levels analysis].

PubMed

Umehara, Y; Miyahara, T; Yoshida, M; Isobe, S; Oba, N; Harada, Y

1990-06-01

Changes in serum CEA levels were analyzed on a time-course basis in 33 patients with stomach cancer and 20 patients with colorectal cancer. A linear relationship between log CEA and time could be evaluated and individual CEA doubling time (CEA D.T.) was calculated. The results obtained are as follows. 1) The CEA D.T. was not constant from the onset of the disease to death in stomach cancer and colorectal cancer. 2) The CEA D.T. was distributed widely with 5 to 140 days in stomach cancer and 8 to 134 days in colorectal cancer. It tended to be shortened at the terminal stage in both tumors. 3) In terms of age, sex and histology, the CEA D.T. tended to be short in the young, female and poorly differentiated cancer. These background appeared to have an influence on the growth of tumor. 4) The CEA D.T. was well correlated with the period of survival of the patients with gastric cancer (r = 0.636, p less than 0.001). The analysis of serial CEA levels on a time-course basis is considered useful in studying the relationship between tumor-bearing hosts and malignancy of the tumor.

Detection of survivin, carcinoembryonic antigen and ErbB2 level in oral squamous cell carcinoma patients.

PubMed

Li, Shu-Xia; Yang, Yan-Qi; Jin, Li-Jian; Cai, Zhi-Gang; Sun, Zheng

2016-01-01

The aim of this study was to detect the survivin, carcinoembryonic antigen (CEA) and ErbB2 in the saliva, serum and local tumor-exfoliated cells of oral squamous cell carcinoma (OSCC) patients, for providing reliable tumor markers for the early detection of oral malignant cancer. The saliva, serum, and local tumor-exfoliated cell samples of 26 OSCC patients without chemotherapy and 10 non-cancer patients were collected in Department of Oral and Maxillofacial Surgery, School of Stomatology, Peking University. The contents of survivin, CEA and ErbB2 using were detected usingenzyme-linked immunosorbent assay. The survivin and CEA levels in saliva and local tumor-exfoliated cells of OSCC patients were significantly higher than those in the non-cancer patients (P < 0.05), but there was no significant difference in the content of the above factors in the serum sample between two groups. There was no significant difference in the ErbB2 content in the saliva, serum or local tumor-exfoliated cells between two groups. Survivin and CEA levels are significantly increased in the saliva and local tumor-exfoliated cells in OSCC patients, and they can be used as reliable markers for the early detection of oral malignant cancer.

The CEA-/lo colorectal cancer cell population harbors cancer stem cells and metastatic cells.

PubMed

Yan, Chang; Hu, Yibing; Zhang, Bo; Mu, Lei; Huang, Kaiyu; Zhao, Hui; Ma, Chensen; Li, Xiaolan; Tao, Deding; Gong, Jianping; Qin, Jichao

2016-12-06

Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA-/lo) levels of CEA. Our findings show that the abundance of CEA-/lo cells correlate with poor differentiation and poor prognosis, and moreover, CEA-/lo cells form more spheres in vitro, generate more tumors and exhibit a higher potential in developing liver and lung metastases than corresponding CEA+ cells. Applying RNAi-mediated approach, we found that IGF1R mediated tumorigenic and capacity of CEA-/lo cells but did not mediate those of CEA+ cells. Notably, our data demonstrated that CEA molecule was capable of protecting CEA-/lo cells from anoikis, implying that CEA+ cells, although themselves possessing less tumorigenic and metastatic capacity, may promote metastasis of CEA-/lo cells via secreting CEA molecule. Our observations suggest that, besides targeting CEA molecule, CEA-/lo cells may represent a critical source of tumor progression and metastasis, and should therefore be the target of future therapies.

The Role of TPS and TPA in the Diagnostics of Distant Metastases.

PubMed

Kucera, Radek; Topolcan, Ondrej; Fiala, Ondrej; Kinkorova, Judita; Treska, Vladislav; Zedníková, Ilona; Slouka, David; Simanek, Vaclav; Safanda, Martin; Babuska, Vaclav

2016-02-01

The aim of the study was to assess the degree to which tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS), as well as carcinoembryonic antigen (CEA), can assist in the detection of distant metastases. We assessed 157 patients with colorectal and breast cancer divided into two groups. The first was a group of patients with cancer at stages 1, 2 and 3; the second was a group of patients with cancer at stage 4 with metastasis. We found significantly higher levels of all biomarkers in the metastatic group compared to the group with cancer at stages 1-3 (p<0.0001). The calculated area under the receiver operating characteristic (ROC) curve was 0.9929 for TPS, 0.9337 for TPA and 0.7234 for CEA. The cut-off was calculated for each biomarker at 95% specificity, TPS cut-off=255 IU/l (sensitivity 95%), TPA cut-off=200 IU/l (sensitivity 70%) and CEA cut-off=18 μg/l (sensitivity 37%). We suggest combining CEA with TPS or TPA in the detection of distant metastases or using only cytokeratins. This approach can significantly increase the quality of detection of the metastatic process. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Value of 18F-FDG PET/CT Combined With Tumor Markers in the Evaluation of Ascites.

PubMed

Han, Na; Sun, Xun; Qin, Chunxia; Hassan Bakari, Khamis; Wu, Zhijian; Zhang, Yongxue; Lan, Xiaoli

2018-05-01

The purpose of this study is to investigate the value of 18 F-FDG PET/CT combined with assessment of tumor markers in serum or ascites for the diagnosing and determining the prognosis of benign and malignant ascites. Patients with ascites of unknown cause who underwent evaluation with FDG PET/CT were included in this retrospective study. The maximum standardized uptake value (SUV max ) and levels of the tumor markers carbohydrate antigen-125 (CA-125) and carcinoembryonic antigen (CEA) in serum and ascites were recorded. The diagnostic values of FDG PET/CT, CEA and CA-125 levels in serum or ascites, and the combination of imaging plus tumor marker assessment were evaluated. Factors that were predictive of survival were also analyzed. A total of 177 patients were included. Malignant ascites was eventually diagnosed in 104 patients, and benign ascites was diagnosed in the remaining 73 patients. With the use of FDG PET/CT, 44 patients (42.3%) were found to have primary tumors. The sensitivity, specificity, and accuracy of FDG PET/CT were 92.3%, 83.6%, and 88.7%, respectively. CA-125 levels in serum and ascites showed much better sensitivity than did CEA levels, but they showed significantly lower specificity. If the combination of tumor markers and FDG PET/CT was analyzed, the sensitivity, specificity, and accuracy of tumor markers in serum were 96.6%, 78.1%, and 88.7%, and those of tumor markers in ascites were 97.7%, 80.0%, and 90.4%, respectively. Sex may be an important factor affecting survival time (hazard ratio, 0.471; p = 0.004), but age, CEA level, and FDG PET/CT findings could not predict survival. FDG PET/CT combined with assessment of tumor markers, especially CEA, increased the efficacy of diagnosis of ascites of unknown causes. Male sex conferred a poorer prognosis, whereas age, CEA level, and FDG uptake had no predictive significance in patients with malignant ascites.

The effect of high level natural ionizing radiation on expression of PSA, CA19-9 and CEA tumor markers in blood serum of inhabitants of Ramsar, Iran.

PubMed

Heidari, Mohammad Hassan; Porghasem, Mohsen; Mirzaei, Nazanin; Mohseni, Jafar Hesam; Heidari, Matine; Azargashb, Eznollah; Movafagh, Abolfazl; Heidari, Reihane; Molouki, Aidin; Larijani, Leila

2014-02-01

Since several high level natural radiation areas (HLNRAs) exist on our planet, considerable attention has been drawn to health issues that may develop as the result of visiting or living in such places. City of Ramsar in Iran is an HNLRA, and is a tourist attraction mainly due to its hot spas. However, the growing awareness over its natural radiation sources has prompted widespread scientific investigation at national level. In this study, using an ELISA method, the level of expression of three tumor markers known as carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and carcino antigen 19-9 (CA19-9) in blood serum of 40 local men of Ramsar (subject group) was investigated and compared to 40 men from the city of Noshahr (control group). Noshahr was previously identified as a normal level natural radiation area (NLNRA) that is some 85 km far from Ramsar. According to statistical analysis, there was a significant difference in the levels of PSA and CA19-9 markers between the two groups (p < 0.001) with those of Ramsar being considerably higher. CEA level did not show any difference. Although some of the volunteers tested positive to the markers, they were in good health as confirmed by the physician. Moreover, the high number of positive markers in Noshahr was considerable. Therefore, future study is needed to further validate this result and to determine the level of positivity to tumor markers in both cities. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multiple myeloma presenting as CEA-producing rectal cancer.

PubMed

Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

2010-03-31

We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas.

Novel flow cytometric analysis of the progress and route of internalization of a monoclonal anti-carcinoembryonic antigen (CEA) antibody.

PubMed

Ford, C H; Tsaltas, G C; Osborne, P A; Addetia, K

1996-03-01

A flow cytometric method of studying the internalization of a monoclonal antibody (Mab) directed against carcinoembryonic antigen (CEA) has been compared with Western blotting, using three human colonic cancer cell lines which express varying amounts of the target antigen. Cell samples incubated for increasing time intervals with fluoresceinated or unlabelled Mab were analyzed using flow cytometry or polyacrylamide gel electrophoresis and Western blotting. SDS/PAGE analysis of cytosolic and membrane components of solubilized cells from the cell lines provided evidence of non-degraded internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 min. Internalized anti-CEA was detected in the case of high CEA expressing cell lines (LS174T, SKCO1). Very similar results were obtained with an anti-fluorescein flow cytometric assay. Given that these two methods consistently provided comparable results, use of flow cytometry for the detection of internalized antibody is suggested as a rapid alternative to most currently used methods for assessing antibody internalization. The question of the endocytic route followed by CEA-anti-CEA complexes was addressed by using hypertonic medium to block clathrin mediated endocytosis.

A peptide sequence on carcinoembryonic antigen binds to a 80kD protein on Kupffer cells.

PubMed

Thomas, P; Petrick, A T; Toth, C A; Fox, E S; Elting, J J; Steele, G

1992-10-30

Clearance of carcinoembryonic antigen (CEA) from the circulation is by binding to Kupffer cells in the liver. We have shown that CEA binding to Kupffer cells occurs via a peptide sequence YPELPK representing amino acids 107-112 of the CEA sequence. This peptide sequence is located in the region between the N-terminal and the first immunoglobulin like loop domain. Using native CEA and peptides containing this sequence complexed with a heterobifunctional crosslinking agent and ligand blotting with biotinylated CEA and NCA we have shown binding to an 80kD protein on the Kupffer cell surface. This binding protein may be important in the development of hepatic metastases.

[Relation between the level of TPS, NSE, CEA and beta2-mG in the serum and the biological behavior of small cell lung cancer].

PubMed

Chen, Ming-sheng; Xu, Yan; Ma, Jing; Wu, Chang-gui; Hao, Xiao-ke; Lu, Bao-bi; Liu, Tian

2007-08-01

To study the relation between the level of tissue polypeptide specific antigen (TPS), neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and beta(2)-microglobulin (beta(2)-mG) in serum and the biological behavior of lung cancer for the more scientific diagnosis of lung cancer. To detect the level of TPS, NSE, CEA and beta(2)-mG in the serum of 94 patients with small cell lung cancer (SCLC), 86 patients with benign pulmonary diseases (BPD) and 89 patients in normal control group, the level of serum were examined by ELISA and immunoradiometric assay. The level of TPS and NSE in the serum of SCLC group [(437.8+/-516.6) U/L, (76.8+/-91.4) microg/L] were much higher than those in BPD group [(143.6+/-78.7) U/L, (13.3+/-10.8) microg/L] and normal group [(98.4+/-58.9) U/L, (10.1+/-5.7) microg/L, P<0.01)], and the level of CEA and beta(2)-mG in the serum of SCLC group were also obviously higher than those in normal group and BPD group (P<0.01). The sensitivity, specificity and accuracy of SCLC'S diagnosis by an indicator of TPS and NSE were 84.4%, 87.8%, 83.6% and 79.3%, 93.7%, 88.3%, respectively, and were much higher than CEA and beta(2)-Mg. In addition, the level of TPS and NSE in the patients' serum with metastatic SCLC were markedly higher than those in the patients with SCLC without metastasis, increased with the number of metastatic focuses. In clinical practice, the possibility of smokers suffering from lung cancer disease is 8 to 10 times higher than that of no-smokers, and 10 to 24 times higher of the people who smoked 30 to 40 cigarettes per day. From this comparison, the amount of smoking was closely related to the occurrence of lung cancer. TPS, NSE, CEA and beta(2)-mG in serum are useful for early diagnosis of lung cancer. There is complementarity in the combined detection of the level of TPS, NSE, CEA and beta(2)-MG. Their levels have close correlation with lung cancer, histological grades and lymphoid nodule metastasis.

Multiple myeloma presenting as CEA-producing rectal cancer

PubMed Central

Talamo, Giampaolo; Barochia, Amitkumar; Zangari, Maurizio; Loughran, Thomas P

2010-01-01

We report the case of a 57-year-old patient with multiple myeloma, characterized by extramedullary involvement of the rectum at presentation. Malignant plasma cells were found to produce carcinoembryonic antigen (CEA), a tumor antigen more commonly associated with rectal adenocarcinomas. PMID:21139949

A monoclonal antibody against neem leaf glycoprotein recognizes carcinoembryonic antigen (CEA) and restricts CEA expressing tumor growth.

PubMed

Das, Arnab; Barik, Subhasis; Banerjee, Saptak; Bose, Anamika; Sarkar, Koustav; Biswas, Jaydip; Baral, Rathindranath; Pal, Smarajit

2014-10-01

Carcinoembryonic antigen (CEA) is one of the promising tumor antigens mainly associated with carcinoma of the colon, lung, breast, etc. and received wide attention for cancer immunotherapy. Neem leaf glycoprotein (NLGP), an effective immunomodulator, is able to generate humoral and cellular immune responses in murine tumor models. We have generated a monoclonal antibody (mAb) against NLGP by fusing NLGP-immunized mice splenocytes with nonsecretory myeloma cells. A highly anti-NLGP mAb secreting clone (1C8; IgG2a in nature) has been identified and propagated in culture. 1C8 recognizes human CEA as good as NLGP by enzyme linked immunosorbent assay, Western blotting, and immunoprecipitation. 1C8 detects CEA on colon cancer tissues by immunochistochemistry. By flow cytometry, 1C8 specifically reacts with CEA(+) human (Colo-205, HCT-116, and HT-29) and mouse (CT-26) colon cancer cells, but it showed minimum reactivity with CEA(-) human (MCF7, SiHa, and SCC084) and mouse (B16MelF10) cancer cells. This anti-NLGP 1C8 mAb revealed significant antitumor activity and better survivability in vivo in animals bearing mouse (CT-26 in BALB/c) and human (Colo-205 in athymic nude) CEA(+) cancer cells. 1C8 has no direct influence on proliferation and migration of CEA(+) cells, however, NK cell-dependent strong antibody-dependent cellular cytotoxicity reaction toward CEA(+) cells and normalization of angiogenesis are chiefly associated with tumor growth restriction. Obtained results provided a new immunotherapeutic approach for the effective management of CEA(+) tumors.

Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis).

PubMed

Bagaria, Bhawna; Sood, Sadhna; Sharma, Rameshwaram; Lalwani, Soniya

2013-09-01

To determine the clinical serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic (ROC) curves were plotted. Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined: in esophageal cancer, sensitivity=28%, negative predictive value (NPV)=61.72%, and AUC=0.742 
(SE=0.05), with a significance level of P<0.0001; in gastric cancer, sensitivity=30%, NPV=58.82%, and AUC=0.734 (SE=0.05), with a significance level of P<0.0001; in colon cancer, sensitivity=74%, NPV=79.36%, and AUC=0.856 
(SE=0.04), with a significance level of P<0.0001. The sensitivity of CA19-9 was also evaluated: in esophageal cancer, sensitivity=18%, NPV=54.94%, and AUC=0.573 (SE =0.05), with a significance level of P=0.2054. In gastric cancer, sensitivity=42%, NPV=63.29%, and AUC=0.679 (SE =0.05), with a significance level of P<0.0011. In colon cancer, sensitivity=26%, NPV=57.47%, and AUC=0.580 (SE =0.05), with a significance level of P=0.1670. The following were the sensitivities of CEA/CA19-9 combined: in esophageal cancer, sensitivity=42%, NPV=63.29%, SE=0.078 (95% CI: 0.0159-0.322); gastric cancer, sensitivity=58%, NPV=70.42%, SE=0.072 (95% CI: -0.0866-0.198); and colon cancer, sensitivity=72%, NPV=78.12%, SE=0.070 (95% CI: 0.137-0.415). CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.

Surface-enhanced Raman scattering study of carcinoembryonic antigen in serum from patients with colorectal cancers

NASA Astrophysics Data System (ADS)

Chen, Gang; Chen, Yanping; Zheng, Xiongwei; He, Cheng; Lu, Jianping; Feng, Shangyuan; Chen, Rong; Zeng, Haisan

2013-12-01

In this work, we developed a SERS platform for quantitative detection of carcinoembryonic antigen (CEA) in serum of patients with colorectal cancers. Anti-CEA-functionalized 4-mercaptobenzoic acid-labeled Au/Ag core-shell bimetallic nanoparticles were prepared first and then used to analyze CEA antigen solutions of different concentrations. A calibration curve was established in the range from 5 × 10-3 to 5 × 105 ng/mL. Finally, this new SERS probe was applied for quantitative detection of CEA in serum obtained from 26 colorectal cancer patients according to the calibration curve. The results were in good agreement with that obtained by electrochemical luminescence method, suggesting that SERS immunoassay has high sensitivity and specificity for CEA detection in serum. A detection limit of 5 pg/ml was achieved. This study demonstrated the feasibility and great potential for developing this new technology into a clinical tool for analysis of tumor markers in the blood.

Simultaneous Detection of α-Fetoprotein and Carcinoembryonic Antigen Based on Si Nanowire Field-Effect Transistors.

PubMed

Zhu, Kuiyu; Zhang, Ye; Li, Zengyao; Zhou, Fan; Feng, Kang; Dou, Huiqiang; Wang, Tong

2015-08-05

Primary hepatic carcinoma (PHC) is one of the most common malignancies worldwide, resulting in death within six to 20 months. The survival rate can be improved by effective treatments when diagnosed at an early stage. The α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) have been identified as markers that are expressed at higher levels in PHC patients. In this study, we employed silicon nanowire field-effect transistors (SiNW-FETs) with polydimethylsiloxane (PDMS) microfluidic channels to simultaneously detect AFP and CEA in desalted human serum. Dual-channel PDMS was first utilized for the selective modification of AFP and CEA antibodies on SiNWs, while single-channel PDMS offers faster and more sensitive detection of AFP and CEA in serum. During the SiNW modification process, 0.1% BSA was utilized to minimize nonspecific protein binding from serum. The linear dynamic ranges for the AFP and CEA detection were measured to be 500 fg/mL to 50 ng/mL and 50 fg/mL to 10 ng/mL, respectively. Our work demonstrates the promising potential of fabricated SiNW-FETs as a direct detection kit for multiple tumor markers in serum; therefore, it provides a chance for early stage diagnose and, hence, more effective treatments for PHC patients.

Carcinoembryonic antigen-stimulated THP-1 macrophages activate endothelial cells and increase cell-cell adhesion of colorectal cancer cells.

PubMed

Aarons, Cary B; Bajenova, Olga; Andrews, Charles; Heydrick, Stanley; Bushell, Kristen N; Reed, Karen L; Thomas, Peter; Becker, James M; Stucchi, Arthur F

2007-01-01

The liver is the most common site for metastasis by colorectal cancer, and numerous studies have shown a relationship between serum carcinoembryonic antigen (CEA) levels and metastasis to this site. CEA activates hepatic macrophages or Kupffer cells via binding to the CEA receptor (CEA-R), which results in the production of cytokines and the up-regulation of endothelial adhesion molecules, both of which are implicated in hepatic metastasis. Since tissue macrophages implicated in the metastatic process can often be difficult to isolate, the aim of this study was to develop an in vitro model system to study the complex mechanisms of CEA-induced macrophage activation and metastasis. Undifferentiated, human monocytic THP-1 (U-THP) cells were differentiated (D-THP) to macrophages by exposure to 200 ng/ml phorbol myristate acetate (PMA) for 18 h. Immunohistochemistry showed two CEA-R isoforms present in both U- and D-THP cells. The receptors were localized primarily to the nucleus in U-THP cells, while a significant cell-surface presence was observed following PMA-differentiation. Incubation of D-THP-1 cells with CEA resulted in a significant increase in tumor necrosis factor-alpha (TNF-alpha) release over 24 h compared to untreated D-THP-1 or U-THP controls confirming the functionality of these cell surface receptors. U-THP cells were unresponsive to CEA. Attachment of HT-29 cells to human umbilical vein endothelial cells significantly increased at 1 h after incubation with both recombinant TNF-alpha and conditioned media from CEA stimulated D-THP cells by six and eightfold, respectively. This study establishes an in vitro system utilizing a human macrophage cell line expressing functional CEA-Rs to study activation and signaling mechanisms of CEA that facilitate tumor cell attachment to activated endothelial cells. Utilization of this in vitro system may lead to a more complete understanding of the expression and function of CEA-R and facilitate the design of anti-CEA-R therapeutic modalities that may significantly diminish the metastatic potential of CEA overexpressing colorectal tumors.

Comparative Study of Carcinoembryonic Antigen Tumor Marker in Stomach and Colon Cancer Patients in Khyber Pakhtunkhwa.

PubMed

Ahmad, Bashir; Gul, Bushra; Ali, Sajid; Bashir, Shumaila; Mahmood, Nourin; Ahmad, Jamshed; Nawaz, Seema

2015-01-01

Due to the increase in morbidity and mortality rate, cancer has become an alarming threat to the human population worldwide. Since cancer is a progressive disorder, timely diagnosis would be helpful to prevent/stop cancer from progressing to severe stage. In Khyber Pakhtunkhwa, Pakistan, most of the time, tumors are diagnosed with endoscopy and biopsy; therefore rare studies exist regarding the diagnosis of gastrointestinal (GIT) carcinomas based on tumor markers, especially CEA. This study made a comparative analysis of CEA in admitted hospitalized stomach and colon cancer patients diagnosed as GIT with biopsy. In this study, a total of 66 cases were included. The level of CEA was determined in the blood of these patients using ELISA technique. Out of 66 patients, the level of CEA was high in 59.1% of the total, 60.7% in colon cancer patients and 57.9 % in stomach cancer patients. Moreover, the incidence of colorectal and stomach cancer was greater in males as compared to females. Patients were more of the age group of 40- 60 and the level of CEA was comparatively higher in patients (51.5%) with histology which was moderately differentiated, than patients with well differentiated and poorly differentiated tumor histology. CEA level was high in more than 50% of the total patients. Moreover, CEA exhibited higher sensitivity for colon than stomach cancer.

Immunohistochemistry of carcinoembryonic antigen: characterisation of cross-reactions with other glycoproteins.

PubMed Central

Isaacson, P; Judd, M A

1977-01-01

In the course of demonstrating carcinoembryonic antigen (CEA) in normal human small intestine cross-reactivity of specific antiserum against red blood cells, vascular endothelium, and Paneth cell granules was noted. Pretreatment of sections with periodic acid eliminated these cross-reactions without affecting the staining of CEA, indicating that the antigenic determinants shared between CEA and other glycoproteins are in the carbohydrate portion of the molecules. These findings emphasise the caution with which immunohistochemical results should be regarded even when they are apparently well controlled. Images Fig. 6 Fig. 7 Fig. 8 Fig. 3 Fig. 4 Fig. 5 Fig. 1 Fig. 2 PMID:73495

Suppression of Murine Colitis and its Associated Cancer by Carcinoembryonic Antigen-Specific Regulatory T Cells

PubMed Central

Blat, Dan; Zigmond, Ehud; Alteber, Zoya; Waks, Tova; Eshhar, Zelig

2014-01-01

The adoptive transfer of regulatory T cells (Tregs) offers a promising strategy to combat pathologies that are characterized by aberrant immune activation, including graft rejection and autoinflammatory diseases. Expression of a chimeric antigen receptor (CAR) gene in Tregs redirects them to the site of autoimmune activity, thereby increasing their suppressive efficiency while avoiding systemic immunosuppression. Since carcinoembryonic antigen (CEA) has been shown to be overexpressed in both human colitis and colorectal cancer, we treated CEA-transgenic mice that were induced to develop colitis with CEA-specific CAR Tregs. Two disease models were employed: T-cell-transfer colitis as well as the azoxymethane–dextran sodium sulfate model for colitis-associated colorectal cancer. Systemically administered CEA-specific (but not control) CAR Tregs accumulated in the colons of diseased mice. In both model systems, CEA-specific CAR Tregs suppressed the severity of colitis compared to control Tregs. Moreover, in the azoxymethane–dextran sodium sulfate model, CEA-specific CAR Tregs significantly decreased the subsequent colorectal tumor burden. Our data demonstrate that CEA-specific CAR Tregs exhibit a promising potential in ameliorating ulcerative colitis and in hindering colorectal cancer development. Collectively, this study provides a proof of concept for the therapeutic potential of CAR Tregs in colitis patients as well as in other autoimmune inflammatory disorders. PMID:24686242

Diagnostic value of soluble B7-H4 and carcinoembryonic antigen in distinguishing malignant from benign pleural effusion.

PubMed

Jing, Xiaogang; Wei, Fei; Li, Jing; Dai, Lingling; Wang, Xi; Jia, Liuqun; Wang, Huan; An, Lin; Yang, Yuanjian; Zhang, Guojun; Cheng, Zhe

2018-03-01

To explore the diagnostic value of joint detection of soluble B7-H4 (sB7-H4) and carcinoembryonic antigen (CEA) in identifying malignant pleural effusion (MPE) from benign pleural effusion (BPE). A total of 97 patients with pleural effusion specimens were enrolled from The First Affiliated Hospital of Zhengzhou University between June 2014 and December 2015. All cases were categorized into malignant pleural effusion group (n = 55) and benign pleural effusion group (n = 42) according to etiologies. Enzyme-linked immunosorbent assay was applied to examine the levels of sB7-H4 in pleural effusion and meanwhile CEA concentrations were detected by electro-chemiluminescence immunoassays. Receiver operating characteristic (ROC) curve was established to assess the diagnostic value of sB7-H4 and CEA in pleural effusion. The correlation between sB7-H4 and CEA levels was analyzed by Pearson's product-moment. The concentrations of sB7-H4 and CEA in MPE exhibited obviously higher than those of BPE ([60.08 ± 35.04] vs. [27.26 ± 9.55] ng/ml, P = .000; [41.49 ± 37.16] vs. [2.41 ± 0.94] ng/ml, P = .000). The AUC area under ROC curve of sB7-H4 and CEA was 0.884 and 0.954, respectively. Two cutoff values by ROC curve analysis of sB7-H4 36.5 ng/ml and CEA 4.18 ng/ml were obtained, with a corresponding sensitivity (81.82%, 87.28%), specificity (90.48%, 95.24%), accuracy (85.57%, 90.72%), positive predictive value (PPV) (91.84%, 96.0%), negative predictive value (NPV) (79.17%, 85.11%), positive likelihood ratio (PLR) (8.614, 18.327), and negative likelihood ratio (NLR) (0.201, 0.134). When sB7-H4 and CEA were combined to detect pleural effusion, it obtained a higher sensitivity 90.91% and specificity 97.62%. Furthermore, correlation analysis result showed that the level of sB7-H4 was correlated with CEA level (r = .770, P = .000). sB7-H4 was a potentially valuable tumor marker in the differentiation between BPE and MPE. The combined detection of sB7-H4 and CEA could improve the diagnostic sensitivity and specificity for MPE. © 2017 John Wiley & Sons Ltd.

Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

PubMed Central

Lee, Hsin-chung; Ling, Qing-Dong; Yu, Wan-Chun; Hung, Chunh-Ming; Kao, Ta-Chun; Huang, Yi-Wei; Higuchi, Akon

2013-01-01

Purpose We evaluated the higher levels of carcinoembryonic antigen (CEA) secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs). Methods The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction. Results Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the untreated LoVo cells. Conclusion Production of CEA by LoVo cells can be stimulated by the addition of anticancer drugs. The drug-resistant subpopulation of LoVo colon cancer cells could stimulate the production of CEA, but these cells did not act as CSCs in in vivo tumor generation experiments. PMID:23818760

Proper exercise decreases plasma carcinoembryonic antigen levels with the improvement of body condition in elderly women.

PubMed

Ko, Il-Gyu; Park, Eung-Mi; Choi, Hye-Jung; Yoo, Jaehyun; Lee, Jong-Kyun; Jee, Yong-Seok

2014-05-01

Aging increases the risk of chronic diseases including cancers. Physical exercise has the beneficial effects for the elderly susceptible to the development of cancers, through maintaining a healthy body condition and improving the immune system. However, excessive or insufficient exercise might increase the risk for cancer. In the present study, we investigated what exercise frequency improves cancer-related biomarkers, such as carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), red blood cell (RBC), and white blood cell (WBC), and the body composition of elderly women. Fifty-four females, aged 70 to 77 years, were divided into 4 groups: control, 1-day exercise (1E), 2-3-day exercise (2-3E), and 5-day exercise (5E) groups. The control group did not participate in any physical activity, while the subjects in the exercise groups underwent the exercise program for 12 weeks. As results, CEA was significantly decreased in the exercise groups, with the lowest values in 2-3E group. In contrast, AFP, RBC and WBC were not significantly changed. CEA is an oncofetal glycoprotein that is overexpressed in adenocarcinomas. Although the function of CEA has not been fully understood, CEA has been suggested to be involved in the release of pro-inflammatory cytokines via stimulating monocytes and macrophages. Moreover, body weight and body mass index were improved in the exercise groups, with the lowest levels in 5E group. Thus, we suggest that exercise for 2-3 days per week decreases the expression of CEA and improves body condition, without loading fatigue or stress, which may contribute to preventing cancer in the elderly women.

Evaluation of tumour markers as differential diagnostic tool in patients with suspicion of liver metastases from breast cancer.

PubMed

Liska, Vaclav; Holubec, Lubos; Treska, Vladislav; Vrzalova, Jindra; Skalicky, Tomas; Sutnar, Alan; Kormunda, Stanislav; Bruha, Jan; Vycital, Ondrej; Finek, Jindrich; Pesta, Martin; Pecen, Ladislav; Topolcan, Ondrej

2011-04-01

The liver is the site of breast cancer metastasis in 50% of patients with advanced disease. Tumour markers have been demonstrated as being useful in follow-up of patients with breast cancer, in early detection of recurrence of breast cancer after radical surgical treatments, and in assessing oncologic therapy effect, but no study has been carried out on their usefullness in distinguishing benign liver lesions from breast cancer metastases. The aim of this study was therefore to evaluate the importance of tumour markers carcinoembryonic antigen (CEA), carbohydrate antigen CA19-9 (CA19-9), thymidine kinase (TK), tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin 19 fragment (CYFRA 21-1) in differential diagnosis between benign liver lesions and liver metastases of breast cancer. The study includes 3 groups: 22 patients with liver metastases of breast cancer; 39 patients with benign liver lesions (hemangioma, focal nodular hyperplasia, liver cyst, hepatocellular adenoma); and 21 patients without any liver disease or lesion that were operated on for benign extrahepatic diseases (groin hernia, varices of lower limbs) as a control group. The serum levels of tumour markers were assessed by means of immunoanalytical methods. Preoperative serum levels of CYFRA 21-1, TPA, TPS and CEA were significantly higher in patients with liver metastases of breast cancer in contrast to healthy controls and patients with benign liver lesions (p-value<0.05). Serum levels of CA19-9 and TK were higher in patients with malignancy in comparison with benign liver disease and healthy controls but these differences were not statistically significant. Tumour markers CEA, CYFRA 21-1, TPA and TPS can be recommended as a good tool for differential diagnosis between liver metastases of breast cancer and benign liver lesions.

Demonstration of monoclonal anti-carcinoembryonic antigen (CEA) antibody internalization by electron microscopy, western blotting and radioimmunoassay.

PubMed

Tsaltas, G; Ford, C H; Gallant, M

1992-01-01

One of the important factors affecting the action of monoclonal antibodies (Mabs) or immunoconjugates on tumour sites depends on whether the Mab is internalized by the cancer cells in question. The underexplored subject of internalization is discussed in this paper, and a number of in vitro techniques for investigating internalization are evaluated, using a model which consists of a well characterized anti-carcinoembryonic antigen (anti-CEA) Mab and a number of CEA expressing human cancer cell lines. Employing two alternative radiolabeling assays, evidence for internalization of the anti-CEA Mab by a CEA-positive colorectal cancer cell line (LS174T) was obtained throughout the time intervals examined (5 min to 150 min). Electronmicroscopy employing horseradish-peroxidase labeled anti-CEA Mab and control antibody permitted direct visualization of anti-CEA Mab-related staining in intracellular compartments of a high CEA-expressor human colorectal cell line (SKCO1). Finally Western blots of samples derived from cytosolic and membrane components of solubilized cells from lung and colonic cancer cell lines provided evidence for internalized anti-CEA Mab throughout seven half hour intervals, starting at 5 minutes. Internalized anti-CEA was detected in all CEA expressing cell lines (LS174T, SKCO1, BENN) but not in the case of a very low CEA expressor line (COLO 320).

Clinical significance and diagnostic capacity of serum TK1, CEA, CA 19-9 and CA 72-4 levels in gastric and colorectal cancer patients.

PubMed

Ning, Shufang; Wei, Wene; Li, Jilin; Hou, Bingbing; Zhong, Jianhong; Xie, Yuxuan; Liu, Haizhou; Mo, Xianwei; Chen, Jiansi; Zhang, Litu

2018-01-01

Despite extensive progress in treatment for cancer in recent decades, the early diagnosis for gastric cancer (GC) and colorectal cancer (CRC) remains poor. In this study, we explore the diagnostic value of joint detection of thymidine kinase 1 (TK1), carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9) and carbohydrate antigen 72-4 (CA 72-4) in the diagnosis of GC and CRC, and to evaluated the relationship between TK1 expression and clinical pathological characteristics in the patients. Serum TK1, CA 19-9, CA 72-4 and CEA levels were measured in 169 patients with GC, 344 patients with CRC and 75 healthy controls using electro-chemiluminescence. The TK1 concentration was significantly higher in patients with cancer than in healthy controls and patients with clinical stage Ⅲ+Ⅳ had higher TK1 levels than clinical stage Ⅰ+Ⅱ ( P <0.05). The levels of TK1 is significantly associated with tumor stage, lymph node metastasis, distant metastasis, tumor differentiation and age ( P <0.05). When the tumor markers (TK1, CA 19-9 and CA 72-4) were detected respectively, the area under receiver operating characteristics curve (AUC) of TK1 for three cancers was the highest (0.823-0.895). However, the combination of AUC was higher than that for each tumor marker detected respectively (0.934-0.953), and the Hosmer-Lemeshow test showed an adequate model of calibration (P>0.05). Moreover, the AUCs varied significantly between the combination tests and single biomarker tests (Z test, P <0.01). In conclusion, serum TK1 may be an independent tumor marker for GC and CRC patients, and the combination of TK1, CA 19-9 and CA 72-4 and CEA performed even better. This study suggests that combination detection of four tumor markers may prove to be useful for the diagnosis of GC and CRC.

Preoperative Carcinoembryonic Antigen and Prognosis of Colorectal Cancer. An Independent Prognostic Factor Still Reliable

PubMed Central

Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

2015-01-01

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this—to date—has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging. PMID:25875542

Preoperative carcinoembryonic antigen and prognosis of colorectal cancer. An independent prognostic factor still reliable.

PubMed

Li Destri, Giovanni; Rubino, Antonio Salvatore; Latino, Rosalia; Giannone, Fabio; Lanteri, Raffaele; Scilletta, Beniamino; Di Cataldo, Antonio

2015-04-01

To evaluate whether, in a sample of patients radically treated for colorectal carcinoma, the preoperative determination of the carcinoembryonic antigen (p-CEA) may have a prognostic value and constitute an independent risk factor in relation to disease-free survival. The preoperative CEA seems to be related both to the staging of colorectal neoplasia and to the patient's prognosis, although this-to date-has not been conclusively demonstrated and is still a matter of intense debate in the scientific community. This is a retrospective analysis of prospectively collected data. A total of 395 patients were radically treated for colorectal carcinoma. The preoperative CEA was statistically compared with the 2010 American Joint Committee on Cancer (AJCC) staging, the T and N parameters, and grading. All parameters recorded in our database were tested for an association with disease-free survival (DFS). Only factors significantly associated (P < 0.05) with the DFS were used to build multivariate stepwise forward logistic regression models to establish their independent predictors. A statistically significant relationship was found between p-CEA and tumor staging (P < 0.001), T (P < 0.001) and N parameters (P = 0.006). In a multivariate analysis, the independent prognostic factors found were: p-CEA, stages N1 and N2 according to AJCC, and G3 grading (grade). A statistically significant difference (P < 0.001) was evident between the DFS of patients with normal and high p-CEA levels. Preoperative CEA makes a pre-operative selection possible of those patients for whom it is likely to be able to predict a more advanced staging.

Doxorubicin-anti-carcinoembryonic antigen immunoconjugate activity in vitro.

PubMed

Richardson, V J; Ford, C H; Tsaltas, G; Gallant, M E

1989-04-01

An in vitro model consisting of a series of 11 human cancer cell lines with varying density of expression of membrane carcinoembryonic antigen (CEA) has been used to evaluate conjugates of doxorubicin (Adriamycin) covalently linked by a carbodiimide method to goat polyclonal antibodies and mouse monoclonal antibodies to CEA. Conjugates were produced which retained both antigen binding and drug cytotoxicity. IC50 values were determined for free drug, free drug mixed with unconjugated antibodies and for the immunoconjugates. Cell lines that were very sensitive to free drug (IC50 less than 100 ng/ml) were also found to be highly sensitive to conjugated drug and similarly cell lines resistant to drug (IC50 greater than 1,000 ng/ml) were also resistant to conjugated drug. Although there was no correlation between CEA expression and conjugates efficacy, competitive inhibition studies using autologous antibody to block conjugate binding to cells indicated immunoconjugates specificity for the CEA target.

In vitro Fab display: a cell-free system for IgG discovery

PubMed Central

Stafford, Ryan L.; Matsumoto, Marissa L.; Yin, Gang; Cai, Qi; Fung, Juan Jose; Stephenson, Heather; Gill, Avinash; You, Monica; Lin, Shwu-Hwa; Wang, Willie D.; Masikat, Mary Rose; Li, Xiaofan; Penta, Kalyani; Steiner, Alex R.; Baliga, Ramesh; Murray, Christopher J.; Thanos, Christopher D.; Hallam, Trevor J.; Sato, Aaron K.

2014-01-01

Selection technologies such as ribosome display enable the rapid discovery of novel antibody fragments entirely in vitro. It has been assumed that the open nature of the cell-free reactions used in these technologies limits selections to single-chain protein fragments. We present a simple approach for the selection of multi-chain proteins, such as antibody Fab fragments, using ribosome display. Specifically, we show that a two-chain trastuzumab (Herceptin) Fab domain can be displayed in a format which tethers either the heavy or light chain to the ribosome while retaining functional antigen binding. Then, we constructed synthetic Fab HC and LC libraries and performed test selections against carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF). The Fab selection output was reformatted into full-length immunoglobulin Gs (IgGs) and directly expressed at high levels in an optimized cell-free system for immediate screening, purification and characterization. Several novel IgGs were identified using this cell-free platform that bind to purified CEA, CEA positive cells and VEGF. PMID:24586053

Two-color immunostaining of liver fine needle aspiration biopsies with CD34 and carcinoembryonic antigen. Potential utilization in the diagnosis of primary hepatocellular carcinoma vs. metastatic tumor.

PubMed

Yoder, Michael; Zimmerman, Robert L; Bibbo, Marluce

2004-04-01

To examine immunohistochemical staining of cell block material with antibodies against vascular marker CD34 and polyclonal carcinoembryonic antigen (pCEA) for their clinical utility as part of a 2-color staining protocol in fine needle aspiration (FNA) biopsy of liver masses to distinguish metastases from primary hepatocellular carcinoma (HCC). The authors obtained cell block material from 96 liver FNAs and performed simultaneous (i.e., "dual-color") immunohistochemical staining utilizing antibodies against vascular marker CD34 and pCEA. Cases were blinded and evaluated by the authors for staining pattern and intensity. A consensus was obtained, the results were unblinded, and the diagnoses were correlated. After staining, 89 cases had sufficient tissue for evaluation. Of the 19 HCC cases, 16 (84%) showed peripheral staining with CD34, and 13 (68%) showed a canalicular or mixed canalicular-cytoplasmic staining pattern for pCEA. Thirteen cases (68%) showed staining for both antigens. All HCC exhibited immunostaining for at least 1 antibody in an appropriate staining pattern. Of the 67 cases of metastatic malignancy, 5 (7%) showed a predominantly transgressing pattern of CD34 staining, 43 (64%) showed a predominantly cytoplasmic or mixed cytoplasmic-canalicular pattern of pCEA staining, and 2 cases (3%) showed staining for both antigens in a transgressing CD34 pattern and cytoplasmic pCEA pattern. None of the 3 normal liver tissue blocks showed staining with either antigen. Two-color immunohistochemical staining of liver cell block material obtained by FNA with antibodies to CD34 and pCEA can be helpful in differentiating metastatic tumors vs. primary HCC.

Evaluation of serum and pleural levels of endostatin and vascular epithelial growth factor in lung cancer patients with pleural effusion.

PubMed

Zhang, Yu; Yu, Li-Ke; Xia, Ning

2012-03-01

To evaluate the diagnostic value of endostatin (ES), vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) in both serum and pleural effusion of lung cancer patients. Levels of ES, VEGF and CEA in 52 malignant pleural effusion due to lung cancer and 50 patients with non-malignant disease were measured by using sandwich enzyme-linked immunosorbent assay and microparticle enzyme immunoassay. The ES, VEGF and CEA levels in pleural effusion and serum, and their ratio (F/S) were higher in lung cancer group than that in benign group, and the differences were statistically significant (P<0.05). The diagnostic efficiency of ES+VEGF for lung cancer was superior to either single detection. The diagnostic efficiency of ES+VEGF+CEA was superior to either ES+VEGF or ES+CEA. The results suggest that ES, VEGF and CEA might be useful in the differentiation between benign and malignant pleural effusion due to lung cancer. In comparison with either single determination of concentration in serum or pleural fluid, the combined detection of two or three markers is of important clinical significance in the diagnosis of lung cancer. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor regression in mouse models of colorectal cancer.

PubMed

Murgas, Paola; Bustamante, Nicolás; Araya, Nicole; Cruz-Gómez, Sebastián; Durán, Eduardo; Gaete, Diana; Oyarce, César; López, Ernesto; Herrada, Andrés Alonso; Ferreira, Nicolás; Pieringer, Hans; Lladser, Alvaro

2018-02-01

Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Single-stranded DNA containing M13 bacteriophages are highly immunogenic and can be specifically targeted to the surface of tumor cells to trigger inflammation and infiltration of activated innate immune cells, overcoming tumor-associated immunosuppression and promoting antitumor immunity. Carcinoembryonic antigen (CEA) is highly expressed in colorectal cancers and has been shown to promote several malignant features of colorectal cancer cells. In this work, we targeted M13 bacteriophage to CEA, a tumor-associated antigen over-expressed in a high proportion of colorectal cancers but largely absent in normal cells. The CEA-targeted M13 bacteriophage was shown to specifically bind to purified CEA and CEA-expressing tumor cells in vitro. Both intratumoral and systemic administration of CEA-specific bacteriophages significantly reduced tumor growth of mouse models of colorectal cancer, as compared to PBS and control bacteriophage administration. CEA-specific bacteriophages promoted tumor infiltration of neutrophils and macrophages, as well as maturation dendritic cells in tumor-draining lymph nodes, suggesting that antitumor T-cell responses were elicited. Finally, we demonstrated that tumor protection provided by CEA-specific bacteriophage particles is mediated by CD8 + T cells, as depletion of circulating CD8 + T cells completely abrogated antitumor protection. In summary, we demonstrated that CEA-specific M13 bacteriophages represent a potential immunotherapy against colorectal cancer.

Magneto-controlled bioelectronics for the antigen-antibody interaction based on magnetic-core/gold-shell nanoparticles functionalized biomimetic interface.

PubMed

Tang, Dianping; Yuan, Ruo; Chai, Yaqin

2008-02-01

A new protein assay system for the antigen-antibody interaction was developed by immobilization of carcinoembryonic antibody (anti-CEA) onto magnetic-core/gold-shell nanoparticles-functionalized biomimetic interface on multiporous polythionine modified magnetic carbon paste electrodes (MCPE). Differential pulse voltammetric (DPV) technique was employed to investigate the antigen-antibody interaction in pH 6.8 acetate acid buffer solution after incubation with various CEA samples for 50 min at room temperature. The peak currents decreased with increased CEA concentration, and were proportional to the CEA concentration in the range of 1.5-60 ng/ml with a detection limit of 0.3 ng/ml at a signal-to-noise ratio of 3. Moreover, the selectivity, reproducibility and stability of the proposed immunoassay system were acceptable. Compared with the conventional immunoassays, the developed immunoassay system was simple and rapid without multiple labeling and separation steps. Importantly, the proposed methodology would be valuable for diagnosis and monitoring of carcinoma and its metastasis.

Role of endoscopic ultrasound-guided fine needle aspiration and ultrasound-guided fine-needle aspiration in diagnosis of cystic pancreatic lesions

PubMed Central

Okasha, Hussein Hassan; Ashry, Mahmoud; Imam, Hala M. K.; Ezzat, Reem; Naguib, Mohamed; Farag, Ali H.; Gemeie, Emad H.; Khattab, Hani M.

2015-01-01

Background and Objective: The addition of fine-needle aspiration (FNA) to different imaging modalities has raised the accuracy for diagnosis of cystic pancreatic lesions. We aim to differentiate benign from neoplastic pancreatic cysts by evaluating cyst fluid carcinoembryonic antigen (CEA), carbohydrate antigen (CA19-9), and amylase levels and cytopathological examination, including mucin stain. Patients and Methods: This prospective study included 77 patients with pancreatic cystic lesions. Ultrasound-FNA (US-FNA) or endoscopic ultrasound-FNA (EUS-FNA) was done according to the accessibility of the lesion. The aspirated specimens were subjected to cytopathological examination (including mucin staining), tumor markers (CEA, CA19-9), and amylase level. Results: Cyst CEA value of 279 or more showed high statistical significance in differentiating mucinous from nonmucinous lesions with sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 73%, 60%, 50%, 80%, and 65%, respectively. Cyst amylase could differentiate between neoplastic and nonneoplastic cysts at a level of 1043 with sensitivity of 58%, specificity of 75%, PPV of 73%, NPV of 60%, and accuracy of 66%. CA19-9 could not differentiate between neoplastic and nonneoplastic cysts. Mucin examination showed a sensitivity of 85%, specificity of 95%, PPV of 92%, NPV of 91%, and accuracy of 91% in differentiating mucinous from non-mucinous lesions. Cytopathological examination showed a sensitivity of 81%, specificity of 94%, PPV of 94%, NPV of 83%, and accuracy of 88%. Conclusion: US or EUS-FNA with analysis of cyst CEA level, CA19-9, amylase, mucin stain, and cytopathological examination increases the diagnostic accuracy of cystic pancreatic lesions. PMID:26020048

Evaluation of diagnostic value of four tumor markers in bronchoalveolar lavage fluid of peripheral lung cancer.

PubMed

Li, Jian; Chen, Ping; Mao, Chao-Ming; Tang, Xing-Ping; Zhu, Li-Rong

2014-06-01

The diagnostic role of carcinoembryonic antigen (CEA), squamous cell carcinoma (SCC) antigen, Cyfra 21-1 and neuron-specific enolase (NSE) in the bronchoalveolar lavage fluid (BALF) for lung cancer is still controversial. The aim of this study was to evaluate the diagnostic value of these four tumor markers in BALF for peripheral lung cancer. We measured and compared the levels of CEA, SCC, Cyfra21-1 and NSE in BALF in 42 patients with peripheral lung cancer and 22 patients with benign lung disease. In the patients with peripheral lung cancer, the BAL was separately performed in the bronchus of the tumor-bearing lung and in the corresponding bronchus of the opposite healthy lung. The levels of CEA, SCC, Cyfra21-1 and NSE were significantly elevated in BALF from the tumor-bearing lung compared with the opposite healthy lung in the lung cancer patients (P < 0.001) or the benign lung disease patients (P < 0.005). The diagnostic sensitivities of Cyfra21-1 (86 and 76%), with a specificity of 91%, were the highest among the four tumor markers for the tumor-bearing lung versus the opposite healthy lung and benign lung disease. The combination of Cyfra21-1 and CEA increased the sensitivity to 93 and 86 percent, respectively. The assay of these tumor markers in BALF may be used as a diagnostic tool to complement a cytological examination in the diagnosis of peripheral lung cancer. © 2013 Wiley Publishing Asia Pty Ltd.

The Diagnostic and Prognostic Value of Tumor Markers (CEA, SCC, CYFRA 21-1, TPS) in Head and Neck Cancer Patients.

PubMed

Barak, Vivian; Meirovitz, Amichay; Leibovici, Vera; Rachmut, Jacob; Peretz, Tamar; Eliashar, Ron; Gross, Menachem

2015-10-01

Establishing prognostic factors is very important in the management of cancer patients. Our aim was to evaluate the clinical significance of a panel of tumor markers, including CEA (Carcino Embryonic Antigen), SCC (Squamous Cell Carcinoma Antigen), TPS (Tissue Polypeptide Specific Antigen) and CYFRA 21-1 in head and neck cancer patients, for assessing treatment response and prognosis of patients. We evaluated 312 blood samples from 143 head and neck cancer patients, from several sub-groups: 82 Larynx Carcinoma pre- and 38 post-therapy, 46 Oral Cavity pre and 29 post-therapy, 12 nasopharynx, 16 parotid and other salivary gland patients. Blood tumor markers levels were evaluated by conventional ELISA assays. Correlations of marker levels to stage of disease, lymph node involvement and therapy, were performed. Serum levels of all four tumor markers were higher before therapy and decreased thereafter in all patients. The decrease in TPS level following therapy was significant (p=0.03). Significantly higher levels of TPS and similarly higher levels of the other tumor markers were demonstrated in advanced disease (stages III and IV) patients, as opposed to early disease (stages I and II) patients (p=0.012). Node positive patients had significantly higher TPS levels as compared to node negative (p=0.02). The same trend was shown by the other markers as well, but did not reach statistical significance. TPS was best correlated to survival of patients; those having low levels had the best clinical outcome and longer survival. CEA, SCC, TPS and CYFRA 21-1 can all serve as useful tumor markers in HNC patients. They assessed response to therapy and were prognostic for recurrence. TPS proved to be the most sensitive predictor of advanced disease and poor prognosis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Diagnostic value of tumor markers for lung adenocarcinoma-associated malignant pleural effusion: a validation study and meta-analysis.

PubMed

Feng, Mei; Zhu, Jing; Liang, Liqun; Zeng, Ni; Wu, Yanqiu; Wan, Chun; Shen, Yongchun; Wen, Fuqiang

2017-04-01

Pleural effusion is one of the most common complications of lung adenocarcinoma and is diagnostically challenging. This study aimed to investigate the diagnostic performance of carcinoembryonic antigen (CEA), cytokeratin fragment (CYFRA) 21-1, and cancer antigen (CA) 19-9 for lung adenocarcinoma-associated malignant pleural effusion (MPE) through a validation study and meta-analysis. Pleural effusion samples were collected from 81 lung adenocarcinoma-associated MPEs and 96 benign pleural effusions. CEA, CYFRA 21-1, and CA19-9 were measured by electrochemiluminescence immunoassay. The capacity of tumor markers was assessed with receiver operating characteristic curve analyses and the area under the curve (AUC) was calculated. Standard methods for meta-analysis of diagnostic studies were used to summarize the diagnostic performance of CEA, CYFRA 21-1, and CA19-9 for lung adenocarcinoma-associated MPE. The pleural levels of CEA, CYFRA 21-1, and CA19-9 were significantly increased in lung adenocarcinoma-associated MPE compared to benign pleural effusion. The cut-off points for CEA, CYFRA 21-1, and CA19-9 were optimally set at 4.55 ng/ml, 43.10 μg/ml, and 12.89 U/ml, and corresponding AUCs were 0.93, 0.85, and 0.81, respectively. The combination of CEA, CYFRA 21-1, and CA19-9 increased the sensitivity to 95.06%, with an AUC of 0.95. Eight studies were included in this meta-analysis. CEA showed the best diagnostic performance with pooled sensitivity, specificity, positive/negative likelihood ratio, and diagnostic odds ratio of 0.75, 0.96, 16.01, 0.23, and 81.49, respectively. The AUC was 0.93. CEA, CYFRA 21-1, and CA19-9 play a role in the diagnosis of lung adenocarcinoma-associated MPE. The combination of these tumor markers increases the diagnostic accuracy.

Clinical value of jointly detection serum lactate dehydrogenase/pleural fluid adenosine deaminase and pleural fluid carcinoembryonic antigen in the identification of malignant pleural effusion.

PubMed

Zhang, Fan; Hu, Lijuan; Wang, Junjun; Chen, Jian; Chen, Jie; Wang, Yumin

2017-09-01

Limited data are available for the diagnostic value, and for the diagnostic sensitivity and specificity of joint detection of serum lactate dehydrogenase (sLDH)/pleural fluid adenosine deaminase (pADA) and pleural fluid carcinoembryonic antigen (pCEA) in malignant pleural effusion (MPE). We collected 987 pleural effusion specimens (of which 318 were malignant pleural effusion, 374 were tubercular pleural effusion, and 295 were parapneumonic effusion specimens) from the First Affiliated Hospital of Wenzhou Medical University from July 2012 to March 2016. The pADA, sLDH, pleural fluid LDH (pLDH), serum C-reactive protein (sCRP), pleural fluid protein, pCEA, white blood cell (WBC), and red blood cell (RBC) were analyzed, and the clinical data of each group were collected for statistical analysis. The level of sLDH/pADA, pCEA, and RBC from the MPE group was markedly higher than the tuberculosis pleural effusion (TB) group (Mann-Whitney U=28422.000, 9278.000, 30518, P=.000, .000, .000) and the parapneumonic pleural fluid group (Mann-Whitney U=5972.500, 7113.000, 36750.500, P=.000, .000, .000). The receiver operating characteristic curve ROC showed that the area under the ROC curve (AUC) (=0.924, 0.841) of pCEA and sLDH/pADA (cutoff=4.9, 10.6) were significantly higher than other markers for the diagnosis of MPE. Thus, joint detection of pCEA and sLDH/pADA suggested that the sensitivity, specificity, and AUC was 0.94, 81.70, and 94.32 at the cutoff 0.16 and diagnostic performance was higher than pCEA or sLDH/pADA. Joint detection of sLDH/pADA and pCEA can be used as a good indicator for the identification of benign and MPE with higher sensitivity and specificity than pCEA or sLDH/pADA. © 2016 Wiley Periodicals, Inc.

The relationship between Glasgow Prognostic Score and serum tumor markers in patients with advanced non-small cell lung cancer.

PubMed

Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

2015-05-10

Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21-1 were 1.5 ng/ml (0.1-3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7-35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4-89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9-134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P< 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman's rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated with CYFRA21-1, CEA and TPS in patients with advanced NSCLC. However, GPS was more efficient in predicting prognosis of advanced NSCLC than these three single prognosis related tumor markers.

[The value of B7-H4 and carcinoembryonic antigen in diagnosing the benign and malignant pleural effusion].

PubMed

Wei, F; Wei, Y; Li, L F; Li, G L; Wang, G J

2017-07-23

Objective: To evaluate the value of combined detection of negative costimulatory molecule B7-H4 and carcinoembryonic antigen (CEA) in diagnosing malignant and benign pleural effusion. Methods: Ninety-seven pleural effusion specimen were collected, 55 of which were diagnosed as malignant pleural effusion and 42 were benign pleural effusion. Enzyme-linked immunosorbent assay(ELISA) was used to examine the concentration of B7-H4 and CEA in pleural effusion. Electro-chemiluminescence immunoassay was used to detect the CEA level in pleural effusion. Receiver operating characteristic (ROC) curve was established to analyze and evaluate the single or combined detection of B7-H4 and CEA in diagnosing malignant and benign pleural effusion. Results: The concentrations of B7-H4 and CEA in malignant pleural effusion (MPE) group were (60.08±35.04) ng/ml and (41.49±37.16) ng/ml, respectively, obviously higher than (27.26±9.55) ng/ml and (2.41±0.94) ng/ml of benign pleural effusion (BPE) group (both P <0.01). Area under curve (AUC) of B7-H4 was 0.884 in MPE groupand the diagnostic sensitivity and specificity were 81.8% and 90.5%, respectively, at the optimized cut off value of 37.25 ng/ml. Likewise, area under curve (AUC) of CEA was 0.954 and the sensitivity and specificity were 87.3% and 95.2%, respectively, at the cut off value of 4.18 ng/ml. When B7-H4 >37.25 ng/ml or CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 90.9% and the specificity was elevated to 88.1%. When B7-H4 >37.25 ng/ml and CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 78.2% and the specificity was elevated to 97.6%. The sensitivity and specificity of combined detection of B7-H4 and CEA to diagnose MPE were elevated to 90.9% and 97.6%, respectively. The level of B7-H4 in MPE and BPE were both positively correlated with CEA ( r =0.670, P =0.001 in MPE and r =0.002, P =0.001 in BEP). Conclusions: B7-H4 is a potential tumor marker in diagnosing the benign and malignant pleural effusion. Although the diagnostic value of B7-H4 may not precede to CEA, the combined detection of B7-H4 and CEA can improve the diagnostic sensitivity and specificity of MPE.

[Comparison of TPS, CEA, CYFRA21-1 and STNFR in diagnosis of lung cancer].

PubMed

Liao, Qiulin; Li, Lianhua; Chen, Mingsheng

2005-08-20

In recent years, new progress has been made in research of tumor markers. And namely tissue polypeptide specific antigen (TPS), cytokeratin 19-fragments (CYFRA21-1) and soluble tumor necrosis factor receptor (STNFR) are new tumor markers that have been used in clinical application. The aim of this study is to determine and compare the diagnostic value of 4 kinds of tumor markers, TPS, carcinoembryonic antigen (CEA), CYFRA21-1 and STNFR in patients with lung cancer. The serum levels of TPS, CEA, CYFRA21-1 and STNFR were determined in 72 patients with lung cancer, 54 patients with pulmonary benign diseases and 32 healthy adults by enzyme-linked immunosorbent assay (ELISA). The levels of the four tumor markers in lung cancer group were significantly higher than those in benign disease group (P < 0.005) and healthy control group (P < 0.001). Among the four markers, STNFR had the highest sensitivity (81.9%), CYFRA21-1 had the highest specificity (91.5%) and TPS had the highest accuracy (83.5%). TPS, CYFRA21-1 and STNFR can be used as very useful and sensitive tumor markers in the diagnosis of lung cancer, in which CYFRA21-1 may be the most useful tumor marker for clinical application.

Surface expression of heterogeneous nuclear RNA binding protein M4 on Kupffer cell relates to its function as a carcinoembryonic antigen receptor.

PubMed

Bajenova, Olga; Stolper, Eugenia; Gapon, Svetlana; Sundina, Natalia; Zimmer, Regis; Thomas, Peter

2003-11-15

Elevated concentrations of carcinoembryonic antigen (CEA) in the blood are associated with the development of hepatic metastases from colorectal cancers. Clearance of circulating CEA occurs through endocytosis by liver macrophages, Kupffer cells. Previously we identified heterogeneous nuclear ribonucleoproteins M4 (hnRNP M4) as a receptor (CEAR) for CEA. HnRNP M4 has two isoform proteins (p80, p76), the full-length hnRNP M4 (CEARL) and a truncated form (CEARS) with a deletion of 39 amino acids between RNA binding domains 1 and 2, generated by alternative splicing. The present study was undertaken to clarify any isoform-specific differences in terms of their function as CEA receptor and localization. We develop anti-CEAR isoform-specific antibodies and show that both CEAR splicing isoforms are expressed on the surface of Kupffer cells and can function as CEA receptor. Alternatively, in P388D1 macrophages CEARS protein has nuclear and CEARL has cytoplasmic localization. In MIP101 colon cancer and HeLa cells the CEARS protein is localized to the nucleus and CEARL to the cytoplasm. These findings imply that different functions are assigned to CEAR isoforms depending on the cell type. The search of 39 amino acids deleted region against the Prosite data base revealed the presence of N-myristylation signal PGGPGMITIP that may be involved in protein targeting to the plasma membrane. Overall, this report demonstrates that the cellular distribution, level of expression, and relative amount of CEARL and CEARS isoforms determine specificity for CEA binding and the expression of alternative spliced forms of CEAR is regulated in a tissue-specific manner.

Reference Intervals of Alpha-Fetoprotein and Carcinoembryonic Antigen in the Apparently Healthy Population.

PubMed

Zhang, Gao-Ming; Guo, Xu-Xiao; Ma, Xiao-Bo; Zhang, Guo-Ming

2016-12-12

BACKGROUND The aim of this study was to calculate 95% reference intervals and double-sided limits of serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI EP28-A3 guideline. MATERIAL AND METHODS Serum AFP and CEA values were measured in samples from 26 000 healthy subjects in the Shuyang area receiving general health checkups. The 95% reference intervals and upper limits were calculated by using MedCalc. RESULTS We provided continuous reference intervals from 20 years old to 90 years old for AFP and CEA. The reference intervals were: AFP, 1.31-7.89 ng/ml (males) and 1.01-7.10 ng/ml (females); CEA, 0.51-4.86 ng/ml (males) and 0.35-3.45ng/ml (females). AFP and CEA were significantly positively correlated with age in both males (r=0.196 and r=0.198) and females (r=0.121 and r=0.197). CONCLUSIONS Different races or populations and different detection systems may result in different reference intervals for AFP and CEA. Continuous reference intervals of age changes are more accurate than age groups.

Nanogold-enwrapped graphene nanocomposites as trace labels for sensitivity enhancement of electrochemical immunosensors in clinical immunoassays: Carcinoembryonic antigen as a model.

PubMed

Zhong, Zhaoyang; Wu, Wei; Wang, Dong; Wang, Dan; Shan, Jinlu; Qing, Yi; Zhang, Zhimin

2010-06-15

A new, highly sensitive electrochemical immunosensor with a sandwich-type immunoassay format was designed to quantify carcinoembryonic antigen (CEA), as a model tumor marker, using nanogold-enwrapped graphene nanocomposites (NGGNs) as trace labels in clinical immunoassays. The device consisted of a glassy carbon electrode coated with Prussian Blue (PB) on whose surface gold nanoparticles were electrochemically deposited to the further modified with the specific analyte-capturing molecule, anti-CEA antibodies. The immunoassay was performed using horseradish peroxidase (HRP)-conjugated anti-CEA as secondary antibodies attached on the NGGN surface (HRP-anti-CEA-NGGN). The method using HRP-anti-CEA-NGGNs as detection antibodies shows high signal amplification, and exhibits a dynamic working range of 0.05-350 ng/mL with a low detection limit of 0.01 ng/mL CEA (at 3s). The assayed results of serum samples with the sensor received an acceptable agreement with the reference values. Importantly, the methodology provides a promising ultrasensitive assay strategy for clinical applications. Copyright 2010 Elsevier B.V. All rights reserved.

Induction of carcinoembryonic antigen expression in a three-dimensional culture system

NASA Technical Reports Server (NTRS)

Jessup, J. M.; Brown, D.; Fitzgerald, W.; Ford, R. D.; Nachman, A.; Goodwin, T. J.; Spaulding, G.

1994-01-01

MIP-101 is a poorly differentiated human colon carcinoma cell line established from ascites that produces minimal amounts of carcinoembryonic antigen (CEA), a 180 kDa glycoprotein tumor marker, and nonspecific cross-reacting antigen (NCA), a related protein that has 50 and 90 kDa isoforms, in vitro in monolayer culture. MIP-101 produces CEA when implanted into the peritoneum of nude mice but not when implanted into subcutaneous tissue. We tested whether MIP-101 cells may be induced to express CEA when cultured on microcarrier beads in three-dimensional cultures, either in static cultures as non-adherent aggregates or under dynamic conditions in a NASA-designed low shear stress bioreactor. MIP- 101 cells proliferated well under all three conditions and increased CEA and NCA production 3 - 4 fold when grown in three-dimensional cultures compared to MIP-101 cells growing logarithmically in monolayers. These results suggest that three-dimensional growth in vitro simulates tumor function in vivo and that three-dimensional growth by itself may enhance production of molecules that are associated with the metastatic process.

AuNPs/CNOs/SWCNTs/chitosan-nanocomposite modified electrochemical sensor for the label-free detection of carcinoembryonic antigen.

PubMed

Rizwan, Mohammad; Elma, Syazwani; Lim, Syazana Abdullah; Ahmed, Minhaz Uddin

2018-06-01

In this work, a nanocomposite of gold nanoparticles (AuNPs), carbon nano-onions (CNOs), single-walled carbon nanotubes (SWCNTs) and chitosan (CS) (AuNPs/CNOs/SWCNTs/CS) was prepared for the development of highly sensitive electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA), clinical tumor marker. Firstly, layer-by-layer fabrication of the CEA-immunosensors was studied using cyclic voltammetry (CV) and square wave voltammetry (SWV). By combining the advantages of large surface area and electronic properties of AuNPs, CNOs, SWCNTs, and film forming properties of CS, AuNPs/CNOs/SWCNTs/CS-nanocomposite-modified glassy carbon electrode showed a 200% increase in effective surface area and electronic conductivity. The calibration plot gave a negative linear relationship between log[concentration] of CEA and electrical current with a correlation coefficient of 0.9875. The CEA-immunosensor demonstrated a wide linear detection range of 100 fg mL -1 to 400 ng mL -1 with a low detection limit of 100 fg mL -1 . In addition to high sensitivity, reproducibility and large stability, CEA-immunosensor provided an excellent selectivity and resistant-to-interference in the presence of other antigens in serum and hence a potential to be used with real samples. Copyright © 2018 Elsevier B.V. All rights reserved.

[Predictive value of serum carcinoembryonic antigen level in efficacy and prognosis for patients with rectal cancer following preoperative radiochemotherapy].

PubMed

Zhang, Dakui; Zhan, Tiancheng; Li, Ming; Gu, Jin

2017-05-25

To examine the association of preoperative carcinoembryonic antigen (CEA) level with the efficacy of neoadjuvant radiochemotherapy and postoperative metastasis and relapse in patients with rectal cancer. Between January 2011 and January 2014, 325 patients with local advanced rectal cancer underwent preoperative radiochemotherapy and radical operation in Department of Colorectal Cancer Surgery, Beijing University Cancer Hospital, including 194 males and 131 females. According to preoperative MRI, all the patients suffered from clinical T3-4 tumors or positive lymph nodes. Their Zubrod-ECOG-WHO score was 0-1. These patients received preoperative intensity modulated radiotherapy which consisted of 50.6 Gy in 22 fractions (IMRT GTV 50.6 Gy/CTV 41.8 Gy/22 f) with capecitabine(825 mg/m 2 , twice per day) as radiosensitizer. According to the preoperative serum CEA level, patients were divided into high group (125 cases) and normal group (200 cases). In high group, serum CEA level decreased into normal range in 60 patients (high-normal group) after radiochemotherapy, while it was still in high level in other 65 patients (high-high group). The differences in sensitivity to radiochemotherapy and 3-year disease free survival (DFS) of these patients were both evaluated. In high group and normal group, the complete response rates were 18.4% (23/125) and 17.5% (35/200) (χ 2 =0.319, P=0.660); the percentages of tumor regression grade(TRG) 0-1 patients were 68.0%(85/125) and 67.5%(135/200)(χ 2 =0.009, P=0.925); the T downstage rates were 63.2%(79/125) and 70.0%(140/200)(χ 2 =1.266, P=0.274), respectively, whose differences were all not significant. The 3-year DFS rate in high group was 62.4%, which was significantly lower than 93.5% in normal group (χ 2 =53.147, P=0.000). There were 65 patients in high-high group, accounting for 52% (65/125) of high group. Among these 65 patients, 44(67.7%) presented recurrence and metastasis within 3 years and the 3-year DFS was 32.3%, which was much lower than 95.0% of 60 patients in high-normal group(χ 2 =182.085, P=0.000). Preoperative serum CEA level may not be used to predict tumor response of rectal cancer patients who receive preoperative radiochemotherapy. However, the prognosis of patients with high CEA level is worse. Recurrence and metastasis are more likely to occur in patients with high CEA level after radiochemotherapy.

Hookah smoking and cancer: carcinoembryonic antigen (CEA) levels in exclusive/ever hookah smokers.

PubMed

Sajid, Khan Mohammad; Chaouachi, Kamal; Mahmood, Rubaida

2008-05-24

We have recently published some work on CEA levels in hookah (also called narghile, shisha elsewhere) and cigarette smokers. Hookah smokers had higher levels of CEA than non-smokers although mean levels were low compared to cigarette smokers. However some of them were also users of other tobacco products (cigarettes, bidis, etc.). To find serum CEA levels in ever/exclusive hookah smokers, i.e. those who smoked only hookah (no cigarettes, bidis, etc.), prepared between 1 and 4 times a day with a quantity of up to 120 g of a tobacco-molasses mixture each (i.e. the tobacco weight equivalent of up to 60 cigarettes of 1 g each) and consumed in 1 to 8 sessions. Enhanced chemiluminescent immunometric technique was applied to measure CEA levels in serum samples from 59 exclusive male smokers with age ranging from 20-80 years (mean = 58.8 +/- 14.7 years) and 8-65 years of smoking (mean = 37.7 +/- 16.8). 36 non-smokers served as controls. Subjects were divided into 3 groups according to the number of preparations; the number of sessions and the total daily smoking time: Light (1; 1; < or = 20 minutes); Medium (1-3; 1-3; >20 min to < or = 2 hrs) and Heavy smokers (2-4; 3-8; >2 hrs to < or = 6 hrs). Because of the nature of distribution of CEA levels among our individuals, Wilcoxon's rank sum two-sample test was applied to compare the variables. The overall CEA levels in exclusive hookah smokers (mean: 3.58 +/- 2.61 ng/ml; n = 59) were not significantly different (p < or = 0.0937) from the levels in non-smokers (2.35 +/- 0.71 ng/ml). Mean levels in light, medium and heavy smokers were: 1.06 +/- 0.492 ng/ml (n = 5); 2.52 +/- 1.15 ng/ml (n = 28) and 5.11 +/- 3.08 ng/ml (n = 26) respectively. The levels in medium smokers and non-smokers were also not significantly different (p < or = 0.9138). In heavy smokers, the CEA levels were significantly higher than in non-smokers (p < or = 0.0001567). Overall CEA levels in exclusive hookah smokers were low compared to cigarette smokers. However, heavy hookah smoking substantially raises CEA levels. Low-nitrosamines smokeless tobacco of the SNUS Swedish type could be envisaged as an alternative to smoking for this category of users and also, in a broad harm reduction perspective, to the prevalent low-quality moist snuff called naswar.

[Clinical and prognostic significance of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer].

PubMed

Chen, Yan; Zheng, Yu-hong; Lin, Ying-ying; Hu, Min-hua; Chen, Yan-song

2011-11-01

To investigate the clinical and prognostic values of preoperative serum CA153, CEA and TPS levels in patients with primary breast cancer. A total of 386 hospitalized patients with stage I ∼ IV breast cancer from Nov 1998 to Feb 2009 were followed up, and their clinicopathological data were analyzed retrospectively to determine the factors affecting their prognosis. First, preoperative serum CA153 expression level was significantly associated with the age of onset and tumor size (P < 0.05), the expression of serum CEA was correlated with tumor size (P < 0.05), and the expression of serum tissue polypeptide specific antigen (TPS) was correlated with tumor size and lymph node metastases (P < 0.05). Second, the overall survival was significantly shorter among patients with elevated serum CA153, CEA or TPS, respectively (P < 0.05 for overall). Finally, multivariate Cox regression analysis indicated that estrogen receptor status (ER) and elevated preoperative values of CA 153 are independent prognostic factors for overall survival (P < 0.05), and CA 153 is a risk factor but estrogen receptor status is a protective factor for overall survival. Higher preoperative expression of serum CA153, CEA or TPS is closely correlated with clinicopathological characteristics and overall survival. The prognosis is poorer in primary breast cancer patients with higher CA15-3 expression level, and pre-treatment CA153 expression level can be used as an independent prognostic parameter in patients with primarily breast cancer.

Deterministic Role of CEA and MSI Status in Predicting Outcome of CRC Patients: a Perspective Study Amongst Hospital Attending Eastern Indian Populations.

PubMed

Koyel, Banerjee; Priyabrata, Das; Rittwika, Bhattacharya; Swati, Dasgupta; Soma, Mukhopadhyay; Jayasri, Basak; Ashis, Mukhopadhyay

2017-12-01

Carcinoembryonic antigen (CEA) is an important deterministic factor in predicting colorectal carcinoma (CRC) progression. It is also evident that microsatellite instability (MSI) which results in a hypermutable phenotype of genomic DNA is common in CRC. Owing to the scarcity of reports from India, our aim of this study was to understand the clinicopathological correlations of CEA status with surgery and chemotherapy, correlate the same with socio-demographic status of the patients, determine the MSI status amongst them and understand the prognostic implications of CEA and MSI as CRC progression marker amongst patients. The serum CEA level was estimated by chemiluminescence assay (CLIA). Serum liver enzyme assay was carried out following the manufacturer's instructions using auto-analysers (E. Merck and Sera mol. Health Care, India). MSI analysis was carried out by PCR-SSCP. From our study, most frequently detected colorectal cancer was in 40-49 years age group (25.26%) with 61.05% male and 38.95% females. CEA showed a significant association with higher TNM staging, tumour size, smoking habit and MSI status ( p  < 0.05) but not with sex and site of cancer ( p  > 0.05). After surgery and chemotherapy, CEA and WBCs were decreased significantly ( p  < 0.05), while liver enzymes did not change significantly ( p  > 0.05). Overall, microsatellite instability was observed in approximately 40% of the populations. From our study, it was also evident that for both, MSI and abnormal CEA level predicted poor prognosis for the patient (by using Kaplan-Meier survival analysis; p  = 0.04). Thus, CEA and initial MSI status can be used as prognostic markers of CRC.

Serum carcinoembryonic antigen levels before initial treatment are associated with EGFR mutations and EML4- ALK fusion gene in lung adenocarcinoma patients.

PubMed

Wang, Wen-Tao; Li, Yin; Ma, Jie; Chen, Xiao-Bing; Qin, Jian-Jun

2014-01-01

Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. Tumor marker levels before first treatment were measured by electrochemiluminescence immunoassay. EGFR mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that a higher serum CEA level before the initial treatment was independently associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In concordance with previous reports, younger age was a clinical feature for these (P=0.008). Seven of the positive cases were never smokers, and no coexistence with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5 ng/ml seemed to be higher than patients with a concentration over 5 ng/ml (P=0.021). No significant difference was observed for time to progression and overall survival between EML4-ALK-positive group and EML4-ALK-negative group or between patients with and without an EGFR mutation. The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.

Association of Preoperative and Postoperative Serum Carcinoembryonic Antigen and Colon Cancer Outcome.

PubMed

Konishi, Tsuyoshi; Shimada, Yoshifumi; Hsu, Meier; Tufts, Lauren; Jimenez-Rodriguez, Rosa; Cercek, Andrea; Yaeger, Rona; Saltz, Leonard; Smith, J Joshua; Nash, Garrett M; Guillem, José G; Paty, Philip B; Garcia-Aguilar, Julio; Gonen, Mithat; Weiser, Martin R

2018-03-01

Guidelines recommend measuring preoperative carcinoembryonic antigen (CEA) in patients with colon cancer. Although persistently elevated CEA after surgery has been associated with increased risk for metastatic disease, prognostic significance of elevated preoperative CEA that normalized after resection is unknown. To investigate whether patients with elevated preoperative CEA that normalizes after colon cancer resection have a higher risk of recurrence than patients with normal preoperative CEA. This retrospective cohort analysis was conducted at a comprehensive cancer center. Consecutive patients with colon cancer who underwent curative resection for stage I to III colon adenocarcinoma at the center from January 2007 to December 2014 were identified. Patients were grouped into 3 cohorts: normal preoperative CEA, elevated preoperative but normalized postoperative CEA, and elevated preoperative and postoperative CEA. Three-year recurrence-free survival (RFS) and hazard function curves over time were analyzed. A total of 1027 patients (461 [50.4%] male; median [IQR] age, 64 [53-75] years) were identified. Patients with normal preoperative CEA had 7.4% higher 3-year RFS (n = 715 [89.7%]) than the combined cohorts with elevated preoperative CEA (n = 312 [82.3%]) (P = .01) but had RFS similar to that of patients with normalized postoperative CEA (n = 142 [87.9%]) (P = .86). Patients with elevated postoperative CEA had 14.9% lower RFS (n = 57 [74.5%]) than the combined cohorts with normal postoperative CEA (n = 857 [89.4%]) (P = .001). The hazard function of recurrence for elevated postoperative CEA peaked earlier than for the other cohorts. Multivariate analyses confirmed that elevated postoperative CEA (hazard ratio [HR], 2.0; 95% CI, 1.1-3.5), but not normalized postoperative CEA (HR, 0.77; 95% CI, 0.45-1.30), was independently associated with shorter RFS. Elevated preoperative CEA that normalizes after resection is not an indicator of poor prognosis. Routine measurement of postoperative, rather than preoperative, CEA is warranted. Patients with elevated postoperative CEA are at increased risk for recurrence, especially within the first 12 months after surgery.

The diagnostic value of serum tumor markers CEA, CA19-9, CA125, CA15-3, and TPS in metastatic breast cancer.

PubMed

Wang, Weigang; Xu, Xiaoqin; Tian, Baoguo; Wang, Yan; Du, Lili; Sun, Ting; Shi, Yanchun; Zhao, Xianwen; Jing, Jiexian

2017-07-01

This study aims to understand the diagnostic value of serum tumor markers carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), cancer antigen 15-3 (CA15-3), and tissue polypeptide-specific antigen (TPS) in metastatic breast cancer (MBC). A total of 164 metastatic breast cancer patients in Shanxi Cancer Hospital were recruited between February 2016 and July 2016. 200 breast cancer patients without metastasis in the same period were randomly selected as the control group. The general characteristics, immunohistochemical, and pathological results were investigated between the two groups, and tumor markers were determined. There were statistical differences in the concentration and the positive rates of CEA, CA19-9, CA125, CA15-3, and TPS between the MBC and control group (P<0.05). The highest sensitivity was in CEA and the highest specificity was in CA125 for the diagnosis of MBC when using a single tumor marker at 56.7% and 97.0%, respectively. In addition, two tumor markers were used for the diagnosis of MBC and the CEA and TPS combination had the highest diagnostic sensitivity with 78.7%, while the CA15-3 and CA125 combination had the highest specificity of 91.5%. Analysis of tumor markers of 164 MBC found that there were statistical differences in the positive rates of CEA and CA15-3 between bone metastases and other metastases (χ 2 =6.00, P=0.014; χ 2 =7.32, P=0.007, respectively). The sensitivity and specificity values of the CEA and CA15-3 combination in the diagnosis of bone metastases were 77.1% and 45.8%, respectively. The positive rate of TPS in the lung metastases group was lower than in other metastases (χ 2 =8.06, P=0.005).There were significant differences in the positive rates of CA15-3 and TPS between liver metastases and other metastases (χ 2 =15.42, P<0.001; χ 2 =9.72, P=0.002, respectively). The sensitivity and specificity of the CA15-3 and TPS combination in the diagnosis of liver metastases were 92.3% and 45.6%, respectively, and the positive rate of CEA in triple-negative metastatic breast cancer is lower than in other subtypes (χ 2 =4.80, P=0.028). Therefore, serum CEA, CA19-9, CA125, CA15-3, and TPS can be used in the diagnosis of MBC, and different combinations of tumor markers have varying diagnostic value. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of CEA in human serum using surface-enhanced Raman spectroscopy coupled with antibody-modified Au and γ-Fe₂O₃@Au nanoparticles.

PubMed

Lin, Yan; Xu, Guanhong; Wei, Fangdi; Zhang, Aixia; Yang, Jing; Hu, Qin

2016-03-20

In this present work, a rapid and simple method to detect carcinoembryonic antigen (CEA) was developed by using surface-enhanced Raman spectroscopy (SERS) coupled with antibody-modified Au and γ-Fe2O3@Au nanoparticles. First, Au@Raman reporter and γ-Fe2O3@Au were prepared, and then modified with CEA antibody. When CEA was present, the immuno-Au@Raman reporter and immuno-γ-Fe2O3@Au formed a complex through antibody-antigen-antibody interaction. The selective and sensitive detection of CEA could be achieved by SERS after magnetic separation. Under the optimal conditions, a linear relationship was observed between the Raman peak intensity and the concentration of CEA in the range of 1-50 ng mL(-1) with an excellent correlation coefficient of 0.9942. The limit of detection based on two times ratio of signal to noise was 0.1 ng/mL. The recoveries of CEA standard solution spiked with human serum samples were in the range of 88.5-105.9% with the relative standard deviations less than 17.4%. The method built was applied to the detection of CEA in human serum, and the relative deviations of the analysis results between the present method and electrochemiluminescence immunoassay were all less than 16.6%. The proposed method is practical and has a potential for clinic test of CEA. Copyright © 2016 Elsevier B.V. All rights reserved.

Imaging of a parapharyngeal hemangiopericytoma. Radioimmunoscintigraphy (SPECT) with indium-111-labeled anti-CEA antibody, and comparison to digital subtraction angiography, computed tomography, and immunohistochemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kairemo, K.J.; Hopsu, E.V.; Melartin, E.J.

1991-01-01

A 27-year-old male patient with a parapharyngeal hemangiopericytoma was investigated radiologically with orthopantomography, computed tomography, and digital subtraction angiography before the operation. Because a malignancy was suspected, the patient was imaged with gamma camera using radiolabeled monoclonal anticarcinoembryonal antigen antibody including single photon emission computed tomography. The radioantibody accumulated strongly into the neoplasm. Tumor to background ratio was 2.2. Samples of the excised tumor were stained immunohistochemically for desmin, vimentin, muscle actin, cytokeratin, CEA (carcinoembryonic antigen), and factor VIII. They showed that the antibody uptake was of unspecific nature and not due to CEA expression in the tumor.

Diagnostic test pepsinogen I and combination with tumor marker CEA in gastric cancer

NASA Astrophysics Data System (ADS)

Sembiring, J.; Sarumpaet, K.; Ganie, R. A.

2018-03-01

Gastric cancer (GC) is the fifth leading cause of cancer and the third leading cause of cancer-related mortality globally. Human pepsinogens (HP) are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and GC. HP are biochemically and immunochemically classified into two groups: pepsinogen I (PG I) and PG II. Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in normal mucosal cells but increased amounts are associated with adenocarcinoma, especially colorectal cancer. CEA in combination with other tumour markers can be used in pre-operative staging and thereby assist in the planning of the type of surgery required and future management options. The purpose of this study was to diagnose test PG I and combination with tumor marker CEA in 32 patients suspected with GC. There was a significant difference in levels of CEA between GC group with non-GC with a value p <0.001. PGI sensitivity was 70.58% and specificity 93.3%. The sensitivity of PGI and CEA combination of 94.1% and specificity 80%. The area of AUC obtained was 92.7% at 95% confidence interval (82.7-100%). This AUC value indicated that the value of diagnostic accuracy of the PGI and CEA combinations of 92.7%.

Evaluation of serum CA27.29, CA15-3 and CEA in patients with breast cancer.

PubMed

Hou, M F; Chen, Y L; Tseng, T F; Lin, C M; Chen, M S; Huang, C J; Huang, Y S; Hsieh, J S; Huang, T J; Jong, S B; Huang, Y F

1999-09-01

The Truquant BR radioimmunoassay (RIA) using monoclonal antibody BR 27.29 to recognize a peptide sequence on the MUC-1 gene product for quantification of the CA 27.29 antigen in serum was used in this report to evaluate in 145 patients with breast cancer and compared the other conventional serum markers such as CA15-3 and CEA. The upper limit of normal (25 u/ml) was determined from CA27.29 values 12.4 +/- 4.1 u/ml (mean +/- 3 S.D.) for 112 female subjects apparently free of disease. The CA15-3 levels above 25 u/ml and CEA levels above 5 ng/ml were considered positive values. Thirty-seven cases of 145 patients studied had elevated CA 27.29 levels (sensitivity: 25.5%), 35 of 145 had positive CA15-3 levels (sensitivity 24.1%) and 27 of 145 patients had positive CEA levels (sensitivity: 18.6%) (p < 0.05). One hundred and ten cases of the breast cancer patients (75.8%) did not have metastatic disease. In this group CA 27.29 sensitivity was 6.4%, while CA15-3 sensitivity was 5.5% and CEA sensitivity was 4.5% (p > 0.05). Mean values were 10.2 +/- 9.2 u/ml for CA 27.29, 14.1 +/- 5.6 u/ml for CA 15-3 and 1.7 +/- 1.5 ng/ml for CEA. Thirty-five patients (24.2%) had metastatic disease. In this group CA 27.29 sensitivity was 85.7%, CA15-3 sensitivity was 82.8% and CEA sensitivity was 62.8% (p < 0.05). Mean values for CA27.29 was 152.6 +/- 131.6 u/ml, CA15-3 was 123.1 +/- 107.6 u/ml and 21.8 +/- 36.9 ng/ml of CEA. With regard to the correlation of three tumor markers with clinical stages, patients had significantly higher levels of CA27.29 than CEA, but they were similar to CA 15-3 in metastatic breast cancer. These results suggest CA27.29 to be more sensitive and specific than CEA, but that it is similar to CA15-3 for metastatic breast cancer detection and monitoring.

Carcinoembryonic antigen induces signal transduction in Kupffer cells.

PubMed

Gangopadhyay, A; Lazure, D A; Thomas, P

1997-09-16

Carcinoembryonic antigen (CEA), an intercellular adhesion molecule and a mediator of hepatic metastasis, is processed by an 80 kDa receptor on murine and human Kupffer cells in the liver. Activation of rat Kupffer cells in vitro by CEA via the 80 kDa receptor produced cytokines IL-1alpha and TNF-alpha which involved tyrosine phosphorylation. The peak response of TNF-alpha was 5.6 times greater than the corresponding IL-1alpha response and was associated with enhanced tyrosine phosphorylation of 108 and 125 kDa proteins. Lipopolysaccharide (LPS) treatment, on the other hand, phosphorylated two major proteins with MW of 93 and 119 kDa associated with the loss of phosphorylation from a 125 kDa protein. Results demonstrate that CEA-induced IL-1alpha and TNF-alpha production involves tyrosine phosphorylation and the signaling in CEA treated cells is different than that seen with LPS stimulation.

Measurement of four tumor marker antigens in the sera of pregnant women.

PubMed

Cheli, C D; Morris, D L; Neaman, I E; Dai, J; Allard, W J; Yeung, K K

1999-01-01

We sought to determine the maternal serum levels of four tumor-associated antigens during the three trimesters of pregnancy in healthy women. CEA, CA 228, CA 15-3, and Her2/neu oncogene product p105 assay values were determined for 90 healthy pregnant women during the three trimesters of pregnancy at five participating evaluation sites. Results were compared to means and cut-off values determined for healthy nonpregnant women. Differences in assay values in the 1st and 3rd trimester were analyzed for statistical significance (Student's t-test). CEA, CA 228 and CA 15-3 assay values in general were found to be within the normal range. CA 15-3 and Her2/neu p105 serum assay values were above the cut-off (3.3% and 8.2%, respectively) and were significantly elevated in the 3rd trimester as compared to the 1st trimester of pregnancy (P < 0.05 and P < 0.001, respectively). CEA and CA 228 may be of potential value in monitoring pregnant women with malignant disease. Normal elevations in 3rd trimester serum Her2/neu p105 and CA 15-3 assay values should be considered when monitoring a pregnant patient with malignant disease.

Introduction to the CEA family: structure, function and secretion.

PubMed

Von Kleist, S

1992-01-01

Due to the phenomenal progress in the field of tumor immunology that took place during the last twenty years, we dispose today of highly specific and sensitive techniques and reagents like monoclonal antibodies (MAbs). In this context the discovery in human carcinomas of tumor-associated antigens, such as CEA, was of primary importance, especially since the latter was found to have clinical relevance as a tumor marker. Based on animal models, a new in vivo technology for the detection of tumors and metastases was developed in recent years, that uses anti-CEA MAbs, or fragments of them, coupled to radio-isotopes. This technique, called radio-immunodetection (RAID), also paved the way for immunotherapeutic procedures, where again CEA served as the target-antigen. This new technique holds great promise, provided the epitope-specificity of the MAbs is well-controlled: it has been shown that CEA belongs to a large gene-family of at least 22 members, which can be subdivided into two subgroups (i.e., the CEA- and the PSG-subgroup) and which in turn belongs to the immunoglobulin-supergene family. Great structural similarities render the distinction of the various cross-reactive molecules by immunological means rather difficult.

Reference Intervals of Alpha-Fetoprotein and Carcinoembryonic Antigen in the Apparently Healthy Population

PubMed Central

Zhang, Gao-Ming; Guo, Xu-Xiao; Ma, Xiao-Bo; Zhang, Guo-Ming

2016-01-01

Background The aim of this study was to calculate 95% reference intervals and double-sided limits of serum alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) according to the CLSI EP28-A3 guideline. Material/Methods Serum AFP and CEA values were measured in samples from 26 000 healthy subjects in the Shuyang area receiving general health checkups. The 95% reference intervals and upper limits were calculated by using MedCalc. Results We provided continuous reference intervals from 20 years old to 90 years old for AFP and CEA. The reference intervals were: AFP, 1.31–7.89 ng/ml (males) and 1.01–7.10 ng/ml (females); CEA, 0.51–4.86 ng/ml (males) and 0.35–3.45ng/ml (females). AFP and CEA were significantly positively correlated with age in both males (r=0.196 and r=0.198) and females (r=0.121 and r=0.197). Conclusions Different races or populations and different detection systems may result in different reference intervals for AFP and CEA. Continuous reference intervals of age changes are more accurate than age groups. PMID:27941709

Radiocurability by Targeting Tumor Necrosis Factor-{alpha} Using a Bispecific Antibody in Carcinoembryonic Antigen Transgenic Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larbouret, Christel; Robert, Bruno; Linard, Christine

2007-11-15

Purpose: Tumor necrosis factor-{alpha} (TNF-{alpha}) enhances radiotherapy (RT) killing of tumor cells in vitro and in vivo. To overcome systemic side effects, we used a bispecific antibody (BsAb) directed against carcinoembryonic antigen (CEA) and TNF-{alpha} to target this cytokine in a CEA-expressing colon carcinoma. We report the evaluation of this strategy in immunocompetent CEA-transgenic mice. Methods and Materials: The murine CEA-transfected colon carcinoma MC-38 was used for all experiments. In vitro, clonogenic assays were performed after RT alone, TNF-{alpha} alone, and RT plus TNF-{alpha}. In vivo, the mice were randomly assigned to treatment groups: control, TNF-{alpha}, BsAb, BsAb plus TNF-{alpha},more » RT, RT plus TNF-{alpha}, and RT plus BsAb plus TNF-{alpha}. Measurements of endogenous TNF-{alpha} mRNA levels and evaluation of necrosis (histologic evaluation) were assessed per treatment group. Results: In vitro, combined RT plus TNF-{alpha} resulted in a significant decrease in the survival fraction at 2 Gy compared with RT alone (p < 0.00001). In vivo, we observed a complete response in 5 (50%) of 10, 2 (20%) of 10, 2 (18.2%) of 11, and 0 (0%) of 12 treated mice in the RT plus BsAb plus TNF-{alpha}, RT plus TNF-{alpha}, RT alone, and control groups, respectively. This difference was statistically significant when TNF-{alpha} was targeted with the BsAb (p = 0.03). The addition of exogenous TNF-{alpha} to RT significantly increased the endogenous TNF-{alpha} mRNA level, particularly when TNF-{alpha} was targeted with BsAb (p < 0.01). The percentages of necrotic area were significantly augmented in the RT plus BsAb plus TNF-{alpha} group. Conclusion: These results suggest that targeting TNF-{alpha} with the BsAb provokes RT curability in a CEA-expressing digestive tumor syngenic model and could be considered as a solid rationale for clinical trials.« less

Cancer imaging with CEA antibodies: historical and current perspectives.

PubMed

Goldenberg, D M

1992-01-01

This article reviews the history and status of cancer imaging with radiolabeled antibodies against carcinoembryonic antigen (CEA). Although CEA and many other cancer-associated antigens are not distinct for neoplasia, the quantitative increase of these markers in malignant tissues provides a sufficient differential for selective antibody targeting. Animal studies with xenografted human tumors provided the first evidence of the prospects of this technology, followed by initial clinical success with purified goat whole IgG antibodies to CEA, labeled with 131I and with the use of dual-isotope subtraction methods. Subsequently, improved and earlier imaging could be accomplished with monoclonal antibody fragments, which then would permit the use of shorter-lived radionuclides, such as 111In, 123I, and 99mTc. The preferred use of a monoclonal anti-CEA IgG Fab' fragment, labeled with 99mTc by a recently developed, simple and rapid kit, has enabled the detection of small lesions, including those in the liver, within 4 h of injection. By means of SPECT imaging, a high sensitivity and specificity for RAID could be achieved.

Hexapeptide fragment of carcinoembryonic antigen which acts as an agonist of heterogeneous ribonucleoprotein M.

PubMed

Palermo, Nicholas Y; Thomas, Peter; Murphy, Richard F; Lovas, Sándor

2012-04-01

Colorectal cancers with metastatic potential secrete the glycoprotein carcinoembryonic antigen (CEA). CEA has been implicated in colorectal cancer metastasis by inducing Kupffer cells to produce inflammatory cytokines which, in turn, make the hepatic micro-environment ideal for tumor cell implantation. CEA binds to the heterogeneous ribonucleoprotein M (hnRNP M) which acts as a cell surface receptor in Kupffer cells. The amino acid sequence in CEA, which binds the hnRNP M receptor, is Tyr-Pro-Glu-Leu-Pro-Lys. In this study, the structure of Ac-Tyr-Pro-Glu-Leu-Pro-Lys-NH₂ (YPELPK) was investigated using electronic circular dichroism, vibrational circular dichroism, and molecular dynamics simulations. The binding of the peptide to hnRNP M was also investigated using molecular docking calculations. The biological activity of YPELPK was studied using differentiated human THP-1 cells, which express hnRNP M on their surface and secrete IL-6 when stimulated by CEA. YPELPK forms a stable polyproline-II helix and stimulates IL-6 production of THP-1 cells at micromolar concentrations. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

Hookah smoking and cancer: carcinoembryonic antigen (CEA) levels in exclusive/ever hookah smokers

PubMed Central

Sajid, Khan Mohammad; Chaouachi, Kamal; Mahmood, Rubaida

2008-01-01

Background We have recently published some work on CEA levels in hookah (also called narghile, shisha elsewhere) and cigarette smokers. Hookah smokers had higher levels of CEA than non-smokers although mean levels were low compared to cigarette smokers. However some of them were also users of other tobacco products (cigarettes, bidis, etc.). Objectives To find serum CEA levels in ever/exclusive hookah smokers, i.e. those who smoked only hookah (no cigarettes, bidis, etc.), prepared between 1 and 4 times a day with a quantity of up to 120 g of a tobacco-molasses mixture each (i.e. the tobacco weight equivalent of up to 60 cigarettes of 1 g each) and consumed in 1 to 8 sessions. Methods Enhanced chemiluminescent immunometric technique was applied to measure CEA levels in serum samples from 59 exclusive male smokers with age ranging from 20–80 years (mean = 58.8 ± 14.7 years) and 8–65 years of smoking (mean = 37.7 ± 16.8). 36 non-smokers served as controls. Subjects were divided into 3 groups according to the number of preparations; the number of sessions and the total daily smoking time: Light (1; 1; ≤ 20 minutes); Medium (1–3; 1–3; >20 min to ≤ 2 hrs) and Heavy smokers (2–4; 3–8; >2 hrs to ≤ 6 hrs). Because of the nature of distribution of CEA levels among our individuals, Wilcoxon's rank sum two-sample test was applied to compare the variables. Results The overall CEA levels in exclusive hookah smokers (mean: 3.58 ± 2.61 ng/ml; n = 59) were not significantly different (p ≤ 0.0937) from the levels in non-smokers (2.35 ± 0.71 ng/ml). Mean levels in light, medium and heavy smokers were: 1.06 ± 0.492 ng/ml (n = 5); 2.52 ± 1.15 ng/ml (n = 28) and 5.11 ± 3.08 ng/ml (n = 26) respectively. The levels in medium smokers and non-smokers were also not significantly different (p ≤ 0.9138). In heavy smokers, the CEA levels were significantly higher than in non-smokers (p ≤ 0.0001567). Conclusion Overall CEA levels in exclusive hookah smokers were low compared to cigarette smokers. However, heavy hookah smoking substantially raises CEA levels. Low-nitrosamines smokeless tobacco of the SNUS Swedish type could be envisaged as an alternative to smoking for this category of users and also, in a broad harm reduction perspective, to the prevalent low-quality moist snuff called naswar. PMID:18501010

Capillary electrophoresis-chemiluminescence detection for carcino-embryonic antigen based on aptamer/graphene oxide structure.

PubMed

Zhou, Zi-Ming; Feng, Zhe; Zhou, Jun; Fang, Bi-Yun; Qi, Xiao-Xiao; Ma, Zhi-Ya; Liu, Bo; Zhao, Yuan-Di; Hu, Xue-Bin

2015-02-15

A new strategy is proposed for determination of carcino-embryonic antigen (CEA) based on aptamer/graphene oxide (Apt/GO) by capillary electrophoresis-chemiluminescence (CE-CL) detection system. CEA aptamer conjugated with horseradish peroxidase (HRP) firstly mixes with GO, and the CL will be quenched because the stack of HRP-Apt on GO leads to chemiluminescence resonance energy transfer (CRET). When CEA exists, the specific combination of HRP-Apt and CEA can form HRP-Apt-CEA complex, which dissociates from GO. Then, the CL catalyzed by HRP-Apt-CEA complex can be detected without any CRET, and the content of CEA can be estimated by the CL intensity. It has been proved that the interference issue resulted from free HRP-Apt is solved well by mixing GO firstly with HRP-Apt, which blocks the free HRP-Apt's CL signal due to CL quenching effect of GO; and the interference resulted from GO to CL is also solved by CE, then the sensitivity and accuracy can be greatly improved. Results also showed that the CL intensity had a linear relationship with the concentration of CEA in the range from 0.0654 to 6.54 ng/mL, and the limit of detection was approximately 4.8 pg/mL (S/N = 3). This proposed method with high specificity offers a new way for separation and determination of biomolecule, and has good potential in application of biochemistry and bioanalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Combination of long noncoding RNA MALAT1 and carcinoembryonic antigen for the diagnosis of malignant pleural effusion caused by lung cancer.

PubMed

Wang, Wan-Wei; Zhou, Xi-Lei; Song, Ying-Jian; Yu, Chang-Hua; Zhu, Wei-Guo; Tong, Yu-Suo

2018-01-01

Long noncoding RNAs (lncRNAs) are present in body fluids, but their potential as tumor biomarkers has never been investigated in malignant pleural effusion (MPE) caused by lung cancer. The aim of this study was to assess the clinical significance of lncRNAs in pleural effusion, which could potentially serve as diagnostic and predictive markers for lung cancer-associated MPE (LC-MPE). RNAs from pleural effusion were extracted in 217 cases of LC-MPE and 132 cases of benign pleural effusion (BPE). Thirty-one lung cancer-associated lncRNAs were measured using quantitative real-time polymerase chain reaction (qRT-PCR). The level of carcinoembryonic antigen (CEA) was also determined. The receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were established to evaluate the sensitivity and specificity of the identified lncRNAs and other biomarkers. The correlations between baseline pleural effusion lncRNAs expression and response to chemotherapy were also analyzed. Three lncRNAs ( MALAT1 , H19 , and CUDR ) were found to have potential as diagnostic markers in LC-MPE. The AUCs for MALAT1 , H19 , CUDR , and CEA were 0.891, 0.783, 0.824, and 0.826, respectively. Using a logistic model, the combination of MALAT1 and CEA (AUC, 0.924) provided higher sensitivity and accuracy in predicting LC-MPE than CEA (AUC, 0.826) alone. Moreover, baseline MALAT1 expression in pleural fluid was inversely correlated with chemotherapy response in patients with LC-MPE. Pleural effusion lncRNAs were effective in differentiating LC-MPE from BPE. The combination of MALAT1 and CEA was more effective for LC-MPE diagnosis.

The carcinoembryonic antigen IgV-like N domain plays a critical role in the implantation of metastatic tumor cells.

PubMed

Abdul-Wahid, Aws; Huang, Eric H-B; Cydzik, Marzena; Bolewska-Pedyczak, Eleonora; Gariépy, Jean

2014-03-01

The human carcinoembryonic antigen (CEA) is a cell adhesion molecule involved in both homotypic and heterotypic interactions. The aberrant overexpression of CEA on adenocarcinoma cells correlates with their increased metastatic potential. Yet, the mechanism(s) by which its adhesive properties can lead to the implantation of circulating tumor cells and expansion of metastatic foci remains to be established. In this study, we demonstrate that the IgV-like N terminal domain of CEA directly participates in the implantation of cancer cells through its homotypic and heterotypic binding properties. Specifically, we determined that the recombinant N terminal domain of CEA directly binds to fibronectin (Fn) with a dissociation constant in the nanomolar range (K(D) 16 ± 3 nM) and interacts with itself (K(D) 100 ± 17 nM) and more tightly to the IgC-like A(3) domain (K(D) 18 ± 3 nM). Disruption of these molecular associations through the addition of antibodies specific to the CEA N or A(3)B(3) domains, or by adding soluble recombinant forms of the CEA N, A(3) or A(3)B(3) domains or a peptide corresponding to residues 108-115 of CEA resulted in the inhibition of CEA-mediated intercellular aggregation and adherence events in vitro. Finally, pretreating CEA-expressing murine colonic carcinoma cells (MC38.CEA) with rCEA N, A3 or A(3)B(3) modules blocked their implantation and the establishment of tumor foci in vivo. Together, these results suggest a new mechanistic insight into how the CEA IgV-like N domain participates in cellular events that can have a macroscopic impact in terms of cancer progression and metastasis. Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Adenovirus tumor targeting and hepatic untargeting by a coxsackie/adenovirus receptor ectodomain anti-carcinoembryonic antigen bispecific adapter.

PubMed

Li, Hua-Jung; Everts, Maaike; Pereboeva, Larisa; Komarova, Svetlana; Idan, Anat; Curiel, David T; Herschman, Harvey R

2007-06-01

Adenovirus vectors have a number of advantages for gene therapy. However, because of their lack of tumor tropism and their preference for liver infection following systemic administration, they cannot be used for systemic attack on metastatic disease. Many epithelial tumors (e.g., colon, lung, and breast) express carcinoembryonic antigen (CEA). To block the natural hepatic tropism of adenovirus and to "retarget" the virus to CEA-expressing tumors, we used a bispecific adapter protein (sCAR-MFE), which fuses the ectodomain of the coxsackie/adenovirus receptor (sCAR) with a single-chain anti-CEA antibody (MFE-23). sCAR-MFE untargets adenovirus-directed luciferase transgene expression in the liver by >90% following systemic vector administration. Moreover, sCAR-MFE can "retarget" adenovirus to CEA-positive epithelial tumor cells in cell culture, in s.c. tumor grafts, and in hepatic tumor grafts. The sCAR-MFE bispecific adapter should, therefore, be a powerful agent to retarget adenovirus vectors to epithelial tumor metastases.

Diagnostic Accuracy of Combinations of Tumor Markers for Malignant Pleural Effusion: An Updated Meta-Analysis.

PubMed

Yang, Yuan; Liu, Ya-Lan; Shi, Huan-Zhong

2017-01-01

The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has not been clearly established. This meta-analysis was performed to establish the overall diagnostic accuracies of combinations of these pleural fluid tumor markers for MPE. The PubMed, Ovid, Embase, Web of Science, and Cochrane bibliographic databases were searched. Sensitivity, specificity, and other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3, CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic review of English-language studies. Twenty studies met the inclusion criteria. For pleural fluid tumor marker combinations including more than 3 studies, the summary estimates of the sensitivity/specificity for diagnosing MPE were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19-9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94. In patients with undiagnosed pleural effusion, the combinations of positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for pleural malignancy, but the sensitivity of these tests is poor. Therefore, their routine role in the diagnostic algorithm of these patients is questionable, and management decisions should depend on positive cytological or biopsy results from the pleura. © 2017 S. Karger AG, Basel.

Ex vivo PD-L1/PD-1 pathway blockade reverses dysfunction of circulating CEA specific T cells in pancreatic cancer patients

PubMed Central

Chen, Y; Xue, SA; Behboudi, S; Mohammad, GH; Pereira, SP; Morris, EC

2017-01-01

Carcinoembryonic antigen (CEA) is a candidate target for cellular immunotherapy of pancreatic cancer (PC). In this study, we have characterised the antigen-specific function of autologous cytotoxic T lymphocytes (CTL) specific for the HLA-A2 restricted peptide, pCEA691–699, isolated from the peripheral T cell repertoire of PC patients and sought to determine if ex vivo PD-L1 & TIM3 blockade could enhance CTL function. CD8+ T cell lines were generated from peripheral blood mononuclear cells (PBMCs) of 18 HLA-A2+ patients with PC and from 15 healthy controls. In vitro peptide specific responses were evaluated by flow cytometry after staining for intracellular cytokine production and CSFE cytotoxicity assays using pancreatic cancer cell lines as targets. Cytokine secreting functional CEA691-specific CTL lines were successfully generated from 10 of 18PC patients, with two CTL lines able to recognise and kill both CEA691 peptide-loaded T2 cells and CEA+ HLA-A2+ pancreatic cancer cell lines. In the presence of ex vivo PD-L1 blockade, functional CEA691-specific CD8+ T cell responses, including IFN-γ secretion and proliferation, were enhanced and this effect was more pronounced on Ag-specific T cells isolated from tumor draining lymph nodes. These data demonstrate that CEA691-specific CTL can be readily expanded from the self-restricted T cell repertoire of PC patients and that their function can be enhanced by PD-L1 blockade. PMID:28710313

Processing of carcinoembryonic antigen by Kupffer cells: recognition of a penta-peptide sequence.

PubMed

Gangopadhyay, A; Thomas, P

1996-10-01

Carcinoembryonic antigen (CEA) binds to an 80-kDa cell surface receptor on Kupffer cells via the peptide sequence PELPK (residues 108-112) located at the hinge region between the N and Al immunoglobulin-like domains. This study is aimed at analyzing the specificity of the peptide binding, determining biodistribution of 80-kDa receptor, and processing of CEA by this receptor. We synthesized a number of bovine serum albumin (BSA) derivatives carrying PELPK and related sequences. A series of peptides (YPELPK, YPDLPK, YPDLPR, and YPELGK) were conjugated to bovine serum albumin using N-hydroxysuccinimidyl-4-azidobenzoate. When 125I peptide conjugates, CEA, and BSA were injected intravenously into rats CEA and the PELPK-albumin conjugate were cleared rapidly. The other peptide conjugates and BSA cleared at a much slower rate. Activity of 125I-labeled CEA and PELPK-albumin conjugate per gram of tissue was highest for the liver and spleen. Clearance of 125I-CEA was inhibited by the presence of higher concentrations of the PELPK-albumin conjugate. With isolated rat Kupffer cells, only CEA and the PELPK-albumin conjugate were bound and internalized in vitro and CEA binding was inhibited by higher concentrations of the PELPK-albumin conjugate. Similarly, binding of the PELPK-albumin conjugate was inhibited by the presence of unlabeled CEA. Use of a heterobifunctional cross linking agent demonstrated reaction of the PELPK-albumin with an 80-kDa protein on the Kupffer cell surface by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). This semisynthetic ligand (PELPK-albumin) allows us to examine the function of the 80-kDa receptor without interference due to other properties of CEA including its ability to bind lectins and to cause homotypic aggregation of cells. The consequences of CEA binding to the 80-kDa receptor may have implications in the development of hepatic metastasis from colorectal cancer.

Efficient induction of anti-tumor immunity by a TAT-CEA fusion protein vaccine with poly(I:C) in a murine colorectal tumor model.

PubMed

Park, Jung-Sun; Kim, Hye-Sung; Park, Hye-Mi; Kim, Chang-Hyun; Kim, Tai-Gyu

2011-11-03

Protein vaccines may be a useful strategy for cancer immunotherapy because recombinant tumor antigen proteins can be produced on a large scale at relatively low cost and have been shown to be safe for clinical application. However, protein vaccines have historically exhibited poor immunogenicity; thus, an improved strategy is needed for successful induction of immune responses. TAT peptide is a protein transduction domain composed of an 11-amino acid peptide (TAT(47-57): YGRKKRRQRRR). The positive charge of this peptide allows protein antigen fused with it to improve cell penetration. Poly(I:C) is a synthetic double-stranded RNA that is negatively charged and favors interaction with the cationic TAT peptide. Poly(I:C) has been reported on adjuvant role in tumor vaccine through promotion of immune responses. Therefore, we demonstrated that vaccine with a mixture of TAT-CEA fusion protein and poly(I:C) can induce anti-tumor immunity in a murine colorectal tumor model. Splenocytes from mice vaccinated with a mixture of TAT-CEA fusion protein and poly(I:C) effectively induced CEA-specific IFN-γ-producing T cells and showed cytotoxic activity specific for MC-38-cea2 tumor cells expressing CEA. Vaccine with a mixture of TAT-CEA fusion protein and poly(I:C) delayed tumor growth in MC-38-cea-2 tumor-bearing mice. Depletion of CD8(+) T cells and NK cells reversed the inhibition of tumor growth in an MC-38-cea2-bearing mice, indicating that CD8(+) T cells and NK cells are responsible for anti-tumor immunity by vaccine with a mixture of TAT-CEA fusion protein and poly(I:C). Taken together, these results suggest that poly(I:C) could be used as a potent adjuvant to induce the anti-tumor immunity of a TAT-CEA fusion protein vaccine in a murine colorectal tumor model. Copyright © 2011 Elsevier Ltd. All rights reserved.

The generation and analyses of a novel combination of recombinant adenovirus vaccines targeting three tumor antigens as an immunotherapeutic

PubMed Central

Gabitzsch, Elizabeth S.; Tsang, Kwong Yok; Palena, Claudia; David, Justin M.; Fantini, Massimo; Kwilas, Anna; Rice, Adrian E.; Latchman, Yvette; Hodge, James W.; Gulley, James L.; Madan, Ravi A.; Heery, Christopher R.; Balint, Joseph P.

2015-01-01

Phenotypic heterogeneity of human carcinoma lesions, including heterogeneity in expression of tumor-associated antigens (TAAs), is a well-established phenomenon. Carcinoembryonic antigen (CEA), MUC1, and brachyury are diverse TAAs, each of which is expressed on a wide range of human tumors. We have previously reported on a novel adenovirus serotype 5 (Ad5) vector gene delivery platform (Ad5 [E1-, E2b-]) in which regions of the early 1 (E1), early 2 (E2b), and early 3 (E3) genes have been deleted. The unique deletions in this platform result in a dramatic decrease in late gene expression, leading to a marked reduction in host immune response to the vector. Ad5 [E1-, E2b-]-CEA vaccine (ETBX-011) has been employed in clinical studies as an active vaccine to induce immune responses to CEA in metastatic colorectal cancer patients. We report here the development of novel recombinant Ad5 [E1-, E2b-]-brachyury and-MUC1 vaccine constructs, each capable of activating antigen-specific human T cells in vitro and inducing antigen-specific CD4+ and CD8+ T cells in vaccinated mice. We also describe the use of a combination of the three vaccines (designated Tri-Ad5) of Ad5 [E1-, E2b-]-CEA, Ad5 [E1-, E2b-]-brachyury and Ad5 [E1-, E2b-]-MUC1, and demonstrate that there is minimal to no “antigenic competition” in in vitro studies of human dendritic cells, or in murine vaccination studies. The studies reported herein support the rationale for the application of Tri-Ad5 as a therapeutic modality to induce immune responses to a diverse range of human TAAs for potential clinical studies. PMID:26374823

The clinical impact of the novel tumor marker DR-70 in unresectable gastric cancer patients.

PubMed

Hung, Yi-Ping; Chen, Ming-Huang; Lin, June-Seng; Hsiao, Chin-Fu; Shan, Yan-Shen; Chen, Yeu-Chin; Chen, Li-Tzong; Liu, Tsang-Wu; Li, Chung-Pin; Chao, Yee

2018-07-01

Gastric cancer tumor markers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), have been applied in clinical practice to screen or monitor treatment responses. However, their sensitivity and specificity are unsatisfactory. Therefore, we assessed the novel tumor marker DR-70 and evaluated its performance in screening and response monitoring. The study included newly diagnosed patients with advanced gastric cancer from March 2012 to October 2015. We measured the DR-70, CEA, and CA 19-9 levels at the time of enrollment. The patients subsequently underwent chemotherapy. We followed-up the patients every 3 months; DR-70 levels and abdominal computed tomography scans were re-evaluated and repeated, respectively, at each follow-up. The correlation between treatment response and DR-70 level after chemotherapy was analyzed. The overall survival and progression-free survival rates were also evaluated. A total of 51 patients with gastric cancer were enrolled. Most (82.4%) had metastatic disease. At enrollment, the sensitivity of DR-70 in our study group was 78.4%, compared with 52.9% and 43.1% for CEA and CA 19-9, respectively. When we used the three tumor markers together, the sensitivity increased to 80.4%. We observed a correlation between treatment response and DR-70 level after chemotherapy. No difference in either overall survival or progression-free survival was observed between the DR-70 positive and negative groups. However, a trend toward poorer overall survival was observed for the high DR-70 group, although this was not statistically significant. DR-70 is a powerful tool not only for screening unresectable gastric cancer but also for treatment response evaluation. Copyright © 2018. Published by Elsevier Taiwan LLC.

Anti-thyroid peroxidase antibodies are associated with the absence of distant metastases in patients with newly diagnosed breast cancer.

PubMed

Farahati, Jamshid; Roggenbuck, Dirk; Gilman, Elena; Schütte, Martin; Jagminaite, Elena; Seyed Zakavi, Rasoul; Löning, Thomas; Heissen, Eberhard

2012-04-01

The presence of thyroid peroxidase antibodies (TPOab) are reported to be associated with improved outcome among breast cancer patients. We evaluated the correlation between TPOab and diagnostic parameters among newly diagnosed breast cancer patients. Three hundred and fourteen newly diagnosed patients with breast cancer, diagnosed and treated in Bethesda Essen between January 2002 and June 2006, were included in this study; 258 (82.2%) without TPOab (≤100 IU/mL) and 56 (17.8%) with TPOab (>100 IU/mL). Blood analysis was performed to measure serum levels of carcinoembryonic antigen (CEA), cancer antigen 15-3 (CA-15-3), free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH) and TPOab by radioimmunoassay. Data regarding age, tumor size, grading, TNM classification, receptor status, lymph node, and distant metastases were collected and analyzed from patient reports. Statistics were performed using Pearson’s χ2-test and logistic regression analysis. There were no incidences of distant metastasis among 56 patients with TPOab, whereas 17 (6.6%) of 258 cases without TPOab displayed distant metastases (p=0.04). Logistic regression showed an inverse association of TPOab with CA-15-3 and CEA levels (p<0.001, respectively). Both groups, with and without TPOab, revealed no significant differences with respect to age, tumor size, grading, TNM classification, fT3, fT4, and receptor status. TPOab positive patients had higher TSH levels (2.55±3.58), compared to TPOab negative cases (1.20±1.15) (p<0.001). TPOab occurrence is associated with significantly lower frequency of distant metastases in breast cancer. TPOab level inversely correlates with the conventional tumor markers CA-15-3 and CEA.

Highly sensitive and selective lateral flow immunoassay based on magnetic nanoparticles for quantitative detection of carcinoembryonic antigen.

PubMed

Liu, Fangming; Zhang, Honglian; Wu, Zhenhua; Dong, Haidao; Zhou, Lin; Yang, Dawei; Ge, Yuqing; Jia, Chunping; Liu, Huiying; Jin, Qinghui; Zhao, Jianlong; Zhang, Qiqing; Mao, Hongju

2016-12-01

Carcinoembryonic antigen (CEA) is an important biomarker in cancer diagnosis. Here, we present an efficient, selective lateral-flow immunoassay (LFIA) based on magnetic nanoparticles (MNPs) for in situ sensitive and accurate point-of-care detection of CEA. Signal amplification mechanism involved linking of detection MNPs with signal MNPs through biotin-modified single-stranded DNA (ssDNA) and streptavidin. To verify the effectiveness of this modified LFIA system, the sensitivity and specificity were evaluated. Sensitivity evaluation showed a broad detection range of 0.25-1000ng/ml for CEA protein by the modified LFIA, and the limit of detection (LOD) of the modified LFIA was 0.25ng/ml, thus producing significant increase in detection threshold compared with the traditional LFIA. The modified LFIA could selectively recognize CEA in presence of several interfering proteins. In addition, this newly developed assay was applied for quantitative detection of CEA in human serum specimens collected from 10 randomly selected patients. The modified LFIA system detected minimum 0.27ng/ml of CEA concentration in serum samples. The results were consistent with the clinical data obtained using commercial electrochemiluminescence immunoassay (ECLIA) (p<0.01). In conclusion, the MNPs based LFIA system not only demonstrated enhanced signal to noise ratio, it also detected CEA with higher sensitivity and selectivity, and thus has great potential to be commercially applied as a sensitive tumor marker filtration system. Copyright © 2016 Elsevier B.V. All rights reserved.

Evidence for carboxyl-terminal processing and glycolipid-anchoring of human carcinoembryonic antigen.

PubMed

Takami, N; Misumi, Y; Kuroki, M; Matsuoka, Y; Ikehara, Y

1988-09-05

We have investigated the post-translational modification of carcinoembryonic antigen (CEA) for membrane-anchoring in QGP-1 cells derived from a human pancreatic carcinoma. Pulse-chase experiments with [3H]leucine demonstrated that CEA was initially synthesized as a precursor form with Mr 150,000 having N-linked high-mannose-type oligosaccharides, which was then converted to a mature form with Mr 200,000 containing the complex type sugar chains. The mature protein thus labeled was found to be released from the cell surface by treatment with phosphatidylinositol-specific phospholipase C, suggesting that CEA is a phosphatidylinositol-linked membrane protein. This was confirmed by metabolic incorporation into CEA of 3H-labeled compounds such as ethanolamine, myo-inositol, palmitic acid, and stearic acid. The 3H-labeled fatty acids incorporated were specifically removed from the protein by nitrous acid deamination as well as by phosphatidylinositol-specific phospholipase C treatment. Since the available cDNA sequence predicts that CEA contains a single methionine residue only in its carboxyl-terminal hydrophobic domain, processing of the carboxyl terminus was examined by pulse-chase experiments with [35S]methionine. It was found that CEA with Mr 150,000 was initially labeled with [35S]methionine but its radioactivity was immediately lost with chase. Taken together, these results suggest that CEA is anchored to the membrane by simultaneously occurring proteolysis of the carboxyl terminus and replacement by the glycophospholipid immediately after the synthesis.

Pre-clinical validation study of a miniaturized electrochemical immunoassay based on square wave voltammetry for early detection of carcinoembryonic antigen in human serum.

PubMed

Martínez-Mancera, Flavio Dolores; García-López, Patricia; Hernández-López, José Luis

2015-04-15

The ELISA format for measuring carcinoembryonic antigen (CEA) serves as a reference standard against which other assays are compared. Because the World Health Organization (WHO) increasingly recommends the use of serum CEA as a diagnostic tool for cancer, it is relevant to explore the reliability of the new decentralized CEA point-of-care-testing (POCT) technologies that are available to physicians and patients, in compliance with mandates of the clinical laboratories' regulatory agencies. Electrochemical immunoassay (ECIA) based on trace lead (Pb) analysis by anodic stripping techniques using sandwich-type immunocomplex conjugates: (MB)Ab/AgCEA/Ab(PbS), and a commercial ELISA test system with optical transmission. The ECIA provides better analytical performance than does the ELISA. The within assay precision coefficient of variance (%CVw) of the ECIA is lower than the value recommended by the Hong Kong Association of Medical Laboratories (HKAML), and the recoveries of CEA at 1.0, 5.0, 10.0, 25.0 and 50.0 ng/ml are in the range of 99-110% for control serum samples. The ECIA showed a minimal positive bias of 0.0267 ± 0.3270 ng/ml (P=0.9389). The proposed CEA screening technology can be practically employed for decentralized clinical analysis of CEA in human serum. Therefore, it can be viewed as a control method for personalized therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

Heterogeneous RNA-binding protein M4 is a receptor for carcinoembryonic antigen in Kupffer cells.

PubMed

Bajenova, O V; Zimmer, R; Stolper, E; Salisbury-Rowswell, J; Nanji, A; Thomas, P

2001-08-17

Here we report the isolation of the recombinant cDNA clone from rat macrophages, Kupffer cells (KC) that encodes a protein interacting with carcinoembryonic antigen (CEA). To isolate and identify the CEA receptor gene we used two approaches: screening of a KC cDNA library with a specific antibody and the yeast two-hybrid system for protein interaction using as a bait the N-terminal part of the CEA encoding the binding site. Both techniques resulted in the identification of the rat heterogeneous RNA-binding protein (hnRNP) M4 gene. The rat ortholog cDNA sequence has not been previously described. The open reading frame for this gene contains a 2351-base pair sequence with the polyadenylation signal AATAAA and a termination poly(A) tail. The mRNA shows ubiquitous tissue expression as a 2.4-kilobase transcript. The deduced amino acid sequence comprised a 78-kDa membrane protein with 3 putative RNA-binding domains, arginine/methionine/glutamine-rich C terminus and 3 potential membrane spanning regions. When hnRNP M4 protein is expressed in pGEX4T-3 vector system in Escherichia coli it binds (125)I-labeled CEA in a Ca(2+)-dependent fashion. Transfection of rat hnRNP M4 cDNA into a non-CEA binding mouse macrophage cell line p388D1 resulted in CEA binding. These data provide evidence for a new function of hnRNP M4 protein as a CEA-binding protein in Kupffer cells.

Evaluation of predictive value of pleural CEA in patients with pleural effusions and histological findings: A prospective study and literature review.

PubMed

Tozzoli, Renato; Basso, Stefano M M; D'Aurizio, Federica; Metus, Paolo; Lumachi, Franco

2016-11-01

Pleural effusion recognizes heterogeneous etiology and pathogenesis and requires invasive diagnostic procedures. Usually, after pleural fluid analysis, 30-50% of patients with malignant pleural effusion exhibit negative pleural cytology, and the sensitivity of image-guided pleural needle-aspiration biopsy ranges between 60% and 70%. With the aim of differentiating between benign (BPE) and malignant (MPE) pleural effusions, several tumor markers have been assayed in the pleural fluid and the majority of studies focus on pleural carcinoembryonic antigen (p-CEA). The aims of this study were to evaluate (i) the diagnostic accuracy of p-CEA of patients with pleural effusions undergoing video-assisted thoracoscopic surgery (VATS) for diagnostic purpose, (ii) the relationship between p-CEA and serum CEA (s-CEA), and (iii) the usefulness of the p-CEA/s-CEA ratio in the diagnosis of malignant pleural effusions (MPE). We prospectively enrolled in the study 134 consecutive patients with pleural effusions, scheduled for having VATS and biopsy. The final diagnosis, based on histopathology of the VATS-guided specimens, was available for all patients. p-CEA and s-CEA was assayed with a chemiluminescence immunoassay method (CLIA), applied on the Maglumi 2000 Plus automated platform (SNIBE, Shenzen, China). The sensitivity and accuracy of p-CEA was significantly higher than that of pleural cytology at the same specificity comparing BPE with MPE and BPE with non-small lung cancer. The sensitivity of p-CEA and PC together reached 100% (BPE vs. NSCLC) and 91.5% (BPE vs. MPE excluding mesothelioma), respectively. The p-CEA measurement in patients with pleural effusion of uncertain etiology is a safe and cost-effective procedure, everywhere easily available, which may help clinicians in selecting patients for further evaluations. An elevated p-CEA level in a patient with pleural effusion and negative pleural cytology suggests the need of more invasive procedure (e.g. VATS-guided biopsies), whilst low p-CEA may support a follow-up. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

TPS, CA 19-9, VEGF-A, and CEA as diagnostic and prognostic factors in patients with mass lesions in the pancreatic head.

PubMed

Sandblom, Gabriel; Granroth, Sofie; Rasmussen, Ib Christian

2008-01-01

Although numerous tumour markers are available for periampullary tumours, including pancreatic cancer, their specificity and sensitivity have been questioned. To assess the diagnostic and prognostic values of tissue polypeptide specific antigen (TPS), carbohydrate antigen 19-9 (CA 19-9), vascular endothelial growth factor (VEGF-A), and carcinoembryonic antigen (CEA) we took serum samples in 56 patients with mass lesions in the pancreatic head. Among these patients, further investigations revealed pancreatic cancer in 20 patients, other malignant diseases in 12 and benign conditions in 24. Median CEA in all patients was 3.4 microg/L (range 0.5-585.0), median CA 19-9 was105 kU/L (range 0.6-1 300 00), median TPS 123.5 U/L (range 15.0-3350) and median VEGF-A 132.5 ng/L (range 60.0-4317). Area under the curve was 0.747, standard error (standard error [SE] =0.075) for CEA, 0.716 (SE=0.078) for CA 19-9 and 0.822 (SE=0.086) for TPS in ROC plots based on the ability of the tumours to distinguish between benign and malignant conditions. None of the markers significantly predicted survival in the subgroup of patients with pancreatic cancer. Our study shows that the markers may be used as fairly reliable diagnostic tools, but cannot be used to predict survival.

Polyaniline modified flexible conducting paper for cancer detection

NASA Astrophysics Data System (ADS)

Kumar, Saurabh; Sen, Anindita; Kumar, Suveen; Augustine, Shine; Yadav, Birendra K.; Mishra, Sandeep; Malhotra, Bansi D.

2016-05-01

We report results of studies relating to the fabrication of a flexible, disposable, and label free biosensing platform for detection of the cancer biomarker (carcinoembryonic antigen, CEA). Polyaniline (PANI) has been electrochemically deposited over gold sputtered paper (Au@paper) for covalent immobilization of monoclonal carcinoembryonic antibodies (anti-CEA). The bovine serum albumin (BSA) has been used for blocking nonspecific binding sites at the anti-CEA conjugated PANI/Au@Paper. The PANI/Au@Paper, anti-CEA/PANI/Au@Paper, and BSA/anti-CEA/PANI/Au@Paper platforms have been characterized using scanning electron microscopy, X-ray diffraction, Fourier transmission infrared spectroscopy, chronoamperometry, and electrochemical impedance techniques. The results of the electrochemical response studies indicate that this BSA/anti-CEA/PANI/Au@paper electrode has sensitivity of 13.9 μA ng-1 ml cm2, shelf life of 22 days, and can be used to estimate CEA in the range of 2-20 ng ml-1. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.

Bifunctional antibody-Renilla luciferase fusion protein for in vivo optical detection of tumors.

PubMed

Venisnik, Katy M; Olafsen, Tove; Loening, Andreas M; Iyer, Meera; Gambhir, Sanjiv S; Wu, Anna M

2006-10-01

An anti-carcinoembryonic antigen (CEA) antibody fragment, the anti-CEA diabody, was fused to the bioluminescence enzyme Renilla luciferase (RLuc) to generate a novel optical imaging probe. Native RLuc or one of two stabilized variants (RLucC124A, RLuc8) was used as the bioluminescent moiety. A bioluminescence ELISA showed that diabody-luciferase could simultaneously bind to CEA and emit light. In vivo optical imaging of tumor-bearing mice demonstrated specific targeting of diabody-RLuc8 to CEA-positive xenografts, with a tumor:background ratio of 6.0 +/- 0.8 at 6 h after intravenous injection, compared with antigen-negative tumors at 1.0 +/- 0.1 (P = 0.05). Targeting and distribution was also evaluated by microPET imaging using (124)I-diabody-RLuc8 and confirmed that the optical signal was due to antibody-mediated localization of luciferase. Renilla luciferase, fused to biospecific sequences such as engineered antibodies, can be administered systemically to provide a novel, sensitive method for optical imaging based on expression of cell surface receptors in living organisms.

Serum p53 antibody as a potential tumor marker in extrahepatic cholangiocarcinoma.

PubMed

Okada, Rei; Shimada, Hideaki; Otsuka, Yuichiro; Tsuchiya, Masaru; Ishii, Jun; Katagiri, Toshio; Maeda, Tetsuya; Kubota, Yoshihisa; Nemoto, Tetsuo; Kaneko, Hironori

2017-12-01

Only a few studies have evaluated the clinicopathological significance of the p53 protein expression and s-p53-Abs level in patients with cholangiocarcinoma. We therefore analyzed the clinicopathological and prognostic significance of s-p53-Abs in patients with extrahepatic cholangiocarcinoma. We prospectively evaluated s-p53-Abs levels before and after surgery in 61 patients with extrahepatic cholangiocarcinoma to determine the relationship between clinicopathological factors and the prognostic significance of s-p53-Abs. Among a total of 61 primary extrahepatic cholangiocarcinoma cases, 23% were positive for s-p53-Abs. Combination of s-p53-Abs with the conventional serum markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) significantly increased the rate of positive extrahepatic cholangiocarcinoma cases (57% for CEA and/or CA19-9 vs. 75% for CEA and/or CA19-9 and/or s-p53-Abs, P = 0.035). There were no significant differences in clinicopathological factors between the p53-seropositive and p53-seronegative patients. An immunohistochemical analysis showed the presence of significant associations between the intensity (P = 0.003) and extent (P = 0.001) of p53 immunoreactivity and p53-seropositivitly. Although s-p53-Abs was not a significant prognostic factor for the survival in either univariate or multivariate analyses, p53 immunoreactivity was independently associated with a poor survival. Among patients positive for s-p53-Abs before surgery, the s-p53-Abs levels were reduced after surgery in most. These findings suggested that s-p53-Abs might be associated with p53 immunoreactivity. In addition, s-p53-Abs may be useful for a diagnosis, but was not useful for predicting tumor recurrence or the survival. This study was registered as UMIN000014530.

Individualized prediction of perineural invasion in colorectal cancer: development and validation of a radiomics prediction model.

PubMed

Huang, Yanqi; He, Lan; Dong, Di; Yang, Caiyun; Liang, Cuishan; Chen, Xin; Ma, Zelan; Huang, Xiaomei; Yao, Su; Liang, Changhong; Tian, Jie; Liu, Zaiyi

2018-02-01

To develop and validate a radiomics prediction model for individualized prediction of perineural invasion (PNI) in colorectal cancer (CRC). After computed tomography (CT) radiomics features extraction, a radiomics signature was constructed in derivation cohort (346 CRC patients). A prediction model was developed to integrate the radiomics signature and clinical candidate predictors [age, sex, tumor location, and carcinoembryonic antigen (CEA) level]. Apparent prediction performance was assessed. After internal validation, independent temporal validation (separate from the cohort used to build the model) was then conducted in 217 CRC patients. The final model was converted to an easy-to-use nomogram. The developed radiomics nomogram that integrated the radiomics signature and CEA level showed good calibration and discrimination performance [Harrell's concordance index (c-index): 0.817; 95% confidence interval (95% CI): 0.811-0.823]. Application of the nomogram in validation cohort gave a comparable calibration and discrimination (c-index: 0.803; 95% CI: 0.794-0.812). Integrating the radiomics signature and CEA level into a radiomics prediction model enables easy and effective risk assessment of PNI in CRC. This stratification of patients according to their PNI status may provide a basis for individualized auxiliary treatment.

A high-sensitivity electrochemical aptasensor of carcinoembryonic antigen based on graphene quantum dots-ionic liquid-nafion nanomatrix and DNAzyme-assisted signal amplification strategy.

PubMed

Huang, Jing-Yi; Zhao, Lang; Lei, Wan; Wen, Wei; Wang, Yi-Jia; Bao, Ting; Xiong, Hua-Yu; Zhang, Xiu-Hua; Wang, Sheng-Fu

2018-01-15

In this work, we have developed an electrochemical aptasensor for high-sensitivity determination of carcinoembryonic antigen (CEA) based on lead ion (Pb 2+ )-dependent DNAzyme-assisted signal amplification and graphene quantum dot-ionic liquid-nafion (GQDs-IL-NF) composite film. We designed hairpin DNA containing CEA-specific aptamers and DNAzyme chains. In the presence of CEA, hairpin DNA recognized the target and performed a DNAzyme-assisted signal amplification reaction to yield a large number of single-stranded DNA. The GQDs-IL-NF composite film was immobilized on the glassy carbon electrode for the interaction with single-stranded DNA through noncovalent π-π stacking interaction. Therefore, the methylene blue-labeled substrate DNA (MB-substrate) was fixed on the electrode and exhibited an initial electrochemical signal. Under optimal conditions, the response current change was proportional to the concentration of CEA, demonstrating a wide linear range from 0.5fgmL -1 to 0.5ngmL -1 , with a low detection limit of 0.34fgmL -1 . Furthermore, the proposed aptasensor was successfully applied in determining CEA in serum samples, showing its superior prospects in clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of the importance of the serum levels of CA-125, CA15-3, CA-19-9, carcinoembryonic antigen and alpha fetoprotein for distinguishing benign and malignant adnexal masses and contribution of different test combinations to diagnostic accuracy.

PubMed

Bozkurt, M; Yumru, A E; Aral, I

2013-01-01

The aim of this study was to investigate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPPV) of the serum levels of CA-125, CA15-3, CA19-9, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) in the differentiation of benign and malignant ovarian tumors histopathologically diagnosed in patients and to determine the effects of the different test combinations on diagnostic accuracy. One-hundred sixty-eight patients that had their preoperative CA-125, CA15-3, CA19-9, CEA, AFP levels assessed and that were subsequently surgically treated for adnexal masses, were included in the study. For each tumor markers in these patients with histopathologically-confirmed diagnosis, the sensitivity, specificity, PPV and NPV, and diagnostic accuracy, and odds ratio were calculated. The sensitivity, specificity, PPV, NPV of CA125 with cut-off 35 U/ml, were found to be 78.9%, 86.9%, 63.8%, and 93.3%, respectively. The diagnostic odds ratio of CA-125 with cut-off of 35 U/ml, was found to be 25. With cut-off65 U/ml, the sensitivity, specificity, PPV, NPV values were 65.7%, 95.3%, 80.6%, and 90.5%, respectively. The sensitivity, specificity, PPV, and NPV of CEA were 16%, 93%, 37%, and 83%, respectively. For AFP, the sensitivity, specificity, PPV and NPV were to be 2.6%, 98%, 33.3%, and 77.5%, respectively. For CA 15-3, the sensitivity, specificity, PPV and NPV were found to be 26.3% 96.1%, 66.6%, and 81.6%, respectively. Likelihood ratio tests: positive (LR+) = 6.83 and negative (LR-) = 0.76, with an odds ratio: 8.9. The risk of malignancy for adnexal masses with higher CA15-3 increased by approximately nine times. For CA19-9, the sensitivity, specificity, PPV and NPV value were found to be 18.4%, 93%, 43.7%, and 79.6%, respectively. CA19-9 was not statistically significant in the differentiation of benign and malignant of adnexal masses. Even the combinations of CA125 + CEA + CA19-9 and CA125 + CEA + CA19-9 +AFP and CA125 + CA15-3 made a small contribution (one, two, and four cases, respectively), but was not statistically significant. The levels of CA-125 and CA15-3 were found to be significant in order to distinguish benign and malign; CA 19-9, CEA, and AFP were not found to be significant. The different test combinations did not have contribution for diagnostic accuracy.

Surface expression and CEA binding of hnRNP M4 protein in HT29 colon cancer cells.

PubMed

Laguinge, Luciana; Bajenova, Olga; Bowden, Emma; Sayyah, Jacqueline; Thomas, Peter; Juhl, Hartmut

2005-01-01

Carcinoembryonic antigen (CEA) has been shown to participate in the progression and metastatic growth of colorectal cancer. However, its biological function remains elusive. Recently, we found that CEA protects colon cancer cells from undergoing apoptosis, suggesting a complex role that includes signal transduction activity. Additionally, it was reported that CEA binds to Kupffer cells and macrophages to a membrane-anchored homolog of heterogeneous nuclear protein M4 (hnRNP M4), which subsequently was named CEA-receptor (CEAR). Cytoplasmatic and membranous expression of CEAR in CEA-positive colon cancer tissues prompted us to analyze the CEA-CEAR interaction in HT29 colon cancer cells. Both, CEA and CEAR were found on the cell surface of HT29 cells, as demonstrated by confocal microscopy. Imaging analysis suggested co-localization and, thus, interaction of both molecules. To confirm this observation, immunoprecipitation experiments and Western blot analysis were performed and indicated binding of CEA and CEAR. Immunoprecipitation of CEA resulted in a pull down of CEAR. The pull down of CEAR correlated with the amount of CEA as demonstrated by ribozyme targeting of CEA. Finally, external treatment of HT29 cells with soluble CEA induced tyrosine phosphorylation of CEAR, suggesting a CEA-dependent role of CEAR in signal transduction. Future experiments will elucidate whether the CEA-CEAR interaction is involved in CEA's antiapoptotic role and mediates the prometastatic properties of CEA in colon cancer cells.

Layer-by-layer multienzyme assembly for highly sensitive electrochemical immunoassay based on tyramine signal amplification strategy.

PubMed

Zhou, Jun; Tang, Juan; Chen, Guonan; Tang, Dianping

2014-04-15

A new sandwich-type electrochemical immunosensor based on nanosilver-doped bovine serum albumin microspheres (Ag@BSA) with a high ratio of horseradish peroxidase (HRP) and detection antibody was developed for quantitative monitoring of biomarkers (carcinoembryonic antigen, CEA, used in this case) by coupling enzymatic biocatalytic precipitation with tyramine signal amplification strategy on capture antibody-modified glassy carbon electrode. Two immunosensing protocols (with and without tyramine signal amplification) were also investigated for the detection of CEA and improved analytical features were acquired with tyramine signal amplification strategy. With the labeling method, the performance and factors influencing the electrochemical immunoassay were studied and evaluated in detail. Under the optimal conditions, the electrochemical immunosensor exhibited a wide dynamic range of 0.005-80 ng mL(-1) toward CEA standards with a low detection limit of 5.0 pg mL(-1). Intra- and inter-assay coefficients of variation were below 11%. No significant differences at the 0.05 significance level were encountered in the analysis of 6 clinical serum specimens and 6 spiked new-born cattle serum samples between the electrochemical immunoassay and the commercialized electrochemiluminescent immunoassay method for the detection of CEA. © 2013 Published by Elsevier B.V.

Polyaniline modified flexible conducting paper for cancer detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Saurabh; Sen, Anindita; Kumar, Suveen

We report results of studies relating to the fabrication of a flexible, disposable, and label free biosensing platform for detection of the cancer biomarker (carcinoembryonic antigen, CEA). Polyaniline (PANI) has been electrochemically deposited over gold sputtered paper (Au@paper) for covalent immobilization of monoclonal carcinoembryonic antibodies (anti-CEA). The bovine serum albumin (BSA) has been used for blocking nonspecific binding sites at the anti-CEA conjugated PANI/Au@Paper. The PANI/Au@Paper, anti-CEA/PANI/Au@Paper, and BSA/anti-CEA/PANI/Au@Paper platforms have been characterized using scanning electron microscopy, X-ray diffraction, Fourier transmission infrared spectroscopy, chronoamperometry, and electrochemical impedance techniques. The results of the electrochemical response studies indicate that this BSA/anti-CEA/PANI/Au@paper electrodemore » has sensitivity of 13.9 μA ng{sup −1} ml cm{sup 2}, shelf life of 22 days, and can be used to estimate CEA in the range of 2–20 ng ml{sup −1}. This paper sensor has been validated by detection of CEA in serum samples of cancer patients via immunoassay technique.« less

1NON-INVASIVE RADIOIODINE IMAGING FOR ACCURATE QUANTITATION OF NIS REPORTER GENE EXPRESSION IN TRANSPLANTED HEARTS

PubMed Central

Ricci, Davide; Mennander, Ari A; Pham, Linh D; Rao, Vinay P; Miyagi, Naoto; Byrne, Guerard W; Russell, Stephen J; McGregor, Christopher GA

2008-01-01

Objectives We studied the concordance of transgene expression in the transplanted heart using bicistronic adenoviral vector coding for a transgene of interest (human carcinoembryonic antigen: hCEA - beta human chorionic gonadotropin: βhCG) and for a marker imaging transgene (human sodium iodide symporter: hNIS). Methods Inbred Lewis rats were used for syngeneic heterotopic cardiac transplantation. Donor rat hearts were perfused ex vivo for 30 minutes prior to transplantation with University of Wisconsin (UW) solution (n=3), with 109 pfu/ml of adenovirus expressing hNIS (Ad-NIS; n=6), hNIS-hCEA (Ad-NIS-CEA; n=6) and hNIS-βhCG (Ad-NIS-CG; n=6). On post-operative day (POD) 5, 10, 15 all animals underwent micro-SPECT/CT imaging of the donor hearts after tail vein injection of 1000 μCi 123I and blood sample collection for hCEA and βhCG quantification. Results Significantly higher image intensity was noted in the hearts perfused with Ad-NIS (1.1±0.2; 0.9±0.07), Ad-NIS-CEA (1.2±0.3; 0.9±0.1) and Ad-NIS-CG (1.1±0.1; 0.9±0.1) compared to UW group (0.44±0.03; 0.47±0.06) on POD 5 and 10 (p<0.05). Serum levels of hCEA and βhCG increased in animals showing high cardiac 123I uptake, but not in those with lower uptake. Above this threshold, image intensities correlated well with serum levels of hCEA and βhCG (R2=0.99 and R2=0.96 respectively). Conclusions These data demonstrate that hNIS is an excellent reporter gene for the transplanted heart. The expression level of hNIS can be accurately and non-invasively monitored by serial radioisotopic single photon emission computed tomography (SPECT) imaging. High concordance has been demonstrated between imaging and soluble marker peptides at the maximum transgene expression on POD 5. PMID:17980613

Differentiation of pancreatobiliary cancer from benign biliary strictures using neutrophil gelatinase-associated lipocalin.

PubMed

Budzynska, A; Nowakowska-Dulawa, E; Marek, T; Boldys, H; Nowak, A; Hartleb, M

2013-02-01

Aim of the study was to investigate the value of serum and bile neutrophil gelatinase-associated lipocalin (NGAL) for distinguishing malignant strictures caused by cholangiocarcinoma (CCA) or pancreatic cancer from benign biliary strictures. The study was performed prospectively on patients admitted for endoscopic or radiologic biliary decompression. Forty patients with dilated biliary ducts, including 16 cases of CCA, 6 cases of pancreatic cancer, and 18 cases of benign biliary stricture were enrolled. Their sera and bile were collected to measure NGAL. Routine biochemistry including measurement of serum levels of carbohydrate antigens (CA) 19-9 and carcinoembryonic antigen (CEA) was also performed. The serum CA19-9, serum CEA, and bile NGAL levels were significantly increased in patients with malignant strictures as compared with patients with benign biliary diseases. Serum NGAL had no significant value for discriminating between malignant and benign biliary strictures. Bile NGAL levels had a receiver characteristic area under the curve of 0.74, sensitivity 77.3, and specificity 72.2% for discriminating between pancreatobiliary cancer and benign biliary diseases. Bile NGAL and serum CA19-9 were independent parameters and their combined use improved diagnostic accuracy (sensitivity 91%, negative predictive value 85.7%). We conclude that measurement of biliary, but not serum NGAL, may differentiate malignant pancreatobiliary from benign biliary strictures, serving as a complementary biomarker for serum CA19-9.

An exploratory study of inflammatory cytokines as prognostic biomarkers in patients with ductal pancreatic adenocarcinoma.

PubMed

Dima, Simona O; Tanase, Cristiana; Albulescu, Radu; Herlea, Vlad; Chivu-Economescu, Mihaela; Purnichescu-Purtan, Raluca; Dumitrascu, Traian; Duda, Dan G; Popescu, Irinel

2012-10-01

We measured the serum concentration of a panel of inflammatory cytokines and evaluated their association with circulating proangiogenic biomarkers and with outcome in patients with pancreatic ductal adenocarcinoma (PDAC). We collected serum samples from 36 patients with PDAC, 9 patients with chronic pancreatitis, and 22 healthy volunteers as a control. Inflammatory cytokines and proangiogenic biomarkers were measured using the multianalyte xMAP array and carcinoembryonic antigen (CEA) and carbohydrate 19-9 by immunoassay. Patients with PDAC had higher circulating levels of interleukin 6 (IL-6) than those of patients with pancreatitis or healthy individuals and higher levels of IL-10 and tumor necrosis factor α (TNF-α) compared with those of healthy individuals. In patients with PDAC, circulating IL-6, TNF-α, IL-1β, and IL-10 correlated with serum concentrations of vascular endothelial growth factor and basic fibroblast growth factor; circulating IL-6, IL-1β, and TNF-α correlated with carbohydrate 19-9; and IL-8, IL-10, and TNF-α correlated with CEA levels. Circulating IL-8, TNF-α, and CEA; tumor stage; and lymph node metastases were associated with a poor outcome. The results of this exploratory study indicate that inflammatory cytokines should be pursued as potential prognostic biomarkers as well as targets for therapy in larger studies in PDAC.

Napsin A levels in epithelial lining fluid as a diagnostic biomarker of primary lung adenocarcinoma.

PubMed

Uchida, Akifumi; Samukawa, Takuya; Kumamoto, Tomohiro; Ohshige, Masahiro; Hatanaka, Kazuhito; Nakamura, Yoshihiro; Mizuno, Keiko; Higashimoto, Ikkou; Sato, Masami; Inoue, Hiromasa

2017-12-12

It is crucial to develop novel diagnostic approaches for determining if peripheral lung nodules are malignant, as such nodules are frequently detected due to the increased use of chest computed tomography scans. To this end, we evaluated levels of napsin A in epithelial lining fluid (ELF), since napsin A has been reported to be an immunohistochemical biomarker for histological diagnosis of primary lung adenocarcinoma. In consecutive patients with indeterminate peripheral lung nodules, ELF samples were obtained using a bronchoscopic microsampling (BMS) technique. The levels of napsin A and carcinoembryonic antigen (CEA) in ELF at the nodule site were compared with those at the contralateral site. A final diagnosis of primary lung adenocarcinoma was established by surgical resection. We performed BMS in 43 consecutive patients. Among patients with primary lung adenocarcinoma, the napsin A levels in ELF at the nodule site were markedly higher than those at the contralateral site, while there were no significant differences in CEA levels. Furthermore, in 18 patients who were undiagnosed by bronchoscopy and finally diagnosed by surgery, the napsin A levels in ELF at the nodule site were identically significantly higher than those at the contralateral site. In patients with non-adenocarcinoma, there were no differences in napsin A levels in ELF. The area under the receiver operator characteristic curve for identifying primary lung adenocarcinoma was 0.840 for napsin A and 0.542 for CEA. Evaluation of napsin A levels in ELF may be useful for distinguishing primary lung adenocarcinoma.

Thymidine kinase 1 combined with CEA, CYFRA21-1 and NSE improved its diagnostic value for lung cancer.

PubMed

Jiang, Z F; Wang, M; Xu, J L

2018-02-01

Thymidine kinase 1 (TK1) is a tumor biomarker in human malignancies. The purpose of this study was to evaluate the diagnostic efficiency of this marker for lung cancer using the combined analysis of carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), neuron specific enolase (NSE) and TK1. From 2013 to 2014, 147 patients with lung cancer and 228 patients with lung benign diseases who were admitted to our hospital were reviewed. Peripheral blood samples were collected for the detection of TK1, CEA, CYFRA21-1 and NSE. The diagnostic value of each marker was analyzed using receiver operating characteristic (ROC) curves and logistic regression equations. The serum levels of TK1, CEA, CYFRA21-1 and NSE were significantly higher than those in patients with lung benign diseases (all P<0.05). The TK1 concentration was dependent on TNM stage (P=0.005). The ROC curve analyses showed that the diagnostic value of TK1 combined with CEA, CYFRA21-1 and NSE in lung cancer was significantly higher than that of each biomarker alone (all P<0.0001). In addition, TK1 combined with CEA, CYFRA21-1, or NSE could also improve the diagnosis of the squamous cell carcinoma, adenocarcinoma and small cell lung cancer subtypes, respectively. The combined detection of TK1 and the other three markers significantly improved the diagnosis of lung cancer. Furthermore, the detection of TK1 combined with that of CYFRA21-1, CEA or NSE increased the diagnostic value of TK1 for lung squamous cell carcinoma, adenocarcinoma and SCLC, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

Dye sensitized photoelectrochemical immunosensor for the tumor marker CEA by using a flower-like 3D architecture prepared from graphene oxide and MoS2.

PubMed

Song, Kaijing; Ding, Chuanmin; Zhang, Bing; Chang, Honghong; Zhao, Zhihuan; Wei, Wenlong; Wang, Junwen

2018-06-01

The authors describe a dye-sensitized photoelectrochemical immunoassay for the tumor marker carcinoembryonic antigen (CEA). The method employs the rhodamine dye Rh123 with red color and absorption maximum at 500 nm for spectral sensitization, and a 3D nanocomposite prepared from graphene oxide and MoS 2 acting as the photoelectric conversion layer. The nanocomposite with flower-like 3D architectures was characterized by transmission electron microscopy, scanning electron microscopy, X-ray powder diffraction, and UV-vis diffuse reflectometry. A photoelectrochemical sandwich immunoassay was developed that is based on the use of the nanocomposite and based on the specific binding of antibody and antigen, and by using a secondary antibody labeled with Rh123 and CdS (Ab 2 -Rh123@CdS). Under optimal conditions and at a typical working voltage of 0 V (vs. Hg/HgCl 2 ), the photocurrent increases linearly 10 pg mL -1 to 80 ng mL -1 CEA concentration range, with a 3.2 pg mL -1 detection limit. Graphical abstract Flower-like GO-MoS 2 complex with high efficiency of electron transport was synthesized to construct photoelectrochemical platform. The sandwich-type immunoassay was built on this platform based on specific binding of antigen and antibody. Carcinoembryonic antigen in sample was detected sensitively by using sensitization of rhodamine dye Rh123 as signal amplification strategy.

Immunohistochemical sweat gland profiles.

PubMed

Noël, Fanchon; Piérard, Gérald E; Delvenne, Philippe; Quatresooz, Pascale; Humbert, Philippe; Piérard-Franchimont, Claudine

2013-09-01

Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. Some immunohistochemical markers are expected to distinguish the sweat gland types in their secretory and excretory parts. This study used two sets of antibodies. The first panel was composed of antibodies directed to well-defined sweat gland structures. The molecular targets included the low-molecular-weight cytokeratins CAM 5.2, the S100-B protein, the epithelial membrane antigen (EMA), the carcinoembryonic antigen (CEA), and the lectin Ulex europaeus agglutinin-1 (UEA-1). A second exploratory panel of antibodies targeted syndecan-1 (CD138), NKI-C3 (CD63), and CD68. They were used to disclose some undescribed antigen expressions in human sweat glands. The first set of antibodies confirmed previous findings. The immunoreactivities of the three sweat gland types were similar in the excretory ducts. By contrast, they were distinguished in the deeper coiled secretory portions of the glands. Clues supporting their distinction and probably their functional activity were obtained by immunohistochemistry using the S100-B protein, CEA and CD63 antibodies. The immunoreactivity to the S100-B protein, CEA and CD63 possibly help identifying apoeccrine sweat glands or a peculiar functional activity of eccrine sweat glands. © 2013 Wiley Periodicals, Inc.

The CEA Second-Look Trial: a randomised controlled trial of carcinoembryonic antigen prompted reoperation for recurrent colorectal cancer

PubMed Central

Treasure, Tom; Monson, Kathryn; Fiorentino, Francesca; Russell, Christopher

2014-01-01

Objective In patients who have undergone a potentially curative resection of colorectal cancer, does a ‘second-look’ operation to resect recurrence, prompted by monthly monitoring of carcinoembryonic antigen, confer a survival benefit? Design A randomised controlled trial recruiting patients from 1982 to 1993 was recovered under the Restoring Invisible and Abandoned Trials (RIAT) initiative. Setting 58 hospitals in the UK. Participants From 1982 to 1993, 1447 patients were enrolled. Of these 216 met the criteria for carcinoembryonic antigen (CEA) elevation and were randomised to ‘Aggressive’ or ‘Conventional’ arms. Interventions ‘Second-look’ surgery with intention to remove any recurrence discovered. Primary outcome measure Survival. Results By February 1993, 91/108 patients had died in the ‘Aggressive arm’ and 88/108 in the ‘Conventional’ arm (relative risk=1.16, 95% CI 0.87 to 1.37). By 2011 a further 25 randomised patients had died. Kaplan-Meier analysis showed no difference in long-term survival. Conclusions The trial was closed in 1993 following a recommendation from the Data Monitoring Committee that it was highly unlikely that any survival advantage would be demonstrated for CEA prompted second-look surgery. This conclusion was confirmed by repeat analysis of survival times after 20 years. Trial registration number ISRCTN76694943. PMID:24823671

Magnetic immunoassay coupled with inductively coupled plasma mass spectrometry for simultaneous quantification of alpha-fetoprotein and carcinoembryonic antigen in human serum

NASA Astrophysics Data System (ADS)

Zhang, Xing; Chen, Beibei; He, Man; Zhang, Yiwen; Xiao, Guangyang; Hu, Bin

2015-04-01

The absolute quantification of glycoproteins in complex biological samples is a challenge and of great significance. Herein, 4-mercaptophenylboronic acid functionalized magnetic beads were prepared to selectively capture glycoproteins, while antibody conjugated gold and silver nanoparticles were synthesized as element tags to label two different glycoproteins. Based on that, a new approach of magnetic immunoassay-inductively coupled plasma mass spectrometry (ICP-MS) was established for simultaneous quantitative analysis of glycoproteins. Taking biomarkers of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) as two model glycoproteins, experimental parameters involved in the immunoassay procedure were carefully optimized and analytical performance of the proposed method was evaluated. The limits of detection (LODs) for AFP and CEA were 0.086 μg L- 1 and 0.054 μg L- 1 with the relative standard deviations (RSDs, n = 7, c = 5 μg L- 1) of 6.5% and 6.2% for AFP and CEA, respectively. Linear range for both AFP and CEA was 0.2-50 μg L- 1. To validate the applicability of the proposed method, human serum samples were analyzed, and the obtained results were in good agreement with that obtained by the clinical chemiluminescence immunoassay. The developed method exhibited good selectivity and sensitivity for the simultaneous determination of AFP and CEA, and extended the applicability of metal nanoparticle tags based on ICP-MS methodology in multiple glycoprotein quantifications.

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

PubMed Central

Kaufman, Howard L; Kim-Schulze, Seunghee; Manson, Kelledy; DeRaffele, Gail; Mitcham, Josephine; Seo, Kang Seok; Kim, Dae Won; Marshall, John

2007-01-01

Purpose An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival. Patients and methods Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM) (PANVAC-V) and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F). Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis. Results The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%). Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; P = .002). Conclusion Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer. PMID:18039393

A dye-sensitized solar cell acting as the electrical reading box of an immunosensor: Application to CEA determination.

PubMed

Truta, Liliana A A N A; Moreira, Felismina T C; Sales, M Goreti F

2018-06-01

Monitoring cancer biomarkers in biological fluids has become a key tool for disease diagnosis, which should be of easy access anywhere in the world. The possibility of reducing basic requirements in the field of electrochemical biosensing may open doors in this direction. This work proposes for this purpose an innovative electrochemical immunosensing system using a photovoltaic cell as an electrical reading box. Immunosensing ensures accuracy, the electrochemical-ground of the device ensures sensitivity and detectability, and the photovoltaic cell drives the system towards electrical autonomy. As proof-of-concept, Carcinoembryonic antigen (CEA) was used herein, a cancer biomarker of clinical relevance. In brief, a conductive glass with a fluorine doped tin oxide film was used as conductive support and modified with anti-CEA by means of a bottom-up approach. All stages involved in the biochemical modification of the FTO surface were followed by electrochemical techniques, namely electrochemical impedance spectroscopy and cyclic voltammetry. This electrode acted as counter electrode of a dye-sensitized solar cells, and the electrical output of this cell was monitored for the different concentrations of CEA. Under optimized conditions, the device displayed a linear behaviour against CEA concentration, from 5 pg/mL to 15 ng/mL. The immunosensor was applied to the analysis of CEA in urine from healthy individual and spiked with the antigen. Overall, the presented approach demonstrates that photovoltaic cells may be employed as an electrical reading box of electrochemical biosensors, yielding a new direction towards autonomous electrochemical biosensing. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Nanoporous gold as a solid support for protein immobilization and development of an electrochemical immunoassay for prostate specific antigen and carcinoembryonic antigen

PubMed Central

Pandey, Binod; Demchenko, Alexei V.; Stine, Keith J.

2013-01-01

Nanoporous gold (NPG) was utilized as a support for immobilizing alkaline phosphatase (ALP) conjugated to monoclonal antibodies against either prostate specific antigen (PSA) or carcinoembryonic antigen (CEA). The antibody-ALP conjugates were coupled to self-assembled monolayers of lipoic acid and used in direct kinetic assays. Using the enzyme substrate p-aminophenylphosphate, the product p-aminophenol was detected by its oxidation near 0.1 V (vs. Ag|AgCl) using square wave voltammetry. The difference in peak current arising from oxidation of p-aminophenol before and after incubation with biomarker increased with biomarker concentration. The response to these two biomarkers was linear up to 10 ng mL-1 for CEA and up to 30 ng mL-1 for PSA. The effect of interference on the PSA assay was studied using bovine serum albumin (BSA) as a model albumin protein. The effect of interference from a serum matrix was examined for the PSA assay using newborn calf serum. A competitive version of the immunoassay using antigen immobilized onto the NPG surface was highly sensitive at lower antigen concentration. Estimates of the surface coverage of the antibody-ALP conjugates on the NPG surface are presented. PMID:23935216

Study of pharmaceutical industrial problems

NASA Technical Reports Server (NTRS)

Pincus, J. H.

1979-01-01

The growth of a human colon carcinoma cell line (SK-CO-1) and its production of carcinoembryonic antigen (CEA) in monolayer culture and on single layers of glass beads in unit gravity were evaluated. The limitations of using a microsphere-cell growth system in unit gravity were identified and how these may be overcome in space was considered. The project had the following tasks: (1) growth of cultured human colon carcinoma cells on a monolayer and CEA production; (2) evaluation of CEA production and release by SK-CO-1 cells grown on glass beads; (3) evaluation of other microcarriers for growing SK-CO-1 cells and determination of the minimum amount of culture medium needed for cell growth; and (4) growth of SK-CO-1 cells on collagen monolayers and CEA production.

Multiplexed Analysis of Serum Breast and Ovarian Cancer Markers by Means of Suspension Bead-quantum Dot Microarrays

NASA Astrophysics Data System (ADS)

Brazhnik, Kristina; Sokolova, Zinaida; Baryshnikova, Maria; Bilan, Regina; Nabiev, Igor; Sukhanova, Alyona

Multiplexed analysis of cancer markers is crucial for early tumor diagnosis and screening. We have designed lab-on-a-bead microarray for quantitative detection of three breast cancer markers in human serum. Quantum dots were used as bead-bound fluorescent tags for identifying each marker by means of flow cytometry. Antigen-specific beads reliably detected CA 15-3, CEA, and CA 125 in serum samples, providing clear discrimination between the samples with respect to the antigen levels. The novel microarray is advantageous over the routine single-analyte ones due to the simultaneous detection of various markers. Therefore the developed microarray is a promising tool for serum tumor marker profiling.

Natural killer cells activity in a metastatic colorectal cancer patient with complete and long lasting response to therapy.

PubMed

Ottaiano, Alessandro; Napolitano, Maria; Capozzi, Monica; Tafuto, Salvatore; Avallone, Antonio; Scala, Stefania

2017-11-16

Here we report a case of a 70-year-old man who received adjuvant chemotherapy with fluorouracile, folinic acid and oxaliplatin after a left hemicolectomy for a stage IIIb adenocarcinoma in May 2009. During follow-up he de-veloped abdominal lymphnodes metastases evidenced by positron emission tomography- computed tomography (PET-CT) scan and increase of carcinoembryonic antigen (CEA) level. Chemotherapy with capecitabine, oxaliplatin and bevacizumab was started in April 2012. Restaging showed a complete response and normalization of CEA. The patient received maintenance therapy with bevacizumab which was stopped in December 2013 for patient choice. In October 2014, a new increase in CEA was documented and PET-CT scan showed lung metastases. Analysis of RAS status revealed the absence of mutations, then the patient started a second-line chemotherapy with fluorouracile, folinic acid, irinotecan (folfiri) and panitumumab achieving, in January 2015, a complete response and normalization of CEA. Thereafter, folfiri was discontinued for toxicity; furthermore, upon the third occurrence of a grade 3 dermatologic toxicity, panitumumab was continued from June 2015 at 60% of the original dose and it was administered every three weeks. Until presentation of this case, the patient maintains a complete response, has no symptoms of disease and CEA is normal. Interestingly, this patient presented a high proportion of circulating natural killer (NK) cells (35.1%) with high cytotoxic activity against tumor cells. Study on the role of NK in patients with advanced colorectal cancer are ongoing.

Platinum porous nanoparticles hybrid with metal ions as probes for simultaneous detection of multiplex cancer biomarkers.

PubMed

Wang, Zifeng; Liu, Na; Ma, Zhanfang

2014-03-15

In this work, platinum porous nanoparticles (PtPNPs) absorbed metal ions as electrochemical signals were fabricated. Clean-surface PtPNPs were prepared by a surfactant-free method and decorated with amino groups via 2-aminoethanethiol. Amino capped PtPNPs complexation with Cd(2+) and Cu(2+) to form PtPNPs-Cd(2+) and PtPNPs-Cu(2+) hybrids, respectively. Anti-CEA and Anti-AFP separately labeled with PtPNPs-Cd(2+) and PtPNPs-Cu(2+) were used as distinguishable signal tags for capturing antigens. The metal ions were detected in a single run through differential pulse voltammetry (DPV) without acid dissolution, electric potentials and peak heights of which reflected the identity and concentrations of the corresponding antigen. Ionic liquid reduced graphene oxide (IL-rGO) modified glassy carbon electrode (GCE) was used as a substrate, which was rich in amino groups to immobilize antibodies by glutaraldehyde through cross-link between aldehyde groups and amino groups. Using the proposed probes and platform, a novel sandwich-type electrochemical immunosensor for simultaneous detecting carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) was successfully developed. This immunoassay possessed good linearity from 0.05 ng mL(-1) to 200 ng mL(-1) for both CEA and AFP. The detection limit of CEA was 0.002 ng mL(-1) and that of AFP was 0.05 ng mL(-1) (S/N=3). Furthermore, analysis of clinical serum samples using this immunosensor was well consistent with the data determined by the enzyme-linked immunosorbent assay (ELISA). It suggested that the proposed electrochemical immunoassay provided a potential application of clinical screening for early-stage cancers. © 2013 Published by Elsevier B.V.

Biomarkers for the early detection of relapses in metastatic colorectal cancers.

PubMed

Chereches, Gabriela; Barbos, Otilia; Buiga, Rares; Balacescu, Ovidiu; Iancu, Dana; Todor, Nicolae; Balacescu, Loredana; Miron, Nicu; Bejinariu, Nona; Ciuleanu, Tudor-Eliade

2017-01-01

To assess prognostic/predictive value of carcinoembryonic antigen (CEA), transthyretin (TRT), αenolase (NNE), β2-microglobulin (β2-micro), B-cell activating factor (BAFF) and circulating tumor cells (CTCs) in metastatic colorectal cancer (mCRC) patients treated with chemotherapy with or without bevacizumab. 72 histologically confirmed mCRC patients treated at Oncology Institute Cluj were included. Biomarker levels were measured through validated methods. A manual method was used for CTCs, involving hemolysis, cytospin centrifugation and immunocytochemical staining for pan-cytokeratin. Statistical endpoints were response, progression- free survival (PFS) and overall survival (OS). Initial chemotherapy was fluoropyrimidine/oxaliplatin-based in 93.1%; bevacizumab was added in 58.3% of the patients. Median PFS and OS were 16.4 and 24.4 months. Two-year OS for CR & PR vs SD vs PD were 90% vs 48% vs 12%, respectively (p<0.01). Two-year OS for chemo/ bevacizumab vs chemotherapy: 65% vs 42% (p=0.09). Baseline CEA ≥5 ng/ml had a negative prognostic impact on OS and PFS (p<0.01). High baseline CEA was predictive of improved OS when adding bevacizumab (2-year OS chemo/bevacizumab vs chemo: 60% vs 17%, p<0.01); adding bevacizumab in patients with normal CEA did not improve OS (p=0.29). Higher than cut-off values for TRT had a positive OS prognostic value (p<0.01); higher levels for NNE, β2-microglobulin and BAFF had a negative impact (p<0.01). Two-year OS for baseline <1 CTC/ml vs ≥1 CTC/ ml was 74% vs 64% respectively (p=0.15). The evaluated biomarkers could be useful prognostic factors for survival. Baseline CEA also has predictive value, suggesting that patients with low levels do not benefit from bevacizumab. A non-statistically significant correlation was observed between the number of CTCs and outcome.

Secretory meningioma: clinicopathologic features of eight cases.

PubMed

Nishio, S; Morioka, T; Suzuki, S; Hirano, K; Fukui, M

2001-07-01

The clinical and morphological features of eight patients with meningothelial meningiomas with numerous pseudopsammoma bodies (secretory meningiomas) are presented. The six female and two male patients ranged in age from 43 to 68 years. Tumours were located at the petroclival region in two, the lateral parasellar region in two, the petrous apex in one and the sphenoid ridge in three patients. On magnetic resonance imaging, they were iso or hypointense on T1-weighted images, and hyper or isointense on T 2-weighted images. Peritumoral brain edema was absent in five cases, and was mild to moderate in three cases. Serum carcinoembryonic antigen (CEA) levels were measured preoperatively in three patients, with one having an elevated serum CEA level which re turned to normal following tumour resection. Immunohistochemical analysis on the resected tumour tissues, pseudopsammoma bodies and surrounding tumour cells were shown to be CEA-positive. Ultrastructurally, pseudopsammoma bodies were composed of granular and filamentous materials located predominantly in the intracellular lumina, which were lined by microvilli. While these morphological features of focal epithelial and secretory differentiation of tumour cells call attention to the broad spectrum of differentiation properties of meningiomas, the biological behavior of the eight tumours reported herein corresponded to those of meningiomas in general. Copyright 2001 Harcourt Publishers Ltd.

Anti-CEA-functionalized superparamagnetic iron oxide nanoparticles for examining colorectal tumors in vivo

NASA Astrophysics Data System (ADS)

Huang, Kai-Wen; Chieh, Jen-Jie; Lin, In-Tsang; Horng, Herng-Er; Yang, Hong-Chang; Hong, Chin-Yih

2013-10-01

Although the biomarker carcinoembryonic antigen (CEA) is expressed in colorectal tumors, the utility of an anti-CEA-functionalized image medium is powerful for in vivo positioning of colorectal tumors. With a risk of superparamagnetic iron oxide nanoparticles (SPIONPs) that is lower for animals than other material carriers, anti-CEA-functionalized SPIONPs were synthesized in this study for labeling colorectal tumors by conducting different preoperatively and intraoperatively in vivo examinations. In magnetic resonance imaging (MRI), the image variation of colorectal tumors reached the maximum at approximately 24 h. However, because MRI requires a nonmetal environment, it was limited to preoperative imaging. With the potentiality of in vivo screening and intraoperative positioning during surgery, the scanning superconducting-quantum-interference-device biosusceptometry (SSB) was adopted, showing the favorable agreement of time-varied intensity with MRI. Furthermore, biological methodologies of different tissue staining methods and inductively coupled plasma (ICP) yielded consistent results, proving that the obtained in vivo results occurred because of targeted anti-CEA SPIONPs. This indicates that developed anti-CEA SPIONPs owe the utilities as an image medium of these in vivo methodologies.

Novel electrochemical redox-active species: one-step synthesis of polyaniline derivative-Au/Pd and its application for multiplexed immunoassay

NASA Astrophysics Data System (ADS)

Wang, Liyuan; Feng, Feng; Ma, Zhanfang

2015-11-01

Electrochemical redox-active species play crucial role in electrochemically multiplexed immunoassays. A one-pot method for synthesizing four kinds of new electrochemical redox-active species was reported using HAuCl4 and Na2PdCl4 as dual oxidating agents and aniline derivatives as monomers. The synthesized polyaniline derivative-Au/Pd composites, namely poly(N-methyl-o-benzenediamine)-Au/Pd, poly(N-phenyl-o-phenylenediamine)-Au/Pd, poly(N-phenyl-p-phenylenediamine)-Au/Pd and poly(3,3’,5,5’-tetramethylbenzidine)-Au/Pd, exhibited electrochemical redox activity at -0.65 V, -0.3 V, 0.12 V, and 0.5 V, respectively. Meanwhile, these composites showed high H2O2 electrocatalytic activity because of the presence of Au/Pd. The as-prepared composites were used as electrochemical immunoprobes in simultaneous detection of four tumor biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199), carbohydrate antigen 72-4 (CA724), and alpha fetoprotein (AFP)). This immunoassay shed light on potential applications in simultaneous gastric cancer (related biomarkers: CEA, CA199, CA724) and liver cancer diagnosis (related biomarkers: CEA, CA199, AFP). The present strategy to the synthesize redox species could be easily extended to other polymers such as polypyrrole derivatives and polythiophene derivatives. This would be of great significance in the electrochemical detection of more analytes.

A nonfouling voltammetric immunosensor for the carcinoembryonic antigen based on the use of polyaniline nanowires wrapped with hyaluronic acid.

PubMed

Wang, Jiasheng; Hui, Ni

2018-06-16

A non-fouling electrochemical immunosensor is described for determination of the tumor biomarker carcinoembryonic antigen (CEA). It is based on the use of composite wires made by chemical grafting of hyaluronic acid onto polyaniline nanowires. The modified nanowires possess excellent antifouling property both in single protein solutions and in dilute serum samples. The current of immunoelectrode exhibits a linear response in the 0.01 pg mL -1 to 10,000 pg mL -1 CEA concentration range and 0.0075 pg mL -1 detection limit. This work demonstrates that coating an electrode with hyaluronic acid can largely reduce unspecific adsorption of proteins on the electrode surface. Graphical abstract Schematic of a nonfouling electrochemical immunosensor for the carcinoembryonic antigen. It is based on novel composite wires made through the chemical grafting of easily available hyaluronic acid (HA) onto polyaniline (PANI) nanowires. The HA/PANI demonstrated excellent antifouling property both in single protein solutions and human serum samples.

[Evaluation of the diagnosis value of carcinoembryonic antigen in malignant pleural effusion].

PubMed

Yu, Y X; Tong, Z H; Zhou, X X; Liang, L R; Wang, Z; Xu, L L; Wang, X J; Wu, Y B; Li, H J; Lu, Z

2018-02-06

Objective: To investigate the diagnostic value of serum and pleural fluid carcinoembryonic antigen (CEA) for malignant pleural effusion (MPE). Methods: The concentration of CEA in serum and pleural fluid of 286 patients with the diagnosis confirmed by pleural biopsy through medical thoracoscopy were retrospectively analyzed. MPE was confirmed in 171 cases which were divided into two groups (adenocarcinoma group with 121cases and non-adenocarcinoma group with 50 cases) and benign pleural effusion in 115 cases. The optimal cutoff for MPE and MPE caused by adenocarcinoma were determined by using the ROC curve. Results: The concentration of serum CEA 12.27(3.80, 58.45) μg/L was significantly higher in MPE caused by adenocarcinoma than that of non-adenocarcinoma 1.91(1.08, 4.55) μg/L and benign effusion 1.32(0.86, 2.27) μg/L (both P <0.001), but there was no statistically significant difference between benign and non-adenocarcinoma effusion ( P =0.728). The concentration of pleural fluid CEA 160.70(30.48, 1 000.00) μg/L was significantly higher in MPE caused by adenocarcinoma than that of non-adenocarcinoma 1.77(0.51, 11.39) μg/L and benign effusion 1.09(0.60, 1.68) μg/L (both P <0.001), and higher in non-adenocarcinoma effusion than that of benign effusion ( P <0.05). The cutoff value of serum and pleural fluid CEA for MPE was 3.10 and 5.83 μg/L, the sensitivity respectively was 67.3% and 74.3%, the specificity respectively was 87.8% and 98.3%, positive predictive value respectively was 89.2% and 98.5%, negative predictive value respectively was 64.3% and 72.0%. The cutoff value of serum and pleural fluid CEA for MPE caused by adenocarcinoma was 3.54 and 7.30 μg/L, the sensitivity respectively was 76.0% and 91.7%, the specificity respectively was 74.0% and 72.0%, positive predictive value respectively was 87.6% and 88.8%, negative predictive value respectively was 56.1% and 78.3%. Conclusions: The concentration of serum and pleural fluid CEA have diagnostic significance to MPE, especially MPE caused by adenocarcinoma. The diagnostic value of pleural fluid CEA is superior to serum CEA.

High levels of serum CA15-3 and residual invasive tumor size are associated with poor prognosis for breast cancer patients with non-pathological complete response after neoadjuvant chemotherapy.

PubMed

Fujimoto, Yukie; Higuchi, Tomoko; Nishimukai, Arisa; Miyagawa, Yoshimasa; Kira, Ayako; Ozawa, Hiromi; Bun, Ayako; Imamura, Michiko; Miyoshi, Yasuo

2018-06-24

To identify surrogate markers for prognosis of breast cancer patients with non-pathological complete response (non-pCR) to neoadjuvant chemotherapy (NAC), our investigation focused on serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA15-3) as well as clinicopathological factors both pre- and post-NAC. A total of 185 breast cancer patients treated with NAC were recruited. Serum CEA and CA15-3 were measured at baseline and at completion of NAC. Among the non-pCR cancers (n = 142), disease-free survival (DFS) of patients with CA15-3-low at baseline (3-year DFS: 0.908, n = 73) was significantly better than of those with CA15-3-high (3-year DFS: 0.681, n = 69, P = 0.0134). Multivariable analysis demonstrated that baseline CA15-3 levels (hazard ratio (HR): 3.31, 95% confidence interval (CI): 1.28-10.23; P = 0.0122) and residual invasive size (HR: 4.47, 1.26-28.39; P = 0.0171) were significant independent factors for DFS. The combination of these factors proved to be accurate predictor for DFS regardless of breast cancer subtypes. The combination of residual invasive size and serum CA15-3 levels at baseline seems to be a significant and independent surrogate marker of poor outcome for patients with non-pCR. These findings suggest that these markers may be useful for identifying patients with inferior prognosis and candidates for additional adjuvant treatments. © 2018 Wiley Periodicals, Inc.

Polyethylene Glycol (PEG) Linked to Near Infrared (NIR) Dyes Conjugated to Chimeric Anti-Carcinoembryonic Antigen (CEA) Antibody Enhances Imaging of Liver Metastases in a Nude-Mouse Model of Human Colon Cancer

PubMed Central

Maawy, Ali A.; Hiroshima, Yukihiko; Zhang, Yong; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

2014-01-01

We report here that polyethylene glycol (PEG) linked to near infrared dyes conjugated to chimeric mouse-human anti-carcinoembryonic antigen (CEA) antibody greatly improves imaging of liver metastases in a nude mouse model of colon-cancer experimental metastases. PEGylated and non-PEGylated DyLight 650 and 750 dyes were conjugated to the chimeric anti-CEA antibody. The dyes were initially injected intravenously into nude mice without tumors. Tissue biodistribution was determined by tissue sonication and analyzing tissue dye concentration profiles over time. PEGylated dyes had significantly lower accumulation in the liver (p = 0.03 for the 650 dyes; p = 0.002 for the 750 dyes) compared to non-PEGylated dyes. In an experimental liver metastasis model of HT-29 colon cancer, PEGylated dyes conjugated to the anti-CEA antibody showed good labeling of metastatic tumors with high contrast between normal and malignant tissue which was not possible with the non-PEGylated dyes since there was so much non-specific accumulation in the liver. PEGylation of the DyLight 650 and 750 NIR dyes significantly altered tissue biodistribution, allowing brighter tissue labeling, decreased accumulation in normal organs, particularly the liver. This enabled high fidelity and high contrast imaging of liver metastases. PMID:24859320

Nonspecific cross-reacting antigen 50/90 is elevated in patients with breast, lung, and colon cancer.

PubMed

Allard, W J; Neaman, I E; Elting, J J; Barnett, T R; Yoshimura, H; Fritsche, H A; Yeung, K K

1994-03-01

A total of 22 genes have been identified in the carcinoembryonic antigen (CEA) gene family. The protein products of this family are highly homologous and include CEA, biliary glycoprotein, nonspecific cross-reacting antigen 50/90 (NCA 50/90), NCA 95, and pregnancy-specific beta-glycoprotein. We used a monoclonal antibody with high affinity to develop a specific enzyme-linked immunosorbent assay (ELISA) method for NCA 50/90 in serum and plasma. Our calibrators were based on affinity-purified recombinant protein from a baculovirus expression system. No significant reactivity with purified CEA, recombinant NCA 95, or recombinant biliary glycoprotein was found by Western blot analysis or in the ELISA method. Only 1 of 15 sera from pregnant women (chorionic gonadotropin > 1000 ng/ml) was positive in the NCA 50/90 ELISA, suggesting that this method does not detect pregnancy-specific glycoprotein. A cutoff value of 18 ng/ml was established based on the 95% value of serum and plasma from 147 healthy volunteers. Only 3 of 31 serum and plasma samples from patients with clinically inactive breast cancer were elevated above the cutoff value, but 44% of 136 samples from patients with clinically active breast cancer were positive. NCA 50/90 measurements were elevated in 7 of 25 patients with active breast cancer whose CEA and CA 15-3 values were below cutoff, and NCA 50/90 values do not correlate with CEA in breast cancer. In addition, we found sensitivities of 70, 39, and 42% for lung cancer, colon cancer, and leukemia, respectively. The sensitivity for non-small cell lung cancer was 85%, however, compared to 50% for small cell lung cancer. Serum from leukemia patients showed an overall sensitivity of 43%, but 71% (10 of 14) sera from patients with chronic myelogenous leukemia were positive compared to, for example, chronic lymphocytic leukemia where 0 of 7 sera had NCA 50/90 values above the cutoff. These studies suggest that NCA 50/90 may have clinical utility in the management of patients with a variety of cancers.

Vaccination of metastatic colorectal cancer patients with matured dendritic cells loaded with multiple major histocompatibility complex class I peptides.

PubMed

Kavanagh, Brian; Ko, Andrew; Venook, Alan; Margolin, Kim; Zeh, Herbert; Lotze, Michael; Schillinger, Brian; Liu, Weihong; Lu, Ying; Mitsky, Peggie; Schilling, Marta; Bercovici, Nadege; Loudovaris, Maureen; Guillermo, Roy; Lee, Sun Min; Bender, James; Mills, Bonnie; Fong, Lawrence

2007-10-01

Developing a process to generate dendritic cells (DCs) applicable for multicenter trials would facilitate cancer vaccine development. Moreover, targeting multiple antigens with such a vaccine strategy could enhance the efficacy of such a treatment approach. We performed a phase 1/2 clinical trial administering a DC-based vaccine targeting multiple tumor-associated antigens to patients with advanced colorectal cancer (CRC). A qualified manufacturing process was used to generate DC from blood monocytes using granulocyte macrophage colony-stimulating factor and IL-13, and matured for 6 hours with Klebsiella-derived cell wall fraction and interferon-gamma (IFN-gamma). DCs were also loaded with 6 HLA-A*0201 binding peptides derived from carcinoembryonic antigen (CEA), MAGE, and HER2/neu, as well as keyhole limpet hemocyanin protein and pan-DR epitope peptide. Four planned doses of 35x10(6) cells were administered intradermally every 3 weeks. Immune response was assessed by IFN-gamma enzyme-linked immunosorbent spot (ELISPOT). Matured DC possessed an activated phenotype and could prime T cells in vitro. In the trial, 21 HLA-A2+ patients were apheresed, 13 were treated with the vaccine, and 11 patients were evaluable. No significant treatment-related toxicity was reported. T-cell responses to a CEA-derived peptide were detected by ELISPOT in 3 patients. T cells induced to CEA possessed high avidity T-cell receptors. ELISPOT after in vitro restimulation detected responses to multiple peptides in 2 patients. All patients showed progressive disease. This pilot study in advanced CRC patients demonstrates DC-generated granulocyte macrophage colony-stimulating factor and IL-13 matured with Klebsiella-derived cell wall fraction and IFN-gamma can induce immune responses to multiple tumor-associated antigens in patients with advanced CRC.

The role of RCAS1 as a biomarker in diagnosing CRC and monitoring tumor recurrence and metastasis.

PubMed

Han, Su-xia; Wang, Jing; Wang, Li-juan; Jin, Gui-hua; Ying, Xia; He, Chen-chen; Guo, Xi-jing; Zhang, Jian-ying; Zhang, Ying; Zhu, Qing

2014-06-01

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) plays an important role in tumor progression by helping tumor cell to escape from host immunological surveillance or modifying the characteristics of connective tissue around. RCAS1 may appropriately reflect the development and prognosis of tumor. In the study, we sought to identify the clinical significance of RCAS1 in colorectal cancer (CRC) diagnosis and tumor recurrence monitoring. Immunohistochemistry (IHC) with tissue array slides was preformed to analyze RCAS1 protein expression in CRC, colorectal polyps, and normal colon tissues. RCAS1 levels in colorectal cancer were significantly higher than those in colorectal polyps and normal colon tissues (P<0.001). Silencing RCAS1 gene in human colonic adenocarcinoma cells decreased cell proliferation and enhanced apoptosis through the p53 signaling pathway. Further analysis by an enzyme-linked immunosorbent assay (ELISA) showed that serum RCAS1 levels in CRC are significantly higher than in healthy controls and polyps (P<0.05), in which the highest serum RCAS1 level is reported in the recurrence group. The serum RCAS1 levels have a significant correlation with clinical stage and pathologic grading. Furthermore, the positive rate of serum RCAS1 in CRC was 82.1 %, which was higher than carcinoembryonic antigen (CEA). Especially in CEA-negative cases, the sensitivity of RCAS1 was 88.2 %. Finally, CRC patients who were followed up showed a serum RCAS1 level which significantly decreased after surgery (P<0.001) and obviously increased in the recurrence group. Taken together, our data demonstrated that RCAS1 is not only a supplementary serological biomarker for CRC diagnosis but also useful for monitoring tumor recurrence. RCAS1 might be a supplementary serological marker for CRC.

Prospective randomised trial of early cytotoxic therapy for recurrent colorectal carcinoma detected by serum CEA.

PubMed Central

Hine, K R; Dykes, P W

1984-01-01

Of 663 patients treated with radical surgery for colorectal cancer, 52 showed a progressive rise in serum carcinoembryonic antigen (CEA) with no other evidence of recurrent disease and were randomised in a prospective study of chemotherapy. Twenty six patients in the treatment group received 5FU and methyl CCNU from the time of randomisation and the remaining 26 controls were given further therapy only if there were clinical indications. All patients were followed for five years or until their death and all but one (control) developed clinical evidence of recurrence. Overall there was no significant difference between the two groups with respect to disease free interval and survival. Whereas the rise in CEA in controls was generally progressive, marked inflections on the CEA curves were seen in the majority of patients receiving early treatment. Eight of 26 treated patients showed a fall in CEA of greater than 20% two months after starting therapy. These patients had a median disease free interval of 90 weeks and a median survival of 107 weeks, these figures being longer than those of treated patients who did not show a fall in CEA and control patients. The serum CEA therefore appeared to give important prognostic information in patients receiving cytotoxic treatment. Early therapy was generally well tolerated. PMID:6376291

A phase I clinical study of immunotherapy for advanced colorectal cancers using carcinoembryonic antigen-pulsed dendritic cells mixed with tetanus toxoid and subsequent IL-2 treatment.

PubMed

Liu, Ko-Jiunn; Chao, Tsu-Yi; Chang, Jang-Yang; Cheng, Ann-Lii; Ch'ang, Hui-Ju; Kao, Woei-Yau; Wu, Yu-Chen; Yu, Wei-Lan; Chung, Tsai-Rong; Whang-Peng, Jacqueline

2016-08-24

To better evaluate and improve the efficacy of dendritic cell (DC)-based cancer immunotherapy, we conducted a clinical study of patients with advanced colorectal cancer using carcinoembryonic antigen (CEA)-pulsed DCs mixed with tetanus toxoid and subsequent interleukin-2 treatment. The tetanus toxoid in the vaccine preparation serves as an adjuvant and provides a non-tumor specific immune response to enhance vaccine efficacy. The aims of this study were to (1) evaluate the toxicity of this treatment, (2) observe the clinical responses of vaccinated patients, and (3) investigate the immune responses of patients against CEA before and after treatment. Twelve patients were recruited and treated in this phase I clinical study. These patients all had metastatic colorectal cancer and failed standard chemotherapy. We first subcutaneously immunized patients with metastatic colorectal cancer with 1 × 10(6) CEA-pulsed DCs mixed with tetanus toxoid as an adjuvant. Patients received 3 successive injections with 1 × 10(6) CEA-pulsed DCs alone. Low-dose interleukin-2 was administered subcutaneously following the final DC vaccination to boost the growth of T cells. Patients were evaluated for adverse event and clinical status. Blood samples collected before, during, and after treatment were analyzed for T cell proliferation responses against CEA. No severe treatment-related side effects or toxicity was observed in patients who received the regular 4 DC vaccine injections. Two patients had stable disease and 10 patients showed disease progression. A statistically significant increase in proliferation against CEA by T cells collected after vaccination was observed in 2 of 9 patients. The results of this study indicate that it is feasible and safe to treat colorectal cancer patients using this protocol. An increase in the anti-CEA immune response and a clinical benefit was observed in a small fraction of patients. This treatment protocol should be further evaluated in additional colorectal cancer patients with modifications to enhance T cell responses. ClinicalTrials.gov (identifier NCT00154713 ), September 8, 2005.

Measurement of Lung Cancer Tumor Markers in a Glass Wool Company Workers Exposed to Respirable Synthetic Vitreous Fiber and Dust.

PubMed

Abtahi, Shabnam; Malekzadeh, Mahyar; Nikravan, Ghafour; Ghaderi, Abbas

2018-01-01

Occupational exposures to respirable synthetic vitreous fiber (SVF) and dust are associated with many lung diseases including lung cancer. Low-dose computed tomography is used for screening patients who are highly suspicious of having lung carcinoma. However, it seems not to be cost-effective. Serum biomarkers could be a useful tool for the surveillance of occupational exposure, by providing the possibility of diagnosing lung cancer in its early stages. To determine if serum carcinoembryonic antigen (CEA) and cytokeratin fragment (CYFRA) 21-1 levels in workers exposed more than normal population to respirable SVF and dust may be used as indicators of progression towards lung cancer. An analytic cross-sectional study, including 145 personnel of a glass wool company, along with 25 age-matched healthy individuals, was conducted to investigate the relationship between occupational exposure to respirable SVFs and dust and serum levels of two lung/pleura serum tumor markers, CEA and CYFRA 21-1, measured by ELISA. Individuals exposed to higher than the recommended levels of respirable SVF had higher serum concentrations of CEA and CYFRA 21-1, compared to controls (p=0.008 and 0.040, respectively), as well as in comparison to those exposed to lower than recommended OSHA levels (p=0.046 and 0.033, respectively). Workers with >9 years work experience, had significantly (p=0.045) higher levels of serum CYFRA 21-1 than those with ≤9 years of experience. It seems that working for >9 years in sites with detectable levels of respirable SVF and dust would increase the levels of known lung cancer serum tumor markers. Transferring these workers to sites with respirable SVF concentrations lower than the limit of detection in the air is recommended.

Serum CA 19-9 as a prognostic factor in patients with metastatic gastric cancer.

PubMed

Jo, Jae-Cheol; Ryu, Min-Hee; Koo, Dong-Hoe; Ryoo, Baek-Yeol; Kim, Hwa Jung; Kim, Tae Won; Choi, Kee Don; Lee, Gin Hyug; Jung, Hwoon-Yong; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kim, Jin-Ho; Kang, Yoon-Koo

2013-12-01

To evaluate tumor markers as prognostic factors in patients with metastatic or recurrent gastric cancer receiving first-line chemotherapy. Between January 2000 and December 2008, 1178 patients with metastatic or recurrent gastric cancer were assayed for expression of three serum tumor markers, CA 19-9, CA 72-4 and carcinoembryonic antigen (CEA), prior to the initiation of first-line chemotherapy. Elevated serum concentrations of carbohydrate antigen (CA) 19-9 (>37 U/mL), CA 72-4 (>4 U/mL) and carcinoembryonic antigen (CEA) (>6 ng/mL) were observed in 38, 56 and 33% of patients, respectively. Univariate analysis showed that elevated serum concentration of each of the three markers, CA 19-9 (P = 0.001), CA 72-4 (P = 0.001) and CEA (P = 0.030), was significantly associated with poor patient prognosis. However, multivariate analysis showed that an elevated CA 19-9 concentration only was significantly associated with shorter survival (hazard ratio [HR] 1.22; 95% CI, 1.08-1.37, P = 0.002). In the good risk and moderate risk groups, previously defined by clinical factors alone, survival was significantly lower in patients with elevated CA 19-9 (P < 0.001 and P = 0.021, respectively), but this difference was not observed in the poor-risk group. Elevated serum CA 19-9 concentration in patients with metastatic or recurrent gastric cancer, especially in good or moderate risk groups, is an independent negative predictor of prognosis. © 2012 Wiley Publishing Asia Pty Ltd.

Multiplexed detection of tumor markers with multicolor quantum dots based on fluorescence polarization immunoassay.

PubMed

Tian, Jianniao; Zhou, Liujin; Zhao, Yanchun; Wang, Yuan; Peng, Yan; Zhao, Shulin

2012-04-15

A multicolor quantum dot (QD)-based nanosensor for multiplex detection of two tumor markers in a homogeneous format based on fluorescence polarization immunoassay was proposed. QDs520 and QDs620 were labeled alpha-fetoprotein(α-AFP) and carcinoembryonic antigen (CEA), respectively. After separated and purified by ultrafiltration, they were used in fluorescence polarization immunoassay for the simultaneous detection of human serum alpha-fetoprotein and carcinoembryonic antigen. Under the optimal conditions, the multi-analyte immunosensor had a wide linear range (from 0.5 ng mL(-1) to 500 ng mL(-1)) for both two tumor markers and good correlation (0.996 for α-AFP and 0.993 for CEA). The detection limits (LOD) were 0.36 ng mL(-1) for CEA and 0.28 ng mL(-1) for α-AFP (S/N=3). The carcinoembryonic antigen and fetoprotein in clinical serum samples were simultaneously detected. The results from 28 serum samples had a good agreement with enzyme-linked immunosorbent assay (ELISA). The relative standard deviation and the recovery suggested that the precision and the accuracy of this analytical method were satisfactory. This strategy with high sensitivity, good specificity, easy procedures and short analysis time shows great promise for clinical diagnoses and basic discovery. The application of QDs with longer fluorescence lifetime and small fluorescence polarization can be used for the determination of high molecular-weight substances which cannot be analyzed using dye fluorescence polarization immunoassay. Copyright © 2012 Elsevier B.V. All rights reserved.

In vitro and in vivo comparison of binding of 99m-Tc-labeled anti-CEA MAb F33-104 with 99m-Tc-labeled anti-CEA MAb BW431/26.

PubMed

Watanabe, N; Oriuchi, N; Sugiyama, S; Kuroki, M; Matsuoka, Y; Tanada, S; Murata, H; Inoue, T; Sasaki, Y

1999-01-01

The purpose of this study was to assess the potential for radio-immunodetection (RAID) of murine anti-carcinoembryonic antigen (CEA) monoclonal antibody (MAb) F33-104 labeled with technetium-99m (99m-Tc) by a reduction-mediated labeling method. The binding capacity of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA by means of in vitro procedures such as immunoradiometric assay and cell binding assay and the biodistribution of 99m-Tc-labeled anti-CEA MAb F33-104 in normal nude mice and nude mice bearing human colon adenocarcinoma LS180 tumor were investigated and compared with 99m-Tc-labeled anti-CEA MAb BW431/26. The in vitro binding rate of 99m-Tc-labeled anti-CEA MAb F33-104 with CEA in solution and attached to the cell membrane was significantly higher than 99m-Tc-labeled anti-CEA MAb BW431/261 (31.4 +/- 0.95% vs. 11.9 +/- 0.55% at 100 ng/mL of soluble CEA, 83.5 +/- 2.84% vs. 54.0 +/- 2.54% at 10(7) of LS 180 cells). In vivo, accumulation of 99m-Tc-labeled anti-CEA MAb F33-104 was higher at 18 h postinjection than 99m-Tc-labeled anti-CEA MAb BW431/26 (20.1 +/- 3.50% ID/g vs. 14.4 +/- 3.30% ID/g). 99m-Tc-activity in the kidneys of nude mice bearing tumor was higher at 18 h postinjection than at 3 h (12.8 +/- 2.10% ID/g vs. 8.01 +/- 2.40% ID/g of 99m-Tc-labeled anti-CEA MAb F33-104, 10.7 +/- 1.70% ID/g vs. 8.10 +/- 1.75% ID/g of 99m-Tc-labeled anti-CEA MAb BW431/26). 99m-Tc-labeled anti-CEA MAb F33-104 is a potential novel agent for RAID of recurrent colorectal cancer.

Lectin-Based Assay for Glycoform-Specific Detection of α2,6-sialylated Transferrin and Carcinoembryonic Antigen in Tissue and Body Fluid.

PubMed

Ito, Hiromi; Hoshi, Kyoka; Honda, Takashi; Hashimoto, Yasuhiro

2018-05-30

Antibodies are useful for detecting glycoprotein antigens, but a conventional antibody recognizes only a protein epitope rather than a glycan. Thus, glycan isoform detection generally requires time- and labor-consuming processes such as lectin affinity column chromatography followed by sandwich ELISA. We recently found antigen-antibody reactions that were inhibited by lectin binding to glycans on the glycoprotein antigen, leading to a convenient glycoform-specific assay. Indeed, Sambucus sieboldiana agglutinin (SSA) lectin, a binder to sialylα2,6galactose residue, inhibited antibody binding to α2,6-sialylated transferrin (Tf) (SSA inhibition). SSA inhibition was not observed with other glycoforms, such as periodate-treated, sialidase-treated and sialidase/galactosidase-treated Tf, suggesting that the assay was glycoform-specific. SSA inhibition was also applicable for visualizing localization of α2,6-sialylated-Tf in a liver section. This is the first immunohistochemical demonstration of glycoform localization in a tissue section. SSA inhibition was utilized for establishing ELISA to quantify α2,6-sialylated carcinoembryonic antigen (CEA), a marker for various cancers. In addition, α2,6-sialylated-CEA was visualized in a colonic adenocarcinoma section by SSA inhibition. The method would further be applicable to a simple and rapid estimation of other α2,6-sialylated glycoproteins and have a potential aid to histopathological diagnosis.

Searching for New Biomarkers and the Use of Multivariate Analysis in Gastric Cancer Diagnostics.

PubMed

Kucera, Radek; Smid, David; Topolcan, Ondrej; Karlikova, Marie; Fiala, Ondrej; Slouka, David; Skalicky, Tomas; Treska, Vladislav; Kulda, Vlastimil; Simanek, Vaclav; Safanda, Martin; Pesta, Martin

2016-04-01

The first aim of this study was to search for new biomarkers to be used in gastric cancer diagnostics. The second aim was to verify the findings presented in literature on a sample of the local population and investigate the risk of gastric cancer in that population using a multivariant statistical analysis. We assessed a group of 36 patients with gastric cancer and 69 healthy individuals. We determined carcinoembryonic antigen, cancer antigen 19-9, cancer antigen 72-4, matrix metalloproteinases (-1, -2, -7, -8 and -9), osteoprotegerin, osteopontin, prothrombin induced by vitamin K absence-II, pepsinogen I, pepsinogen II, gastrin and Helicobacter pylori for each sample. The multivariate stepwise logistic regression identified the following biomarkers as the best gastric cancer predictors: CEA, CA72-4, pepsinogen I, Helicobacter pylori presence and MMP7. CEA and CA72-4 remain the best markers for gastric cancer diagnostics. We suggest a mathematical model for the assessment of risk of gastric cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

CEA (Carcinoembryonic Antigen) Test

MedlinePlus

... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Semen Analysis Serotonin Serum Free Light Chains Sex Hormone Binding Globulin ... Transferrin Receptor Stool Culture Stool Elastase Strep ...

CEA blood test

MedlinePlus

Carcinoembryonic antigen blood test ... A blood sample is needed . ... When the needle is inserted to draw blood, some people feel moderate pain. Others feel only a prick or stinging. Afterward, there may be some throbbing or a slight bruise. This ...

Serum VEGF levels in the early diagnosis and severity assessment of non-small cell lung cancer

PubMed Central

Lai, Yanzhen; Wang, Xueping; Zeng, Tao; Xing, Shan; Dai, Shuqin; Wang, Junye; Chen, Shulin; Li, Xiaohui; Xie, Ying; Zhu, Yuanying; Liu, Wanli

2018-01-01

Background: Effective biomarkers are essential to the differential diagnosis and severity assessment of non-small cell lung cancer (NSCLC). This study explored the use of the serum vascular endothelial growth factor (VEGF) levels as a biomarker with the aim of achieving better management of NSCLC. Methods: Serum VEGF levels were assayed via enzyme-linked immunosorbent assay in 180 patients with NSCLC, 136 patients with benign pulmonary nodules, and 119 healthy controls. We additionally detected the serum concentration of three traditional biomarkers—carcinoembryonic antigen (CEA), cancer antigen (CA)-125, and cytokeratin 19 fragments (Cyfra 21-1)—to comparatively evaluate the efficiency and diagnostic value of VEGF in patients with NSCLC. We further evaluated the relationship between serum VEGF levels and clinicopathologic parameters. VEGF levels were compared between pro- and post-surgical patients using the Wilcoxon matched-pairs signed-rank test. DNA was isolated from the primary tumors. EGFR mutations were detected by Scorpions amplification refractory mutation system (ARMS). Results: Patients with NSCLC had significantly higher serum concentration of VEGF, compared to those with benign pulmonary nodules and healthy controls (P <0.0001). As a diagnostic biomarker of NSCLC, VEGF had area under the curve values of 0.824 and 0.839, sensitivities of 75.0% and 75.0%, and specificities of 93.3% and 95.6% when compared with healthy people and patients with benign pulmonary nodules, respectively; notably, these values were greater than those of CA125, Cyfra 21-1 and CEA. Furthermore, a model in which VEGF was combined with CEA, CA125, and Cyfra 21-1 was more effective for NSCLC diagnosis than VEGF alone (sensitivity, 85.0% and 84.4; specificity, 90.0% and 91.9% vs. healthy controls and patients with benign pulmonary nodules, respectively). When use to identify early-stage NSCLC, VEGF showed a better diagnostic efficacy than other biomarkers. The pro-surgical VEGF levels were significantly higher than those measured 25-30 days after surgery. Moreover, VEGF concentration differed significantly among cases according to TNM stages and malignant grades (P <0.0001). EGFR mutations and the size of benign pulmonary nodules did not affect the level of serum VEGF significantly. Conclusion: The serum VEGF levels exhibited relatively high sensitivity and specificity for NSCLC, and may therefore be a useful diagnostic biomarker. Furthermore, the serum VEGF levels could be used to assess prognosis and curative effects. PMID:29760791

Application of boronated anti-CEA immunoliposome to tumour cell growth inhibition in in vitro boron neutron capture therapy model.

PubMed Central

Yanagië, H.; Tomita, T.; Kobayashi, H.; Fujii, Y.; Takahashi, T.; Hasumi, K.; Nariuchi, H.; Sekiguchi, M.

1991-01-01

An immunoliposome containing a 10B-compound has been examined as a selective drug delivery system in boron neutron-capture therapy. Liposomes, conjugated with monoclonal antibodies specific for carcinoembryonic antigen (CEA) were shown to bind selectively to cells bearing CEA on their surface. The immunoliposomes attached to tumour cells suppressed growth in vitro upon thermal neutron irradiation and suppression was dependent upon the concentration of the 10B-compound in the liposomes and on the density of antibody conjugated to the liposomes. The results suggest that immunoliposomes containing the 10B-compound could act as a selective and efficient carrier of 10B atoms to target tumour cells in boron neutron-capture therapy. Images Figure 1 PMID:2021537

A novel classifier based on three preoperative tumor markers predicting the cancer-specific survival of gastric cancer (CEA, CA19-9 and CA72-4).

PubMed

Guo, Jing; Chen, Shangxiang; Li, Shun; Sun, Xiaowei; Li, Wei; Zhou, Zhiwei; Chen, Yingbo; Xu, Dazhi

2018-01-12

Several studies have highlighted the prognostic value of the individual and the various combinations of the tumor markers for gastric cancer (GC). Our study was designed to assess establish a new novel model incorporating carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4). A total of 1,566 GC patients (Primary cohort) between Jan 2000 and July 2013 were analyzed. The Primary cohort was randomly divided into Training set (n=783) and Validation set (n=783). A three-tumor marker classifier was developed in the Training set and validated in the Validation set by multivariate regression and risk-score analysis. We have identified a three-tumor marker classifier (including CEA, CA19-9 and CA72-4) for the cancer specific survival (CSS) of GC (p<0.001). Consistent results were obtained in the both Training set and Validation set. Multivariate analysis showed that the classifier was an independent predictor of GC (All p value <0.001 in the Training set, Validation set and Primary cohort). Furthermore, when the leave-one-out approach was performed, the classifier showed superior predictive value to the individual or two of them (with the highest AUC (Area Under Curve); 0.618 for the Training set, and 0.625 for the Validation set), which ascertained its predictive value. Our three-tumor marker classifier is closely associated with the CSS of GC and may serve as a novel model for future decisions concerning treatments.

Crystal structure of the anti-(carcinoembryonic antigen) single-chain Fv antibody MFE-23 and a model for antigen binding based on intermolecular contacts.

PubMed

Boehm, M K; Corper, A L; Wan, T; Sohi, M K; Sutton, B J; Thornton, J D; Keep, P A; Chester, K A; Begent, R H; Perkins, S J

2000-03-01

MFE-23 is the first single-chain Fv antibody molecule to be used in patients and is used to target colorectal cancer through its high affinity for carcinoembryonic antigen (CEA), a cell-surface member of the immunoglobulin superfamily. MFE-23 contains an N-terminal variable heavy-chain domain joined by a (Gly(4)Ser)(3) linker to a variable light-chain (V(L)) domain (kappa chain) with an 11-residue C-terminal Myc-tag. Its crystal structure was determined at 2.4 A resolution by molecular replacement with an R(cryst) of 19.0%. Five of the six antigen-binding loops, L1, L2, L3, H1 and H2, conformed to known canonical structures. The sixth loop, H3, displayed a unique structure, with a beta-hairpin loop and a bifurcated apex characterized by a buried Thr residue. In the crystal lattice, two MFE-23 molecules were associated back-to-back in a manner not seen before. The antigen-binding site displayed a large acidic region located mainly within the H2 loop and a large hydrophobic region within the H3 loop. Even though this structure is unliganded within the crystal, there is an unusually large region of contact between the H1, H2 and H3 loops and the beta-sheet of the V(L) domain of an adjacent molecule (strands DEBA) as a result of intermolecular packing. These interactions exhibited remarkably high surface and electrostatic complementarity. Of seven MFE-23 residues predicted to make contact with antigen, five participated in these lattice contacts, and this model for antigen binding is consistent with previously reported site-specific mutagenesis of MFE-23 and its effect on CEA binding.

Survivin gene levels in the peripheral blood of patients with gastric cancer independently predict survival

PubMed Central

2009-01-01

Background The detection of circulating tumor cells (CTC) is considered a promising tool for improving risk stratification in patients with solid tumors. We investigated on whether the expression of CTC related genes adds any prognostic power to the TNM staging system in patients with gastric carcinoma. Methods Seventy patients with TNM stage I to IV gastric carcinoma were retrospectively enrolled. Peripheral blood samples were tested by means of quantitative real time PCR (qrtPCR) for the expression of four CTC related genes: carcinoembryonic antigen (CEA), cytokeratin-19 (CK19), vascular endothelial growth factor (VEGF) and Survivin (BIRC5). Results Gene expression of Survivin, CK19, CEA and VEGF was higher than in normal controls in 98.6%, 97.1%, 42.9% and 38.6% of cases, respectively, suggesting a potential diagnostic value of both Survivin and CK19. At multivariable survival analysis, TNM staging and Survivin mRNA levels were retained as independent prognostic factors, demonstrating that Survivin expression in the peripheral blood adds prognostic information to the TNM system. In contrast with previously published data, the transcript abundance of CEA, CK19 and VEGF was not associated with patients' clinical outcome. Conclusions Gene expression levels of Survivin add significant prognostic value to the current TNM staging system. The validation of these findings in larger prospective and multicentric series might lead to the implementation of this biomarker in the routine clinical setting in order to optimize risk stratification and ultimately personalize the therapeutic management of these patients. PMID:20028510

[Usefulness of evaluation of carcinoembryonic antigen (CEA) and soluble fragments of cytokeratin 18-th (TPS) in postoperative monitoring of patients with colorectal cancer].

PubMed

Sandelewski, Artur; Kokocińska, Danuta; Partyka, Robert; Kocot, Jacek; Starzewski, Jacek; Chanek, Izabela; Jałowiecki, Przemysław

2005-06-01

The aim of this study is to diagnose the evaluation of concentration of CEA and TPS in postoperative monitoring of patients with colorectal cancer. We measured 178 consecutive patients with histopathologically confirmed colorectal cancer: 101 men and 78 women ages 22-86 (average age 54.7). Markers' CEA nad TPS concentration were evaluated before operation and every month after operation during the first 3 months and then every 3 months during 2 years. Relapse was detected in 47 patients. In postoperative period in non-relapse group the mean (the average) concentration of CEA was 1.92+/-2.03 ng/ml and TPS 65.54+/-33.96 U/l and respectively in relapse group for CEA was 1.92+/-2.03 ng/ml and for TPS 65.54+/-33.96 U/l. The obtained results in investigated group show significantly statistical. The relapse was confirmed by using CEA concentration in 42 patients (89.4%). In case of TPS concentration relapse was confirmed in 38 patients (80.85%). The relapse was detected in 45 patients (95.74) if increase in CEA or TPS concentration was treated as a way of detecting relapse. TPS markers point out that the increase of TPS concentartion may be ahead of relapse symptoms at about 2-6 months. TPS is a useful marker in postoperative monitoring of patients with colorectal cancer. The evaluation of TPS concentration allow to diagnose the recurrence of colorectal cancer earlier than by using burden markers--CEA. Common evaluation of TPS and CEA increase sensitivity in detection of relapse in patients with colorectal cancer.

The role of pleural fluid MAGE RT-nested PCR in the diagnosis of malignant pleural effusion.

PubMed

Jeon, Eun Ju; Park, Hye Kyeong; Jeon, Kyeongman; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kim, Hojoong; Kwon, O Jung; Ki, Chang-Seok; Kim, Jong-Won; Shim, Young Mog; Um, Sang-Won

2012-11-01

  Melanoma antigen (MAGE) genes are expressed in tumor cells, the testis and the placenta. The purpose of this prospective study was to investigate the sensitivity, specificity, and accuracy of the carcinoembryonic antigen (CEA), MAGE reverse transcriptase-nested polymerase chain reaction (RT-nested PCR), and cytology of pleural fluid in the diagnosis of malignant pleural effusion.   Patients in whom unilateral pleural effusion was identified on chest radiography from January to December 2009 were included in the study. MAGE genes were analyzed by RT-nested PCR using MAGE A1-6 common primers.   Of 81 enrolled patients, 46 were diagnosed as malignant pleural effusion, and 24 were diagnosed as benign pleural effusion. The diagnoses of 11 patients were not confirmed in this study. The diagnostic sensitivity, specificity, and accuracy of MAGE RT-nested PCR were 61.4%, 95.7%, and 73.1%, respectively. The diagnostic sensitivities of cytology and CEA (>5 ng/mL) were 61.4% and 75.0%, respectively. Among 17 patients with negative cytology who had malignant pleural effusion, 12 and 10 patients were positive for CEA (>5.0 ng/mL) and MAGE RT-nested PCR, respectively. However, of five patients with malignant pleural effusion that was not recognized by cytology and CEA, MAGE RT-nested PCR correctly predicted a malignant etiology in only one additional patient (20%).   MAGE RT-nested PCR seems to add little on the combination of conventional methods in the diagnosis of malignant effusion. © 2012 Tianjin Lung Cancer Institute and Wiley Publishing Asia Pty. Ltd.

A sensitive label-free amperometric CEA immunosensor based on graphene-nafion nanocomposite film as an enhanced sensing platform.

PubMed

Li, Yan; Yang, Wei-Kang; Fan, Man-Qi; Liu, Ao

2011-01-01

A novel approach to fabricate a label-free amperometric immunosensor for the detection of carcinoembryonic antigen (CEA) was described. Herein, methylene blue (MB), gold nanoparticles (AuNPs) and carcinoembryonic antibody (anti-CEA) were layer-by-layer assembled on the graphene-Nafion nanocomposite film-modified electrode by means of a self-assembling technique and the opposite-charged adsorption. Subsequently, the stepwise self-assembling procedure of the immunosensor was further characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The factors influencing the performance of the resulting immunosensor were studied in detail. The developed procedure showed improved features, including larger amount and higher immunoactivity of the immobilized antibody and repeatable regeneration of the sensor, as well as direct, rapid and simple determination for the antigen without multiple separation and labeling steps. The immunosensor could detect the target protein in a range of 0.5 to 120 ng/mL with a limit of 0.17 ng/mL (at 3σ). Finally, the immunosensing system was evaluated on several clinical samples. Analytical results were found to be in satisfactory agreement with those detected by the enzyme-linked immunosorbent assay (ELISA) method, indicating that this new method was a promising alternative tool for clinical diagnosis.

Electrochemical immunoassay for carcinoembryonic antigen based on signal amplification strategy of nanotubular mesoporous PdCu alloy.

PubMed

Cai, Yanyan; Li, He; Li, Yuyang; Zhao, Yanfang; Ma, Hongmin; Zhu, Baocun; Xu, Caixia; Wei, Qin; Wu, Dan; Du, Bin

2012-01-01

Interests in using nanoporous metals for biosensing applications have been increasing. Herein, nanotubular mesoporous PdCu (NM-PdCu) alloy is used to fabricate a novel label-free electrochemical immunosensor for cancer biomarker carcinoembryonic antigen (CEA). It operates through physisorption of anti-CEA on NM-PdCu and the mixture of sulfonated graphene sheets (HSO(3)-GS) and thionine (TH) functionalized glassy carbon electrode interface as the detection platform. In this study, chitosan (CS)-PdCu is bound very strongly to carcinoembryonic antibody (anti-CEA), because of the good electron conductivity, high surface area, and good biocompatibility. CS-PdCu is immobilized on electrodes by electrostatic interactions between the negatively charged sulfo group of HSO(3)-GS and the abundant positively charged amino groups of chitosan. TH acts as the redox probe. Under the optimized conditions, the electrochemical immunosensor exhibits a wide working range from 0.01 to 12 ng/mL with a low detection limit of 4.86 pg/mL. The accuracy, reproducibility, and stability of the immunosensor are acceptable. The assay is evaluated for real serum samples, receiving satisfactory results. The nanoporous metal materials-based immunoassay provides a promising approach in clinical application and thus represents a versatile detection method. Copyright © 2012 Elsevier B.V. All rights reserved.

Breast carcinoma metastasis to the lacrimal gland: Two case reports

PubMed Central

NICKELSEN, MARIE N.; VON HOLSTEIN, SARAH; HANSEN, ALASTAIR B.; PRAUSE, JAN U.; HEEGAARD, STEFFEN

2015-01-01

A 77-year-old female, with proptosis, reduced eye motility and diplopia which had developed over two to three months and a 69-year-old female with proptosis, oedema of the eyelid, reduced motility and ptosis, which had developed over three weeks, are presented in the present study. Computed tomography scans revealed irregular lacrimal gland tumours in the two patients. The two patients had history of breast cancer. The first breast cancer metastasis in the lacrimal gland demonstrated a cribriform growth pattern containing ductal elements. The epithelial tumour cells stained positive for cytokeratin (1–8, 10, 14–16, 18 and 19), oestrogen receptor, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and gross cystic disease fluid protein 15 (GCDFP-15). The second metastatic tumour was positive for EMA and estrogen receptor, but variably positive for CEA and GCDFP-15. The metastasis in the lacrimal gland was a pleomorphic tumour. The tumour cells were positive for EMA and variably positive for oestrogen and CEA. Metastases to the lacrimal gland are extremely rare, and metastases to the lacrimal gland should be considered in the diagnoses of lacrimal gland tumours. The present study aimed to describe two such cases and draw attention to breast carcinomas as a differential diagnosis and the most frequent cause of lacrimal gland metastasis. PMID:26622620

Cell membrane antigen-antibody complex dissociation by the widely used glycine-HCL method: an unreliable procedure for studying antibody internalization.

PubMed

Tsaltas, G; Ford, C H

1993-02-01

Methods following the process of binding and internalization of antibodies to cell surface antigens have often employed low pH isoosmolar buffers in order to dissociate surface antigen-antibody complexes. One of the most widely used buffers is a 0.05 M glycine-HCL buffer pH 2.8. Since the efficacy of action of this buffer was critical to a series of internalization experiments employing monoclonal antibodies (Mabs) to carcinoembryonic antigen (CEA) expressing cancer cell lines in this laboratory, we tested its performance in a number of different assays. Our results indicate that this buffer only partially dissociates antigen-antibody bonds and therefore can introduce major inaccuracies in internalization experiments.

Electrochemical immunosensor for simultaneous detection of multiplex cancer biomarkers based on graphene nanocomposites.

PubMed

Chen, Xia; Jia, Xinle; Han, Jingman; Ma, Jie; Ma, Zhanfang

2013-12-15

In this work, a sandwich-format electrochemical immunosensor for simultaneous determination of carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) was fabricated using biofunctional carboxyl graphene nanosheets (CGS) as immunosensing probes, which were fabricated by means of immobilization of toluidine blue (TB) and labeled anti-CEA (Ab2,1), Prussian blue (PB) and anti-AFP (Ab2,2) successively on CGS. The capture anti-CEA (Ab1,1) and anti-AFP (Ab1,2) were immobilized onto the chitosan-Au nanoparticles (CHIT-AuNPs) modified electrode through 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and N-hydroxy succinimide (EDC/NHS). Experimental results revealed that this sandwich-type immunoassay enabled simultaneous detection of CEA and AFP with linear range of 0.5-60 ng mL(-1) for both analytes. The detection limit was 0.1 ng mL(-1) for CEA and 0.05 ng mL(-1) for AFP (S/N=3). The assay results of serum samples with the proposed method were in a good agreement with the reference values from the standard ELISA method. And the negligible cross-reactivity between the two analytes allows it to possess potential promise in clinical diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Decreased levels of circulating sex hormones as a biomarker of lung cancer in male patients with solitary pulmonary nodules.

PubMed

Gu, Tao; Wen, Zongmei; Xu, Shufeng; Hua, Haixia; Zhang, Zhi; Wen, Tao; Fu, Zhanzhao; Lv, Xin

2014-06-01

An early differentiation of malignant from benign solitary pulmonary nodules (SPNs) is essential for management and prognosis of lung cancer. Here we investigated whether measurement of circulating sex hormones could be useful for an early detection of malignancy among patients with SPNs. We recruited 47 patients with malignant SPNs 45 patients with benign SPNs, and 32 healthy persons. Testosterone, estradiol, and progesterone were measured. Carcinoembryonic antigen (CEA) as well as TNF-α, IL-1 and IL-6 were also measured. We found that sex hormones were decreased significantly in patients with malignant SPNs, as compared to patients with benign SPNs and healthy controls (P<0.05). Sex hormones levels showed a trend to decline in patients with benign SPNs as compared to normal controls, but the difference was not statistically significant (P>0.05). CEA levels were only abnormally elevated in eight patients with lung adenocarcinoma. The inflammatory cytokines were remarkably higher in both patients than in normal controls. However, there was no statistical difference in these cytokines among patients. The reduced sex hormones levels seemed to be uniquely associated with lung cancer. Therefore, measurement of sex hormones may have clinical potential in the diagnosis of malignancy in patients with SPNs.

Irinotecan as a new agent for urachal cancer.

PubMed

Kume, Haruki; Tomita, Kyoichi; Takahashi, Sayuri; Fukutani, Keiko

2006-01-01

The urachal carcinoma, in a 64-year-old male with multiple lung metastases, had shown the resistance to several anti-neoplastic agents including cisplatinum, methotrexate, 5-FU, doxorubicin, epirubicin, and mitomycin C. Because the tumor was adenocarcinoma producing mucin and serum carcinoembryonic antigen (CEA) increased, which resembled colorectal carcinoma, we administrated Irinotecan, which was very effective as the CEA decreased from 98.3 to 38.7 ng/ml and the pulmonary metastatic lesions were reduced by 60%. To our knowledge, this is the first case with urachal carcinoma in which Irinotecan was effective. Copyright (c) 2006 S. Karger AG, Basel.

CA 125 and other tumor markers in uterine leiomyomas and their association with lesion characteristics

PubMed Central

Babacan, Ali; Kizilaslan, Cem; Gun, Ismet; Muhcu, Murat; Mungen, Ercument; Atay, Vedat

2014-01-01

The aim of this study was to investigate the factors associated with serum levels of several tumor markers in a group of patients operated for uterine myoma. One hundred thirty-seven female patients operated for uterine myoma were included. Serum samples were examined for CA 125, CA 19-9, CA 15-3, carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) levels as part of routine workup. Pathological and morphological characteristics of the patients were retrieved from medical records. The mean age was 46.7 ± 8.8 years (range, 22-85 y). Abnormally high levels of CA 125, CA 19-9, CA 15-3, CEA, and AFP were found in 19.7%, 6.6%, 5.1%, 3.7%, and 1.5% of the patients, respectively. Patients with additional adenomyosis and patients with at least one large myoma (≥ 5 cm diameter) had significantly higher levels of CA 125. Multivariate analysis identified coexistence of adenomyosis (OR 7.7 [95% CI, 2.6-23.0], p < 0.001) and presence of at least one large myoma (OR 5.6 [1.4-22.8], p = 0.016) as independent predictors of abnormally high CA 125 levels. CA 125 levels are affected by the tumor size and coexistence of adenomyosis in uterine leiomyomas. Indirect mechanisms caused by large myoma size such as peritoneal irritation may be responsible for CA 125 elevations. PMID:24955185

Indicators of inappropriate tumour marker use through the mining of electronic health records.

PubMed

Gion, Massimo; Cardinali, Giulia; Trevisiol, Chiara; Zappa, Marco; Rainato, Giulia; Fabricio, Aline S C

2017-08-01

Although the issue of monitoring appropriateness of tumour markers (TMs) request in outpatients remains crucial, proper indicators are still demanding. The present study developed and explored indicators of inappropriate TM ordering in outpatients through the data mining of electronic health records (EHRs). Carcinoembryonic antigen (CEA), alfa-fetoprotein (AFP), carbohydrate antigen (CA)125, CA15.3, CA19.9, and prostate-specific antigen (PSA) ordered in outpatients during a year were examined by mining EHRs of a Local Health Authority in Italy. Evidence-based criteria were used to develop performance indicators. Demographic and clinical information associated with TM orders were examined. A total of 80 813 TMs were ordered in 52 536 outpatients (1.54 markers/patient). Indicators related to disease codes, gender, age, and TM repetitions were developed, and their application showed that (1) CA15.3 and CEA are prevalently requested in patients with cancer (79.2% and 65.6%) whereas the other TMs are largely requested also in patients without cancer; (2) requests of PSA in women and of CA125 or CA15.3 in men are negligible; (3) although requests in people older than 80 years are relevant (16.4% of total), the highest rate of request of all markers occurs in patients aged 40 to 79 years; (4) CA15.3 and CEA are mainly requested in cancer cases between 50 and 79 years and AFP, CA19.9, and CA125 in those between 60 and 69 years; (5) <50% of PSA orders are associated with cancer code for all age intervals; and (6) multiple repetitions of AFP, CA125, CA15.3, CA19.9, and CEA are prevalent in cancer patients or benign diseases to which TMs are appropriate, whereas PSA repetitions occur mainly in patients without cancer. The developed indicators resulted suitable to monitor TM overordering in outpatients through the mining of EHRs. The present study is a first approach towards the use of big-data mining for TM appropriateness evaluation purposes. © 2017 John Wiley & Sons, Ltd.

Clinical Significance of Fluorine-18-fluorodeoxyglucose Positron Emission Tomography/computed Tomography in the Follow-up of Colorectal Cancer: Searching off Approaches Increasing Specificity for Detection of Recurrence

PubMed Central

Okuyucu, Kursat; Hancerliogulları, Oguz; Alagoz, Engin; San, Huseyin; Arslan, Nuri

2017-01-01

Abstract Background Nearly 40% of colorectal cancer (CRC) recurs within 2 years after resection of primary tumor. Imaging with fluorine-18-fluorodeoxyglucose (l8F-FDG) positron emission tomography/computed tomography (PET/CT) is the most recent modality and often applied for the evaluation of metastatic spread during the follow-up period. Our goal was to study the diagnostic importance of 18F-FDG-PET/CT data of maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and the difference of SUVmax on dual-time imaging in CRC. Patients and methods We examined the SUVmax value of lesions on control or restaging 18F-FDG-PET/CT of 53 CRC patients. All lesions with increased SUVmax values were confirmed by colonoscopy or histopathology. We compared PET/CT results with conventional imaging modalities (CT, MRI) and tumor markers (carbohydrate antigen 19-9 [Ca 19-9], carcinoembryonic antigen [CEA]). Results Mean SUVmax was 6.9 ± 5.6 in benign group, 12.7 ± 6.1 in malignant group. Mean TLG values of malignant group and benign group were 401 and 148, respectively. 18F-FDG-PET/CT was truely positive in 48% of patients with normal Ca 19-9 or CEA levels and truely negative in 10% of cases with elevated Ca 19-9 or CEA. CT or MRI detected suspicious malignancy in 32% of the patients and 18F-FDG-PET/CT was truely negative in 35% of these cases. We found the most important and striking statistical difference of TLG value between the groups with benign and recurrent disease. Conclusions Although SUVmax is a strong metabolic parameter (p = 0.008), TLG seems to be the best predictor in recurrence of CRC (p = 0.001); both are increasing the specificity of 18F-FDG-PET/CT. PMID:29333115

Clinical Significance of Fluorine-18-fluorodeoxyglucose Positron Emission Tomography/computed Tomography in the Follow-up of Colorectal Cancer: Searching off Approaches Increasing Specificity for Detection of Recurrence.

PubMed

Ince, Semra; Okuyucu, Kursat; Hancerliogulları, Oguz; Alagoz, Engin; San, Huseyin; Arslan, Nuri

2017-12-01

Nearly 40% of colorectal cancer (CRC) recurs within 2 years after resection of primary tumor. Imaging with fluorine-18-fluorodeoxyglucose ( l8 F-FDG) positron emission tomography/computed tomography (PET/CT) is the most recent modality and often applied for the evaluation of metastatic spread during the follow-up period. Our goal was to study the diagnostic importance of 18 F-FDG-PET/CT data of maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and the difference of SUVmax on dual-time imaging in CRC. We examined the SUVmax value of lesions on control or restaging 18 F-FDG-PET/CT of 53 CRC patients. All lesions with increased SUVmax values were confirmed by colonoscopy or histopathology. We compared PET/CT results with conventional imaging modalities (CT, MRI) and tumor markers (carbohydrate antigen 19-9 [Ca 19-9], carcinoembryonic antigen [CEA]). Mean SUVmax was 6.9 ± 5.6 in benign group, 12.7 ± 6.1 in malignant group. Mean TLG values of malignant group and benign group were 401 and 148, respectively. 18 F-FDG-PET/CT was truely positive in 48% of patients with normal Ca 19-9 or CEA levels and truely negative in 10% of cases with elevated Ca 19-9 or CEA. CT or MRI detected suspicious malignancy in 32% of the patients and 18 F-FDG-PET/CT was truely negative in 35% of these cases. We found the most important and striking statistical difference of TLG value between the groups with benign and recurrent disease. Although SUVmax is a strong metabolic parameter (p = 0.008), TLG seems to be the best predictor in recurrence of CRC (p = 0.001); both are increasing the specificity of 18 F-FDG-PET/CT.

A Pilot Study to Evaluate the Safety and Clinical Outcomes of Vaccination with Recombinant CEA-MUC-1-TRICOM (PANVAC) Poxviral-based Vaccines in Patients with Metastatic Carcinoma

PubMed Central

Gulley, James L.; Arlen, Philip M.; Tsang, Kwong-Yok; Yokokawa, Junko; Palena, Claudia; Poole, Diane J.; Remondo, Cinzia; Cereda, Vittore; Jones, Jacquin L.; Pazdur, Mary P.; Higgins, Jack P.; Hodge, James W.; Steinberg, Seth M.; Kotz, Herbert; Dahut, William L.; Schlom, Jeffrey

2009-01-01

Purpose: Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary endpoint of this study was vaccine safety, with immunologic and clinical responses as secondary endpoints. Experimental Design: We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM, composed of B7.1, ICAM-1, and LFA-3) engineered into vaccinia (PANVAC-V) as a prime and fowlpox (PANVAC-F) as booster vaccinations. Results: The vaccine was well-tolerated. Apart from injection-site reaction, no grade II or greater toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccine in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of > 20% in the size of large liver metastasis. Conclusions: This vaccine strategy appears to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted. PMID:18483372

Simultaneous quantitation of cytokeratin-19 fragment and carcinoembryonic antigen in human serum via quantum dot-doped nanoparticles.

PubMed

Chen, Zhenhua; Liang, Rongliang; Guo, Xinxin; Liang, Junyu; Deng, Qiaoting; Li, Min; An, Taixue; Liu, Tiancai; Wu, Yingsong

2017-05-15

A novel quantum dot-doped polystyrene nanoparticles-based lateral flow test strips (QPs-LFTS) system was developed to simultaneously detect a cytokeratin-19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA) in human serum to aid the diagnosis and prognosis of lung cancer. Quantum dot-doped carboxylate-functionalized polystyrene nanoparticles (QPs) were prepared and introduced as fluorescent reporters in QPs-LFTS. The detection was based on a sandwich immunoassay and performed on lateral flow test strips, with an assay time of 15min. The strips were read by a fluorescence strip reader to obtain the fluorescence peak heights of the test lines (H T ) and the control line (H C ). The ratio of H T /H C was used for quantitation. The QPs showed excellent photoproperties and good performance. Under optimal conditions, the QPs-LFTS system exhibited a wide linear range for CYFRA 21-1 (1.3-480ng/mL) and CEA (2.8-680ng/mL). The detection limits for CYFRA 21-1 and CEA were 0.16 and 0.35ng/mL, respectively. The recovery and reproducibility of the method were satisfactory. Furthermore, excellent correlations (n =120, R 2 =0.9862, P<0.0001 for CYFRA 21-1; n =70, R 2 =0.9509, P<0.0001 for CEA) were obtained between the QPs-LFTS and commercially available chemiluminescence immunoassay kits in clinical serum testing. The results indicate that this developed test system is highly efficient and is expected to be useful for early screening and prognosis evaluation for lung cancer patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Pretargeting of carcinoembryonic antigen-expressing cancers with a trivalent bispecific fusion protein produced in myeloma cells.

PubMed

Rossi, Edmund A; Chang, Chien-Hsing; Losman, Michele J; Sharkey, Robert M; Karacay, Habibe; McBride, William; Cardillo, Thomas M; Hansen, Hans J; Qu, Zhengxing; Horak, Ivan D; Goldenberg, David M

2005-10-01

To characterize a novel trivalent bispecific fusion protein and evaluate its potential utility for pretargeted delivery of radionuclides to tumors. hBS14, a recombinant fusion protein that binds bispecifically to carcinoembryonic antigen (CEA) and the hapten, histamine-succinyl-glycine (HSG), was produced by transgenic myeloma cells and purified to near homogeneity in a single step using a novel HSG-based affinity chromatography system. Biochemical characterization included size-exclusion high-performance liquid chromatography (SE-HPLC), SDS-PAGE, and isoelectric focusing. Functional characterization was provided by BIAcore and SE-HPLC. The efficacy of hBS14 for tumor pretargeting was evaluated in CEA-expressing GW-39 human colon tumor-bearing nude mice using a bivalent HSG hapten (IMP-241) labeled with (111)In. Biochemical analysis showed that single-step affinity chromatography provided highly purified material. SE-HPLC shows a single protein peak consistent with the predicted molecular size of hBS14. SDS-PAGE analysis shows only two polypeptide bands, which are consistent with the calculated molecular weights of the hBS14 polypeptides. BIAcore showed the bispecific binding properties and suggested that hBS14 possesses two functional CEA-binding sites. This was supported by SE-HPLC immunoreactivity experiments. All of the data suggest that the structure of hBS14 is an 80 kDa heterodimer with one HSG and two CEA binding sites. Pretargeting experiments in the mouse model showed high uptake of radiopeptide in the tumor, with favorable tumor-to-nontumor ratios as early as 3 hours postinjection. The results indicate that hBS14 is an attractive candidate for use in a variety of pretargeting applications, particularly tumor therapy with radionuclides and drugs.

The diagnostic value of cytokeratins and carcinoembryonic antigen immunostaining in differentiating hepatocellular carcinomas from intrahepatic cholangiocarcinomas.

PubMed

Stroescu, Cezar; Herlea, Vlad; Dragnea, Adrian; Popescu, Irinel

2006-03-01

To study the differences between the hepatocellular carcinoma (HCC) and peripheral type of cholangiocarcinoma (CHC) using cytokeratin (CK) and carcinoembryonic antigen (CEA) expressions and assessing their accuracy on paraffin sections in the differential diagnosis. The following antibodies were analyzed: AB1 complex (anti CK9-CK20), AB2 complex (anti CK1-CK8), pCEA, and the monoclonal antibodies against cytokeratins CK7, CK8/18, CK17 and CK19. In the mmunohistochemical studies, 15 selected surgically resected liver tumors, 10 HCCs and 5 CHCs, with well established diagnosis (by morphological criteria) were included. Other markers, such as AFP si CA 19-9, were not available. No CHC, but 50% of HCCs were positive for CEA, presenting a canalicular staining pattern. For CK 7, all but one (which was focally positive), meaning 80% of CHCs were diffusely positive, whereas only two HCCs were positive. For CK 19, 80% of CHCs were diffusely positive, while all but two HCCs (a moderately and a poorly differentiated tumor) were negative. For CK 8/18, 70% of HCCs were diffusely positive, whereas only 20% of CHCs were positive. For CK 17, 60% of CHCs were positive, while all HCCs were negative. 80% of CHCs were positive for AB1 anti-CKs complex, whereas only 50% of HCCs were positive, and relating to AB2 anti-CKs complex, 50% of HCCs were diffusely positive and only 20% of CHCs. The immunohistochemical expression of CKs and CEA might be considered helpful in addition to other diagnostic criteria for the differential diagnosis of primary carcinomas of the liver, especially in difficult cases.

Gold nanoparticle-based low limit of detection Love wave biosensor for carcinoembryonic antigens.

PubMed

Li, Shuangming; Wan, Ying; Su, Yan; Fan, Chunhai; Bhethanabotla, Venkat R

2017-09-15

In this work, a Love wave biosensing platform is described for detecting cancer-related biomarker carcinoembryonic antigen (CEA). An ST 90°-X quartz Love wave device with a layer of SiO 2 waveguide was combined with gold nanoparticles (Au NPs) to amplify the mass loading effect of the acoustic wave sensor to achieve a limit of detection of 37pg/mL. The strategy involves modifying the Au NPs with anti-CEA antibody conjugates to form nanoprobes in a sandwich immunoassay. The unamplified detection limit of the Love wave biosensor is 9.4ng/mL. This 2-3 order of magnitude reduction in the limit of detection brings the SAW platform into the range useful for clinical diagnosis. Measurement electronics and microfluidics are easily constructed for acoustic wave biosensors, such as the Love wave device described here, allowing for robust platforms for point of care applications for cancer biomarkers in general. Copyright © 2017 Elsevier B.V. All rights reserved.

Predictors of the patency of self-expandable metallic stents in malignant gastroduodenal obstruction.

PubMed

Kim, Seung Han; Chun, Hoon Jai; Yoo, In Kyung; Lee, Jae Min; Nam, Seung Joo; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck

2015-08-14

To investigate the predictive factors of self-expandable metallic stent patency after stent placement in patients with inoperable malignant gastroduodenal obstruction. A total of 116 patients underwent stent placements for inoperable malignant gastroduodenal obstruction at a tertiary academic center. Clinical success was defined as acceptable decompression of the obstructive lesion within the malignant gastroduodenal neoplasm. We evaluated patient comorbidities and clinical statuses using the World Health Organization's scoring system and categorized patient responses to chemotherapy using the Response Evaluation Criteria in Solid Tumors criteria. We analyzed the relationships between possible predictive factors and stent patency. Self-expandable metallic stent placement was technically successful in all patients (100%), and the clinical success rate was 84.2%. In a multivariate Cox proportional hazards model, carcinoembryonic antigen (CEA) levels were correlated with a reduction in stent patency [P = 0.006; adjusted hazard ratio (aHR) = 2.92, 95%CI: 1.36-6.25]. Palliative chemotherapy was statistically associated with an increase in stent patency (P = 0.009; aHR = 0.27, 95%CI: 0.10-0.72). CEA levels can easily be measured at the time of stent placement and may help clinicians to predict stent patency and determine the appropriate stent procedure.

Brenner tumor of the ovary: a comparative immunohistochemical and ultrastructural study with transitional cell carcinoma of the bladder.

PubMed

Ordóñez, N G; Mackay, B

2000-01-01

Because of a fancied light microscopic resemblance to transitional epithelium (urothelium), Brenner tumor (BT) of the ovary is commonly described as a transitional cell neoplasm. An inability to detect a great deal of similarity between the two at the ultrastructural level prompted this electron microscopic study comparing 3 benign Brenner tumors with normal urothelium and 6 transitional cell carcinomas (TCC) of varying histologic grade from the urinary bladder. To complement the ultrastructural observations, the immunophenotype of 8 benign BTs was evaluated together with that of 12 TCCs of the bladder using antibodies to thrombomodulin (TM), cytokeratin 20, cytokeratin 7, and carcinoembryonic antigen (CEA), all of which have been shown to react with TCCs of urothelial origin. At the ultrastructural level, there was only limited evidence of a morphologic likeness between the epithelial cells of BTs and those of the benign or neoplastic urothelium. The immunophenotype of the two tumors also differed significantly in that there was no reactivity for TM or cytokeratin 20 in the BTs, while these markers were expressed in the TCCs. Both BTs and TCCs were positive for cytokeratin 7 and may express CEA.

Preparation of Fe(3)O(4)@C@CNC multifunctional magnetic core/shell nanoparticles and their application in a signal-type flow-injection photoluminescence immunosensor.

PubMed

Chu, Chengchao; Li, Meng; Li, Long; Ge, Shenguang; Ge, Lei; Yu, Jinghua; Yan, Mei; Song, Xianrang

2013-11-01

We describe here the preparation of carbon-coated Fe3O4 magnetic nanoparticles that were further fabricated into multifunctional core/shell nanoparticles (Fe3O4@C@CNCs) through a layer-by-layer self-assembly process of carbon nanocrystals (CNCs). The nanoparticles were applied in a photoluminescence (PL) immunosensor to detect the carcinoembryonic antigen (CEA), and CEA primary antibody was immobilized onto the surface of the nanoparticles. In addition, CEA secondary antibody and glucose oxidase were covalently bonded to silica nanoparticles. After stepwise immunoreactions, the immunoreagent was injected into the PL cell using a flow-injection PL system. When glucose was injected, hydrogen peroxide was obtained because of glucose oxidase catalysis and quenched the PL of the Fe3O4@C@CNC nanoparticles. The here proposed PL immunosensor allowed us to determine CEA concentrations in the 0.005–50 ng·mL-1 concentration range, with a detection limit of 1.8 pg·mL-1.

[Potential role of cholesterol in distinguishing malignant from benign pleural effusion].

PubMed

Plavec, Goran; Tomić, Ilija; Nidzović, Natasa; Radojcić, Branko; Aćimović, Slobodan; Bokun, Radojka

2004-01-01

Cholesterol and carcinoembryonic antigen (CEA) levels in pleural effusion and sera, were measured in 199 patients with pleural effusions of various origins. Malignant cause was found in 93, and nonmalignant in 106 patients. Mean cholesterol level in sera of patient with malignant disease was 5.0 +/- 0.93 mmol/L, and in nonmalignant group 4.34 +/- 1.32 mmol/L. The difference was not statistically significant. Mean cholesterol level in nonmalignant pleural effusions was higher thAn those in malignant (2.51 +/- 1.23 mmol/L; and 2.28 +/- 1.06 mmol/L), but the difference was also not significant. Average pleural fluid/serum cholesterol ratio (Holl/S) in nonmalignant group was 0.61 +/- 0.32 and in malignant group 0.46 +/- 0.22. The difference between those mean values was significant. Higher ratio, at the cut off value of 0.5 was found in 79/106 and in 25/93 malignant patients. Calculated sensitivity was 75%, specificity 73%, positive predictive value 76%, negative predictive value 65% and accuracy 69%. Significant negative correlation between Holi/S and pleural fluid CEA was found (p < 0.05). It was assumed that pleural fluid/serum cholesterol ratio lower than 0.5 could be of great benefit, as an additional test in the differentiation of malignant from benign pleural effusion.

An immunohistochemical study of primary signet-ring cell carcinoma of the stomach and colorectum: III. expressions of EMA, CEA, CA19-9, CDX-2, p53, Ki-67 antigen, TTF-1, vimentin, and p63 in normal mucosa and in 42 cases

PubMed Central

Terada, Tadashi

2013-01-01

There have no comprehensive immunohistochemical studies of primary signet ring cell carcinoma (SRCC) in the stomach and colorectum. The author examined the expression of nine common antigens (EMA, CEA, CA19-9, CDX-2, p53, Ki-67 antigen, TTF-1, vimentin, and p63) in the non-tumorous normal epithelium of the stomach and colorectum and in 42 cases of primary SRCC of the stomach (30 cases) and colorectum (12 cases). The normal epithelium of the stomach and colon consistently (100%) expressed EMA, CEA, CA19-9, CDX-2, and Ki-67 (labeling <15%). Normal epithelium of these locations never expressed p53, TTF-1, vimentin, and p63. In the primary gastric SRCC, the expression percentage of EMA was 57% (17/30), CEA 100% (30/30), CA19-9 100% (30/30), CDX-2 43% (13/30), p53 83% (25/30), Ki-67 100% (30/30) (labeling index= 36 ± 23 %), TTF-1 0% (0/30), vimentin 0% (0/30), and p63 0% (0/30). In primary colorectal SRCC, the expression percentage of EMA was 25% (3/12), CEA 100% (12/12), CA19-9 100% (12/12), CDX-2 93% (28/30), p53 75% (9/12), Ki-67 100% (30/30) (labeling index= 47% ± 26 %), TTF-1 0% (0/12), vimentin 0% (0/12), and p63 0% (0/12). A comparative statistical analysis showed significant difference in EMA (gastric SRCC 57% vs colorectal SRCC 25%) and CDX-2 (43% vs 93%). There were no significant differences in the other seven antigens’ expression between primary gastric SRCC and primary colorectal SRCC. These findings provide much knowledge of primary SRCC of the stomach and colorectum. The data indicated primary gastric SRCC frequently express EMA but not CDX-2 whereas primary colorectal SRCC frequently express CDX-2 but not EMA. These findings also suggest that EMA and CDX-2 are down-regulated during the gastric SRCC carcinogenesis. This down regulations may be associated with the malignant transformation of gastric SRCC. The data of colorectal SRCC suggest EMA is markedly down-regulated and also suggest that this EMA down-regulation may be associated with the carcinogenesis of colorectal SRCC. The expression pattern of EMA and CDX-2 may be useful in differential diagnosis between primary gastric SRCC and primary colorectal SRCC in the metastatic sites of SRCC. PMID:23573309

CEA monitoring of palliative treatment for colorectal carcinoma.

PubMed Central

Herrera, M A; Chu, T M; Holyoke, E D; Mittelman, A

1977-01-01

Palliative treatment was applied to 131 cases of unresectable or palliatively resected colorectal carcinoma being monitored with serial CEA determinations. There were 84 instances of disease progression with 67 (80%) of them showing an increase in CEA above pretreatment levels or maintaining high levels, and 17 (20%) showing a fall when compared to pretreatment values or maintaining low initial values. There was a clear-cut regression of the disease in only 9 instances. In all 9, the CEA clearly dropped or maintained low valles throughout the period of regression. No patient in regression had a rise or maintained an elevated CEA level. These changes in CEA followed closely the clinical response of our patient to the use of a particular agent, although for the Nitrosourea compounds there may be a tendency to lower the CEA regardless of the patient's tumor response to the drug. This could be due to the fact that the Nitrosoureas produce a diffuse block of cellular activity, both at the nucleous and cytoplasm; while other compounds act as alkylating agents or by inhibition of enzymes involved in the metabolism of nucleic acids (i.e., 5-FU inhibiting thymidylate synthetase). In general, longer survival was found in those patients who had initially lower levels of CEA as compared to those with high initial levels. The patients with a favorable CEA response to the treatment (falling CEA or maintained low value), even in many who did not show a clinical response had a longer survival than the group with rising or stable high levels. The main value in CEA monitoring of patients resides in its correlation with the amount of disease present and then its ability to detect progression of tumor mass which is not clinically measurable. PMID:64132

Role of β1-Integrin in Colorectal Cancer: Case-Control Study

PubMed Central

Oh, Bo-Young; Kim, Kwang Ho; Chung, Soon Sup; Hong, Kyoung Sook

2014-01-01

Purpose In the metastatic process, interactions between circulating tumor cells (CTCs) and the extracellular matrix or surrounding cells are required. β1-Integrin may mediate these interactions. The aim of this study was to investigate whether β1-integrin is associated with the detection of CTCs in colorectal cancer. Methods We enrolled 30 patients with colorectal cancer (experimental group) and 30 patients with benign diseases (control group). Blood samples were obtained from each group, carcinoembryonic antigen (CEA) mRNA for CTCs marker and β1-integrin mRNA levels were estimated by using reverse transcription-polymerase chain reaction, and the results were compared between the two groups. In the experimental group, preoperative results were compared with postoperative results for each marker. In addition, we analyzed the correlation between the expressions of β1-integrin and CEA. Results CEA mRNA was detected more frequently in colorectal cancer patients than in control patients (P = 0.008). CEA mRNA was significantly reduced after surgery in the colorectal cancer patients (P = 0.032). β1-Integrin mRNA was detected more in colorectal cancer patients than in the patients with benign diseases (P < 0.001). In colorectal cancer patients, expression of β1-integrin mRNA was detected more for advanced-stage cancer than for early-stage cancer (P = 0.033) and was significantly decreased after surgery (P < 0.001). In addition, expression of β1-integrin mRNA was significantly associated with that of CEA mRNA in colorectal cancer patients (P = 0.001). Conclusion In conclusion, β1-integrin is a potential factor for forming a prognosis following surgical resection in colorectal cancer patients. β1-Integrin may be a candidate for use as a marker for early detection of micrometastatic tumor cells and for monitoring the therapeutic response in colorectal cancer patients. PMID:24851215

Efficacy, Safety, and Cost of Therapy of the Traditional Chinese Medicine, Catalpol, in Patients Following Surgical Resection for Locally Advanced Colon Cancer.

PubMed

Fei, Baogang; Dai, Wei; Zhao, Shouhe

2018-05-15

BACKGROUND The aim of this study was to evaluate the efficacy, safety, and cost of treatment of the traditional Chinese herbal medicine, catalpol, in patients following surgical resection for locally advanced colon cancer. MATERIAL AND METHODS The 345 patients who had undergone surgical resection for locally advanced colon adenocarcinoma, were divided into three groups: a placebo-treated group (n=115); patients treated with an intraperitoneal injection of 10 mg/kg catalpol twice a day for 12 weeks (treatment group) (n=115); patients treated with 5 mg/kg intravenous bevacizumab twice a week for 12 weeks (control group) (n=115). Serum levels of carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), matrix metalloproteinases-2 (MMP-2), and matrix metalloproteinases-9 (MMP-9) were measured. Patient overall survival (OS), cancer-free survival (CFS), adverse effects, and cost of therapy were evaluated. Statistical analysis included the Wilcoxon rank sum test and Tukey's test for clinicopathological response at 95% confidence interval (CI). RESULTS Patients in the catalpol-treated group had significantly reduced serum levels of CA 19-9 (p=0.0002, q=3.202), CEA (p=0.0002, q=3.007), MMP-2 (p£0.0001, q=6.883), and MMP-9 (p<0.0001, q=3.347). Only non-fatal adverse effects occurred in the catalpol treatment group (p<0.0001, q=5.375). OS and CFS were significantly increased in the catalpol treatment group compared with the placebo group (p<0.0001 q=7.586). The cost of catalpol treatment compared favorably with other treatments (p<0.0001, q=207.17). CONCLUSIONS In this preliminary study, treatment with the Chinese herbal medicine, catalpol, showed benefits in clinical outcome, at low cost, and with no serious complications.

Myxedema coma and cardiac ischemia in relation to thyroid hormone replacement therapy in a 38-year-old Japanese woman.

PubMed

Taguchi, Takafumi; Iwasaki, Yasumasa; Asaba, Koichi; Takao, Toshihiro; Hashimoto, Kozo

2007-12-01

Although thyroid hormone deficiency, either clinical or subclinical, is an established risk factor for cardiovascular disease, coronary ischemia in a premenopausal woman in her 30s is relatively rare. A 38-year-old woman was referred to our hospital with severe breathlessness and depressed consciousness. Physical examination found facial, abdominal, and pretibial edema; coarse hair, hoarse voice, and dry skin; engorged jugular veins; a distant heart sound; and reduced bilateral entry of air into the chest. Laboratory examinations revealed severe hypothyroidism, hyperlipidemia, and elevated serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125). A computed tomography scan showed massive pleural and pericardial effusions. After 3 months of levothyroxine replacement therapy (initial dose: 12.5 microg/d; maintenance dose: 125 microg/d), all abnormal laboratory values associated with hypothyroidism returned to within normal ranges, with the exception of a transient and paradoxical rise in serum thyroid-stimulating hormone levels. However, 3 weeks after the initiation of therapy, the patient reported intermittent chest pains during the course of therapy, and a coronary artery angiogram revealed diffuse stenosis of all 3 branches. The patient underwent coronary artery bypass grafting, with subsequent improvement in coronary perfusion. Careful cardiovascular evaluation is recommended before the start of thyroid hormone replacement therapy. In addition, care should be taken in the interpretation of serum biomarkers of malignancy (eg, CEA, CA125) in patients with myxedema, as values may be elevated in a hypothyroid state. Long-standing hypothyroidism may be associated with severe coronary atherosclerosis, even in a relatively young, premenopausal woman. The potential adverse cardiovascular effects of thyroid hormone must be considered during replacement therapy, even in relatively young patients.

Glucose oxidase-initiated cascade catalysis for sensitive impedimetric aptasensor based on metal-organic frameworks functionalized with Pt nanoparticles and hemin/G-quadruplex as mimicking peroxidases.

PubMed

Zhou, Xingxing; Guo, Shijing; Gao, Jiaxi; Zhao, Jianmin; Xue, Shuyan; Xu, Wenju

2017-12-15

Based on cascade catalysis amplification driven by glucose oxidase (GOx), a sensitive electrochemical impedimetric aptasensor for protein (carcinoembryonic antigen, CEA as tested model) was proposed by using Cu-based metal-organic frameworks functionalized with Pt nanoparticles, aptamer, hemin and GOx (Pt@CuMOFs-hGq-GOx). CEA aptamer loaded onto Pt@CuMOFs was bound with hemin to form hemin@G-quadruplex (hGq) with mimicking peroxidase activity. Through sandwich-type reaction of target CEA and CEA aptamers (Apt1 and Apt2), the obtained Pt@CuMOFs-hGq-GOx as signal transduction probes (STPs) was captured to the modified electrode interface. When 3,3-diaminobenzidine (DAB) and glucose were introduced, the cascade reaction was initiated by GOx to catalyze the oxidation of glucose, in situ generating H 2 O 2 . Simultaneously, the decomposition of the generated H 2 O 2 was greatly promoted by Pt@CuMOFs and hGq as synergistic peroxide catalysts, accompanying with the significant oxidation process of DAB and the formation of nonconductive insoluble precipitates (IPs). As a result, the electron transfer in the resultant sensing interface was effectively hindered and the electrochemical impedimetric signal (EIS) was efficiently amplified. Thus, the high sensitivity of the proposed CEA aptasensor was successfully improved with 0.023pgmL -1 , which may be promising and potential in assaying certain clinical disease related to CEA. Copyright © 2017 Elsevier B.V. All rights reserved.

Label-free fluorimetric detection of CEA using carbon dots derived from tomato juice.

PubMed

Miao, Hong; Wang, Lan; Zhuo, Yan; Zhou, Zinan; Yang, Xiaoming

2016-12-15

A facile-green strategy to synthesize carbon dots (CDs) with a quantum yield (QY) of nearly 13.9% has been built up, while tomato juice served as the carbon source. Interestingly, not only the precursor of CDs and the whole synthesis procedure were environmental-friendly, but this type of CDs also exhibited multiple advantages including high fluorescent QY, excellent photostability, non-toxicity and satisfactory stability. Significantly, a label-free sensitive assay for detecting carcinoembryonic antigen (CEA) in a continuous and recyclable way has been proposed on the basis of adsorption and desorption of aptamers by the surface of CDs through a competitive mechanism. To be specific, the richness of carboxyl groups of the CDs enabled strong adsorption of ssDNA to the surface of CDs through π-π stacking interactions, resulting in the effective fluorescence quenching by forming CDs-aptamer complexes. The stronger binding affinity between CEA and CEA-aptamer than the π-π stacking interactions has been taken advantage to achieve immediate recovery of the fluorescence of CDs once CEA was introduced. Thereby, quantitative evaluation of CEA concentration in a broad range from 1ngmL(-1) to 0.5ngmL(-1) with the detection limit of 0.3ngmL(-1) was realized in this way. This strategy can be applied in a recyclable way, broadening the sensing application of CDs with biocompatibility. Besides, the CDs were used for cell imaging, potentiating them towards diverse purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Recognizes a Novel Ligand, Mac-2-binding Protein, Characteristically Expressed on Human Colorectal Carcinomas*

PubMed Central

Nonaka, Motohiro; Ma, Bruce Yong; Imaeda, Hirotsugu; Kawabe, Keiko; Kawasaki, Nobuko; Hodohara, Keiko; Kawasaki, Nana; Andoh, Akira; Fujiyama, Yoshihide; Kawasaki, Toshisuke

2011-01-01

Dendritic cell (DC)-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) is a type II transmembrane C-type lectin expressed on DCs such as myeloid DCs and monocyte-derived DCs (MoDCs). Recently, we have reported that DC-SIGN interacts with carcinoembryonic antigen (CEA) expressed on colorectal carcinoma cells. CEA is one of the most widely used tumor markers for gastrointestinal cancers such as colorectal cancer. On the other hand, other groups have reported that the level of Mac-2-binding protein (Mac-2BP) increases in patients with pancreatic, breast, and lung cancers, virus infections such as human immunodeficiency virus and hepatitis C virus, and autoimmune diseases. Here, we first identified Mac-2BP expressed on several colorectal carcinoma cell lines as a novel DC-SIGN ligand through affinity chromatography and mass spectrometry. Interestingly, we found that DC-SIGN selectively recognizes Mac-2BP derived from some colorectal carcinomas but not from the other ones. Furthermore, we found that the α1-3,4-fucose moieties of Le glycans expressed on DC-SIGN-binding Mac-2BP were important for recognition. DC-SIGN-dependent cellular interactions between immature MoDCs and colorectal carcinoma cells significantly inhibited MoDC functional maturation, suggesting that Mac-2BP may provide a tolerogenic microenvironment for colorectal carcinoma cells through DC-SIGN-dependent recognition. Importantly, Mac-2BP was detected as a predominant DC-SIGN ligand expressed on some primary colorectal cancer tissues from certain parts of patients in comparison with CEA from other parts, suggesting that DC-SIGN-binding Mac-2BP bearing tumor-associated Le glycans may become a novel potential colorectal cancer biomarker for some patients instead of CEA. PMID:21515679

Uropathogenic E. coli Exploit CEA to Promote Colonization of the Urogenital Tract Mucosa

PubMed Central

Muenzner, Petra; Kengmo Tchoupa, Arnaud; Klauser, Benedikt; Brunner, Thomas; Putze, Johannes; Dobrindt, Ulrich; Hauck, Christof R.

2016-01-01

Attachment to the host mucosa is a key step in bacterial pathogenesis. On the apical surface of epithelial cells, members of the human carcinoembryonic antigen (CEA) family are abundant glycoproteins involved in cell-cell adhesion and modulation of cell signaling. Interestingly, several gram-negative bacterial pathogens target these receptors by specialized adhesins. The prototype of a CEACAM-binding pathogen, Neisseria gonorrhoeae, utilizes colony opacity associated (Opa) proteins to engage CEA, as well as the CEA-related cell adhesion molecules CEACAM1 and CEACAM6 on human epithelial cells. By heterologous expression of neisserial Opa proteins in non-pathogenic E. coli we find that the Opa protein-CEA interaction is sufficient to alter gene expression, to increase integrin activity and to promote matrix adhesion of infected cervical carcinoma cells and immortalized vaginal epithelial cells in vitro. These CEA-triggered events translate in suppression of exfoliation and improved colonization of the urogenital tract by Opa protein-expressing E. coli in CEA-transgenic compared to wildtype mice. Interestingly, uropathogenic E. coli expressing an unrelated CEACAM-binding protein of the Afa/Dr adhesin family recapitulate the in vitro and in vivo phenotype. In contrast, an isogenic strain lacking the CEACAM-binding adhesin shows reduced colonization and does not suppress epithelial exfoliation. These results demonstrate that engagement of human CEACAMs by distinct bacterial adhesins is sufficient to blunt exfoliation and to promote host infection. Our findings provide novel insight into mucosal colonization by a common UPEC pathotype and help to explain why human CEACAMs are a preferred epithelial target structure for diverse gram-negative bacteria to establish a foothold on the human mucosa. PMID:27171273

Evaluation of a CLEIA automated assay system for the detection of a panel of tumor markers.

PubMed

Falzarano, Renato; Viggiani, Valentina; Michienzi, Simona; Longo, Flavia; Tudini, Silvestra; Frati, Luigi; Anastasi, Emanuela

2013-10-01

Tumor markers are commonly used to detect a relapse of disease in oncologic patients during follow-up. It is important to evaluate new assay systems for a better and more precise assessment, as a standardized method is currently lacking. The aim of this study was to assess the concordance between an automated chemiluminescent enzyme immunoassay system (LUMIPULSE® G1200) and our reference methods using seven tumor markers. Serum samples from 787 subjects representing a variety of diagnoses, including oncologic, were analyzed using LUMIPULSE® G1200 and our reference methods. Serum values were measured for the following analytes: prostate-specific antigen (PSA), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9), and cytokeratin 19 fragment (CYFRA 21-1). For the determination of CEA, AFP, and PSA, an automatic analyzer based on chemiluminescence was applied as reference method. To assess CYFRA 21-1, CA125, CA19-9, and CA15-3, an immunoradiometric manual system was employed. Method comparison by Passing-Bablok analysis resulted in slopes ranging from 0.9728 to 1.9089 and correlation coefficients from 0.9977 to 0.9335. The precision of each assay was assessed by testing six serum samples. Each sample was analyzed for all tumor biomarkers in duplicate and in three different runs. The coefficients of variation were less than 6.3 and 6.2 % for within-run and between-run variation, respectively. Our data suggest an overall good interassay agreement for all markers. The comparison with our reference methods showed good precision and reliability, highlighting its usefulness in clinical laboratory's routine.

Graphene oxide-labeled sandwich-type impedimetric immunoassay with sensitive enhancement based on enzymatic 4-chloro-1-naphthol oxidation.

PubMed

Hou, Li; Cui, Yuling; Xu, Mingdi; Gao, Zhuangqiang; Huang, Jianxin; Tang, Dianping

2013-09-15

A new sandwich-type impedimetric immunosensor based on functionalized graphene oxide nanosheets with a high ratio of horseradish peroxidase (HRP) and detection antibody was developed for the detection of carcinoembryonic antigen (CEA) by coupling with enzymatic biocatalytic precipitation of 4-chloro-1-naphthol (4-CN) on the captured antibody-modified glassy carbon electrode. Two molecular tags (with and without the graphene oxide nanosheets) were investigated for the detection of CEA and improved analytical features were acquired with the graphene-based labeling. With the labeling method, the performance and factors influencing the properties of the impedimetric immunosensors were also studied and evaluated. Under the optimal conditions, the dynamic concentration range of the impedimetric immunosensors spanned from 1.0pgmL(-1) to 80ngmL(-1) CEA with a detection limit (LOD) of 0.64pgmL(-1). Intra- and inter-assay coefficients of variation were less than 7.5% and 11%, respectively. Additionally, the methodology was evaluated for CEA analysis of 10 clinical serum samples and 5 diluted serum samples, receiving in a good accordance with the results obtained by the impedimetric immunoassay and the commercialized electrochemiluminescent method. Copyright © 2013 Elsevier B.V. All rights reserved.

Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including early detection of cancers

DOEpatents

Martinez, Jennifer S [Santa Fe, NM; Swanson, Basil I [Los Alamos, NM; Shively, John E [Arcadia, CA; Li, Lin [Monrovia, CA

2009-06-02

An assay element is described including recognition ligands adapted for binding to carcinoembryonic antigen (CEA) bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of CEA is described including injecting a possible CEA-containing sample into a sensor cell including the assay element, maintaining the sample within the sensor cell for time sufficient for binding to occur between CEA present within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

[A case of brain metastasis discovered after surgery for lung cancer based on changes in CEA, in which long-term survival was obtained by repeated gammaknife irradiation].

PubMed

Kakeya, Hiroshi; Inoue, Yuichi; Sawai, Toyomitsu; Ikuta, Yasushi; Ohno, Hideaki; Yanagihara, Katsunori; Higashiyama, Yasuhito; Miyazaki, Yoshitsugu; Soda, Hiroshi; Tashiro, Takayoshi; Kohno, Shigeru

2005-12-01

A 58-year-old man underwent right lower lobectomy for lung adenocarcinoma in June 1998. Since a high level of tumor marker CEA persisted after surgery, chemotherapy was additionally performed, and the CEA level subsequently normalized. However, the CEA level increased in April 1999, and brain metastasis was found in the left occipital lobe, and the first gammaknife irradiation was performed. Multiple brain metastases were found when CEA increased again in August 1999, and the second gammaknife irradiation was performed. Moreover, brain metastases were found in the left frontal and occipital lobes in February 2000, and the third gammaknife irradiation was performed. CEA normalized thereafter, but increased in February 2001. Brain metastasis was found in the right occipital lobe, and the fourth gammaknife irradiation was performed. CEA has remained within the normal range for about 4 years thereafter. Long-term survival was possible by repeated gammaknife irradiation for brain metastases. Monitoring of CEA played an important role in finding recurrent brain metastasis in this patient.

Hidradenocarcinoma: a histological and immunohistochemical study.

PubMed

Ko, Christine J; Cochran, Alistair J; Eng, William; Binder, Scott W

2006-11-01

The diagnosis of hidradenocarcinoma is difficult due to a combination of factors including inconsistent nomenclature/ classification, rarity of the neoplasm, and variable morphology of cells composing the neoplasm. Immunohistochemistry has not been previously performed on a series of hidradenocarcinomas. We evaluated six cases of hidradenocarcinoma histologically and immunohistochemically using antibodies to gross cystic disease fluid protein-15 (GCDFP-15), carcino-embryonic antigen (CEA), epithelial membrane antigen (EMA), S-100 protein, keratin AE1/3, cytokeratin 5/6, p53, bcl-1, bcl-2, and Ki67. Histology suggested concurrent eccrine and apocrine differentiation of the cases. Ki67 and p53 staining was strongly positive in five of six tumors. The neoplasms stained with antibodies to CEA, S-100 protein, GCDFP-15, EMA, bcl-1, and bcl-2 in no consistent pattern. All tumors studied stained positively for keratin AE1/3 and cytokeratin 5/6. In making the diagnosis of hidradenocarcinoma, it may be unnecessary to separate hidradenocarcinoma into eccrine and apocrine categories, and although Ki67 and p53 may be helpful, histological parameters remain paramount.

Predictors of the patency of self-expandable metallic stents in malignant gastroduodenal obstruction

PubMed Central

Kim, Seung Han; Chun, Hoon Jai; Yoo, In Kyung; Lee, Jae Min; Nam, Seung Joo; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck

2015-01-01

AIM: To investigate the predictive factors of self-expandable metallic stent patency after stent placement in patients with inoperable malignant gastroduodenal obstruction. METHODS: A total of 116 patients underwent stent placements for inoperable malignant gastroduodenal obstruction at a tertiary academic center. Clinical success was defined as acceptable decompression of the obstructive lesion within the malignant gastroduodenal neoplasm. We evaluated patient comorbidities and clinical statuses using the World Health Organization’s scoring system and categorized patient responses to chemotherapy using the Response Evaluation Criteria in Solid Tumors criteria. We analyzed the relationships between possible predictive factors and stent patency. RESULTS: Self-expandable metallic stent placement was technically successful in all patients (100%), and the clinical success rate was 84.2%. In a multivariate Cox proportional hazards model, carcinoembryonic antigen (CEA) levels were correlated with a reduction in stent patency [P = 0.006; adjusted hazard ratio (aHR) = 2.92, 95%CI: 1.36-6.25]. Palliative chemotherapy was statistically associated with an increase in stent patency (P = 0.009; aHR = 0.27, 95%CI: 0.10-0.72). CONCLUSION: CEA levels can easily be measured at the time of stent placement and may help clinicians to predict stent patency and determine the appropriate stent procedure. PMID:26290640

Diagnostic value of bronchoalveolar lavage fluid and serum tumor markers for lung cancer.

PubMed

Wang, Hongmin; Zhang, Xiaohong; Liu, Xinkui; Liu, Kangdong; Li, Yuexia; Xu, Haijiang

2016-01-01

To analyze the changes of bronchoalveolar lavage fluid (BALF) and serum tumor markers in lung cancer. Fifty patients with lung cancer (study group) and 50 cases with benign lung lesions (control group) were selected from May, 2010 to May, 2013. The observation group included squamous cell carcinoma subgroup (n = 25), adenocarcinoma subgroup (n = 19), and small cell undifferentiated carcinoma subgroup (n = 6). The carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and cytokeratin 19 fragment (CYFRA21-1) concentration were compared; and the comparisons among subgroups were also performed. Three kinds of tumor markers in BALF and serum of the observation group were higher than that of the control group. NSE concentration of small.cell lung cancer was the highest, CYFRA21.1 concentration was highest in the squamous cell carcinoma, and CEA concentration was highest in the adenocarcinoma group; the former increased more significantly. BALF and serum NSE, CEA, and CYFRA21.1 elevated in lung cancer, which had prompt value for pathology, especially significant for BALF.

Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis.

PubMed

van der Waaij, Laurens A; van Dullemen, Hendrik M; Porte, Robert J

2005-09-01

Pancreatic cystic tumors commonly include serous cystadenoma (SCA), mucinous cystadenoma (MCA), and mucinous cystadenocarcinoma (MCAC). A differential diagnosis with pseudocysts (PC) can be difficult. Radiologic criteria are not reliable. The objective of the study is to investigate the value of cyst fluid analysis in the differential diagnosis of benign (SCA, PC) vs. premalignant or malignant (MCA, MCAC) lesions. A search in PubMed was performed with the search terms cyst, pancrea, and fluid. Articles about cyst fluid analysis of pancreatic lesions that contained the individual data of at least 7 patients were included in the study. Data of all individual patients were combined and were plotted in scatter grams. Cutoff levels were determined. Twelve studies were included, which comprised data of 450 patients. Cysts with an amylase concentration <250 U/L were SCA, MCA, or MCAC (sensitivity 44%, specificity 98%) and, thus, virtually excluded PC. A carcinoembryonic antigen (CEA) <5 ng/mL suggested a SCA or PC (sensitivity 50%, specificity 95%). A CEA >800 ng/mL strongly suggested MCA or MCAC (sensitivity 48%, specificity 98%). A carbohydrate-associated antigen (CA) 19-9 <37 U/mL strongly suggested PC or SCA (sensitivity 19%, specificity 98%). Cytologic examination revealed malignant cells in 48% of MCAC (n = 111). Most pancreatic cystic tumors should be resected without the need for cyst fluid analysis. However, in asymptomatic patients, in patients with an increased surgical risk, and, in patients in whom there is a diagnostic uncertainty about the presence of a PC, cyst fluid analysis helps to determine the optimal therapeutic strategy.

Multiplexed detection of serological cancer markers with plasmon-enhanced Raman spectro-immunoassay.

PubMed

Li, Ming; Kang, Jeon Woong; Sukumar, Saraswati; Dasari, Ramachandra Rao; Barman, Ishan

2015-07-01

Circulating biomarkers have emerged as promising non-invasive, real-time surrogates for cancer diagnosis, prognostication and monitoring of therapeutic response. Emerging data, however, suggest that single markers are inadequate in describing complex pathologic transformations. Architecting assays capable of parallel measurements of multiple biomarkers can help achieve the desired clinical sensitivity and specificity while conserving patient specimen and reducing turn-around time. Here we describe a plasmon-enhanced Raman spectroscopic assay featuring nanostructured biomolecular probes and spectroscopic imaging for multiplexed detection of disseminated breast cancer markers cancer antigen (CA) 15-3, CA 27-29 and cancer embryonic antigen (CEA). In the developed SERS assay, both the assay chip and surface-enhanced Raman spectroscopy (SERS) tags are functionalized with monoclonal antibodies against CA15-3, CA27-29 and CEA, respectively. Sequential addition of biomarkers and functionalized SERS tags onto the functionalized assay chip enable the specific recognition of these biomarkers through the antibody-antigen interactions, leading to a sandwich spectro-immunoassay. In addition to offering extensive multiplexing capability, our method provides higher sensitivity than conventional immunoassays and demonstrates exquisite specificity owing to selective formation of conjugated complexes and fingerprint spectra of the Raman reporter. We envision that clinical translation of this assay may further enable asymptomatic surveillance of cancer survivors and speedy assessment of treatment benefit through a simple blood test.

Anti-idiotype antibody induced cellular immunity in mice transgenic for human carcinoembryonic antigen.

PubMed

Saha, Asim; Chatterjee, Sunil K; Foon, Kenneth A; Bhattacharya-Chatterjee, Malaya

2006-08-01

In the present study, we have analysed the detailed cellular immune mechanisms involved in tumour rejection in carcinoembryonic antigen (CEA) transgenic mice after immunization with dendritic cells (DC) pulsed with an anti-idiotype (Id) antibody, 3H1, which mimics CEA. 3H1-pulsed DC vaccinations resulted in induction of CEA specific cytotoxic T lymphocyte (CTL) responses in vitro and the rejection of CEA-transfected MC-38 murine colon carcinoma cells, C15, in vivo (Saha et al.,Cancer Res 2004; 64: 4995-5003). These CTL mediated major histocompatibility complex (MHC) class I-restricted tumour cell lysis, production of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and expression of Fas ligand (FasL) and TNF-related apoptosis-inducing ligand (TRAIL) in response to C15 cells. CTL used perforin-, FasL-, and TRAIL-mediated death pathways to lyse C15 cells, although perforin-mediated killing was the predominant lytic mechanism in vitro. The cytokines IFN-gamma and TNF-alpha synergistically enhanced surface expression of Fas, TRAIL receptor, MHC class I and class II on C15 cells that increased the sensitivity of tumour cells to CTL lysis. CTL activity generated in 3H1-pulsed DC immunized mice was directed against an epitope defined by the idio-peptide LCD-2, derived from 3H1. In vivo lymphocyte depletion experiments demonstrated that induction of CTL response and antitumour immunity was dependent on both CD4+ and CD8+ T cells. The analysis of splenocytes of immunized mice that had rejected C15 tumour growth revealed up-regulated surface expression of memory phenotype Ly-6C and CD44 on both CD4+ and CD8+ T cells. The adoptive transfer experiments also suggested the role of both CD4+ and CD8+ T cells in this model system. Furthermore, mice that had rejected C15 tumour growth, developed tumour-specific immunological memory.

Enhanced peroxidase-like properties of Au@Pt DNs/NG/Cu2+ and application of sandwich-type electrochemical immunosensor for highly sensitive detection of CEA.

PubMed

Lv, Hui; Li, Yueyun; Zhang, Xiaobo; Gao, Zengqiang; Zhang, Chunyan; Zhang, Shuan; Dong, Yunhui

2018-07-30

Effective treatment of cancer depends upon the early detection of the tumor marker. Here, we report on the development of a new immunosensor for early detection of carcinoembryonic antigen (CEA). Cubic Au@Pt dendritic nanomaterials functionalized nitrogen-doped graphene loaded with copper ion (Au@Pt DNs/NG/Cu 2+ ) with enhanced peroxidase-like properties was synthesized as labels to effectively capture and immobilize secondary anti-CEA. The Au@Pt DNs with more active surface area could efficiently enhance electrocatalysis for reduction of hydrogen peroxide (H 2 O 2 ). Meanwhile, with good conductivity and large specific surface area, NG can immobilize a large amount of Au@Pt DNs. Furthermore, after adsorbed Cu 2+ can further promote the redox of H 2 O 2 and amplify the signal of the immunosensor. For the immobilization of primary antibodies, Au nanoparticles functionalized polydopamine (Au@PDA) were used as transducing materials to modify glassy carbon electrodes and enhance the electron transfer efficiently. Under optimal conditions, the immunosensor exhibited a satisfactory response to CEA with a limit detection of 0.167 pg/mL and linear detection range from 0.5 pg/mL to 50 ng/mL. Based on the high sensitivity and specificity of the immunosensor, we propose this multiple amplified biosensor for early detection of CEA. Copyright © 2018 Elsevier B.V. All rights reserved.

Levels of soluble LR11/SorLA are highly increased in the bile of patients with biliary tract and pancreatic cancers.

PubMed

Terai, Kensuke; Jiang, Meizi; Tokuyama, Wataru; Murano, Takeyoshi; Takada, Nobuo; Fujimura, Kengo; Ebinuma, Hiroyuki; Kishimoto, Toshihiko; Hiruta, Nobuyuki; Schneider, Wolfgang J; Bujo, Hideaki

2016-06-01

The utility of molecules derived from cancer cells as biomarkers of the pathological status in biliary tract and pancreatic cancers is still limited. Soluble LDL receptor relative with 11 ligand-binding repeats (sLR11), a molecule released from immature cells, has been shown to be a circulating biomarker for early stage hematological malignancies. We have evaluated the pathological significance of bile sLR11 levels in 147 samples from 72 patients with biliary tract cancer (BTC), pancreatic cancer (PC), or benign diseases. The bile sLR11 levels in the cancer patients were significantly increased compared with those in patients without cancer, independent of cytological detection of cancer cells in bile. The average bile sLR11 levels in cancer patients were significantly higher than in those with benign diseases, while levels of bile carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were not different. LR11 protein was found to be highly expressed in the BTC and PC cells. The LR11 transcript levels in cholangiocarcinoma and pancreatic cancer cell lines were sharply induced during proliferation and significantly increased under hypoxic conditions. Therefore, sLR11 levels in bile may be indicative of cancer cell conditions and may serve as potential novel biomarker in patients with BTC and PC. Copyright © 2016 Elsevier B.V. All rights reserved.

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center.

PubMed

Otoshi, Takehiro; Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

2017-01-01

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung's criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.

The use of cultured epithelial autograft in the treatment of major burn injuries: a critical review of the literature.

PubMed

Wood, F M; Kolybaba, M L; Allen, P

2006-06-01

The need to achieve rapid wound closure in patients with massive burns and limited skin donor sites led to the investigation of in vitro cellular expansion of keratinocytes. The use of cultured epithelial autografts (CEA) was first reported in the treatment of major burns in 1981. Since that time, support for the use of CEA has varied, ranging from 'a useful agent' to having 'no demonstrable effect on the outcome of extensively burned patients'. This critical review of the literature examines issues associated with the use of CEA and the introduction of the technology into clinical practice. The factors potentially limiting the use of cultured CEA are the time necessary to culture CEA sheets, the reliability of 'take', vulnerability of grafts on the newly healed surface, long-term durability and the cost implications of such treatment. The available literature was located and critically evaluated using the Australian National Health and Medical Research Council Guidelines. In the identified literature, the level of evidence to support the use of CEA in major burn injures is limited and often restricted to case studies and case series with no Level 1 evidence currently available. The main question arising 'Does CEA have a role in the treatment of major burns?' has proven difficult to answer due to the wide variation in both the quality of study design and the findings. At best, the literature review has highlighted areas of concern that have hindered the successful use of CEA. Our review critically evaluates the use of CEA and explores the advances in techniques towards attempting to improve reliable clinical implementation of CEA. The need for higher level research into the use of CEA is emphasised by this review.

Parvalbumin Interneurons of Central Amygdala Regulate the Negative Affective States and the Expression of Corticotrophin-Releasing Hormone During Morphine Withdrawal

PubMed Central

Wang, Li; Shen, Minjie; Jiang, Changyou

2016-01-01

Background: The central nucleus of the amygdala (CeA) is a crucial component of the neuronal circuitry mediating aversive emotion. Its role in the negative affective states during drug withdrawal includes changes in opioidergic, GABAergic, and corticotropin-releasing factor neurotransmission. However, the modulation of the neurobiological interconnectivity in the CeA and its effects in the negative reinforcement of drug dependents are poorly understood. Method: We performed electrophysiological recordings to assess the membrane excitability of parvalbumin (PV)+ interneurons in the CeA during chronic morphine withdrawal. We tested the morphine withdrawal–induced negative affective states, such as the aversive (assessed by conditioned place aversion), anxiety (assessed by elevated plus maze), and anhedonic-like (assessed by saccharin preference test) behaviors, as well as the mRNA level of corticotropin-releasing hormone (CRH) via optogenetic inhibition or activation of PV+ interneurons in the CeA. Result: Chronic morphine withdrawal increased the firing rate of CeA PV+ interneurons. Optogenetic inhibition of the activity of CeA PV+ interneurons attenuated the morphine withdrawal–induced negative affective states, such as the aversive, anxiety, and anhedonic-like behaviors, while direct activation of CeA PV+ interneurons could trigger those negative affective-like behaviors. Optogenetic inhibition of the CeA PV+ interneurons during the morphine withdrawal significantly attenuated the elevated CRH mRNA level in the CeA. Conclusion: The activity of PV+ interneurons in the CeA was up-regulated during chronic morphine withdrawal. The activation of PV+ interneurons during morphine withdrawal was crucial for the induction of the negative emotion and the up-regulation of CRH mRNA levels in the CeA. PMID:27385383

A Prospective Examination of the Relations between Emotional Abuse and Anxiety: Moderation by Distress Tolerance

PubMed Central

Banducci, Anne N.; Lejuez, C.W.; Dougherty, Lea R.; MacPherson, Laura

2016-01-01

Objective Anxiety, the most common and impairing psychological problem experienced by youth, is associated with numerous individual and environmental factors. Two such factors include childhood emotional abuse (CEA) and low distress tolerance (DT). The current study aimed to understand how CEA and low DT impacted anxiety symptoms measured annually across five years among a community sample of youth. We hypothesized DT would moderate the relationship between CEA and anxiety, such that youth with higher levels of CEA and lower levels of DT would have elevated anxiety over time. Method Community youth (N = 244) were annually assessed across five years using the Revised Child Anxiety and Depression Scale, Childhood Trauma Questionnaire, and Behavioral Indicator of Resiliency to Distress. Results Higher CEA at baseline was associated with higher anxiety at baseline, higher anxiety at each annual assessment, and with greater overall decreases in anxiety over time. Lower DT was associated with higher anxiety at baseline, but did not predict changes in anxiety over time. Baseline DT significantly moderated the relationship between baseline CEA and anxiety, such that youth with both higher CEA and lower DT had the highest anxiety at each annual assessment. Conclusions Youth with lower DT and higher CEA scores had the highest level of anxiety symptoms across time. PMID:27501698

A Prospective Examination of the Relations Between Emotional Abuse and Anxiety: Moderation by Distress Tolerance.

PubMed

Banducci, Anne N; Lejuez, C W; Dougherty, Lea R; MacPherson, Laura

2017-01-01

Anxiety, the most common and impairing psychological problem experienced by youth, is associated with numerous individual and environmental factors. Two such factors include childhood emotional abuse (CEA) and low distress tolerance (DT). The current study aimed to understand how CEA and low DT impacted anxiety symptoms measured annually across 5 years among a community sample of youth. We hypothesized DT would moderate the relationship between CEA and anxiety, such that youth with higher levels of CEA and lower levels of DT would have elevated anxiety over time. Community youth (N = 244) were annually assessed across 5 years using the Revised Child Anxiety and Depression Scale, Childhood Trauma Questionnaire, and Behavioral Indicator of Resiliency to Distress. Higher CEA at baseline was associated with higher anxiety at baseline, higher anxiety at each annual assessment, and with greater overall decreases in anxiety over time. Lower DT was associated with higher anxiety at baseline, but did not predict changes in anxiety over time. Baseline DT significantly moderated the relationship between baseline CEA and anxiety, such that youth with both higher CEA and lower DT had the highest anxiety at each annual assessment. Youth with lower DT and higher CEA scores had the highest level of anxiety symptoms across time.

Plasma treatment of paper for protein immobilization on paper-based chemiluminescence immunodevice.

PubMed

Zhao, Mei; Li, Huifang; Liu, Wei; Guo, Yumei; Chu, Weiru

2016-05-15

A novel protein immobilization method based on plasma treatment of paper on the low-cost paper-based immunodevice was established in this work. By using a benchtop plasma cleaner, the paper microzone was treated by oxygen plasma treatment for 4 min and then the antibody can be directly immobilized on the paper surface. Aldehyde group was produced after the plasma treatment, which can be verified from the fourier transform infrared spectroscopy (FT-IR) spectra and x-ray photoelectron spectroscopy (XPS) spectra. By linked to aldehyde group, the antibody can be immobilized on the paper surface without any other pretreatment. A paper-based immunodevice was introduced here through this antibody immobilization method. With sandwich chemiluminescence (CL) immunoassay method, the paper-based immunodevice was successfully performed for carcinoembryonic antigen (CEA) detection in human serum with a linear range of 0.1-80.0 ng/mL. The detection limit was 0.03 ng/mL, which was 30 times lower than the clinical CEA level. Comparing to the other protein immobilization methods on paper-based device, this strategy was faster and simpler and had potential applications in point-of-care testing, public health and environmental monitoring. Copyright © 2015 Elsevier B.V. All rights reserved.

Immunoliposome-PCR: a generic ultrasensitive quantitative antigen detection system

PubMed Central

2012-01-01

Background The accurate quantification of antigens at low concentrations over a wide dynamic range is needed for identifying biomarkers associated with disease and detecting protein interactions in high-throughput microarrays used in proteomics. Here we report the development of an ultrasensitive quantitative assay format called immunoliposome polymerase chain reaction (ILPCR) that fulfills these requirements. This method uses a liposome, with reporter DNA encapsulated inside and biotin-labeled polyethylene glycol (PEG) phospholipid conjugates incorporated into the outer surface of the liposome, as a detection reagent. The antigenic target is immobilized in the well of a microplate by a capture antibody and the liposome detection reagent is then coupled to a biotin-labeled second antibody through a NeutrAvidin bridge. The liposome is ruptured to release the reporter DNA, which serves as a surrogate to quantify the protein target using real-time PCR. Results A liposome detection reagent was prepared, which consisted of a population of liposomes ~120 nm in diameter with each liposome possessing ~800 accessible biotin receptors and ~220 encapsulated reporters. This liposome detection reagent was used in an assay to quantify the concentration of carcinoembryonic antigen (CEA) in human serum. This ILPCR assay exhibited a linear dose–response curve from 10-10 M to 10-16 M CEA. Within this range the assay coefficient of variance was <6 % for repeatability and <2 % for reproducibility. The assay detection limit was 13 fg/mL, which is 1,500-times more sensitive than current clinical assays for CEA. An ILPCR assay to quantify HIV-1 p24 core protein in buffer was also developed. Conclusions The ILPCR assay has several advantages over other immuno-PCR methods. The reporter DNA and biotin-labeled PEG phospholipids spontaneously incorporate into the liposomes as they form, simplifying preparation of the detection reagent. Encapsulation of the reporter inside the liposomes allows nonspecific DNA in the assay medium to be degraded with DNase I prior to quantification of the encapsulated reporter by PCR, which reduces false-positive results and improves quantitative accuracy. The ability to encapsulate multiple reporters per liposome also helps overcome the effect of polymerase inhibitors present in biological specimens. Finally, the biotin-labeled liposome detection reagent can be coupled through a NeutrAvidin bridge to a multitude of biotin-labeled probes, making ILPCR a highly generic assay system. PMID:22726242

Circular RNA hsa_circ_0000745 may serve as a diagnostic marker for gastric cancer.

PubMed

Huang, Mei; He, Yi-Ren; Liang, Li-Chuan; Huang, Qiang; Zhu, Zhi-Qiang

2017-09-14

To determine whether circular RNAs (circRNAs) are involved in pathological processes of gastric cancer (GC). Three circRNAs with differential expression in GC and colorectal cancer were randomly selected for validation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), using 20 pairs of gastric tissues and normal tissues. Based on the predicted circRNA-miRNA network, we then focused on hsa_circ_0000745, which was found to be down-regulated in 20 GC tissues compared with normal tissues. The hsa_circ_0000745 levels were further analyzed by qRT-PCR in 60 GC tissues and paired adjacent non-tumor tissues, as well as 60 plasma samples from GC patients and 60 plasma samples from healthy controls. The associations between the levels of hsa_circ_0000745 and the clinicopathological features of GC patients were statistically assessed. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_0000745 in GC. Hsa_circ_0000745 was down-regulated in GC tissues vs non-tumorous tissues ( P < 0.001) and in plasma samples from patients with GC vs healthy controls ( P < 0.001). The expression level of hsa_circ_0000745 in GC tissues correlated with tumor differentiation, while the expression level in plasma correlated with tumor-node-metastasis stage. The area under the ROC curve (AUC) of hsa_circ_0000745 in plasma was 0.683, suggesting good diagnostic value. Plasma hsa_circ_0000745 level combined with carcinoembryogenic antigen (CEA) level increased the AUC to 0.775. Hsa_circ_0000745 plays an important role in GC and its expression level in plasma in combination with CEA level is a promising diagnostic marker for this malignancy.

Mucinous breast carcinoma with myoepithelial-like spindle cells.

PubMed

Miyake, Yasuyuki; Hirokawa, Mitsuyoshi; Norimatsu, Yoshiaki; Kanahara, Takuo; Monobe, Yasumasa; Ohno, Setsuyo; Miyamoto, Tomoyuki; Yakushiji, Hiromasa; Sakaguchi, Takuya; Aratake, Yatsuki; Ohno, Eiji

2009-06-01

Appearance of spindle cells has been believed as a benign index of breast cytology. But, we have frequently observed the spindle cells in smears from mucinous carcinoma of the breast. Here, we characterized the biochemical nature of the spindle cells, so as to clarify their identity in cytology. Nineteen cases of breast mucinous carcinoma were used for cytological examination. The spindle cells were located at edges of tumor cell nests and in the backgrounds of cytological specimens. Immunohistological examination revealed that the spindle cells exhibited both immunoreactivity against carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Immunoreactivity against vimentin, cytokeratin, or alpha-smooth muscle actin was, however, not observed. The mode of distribution of biochemical markers suggests that the positive cells for anti-CEA antibody and anti-EMA antibody are tumor cells compressed by mucin, while the vimentin-positive cells are fibroblasts. We assert that the presence of spindle cells can be a characteristic feature of mucinous carcinoma of the breast. Discrimination of the spindle cells in mucinous carcinoma from myoepithelial cells and naked bipolar nuclei in benign lesions was established here. It should facilitate precise diagnosis of breast cancer. (c) 2009 Wiley-Liss, Inc.

Serum tumor markers in breast cancer: are they of clinical value?

PubMed

Duffy, Michael J

2006-03-01

Although multiple serum-based tumor markers have been described for breast cancer, such as CA 15-3, BR 27.29 (CA27.29), carcinoembryonic antigen (CEA), tissue polypeptide antigen, tissue polypeptide specific antigen, and HER-2 (the extracellular domain), the most widely used are CA 15-3 and CEA. The literature relevant to serum tumor markers in breast cancer was reviewed. Particular attention was given to systematic reviews, prospective randomized trials, and guidelines issued by expert panels. Because of a lack of sensitivity for early disease and lack of specificity, none of the available markers is of value for the detection of early breast cancer. High preoperative concentrations of CA 15-3 are, however, associated with adverse patient outcome. Although serial determinations of tumor markers after primary treatment for breast cancer can preclinically detect recurrent/metastatic disease with lead times of approximately 2-9 months, the clinical value of this lead time remains to be determined. Serum markers, however, are the only validated approach for monitoring treatment in patients with advanced disease that cannot be evaluated by use of conventional criteria. CA 15-3 is one of the first circulating prognostic factors for breast cancer. Preoperative concentrations thus might be combined with existing prognostic factors for predicting outcome in patients with newly diagnosed breast cancer. At present, the most important clinical application of CA 15-3 is in monitoring therapy in patients with advanced breast cancer that is not assessable by existing clinical or radiologic procedures.

Top-down nanofabrication of silicon nanoribbon field effect transistor (Si-NR FET) for carcinoembryonic antigen detection.

PubMed

Bao, Zengtao; Sun, Jialin; Zhao, Xiaoqian; Li, Zengyao; Cui, Songkui; Meng, Qingyang; Zhang, Ye; Wang, Tong; Jiang, Yanfeng

2017-01-01

Sensitive and quantitative detection of tumor markers is highly required in the clinic for cancer diagnosis and consequent treatment. A field-effect transistor-based (FET-based) nanobiosensor emerges with characteristics of being label-free, real-time, having high sensitivity, and providing direct electrical readout for detection of biomarkers. In this paper, a top-down approach is proposed and implemented to fulfill a novel silicon nano-ribbon FET, which acts as biomarker sensor for future clinical application. Compared with the bottom-up approach, a top-down fabrication approach can confine width and length of the silicon FET precisely to control its electrical properties. The silicon nanoribbon (Si-NR) transistor is fabricated on a Silicon-on-Insulator (SOI) substrate by a top-down approach with complementary metal oxide semiconductor (CMOS)-compatible technology. After the preparation, the surface of Si-NR is functionalized with 3-aminopropyltriethoxysilane (APTES). Glutaraldehyde is utilized to bind the amino terminals of APTES and antibody on the surface. Finally, a microfluidic channel is integrated on the top of the device, acting as a flowing channel for the carcinoembryonic antigen (CEA) solution. The Si-NR FET is 120 nm in width and 25 nm in height, with ambipolar electrical characteristics. A logarithmic relationship between the changing ratio of the current and the CEA concentration is measured in the range of 0.1-100 ng/mL. The sensitivity of detection is measured as 10 pg/mL. The top-down fabricated biochip shows feasibility in direct detecting of CEA with the benefits of real-time, low cost, and high sensitivity as a promising biosensor for tumor early diagnosis.

Nanoporous Gold as a Solid Support for Protein Immobilization for the Development of Immunoassays, and for Biomolecular Interaction Studies

NASA Astrophysics Data System (ADS)

Pandey, Binod Prasad

Nanoporous gold (NPG) is a versatile material of high surface area to volume ratio that can be readily modified with self-assembled monolayers of alkanethiols to which biomolecules can be linked. NPG presents new opportunities for the development of immunoassays, and for the development of carbohydrate based assays. This thesis explores the use of NPG as a support for self-assembled monolayers, their linkage to antibody-enzyme conjugates for immunoassay development, and for the study and application of carbohydrate-protein interactions. Direct kinetic electrochemical immunoassays were developed on NPG for prostate specific antigen (PSA) and carcinoembryonic antigen (CEA). The decrease in enzymatic conversion of p-aminophenylphosphate to p-aminophenol, by alkaline phosphatase conjugated to an antibody, due to steric hindrance caused by the presence of antigen on antibody, was observed as a drop in peak current in square-wave voltammetry. Detection limit of these assays was 0.075 ng mL -1 and 0.015 ng mL-1 for PSA and CEA, respectively. Similarly, the linear range of determination of these biomarkers extended up to 30 ng mL-1 and 10 ng mL-1 for PSA and CEA, respectively. Minimal interference was observed using newborn calf serum as a substitute for the human serum matrix. A rapid and sensitive enzyme linked lectinsorbant assay was also developed for the study of glycoprotein-lectin interactions on the NPG surface. Self-assembled monolayers of alkanethiols on NPG were characterized by cyclic voltammetry and electrochemical impedance spectroscopy. Similarly, the applicability of this surface for the formation of carbohydrate monolayers and its application for lectin carbohydrate interactions was also studied. Pure and mixed SAMs of 8-mercaptooctyl β-D-mannopyranoside (αMan-C8-SH) and α-D-Gal-(1→4)-β-D-Gal-(1α)-D-Glc-1-O-mercaptooctane (Gb3-C8-SH) with alkanethiols having varying tail groups were prepared. Binding affinity and binding kinetics of concanavalin A to mannoside and soybean agglutinin to galactose in these SAMs were found to be different on NPG than on flat polycrystalline gold, and was also sensitive to the chemical composition of the modified surfaces.

Using Antigen-Specific B Cells to Combine Antibody and T Cell-Based Cancer Immunotherapy.

PubMed

Wennhold, Kerstin; Thelen, Martin; Schlößer, Hans Anton; Haustein, Natalie; Reuter, Sabrina; Garcia-Marquez, Maria; Lechner, Axel; Kobold, Sebastian; Rataj, Felicitas; Utermöhlen, Olaf; Chakupurakal, Geothy; Theurich, Sebastian; Hallek, Michael; Abken, Hinrich; Shimabukuro-Vornhagen, Alexander; von Bergwelt-Baildon, Michael

2017-09-01

Cancer immunotherapy by therapeutic activation of T cells has demonstrated clinical potential. Approaches include checkpoint inhibitors and chimeric antigen receptor T cells. Here, we report the development of an alternative strategy for cellular immunotherapy that combines induction of a tumor-directed T-cell response and antibody secretion without the need for genetic engineering. CD40 ligand stimulation of murine tumor antigen-specific B cells, isolated by antigen-biotin tetramers, resulted in the development of an antigen-presenting phenotype and the induction of a tumor antigen-specific T-cell response. Differentiation of antigen-specific B cells into antibody-secreting plasma cells was achieved by stimulation with IL21, IL4, anti-CD40, and the specific antigen. Combined treatment of tumor-bearing mice with antigen-specific CD40-activated B cells and antigen-specific plasma cells induced a therapeutic antitumor immune response resulting in remission of established tumors. Human CEA or NY-ESO-1-specific B cells were detected in tumor-draining lymph nodes and were able to induce antigen-specific T-cell responses in vitro, indicating that this approach could be translated into clinical applications. Our results describe a technique for the exploitation of B-cell effector functions and provide the rationale for their use in combinatorial cancer immunotherapy. Cancer Immunol Res; 5(9); 730-43. ©2017 AACR . ©2017 American Association for Cancer Research.

Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

PubMed Central

Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

2017-01-01

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy. PMID:28968445

77 FR 41110 - Exemptive Order Regarding Compliance With Certain Swap Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-12

... delay compliance with certain entity-level requirements of the CEA (and Commission regulations promulgated thereunder), subject to specified conditions. Additionally, with respect to transaction-level.... major swap participants may delay compliance with certain entity-level requirements of the CEA (and...

Multiplexed detection of serological cancer markers with plasmon-enhanced Raman spectro-immunoassay† †Electronic supplementary information (ESI) available: Fig. S1–S7 and Table S1. See DOI: 10.1039/c5sc01054c Click here for additional data file.

PubMed Central

Kang, Jeon Woong; Sukumar, Saraswati; Dasari, Ramachandra Rao

2015-01-01

Circulating biomarkers have emerged as promising non-invasive, real-time surrogates for cancer diagnosis, prognostication and monitoring of therapeutic response. Emerging data, however, suggest that single markers are inadequate in describing complex pathologic transformations. Architecting assays capable of parallel measurements of multiple biomarkers can help achieve the desired clinical sensitivity and specificity while conserving patient specimen and reducing turn-around time. Here we describe a plasmon-enhanced Raman spectroscopic assay featuring nanostructured biomolecular probes and spectroscopic imaging for multiplexed detection of disseminated breast cancer markers cancer antigen (CA) 15-3, CA 27-29 and cancer embryonic antigen (CEA). In the developed SERS assay, both the assay chip and surface-enhanced Raman spectroscopy (SERS) tags are functionalized with monoclonal antibodies against CA15-3, CA27-29 and CEA, respectively. Sequential addition of biomarkers and functionalized SERS tags onto the functionalized assay chip enable the specific recognition of these biomarkers through the antibody-antigen interactions, leading to a sandwich spectro-immunoassay. In addition to offering extensive multiplexing capability, our method provides higher sensitivity than conventional immunoassays and demonstrates exquisite specificity owing to selective formation of conjugated complexes and fingerprint spectra of the Raman reporter. We envision that clinical translation of this assay may further enable asymptomatic surveillance of cancer survivors and speedy assessment of treatment benefit through a simple blood test. PMID:26405519

Combined evaluation of the Glasgow prognostic score and carcinoembryonic antigen concentration prior to hepatectomy predicts postoperative outcomes in patients with liver metastasis from colorectal cancer.

PubMed

Kobayashi, Takashi; Kawakamil, Masayo; Hara, Yoshiaki; Shioiri, Sadaaki; Yasuno, Masamichi; Teruya, Masanori; Kaminishi, Michio

2014-01-01

Little is known about the ability of the inflammation-based Glasgow prognostic score (GPS). 106 patients who underwent curative resection for colorectal liver metastasis (CRLM) were analyzed. Patients with an elevated Creactive protein concentration (>10 mg/L) and hypoalbuminemia (<35 g/L) at admission were assigned a GPS 2, those with only 1 of these biochemical abnormalities were assigned a GPS 1, and those without either abnormality were assigned a GPS 0. Multivariate analysis showed that 2 variables, carcinoembryonic antigen (CEA) concentration > 30 ng/mL and a GPS 1 or 2, were independently prognostic of survival. Patients were classified into 3 groups on the basis of these 2 variables. Patients with GPS 1 or 2 and CEA concentration > 30 ng/mL were assigned a new score of 2, those with either 1 factor were assigned a new score of 1, and those with neither factors were assigned a new score of 0. The 5-year overall survival rates of new scores of 0, 1, 2 were 71.5%, 31.6%, and 0%, respectively (P < 0.0001). This simple staging system may be able to identify a subgroup of patients who are eligible for curative resection but show poor prognosis.

Rotational paper-based electrochemiluminescence immunodevices for sensitive and multiplexed detection of cancer biomarkers.

PubMed

Sun, Xiange; Li, Bowei; Tian, Chunyuan; Yu, Fabiao; Zhou, Na; Zhan, Yinghua; Chen, Lingxin

2018-05-12

This paper describes a novel rotational paper-based analytical device (RPAD) to implement multi-step electrochemiluminescence (ECL) immunoassays. The integrated paper-based rotational valves can be easily controlled by rotating paper discs manually and this advantage makes it user-friendly to untrained users to carry out the multi-step assays. In addition, the rotational valves are reusable and the response time can be shortened to several seconds, which promotes the rotational paper-based device to have great advantages in multi-step operations. Under the control of rotational valves, multi-step ECL immunoassays were conducted on the rotational device for the multiplexed detection of carcinoembryonic antigen (CEA) and prostate specific antigen (PSA). The rotational device exhibited excellent analytical performance for CEA and PSA, and they could be detected in the linear ranges of 0.1-100 ng mL -1 and 0.1-50 ng mL -1 with detection limits down to 0.07 ng mL -1 and 0.03 ng mL -1 , respectively, which were within the ranges of clinical concentrations. We hope this technique will open a new avenue for the fabrication of paper-based valves and provide potential application in clinical diagnostics. Copyright © 2017 Elsevier B.V. All rights reserved.

To fine needle aspiration or not? An endosonographer's approach to pancreatic cystic lesions

PubMed Central

But, David Yiu-Kuen; Poley, Jan-Werner

2014-01-01

Endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) is an established diagnostic tool in the management of pancreatic cystic lesions (PCLs). Due to the proximity to the target lesion, the fine diagnostic needle travels through only minimal normal tissues. The risks of bleeding, pancreatitis and infection are small. Valuable diagnostic morphological information can be obtained by EUS before the use of FNA. The additional cytopathologic and cyst fluid analysis for the conventional markers such as amylase, carcinoembryonic antigen (CEA) and CA19.9 improves the diagnostic capability. Pancreatic cyst fluid CEA concentration of 192 ng/mL is generally the most agreed cutoff to differentiate mucinous from non-mucinous lesion. A fluid amylase level of <250 IU/L excludes the diagnosis of pseudocyst. Technical tips of EUS-FNA and the limitations of the procedure are discussed. Promising technique and FNA needle modifications have been described to improve the diagnostic yield at the cytopathologic analysis. The use of novel cyst fluid proteomics and deoxyribonucleic acid-based biomarkers of the PCLs are reviewed. Although it is considered a safe procedure, EUS-FNA is not a routine in every patient. Recommendations of the role of EUS-FNA at various common clinical scenarios are discussed. PMID:24955337

Cerium oxide-triggered 'one-to-many' catalytic cycling strategy for in situ amplified electronic signal of low-abundance protein.

PubMed

Tang, Juan; Chen, Xian; Zhou, Jun; Li, Qunfang; Chen, Guonan; Tang, Dianping

2013-08-07

Multifunctionalized thionine-modified cerium oxide (Thi-CeO2) nanostructures with redox ability and catalytic activity were designed as the bionanolabels for in situ amplified electronic signal of low-abundance protein (carcinoembryonic antigen, CEA, used as a model) based on a cerium oxide-triggered 'one-to-many' catalytic cycling strategy. Initially, the carried CeO2 nanoparticles autocatalytically hydrolyzed the phosphate ester bond of l-ascorbic acid 2-phosphate (AAP) to produce a new reactant (l-ascorbic acid, AA), then the generated AA was electrochemically oxidized by the assembled thionine on the Thi-CeO2, and the resultant product was then reduced back to AA by the added tris(2-carboxyethy)phosphine (TCEP). The catalytic cycling could be re-triggered by the thionine and TCEP, resulting in amplification of the electrochemical signal. Under the optimized conditions, the electrochemical immunosensor exhibited a wide linear range of 0.1 pg mL(-1) to 80 ng mL(-1) with a low detection limit of 0.08 pg mL(-1) CEA at the 3σblank level. In addition, the methodology was evaluated for the analysis of clinical serum samples, and was in good accordance with values obtained using the commercialized enzyme-linked immunosorbent assay (ELISA) method.

Reliability of plain radiographic parameters for developmental dysplasia of the hip in children.

PubMed

Upasani, Vidyadhar V; Bomar, James D; Parikh, Gaurav; Hosalkar, Harish

2012-07-01

Few studies have evaluated the reliability and reproducibility of the femoral neck-shaft angle (NSA), center-edge angle (CEA), and acetabular index (AI) in young children with developmental dysplasia of the hip (DDH). We wanted to determine whether these parameters could be used reliably by practitioners. Fifty radiographs from 21 children with DDH were reviewed. Analysis was performed by three observers, at two time periods. The intra- and inter-observer reliability for each measure was assessed. At time period one, we noted a "high" level of agreement between observers when measuring the NSA, a "low" level when measuring the CEA, and a "moderate" level when measuring the AI. At time period two, we noted a "very high" level of agreement between observers when measuring the NSA and a "high" level when measuring the CEA and AI. When comparing the measurements of observer 1 at the two different time periods, we noted nearly "very high" agreement when measuring the NSA, a "moderate" agreement when measuring the CEA, and a "high" agreement for the AI. In comparing the measurements of observer 2, we noted "very high" agreement for the NSA and "high" agreement for the CEA and AI. In comparing the measurements for observer 3, we noted nearly "very high" agreement for the NSA, nearly "high" agreement for the CEA, and "high" agreement for the AI. It is difficult to reliably measure three-dimensional pelvic morphology on a frontal plane radiograph, especially when important pelvic landmarks have yet to ossify.

Overexpression of MutL homolog 1 and MutS homolog 2 proteins have reversed prognostic implications for stage I-II colon cancer patients.

PubMed

Huang, Shih-Chiang; Huang, Shiu-Feng; Chen, Ya-Ting; Chang, Yu; Chiu, Yu-Ting; Chang, Il-Chi; Wu, Hong-Dar Isaac; Chen, Jinn-Shiun

2017-02-01

The outcome of colon cancer patients without lymph node metastasis is heterogeneous. Searching for new prognostic markers is warranted. One hundred twenty stage I-II colon cancer patients who received complete surgical excision during 1995-2004 were selected for this biomarker study. Immunohistochemical method was used to assess p53, epidermal growth factor receptor, MLH1, and MSH2 status. KRAS mutation was examined by direct sequencing. Thirty three patients (27.5%) developed metachronous metastasis during follow up. By multivariate analysis, only female gender (p = 0.03), high serum carcinoembryonic antigen (CEA) level (≧5 ng/ml) (p = 0.04), and MLH1 overexpression (p = 0.003) were associated with the metastasis group. The 5-year-survival rate were also significantly lower for female gender (71.7% versus 88.9%, p = 0.025), high CEA level (64.9% versus 92.4%, p < 0.001), and MLH1 overexpression (77.5% versus 94.4%, p = 0.039). In contrast, MSH2 overexpression was associated with better survival, 95.1% versus 75.5% (p = 0.024). The reversed prognostic implications in the overexpression of MLH1 and MSH2 for stage I-II colon cancer patients is a novel finding and worthy of further confirmation. Copyright © 2017 Chang Gung University. Published by Elsevier B.V. All rights reserved.

Recombinant human alpha fetoprotein synergistically potentiates the anti-cancer effects of 1'-S-1'-acetoxychavicol acetate when used as a complex against human tumours harbouring AFP-receptors.

PubMed

Arshad, Norhafiza M; In, Lionel L A; Soh, Tchen Lin; Azmi, Mohamad Nurul; Ibrahim, Halijah; Awang, Khalijah; Dudich, Elena; Tatulov, Eduard; Nagoor, Noor Hasima

2015-06-30

Previous in vitro and in vivo studies have reported that 1'-S-1'-acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis-mediated cell death in tumour cells via dysregulation of the NF-κB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tumour cells. In the present study, all the problems above were addressed using the novel drug complex formulation involving recombinant human alpha fetoprotein (rhAFP) and ACA. To study the synergistic effect of both agents on human cancer xenografts, athymic nude (Nu/Nu) mice were used and treated with various combination regimes intraperitoneally. Serum levels of tumour markers for carcinoembryonic antigen (CEA) and prostate specific antigen (PSA) were assessed using sandwich ELISA. IHC and Western blotting were also conducted on in vivo tumour biopsies to investigate the involvement of NF-κB regulated genes and inflammatory biomarkers. Quantification and correlation between drug efficacies and AFP-receptors were done using IF-IC and Pearson's correlation analysis. Mice exposed to combined treatments displayed higher reductions in tumour volume compared to stand alone agents, consistent with in vitro cytotoxicity assays. Milder signs of systemic toxicity, such as loss in body weight and inflammation of vital organs were also demonstrated compared to stand alone treatments. Tumour marker levels were consistent within all rhAFP/ACA treatment groups where levels of CEA and PSA were initially elevated upon commencement of treatment, and consecutively reduced corresponding to a decrease in tumour bulk volume. Both IHC and Western blotting results indicated that the combined action of rhAFP/ACA was not only able to down-regulate NF-κB activation, but also reduce the expression of NF-κB regulated genes and inflammatory biomarkers. The efficacy of rhAFP/ACA complex was also found to be weakly negatively correlated to the level of surface AFP-receptors between tumour types. This drug complex formulation shows great therapeutic potential against AFP-receptor positive tumours, and serves as a basis to overcome insoluble and non-specific anti-neoplastic molecules.

Recombinant human alpha fetoprotein synergistically potentiates the anti-cancer effects of 1′-S-1′-acetoxychavicol acetate when used as a complex against human tumours harbouring AFP-receptors

PubMed Central

Arshad, Norhafiza M.; In, Lionel L.A.; Soh, Tchen Lin; Azmi, Mohamad Nurul; Ibrahim, Halijah; Awang, Khalijah; Dudich, Elena; Tatulov, Eduard; Nagoor, Noor Hasima

2015-01-01

Purpose Previous in vitro and in vivo studies have reported that 1′-S-1′-acetoxychavicol acetate (ACA) isolated from rhizomes of the Malaysian ethno-medicinal plant Alpinia conchigera Griff (Zingiberaceae) induces apoptosis-mediated cell death in tumour cells via dysregulation of the NF-κB pathway. However there were some clinical development drawbacks such as poor in vivo solubility, depreciation of biological activity upon exposure to an aqueous environment and non-specific targeting of tumour cells. In the present study, all the problems above were addressed using the novel drug complex formulation involving recombinant human alpha fetoprotein (rhAFP) and ACA. Experimental Design To study the synergistic effect of both agents on human cancer xenografts, athymic nude (Nu/Nu) mice were used and treated with various combination regimes intraperitoneally. Serum levels of tumour markers for carcinoembryonic antigen (CEA) and prostate specific antigen (PSA) were assessed using sandwich ELISA. IHC and Western blotting were also conducted on in vivo tumour biopsies to investigate the involvement of NF-κB regulated genes and inflammatory biomarkers. Quantification and correlation between drug efficacies and AFP-receptors were done using IF-IC and Pearson's correlation analysis. Results Mice exposed to combined treatments displayed higher reductions in tumour volume compared to stand alone agents, consistent with in vitro cytotoxicity assays. Milder signs of systemic toxicity, such as loss in body weight and inflammation of vital organs were also demonstrated compared to stand alone treatments. Tumour marker levels were consistent within all rhAFP/ACA treatment groups where levels of CEA and PSA were initially elevated upon commencement of treatment, and consecutively reduced corresponding to a decrease in tumour bulk volume. Both IHC and Western blotting results indicated that the combined action of rhAFP/ACA was not only able to down-regulate NF-κB activation, but also reduce the expression of NF-κB regulated genes and inflammatory biomarkers. The efficacy of rhAFP/ACA complex was also found to be weakly negatively correlated to the level of surface AFP-receptors between tumour types. Conclusions This drug complex formulation shows great therapeutic potential against AFP-receptor positive tumours, and serves as a basis to overcome insoluble and non-specific anti-neoplastic molecules. PMID:26158863

Nanogold-functionalized DNAzyme concatamers with redox-active intercalators for quadruple signal amplification of electrochemical immunoassay.

PubMed

Zhou, Jun; Lai, Wenqiang; Zhuang, Junyang; Tang, Juan; Tang, Dianping

2013-04-10

A novel and in situ amplified immunoassay strategy with quadruple signal amplification was designed for highly efficient electrochemical detection of low-abundance proteins (carcinoembryonic antigen, CEA, as a model) by using nanogold-functionalized DNAzyme concatamers with redox-active intercalators. To construct such an in situ amplification system, streptavidin-labeled gold nanoparticles (AuNP-SA) were initially used for the labelling of initiator strands (S0) and detection antibody (mAb2) with a large ratio (mAb2-AuNP-S0), and then two auxiliary DNA strands S1 and S2 were designed for in situ propagation of DNAzyme concatamers with the hemin/G-quadruplex format. The quadruple signal amplification was implemented by using the avidin-biotin chemistry, nanogold labels, DNA concatamers, and DNAzymes. In the presence of target CEA, the sandwiched immunocomplex was formed between the immobilized primary antibodies on the electrode and the conjugated detection antibodies on the mAb2-AuNP-S0. The carried S0 initiator strands could progress a chain reaction of hybridization events between alternating S1/S2 DNA strands to form a nicked double-helix. Upon addition of hemin, the hemin-binding aptamers could be bound to form the hemin/G-quadruplex-based DNAzymes. The formed double-helix DNA polymers could cause the intercalation of numerous electroactive methylene blue molecules. During the electrochemical measurement, the formed DNAzymes could catalyze the reduction of H2O2 in the solution to amplify the electrochemical signal of the intercalated methylene blue. Under optimal conditions, the electrochemical immunoassay exhibited a wide dynamic range of 1.0 fg mL(-1) to 20 ng mL(-1) toward CEA standards with a low detection limit of 0.5 fg mL(-1). Intra-assay and inter-assay coefficients of variation (CV) were less than 8.5% and 11.5%, respectively. No significant differences at the 0.05 significance level were encountered in the analysis of 14 clinical serum specimens between the developed immunoassay and commercialized electrochemiluminescent (ECL) method for detection of CEA.

Radiolabelling of glycosylated MFE-23::CPG2 fusion protein (MFECP1) with 99mTc for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT).

PubMed

Francis, R J; Mather, S J; Chester, K; Sharma, S K; Bhatia, J; Pedley, R B; Waibel, R; Green, A J; Begent, R H J

2004-08-01

MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was 99mTc-carbonyl [99mTc(H2O)3(CO)3]+ (abbreviated to TcCO) mediated labelling of 99mTc to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody-antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins.

Deregulation of the CEACAM expression pattern causes undifferentiated cell growth in human lung adenocarcinoma cells.

PubMed

Singer, Bernhard B; Scheffrahn, Inka; Kammerer, Robert; Suttorp, Norbert; Ergun, Suleyman; Slevogt, Hortense

2010-01-18

CEACAM1, CEA/CEACAM5, and CEACAM6 are cell adhesion molecules (CAMs) of the carcinoembryonic antigen (CEA) family that have been shown to be deregulated in lung cancer and in up to 50% of all human cancers. However, little is known about the functional impact of these molecules on undifferentiated cell growth and tumor progression. Here we demonstrate that cell surface expression of CEACAM1 on confluent A549 human lung adenocarcinoma cells plays a critical role in differentiated, contact-inhibited cell growth. Interestingly, CEACAM1-L, but not CEACAM1-S, negatively regulates proliferation via its ITIM domain, while in proliferating cells no CEACAM expression is detectable. Furthermore, we show for the first time that CEACAM6 acts as an inducer of cellular proliferation in A549 cells, likely by interfering with the contact-inhibiting signal triggered by CEACAM1-4L, leading to undifferentiated anchorage-independent cell growth. We also found that A549 cells expressed significant amounts of non-membrane anchored variants of CEACAM5 and CEACAM6, representing a putative source for the increased CEACAM5/6 serum levels frequently found in lung cancer patients. Taken together, our data suggest that post-confluent contact inhibition is established and maintained by CEACAM1-4L, but disturbances of CEACAM1 signalling by CEACAM1-4S and other CEACAMs lead to undifferentiated cell growth and malignant transformation.

Analysis and comparison of the cost-effectiveness of statins according to the baseline low-density lipoprotein cholesterol level in Korea.

PubMed

Jeong, Y J; Kim, H; Baik, S J; Kim, T M; Yang, S J; Lee, S-H; Cho, J-H; Lee, H; Yim, H W; Choi, I Y; Yoon, K-H; Kim, H-S

2017-06-01

There are a few Korean studies on the economics of statins based on reduction in low-density lipoprotein cholesterol (LDL-C) data from other countries. This study aimed to analyse and compare the cost-effectiveness of statins according to the baseline LDL-C level in Korea. Between January 2009 and December 2015, the data of patients who were prescribed statins for the first time were extracted from electronic medical records. We performed a cost-effectiveness analysis (CEA) based on the LDL-C reduction rate (CEA-RR) and target achievement rate. Among high-intensity statins, the CEA-RR value of rosuvastatin (20 mg) was significantly lower than that of atorvastatin (40 mg) at all baseline LDL-C levels, except levels of 160-189 mg/dL. Additionally, at baseline LDL-C levels of 130-159 mg/dL, the CEA-RR value of rosuvastatin (20 mg) was three times lower than that of atorvastatin (40 mg) (9·1 ± 2·5 $/% vs. 31·7 ± 15·0 $/%, P < 0·001). Among moderate-to-low-intensity statins, rosuvastatin (5 mg) showed the lowest CEA-RR value (4·0 ± 0·6 $/%), and the value significantly increased for pitavastatin (2 mg) (8·0 ± 0·6 $/%), atorvastatin (10 mg) (9·5 ± 0·5 $/%), simvastatin (10·8 ± 1·1 $/%) and pravastatin (40 mg) (11·5 ± 0·9 $/%) in order (P < 0·0001). On changing from atorvastatin (10 mg) to atorvastatin (20 mg), the additional yearly cost was 16·0 and additional CEA-RR value was 2·74 $/%. On the other hand, on changing from atorvastatin (10 mg) to rosuvastatin (10 mg), the additional yearly cost was -16·3 and additional CEA-RR value was -1·8 $/%. We successfully compared the cost-effectiveness of statins according to the baseline LDL-C level in Korea. It is expected that our findings will help clinical decision-making with regard to statin prescription, and this will help reduce national medical expenditure. © 2017 John Wiley & Sons Ltd.

Intracellular Acidosis Promotes Mitochondrial Apoptosis Pathway: Role of EMMPRIN Down-regulation via Specific Single-chain Fv Intrabody

PubMed Central

Thammasit, Patcharin; Sangboonruang, Sirikwan; Suwanpairoj, Supattara; Khamaikawin, Wannisa; Intasai, Nutjeera; Kasinrerk, Watchara; Tayapiwatana, Chatchai; Tragoolpua, Khajornsak

2015-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN) is a human leukocyte surface molecule that is enriched on the surface of many cancer cells, and it plays an important role in proliferation and metastasis. In this study, we utilized the chimeric adenoviral vector Ad5/F35 carrying gene encoding scFv against EMMPRIN (scFv-M6-1B9) to down-regulate EMMPRIN cell surface expression and investigated programmed cell death response in colorectal cancer (CRC) cell, Caco-2. The scFv-M6-1B9 intrabody exhibits robust activity in reducing EMMPRIN cell surface expression. This approach led to the inducing of apoptosis, which was relative to the increasing of apoptotic bodies in sub-G1 peak, phosphatidylserine externalization, as well as TUNEL-positive cells. In addition, real-time RT-PCR and western blotting analysis indicated that apoptosis was enhanced through the mitochondrial pathway, a marked reduction of Bcl-2, leading to the translocation of cytochrome c and also the dramatic activation of caspase-3. Moreover, carcinoembryonic antigen (CEA), a tumor marker for CRC, was found to have significantly diminished in both secreted protein and mRNA levels. In conclusion, these findings suggest that EMMPRIN down-regulation by scFv-M6-1B9 intrabody has great potential in enhancing the efficacy of apoptosis induction through the mitochondrial pathway and in effecting a decline in the CEA level. Thus, its benefits could be applied to project the future prospects for targeted gene therapy and therapeutic application in monitoring colorectal cancer. PMID:25663946

Biomarkers in pancreatic adenocarcinoma: current perspectives.

PubMed

Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

2016-01-01

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC.

Biomarkers in pancreatic adenocarcinoma: current perspectives

PubMed Central

Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

2016-01-01

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. PMID:28003762

Factors associated with parent support for condom education and availability.

PubMed

AugsJoost, Brett; Jerman, Petra; Deardorff, Julianna; Harley, Kim; Constantine, Norman A

2014-04-01

Expanding condom-related knowledge and skills and reducing barriers to condom use have the potential to help reduce pregnancies and sexually transmitted infections among youth. These goals are sometimes addressed through condom education and availability (CEA) programs as part of sexuality education in school. Parents are a key constituency in efforts to implement such programs. A representative statewide sample of households with children (N = 1,093) in California was employed to examine parent support for CEA and the potential influences of demographics (gender, age, and Hispanic ethnicity), sociodemographics (education, religious affiliation, religious service attendance, and political ideology), and condom-related beliefs (belief in condom effectiveness and belief that teens who use condoms during sex are being responsible) on parent support for CEA. The parents in our sample reported a high level of support for CEA (M = 3.23 on a 4-point scale) and believing in a high level of condom effectiveness (M = 3.36 on a 4-point scale). In addition, 84% of the parents agreed that teens who use condoms during sex are being responsible. Hierarchical regression analyses showed that parents who were younger, Hispanic, with a lower educational attainment, without a religious affiliation, less religiously observant, and politically liberal were more supportive of CEA. After controlling for these demographic and sociodemographic factors, condom effectiveness and responsibility beliefs each added independently to the predictability of parent support for CEA. These findings suggest that parent education related to condom effectiveness could help increase support for school-based CEA programs.

Relationship between serum calcium and CA 19-9 levels in colorectal cancer

PubMed Central

Fuszek, Peter; Lakatos, Peter; Tabak, Adam; Papp, Janos; Nagy, Zsolt; Takacs, Istvan; Horvath, Henrik Csaba; Lakatos, Peter Laszlo; Speer, Gabor

2004-01-01

AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n = 32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25 (OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer. PMID:15222030

Effects of Fresh Yellow Onion Consumption on CEA, CA125 and Hepatic Enzymes in Breast Cancer Patients: A Double- Blind Randomized Controlled Clinical Trial.

PubMed

Jafarpour-Sadegh, Farnaz; Montazeri, Vahid; Adili, Ali; Esfehani, Ali; Rashidi, Mohammad-Reza; Mesgari, Mehran; Pirouzpanah, Saeed

2015-01-01

Onion (Allium cepa) consumption has been remarked in folk medicine which has not been noted to be administered so far as an adjunct to conventional doxorubicin-based chemotherapy in breast cancer patients. To our knowledge, this is the first study aimed to investigate the effects of consuming fresh yellow onions on hepatic enzymes and cancer specific antigens compared with a low-onion containing diet among breast cancer (BC) participants treated with doxorubicin. This parallel design randomized controlled clinical trial was conducted on 56 BC patients whose malignancy was confirmed with histopathological examination. Subjects were assigned in a stratified-random allocation into either group received body mass index dependent 100-160 g/d of onion as high onion group (HO; n=28) or 30-40 g/d small onion in low onion group (LO; n=28) for eight weeks intervention. Participants, care givers and laboratory assessor were blinded to the assignments (IRCT registry no: IRCT2012103111335N1). The compliance of participants in the analysis was appropriate (87.9%). Comparing changes throughout pre- and post-dose treatments indicated significant controls on carcinoembryonic antigen, cancer antigen-125 and alkaline phosphatase levels in the HO group (P<0.05). Our findings for the first time showed that regular onion administration could be effective for hepatic enzyme conveying adjuvant chemotherapy relevant toxicity and reducing the tumor markers in BC during doxorubicin-based chemotherapy.

[Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

PubMed

Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J

2017-01-25

Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t -tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found ( P >0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls ( t =-3.536, P =0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group ( r =0.494, P <0.01), and the same correlation as CEA and CA(199) group ( r =0.897, P <0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group ( P >0.05), while significant differences were found in CA(125) and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type ( P <0.05). The multiple factors analysis showed that the high level of CA(125) was a independent risk factor of BRCA mutations in sporadic HGSOC ( P =0.007). Conclusion: The combination of CA(125) with BRCA have great clinical significance, the mutation of BRCA gene could guild the clinical chemotherapy regiments.

Intramolecular trimerization, a novel strategy for making multispecific antibodies with controlled orientation of the antigen binding domains

PubMed Central

Alvarez-Cienfuegos, Ana; Nuñez-Prado, Natalia; Compte, Marta; Cuesta, Angel M.; Blanco-Toribio, Ana; Harwood, Seandean Lykke; Villate, Maider; Merino, Nekane; Bonet, Jaume; Navarro, Rocio; Muñoz-Briones, Clara; Sørensen, Karen Marie Juul; Mølgaard, Kasper; Oliva, Baldo; Sanz, Laura; Blanco, Francisco J.; Alvarez-Vallina, Luis

2016-01-01

Here, we describe a new strategy that allows the rapid and efficient engineering of mono and multispecific trivalent antibodies. By fusing single-domain antibodies from camelid heavy-chain-only immunoglobulins (VHHs) to the N-terminus of a human collagen XVIII trimerization domain (TIEXVIII) we produced monospecific trimerbodies that were efficiently secreted as soluble functional proteins by mammalian cells. The purified VHH-TIEXVIII trimerbodies were trimeric in solution and exhibited excellent antigen binding capacity. Furthermore, by connecting with two additional glycine-serine-based linkers three VHH-TIEXVIII modules on a single polypeptide chain, we present an approach for the rational design of multispecific tandem trimerbodies with defined stoichiometry and controlled orientation. Using this technology we report here the construction and characterization of a tandem VHH-based trimerbody capable of simultaneously binding to three different antigens: carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR) and green fluorescence protein (GFP). Multispecific tandem VHH-based trimerbodies were well expressed in mammalian cells, had good biophysical properties and were capable of simultaneously binding their targeted antigens. Importantly, these antibodies were very effective in inhibiting the proliferation of human epidermoid carcinoma A431 cells. Multispecific VHH-based trimerbodies are therefore ideal candidates for future applications in various therapeutic areas. PMID:27345490

A versatile quantitation platform based on platinum nanoparticles incorporated volumetric bar-chart chip for highly sensitive assays.

PubMed

Wang, Yuzhen; Zhu, Guixian; Qi, Wenjin; Li, Ying; Song, Yujun

2016-11-15

Platinum nanoparticles incorporated volumetric bar-chart chip (PtNPs-V-Chip) is able to be used for point-of-care tests by providing quantitative and visualized readout without any assistance from instruments, data processing, or graphic plotting. To improve the sensitivity of PtNPs-V-Chip, hybridization chain reaction was employed in this quantitation platform for highly sensitive assays that can detect as low as 16 pM Ebola Virus DNA, 0.01ng/mL carcinoembryonic antigen (CEA), and the 10 HER2-expressing cancer cells. Based on this amplified strategy, a 100-fold decrease of detection limit was achieved for DNA by improving the number of platinum nanoparticle catalyst for the captured analyte. This quantitation platform can also distinguish single base mismatch of DNA hybridization and observe the concentration threshold of CEA. The new strategy lays the foundation for this quantitation platform to be applied in forensic analysis, biothreat detection, clinical diagnostics and drug screening. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparative study of label-free electrochemical immunoassay on various gold nanostructures

NASA Astrophysics Data System (ADS)

Rafique, S.; Gao, C.; Li, C. M.; Bhatti, A. S.

2013-10-01

Electrochemical methods such as amperometry and impedance spectroscopy provide the feasibility of label-free immunoassay. However, the performance of electrochemical interfaces varies with the shape of gold nanostructures. In the present work three types of gold nanostructures including pyramid, spherical, and rod-like nanostructures were electrochemically synthesized on the gold electrode and were further transformed into immunosensor by covalent binding of antibodies. As a model protein, a cancer biomarker, Carcinoembryonic Antigen (CEA) was detected using amperometric and impedimetric techniques on three nanostructured electrodes, which enabled to evaluate and compare the immunoassay's performance. It was found that all three immunosensors showed improved linear electrochemical response to the concentration of CEA compared to bare Au electrode. Among all the spherical gold nanostructure based immunosensors displayed superior performance. Under optimal condition, the immunosensors exhibited a limit of detection of 4.1 pg ml-1 over a concentration range of five orders of magnitude. This paper emphasizes that fine control over the geometry of nanostructures is essentially important for high-performance electrochemical immunoassay.

Levels of CEA among vinyl chloride and polyvinyl chloride exposed workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, H.A.; Snyder, J.; Lewinson, T.

1978-09-01

In 1974, vinyl chloride exposed workers were found to have an increased risk of malignant disease (hemangiosarcoma of the liver). We have examined 1,147 workers exposed to vinyl chloride monomer in three VC/PVC polymerization plants, and 269 workers from a PVC extrusion plant manufacturing PVC textile leather, exposed to much lower concentrations of vinyl chloride. Included among the comprehensive clinical and laboratory studies conducted was the CEA titer. We obtained, respectively, 1,115 and 248 CEA titers. Multiple factors were demonstrated which affected the distribution of CEA titers. Cigarette use had the greatest effect, followed by history of specific past illnessesmore » and alcohol intake history. After removing these possible confounding effects, the distribution of CEA titers among the polymerization workers was significantly different from the extrusion plant group and from an unexposed comparison group. Of the six job categories analyzed, only production and maintenance workers had CEA titer distributions significantly different from the comparison group and the extrusion workers. The investigation demonstrates that occupational exposures in VC/PVC polymerization plants can cause elevations in the CEA titers of otherwise healthy individuals. Prospective follow-up is necessary before conclusions can be drawn concerning the usefulness of the CEA titer as a predictive indicator of possible increased risk.« less

Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer.

PubMed

Weihrauch, Martin R; Ansén, Sascha; Jurkiewicz, Elke; Geisen, Caroline; Xia, Zhinan; Anderson, Karen S; Gracien, Edith; Schmidt, Manuel; Wittig, Burghardt; Diehl, Volker; Wolf, Juergen; Bohlen, Heribert; Nadler, Lee M

2005-08-15

We conducted a phase I/II randomized trial to evaluate the clinical and immunologic effect of chemotherapy combined with vaccination in primary metastatic colorectal cancer patients with a carcinoembryonic antigen-derived peptide in the setting of adjuvants granulocyte macrophage colony-stimulating factor, CpG-containing DNA molecules (dSLIM), and dendritic cells. HLA-A2-positive patients with confirmed newly diagnosed metastatic colorectal cancer and elevated serum carcinoembryonic antigen (CEA) were randomized to receive three cycles of standard chemotherapy (irinotecan/high-dose 5-fluorouracil/leucovorin) and vaccinations with CEA-derived CAP-1 peptide admixed with different adjuvants [CAP-1/granulocyte macrophage colony-stimulating factor/interleukin-2 (IL-2), CAP-1/dSLIM/IL-2, and CAP-1/IL-2]. After completion of chemotherapy, patients received weekly vaccinations until progression of disease. Immune assessment was done at baseline and after three cycles of combined chemoimmunotherapy. HLA-A2 tetramers complexed with the peptides CAP-1, human T-cell lymphotrophic virus type I TAX, cytomegalovirus (CMV) pp65, and EBV BMLF-1 were used for phenotypic immune assessment. IFN-gamma intracellular cytokine assays were done to evaluate CTL reactivity. Seventeen metastatic patients were recruited, of whom 12 completed three cycles. Therapy resulted in five complete response, one partial response, five stable disease, and six progressive disease. Six grade 1 local skin reactions and one mild systemic reaction to vaccination treatment were observed. Overall survival after a median observation time of 29 months was 17 months with a survival rate of 35% (6 of 17) at that time. Eight patients (47%) showed elevation of CAP-1-specific CTLs. Neither of the adjuvants provided superiority in eliciting CAP-1-specific immune responses. During three cycles of chemotherapy, EBV/CMV recall antigen-specific CD8+ cells decreased by an average 14%. The presented chemoimmunotherapy is a feasible and safe combination therapy with clinical and immunologic efficacy. Despite concurrent chemotherapy, increases in CAP-1-specific T cells were observed in 47% of patients after vaccination.

The diagnostic value of tumor markers in bronchoalveolar lavage fluid for the peripheral pulmonary carcinoma.

PubMed

Zhang, Shi; Zhao, Yun-Feng; Zhang, Ming-Zhou; Wu, Xue-Ling

2017-07-01

To investigate the value of Ubiquitin specific peptidase 8 (USP8), Chitinase 3-like 1 (YKL40), Heat shock protein 90a (HSP90α), glutathione S-transferase P1 (GSTP1), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) and cytokeratin fragment antiogen 21-1 (CYFRA21-1) in bronchoalveolar lavage fluid (BALF) and serum for diagnosis in patients with peripheral lung cancer. The concentration of these markers were measured in 50 patients with peripheral lung cancer and 50 patients with benign lung diseases by using enzyme-linked immuno sorbent assay methods. There were significant differences between the peripheral lung cancer group and the benign lung disease group (P < 0.05) in the BALF of USP8, YKL40, HSP90α, CEA, NSE and CYFRA21-1. There were significant differences between the peripheral lung cancer group and the benign lung disease group (P < 0.05) in the serum of HSP90α and CEA. There were no differences in others. There were no correlation between the concentration of all markers and age, histological type, TNM stage (I-IV). There was a weak correlation between the primary foci diameters and the concentration of YKL40 in BALF. (Pearson's correlation: 0.203, P = 0.048) The diagnostic efficiencies of USP8, YKL40, HSP90α were superior to CYFRA21-1 and NSE, being lower CEA. Detection of tumor markers in BALF was superior to serum specimens. The measurement of USP8, HSP90α and YKL40 in BALF had more clinical value for the diagnosis of peripheral pulmonary carcinoma. © 2015 John Wiley & Sons Ltd.

Potentiometric Sensors Based on Surface Molecular Imprinting: Detection of Cancer Biomarkers and Viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Y.; Zhang, Z; Jain, V

2010-01-01

The continuing discovery of cancer biomarkers necessitates improved methods for their detection. Molecular imprinting using artificial materials provides an alternative to the detection of a wide range of substances. We applied surface molecular imprinting using self-assembled monolayers to design sensing elements for the detection of cancer biomarkers and other proteins. These elements consist of a gold-coated silicon chip onto which hydroxyl-terminated alkanethiol molecules and template biomolecule are co-adsorbed, where the thiol molecules are chemically bound to the metal substrate and self-assembled into highly ordered monolayers, the biomolecules can be removed, creating the foot-print cavities in the monolayer matrix for thismore » kind of template molecules. Re-adsorption of the biomolecules to the sensing chip changes its potential, which can be measured potentiometrically. We applied this method to the detection of carcinoembryonic antigen (CEA) in both solutions of purified CEA and in the culture medium of a CEA-producing human colon cancer cell line. The CEA assay, validated also against a standard immunoassay, was both sensitive (detection range 2.5-250 ng/mL) and specific (no cross-reactivity with hemoglobin; no response by a non-imprinted sensor). Similar results were obtained for human amylase. In addition, we detected virions of poliovirus in a specific manner (no cross-reactivity to adenovirus, no response by a non-imprinted sensor). Our findings demonstrate the application of the principles of molecular imprinting to the development of a new method for the detection of protein cancer biomarkers and to protein-based macromolecular structures such as the capsid of a virion. This approach has the potential of generating a general assay methodology that could be highly sensitive, specific, simple and likely inexpensive.« less

Combination immunotherapy and active-specific tumor cell vaccination augments anti-cancer immunity in a mouse model of gastric cancer

PubMed Central

2011-01-01

Background Active-specific immunotherapy used as an adjuvant therapeutic strategy is rather unexplored for cancers with poorly characterized tumor antigens like gastric cancer. The aim of this study was to augment a therapeutic immune response to a low immunogenic tumor cell line derived from a spontaneous gastric tumor of a CEA424-SV40 large T antigen (CEA424-SV40 TAg) transgenic mouse. Methods Mice were treated with a lymphodepleting dose of cyclophosphamide prior to reconstitution with syngeneic spleen cells and vaccination with a whole tumor cell vaccine combined with GM-CSF (a treatment strategy abbreviated as LRAST). Anti-tumor activity to subcutaneous tumor challenge was examined in a prophylactic as well as a therapeutic setting and compared to corresponding controls. Results LRAST enhances tumor-specific T cell responses and efficiently inhibits growth of subsequent transplanted tumor cells. In addition, LRAST tended to slow down growth of established tumors. The improved anti-tumor immune response was accompanied by a transient decrease in the frequency and absolute number of CD4+CD25+FoxP3+ T cells (Tregs). Conclusions Our data support the concept that whole tumor cell vaccination in a lymphodepleted and reconstituted host in combination with GM-CSF induces therapeutic tumor-specific T cells. However, the long-term efficacy of the treatment may be dampened by the recurrence of Tregs. Strategies to counteract suppressive immune mechanisms are required to further evaluate this therapeutic vaccination protocol. PMID:21859450

The Central Nucleus of the Amygdala and Corticotropin-Releasing Factor: Insights into Contextual Fear Memory

PubMed Central

Pitts, Matthew W.; Todorovic, Cedomir; Blank, Thomas; Takahashi, Lorey K.

2009-01-01

The central nucleus of the amygdala (CeA) has been traditionally viewed in fear conditioning to serve as an output neural center that transfers conditioned information formed in the basolateral amygdala to brain structures that generate emotional responses. Recent studies suggest that the CeA may also be involved in fear memory consolidation. In addition, corticotropin-releasing factor systems were shown to facilitate memory consolidation in the amygdala, which contains a high density of CRF immunoreactive cell bodies and fibers in the lateral part of the CeA (CeAl). However, the involvement of CeA CRF in contextual fear conditioning remains poorly understood. Therefore, we first conducted a series of studies using fiber-sparing lesion and reversible inactivation methods to assess the general role of the CeA in contextual fear. We then used identical training and testing procedures to compare and evaluate the specific function of CeA CRF using CRF antisense oligonucleotides (CRF ASO). Rats microinjected with ibotenic acid, muscimol, or a CRF ASO into the CeA prior to contextual fear conditioning showed typical levels of freezing during acquisition training but exhibited significant reductions in contextual freezing in a retention test 48 h later. Furthermore, CeA inactivation induced by either muscimol or CRF ASO administration immediately prior to retention testing did not impair freezing, suggesting that the previously observed retention deficits were due to inhibition of consolidation rather than fear expression. Collectively, our results suggest CeA involvement in the consolidation of contextual fear memory and specifically implicate CeA CRF as an important mediator. PMID:19494159

National variation in preoperative imaging, carotid duplex ultrasound criteria, and threshold for surgery for asymptomatic carotid artery stenosis.

PubMed

Arous, Edward J; Simons, Jessica P; Flahive, Julie M; Beck, Adam W; Stone, David H; Hoel, Andrew W; Messina, Louis M; Schanzer, Andres

2015-10-01

Carotid endarterectomy (CEA) for asymptomatic carotid artery stenosis is among the most common procedures performed in the United States. However, consensus is lacking regarding optimal preoperative imaging, carotid duplex ultrasound criteria, and ultimately, the threshold for surgery. We sought to characterize national variation in preoperative imaging, carotid duplex ultrasound criteria, and threshold for surgery for asymptomatic CEA. The Society for Vascular Surgery Vascular Quality Initiative (VQI) database was used to identify all CEA procedures performed for asymptomatic carotid artery stenosis between 2003 and 2014. VQI currently captures 100% of CEA procedures performed at >300 centers by >2000 physicians nationwide. Three analyses were performed to quantify the variation in (1) preoperative imaging, (2) carotid duplex ultrasound criteria, and (3) threshold for surgery. Of 35,695 CEA procedures in 33,488 patients, the study cohort was limited to 19,610 CEA procedures (55%) performed for asymptomatic disease. The preoperative imaging modality used before CEA varied widely, with 57% of patients receiving a single preoperative imaging study (duplex ultrasound imaging, 46%; computed tomography angiography, 7.5%; magnetic resonance angiography, 2.0%; cerebral angiography, 1.3%) and 43% of patients receiving multiple preoperative imaging studies. Of the 16,452 asymptomatic patients (89%) who underwent preoperative duplex ultrasound imaging, there was significant variability between centers in the degree of stenosis (50%-69%, 70%-79%, 80%-99%) designated for a given peak systolic velocity, end diastolic velocity, and internal carotid artery-to-common carotid artery ratio. Although 68% of CEA procedures in asymptomatic patients were performed for an 80% to 99% stenosis, 26% were performed for a 70% to 79% stenosis, and 4.1% were performed for a 50% to 69% stenosis. At the surgeon level, the range in the percentage of CEA procedures performed for a <80% asymptomatic carotid artery stenosis is from 0% to 100%. Similarly, at the center level, institutions range in the percentage of CEA procedures performed for a <80% asymptomatic carotid artery stenosis from 0% to 100%. Despite CEA being an extremely common procedure, there is widespread variation in the three primary determinants-preoperative imaging, carotid duplex ultrasound criteria, and threshold for surgery-of whether CEA is performed for asymptomatic carotid stenosis. Standardizing the approach to care for asymptomatic carotid artery stenosis will mitigate the significant downstream effects of this variation on health care costs. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Proximity hybridization-regulated chemiluminescence resonance energy transfer for homogeneous immunoassay.

PubMed

Liu, Mengmeng; Wu, Jie; Yang, Kaili; Zong, Chen; Lei, Jianping; Ju, Huangxian

2016-07-01

Chemiluminescence resonance energy transfer (CRET) and the proximity ligation assay have been widely used in design of sensors for the bioanalysis. Here, a wash-free and homogeneous strategy was proposed to detect carcino-embryonic antigen (CEA) based on proximity hybridization-regulated CRET. The Cy5 demonstrated strong chemiluminescence (CL) via the oxidation of TCPO in the presence of H2O2 and energy transfer between excited TCPO and Cy5. Graphene oxide (GO) as an excellent quencher was used to produce the "Signal off" mode that little CL emission was observed through CRET between GO and the Cy5-labelled DNA3. Once CEA was introduced, the target-induced proximity hybridization occurred to form a proximate complex, which inhibited the CRET by preventing GO from absorbing Cy5-labelled DNA3. Furthermore, taking advantage of nicking endonuclease Nt.BbvCI for in situ recycling, the signal could be further amplified for highly sensitive CL detection. Our results showed that this strategy enabled a specific response to CEA with a detection range of 5 orders of magnitude, along with a detection limit of 3.2pg mL(-1). Apart from its easy operation, high sensitivity and acceptable accuracy, the proposed method needed only 0.3μL of sample, indicating its great opportunity for commercial application. Copyright © 2016 Elsevier B.V. All rights reserved.

Personalized Risk Assessment in Never, Light, and Heavy Smokers in a prospective cohort in Taiwan.

PubMed

Wu, Xifeng; Wen, Chi Pang; Ye, Yuanqing; Tsai, MinKwang; Wen, Christopher; Roth, Jack A; Pu, Xia; Chow, Wong-Ho; Huff, Chad; Cunningham, Sonia; Huang, Maosheng; Wu, Shuanbei; Tsao, Chwen Keng; Gu, Jian; Lippman, Scott M

2016-11-02

The objective of this study was to develop markedly improved risk prediction models for lung cancer using a prospective cohort of 395,875 participants in Taiwan. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC). In multivariate Cox regression analysis, age, gender, smoking pack-years, family history of lung cancer, personal cancer history, BMI, lung function test, and serum biomarkers such as carcinoembryonic antigen (CEA), bilirubin, alpha fetoprotein (AFP), and c-reactive protein (CRP) were identified and included in an integrative risk prediction model. The AUC in overall population was 0.851 (95% CI = 0.840-0.862), with never smokers 0.806 (95% CI = 0.790-0.819), light smokers 0.847 (95% CI = 0.824-0.871), and heavy smokers 0.732 (95% CI = 0.708-0.752). By integrating risk factors such as family history of lung cancer, CEA and AFP for light smokers, and lung function test (Maximum Mid-Expiratory Flow, MMEF 25-75% ), AFP and CEA for never smokers, light and never smokers with cancer risks as high as those within heavy smokers could be identified. The risk model for heavy smokers can allow us to stratify heavy smokers into subgroups with distinct risks, which, if applied to low-dose computed tomography (LDCT) screening, may greatly reduce false positives.

Reverse Fluorescence Enhancement and Colorimetric Bimodal Signal Readout Immunochromatography Test Strip for Ultrasensitive Large-Scale Screening and Postoperative Monitoring.

PubMed

Yao, Yingyi; Guo, Weisheng; Zhang, Jian; Wu, Yudong; Fu, Weihua; Liu, Tingting; Wu, Xiaoli; Wang, Hanjie; Gong, Xiaoqun; Liang, Xing-Jie; Chang, Jin

2016-09-07

Ultrasensitive and quantitative fast screening of cancer biomarkers by immunochromatography test strip (ICTS) is still challenging in clinic. The gold nanoparticles (NPs) based ICTS with colorimetric readout enables a quick spectrum screening but suffers from nonquantitative performance; although ICTS with fluorescence readout (FICTS) allows quantitative detection, its sensitivity still deserves more efforts and attentions. In this work, by taking advantages of colorimetric ICTS and FICTS, we described a reverse fluorescence enhancement ICTS (rFICTS) with bimodal signal readout for ultrasensitive and quantitative fast screening of carcinoembryonic antigen (CEA). In the presence of target, gold NPs aggregation in T line induced colorimetric readout, allowing on-the-spot spectrum screening in 10 min by naked eye. Meanwhile, the reverse fluorescence enhancement signal enabled more accurately quantitative detection with better sensitivity (5.89 pg/mL for CEA), which is more than 2 orders of magnitude lower than that of the conventional FICTS. The accuracy and stability of the rFICTS were investigated with more than 100 clinical serum samples for large-scale screening. Furthermore, this rFICTS also realized postoperative monitoring by detecting CEA in a patient with colon cancer and comparing with CT imaging diagnosis. These results indicated this rFICTS is particularly suitable for point-of-care (POC) diagnostics in both resource-rich and resource-limited settings.

[Significance of the TPS cytokeratin marker in the postoperative follow up of colorectal carcinoma patients].

PubMed

Rupert, K; Holubec, L; Nosek, J; Houdek, K; Topolcan, O; Treska, V

2009-08-01

Examination of tumour markers conducive to follow up of the patients with colorectal carcinoma. The tumour markers were examined in the population of patients with primarily established and histologically verified colorectal adenocarcinoma. The resection therapy resulted in the decrease in post-operative CEA levels. There were no changes in pre- and post-operative CA 19-9 levels; unlike with post-operative TPS levels having been significantly increased, probably due to reparation processes resulting from the surgery. It can be concluded that pre- and post-operative CEA levels are the most suitable markers to check the effect of surgery. With a 95%-specificity for the establishment of recidives, the highest sensitivity was reached with TPS (83%); the sensitivities of the classical tumour markers CEA and CA 19-9 were significantly lower (41% and 25%, respectively). The results should be interpreted with caution due to a small number of relapses regarding a short follow up and rather local-regional character of the recidives. However, TPS seems to be a promising marker for the follow up of the patients with colorectal carcinoma. Thus, an ideal combination seems to be that of CEA and TPS.

Parameters of blood count and tumor markers in patients with borderline ovarian tumors: a retrospective analysis and relation to staging.

PubMed

Nomelini, Rosekeila Simões; da Silva, Taísa Morete; Tavares Murta, Beatriz Martins; Murta, Eddie Fernando Candido

2012-01-01

The aim of this paper was to evaluate the parameters of blood count and tumor markers in borderline ovarian tumors. We evaluated 21 patients who had confirmed histopathologic diagnosis of borderline ovarian tumor. We recorded age, parity, tumor type, stage of cancer, serum levels of tumor markers (CA-125, CA-15.3, CA-19.9, CEA, AFP), and the parameters of blood count, fasting glucose, disease-free survival and overall. The patients were divided into two groups, stage IA (n = 13) and stage IB-IIIC (n = 8). The unpaired t-test and Fisher's exact test were used, with P values of less than 0.05 being considered to indicate statistical significance. Levels of red blood cells, hematocrit, and hemoglobin were significantly higher in stage IA when compared with stage IB-IIIC (P < 0.05). The levels of tumor marker CEA had a tendency to be higher in the group stage IB-IIIC (0.08). Abnormal levels of CEA and CA-19.9 were found more frequently in stages IB-IIIC. Therefore, parameters of blood count, CEA, and CA-19.9 should be targeted for further research in identifying prognostic factors in borderline tumors.

Ethanol produces corticotropin releasing factor receptor-dependent enhancement of spontaneous glutamatergic transmission in the mouse central amygdala

PubMed Central

Silberman, Yuval; Fetterly, Tracy L.; Awad, Elias K.; Milano, Elana J.; Usdin, Ted B.; Winder, Danny G.

2015-01-01

Background Ethanol modulation of Central Amygdala (CeA) neurocircuitry plays a key role in the development of alcoholism via activation of the corticotropin releasing factor (CRF) receptor system. Previous work has predominantly focused on ethanol/CRF interactions on the CeA GABA circuitry; however our lab recently showed that CRF enhances CeA glutamatergic transmission. Therefore, this study sought to determine if ethanol modulates CeA glutamate transmission via activation of CRF signaling. Methods The effects of ethanol on spontaneous excitatory postsynaptic currents (sEPSCs) and basal resting membrane potentials were examined via standard electrophysiology methods in adult male C57BL/6J mice. Local ablation of CeA CRF neurons (CRFCeAhDTR) was achieved by targeting the human diphtheria toxin receptor (hDTR) to CeA CRF neurons with an adeno-associated virus. Ablation was quantified post-hoc with confocal microscopy. Genetic targeting of the diphtheria toxin active subunit to CRF neurons (CRFDTA mice) ablated CRF neurons throughout the CNS, as assessed by qRT-PCR quantification of CRF mRNA. Results Acute bath application of ethanol significantly increased sEPSC frequency in a concentration dependent manner in CeA neurons, and this effect was blocked by pretreatment of co-applied CRF receptor 1 and CRF receptor 2 antagonists. In experiments utilizing a CRF-tomato reporter mouse, ethanol did not significantly alter the basal membrane potential of CeA CRF neurons. The ability of ethanol to enhance CeA sEPSC frequency was not altered in CRFCeAhDTR mice despite a ~78% reduction in CeA CRF cell counts. The ability of ethanol to enhance CeA sEPSC frequency was also not altered in the CRFDTA mice despite a three-fold reduction in CRF mRNA levels. Conclusion These findings demonstrate that ethanol enhances spontaneous glutamatergic transmission in the CeA via a CRF receptor dependent mechanism. Surprisingly, our data suggest that this action may not require endogenous CRF. PMID:26503065

Wisteria floribunda agglutinin-sialylated mucin core polypeptide 1 is a sensitive biomarker for biliary tract carcinoma and intrahepatic cholangiocarcinoma: a multicenter study.

PubMed

Shoda, Junichi; Matsuda, Atsushi; Shida, Takashi; Yamamoto, Masakazu; Nagino, Masato; Tsuyuguchi, Toshio; Yasaka, Takahiro; Tazuma, Susumu; Uchiyama, Kazuhisa; Unno, Michiaki; Ohkohchi, Nobuaki; Nakanuma, Yasuni; Kuno, Atsushi; Narimatsu, Hisashi

2017-02-01

Wisteria floribunda agglutinin (WFA)-sialylated mucin core polypeptide 1 (MUC1) was investigated as a new glycoprotein marker for cholangiocarcinoma (CC) using glycoproteomics technologies. In this multicenter study, WFA-sialylated MUC1 levels in serum and bile samples were measured to determine their diagnostic capability in biliary tract carcinoma (BTC) and intrahepatic (Ih) CC. The study included 244 patients with BTC, 59 patients with IhCC, 287 patients with benign biliary tract diseases, and 44 control subjects. Serum WFA-sialylated MUC1 levels were significantly higher in patients with either BTC or IhCC than in control subjects and those with benign biliary tract diseases. Patients with IhCC showed higher WFA-sialylated MUC1 levels than patients with tumors at other sites. No significant differences in WFA-sialylated MUC1 levels were found with regard to cancer stage or tissue type. Receiver operating characteristic curve analysis showed that WFA-sialylated MUC1 was superior to carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) for the diagnosis of benign biliary tract diseases, BTC, and IhCC, as well as for stage I and II carcinomas. Significantly higher levels of biliary WFA-sialylated MUC1 were observed in BTC/IhCC than in benign biliary tract diseases. The diagnostic capability of biliary WFA-sialylated MUC1 was also superior to that of CA19-9, and diagnostic sensitivity was higher than that of biliary cytology for BTC/IhCC. WFA-sialylated MUC1 is a useful novel biomarker for BTC/IhCC. In the future, this measurement should be applied in the clinical setting.

Biochemical and molecular evidences for the antitumor potential of Ginkgo biloba leaves extract in rodents.

PubMed

Ahmed, Hanaa H; Shousha, Wafaa Gh; El-Mezayen, Hatem A; El-Toumy, Sayed A; Sayed, Alaa H; Ramadan, Aesha R

2017-01-01

Hepatocellular carcinoma (HCC) is one of the deadliest primary cancers, with a 5-year survival rate of 10% or less. This study was undertaken to elucidate the underlying biochemical and molecular mechanisms in favor of N-nitrosodiethylamine-induced hepatocellular carcinoma. Furthermore, the aim of this work was extended to explore the efficacy of Ginkgo biloba leaves extract in deterioration of HCC in rats. In the current study, HCC group experienced significant downregulation of ING-3 gene expression and upregulation of Foxp-1 gene expression in liver. Treatment of HCC groups with Ginkgo biloba leaves extract resulted in upregulation of ING-3 and downregulation of Foxp-1 gene expression in liver. In addition, there was significant increase in serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and glypican-3 (GPC-3) levels in HCC group versus the negative control group. In contrast, the groups with HCC subjected to either high or low dose of Ginkgo biloba leaves extract elicited significant reduction (P<0.05) of AFP, CEA and GPC-3 in serum compared to the untreated HCC rats. Besides, histological examination of liver tissue sections of rats in HCC group revealed typical anaplasia. Interestingly, treatment with Ginkgo biloba leaves extract elicited marked improvement in the histological feature of liver tissue in HCC groups. In conclusion, this research indicated that the carcinogenic potency of N-nitrosodiethylamine targeted multiple systems on the cellular and molecular levels. In addition, the results of the current study shed light on the promising anticancer activity of Ginkgo biloba leaves extract in treatment of hepatocellular carcinoma induced chemically in the experimental model through its apoptotic and antiproliferative properties.

Technical feasibility, diagnostic yield, and safety of microforceps biopsies during EUS evaluation of pancreatic cystic lesions (with video).

PubMed

Mittal, Chetan; Obuch, Joshua C; Hammad, Hazem; Edmundowicz, Steven A; Wani, Sachin; Shah, Raj J; Brauer, Brian C; Attwell, Augustin R; Kaplan, Jeffrey B; Wagh, Mihir S

2018-05-01

Through-the-needle microforceps are a recent addition to the EUS armamentarium for evaluation of pancreatic cystic lesions (PCLs). The main aim of this study was to assess the technical feasibility, diagnostic yield, and safety of EUS-guided microforceps biopsy for PCLs. Our electronic endoscopy database was queried to identify patients who underwent EUS-guided FNA (EUS-FNA) of PCLs and microforceps biopsies during the same procedure. A biopsy was done on the wall of the cyst with the microforceps through the 19-gauge needle, and cyst fluid was collected for cytology and carcinoembryonic antigen (CEA) levels. Adverse events were recorded per published American Society for Gastrointestinal Endoscopy criteria. Twenty-seven patients underwent EUS-FNA and microforceps biopsy of PCLs from February 2016 to July 2017. Fourteen cysts were located in the pancreatic head and/or uncinate, and 13 were located in the body and/or tail region. Microforceps biopsies were technically successful in all cases and provided a pathology diagnosis in 24 of 27 cases (yield 88.9%). Microforceps biopsies diagnosed mucinous cyst in 9 patients (33.3%), serous cystadenoma in 4 (14.8%), neuroendocrine tumor in 1 (3.7%), and benign and/or inflammatory cyst in 10 (37.1%). In 7 patients (26%), microforceps biopsy results drastically changed the diagnosis, providing diagnoses otherwise not suggested by cytology or cyst fluid CEA levels. However, cytology provided a diagnosis of mucinous cyst in 4 cases (14.8%) not detected by microforceps biopsies. No adverse events were noted. Microforceps biopsies were associated with high technical success, and an excellent safety profile and may be a useful adjunctive tool, complementing existing EUS-FNA sampling protocols for PCLs. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Optogenetic Excitation of Central Amygdala Amplifies and Narrows Incentive Motivation to Pursue One Reward Above Another

PubMed Central

Warlow, Shelley M.; Berridge, Kent C.

2014-01-01

Choosing one reward above another is important for achieving adaptive life goals. Yet hijacked into excessive intensity in disorders such as addiction, single-minded pursuit becomes maladaptive. Here, we report that optogenetic channelrhodopsin stimulation of neurons in central nucleus of amygdala (CeA), paired with earning a particular sucrose reward in rats, amplified and narrowed incentive motivation to that single reward target. Therefore, CeA rats chose and intensely pursued only the laser-paired sucrose reward while ignoring an equally good sucrose alternative. In contrast, reward-paired stimulation of basolateral amygdala did not hijack choice. In a separate measure of incentive motivation, CeA stimulation also increased the progressive ratio breakpoint or level of effort exerted to obtain sucrose reward. However, CeA stimulation by itself failed to support behavioral self-stimulation in the absence of any paired external food reward, suggesting that CeA photo-excitation specifically transformed the value of its external reward (rather than adding an internal reinforcement state). Nor did CeA stimulation by itself induce any aversive state that motivated escape. Finally, CeA stimulation also failed to enhance ‘liking’ reactions elicited by sucrose taste and did not simply increase the general motivation to eat. This pattern suggests that CeA photo-excitation specifically enhances and narrows incentive motivation to pursue an associated external reward at the expense of another comparable reward. PMID:25505310

Chronic Electrical Stimulation at Acupoints Reduces Body Weight and Improves Blood Glucose in Obese Rats via Autonomic Pathway.

PubMed

Liu, Jiemin; Jin, Haifeng; Foreman, Robert D; Lei, Yong; Xu, Xiaohong; Li, Shiying; Yin, Jieyun; Chen, Jiande D Z

2015-07-01

The aim of this study was to investigate effects and mechanisms of chronic electrical stimulation at acupoints (CEA) using surgically implanted electrodes on food intake, body weight, and metabolisms in diet-induced obese (DIO) rats. Thirty-six DIO rats were chronically implanted with electrodes at acupoints ST-36 (Zusanli). Three sets of parameters were tested: electrical acupuncture (EA) 1 (2-s on, 3-s off, 0.5 ms, 15 Hz, 6 mA), EA2 (same as EA1 but continuous pulses), and EA3 (same as EA2 but 10 mA). A chronic study was then performed to investigate the effects of CEA on body weight and mechanisms involving gastrointestinal hormones and autonomic functions. EA2 significantly reduced food intake without uncomfortable behaviors. CEA at EA2 reduced body weight and epididymal fat pad weight (P < 0.05). CEA reduced both postprandial blood glucose and HbA1c (P < 0.05). CEA delayed gastric emptying (P < 0.03) and increased small intestinal transit (P < 0.02). CEA increased fasting plasma level of glucagon-like peptide-1 (GLP-1) and peptide YY (P < 0.05); the increase of GLP-1 was inversely correlated with postprandial blood glucose (R (2) = 0.89, P < 0.05); and the plasma ghrelin level remained unchanged. EA increased sympathetic activity (P < 0.01) and reduced vagal activity (P < 0.01). CEA at ST-36 reduces body weight and improves blood glucose possibly attributed to multiple mechanisms involving gastrointestinal motility and hormones via the autonomic pathway.

Does the academic performance of psychiatrists influence success in the NHS Clinical Excellence Award Scheme?

PubMed Central

Mitchell, Alex J; Crowfoot, Daniel; Leaver, James; Hughes, Samantha

2011-01-01

Objectives Given the uncertainty about factors that influence receipt of Clinical Excellence Awards (CEA) and recent availability of advanced research metrics, we examined the factors that predict CEA success using a convenience sample of English psychiatrists. Design Observational study examining region, subspecialty, H-index, M-index, number of publications, years since registration and years in specialty. Setting ACCEA Nominal Roll, cross-referenced with data from the GMC's list of registered medical practitioners and Thompson's Web of Science database. Participants A total of 494 psychiatrists including 245 with national levels awards and a random sample with local level awards. Main outcome measures Receipt of local or national CEA awards in 2008 and 2009. Results Of those with national awards, 126 had university contracts and 119 NHS contracts. Across all staff, years since qualification in medicine and H-index were the dominant influences. For local awards we found that years worked in the specialty was the main predictor of a CEA award with a smaller contribution from H-index. For national awards to university staff (academics) years on the medical register and publication rate were significant predictors. For national awards to NHS staff (non-academics) H-index and total cites were predictive, but these were themselves related to age. Conclusions Progression in CEAs among psychiatrists is strongly influenced by age (years spent in specialty and years on the medical register) with an additional contribution from research productivity. Currently, research impact is crudely assessed in the CEA process. We suggest that CEA committees formally assess the impact of NHS-related research using standardized research metrics which are openly available. We also suggest that supporting organizations and local trusts adhere to the rules mandated by the ACCEA. PMID:21541089

Comparison of CEAS and Williams-type models for spring wheat yields in North Dakota and Minnesota

NASA Technical Reports Server (NTRS)

Barnett, T. L. (Principal Investigator)

1982-01-01

The CEAS and Williams-type yield models are both based on multiple regression analysis of historical time series data at CRD level. The CEAS model develops a separate relation for each CRD; the Williams-type model pools CRD data to regional level (groups of similar CRDs). Basic variables considered in the analyses are USDA yield, monthly mean temperature, monthly precipitation, and variables derived from these. The Williams-type model also used soil texture and topographic information. Technological trend is represented in both by piecewise linear functions of year. Indicators of yield reliability obtained from a ten-year bootstrap test of each model (1970-1979) demonstrate that the models are very similar in performance in all respects. Both models are about equally objective, adequate, timely, simple, and inexpensive. Both consider scientific knowledge on a broad scale but not in detail. Neither provides a good current measure of modeled yield reliability. The CEAS model is considered very slightly preferable for AgRISTARS applications.

Optogenetic excitation of central amygdala amplifies and narrows incentive motivation to pursue one reward above another.

PubMed

Robinson, Mike J F; Warlow, Shelley M; Berridge, Kent C

2014-12-10

Choosing one reward above another is important for achieving adaptive life goals. Yet hijacked into excessive intensity in disorders such as addiction, single-minded pursuit becomes maladaptive. Here, we report that optogenetic channelrhodopsin stimulation of neurons in central nucleus of amygdala (CeA), paired with earning a particular sucrose reward in rats, amplified and narrowed incentive motivation to that single reward target. Therefore, CeA rats chose and intensely pursued only the laser-paired sucrose reward while ignoring an equally good sucrose alternative. In contrast, reward-paired stimulation of basolateral amygdala did not hijack choice. In a separate measure of incentive motivation, CeA stimulation also increased the progressive ratio breakpoint or level of effort exerted to obtain sucrose reward. However, CeA stimulation by itself failed to support behavioral self-stimulation in the absence of any paired external food reward, suggesting that CeA photo-excitation specifically transformed the value of its external reward (rather than adding an internal reinforcement state). Nor did CeA stimulation by itself induce any aversive state that motivated escape. Finally, CeA stimulation also failed to enhance 'liking' reactions elicited by sucrose taste and did not simply increase the general motivation to eat. This pattern suggests that CeA photo-excitation specifically enhances and narrows incentive motivation to pursue an associated external reward at the expense of another comparable reward. Copyright © 2014 the authors 0270-6474/14/3416567-14$15.00/0.

Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review.

PubMed

Tshering, Gyem; Dorji, Palden Wangyel; Chaijaroenkul, Wanna; Na-Bangchang, Kesara

2018-06-01

Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical settings.

Study of Aided Diagnosis of Hepatic Carcinoma Based on Artificial Neural Network Combined with Tumor Marker Group

NASA Astrophysics Data System (ADS)

Tan, Shanjuan; Feng, Feifei; Wu, Yongjun; Wu, Yiming

To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) combined with tumor markers for diagnosis of hepatic carcinoma (HCC) as a clinical assistant method. 140 serum samples (50 malignant, 40 benign and 50 normal) were analyzed for α-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), sialic acid (SA) and calcium (Ca). The five tumor marker values were then used as ANN inputs data. The result of ANN was compared with that of discriminant analysis by receiver operating characteristic (ROC) curve (AUC) analysis. The diagnostic accuracy of ANN and discriminant analysis among all samples of the test group was 95.5% and 79.3%, respectively. Analysis of multiple tumor markers based on ANN may be a better choice than the traditional statistical methods for differentiating HCC from benign or normal.

Can outcome of pancreatic pseudocysts be predicted? Proposal for a new scoring system.

PubMed

Şenol, Kazım; Akgül, Özgür; Gündoğdu, Salih Burak; Aydoğan, İhsan; Tez, Mesut; Coşkun, Faruk; Tihan, Deniz Necdet

2016-03-01

The spontaneous resolution rate of pancreatic pseudocysts (PPs) is 86%, and the serious complication rate is 3-9%. The aim of the present study was to develop a scoring system that would predict spontaneous resolution of PPs. Medical records of 70 patients were retrospectively reviewed. Two patients were excluded. Demographic data and laboratory measurements were obtained from patient records. Mean age of the 68 patients included was 56.6 years. Female:male ratio was 1.34:1. Causes of pancreatitis were stones (48.5%), alcohol consumption (26.5%), and unknown etiology (25%). Mean size of PP was 71 mm. Pseudocysts disappeared in 32 patients (47.1%). With univariate analysis, serum direct bilirubin level (>0.95 mg/dL), cyst carcinoembryonic antigen (CEA) level (>1.5), and cyst diameter (>55 mm) were found to be significantly different between patients with and without spontaneous resolution. In multivariate analysis, these variables were statistically significant. Scores were calculated with points assigned to each variable. Final scores predicted spontaneous resolution in approximately 80% of patients. The scoring system developed to predict resolution of PPs is simple and useful, but requires validation.

Personalized Risk Assessment in Never, Light, and Heavy Smokers in a prospective cohort in Taiwan

PubMed Central

Wu, Xifeng; Wen, Chi Pang; Ye, Yuanqing; Tsai, MinKwang; Wen, Christopher; Roth, Jack A.; Pu, Xia; Chow, Wong-Ho; Huff, Chad; Cunningham, Sonia; Huang, Maosheng; Wu, Shuanbei; Tsao, Chwen Keng; Gu, Jian; Lippman, Scott M.

2016-01-01

The objective of this study was to develop markedly improved risk prediction models for lung cancer using a prospective cohort of 395,875 participants in Taiwan. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC). In multivariate Cox regression analysis, age, gender, smoking pack-years, family history of lung cancer, personal cancer history, BMI, lung function test, and serum biomarkers such as carcinoembryonic antigen (CEA), bilirubin, alpha fetoprotein (AFP), and c-reactive protein (CRP) were identified and included in an integrative risk prediction model. The AUC in overall population was 0.851 (95% CI = 0.840–0.862), with never smokers 0.806 (95% CI = 0.790–0.819), light smokers 0.847 (95% CI = 0.824–0.871), and heavy smokers 0.732 (95% CI = 0.708–0.752). By integrating risk factors such as family history of lung cancer, CEA and AFP for light smokers, and lung function test (Maximum Mid-Expiratory Flow, MMEF25–75%), AFP and CEA for never smokers, light and never smokers with cancer risks as high as those within heavy smokers could be identified. The risk model for heavy smokers can allow us to stratify heavy smokers into subgroups with distinct risks, which, if applied to low-dose computed tomography (LDCT) screening, may greatly reduce false positives. PMID:27805040

Unlabeled multi tumor marker detection system based on bioinitiated light addressable potentiometric sensor.

PubMed

Jia, Yun-Fang; Gao, Chun-Ying; He, Jia; Feng, Dao-Fu; Xing, Ke-Li; Wu, Ming; Liu, Yang; Cai, Wen-Sheng; Feng, Xi-Zeng

2012-08-21

Multi biomarkers' assays are of great significance in clinical diagnosis. A label-free multi tumor markers' parallel detection system was proposed based on a light addressable potentiometric sensor (LAPS). Arrayed LAPS chips with basic structure of Si(3)N(4)-SiO(2)-Si were prepared on silicon wafers, and the label-free parallel detection system for this component was developed with user friendly controlling interfaces. Then the l-3,4-dihydroxyphenyl-alanine (L-Dopa) hydrochloric solution was used to initiate the surface of LAPS. The L-Dopa immobilization state was investigated by the theoretical calculation. L-Dopa initiated LAPS' chip was biofunctionalized respectively by the antigens and antibodies of four tumor markers, α-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and Ferritin. Then unlabeled antibodies and antigens of these four biomarkers were detected by the proposed detection systems. Furthermore physical and measuring principles in this system were described, and qualitative understanding for experimental data were given. The measured response ranges were compared with their clinical cutoff values, and sensitivities were calculated by OriginLab. The results indicate that this bioinitiated LAPS based label-free detection system may offer a new choice for the realization of unlabeled multi tumor markers' clinical assay.

Esophageal adenosquamous carcinoma mimicking acantholytic squamous cell carcinoma

PubMed Central

Matsukuma, Susumu; Takahashi, Oh; Utsumi, Yoshitaka; Tsuda, Masaki; Miyai, Kosuke; Okada, Kenji; Takeo, Hiroaki

2017-01-01

Herein is described a unique case of esophageal cancer mimicking acantholytic squamous cell carcinoma (SCC). The patient succumbed to the disease within one month of diagnosis. Autopsy revealed a 10-cm esophageal tumor, characterized by prominent acantholysis-like areas composed of discohesive cancer cells, along with nested growth of SCC. These discohesive cancer cells focally exhibited pagetoid extension into adjacent esophageal epithelium, comprised ~60% of the esophageal tumor volume and had widely metastasized to the lungs, chest wall, liver, spleen, right adrenal gland, bones and lymph nodes. No metastases of SCC were observed. SCC cells were immunohistochemically positive for keratin 5/6 and E-cadherin and were negative for mucin and carcinoembryonic antigen (CEA). However, the discohesive cancer cells exhibited negativity for keratin 5/6, positivity for mucin and CEA, and diminished or no immunostaining for E-cadherin. Thus, these discohesive cells represented true adenocarcinomatous differentiation rather than acantholytic SCC cells. It was concluded that this tumor was an esophageal adenosquamous carcinoma with ‘pseudo’-acantholytic adenocarcinoma components, which should be considered as a rare but distinctive type of aggressive cancer. PMID:29085501

Site-specific PEGylation of an anti-CEA/CD3 bispecific antibody improves its antitumor efficacy

PubMed Central

Pan, Haitao; Liu, Jiayu; Deng, Wentong; Xing, Jieyu; Li, Qing; Wang, Zhong

2018-01-01

Introduction Bispecific antibodies that engage immune cells to kill cancer cells are actively pursued in cancer immunotherapy. Different types of bispecific antibodies, including single-chain fragments, Fab fragments, nanobodies, and immunoglobulin Gs (IgGs), have been studied. However, the low molecular weight of bispecific antibodies with single-chain or Fab fragments generally leads to their rapid clearance in vivo, which limits the therapeutic potential of these bispecific antibodies. Materials and methods In this study, we used a site-specific PEGylation strategy to modify the bispecific single-domain antibody-linked Fab (S-Fab), which was designed by linking an anticarcinoembryonic antigen (anti-CEA) nanobody with an anti-CD3 Fab. Results The half-life (t1/2) of PEGylated S-Fab (polyethylene glycol-S-Fab) was increased 12-fold in vivo with a slightly decreased tumor cell cytotoxicity in vitro as well as more potent tumor growth inhibition in vivo compared to S-Fab. Conclusion This study demonstrated that PEGylation is an effective approach to enhance the antitumor efficacy of bispecific antibodies. PMID:29881272

Joint modelling of longitudinal CEA tumour marker progression and survival data on breast cancer

NASA Astrophysics Data System (ADS)

Borges, Ana; Sousa, Inês; Castro, Luis

2017-06-01

This work proposes the use of Biostatistics methods to study breast cancer in patients of Braga's Hospital Senology Unit, located in Portugal. The primary motivation is to contribute to the understanding of the progression of breast cancer, within the Portuguese population, using a more complex statistical model assumptions than the traditional analysis that take into account a possible existence of a serial correlation structure within a same subject observations. We aim to infer which risk factors aect the survival of Braga's Hospital patients, diagnosed with breast tumour. Whilst analysing risk factors that aect a tumour markers used on the surveillance of disease progression the Carcinoembryonic antigen (CEA). As survival and longitudinal processes may be associated, it is important to model these two processes together. Hence, a joint modelling of these two processes to infer on the association of these was conducted. A data set of 540 patients, along with 50 variables, was collected from medical records of the Hospital. A joint model approach was used to analyse these data. Two dierent joint models were applied to the same data set, with dierent parameterizations which give dierent interpretations to model parameters. These were used by convenience as the ones implemented in R software. Results from the two models were compared. Results from joint models, showed that the longitudinal CEA values were signicantly associated with the survival probability of these patients. A comparison between parameter estimates obtained in this analysis and previous independent survival[4] and longitudinal analysis[5][6], lead us to conclude that independent analysis brings up bias parameter estimates. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary. Results indicate that the longitudinal progression of CEA is signicantly associated with the probability of survival of these patients. Hence, an assumption of association between the two processes in a joint model of breast cancer data is necessary.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwok, C; Williams, L

Purpose: Animal biodistribution data are required prior to introducing a new radiopharmaceutical into clinical trials. Protein engineering, using recombinant DNA techniques can produce a large number of related (cognate) antibodies to a given molecular target. Thus, it is important that these constructs be numerically related to one another via a single criterion. In the following, we use the mean residence time (MRT) in murine blood as this criterion. Methods: Five cognate anti-CEA (Carcinoembryonic Antigen) antibodies were compared with regard to their MRT in whole blood of CEA-positive tumor-bearing (LS174T) mice. MRT was defined by blood AUC (area under the curve)more » divided by the initial blood uptake value; all in units of percent injected dose per gram (%ID/g). Cognates included single chain scFv (25 kDa), diabody (50 kDa), minibody (80 kDa), F(ab')2 (120 kDa), and intact (155 kDa) forms of the murine cT84.66 antibody against CEA. All were labeled with radioactive iodine. Results: The agents, in the sequence listed, exhibited MRT values of 1.16 +/- 0.01 h, 0.99 h, 5.06 +/- 0.70 h, 6.61 +/- 0.36 h, and 59.3 +/- 2.4 h respectively. Because of the monotonic nature of the sequence, a linear correlation analysis was performed between molecular weight (MW) and MRT or ln(MRT) of the 5 proteins. Probability of random correlation was 0.10 for MRT and 0.01 for ln(MRT). Conclusion: MRT values of cognate anti-CEA antibodies were found to be a monotonically increasing sequence with respect to MW. Cognate MW values correlated best to ln(MRT) of the protein species. Thus MRT was proportional to an exponential function of molecular weight. The extended intact antibody circulation time presumably reflected its relatively maximal MW. Presence of an intact FC segment on this native antibody may also have influenced these results.« less

Radiolabelled polymeric IgA: from biodistribution to a new molecular imaging tool in colorectal cancer lung metastases

PubMed Central

Carpenet, Helene; Cuvillier, Armelle; Perraud, Aurélie; Martin, Ophélie; Champier, Gaël; Jauberteau, Marie-Odile; Monteil, Jacques; Quelven, Isabelle

2017-01-01

By radiolabelling monomeric (m) and polymeric (p) IgA with technetium 99m (99mTc), this study assessed IgA biodistribution and tumour-targeting potency. IgA directed against carcinoembryonic antigen (CEA), a colorectal cancer marker, was selected to involve IgA mucosal tropism. Ig was radiolabelled with 99mTc-tricarbonyl after derivatisation by 2-iminothiolane. 99mTc-IgA was evaluated by in vitro analysis. The biodistributions of radiolabelled anti-CEA mIgA, pIgA and IgG were compared in normal mice. Anti-CEA pIgA tumour uptake was studied in mice bearing the WiDr caecal orthotopic graft. IgA radiolabelling was obtained with a high yield, was stable in PBS and murine plasma, and did not alter IgA binding functionality (Kd ≈ 25 nM). Biodistribution studies in normal mice confirmed that radiolabelled pIgA – and to a lesser extent, mIgA – showed strong and fast mucosal tropism and a shorter serum half-life than IgG. In caecal tumour model mice, evaluation of the anti-CEA-pIgA biodistribution showed a high uptake in lung metastases, confirmed by histological analysis. However, no radioactivity uptake increase in the tumoural caecum was discerned from normal intestinal tissue, probably due to high IgA caecal natural tropism. In microSPECT/CT imaging, 99mTc-IgA confirmed its diagnostic potency of tumour in mucosal tissue, even if detection threshold by in vivo imaging was higher than post mortem studies. Contribution of the FcαRI receptor, studied with transgenic mouse model (Tsg SCID-CD89), did not appear to be determinant in 99mTc-IgA uptake. Pre-clinical experiments highlighted significant differences between 99mTc-IgA and 99mTc-IgG biodistributions. Furthermore, tumoural model studies suggested potential targeting potency of pIgA in mucosal tissues. PMID:29156712

The concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid can be useful indicators for diagnosis of meningeal carcinomatosis of lung cancer.

PubMed

Wang, Peng; Piao, Yingzhe; Zhang, Xiaohui; Li, Wenliang; Hao, Xishan

2013-01-01

We aimed to investigate the concentration of CYFRA 21-1, NSE and CEA in cerebro-spinal fluid (CSF) and to explore their clinical value in the meningeal carcinomatosis (MC) of lung cancer. So that, sensitive and specificity of CSF examination can be improved in the initial diagnosis of MC. A total of 35 lung cancer patients and 35 patients with benign brain tumor in the same period enrolled in this study. The concentrations of tumor markers CEA, CYFRA 21-1 and NSE in CSF and peripheral blood were examined. The concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum and CSF were obviously higher than that of benign disease group. In MC patients, the concentrations of three tumor markers of CYFRA 21-1, NSE and CEA in blood serum were significant lower than that in CSF. The maximum of Youden's index was identified as the cutoff value of indicator of MC in three tumor markers in CSF which were CEA > 4.7 μg/L, NSE > 14.6 μg/L and CYFRA21-1 > 5.5 μg/L respectively. Based on the cutoff values, the CEA had the highest sensitivity while the CYFRA21-1 had the highest specificitiy. Three tumor markers in the CSF had higher positive rate than those in blood serum. We combined the levels of CEA, NSE and CYFRA21-1 in CSF to diagnosis of MC. Positive of CEA or CYFRA21-1 had the greatest sensitivity of 100% while the specificity of 91.4%; the positive of both CEA and CYFRA21-1 had the highest specificity of 100% while the sensitivity of 74.3%. Both positive predictive value and negative predictive value were 100% when combination positive were confirmed when the all three markers were positive. The combination of CEA and CYFRA21-1 can be recommended in early screening of meningeal carcinoma. Especially, for the patient who was difficult to be diagnosed by CSF histology and MRI, it will be a useful auxiliary marker in diagnosis of MC. The combination of CEA, NSE and CYFRA21-1 can be an effective clinically confirmation and exclusively diagnose indictor of MC.

Development and validation of a preoperative prediction model for colorectal cancer T-staging based on MDCT images and clinical information.

PubMed

Sa, Sha; Li, Jing; Li, Xiaodong; Li, Yongrui; Liu, Xiaoming; Wang, Defeng; Zhang, Huimao; Fu, Yu

2017-08-15

This study aimed to establish and evaluate the efficacy of a prediction model for colorectal cancer T-staging. T-staging was positively correlated with the level of carcinoembryonic antigen (CEA), expression of carbohydrate antigen 19-9 (CA19-9), wall deformity, blurred outer edges, fat infiltration, infiltration into the surrounding tissue, tumor size and wall thickness. Age, location, enhancement rate and enhancement homogeneity were negatively correlated with T-staging. The predictive results of the model were consistent with the pathological gold standard, and the kappa value was 0.805. The total accuracy of staging improved from 51.04% to 86.98% with the proposed model. The clinical, imaging and pathological data of 611 patients with colorectal cancer (419 patients in the training group and 192 patients in the validation group) were collected. A spearman correlation analysis was used to validate the relationship among these factors and pathological T-staging. A prediction model was trained with the random forest algorithm. T staging of the patients in the validation group was predicted by both prediction model and traditional method. The consistency, accuracy, sensitivity, specificity and area under the curve (AUC) were used to compare the efficacy of the two methods. The newly established comprehensive model can improve the predictive efficiency of preoperative colorectal cancer T-staging.

Patient risk perceptions for carotid endarterectomy: which patients are strongly averse to surgery?

PubMed

Bosworth, Hayden B; Stechuchak, Karen M; Grambow, Steven C; Oddone, Eugene Z

2004-07-01

Patient risk perception for surgery may be central to their willingness to undergo surgery. This study examined potential factors associated with patient aversion of surgery. This is a secondary data analysis of a prospective cohort study that examined patients referred for evaluation of carotid artery stenosis at five Veterans Affairs Medical Centers. The study collected demographic, clinical, and psychosocial information related to surgery. This analysis focused on patient response to a question assessing their aversion to surgery. Among the 1065 individuals, at the time of evaluation for carotid endarterectomy (CEA), 66% of patients had no symptoms, 16% had a transient ischemic attack, and 18% had stroke. Twelve percent of patients referred for CEA evaluation were averse to surgery. In adjusted analyses, increased age, black race, no previous surgery, lower level of chance locus of control, less trust of physicians, and less social support were significantly related to greater likelihood of surgery aversion among individuals referred for CEA evaluation. Patient degree of medical comorbidity and a validated measure of preoperative risk score were not associated with increased aversion to surgery. In previous work, aversion to CEA was associated with lack of receipt of CEA even after accounting for patient clinical appropriateness for surgery. We identified important patient characteristics associated with aversion to CEA. Interventions designed to assist patient decision making should focus on these more complex factors related to CEA aversion rather than the simple explanation of clinical usefulness.

Applications of CELSS technology to controlled environment agriculture

NASA Technical Reports Server (NTRS)

Bates, Maynard E.; Bubenheim, David L.

1991-01-01

Controlled environment agriculture (CEA) is defined as the use of environmental manipulation for the commercial production of organisms, whether plants or animals. While many of the technologies necessary for aquaculture systems in North America is nevertheless doubling approximately every five years. Economic, cultural, and environmental pressures all favor CEA over field production for many non-commodity agricultural crops. Many countries around the world are already dependent on CEA for much of their fresh food. Controlled ecological life support systems (CELSS), under development at ARC, KSC, and JSC expand the concept of CEA to the extent that all human requirements for food, oxygen, and water will be provided regenerated by processing of waste streams to supply plant inputs. The CELSS will likely contain plants, humans, possibly other animals, microorganisms and physically and chemical processors. In effect, NASA will create engineered ecosystems. In the process of developing the technology for CELSS, NASA will develop information and technology which will be applied to improving the efficiency, reliability, and cost effectiveness for CEA, improving its resources recycling capabilities, and lessening its environmental impact to negligible levels.

Significant Association of Annual Hospital Volume With the Risk of Inhospital Stroke or Death Following Carotid Endarterectomy but Likely Not After Carotid Stenting: Secondary Data Analysis of the Statutory German Carotid Quality Assurance Database.

PubMed

Kuehnl, Andreas; Tsantilas, Pavlos; Knappich, Christoph; Schmid, Sofie; König, Thomas; Breitkreuz, Thorben; Zimmermann, Alexander; Mansmann, Ulrich; Eckstein, Hans-Henning

2016-11-01

Associations between hospital volume and the risk of stroke or death following carotid endarterectomy (CEA) and carotid artery stenting (CAS) on a national level in Germany were analyzed. Secondary data analysis using microdata from the nationwide statutory German quality assurance database on all surgical or endovascular carotid interventions on the extracranial carotid artery between 2009 and 2014. Hospitals were categorized into empirically determined quintiles according to the annual case volume. The resulting volume thresholds were 10, 25, 46, and 79 for CEA and 2, 6, 12, and 26 for CAS procedures. The primary outcome was any stroke or death before hospital discharge. For risk-adjusted analyses, a multilevel regression model was applied. The analysis included 161 448 CEA and 17 575 CAS procedures. In CEA patients, the crude risk of stroke or death decreased monotonically from 4.2% (95% confidence interval, 3.6%-4.9%) in low-volume hospitals (first quintile 1-10 CEA per year) to 2.1% (2.0%-2.2%) in hospitals providing ≥80 CEA per year (fifth quintile; P<0.001 for trend). The overall risk of any stroke or death in CAS patients was 3.7% (3.5%-4.0%), but no trend on annual volume was seen (P=0.304). Risk-adjusted analyses confirmed a significant inverse relationship between hospital volume (categorized or continuous) and the risk of stroke or death after CEA but not CAS procedures. An inverse volume-outcome relationship in CEA-treated patients was demonstrated. No significant association between hospital volume and the risk of stroke or death was found for CAS. © 2016 American Heart Association, Inc.

A case of myxedema coma caused by isolated thyrotropin stimulating hormone deficiency and Hashimoto's thyroiditis.

PubMed

Iida, Keiji; Hino, Yasuhisa; Ohara, Takeshi; Chihara, Kazuo

2011-01-01

Myxedema coma (MC) is a rare, but often fatal endocrine emergency. The majority of cases that occur in elderly women with long-standing primary hypothyroidism are caused by particular triggers. Conversely, MC of central origin is extremely rare. Here, we report a case of MC with both central and primary origins. A 56-year-old woman was transferred to our hospital due to loss of consciousness; a chest x-ray demonstrated severe cardiomegaly. Low body temperature, bradycardia, and pericardial effusion suggested the presence of hypothyroidism. Endocrinological examination revealed undetectable levels of serum free thyroxine (T(4)) and free triiodothyronine (T(3)), whereas serum thyroid-stimulating hormone (TSH) levels were not elevated. The woman's serum anti-thyroid peroxidase antibody and anti-thyroglobulin antibody tests were positive, indicating that she had Hashimoto's thyroiditis. Provocative tests to the anterior pituitary revealed that she had TSH and growth hormone (GH) deficiency; however, GH levels were restored after supplementation with levothyroxine for 5 months. This was not only a rare case of MC with TSH deficiency and Hashimoto's thyroiditis; the patient also developed severe osteoporosis and possessed transient elevated levels of serum carcinoembryonic antigen (CEA). This atypical case may suggest the role of anterior pituitary hormone deficiencies, as well as hypothyroidism, in the regulation of bone metabolism.

[Experience of a Break-Even Point Analysis for Make-or-Buy Decision.].

PubMed

Kim, Yunhee

2006-12-01

Cost containment through continuous quality improvement of medical service is required in an age of a keen competition of the medical market. Laboratory managers should examine the matters on make-or-buy decision periodically. On this occasion, a break-even point analysis can be useful as an analyzing tool. In this study, cost accounting and break-even point (BEP) analysis were performed in case that the immunoassay items showing a recent increase in order volume were to be in-house made. Fixed and variable costs were calculated in case that alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate-specific antigen (PSA), ferritin, free thyroxine (fT4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), CA 125, CA 19-9, and hepatitis B envelope antibody (HBeAb) were to be tested with Abbott AxSYM instrument. Break-even volume was calculated as fixed cost per year divided by purchasing cost per test minus variable cost per test and BEP ratio as total purchasing costs at break-even volume divided by total purchasing costs at actual annual volume. The average fixed cost per year of AFP, CEA, PSA, ferritin, fT4, T3, TSH, CA 125, CA 19-9, and HBeAb was 8,279,187 won and average variable cost per test, 3,786 won. Average break-even volume was 1,599 and average BEP ratio was 852%. Average BEP ratio without including quality costs such as calibration and quality control was 74%. Because the quality assurance of clinical tests cannot be waived, outsourcing all of 10 items was more adequate than in-house make at the present volume in financial aspect. BEP analysis was useful as a financial tool for make-or-buy decision, the common matter which laboratory managers meet with.

Amplified cathodic electrochemiluminescence of luminol based on Pd and Pt nanoparticles and glucose oxidase decorated graphene as trace label for ultrasensitive detection of protein.

PubMed

Cao, Yaling; Yuan, Ruo; Chai, Yaqin; Liu, Huijing; Liao, Yuhong; Zhuo, Ying

2013-09-15

An ultrasensitive electrochemiluminescence (ECL) immunosensor was constructed for ultrasensitive detection of carcinoembryonic antigen (CEA) based on an amplified cathodic ECL of luminol at low potential. Firstly, Au nanoparticles (AuNPs) were electrodeposited onto single walled carbon nanotube-graphene composites (CNTs-Gra) coated glass carbon electrode (GCE) with enhanced surface area and good biocompatibility to capture primary antibody (Ab1) and then bind the antigen analytes. Secondly, Pd and Pt nanoparticles (Pd&PtNPs) decorated reduced graphene oxide (Pd&PtNPs@rGO) and glucose oxidase (GOD) labeled secondary antibody (Pd&PtNPs@ rGO-GOD-Ab2) could be captured onto the electrode surface by a sandwich immunoassay protocol to generate amplified cathodic ECL signals of luminol in the presence of glucose. The Pd&PtNPs@rGO composites and loaded GOD promoted luminol cathodic ECL response by efficiently catalyzing glucose to in-situ produce amount of hydrogen peroxide (H2O2) working as a coreactant of luminol. Then in turn Pd&PtNPs catalyzed H2O2 to generate various reactive oxygen species (ROSs), which accelerated the cathodic ECL reaction of luminol, enhanced the cathodic ECL intensity of luminol and improved the sensitivity of the immunosensor. The as-proposed ECL immunosensor exhibited sensitive response on the detection of CEA ranging from 0.0001 ng mL(-1) to 160 ng mL(-1) with a detection limit of 0.03 pg mL(-1) (S/N=3). Moreover, the stability, specificity, lifetime and reproducibility tests demonstrated the feasibility of the developed immunoassay, which can be further extended to the detection of other disease biomarkers. Copyright © 2013 Elsevier B.V. All rights reserved.

In vitro autoradiography of carcinoembryonic antigen in tissue from patients with colorectal cancer using multifunctional antibody TF2 and 67/68Ga-labeled haptens by pretargeting

PubMed Central

Hall, Håkan; Velikyan, Irina; Blom, Elisabeth; Ulin, Johan; Monazzam, Azita; Påhlman, Lars; Micke, Patrick; Wanders, Alkwin; McBride, William; Goldenberg, David M.; Långström, Bengt

2012-01-01

The carcinoembryonic antigen (CEA) was visualized in vitro in tissue from patients with colorectal cancer with trivalent bispecific antibody TF2 and two hapten molecules, [67/68Ga]Ga-IMP461 and [67/68Ga]Ga-IMP485 by means of pretargeting. Colorectal cancer tissue samples obtained from surgery at Uppsala University Hospital, were frozen fresh and cryosectioned. The two hapten molecules comprising 1,4,7-triazacyclononanetriacetic acid chelate moiety (NOTA) were labeled with 67Ga or 68Ga. The autoradiography was conducted by incubating the tissue samples with the bispecific antibody TF2, followed by washing and incubation with one of the radiolabeled hapten molecules. After washing, drying and exposure to phosphor imager plates, the autoradiograms were analyzed and compared to standard histochemistry (hematoxylin-eosin). Pronounced binding was found in the tissue from colorectal cancer using the bispecific antibody TF2 and either of the haptens [67/68Ga]Ga-IMP461 and [67/68Ga]Ga-IMP485. Distinct binding was also detected in the epithelium of most samples of neighboring tissue, taken at a minimum of 10 cm from the site of the tumor. It is concluded that pretargeting CEA with the bispecific antibody TF2 followed by the addition of 67/68Ga-labeled hapten is extremely sensitive for visualizing this marker for colorectal cancer. This methodology is therefore a very specific complement to other histochemical techniques in the diagnosis of biopsies or in samples taken from surgery. Use of the pretargeting technique in vivo may also be an advance in diagnosing patients with colorectal cancer, either using 67Ga and SPECT or 68Ga and PET. PMID:23133809

A Novel Electrochemical Microfluidic Chip Combined with Multiple Biomarkers for Early Diagnosis of Gastric Cancer

NASA Astrophysics Data System (ADS)

Xie, Yao; Zhi, Xiao; Su, Haichuan; Wang, Kan; Yan, Zhen; He, Nongyue; Zhang, Jingpu; Chen, Di; Cui, Daxiang

2015-12-01

Early diagnosis is very important to improve the survival rate of patients with gastric cancer and to understand the biology of cancer. In order to meet the clinical demands for early diagnosis of gastric cancer, we developed a disposable easy-to-use electrochemical microfluidic chip combined with multiple antibodies against six kinds of biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), Helicobacter pylori CagA protein (H.P.), P53oncoprotein (P53), pepsinogen I (PG I), and PG-II). The six kinds of biomarkers related to gastric cancer can be detected sensitively and synchronously in a short time. The specially designed three electrodes system enables cross-contamination to be avoided effectively. The linear ranges of detection of the electrochemical microfluidic chip were as follows: 0.37-90 ng mL-1 for CEA, 10.75-172 U mL-1 for CA19-9, 10-160 U L-1 for H.P., 35-560 ng mL-1 for P53, 37.5-600 ng mL-1 for PG I, and 2.5-80 ng mL-1for PG II. This method owns better sensitivity compared with enzyme-linked immunosorbent assay (ELISA) results of 394 specimens of gastric cancer sera. Furthermore, we established a multi-index prediction model based on the six kinds of biomarkers for predicting risk of gastric cancer. In conclusion, the electrochemical microfluidic chip for detecting multiple biomarkers has great potential in applications such as early screening of gastric cancer patients, and therapeutic evaluation, and real-time dynamic monitoring the progress of gastric cancer in near future.

Detection of bone metastases in breast cancer patients in the PET/CT era: Do we still need the bone scan?

PubMed

Caglar, M; Kupik, O; Karabulut, E; Høilund-Carlsen, P F

2016-01-01

To examine the value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for the detection of bone metastasis in breast cancer patients and assess whether whole body bone scan (BS) with (99m)Tc-methylene diphosphonate provides any additional information. Study group comprised 150 patients, mean age 52 years (range 27-85) with breast cancer, suspected of having bone metastases. All patients had undergone both FDG-PET/CT and BS with or without single photon emission tomography/computed tomography (SPECT/CT) within a period of 6 weeks. The final diagnosis of bone metastasis was established by histopathological findings, additional imaging, or clinical follow-up longer than 10 months. Cancer antigen 15-3 (CA15-3) and carcinoembryogenic antigen (CEA) were measured in all patients. Histologically 83%, 7% and 10% had infiltrating ductal, lobular and mixed carcinoma respectively. Confirmed bone metastases were present in 86 patients (57.3%) and absent in 64 (42.7%). Mean CA15-3 and CEA values in patients with bone metastases were 74.6ng/mL and 60.4U/mL respectively, compared to 21.3ng/mL and 3.2U/mL without metastases (p<0.001). The sensitivity of FDG-PET/CT for the detection of bone metastases was 97.6% compared to 89.5% with SPECT/CT. In 57 patients, FDG-PET/CT correctly identified additional pulmonary, hepatic, nodal and other soft tissue metastases, not detected by BS. Our findings suggest that FDG-PET/CT is superior to BS with or without SPECT/CT. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Magneto-optical relaxation measurements for the characterization of biomolecular interactions

NASA Astrophysics Data System (ADS)

Aurich, K.; Glöckl, G.; Romanus, E.; Weber, P.; Nagel, S.; Weitschies, W.

2006-09-01

Measurements of the magneto-optical relaxation of ferrofluids (MORFF) were applied as a novel homogeneous immunoassay for the investigation of biomolecular interactions. The technique is based on magnetic nanoparticles (MNP) functionalized with antibodies. The relaxation time of the optical birefringence that occurs when a pulsed magnetic field is applied to the nanoparticle suspension depends on the particle size. This enables the detection of particle aggregates formed after the addition of the antigen coupling partner. MORFF size measurements on the original ferrofluid and its fractions obtained by magnetic fractionation are comparable with results from other methods such as atomic force microscopy and photon correlation spectroscopy. In kinetic studies, the binding properties of five antigens and their polyclonal antibodies were investigated: human immunoglobulin G (hIgG), human immunoglobulin M (hIgM), human Eotaxin (hEotaxin), human carcinoembryonic antigen (hCEA), and human insulin (hInsulin). The enlargement of the relaxation time observed during the coupling experiments is expressed in terms of a size distribution function, which includes MNP monomers as well as aggregates. The kinetic process can be described by a model of stepwise polymerization. The kinetic parameters obtained are compared to results of surface plasmon resonance measurements.

Knocking down amygdalar PTP1B in diet-induced obese rats improves insulin signaling/action, decreases adiposity and may alter anxiety behavior.

PubMed

Mendes, Natalia Ferreira; Castro, Gisele; Guadagnini, Dioze; Tobar, Natalia; Cognuck, Susana Quiros; Elias, Lucila Leico Kagohara; Boer, Patricia Aline; Prada, Patricia Oliveira

2017-05-01

Protein tyrosine phosphatase 1B (PTP1B) has been extensively implicated in the regulation of body weight, food intake, and energy expenditure. The role of PTP1B appears to be cell and brain region dependent. Herein, we demonstrated that chronic high-fat feeding enhanced PTP1B expression in the central nucleus of the amygdala (CeA) of rats compared to rats on chow. Knocking down PTP1B with oligonucleotide antisense (ASO) decreased its expression and was sufficient to improve the anorexigenic effect of insulin through IR/Akt signaling in the CeA. ASO treatment reduces body weight, fat mass, serum leptin levels, and food intake and also increases energy expenditure, without altering ambulatory activity. These changes were explained, at least in part, by the improvement of insulin sensitivity in the CeA, decreasing NPY and enhancing oxytocin expression. There was a slight decline in fasting blood glucose and serum insulin levels possibly due to leanness in rats treated with ASO. Surprisingly, the elevated plus maze test revealed an anxiolytic behavior after reduction of PTP1B in the CeA. Thus, the present study highlights the deleterious role that the amygdalar PTP1B has on energy homeostasis in obesity states. The reduction of PTP1B in the CeA may be a strategy for the treatment of obesity, insulin resistance and anxiety disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Interactions of Stress and CRF in Ethanol-Withdrawal Induced Anxiety in Adolescent and Adult Rats

PubMed Central

Wills, Tiffany A.; Knapp, Darin J.; Overstreet, David H.; Breese, George R.

2010-01-01

Background Repeated stress or administration of corticotropin-releasing factor (CRF) prior to ethanol exposure sensitizes anxiety-like behavior in adult rats. Current experiments determined whether adolescent rats were more sensitive to these challenges in sensitizing ethanol withdrawal-induced anxiety and altering CRF levels in brain during withdrawal. Methods Male adult and adolescent Sprague–Dawley rats were restraint stressed (1 hour) twice 1 week apart prior to a single 5-day cycle of ethanol diet (ED; stress/withdrawal paradigm). Other rats received control diet (CD) and three 1-hour restraint stress sessions. Rats were then tested 5, 24, or 48 hours after the final withdrawal for anxiety-like behavior in the social interaction (SI) test. In other experiments, adolescent rats were given two microinjections of CRF icv 1 week apart followed by 5-days of either CD or ED and tested in social interaction 5 hours into withdrawal. Finally, CRF immunoreactivity was measured in the central nucleus of the amygdala (CeA) and paraventricular nucleus (PVN) after rats experienced control diet, repeated ethanol withdrawals, or stress/withdrawal. Results Rats of both ages had reduced SI following the stress/withdrawal paradigm, and this effect recovered within 24 hours. Higher CRF doses were required to reduce SI in adolescents than previously reported in adults. CRF immunohistochemical levels were higher in the PVN and CeA of CD-exposed adolescents. In adolescent rats, repeated ethanol withdrawals decreased CRF in the CeA but was not associated with decreased CRF cell number. There was no change in CRF from adult treatments. Conclusions In the production of anxiety-like behavior, adolescent rats have equal sensitivity with stress and lower sensitivity with CRF compared to adults. Further, adolescents had higher basal levels of CRF within the PVN and CeA and reduced CRF levels following repeated ethanol withdrawals. This reduced CRF within the CeA could indicate increased release of CRF, and future work will determine how this change relates to behavior. PMID:20586753

Validation of Carotid Artery Revascularization Coding in Ontario Health Administrative Databases.

PubMed

Hussain, Mohamad A; Mamdani, Muhammad; Saposnik, Gustavo; Tu, Jack V; Turkel-Parrella, David; Spears, Julian; Al-Omran, Mohammed

2016-04-02

The positive predictive value (PPV) of carotid endarterectomy (CEA) and carotid artery stenting (CAS) procedure and post-operative complication coding were assessed in Ontario health administrative databases. Between 1 April 2002 and 31 March 2014, a random sample of 428 patients were identified using Canadian Classification of Health Intervention (CCI) procedure codes and Ontario Health Insurance Plan (OHIP) billing codes from administrative data. A blinded chart review was conducted at two high-volume vascular centers to assess the level of agreement between the administrative records and the corresponding patients' hospital charts. PPV was calculated with 95% confidence intervals (CIs) to estimate the validity of CEA and CAS coding, utilizing hospital charts as the gold standard. Sensitivity of CEA and CAS coding were also assessed by linking two independent databases of 540 CEA-treated patients (Ontario Stroke Registry) and 140 CAS-treated patients (single-center CAS database) to administrative records. PPV for CEA ranged from 99% to 100% and sensitivity ranged from 81.5% to 89.6% using CCI and OHIP codes. A CCI code with a PPV of 87% (95% CI, 78.8-92.9) and sensitivity of 92.9% (95% CI, 87.4-96.1) in identifying CAS was also identified. PPV for post-admission complication diagnosis coding was 71.4% (95% CI, 53.7-85.4) for stroke/transient ischemic attack, and 82.4% (95% CI, 56.6-96.2) for myocardial infarction. Our analysis demonstrated that the codes used in administrative databases accurately identify CEA and CAS-treated patients. Researchers can confidently use administrative data to conduct population-based studies of CEA and CAS.

[Cytosine deaminase and thymidine kinase double suicide gene system driven by carcinoembryonic antigen promoter for the treatment of colorectal carcinoma xenograft in nude mice].

PubMed

Huang, Zheng-jie; Feng, Qing-zhao; You, Jun; Xu, Lin; Luo, Wei-yuan; Yi, Wen-cheng; Zeng, Yue-yue; Luo, Qi

2013-07-23

To explore the therapeutic efficacy of double suicide gene system driven by carcinoembryonic antigen (CEA) promoter (Cp-CDglyTK) on colorectal carcinoma xenograft in nude mice. The plasmid pcDNA3.1(-)Cp-CDglyTK was transfected into the CEA-positive SW480 and CEA-negative HeLa cells respectively. The expression of suicide gene was detected by RT-PCR. And the transfected cells were treated with 5-fluorocytosine (5-FC) and ganciclovir (GCV) at different concentrations and the cell-killing and bystander effects assayed by methyl thiazolyl tetrazolium (MTT). By a transplantation of cultivated cells, SW480 or HeLa cell lines were injected subcutaneously into right axillary of nude mice to establish 96 SW480 and 72 HeLa tumor animal models. Nude mice were completely randomized with statistical software according to tumor volume. For prodrug therapy, 48 SW480-bearing mice were divided equally into 4 groups of I-IV. At the same time, 48 HeLa-bearing mice were divided equally into 4 groups of V-VIII. Groups I & V received an intratumoral injection of PBS, groups II & VIGCV and 5-FC intratumorally, groups III & VII PBS intraperitoneally and groups IV & VIII GCV and 5-FC intraperitoneally. Forty-eight SW480-bearing mice were divided equally into 4 groups of IX∼XII and 24 Hela-bearing ones into groups of & in therapy experiment by suicide gene plus prodrug. Six groups received an intratumoral injection of liposome Lipofectamine and plasmid CP-CDglyTK and then an intraperitoneal injection of drug. The groups of IX and received an injection of PBS, group X GCV, group XI 5-FC and groups XII & GCV and 5-FC. The observation parameters included tumor bulk, tumor weight, survival time and treatment effect in each group. SW480 cells transfected by plasmid pcDNA3.1(-)Cp- CDglyTK expressed CDglyTK gene. The inhibition rates of GCV and 5-FC were significantly higher than those of HeLa cells (59.87% ± 0.21% vs 9.90% ± 0.09%, P < 0.01). And higher inhibition rates and stronger bystander effect existed in double versus single produg (all P < 0.05). Tumor size, final tumor weight and survival time of nude mice in groups ofII, IV, VI & VIII had no significant difference with groups ofI, III, V & VII (all P < 0.05). Final tumor size and weight of group XII was significantly smaller than those of groups of IX, X and XI ((150.0 ± 3.2) vs (522.5 ± 1.9) and (256.8 ± 10.4) and (260.7 ± 2.2) mm(3), (54.1 ± 10.4) vs (682.0 ± 12.0) and (251.8 ± 15.1) and (271.6 ± 17.7) mg, all P < 0.05). Meanwhile, the tumor inhibition rate and survival time of group XII(92.1% and (25.7 ± 0.8)d) were significant higher and longer than group X (63.1% and (21.8 ± 0.5) d) and group XI (60.2% and (18.0 ± 0.9) d) (all P < 0.05). However, no significant difference existed in tumor size, final tumor weight and survival time between groups and (all P > 0.05). The inhibition rate of group was merely 0.9%. CDglyTK double suicide gene system driven by CEA promoter may inhibit CEA positive colorectal cancer xenograft in prodrug-treated nude mice.

A Dual Reporter Iodinated Labeling Reagent for Cancer Positron Emission Tomography Imaging and Fluorescence-Guided Surgery

PubMed Central

2018-01-01

The combination of early diagnosis and complete surgical resection offers the greatest prospect of curative cancer treatment. An iodine-124/fluorescein-based dual-modality labeling reagent, 124I-Green, constitutes a generic tool for one-step installation of a positron emission tomography (PET) and a fluorescent reporter to any cancer-specific antibody. The resulting antibody conjugate would allow both cancer PET imaging and intraoperative fluorescence-guided surgery. 124I-Green was synthesized in excellent radiochemical yields of 92 ± 5% (n = 4) determined by HPLC with an improved one-pot three-component radioiodination reaction. The A5B7 carcinoembryonic antigen (CEA)-specific antibody was conjugated to 124I-Green. High tumor uptake of the dual-labeled A5B7 of 20.21 ± 2.70, 13.31 ± 0.73, and 10.64 ± 1.86%ID/g was observed in CEA-expressing SW1222 xenograft mouse model (n = 3) at 24, 48, and 72 h post intravenous injection, respectively. The xenografts were clearly visualized by both PET/CT and ex vivo fluorescence imaging. These encouraging results warrant the further translational development of 124I-Green for cancer PET imaging and fluorescence-guided surgery. PMID:29388770

The role of immunohistochemistry, electron microscopy, and ultrastructural cytochemistry in the diagnosis of mixed carcinoma-neuroendocrine neoplasms.

PubMed

Graham, A R; Payne, C M; Nagle, R B; Angel, E

1987-02-01

We studied four mixed carcinoma-neuroendocrine neoplasms from gastrointestinal tract and pancreas by routine light microscopy (LM), immunohistochemistry (IH), electron microscopy (EM), and ultrastructural cytochemistry (UC). By LM, the individual tumors showed fairly pure neuroendocrine (carcinoid) or epithelial (papillary) patterns, mixed neuroendocrine-carcinoma features and poorly-differentiated tumor in sheets and nests which did not lend itself to morphologic characterization. IH demonstrated mixed expression, within different areas of the same neoplasm, of epithelial antigens (keratins and carcinoembryonic antigen [CEA]) and neuroendocrine markers (neuron-specific enolase [NSE], bombesin and neurohormonal peptides). By EM, each tumor showed ultrastructural features of epithelial and neuroendocrine differentiation which varied substantially in terms of number of cells involved and their distribution; two of the neoplasms showed biphasic differentiation within single cells. The nature of the neurosecretory granules was verified with the uranaffin reaction (UR). This study illustrates the value of combining LM, IH, EM and UC for the identification of mixed carcinoma-neuroendocrine lesions.

Impact of Provider Characteristics on Outcomes of Carotid Endarterectomy for Asymptomatic Carotid Stenosis in New York State.

PubMed

Meltzer, Andrew J; Agrusa, Christopher; Connolly, Peter H; Schneider, Darren B; Sedrakyan, Art

2017-11-01

The purpose of this study is to explore the impact of surgeon characteristics (including annual volume, specialty, and years in practice) on outcomes of carotid endarterectomy (CEA) for asymptomatic carotid atherosclerosis in New York State. The New York Statewide Planning and Cooperation System database was utilized to identify patients undergoing CEA from 2004 to 2011. Provider characteristics were determined by linkage to the New York Office of Professions and National Provider Identification databases. Provider-level factors were characterized by defining 5 quintiles of equal size for each factor. Hierarchical logistic regression models were created to evaluate the impact of provider characteristics on outcome. In total, 36,495 patients underwent CEA for asymptomatic disease performed by vascular (75.7%), general (16.1%), cardiac (6%), and neuro (2.1%) surgeons. Outcomes of interest included in-hospital mortality (0.26%), stroke (0.45%), and the composite end point of mortality, stroke, or cardiac complication (2.2%). Unadjusted outcomes improved with increasing surgeon annual CEA volume. Mid-career surgeons had lower mortality and stroke rates than early or late-career surgeons. Odds of mortality were increased when surgery was performed by the lowest volume providers (quintile 1; 0-11 CEA/year) (odds ratio [OR] 2.62, 95% confidence interval [CI] 1.3-5.28) or a nonspecialty trained (general) surgeon (OR 1.64, 95% 1.01-2.67). After adjustment for all patient-level factors, provider volume remained an independent predictor of outcome, with significantly increased odds of mortality for volume quintile 1 (OR 2.57, 95% CI 1.27-5.23) and quintile 2 (12-22 CEA/year) (0.30%; OR 2.07, 95% CI 1-4.27) surgeons. Adverse events after CEA for asymptomatic disease are comparatively rare. However, surgeon characteristics impact outcome, with the best results offered by high-volume, mid-career, specialty-trained surgeons. Efforts to define the optimal treatment of asymptomatic carotid atherosclerosis must account for the impact of surgeon characteristics on patient outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy and Safety of 3 Different Anesthesia Techniques Used in Total Hip Arthroplasty

PubMed Central

Liang, Chengwei; Wei, Jionglin; Cai, Xiaoxi; Lin, Weilong; Fan, Yongqian; Yang, Fengjian

2017-01-01

Background This study compared the efficacy and safety of 3 different anesthesia techniques used in total hip arthroplasty (THA). Material/Methods We allocated 198 patients preparing to undertake THA into 3 groups: general anesthesia group (GA group, n=66), caudal epidural anesthesia group (CEA group, n=66), and spinal-epidural anesthesia group (SEA group, n=66). We compared postoperative adverse effects occurring in patients of the 3 anesthesia groups. The Visual Analog Scale (VAS) score, Minimum Mental State Examination (MMSE) score, and β-amyloid (Aβ) expression were calculated to determine the effects of different anesthesia on the postoperative pain and cognitive dysfunction of patients. Results The CEA and SEA groups had lower rates of perioperative adverse effects than in the GA group. Patients in the GA group required significantly higher administration of analgesics after the surgery than those in CEA and SEA groups. Higher Aβ expression levels and VAS scores, as well as lower MMSE scores, were also seen in the GA group compared with the other 2 groups. Conclusions CEA and SEA were more effective than GA in THA, and CEA seemed to be a better anesthesia technique than SEA. PMID:28767640

Rechallenge and maintenance therapy using cetuximab and chemotherapy administered to a patient with metastatic colorectal cancer.

PubMed

Ma, Jian; Yang, Quan-Liang; Ling, Yang

2017-02-14

Cetuximab combined with chemotherapy is one of the first-line treatments of metastatic colorectal cancer. Although disease progression inevitably occurs, rechallenge and maintenance therapies using cetuximab-based regimens may be beneficial, particularly for patients with wild-type (WT) KRAS. A 47-year-old female patient who underwent right hemicolectomy presented with an ulcerative adenocarcinoma (grade 2) revealed by histopathological analysis. The patient received three cycles of adjuvant chemotherapy, but disease recurred 15 months later. Cetuximab and a FOLFOX-4 regimen were administered, followed by surgery and adjuvant chemotherapy that was administered for approximately one year. Three years after completing adjuvant therapy, her serum carcinoembryonic antigen levels rapidly increased, and enhanced computed tomography showed widespread metastases. Rechallenge with cetuximab and the FOLFIRI regimen was then initiated, and after 12 cycles, lesions in the lung and liver shrank significantly, and serum CEA levels dramatically declined. Maintenance therapy with cetuximab and capecitabine was then administered for 10 months until the metastatic lesions in the lung and liver enlarged. Rechallenge and maintenance therapy with cetuximab-based chemotherapy were relatively effective for managing a female patient with WT KRAS. Optimization of this strategy requires further in-depth investigations of more patients.

Child with RET proto-oncogene codon 634 mutation.

PubMed

İnce, Dilek; Demirağ, Bengü; Ataseven, Eda; Oymak, Yeşim; Tuhan, Hale; Karakuş, Osman Zeki; Hazan, Filiz; Abacı, Ayhan; Özer, Erdener; Mutafoglu, Kamer; Olgun, Nur

2017-01-01

İnce D, Demirağ B, Ataseven E, Oymak Y, Tuhan H, Karakuş OZ, Hazan F, Abacı A, Özer E, Mutafoglu K, Olgun N. Child with RET proto-oncogene codon 634 mutation. Turk J Pediatr 2017; 59: 590-593. Herein we reported a 7-year-old child with RET proto-oncogene c634 mutation. Her mother had been diagnosed with medullary thyroid carcinoma (MTC), and treated six years ago. Heterozygous mutation of the RET proto-oncogene at c634 had been detected in her mother. Genetic analysis showed the presence of the same mutation in our patient. Thyroid functions were normal. Serum calcitonin level was found mildly elevated. Parathormone (PTH) and carcinoembrionic antigen (CEA) levels were normal. Prophylactic thyroidectomy and sampling of cervical lymph nodes were performed. Histopathologic examination revealed hyperplasia in thyroid C cells, and reactive lymphadenopathy. The risk of MTC has been reported 100% through the life of patients with RET proto-oncogene mutation. It has been reported that particularly patients with c634 mutation have more risk of occurence of metastatic and progressive/recurrent MTC. Prophylactic `thyroidectomy, cervical lymph node dissection` before 5-years-of-age should be considered for these patients.

Diagnostic Value of Combining Tumor and Inflammatory Markers in Lung Cancer

PubMed Central

Yoon, Ho Il; Kwon, Oh-Ran; Kang, Kyung Nam; Shin, Yong Sung; Shin, Ho Sang; Yeon, Eun Hee; Kwon, Keon Young; Hwang, Ilseon; Jeon, Yoon Kyung; Kim, Yongdai; Kim, Chul Woo

2016-01-01

Background Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. Methods We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets. After measuring serum levels of 6 biomarkers (human epididymis secretory protein 4 [HE4], carcinoembryonic antigen [CEA], regulated on activation, normal T cell expressed and secreted [RANTES], apolipoprotein A2 [ApoA2], transthyretin [TTR], and secretory vascular cell adhesion molecule-1 [sVCAM-1]), we tested various sets of biomarkers for their diagnostic performance in lung cancer. Results In a training dataset, the area under the curve (AUC) values were 0.821 for HE4, 0.753 for CEA, 0.858 for RANTES, 0.867 for ApoA2, 0.830 for TTR, and 0.552 for sVCAM-1. A model using all 6 biomarkers and age yielded an AUC value of 0.986 and sensitivity of 93.2% (cutoff at specificity 94%). Applying this model to the validation dataset showed similar results. The AUC value of the model was 0.988, with sensitivity of 93.33% and specificity of 92.00% at the same cutoff point used in the validation dataset. Analyses by stages and histologic subtypes all yielded similar results. Conclusions Combining multiple tumor and systemic inflammatory markers proved to be a valid strategy in the diagnosis of lung cancer. PMID:27722145

Diagnostic Value of Combining Tumor and Inflammatory Markers in Lung Cancer.

PubMed

Yoon, Ho Il; Kwon, Oh-Ran; Kang, Kyung Nam; Shin, Yong Sung; Shin, Ho Sang; Yeon, Eun Hee; Kwon, Keon Young; Hwang, Ilseon; Jeon, Yoon Kyung; Kim, Yongdai; Kim, Chul Woo

2016-09-01

Despite major advances in lung cancer treatment, early detection remains the most promising way of improving outcomes. To detect lung cancer in earlier stages, many serum biomarkers have been tested. Unfortunately, no single biomarker can reliably detect lung cancer. We combined a set of 2 tumor markers and 4 inflammatory or metabolic markers and tried to validate the diagnostic performance in lung cancer. We collected serum samples from 355 lung cancer patients and 590 control subjects and divided them into training and validation datasets. After measuring serum levels of 6 biomarkers (human epididymis secretory protein 4 [HE4], carcinoembryonic antigen [CEA], regulated on activation, normal T cell expressed and secreted [RANTES], apolipoprotein A2 [ApoA2], transthyretin [TTR], and secretory vascular cell adhesion molecule-1 [sVCAM-1]), we tested various sets of biomarkers for their diagnostic performance in lung cancer. In a training dataset, the area under the curve (AUC) values were 0.821 for HE4, 0.753 for CEA, 0.858 for RANTES, 0.867 for ApoA2, 0.830 for TTR, and 0.552 for sVCAM-1. A model using all 6 biomarkers and age yielded an AUC value of 0.986 and sensitivity of 93.2% (cutoff at specificity 94%). Applying this model to the validation dataset showed similar results. The AUC value of the model was 0.988, with sensitivity of 93.33% and specificity of 92.00% at the same cutoff point used in the validation dataset. Analyses by stages and histologic subtypes all yielded similar results. Combining multiple tumor and systemic inflammatory markers proved to be a valid strategy in the diagnosis of lung cancer.

Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer.

PubMed

Yang, Yunben; Shao, Yongfu; Zhu, Mengying; Li, Qier; Yang, Fang; Lu, Xuwen; Xu, Chunjing; Xiao, Bingxiu; Sun, Yanke; Guo, Junming

2016-01-01

Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.

Soluble CEACAM1 and CEACAM6 are differently expressed in blood serum of pregnant women during normal pregnancy.

PubMed

Mach, Pawel; Gellhaus, Alexandra; Prager, Sebastian; Moore, Tom; Wennemuth, Gunther; Kimmig, Rainer; Köninger, Angela; Singer, Bernhard B

2017-10-01

CEACAM1 and CEACAM6 belong to the carcinoembryonic antigen (CEA) family and may play an immune-modulatory role during pregnancy. The aim of the study was to determine the blood serum levels of soluble CEACAM1 and CEACAM6 over the course of pregnancy and postpartum. CEACAM1 and CEACAM6 levels were determined with customized in-house Sandwich-enzyme-linked immunosorbent assay (ELISA) systems. The study population (n=125) was divided into four groups according to the pregnancy trimester and postpartum. Additionally, samples of non-pregnant women (n=14) were analyzed. Serum levels of CEACAM1 in healthy pregnant women were much lower than in non-pregnant women, a difference not seen for CEACAM6. Comparison between the trimesters and postpartum revealed a significant difference in CEACAM1 serum levels. The highest CEACAM1 levels were detected in third trimester. These levels were statistically significantly different from the CEACAM1 levels in first trimester and second trimester. The lowest levels were observed in the second trimester. Postpartum CEACAM1 serum concentrations were slightly lower than in the third trimester, but higher than in the first trimester and significantly higher compared to levels in the second trimester. Decreased concentration of CEACAM1 during the pregnancy suggests its regulatory role in the immune tolerance during the course of pregnancy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Significance of CEA in gastric and colorectal cancer].

PubMed

Uehara, K; Miyamoto, Y; Izuo, M; Shiozaki, H; Aiba, S; Matsumoto, H

1985-04-01

The determination of serum CEA (Sandwich method) and CEA staining (PAP method) of excised specimens were performed in patients with gastric or colorectal cancer, and the biological characteristics of each cancer and the factors to increase serum CEA were studied with the following results: As colonic cancer has strong CEA productivity, serum CEA can be useful for the detection of cancer, and especially effective for the postoperative observation. Gastric cancer has weak CEA productivity, and serum CEA is not so useful in the detection of cancer and the judgement of resectability. The CEA positive rate of tissue with CEA staining was 80% in gastric cancer, 100% in colonic cancer, and were nearly equal to the CEA positive rate of serum in the group of terminal stage. In the mode of CEA staining of cancerous cells, IV type was observed most frequently in gastric cancer, and I type in colonic cancer. Among the resected cases showing more than 7ng/ml serum CEA, differentiated type, lymph node metastasis (+), the degree of tissue staining with CEA staining, the mode of cell staining O or I type in gastric cancer and I type in colonic cancer were observed in common.

Development activities on NIR large format MCT detectors for astrophysics and space science at CEA and SOFRADIR

NASA Astrophysics Data System (ADS)

Boulade, Olivier; Moreau, Vincent; Mulet, Patrick; Gravrand, Olivier; Cervera, Cyril; Zanatta, Jean-Paul; Castelein, Pierre; Guellec, Fabrice; Fièque, Bruno; Chorier, Philippe; Roumegoux, Julien

2016-07-01

CEA and SOFRADIR have been manufacturing and characterizing near infrared detectors in the frame of ESA's near infrared large format sensor array roadmap to develop a 2Kx2K large format low flux low noise device for space applications such as astrophysics. These detectors use HgCdTe as the absorbing material and p/n diode technology. The technological developments (photovoltaic technology, readout circuit, ...) are shared between CEA/LETI and SOFRADIR, both in Grenoble, while most of the performances are evaluated at CEA/IRFU in Saclay where a dedicated test facility has been developed, in particular to measure very low dark currents. The paper will present the current status of these developments at the end of ESA's NIRLFSA phase 2. The performances of the latest batch of devices meet or are very close to all the requirements (quantum efficiency, dark current, cross talk, readout noise, ...) even though a glow induced by the ROIC prevents the accurate measurement of the dark current. The current devices are fairly small, 640x512 15μm pixels, and the next phase of activity will target the development of a full size 2Kx2K detector. From the design and development, to the manufacturing and finally the testing, that type of detector requests a high level of mastering. An appropriate manufacturing and process chain compatible with such a size is needed at industrial level and results obtained with CEA technology coupled with Sofradir industrial experience and work on large dimension detector allow French actors to be confident to address this type of future missions.

Alternative forms of lethality in mitomycin C-induced bacteria carrying ColE1 plasmids

PubMed Central

Suit, Joan L.; Fan, M.-L. Judy; Sabik, Joseph F.; Labarre, Robert; Luria, S. E.

1983-01-01

We have studied the physiological effects of mitomycin C induction on cells carrying ColE1 plasmids with differing configurations of three genes: the structural gene coding for colicin (cea), a gene responsible for mitomycin C lethality (kil) that we located as part of an operon with cea, and the immunity (imm) gene, which lies near cea but is not in the same operon. kil is close to or overlaps imm. When cea+ plasmids are present mitomycin C induction results in 100-fold or greater increases in the level of colicin. Within an hour after induction more than 90% of cells carrying cea+kil+ plasmids are killed and macromolecular synthesis stops, capacity for transport of proline, thiomethyl β-D-galactoside, and α-methyl glucoside is lost, and the membrane becomes abnormally permeable as indicated by an increased accessibility of intracellular β-galactosidase to the substrate o-nitrophenyl β-D-galactoside. All of these events occur when a cea-kil+imm+ plasmid is present and none does when the plasmid is cea+kil-imm+, so the damage can be attributed solely to the Kil function and not to the presence of colicin. However, cells carrying a cea+kil-imm- plasmid are killed upon induction, apparently by action of endogenous colicin on the nonimmune cytoplasmic membrane. The pattern of accompanying physiological damage is distinguished from the kil+-associated damage by an enhancement of α-methyl glucoside uptake and accumulation and efflux of α-methyl glucoside 6-phosphate and by an absence of the alteration in membrane permeability for o-nitrophenyl β-D-galactoside. These features are typical of colicin E1 action on the membrane. The induced damage is not prevented by trypsin and occurs in cells of a strain specifically tolerant to exogenous colicin E1, indicating that the attack is from inside the cell. PMID:6403939

Association between age and risk of stroke or death from carotid endarterectomy and carotid stenting: a meta-analysis of pooled patient data from four randomised trials.

PubMed

Howard, George; Roubin, Gary S; Jansen, Olav; Hendrikse, Jeroen; Halliday, Alison; Fraedrich, Gustav; Eckstein, Hans-Henning; Calvet, David; Bulbulia, Richard; Bonati, Leo H; Becquemin, Jean-Pierre; Algra, Ale; Brown, Martin M; Ringleb, Peter A; Brott, Thomas G; Mas, Jean-Louis

2016-03-26

Age was reported to be an effect-modifier in four randomised controlled trials comparing carotid artery stenting (CAS) and carotid endarterectomy (CEA), with better CEA outcomes than CAS outcomes noted in the more elderly patients. We aimed to describe the association of age with treatment differences in symptomatic patients and provide age-specific estimates of the risk of stroke and death within narrow (5 year) age groups. In this meta-analysis, we analysed individual patient-level data from four randomised controlled trials within the Carotid Stenosis Trialists' Collaboration (CSTC) involving patients with symptomatic carotid stenosis. We included only trials that randomly assigned patients to CAS or CEA and only patients with symptomatic stenosis. We assessed rates of stroke or death in 5-year age groups in the periprocedural period (between randomisation and 120 days) and ipsilateral stroke during long-term follow-up for patients assigned to CAS or CEA. We also assessed differences between CAS and CEA. All analyses were done on an intention-to-treat basis. Collectively, 4754 patients were randomly assigned to either CEA or CAS treatment in the four studies. 433 events occurred over a median follow-up of 2·7 years. For patients assigned to CAS, the periprocedural hazard ratio (HR) for stroke and death in patients aged 65-69 years compared with patients younger than 60 years was 2·16 (95% CI 1·13-4·13), with HRs of roughly 4·0 for patients aged 70 years or older. We noted no evidence of an increased periprocedural risk by age group in the CEA group (p=0·34). These changes underpinned a CAS-versus CEA periprocedural HR of 1·61 (95% CI 0·90-2·88) for patients aged 65-69 years and an HR of 2·09 (1·32-3·32) for patients aged 70-74 years. Age was not associated with the postprocedural stroke risk either within treatment group (p≥0·09 for CAS and 0·83 for CEA), or between treatment groups (p=0·84). In these RCTs, CEA was clearly superior to CAS in patients aged 70-74 years and older. The difference in older patients was almost wholly attributable to increasing periprocedural stroke risk in patients treated with CAS. Age had little effect on CEA periprocedural risk or on postprocedural risk after either procedure. None. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala

PubMed Central

Varodayan, Florence P.; Soni, Neeraj; Bajo, Michal; Luu, George; Madamba, Samuel G.; Schweitzer, Paul; Parsons, Loren H.; Roberto, Marisa

2015-01-01

The endogenous cannabinoids (eCBs) influence the acute response to ethanol and the development of tolerance, dependence and relapse. Chronic alcohol exposure alters eCB levels and type 1 cannabinoid receptor (CB1) expression and function in brain regions associated with addiction. CB1 inhibits GABA release, and GABAergic dysregulation in the central nucleus of the amygdala (CeA) is critical in the transition to alcohol dependence. We investigated possible disruptions in CB1 signaling of rat CeA GABAergic transmission following intermittent ethanol exposure. In the CeA of alcohol-naïve rats, CB1 agonist WIN 55,212-2 (WIN) decreased the frequency of spontaneous and miniature GABAA receptor-mediated inhibitory postsynaptic currents (s/mIPSCs). This effect was prevented by CB1 antagonism, but not type 2 cannabinoid receptor (CB2) antagonism. After 2–3 weeks of intermittent ethanol exposure, these WIN inhibitory effects were attenuated, suggesting ethanol-induced impairments in CB1 function. The CB1 antagonist AM251 revealed a tonic eCB/CB1 control of GABAergic transmission in the alcohol-naïve CeA that was occluded by calcium chelation in the postsynaptic cell. Chronic ethanol exposure abolished this tonic CB1 influence on mIPSC, but not sIPSC, frequency. Finally, acute ethanol increased CeA GABA release in both naïve and ethanol exposed rats. Although CB1 activation prevented this effect, the AM251- and ethanol-induced GABA release were additive, ruling out a direct participation of CB1 signaling in the ethanol effect. Collectively, these observations demonstrate an important CB1 influence on CeA GABAergic transmission and indicate that the CeA is particularly sensitive to alcohol-induced disruptions of CB1 signaling. PMID:25940135

Harnessing Raman spectroimmunoassay for detection of serological breast cancer markers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Barman, Ishan; Li, Ming

2017-02-01

Two critical, unmet needs in breast cancer are the early detection of cancer metastasis and recurrence, and the sensitive assessment of temporal changes in tumor burden in response to therapy. The present research is directed towards developing a non-invasive, ultrasensitive and specific tool that provides a comprehensive real-time picture of the metastatic tumor burden and provides a radically new route to address these overarching challenges. As the continuing search for better diagnostic and prognostic clues has shifted away from a singular focus on primary tumor lesions, circulating and disseminated biomarkers have surfaced as attractive candidates due to the intrinsic advantages of a non-invasive, repeatable "liquid biopsy" procedure. However, a reproducible, facile blood-based test for diagnosis and follow-up of breast cancer has yet to be incorporated into a clinical laboratory assay due to the limitations of existing assays in terms of sensitivity, extensive sample processing requirements and, importantly, multiplexing capability. Here, by architecting nano-structured probes for detection of specific molecular species, we engineer a novel plasmon-enhanced Raman spectroscopic platform that offers a paradigmatic shift from the capabilities of today's diagnostic test platforms. Specifically, quantitative single-droplet serum tests reveal ultrasensitive and multiplexed detection of three key breast cancer biomarkers, cancer antigen 15-3 (CA15-3), CA27-29 and carcinoembryonic antigen (CEA), over several order of magnitude range of biomarker concentration and clear segmentation of the sera between normal and metastatic cancer levels.

All-in-one bioprobe devised with hierarchical-ordered magnetic NiCo2O4 superstructure for ultrasensitive dual-readout immunosensor for logic diagnosis of tumor marker.

PubMed

Dai, Hong; Gong, Lingshan; Zhang, Shupei; Xu, Guifang; Li, Yilin; Hong, Zhensheng; Lin, Yanyu

2016-03-15

A new enzyme-free all-in-one bioprobe, consisted of hematin decorated magnetic NiCo2O4 superstructure (ATS-MNS-Hb), was designed for ultrasensitive photoelectrochemical and electrochemical dual-readout immunosensing of carcinoembryonic antigen (CEA) on carbon nanohorns (CNH) support. Herein, the MNS, possessed hierarchical-ordered structure, good porosity and magnetism, acted as nanocarrier to absorb abundant Hb molecular after functionalization, providing a convenient collection means by magnetic control as well as enhanced dual-readout sensing performances. CNH superstructures were employed as support to immobilize abounding captured antibodies, and then as-designed dual mode bioprobe, covalent binding with secondary antibody of CEA, was introduced for ultrasensitive detection of CEA by sandwich immunosensing. Photoelectrochemical response originated from plentiful hematin molecular, a excellent photosensitizer with good visible light harvesting efficiency, absorbed by functionalized porous MNS. The resultant concentration dependant linear calibration range was from 10 fg/mL to 1 ng/mL with ultralow detection limit of 10 fg/mL. For electrochemical process, catalase-like property of MNS was validated, moreover, MNS-Hb hybrid exhibited much higher mimic enzyme catalytic activity and evidently amplified electrocatalytic signal, performing a wide dynamic linear range from 1 ng/mL to 40 ng/mL with low detection limit of 1 ng/mL. Additionally, due to the improved accuracy of dual signals detection, the exact diagnoses of serum samples were gotten by operating resulting dual signals with AND logic system. This work demonstrated the promising application of MNS in developing ultrasensitive, cost-effective and environment friendly dual-readout immunosensor and accurate diagnoses strategy for tumor markers. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting.

PubMed

Werner, Simone; Krause, Friedemann; Rolny, Vinzent; Strobl, Matthias; Morgenstern, David; Datz, Christian; Chen, Hongda; Brenner, Hermann

2016-04-01

In initial studies that included colorectal cancer patients undergoing diagnostic colonoscopy, we had identified a serum marker combination able to detect colorectal cancer with similar diagnostic performance as fecal immunochemical test (FIT). In this study, we aimed to validate the results in participants of a large colorectal cancer screening study conducted in the average-risk, asymptomatic screening population. We tested serum samples from 1,200 controls, 420 advanced adenoma patients, 4 carcinoma in situ patients, and 36 colorectal cancer patients with a 5-marker blood test [carcinoembryonic antigen (CEA)+anti-p53+osteopontin+seprase+ferritin]. The diagnostic performance of individual markers and marker combinations was assessed and compared with stool test results. AUCs for the detection of colorectal cancer and advanced adenomas with the 5-marker blood test were 0.78 [95% confidence interval (CI), 0.68-0.87] and 0.56 (95% CI, 0.53-0.59), respectively, which now is comparable with guaiac-based fecal occult blood test (gFOBT) but inferior to FIT. With cutoffs yielding specificities of 80%, 90%, and 95%, the sensitivities for the detection of colorectal cancer were 64%, 50%, and 42%, and early-stage cancers were detected as well as late-stage cancers. For osteopontin, seprase, and ferritin, the diagnostic performance in the screening setting was reduced compared with previous studies in diagnostic settings while CEA and anti-p53 showed similar diagnostic performance in both settings. Performance of the 5-marker blood test under screening conditions is inferior to FIT even though it is still comparable with the performance of gFOBT. CEA and anti-p53 could contribute to the development of a multiple marker blood-based test for early detection of colorectal cancer. ©2015 American Association for Cancer Research.

Five common tumor biomarkers and CEA for diagnosing early gastric cancer: A protocol for a network meta-analysis of diagnostic test accuracy.

PubMed

Shen, Minghui; Wang, Hui; Wei, Kongyuan; Zhang, Jianling; You, Chongge

2018-05-01

Although surgical resection is the recommended treatment for the patients with gastric cancer, lots of patients show advanced or metastatic gastric cancer at the time of diagnosis. Detection of gastric cancer at early stages is a huge challenge because of lack of appropriate detection tests. Unfortunately, existing clinical guidelines focusing on early diagnosis of gastric cancer do not provide consistent and prudent evidence. Serum carcinoembryonic antigen was considered as a complementary test, although it is not good enough to diagnose early gastric cancer. There are no other tumor markers recommended for diagnosing early gastric cancer. This study aims to evaluate and compare the diagnostic accuracy of 5 common tumor biomarkers (CA19-9, CA125, PG, IncRNA, and DNA methylation) and CEA and their combinations for diagnosing gastric cancer through network meta-analysis method, and to rank these tests using a superiority index. PubMed, EMBASE.com, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched from their inception to March 2018. We will include diagnostic tests which assessed the accuracy of the above-mentioned tumor biomarkers and CEA for diagnosing gastric cancer. The risk of bias for each study will be independently assessed as low, moderate, or high using criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Network meta-analysis will be performed using STATA 12.0 and R 3.4.1 software. The competing diagnostic tests will be ranked by a superiority index. This study is ongoing and will be submitted to a peer-reviewed journal for publication. This study will provide systematically suggestions to select different tumor biomarkers for detecting the early gastric cancer.

Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells.

PubMed

Ojima, Toshiyasu; Iwahashi, Makoto; Nakamura, Masaki; Matsuda, Kenji; Nakamori, Mikihito; Ueda, Kentaro; Naka, Teiji; Katsuda, Masahiro; Miyazawa, Motoki; Yamaue, Hiroki

2007-10-01

Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined. A cytotoxic assay using peripheral blood mononuclear cell (PBMC)-derived cytotoxic T lymphocytes (CTLs) was performed in a 4-h 51Cr release assay. The apoptosis of DCs was examined by TdT-mediated dUTP-FITC nick end labeling (TUNEL) assay. CEA-specific CTLs were generated from PBMCs stimulated with genetically modified DCs expressing CEA. The cytotoxicity of these CTLs was augmented by co-transduction of DCs with the GM-CSF gene. Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-x(L) expression, leading to the extension of the lifespan of these DCs. Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-beta1 (TGFbeta-1). Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFbeta-1 in the regional lymph nodes.

A risk factor-based predictive model of outcomes in carotid endarterectomy: the National Surgical Quality Improvement Program 2005-2010.

PubMed

Bekelis, Kimon; Bakhoum, Samuel F; Desai, Atman; Mackenzie, Todd A; Goodney, Philip; Labropoulos, Nicos

2013-04-01

Accurate knowledge of individualized risks and benefits is crucial to the surgical management of patients undergoing carotid endarterectomy (CEA). Although large randomized trials have determined specific cutoffs for the degree of stenosis, precise delineation of patient-level risks remains a topic of debate, especially in real world practice. We attempted to create a risk factor-based predictive model of outcomes in CEA. We performed a retrospective cohort study involving patients who underwent CEAs from 2005 to 2010 and were registered in the American College of Surgeons National Quality Improvement Project database. Of the 35 698 patients, 20 015 were asymptomatic (56.1%) and 15 683 were symptomatic (43.9%). These patients demonstrated a 1.64% risk of stroke, 0.69% risk of myocardial infarction, and 0.75% risk of death within 30 days after CEA. Multivariate analysis demonstrated that increasing age, male sex, history of chronic obstructive pulmonary disease, myocardial infarction, angina, congestive heart failure, peripheral vascular disease, previous stroke or transient ischemic attack, and dialysis were independent risk factors associated with an increased risk of the combined outcome of postoperative stroke, myocardial infarction, or death. A validated model for outcome prediction based on individual patient characteristics was developed. There was a steep effect of age on the risk of myocardial infarction and death. This national study confirms that that risks of CEA vary dramatically based on patient-level characteristics. Because of limited discrimination, it cannot be used for individual patient risk assessment. However, it can be used as a baseline for improvement and development of more accurate predictive models based on other databases or prospective studies.

Cost-effectiveness analysis using data from multinational trials: The use of bivariate hierarchical modelling

PubMed Central

Manca, Andrea; Lambert, Paul C; Sculpher, Mark; Rice, Nigel

2008-01-01

Healthcare cost-effectiveness analysis (CEA) often uses individual patient data (IPD) from multinational randomised controlled trials. Although designed to account for between-patient sampling variability in the clinical and economic data, standard analytical approaches to CEA ignore the presence of between-location variability in the study results. This is a restrictive limitation given that countries often differ in factors that could affect the results of CEAs, such as the availability of healthcare resources, their unit costs, clinical practice, and patient case-mix. We advocate the use of Bayesian bivariate hierarchical modelling to analyse multinational cost-effectiveness data. This analytical framework explicitly recognises that patient-level costs and outcomes are nested within countries. Using real life data, we illustrate how the proposed methods can be applied to obtain (a) more appropriate estimates of overall cost-effectiveness and associated measure of sampling uncertainty compared to standard CEA; and (b) country-specific cost-effectiveness estimates which can be used to assess the between-location variability of the study results, while controlling for differences in country-specific and patient-specific characteristics. It is demonstrated that results from standard CEA using IPD from multinational trials display a large degree of variability across the 17 countries included in the analysis, producing potentially misleading results. In contrast, ‘shrinkage estimates’ obtained from the modelling approach proposed here facilitate the appropriate quantification of country-specific cost-effectiveness estimates, while weighting the results based on the level of information available within each country. We suggest that the methods presented here represent a general framework for the analysis of economic data collected from different locations. PMID:17641141

Rimonabant Precipitates Anxiety in Rats Withdrawn from Palatable Food: Role of the Central Amygdala

PubMed Central

Blasio, Angelo; Iemolo, Attilio; Sabino, Valentina; Petrosino, Stefania; Steardo, Luca; Rice, Kenner C; Orlando, Pierangelo; Iannotti, Fabio Arturo; Di Marzo, Vincenzo; Zorrilla, Eric P; Cottone, Pietro

2013-01-01

The anti-obesity medication rimonabant, an antagonist of cannabinoid type-1 (CB1) receptor, was withdrawn from the market because of adverse psychiatric side effects, including a negative affective state. We investigated whether rimonabant precipitates a negative emotional state in rats withdrawn from palatable food cycling. The effects of systemic administration of rimonabant on anxiety-like behavior, food intake, body weight, and adrenocortical activation were assessed in female rats during withdrawal from chronic palatable diet cycling. The levels of the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), and the CB1 receptor mRNA and the protein in the central nucleus of the amygdala (CeA) were also investigated. Finally, the effects of microinfusion of rimonabant in the CeA on anxiety-like behavior, and food intake were assessed. Systemic administration of rimonabant precipitated anxiety-like behavior and anorexia of the regular chow diet in rats withdrawn from palatable diet cycling, independently from the degree of adrenocortical activation. These behavioral observations were accompanied by increased 2-AG, CB1 receptor mRNA, and protein levels selectively in the CeA. Finally, rimonabant, microinfused directly into the CeA, precipitated anxiety-like behavior and anorexia. Our data show that (i) the 2-AG-CB1 receptor system within the CeA is recruited during abstinence from palatable diet cycling as a compensatory mechanism to dampen anxiety, and (ii) rimonabant precipitates a negative emotional state by blocking the beneficial heightened 2-AG-CB1 receptor signaling in this brain area. These findings help elucidate the link between compulsive eating and anxiety, and it will be valuable to develop better pharmacological treatments for eating disorders and obesity. PMID:23793355

Possible Protective Effects of Quercetin and Sodium Gluconate Against Colon Cancer Induction by Dimethylhydrazine in Mice.

PubMed

Saleem, T H; Attya, A M; Ahmed, E A; Ragab, S M M; Ali Abdallah, M A; Omar, H M

2015-01-01

Micronutrients in food have been found to have chemopreventive effects, supporting the conclusions from epidemiologie studies that consumption of fresh fruits and vegetables reduces cancer risk. The present study was carried out to evaluate the role of querctin (Q) and sodium gluconate (GNA) supplementation separately or in combination in ameliorating promotion of colon tumor development by dimethyl-hydrazine (DMH) in mice. Histopathological observation of colons in mice treated with DMH showed goblet cell dysplasia with inflammatory cell infiltration. This pathological finding was associated with significant alteration in oxidative stress markers in colon tissues and carcinoembryonic antigen (CEA) levels in plasma. Mice co-treated with GNA and Q showed mild changes of absorptive and goblet cells and inflammatory cell infiltration in lamina properia, with improvement in oxidative stress markers. In conclusion, findings of the present study indicate significant roles for reactive oxygen species (ROS) in pathogenesis of DMH-induced colon toxicity and initiation of colon cancer. Also, they suggest that Q, GNA or the combination of both have a positive beneficial effect against DMH induced colonic cancer induction in mice.

Expression of Colocasia esculenta tuber agglutinin in Indian mustard provides resistance against Lipaphis erysimi and the expressed protein is non-allergenic.

PubMed

Das, Ayan; Ghosh, Prithwi; Das, Sampa

2018-06-01

Transgenic Brassica juncea plants expressing Colocasia esculenta tuber agglutinin (CEA) shows the non-allergenic nature of the expressed protein leading to enhanced mortality and reduced fecundity of mustard aphid-Lipaphis erysimi. Lipaphis erysimi (common name: mustard aphid) is the most devastating sucking insect pest of Indian mustard (Brassica juncea L.). Colocasia esculenta tuber agglutinin (CEA), a GNA (Galanthus nivalis agglutinin)-related lectin has previously been reported by the present group to be effective against a wide array of hemipteran insects in artificial diet-based bioassays. In the present study, efficacy of CEA in controlling L. erysimi has been established through the development of transgenic B. juncea expressing this novel lectin. Southern hybridization of the transgenic plants confirmed stable integration of cea gene. Expression of CEA in T 0 , T 1 and T 2 transgenic plants was confirmed through western blot analysis. Level of expression of CEA in the T 2 transgenic B. juncea ranged from 0.2 to 0.47% of the total soluble protein. In the in planta insect bioassays, the CEA expressing B. juncea lines exhibited enhanced insect mortality of 70-81.67%, whereas fecundity of L. erysimi was reduced by 49.35-62.11% compared to the control plants. Biosafety assessment of the transgenic B. juncea protein containing CEA was carried out by weight of evidence approach following the recommendations by FAO/WHO (Evaluation of the allergenicity of genetically modified foods: report of a joint FAO/WHO expert consultation, 22-25 Jan, Rome, http://www.fao.org/docrep/007/y0820e/y0820e00.HTM , 2001), Codex (Codex principles and guidelines on foods derived from biotechnology, Food and Agriculture Organization of the United Nations, Rome; Codex, Codex principles and guidelines on foods derived from biotechnology, Food and Agriculture Organization of the United Nations, Rome, 2003) and ICMR (Indian Council of Medical Research, guidelines for safety assessment of food derived from genetically engineered plants, http://www.icmr.nic.in/guide/Guidelines%20for%20Genetically%20Engineered%20Plants.pdf , 2008). Bioinformatics analysis, pepsin digestibility, thermal stability assay, immuno-screening and allergenicity assessment in BALB/c mice model demonstrated that the expressed CEA protein from transgenic B. juncea does not incite any allergenic response. The present study establishes CEA as an efficient insecticidal and non-allergenic protein to be utilized for controlling mustard aphid and similar hemipteran insects through the development of genetically modified plants.

Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics.

PubMed

Jin, Zhe; Bhandage, Amol K; Bazov, Igor; Kononenko, Olga; Bakalkin, Georgy; Korpi, Esa R; Birnir, Bryndis

2014-01-01

The central amygdala (CeA) has a role for mediating fear and anxiety responses. It is also involved in emotional imbalance caused by alcohol abuse and dependence and in regulating relapse to alcohol abuse. Growing evidences suggest that excitatory glutamatergic and inhibitory γ-aminobutyric acid-ergic (GABAergic) transmissions in the CeA are affected by chronic alcohol exposure. Human post-mortem CeA samples from male alcoholics (n = 9) and matched controls (n = 9) were assayed for the expression level of ionotropic glutamate and GABA-A receptors subunit mRNAs using quantitative real-time reverse transcription-PCR (RT-qPCR). Our data revealed that out of the 16 ionotropic glutamate receptor subunits, mRNAs encoding two AMPA [2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid] receptor subunits GluA1 and GluA4; one kainate receptor subunit GluK2; one NMDA (N-methyl-D-aspartate) receptor subunit GluN2D and one delta receptor subunit GluD2 were significantly decreased in the CeA of alcoholics. In contrast, of the 19 GABA-A receptor subunits, only the mRNA encoding the α2 subunit was significantly down-regulated in the CeA of the alcoholics as compared with control subjects. Our findings imply that the down-regulation of specific ionotropic glutamate and GABA-A receptor subunits in the CeA of alcoholics may represent one of the molecular substrates underlying the new balance between excitatory and inhibitory neurotransmission in alcohol dependence.

Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics

PubMed Central

Jin, Zhe; Bhandage, Amol K.; Bazov, Igor; Kononenko, Olga; Bakalkin, Georgy; Korpi, Esa R.; Birnir, Bryndis

2014-01-01

The central amygdala (CeA) has a role for mediating fear and anxiety responses. It is also involved in emotional imbalance caused by alcohol abuse and dependence and in regulating relapse to alcohol abuse. Growing evidences suggest that excitatory glutamatergic and inhibitory γ-aminobutyric acid-ergic (GABAergic) transmissions in the CeA are affected by chronic alcohol exposure. Human post-mortem CeA samples from male alcoholics (n = 9) and matched controls (n = 9) were assayed for the expression level of ionotropic glutamate and GABA-A receptors subunit mRNAs using quantitative real-time reverse transcription-PCR (RT-qPCR). Our data revealed that out of the 16 ionotropic glutamate receptor subunits, mRNAs encoding two AMPA [2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid] receptor subunits GluA1 and GluA4; one kainate receptor subunit GluK2; one NMDA (N-methyl-D-aspartate) receptor subunit GluN2D and one delta receptor subunit GluD2 were significantly decreased in the CeA of alcoholics. In contrast, of the 19 GABA-A receptor subunits, only the mRNA encoding the α2 subunit was significantly down-regulated in the CeA of the alcoholics as compared with control subjects. Our findings imply that the down-regulation of specific ionotropic glutamate and GABA-A receptor subunits in the CeA of alcoholics may represent one of the molecular substrates underlying the new balance between excitatory and inhibitory neurotransmission in alcohol dependence. PMID:25278838

Bayesian hierarchical models for cost-effectiveness analyses that use data from cluster randomized trials.

PubMed

Grieve, Richard; Nixon, Richard; Thompson, Simon G

2010-01-01

Cost-effectiveness analyses (CEA) may be undertaken alongside cluster randomized trials (CRTs) where randomization is at the level of the cluster (for example, the hospital or primary care provider) rather than the individual. Costs (and outcomes) within clusters may be correlated so that the assumption made by standard bivariate regression models, that observations are independent, is incorrect. This study develops a flexible modeling framework to acknowledge the clustering in CEA that use CRTs. The authors extend previous Bayesian bivariate models for CEA of multicenter trials to recognize the specific form of clustering in CRTs. They develop new Bayesian hierarchical models (BHMs) that allow mean costs and outcomes, and also variances, to differ across clusters. They illustrate how each model can be applied using data from a large (1732 cases, 70 primary care providers) CRT evaluating alternative interventions for reducing postnatal depression. The analyses compare cost-effectiveness estimates from BHMs with standard bivariate regression models that ignore the data hierarchy. The BHMs show high levels of cost heterogeneity across clusters (intracluster correlation coefficient, 0.17). Compared with standard regression models, the BHMs yield substantially increased uncertainty surrounding the cost-effectiveness estimates, and altered point estimates. The authors conclude that ignoring clustering can lead to incorrect inferences. The BHMs that they present offer a flexible modeling framework that can be applied more generally to CEA that use CRTs.

Development and characterisation of MCT detectors for space astrophysics at CEA

NASA Astrophysics Data System (ADS)

Boulade, O.; Baier, N.; Castelein, P.; Cervera, C.; Chorier, P.; Destefanis, G.; Fièque, B.; Gravrand, O.; Guellec, F.; Moreau, V.; Mulet, P.; Pinsard, F.; Zanatta, J.-P.

2017-11-01

The Laboratoire Electronique et Traitement de l'Information (LETI) of the Commissariat à l'Energie Atomique (CEA, Grenoble, France) has been involved in the development of infrared detectors based on HgCdTe (MCT) material for over 30 years, mainly for defence and security programs [1]. Once the building blocks are developed at LETI (MCT material process, diode technology, hybridization, …), the industrialization is performed at SOFRADIR (also in Grenoble, France) which also has its own R&D program [2]. In past years, LETI also developed infrared detectors for space astrophysics in the mid infrared range - the long wave detector of the ISOCAM camera onboard ISO - as well as in the far infrared range - the bolometer arrays of the Herschel/PACS photometer unit -, both instruments which were under the responsibility of the Astrophysics department of CEA (IRFU/SAp, Saclay, France). Nowadays, the infrared detectors used in space and ground based astronomical instruments all come from vendors in the US. For programmatic reasons - increase the number of available vendors, decrease the cost, mitigate possible export regulations, …- as well as political ones - spend european money in Europe -, the European Space Agency (ESA) defined two roadmaps (one in the NIR-SWIR range, one in the MWIR-LWIR range) that will eventually allow for the procurement of infrared detectors for space astrophysics within Europe. The French Space Agency (CNES) also started the same sort of roadmaps, as part of its contribution to the different space missions which involve delivery of instruments by French laboratories. It is important to note that some of the developments foreseen in these roadmaps also apply to Earth Observations. One of the main goal of the ESA and CNES roadmaps is to reduce the level of dark current in MCT devices at all wavelengths. The objective is to use the detectors at the highest temperature where the noise induced by the dark current stays compatible with the photon noise, as the detector operating temperature has a very strong impact at system level. A consequence of reaching low levels of dark current is the need for very low noise readout circuits. CEA and SOFRADIR are involved in a number of activities that have already started in this framework. CEA/LETI does the development of the photo-voltaic (PV) layers - MCT material growth, diode technologies-, as well as some electro-optical characterisation at wafer, diode and hybrid component levels, and CEA/IRFU/SAp does all the electro-optical characterisation involving very low flux measurements (mostly dark current measurements). Depending of the program, SOFRADIR can also participate in the development of the hybrid components, for instance the very low noise readout circuits (ROIC) can be developed either at SOFRADIR or at CEA/LETI. Depending of the component specifications, the MCT epitaxy can be either liquid phase (LPE, which is the standard at SOFRADIR for production purposes) or molecular beam (MBE), the diode technology can be n/p (standard at LETI and SOFRADIR) or p/n (under development for several years now) [3], and the input stage of the ROIC can be Source Follower per Detector (SFD for very low flux low noise programs) or Capacitive Trans Impedance Amplifier (CTIA for intermediate flux programs) [4]. This paper will present the different developments and results obtained so far in the two NIR-SWIR and MWIR-LWIR spectral ranges, as well as the perspectives for the near future. CEA/LETI is also involved in the development of MCT Avalanche Photo Diodes (APD) that will be discussed in other papers [5,6].

Biodegradable double-targeted PTX-mPEG-PLGA nanoparticles for ultrasound contrast enhanced imaging and antitumor therapy in vitro.

PubMed

Ma, Jing; Shen, Ming; Xu, Chang Song; Sun, Ying; Duan, You Rong; Du, Lian Fang

2016-11-29

A porous-structure nano-scale ultrasound contrast agent (UCA) was made of monomethoxypoly (ethylene glycol)-poly (lactic-co-glycolic acid) (mPEG-PLGA), and modified by double-targeted antibody: anti-carcinoembryonic antigen (CEA) and anti-carbohydrate antigen 19-9 (CA19-9), as a double-targeted nanoparticles (NPs). Anti-tumor drug paclitaxel (PTX) was encapsulated in the double-targeted nanoparticles (NPs). The morphor and release curve were characterized. We verified a certain anticancer effect of PTX-NPs through cytotoxicity experiments. The cell uptake result showed much more NPs may be facilitated to ingress the cells or tissues with ultrasound (US) or ultrasound targeted microbubble destruction (UTMD) transient sonoporation in vitro. Ultrasound contrast-enhanced images in vitro and in vivo were investigated. Compared with SonoVue, the NPs prolonged imaging time in rabbit kidneys and tumor of nude mice, which make it possible to further enhance anti-tumor effects by extending retention time in the tumor region. The novel double-targeted NPs with the function of ultrasound contrast enhanced imaging and anti-tumor therapy can be a promising way in clinic.

Two-marker combinations for preoperative discrimination of benign and malignant ovarian masses.

PubMed

Freydanck, Maj Kristin; Laubender, Ruediger Paul; Rack, Brigitte; Schuhmacher, Lan; Jeschke, Udo; Scholz, Christoph

2012-05-01

When caring for patients with ovarian neoplasms, correct preoperative discrimination of benign and malignant disease is deemed vital. In this study, we tested serum biomarkers' alone and in combination, to achieve this aim. We measured the concentrations of Cancer Antigen (CA)-125, CA15-3, CA27-29, Carcinoembryonic Antigen (CEA), CA19-9, human chorionic gonadotropin (hCG), Placental Protein (PP)1490, CA72-4, galectin-3, galectin-1 and Human epididymis protein (HE)4 in sera of 133 patients with pelvic masses by ELISA and correlated the results to subsequent histology. We used the area under the curve (AUC) of biomarkers and their combinations and calculated the 95% confidence intervals by using casewise resampling. The best single biomarkers were CA-125 (sensitivity and AUC) and HE4 (specificity). Combinations with HE4 and CA19-9 improved the predictive power of CA-125. The best discrimination was achieved by the combination of CA-125 and HE4, with an AUC of 0.961. A combination of CA-125 with HE4 could facilitate the identification of women at risk for ovarian cancer.

An Information Building on Radioactivity and Nuclear Energy for the French CEA Cadarache Research Center - 13492

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brunel, Guy; Denis, Dominique; Boulet, Alain

The CEA Cadarache research center is one of the 10 research centers of the French Alternative Energies and Atomic Energy Commission (CEA). Distributed throughout various research platforms, it focuses on nuclear fission, nuclear fusion, new energy technologies (hydrogen, solar, biomass) and fundamental research in the field of vegetal biology. It is the most important technological research and development centers for energy in Europe. Considering the sensitive nature of nuclear activities, the questions surrounding the issue of radioactive waste, the nuclear energy and the social, economic and environmental concerns for present and future generations, the French Government asked nuclear actors tomore » open communication and to give all the information asked by the Local Information Commission (CLI) and the public [1]. In this context, the CEA Cadarache has decided to better show and explain its expertise and experience in the area of nuclear energy and nuclear power plant design, and to make it available to stakeholders and to the public. CEA Cadarache receives each year more than 9000 visitors. To complete technical visits of the research facilities and laboratories, a scientific cultural center has been built in 2011 to inform the public on CEA Cadarache research activities and to facilitate the acceptance of nuclear energy in a way suited to the level of knowledge of the visitors. A modern interactive exhibition of 150 m{sup 2} allows visitors to find out more about energy, CEA Cadarache research programs, radioactive waste management and radiological impact on the research center activities. It also offers an auditorium for group discussions and for school groups to discover science through enjoyment. This communication center has received several thousand visitors since its opening on October 2011; the initial results of this experience are now available. It's possible to explain the design of this exhibition, to give some statistics on the number of the visitors, their characteristics and their perception after their center visits. (authors)« less

Combination of preoperative NLR, PLR and CEA could increase the diagnostic efficacy for I-III stage CRC.

PubMed

Peng, Hong-Xin; Yang, Lin; He, Bang-Shun; Pan, Yu-Qin; Ying, Hou-Qun; Sun, Hui-Ling; Lin, Kang; Hu, Xiu-Xiu; Xu, Tao; Wang, Shu-Kui

2017-09-01

Inflammation plays an important role in the development and progression of CRC. The members of inflammatory biomarkers, preoperative NLR and PLR, have been proved by numerous studies to be promising prognostic biomarkers for CRC. However, the diagnostic value of the two biomarkers in CRC remains unknown, and no study reported the combined diagnostic efficacy of NLR, PLR and CEA. Five hundred and fifty-nine patients with I-III stage CRC undergoing surgical resection and 559 gender- and age-matched healthy controls were enrolled in this retrospective study. NLR and PLR were calculated from preoperative peripheral blood cell count detected using white blood cell five classification by Sysmex XT-1800i Automated Hematology System and serum CEA were measured by electrochemiluminescence by ELECSYS 2010. The diagnostic performance of NLR, PLR and CEA for CRC was evaluated by ROC curve. Levels of NLR and PLR in the cases were significantly higher than them in the healthy controls. ROC curves comparison analyses showed that the diagnostic efficacy of NLR (AUC=.755, 95%CI=.728-.780) alone for CRC was significantly higher than PLR (AUC=.723, 95%CI=.696-.749, P=.037) and CEA (AUC=.690, 95%CI=.662-.717, P=.002) alone. In addition, the diagnostic efficacy of the combination of NLR, PLR and CEA(AUC=.831, 95%CI=.807-.852)for CRC was not only significantly higher than NLR alone but also higher than any combinations of the two of these three biomarkers (P<.05). Moreover, the NLR and PLR in the patients with TNM stage I/II was higher than that in the healthy controls, and patients with stage III had a higher NLR and PLR than those with stage I/II, but no significant difference was observed. Our study indicated that preoperative NLR could be a CRC diagnostic biomarker, even for early stage CRC, and the combination of NLR, PLR and CEA could significantly improve the diagnostic efficacy. © 2016 Wiley Periodicals, Inc.

Role of the oxytocin system in amygdala subregions in the regulation of social interest in male and female rats

PubMed Central

Dumais, Kelly M.; Alonso, Andrea G.; Bredewold, Remco; Veenema, Alexa H.

2016-01-01

We previously found that oxytocin (OT) receptor (OTR) binding density in the medial amygdala (MeA) correlated positively with social interest (i.e., the motivation to investigate a conspecific) in male rats, while OTR binding density in the central amygdala (CeA) correlated negatively with social interest in female rats. Here, we determined the causal involvement of OTR in the MeA and CeA in the sex-specific regulation of social interest in adult rats by injecting an OTR antagonist (5 ng/0.5 µl/side) or OT (100 pg/0.5 µl/side) before the social interest test (4-min same-sex juvenile exposure). OTR blockade in the CeA decreased social interest in males but not females, while all other treatments had no behavioral effect. To further explore the sex-specific involvement of the OT system in the CeA in social interest, we used in vivo microdialysis to determine possible sex differences in endogenous OT release in the CeA during social interest. Interestingly, males and females showed similar levels of extracellular OT release at baseline and during social interest, suggesting that factors other than local OT release mediate the sex-specific role of CeA-OTR in social interest. Moreover, we found a positive correlation between CeA-OT release and social investigation time in females. This was further reflected by reduced CeA-OT release during social interest in females that expressed low compared to high social interest. We discuss the possibility that this reduction in OT release may be a consequence, rather than a cause, of exposure to a social stimulus. Overall, our findings show for the first time that extracellular OT release in the CeA is similar between males and females and that OTR in the CeA plays a causal role in the regulation of social interest towards juvenile conspecifics in males. PMID:27235738

Divergent functions of the left and right central amygdala in visceral nociception

PubMed Central

Sadler, Katelyn E.; McQuaid, Neal A.; Cox, Abigail C.; Behun, Marissa N.; Trouten, Allison M.; Kolber, Benedict J.

2017-01-01

The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2–mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase–activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2–mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain–like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries. PMID:28225716

Divergent functions of the left and right central amygdala in visceral nociception.

PubMed

Sadler, Katelyn E; McQuaid, Neal A; Cox, Abigail C; Behun, Marissa N; Trouten, Allison M; Kolber, Benedict J

2017-04-01

The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2-mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase-activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2-mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain-like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.

MMP13 is potentially a new tumor marker for breast cancer diagnosis.

PubMed

Chang, Hui-Jen; Yang, Ming-Je; Yang, Yu-Hsiang; Hou, Ming-Feng; Hsueh, Er-Jung; Lin, Shiu-Ru

2009-11-01

Within the past decade, the incidence of breast cancer in Taiwan has been rising year after year. Breast cancer is the first most prevalent cancer and the fourth leading cause of cancer-related deaths among women in Taiwan. The early stage of breast cancer not only have a wider range of therapeutic options, but also obtain a higher success rate of therapy than those with advanced breast cancer. A test for tumor markers is the most convenient method to screen for breast cancer. However, the tumor markers currently available for breast cancer detection include carcinoembryonic antigen (CEA), carbohydrate antigen 15.3 (CA15.3), and carbohydrate antigen 27.29 (CA27.29) exhibited certain limitations. Poor sensitivity and specificity greatly limits the diagnostic accuracy of these markers. This study aims to identify potential tumor markers for breast cancer. At first, we analyzed genes expression in infiltrating lobular carcinoma, metaplastic carcinoma, and infiltrating ductal carcinoma of paired specimens (tumor and normal tissue) from breast cancer patients using microarray technology. We selected 371 overexpressed genes in all of the three cell type. In advanced breast cancer tissue, we detected four genes MMP13, CAMP, COL10A1 and FLJ25416 from 25 overexpressed genes which encoded secretion protein more specifically for breast cancer than other genes. After validation with 15 pairs of breast cancer tissue and paired to normal adjacent tissues by membrane array and quantitative RT-PCR, we found MMP13 was 100% overexpressed and confirmed to be a secreted protein by Western blot analysis of the cell culture medium. The expression level of MMP13 was also measured by immunohistochemical staining. We suggest that MMP13 is a highly overexpressed secretion protein in breast cancer tissue. It has potential to be a new tumor marker for breast cancer diagnosis.

Monitoring carcinogenesis in a case of oral squamous cell carcinoma using a panel of new metabolic blood biomarkers as liquid biopsies.

PubMed

Grimm, Martin; Hoefert, Sebastian; Krimmel, Michael; Biegner, Thorsten; Feyen, Oliver; Teriete, Peter; Reinert, Siegmar

2016-09-01

One of the common malignant tumors of the head and neck worldwide with generally unfavorable prognosis is squamous cell carcinoma (OSCC) of the oral cavity. Early detection of primary, secondary, or recurrent OSCC by liquid biopsy tools is much needed. Twelve blood biomarkers were used for monitoring a case of OSCC suffering from precancerous oral lichen ruber planus mucosae (OLP). After curative R0 tumor resection of primary OSCC (buccal mucosa), elevated epitope detection in monocytes (EDIM)-Apo10, EDIM-transketolase-like-1 (TKTL1), squamous cell carcinoma antigen (SCC-Ag), total serum lactate dehydrogenase (LDH), and its anaerobic isoforms (LDH-4, LDH-5) decreased to normal levels. Three and six months after surgery, transformation of suspicious mucosal lesions has been accompanied with an increase of EDIM scores, total serum LDH values, and a metabolic shift from aerobic (decrease of LDH-1, LDH-2) to anaerobic (increase of LDH-4, LDH-5) conditions. Two months later, secondary OSCC was histopathologically analyzed after tissue biopsy. Cytokeratin fraction 21-1 (CYFRA 21-1), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) were not affected during the clinical course of carcinogenesis. A combination strategy using a standardized panel of established (metabolic) blood biomarkers (TKTL1, LDH, LDH isoenzymes) is worth and can be recommended among others (apoptosis resistance-related Apo10, SCC-Ag) for early detection and diagnosis of primary, secondary, and recurrent OSCC. A tandem strategy utilizing (metabolic pronounced) routine liquid biopsies with imaging techniques may enhance diagnosis of OSCC in the future. Although we demonstrated the diagnostic utility of separated liquid biopsies in our previous study cohorts, further investigations in a larger patient cohort are necessary to recommend this combination strategy (EDIM blood test, LDH value, metabolic shift of LDH isoenzymes, and others, e.g., SCC-Ag or immunophenotyping) as a diagnostic tool for the addition to the OSCC staging system and as a routine procedure in the aftercare.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glascoe, Lee; Gowardhan, Akshay; Lennox, Kristin

In the interest of promoting the international exchange of technical expertise, the US Department of Energy’s Office of Emergency Operations (NA-40) and the French Commissariat à l'Energie Atomique et aux énergies alternatives (CEA) requested that the National Atmospheric Release Advisory Center (NARAC) of Lawrence Livermore National Laboratory (LLNL) in Livermore, California host a joint table top exercise with experts in emergency management and atmospheric transport modeling. In this table top exercise, LLNL and CEA compared each other’s flow and dispersion models. The goal of the comparison is to facilitate the exchange of knowledge, capabilities, and practices, and to demonstrate themore » utility of modeling dispersal at different levels of computational fidelity. Two modeling approaches were examined, a regional scale modeling approach, appropriate for simple terrain and/or very large releases, and an urban scale modeling approach, appropriate for small releases in a city environment. This report is a summary of LLNL and CEA modeling efforts from this exercise. Two different types of LLNL and CEA models were employed in the analysis: urban-scale models (Aeolus CFD at LLNL/NARAC and Parallel- Micro-SWIFT-SPRAY, PMSS, at CEA) for analysis of a 5,000 Ci radiological release and Lagrangian Particle Dispersion Models (LODI at LLNL/NARAC and PSPRAY at CEA) for analysis of a much larger (500,000 Ci) regional radiological release. Two densely-populated urban locations were chosen: Chicago with its high-rise skyline and gridded street network and Paris with its more consistent, lower building height and complex unaligned street network. Each location was considered under early summer daytime and nighttime conditions. Different levels of fidelity were chosen for each scale: (1) lower fidelity mass-consistent diagnostic, intermediate fidelity Navier-Stokes RANS models, and higher fidelity Navier-Stokes LES for urban-scale analysis, and (2) lower-fidelity single-profile meteorology versus higher-fidelity three-dimensional gridded weather forecast for regional-scale analysis. Tradeoffs between computation time and the fidelity of the results are discussed for both scales. LES, for example, requires nearly 100 times more processor time than the mass-consistent diagnostic model or the RANS model, and seems better able to capture flow entrainment behind tall buildings. As anticipated, results obtained by LLNL and CEA at regional scale around Chicago and Paris look very similar in terms of both atmospheric dispersion of the radiological release and total effective dose. Both LLNL and CEA used the same meteorological data, Lagrangian particle dispersion models, and the same dose coefficients. LLNL and CEA urban-scale modeling results show consistent phenomenological behavior and predict similar impacted areas even though the detailed 3D flow patterns differ, particularly for the Chicago cases where differences in vertical entrainment behind tall buildings are particularly notable. Although RANS and LES (LLNL) models incorporate more detailed physics than do mass-consistent diagnostic flow models (CEA), it is not possible to reach definite conclusions about the prediction fidelity of the various models as experimental measurements were not available for comparison. Stronger conclusions about the relative performances of the models involved and evaluation of the tradeoffs involved in model simplification could be made with a systematic benchmarking of urban-scale modeling. This could be the purpose of a future US / French collaborative exercise.« less

Cost-effectiveness analysis: role and implications.

PubMed

Marsden, G; Wonderling, D

2013-03-01

Cost-effectiveness analysis (CEA) is often misperceived to be a cost-cutting exercise. The intention of CEA is not to identify and implement cheap technologies, but rather those which offer maximum health gain, subject to available funds. Such analysis is crucial for decision making in health care, as tight budget constraints mean spending in one area of healthcare displaces spending elsewhere. Therefore in order to achieve the greatest health gain for the overall population, treatments must be selected which provide the greatest health gain within the available funds. The relevance of CEA in health care systems is explained, using varicose vein treatment in the UK NHS as an example. Treatment for varicose veins is often not commissioned to at a local level, most likely because it is misperceived to be a cosmetic problem. However, this view does not take into account the impact of quality of life. CEA balances costs against a quantitative measure of health related quality of life, and could therefore be used to determine whether it is cost-effective to provide varicose vein treatment. The current literature on the cost-effectiveness of varicose vein treatment is reviewed, and an overview of cost-effectiveness principles is provided. Concepts such as economic modelling, incremental cost-effectiveness ratios (ICERs), net monetary benefit (NMB) and sensitivity analysis are explained, using examples relevant to varicose veins where appropriate. This article explains how, far from cutting costs and sacrificing patient health, CEA provides a useful tool to maximise the health of the population in the face of ever tightening budget constraints. CEA could be used to compare the cost-effectiveness of the various treatment options for varicose veins, and efficiencies realised.

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate

PubMed Central

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-01-01

The central extended amygdala (CEA) has been conceptualized as a ‘macrosystem’ that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the ‘limbic-associative’ striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning. PMID:28220796

Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

PubMed

Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

2017-07-01

The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

Standard duplex criteria overestimate the degree of stenosis after eversion carotid endarterectomy.

PubMed

Benzing, Travis; Wilhoit, Cameron; Wright, Sharee; McCann, P Aaron; Lessner, Susan; Brothers, Thomas E

2015-06-01

The eversion technique for carotid endarterectomy (eCEA) offers an alternative to longitudinal arteriotomy and patch closure (pCEA) for open carotid revascularization. In some reports, eCEA has been associated with a higher rate of >50% restenosis of the internal carotid when it is defined as peak systolic velocity (PSV) >125 cm/s by duplex imaging. Because the conformation of the carotid bifurcation may differ after eCEA compared with native carotid arteries, it was hypothesized that standard duplex criteria might not accurately reflect the presence of restenosis after eCEA. In a case-control study, the outcomes of all patients undergoing carotid endarterectomy by one surgeon during the last 10 years were analyzed retrospectively, with a primary end point of PSV >125 cm/s. Duplex flow velocities were compared with luminal diameter measurements for any carotid computed tomography arteriography or magnetic resonance angiography study obtained within 2 months of duplex imaging, with the degree of stenosis calculated by the methodology used in the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the European Carotid Surgery Trial (ECST) as well as cross-sectional area (CSA) reduction. Simulations were generated and analyzed by computational model simulations of the eCEA and pCEA arteries. Eversion and longitudinal arteriotomy with patch techniques were used in 118 and 177 carotid arteries, respectively. Duplex follow-up was available in 90 eCEA arteries at a median of 16 (range, 2-136) months and in 150 pCEA arteries at a median of 41 (range, 3-115) months postoperatively. PSV >125 cm/s was present at some time during follow-up in 31% of eCEA and pCEA carotid arteries, each, and in the most recent duplex examination in 7% after eCEA and 21% after pCEA (P = .003), with no eCEA and two pCEA arteries occluding completely during follow-up (P = .29). In 19 carotid arteries with PSV >125 cm/s after angle correction (median, 160 cm/s; interquartile range, 146-432 cm/s) after eCEA that were subsequently examined by axial imaging, the mean percentage stenosis was 8% ± 11% by NASCET, 11% ± 5% by ECST, and 20% ± 9% by CSA criteria. For eight pCEA arteries with PSV >125 cm/s (median velocity, 148 cm/s; interquartile range, 139-242 cm/s), the corresponding NASCET, ECST, and CSA stenoses were 8% ± 35%, 26% ± 32%, and 25% ± 33%, respectively. NASCET internal carotid diameter reduction of at least 50% was noted by axial imaging after two of the eight pCEAs, and the PSV exceeded 200 cm/s in each case. The presence of hemodynamically significant carotid artery restenosis may be overestimated by standard duplex criteria after eCEA and perhaps after pCEA. Insufficient information currently exists to determine what PSV does correspond to hemodynamically significant restenosis. Published by Elsevier Inc.

Simulated microgravity does not alter epithelial cell adhesion to matrix and other molecules

NASA Technical Reports Server (NTRS)

Jessup, J. M.; Brown, K.; Ishii, S.; Ford, R.; Goodwin, T. J.; Spaulding, G.

1994-01-01

Microgravity has advantages for the cultivation of tissues with high fidelity; however, tissue formation requires cellular recognition and adhesion. We tested the hypothesis that simulated microgravity does not affect cell adhesion. Human colorectal carcinoma cells were cultured in the NASA Rotating Wall Vessel (RWV) under low shear stress with randomization of the gravity vector that simulates microgravity. After 6 - 7 days, cells were assayed for binding to various substrates and compared to cells grown in standard tissue culture flasks and static suspension cultures. The RWV cultures bound as well to basement membrane proteins and to Carcinoembryonic Antigen (CEA), an intercellular adhesion molecule, as control cultures did. Thus, microgravity does not alter epithelial cell adhesion and may be useful for tissue engineering.

Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid.

PubMed

Caobelli, Federico; Chiaravalloti, Agostino; Evangelista, Laura; Saladini, Giorgio; Schillaci, Orazio; Vadrucci, Manuela; Scalorbi, Federica; Donner, Davide; Alongi, Pierpaolo

2018-01-01

Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5-8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of 18 F-DOPA PET/CT in patients with recurrent MTC. 60 patients (mean age 64 ± 13 years, range 44-82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging 18 F-DOPA PET/CT, performed at least 6 months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21 ± 11 months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of 18 F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan-Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis. 18 F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p = 0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p = 0.04). 18 F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p < 0.001 and p = 0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC. 18 F-DOPA PET/CT scan has an important prognostic value in predicting disease progression and mortality rate.

Molecular Mechanism Underlying the Entomotoxic Effect of Colocasia esculenta Tuber Agglutinin against Dysdercus cingulatus

PubMed Central

Roy, Amit; Das, Sampa

2015-01-01

Colocasia esculenta tuber agglutinin (CEA), a mannose binding lectin, exhibits insecticidal efficacy against different hemipteran pests. Dysdercus cingulatus, red cotton bug (RCB), has also shown significant susceptibility to CEA intoxication. However, the molecular basis behind such entomotoxicity of CEA has not been addressed adequately. The present study elucidates the mechanism of insecticidal efficacy of CEA against RCB. Confocal and scanning electron microscopic analyses documented CEA binding to insect midgut tissue, resulting in an alteration of perimicrovillar membrane (PMM) morphology. Internalization of CEA into insect haemolymph and ovary was documented by western blotting analyses. Ligand blot followed by mass spectrometric identification revealed the cognate binding partners of CEA as actin, ATPase and cytochrome P450. Deglycosylation and mannose inhibition assays indicated the interaction to probably be mannose mediated. Bioinformatic identification of putative glycosylation or mannosylation sites in the binding partners further supports the sugar mediated interaction. Correlating entomotoxicity of CEA with immune histological and binding assays to the insect gut contributes to a better understanding of the insecticidal potential of CEA and endorses its future biotechnological application.

High-grade carotid artery stenosis: A forgotten area in cardiovascular risk management.

PubMed

Good, Elin; Länne, Toste; Wilhelm, Elisabeth; Perk, Joep; Jaarsma, Tiny; de Muinck, Ebo

2016-09-01

Patients with high-grade (≥70%) carotid artery stenosis (CAS) rank in the highest risk category for future cardiovascular (CV) events, but the quality of cardiovascular risk management in this patient group is unknown. Cross-sectional retrospective study. Data were collected for all patients diagnosed with high-grade CAS in Östergötland county, Sweden between 1 January 2009 and 31 July 2012 regarding the quality of cardiovascular risk management, co-morbidity and outcomes during the 2-year follow-up period after a diagnosis of CAS with a carotid ultrasound scan. Patients were included regardless of whether they underwent carotid endarterectomy (CEA). A total of 393 patients with CAS were included in the study; 133 (33.8%) underwent CEA and 260 (66.2%) were assigned to a conservative management (CM) group. In both groups of patients the prescription of platelet inhibitors, statins and antihypertensive drugs increased significantly (p < 0.001) after diagnosis. However treatment targets were not met in the majority of patients and the low-density lipoprotein level was on target in only 13.5% of patients. During follow-up, low-density lipoprotein levels were not measured in 19.8% of patients who underwent CEA and 44.2% of patients in the CM group (p < 0.001); HbA1c was not measured in 24.4% of patients with diabetes in the CEA group and in 18.8% of patients in the CM group (p = 0.560). There was no documentation of counselling on diet, exercise, smoking cessation or adherence to medication. The combined clinical event rate (all-cause mortality, cardiovascular mortality and non-fatal cardiovascular events) was high in both groups (CEA 36.8% and CM 36.9%; p = 1.00) with no difference in the occurrence of ipsilateral ischaemic stroke. The clinical event rate was high in patients with high-grade CAS and the management of cardiovascular risk was deficient in all aspects. © The European Society of Cardiology 2016.

Development and potential applications of microarrays based on fluorescent nanocrystal-encoded beads for multiplexed cancer diagnostics

NASA Astrophysics Data System (ADS)

Brazhnik, Kristina; Grinevich, Regina; Efimov, Anton E.; Nabiev, Igor; Sukhanova, Alyona

2014-05-01

Advanced multiplexed assays have recently become an indispensable tool for clinical diagnostics. These techniques provide simultaneous quantitative determination of multiple biomolecules in a single sample quickly and accurately. The development of multiplex suspension arrays is currently of particular interest for clinical applications. Optical encoding of microparticles is the most available and easy-to-use technique. This technology uses fluorophores incorporated into microbeads to obtain individual optical codes. Fluorophore-encoded beads can be rapidly analyzed using classical flow cytometry or microfluidic techniques. We have developed a new generation of highly sensitive and specific diagnostic systems for detection of cancer antigens in human serum samples based on microbeads encoded with fluorescent quantum dots (QDs). The designed suspension microarray system was validated for quantitative detection of (1) free and total prostate specific antigen (PSA) in the serum of patients with prostate cancer and (2) carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3) in the serum of patients with breast cancer. The serum samples from healthy donors were used as a control. The antigen detection is based on the formation of an immune complex of a specific capture antibody (Ab), a target antigen (Ag), and a detector Ab on the surface of the encoded particles. The capture Ab is bound to the polymer shell of microbeads via an adapter molecule, for example, protein A. Protein A binds a monoclonal Ab in a highly oriented manner due to specific interaction with the Fc-region of the Ab molecule. Each antigen can be recognized and detected due to a specific microbead population carrying the unique fluorescent code. 100 and 231 serum samples from patients with different stages of prostate cancer and breast cancer, respectively, and those from healthy donors were examined using the designed suspension system. The data were validated by comparing with the results of the "gold standard" enzyme-linked immunosorbent assay (ELISA). They have shown that our approach is a good alternative to the diagnostics of cancer markers using conventional assays, especially in early diagnostic applications.

Stenting versus endarterectomy for restenosis following prior ipsilateral carotid endarterectomy: an individual patient data meta-analysis.

PubMed

Fokkema, Margriet; Vrijenhoek, Joyce E P; Den Ruijter, Hester M; Groenwold, Rolf H H; Schermerhorn, Marc L; Bots, Michiel L; Pasterkamp, Gerard; Moll, Frans L; De Borst, Gert Jan

2015-03-01

To study perioperative results and restenosis during follow-up of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) for restenosis after prior ipsilateral CEA in an individual patient data (IPD) meta-analysis. The optimal treatment strategy for patients with restenosis after CEA remains unknown. A comprehensive search of electronic databases (Medline, Embase) until July 1, 2013, was performed, supplemented by a review of references. Studies were considered for inclusion if they reported procedural outcome of CAS or CEA after prior ipsilateral CEA of a minimum of 5 patients. IPD were combined into 1 data set and an IPD meta-analysis was performed. The primary endpoint was perioperative stroke or death and the secondary endpoint was restenosis greater than 50% during follow-up, comparing CAS and CEA. In total, 13 studies were included, contributing to 1132 unique patients treated by CAS (10 studies, n = 653) or CEA (7 studies; n = 479). Among CAS and CEA patients, 30% versus 40% were symptomatic, respectively (P < 0.01). After adjusting for potential confounders, the primary endpoint did not differ between CAS and CEA groups (2.3% vs 2.7%, adjusted odds ratio 0.8, 95% confidence interval (CI): 0.4-1.8). Also, the risk of restenosis during a median follow-up of 13 months was similar for both groups (hazard ratio 1.4, 95% (CI): 0.9-2.2). Cranial nerve injury (CNI) was 5.5% in the CEA group, while CAS was in 5% associated with other procedural related complications. In patients with restenosis after CEA, CAS and CEA showed similar low rates of stroke, death, and restenosis at short-term follow-up. Still, the risk of CNI and other procedure-related complications should be taken into account.

Endarterectomy achieves lower stroke and death rates compared with stenting in patients with asymptomatic carotid stenosis.

PubMed

Kakkos, Stavros K; Kakisis, Ioannis; Tsolakis, Ioannis A; Geroulakos, George

2017-08-01

It is currently unclear if carotid artery stenting (CAS) is as safe as carotid endarterectomy (CEA) for patients with significant asymptomatic stenosis. The aim of our study was to perform a systematic review and meta-analysis of trials comparing CAS with CEA. On March 17, 2017, a search for randomized controlled trials was performed in MEDLINE and Scopus databases with no time limits. We performed meta-analyses with Peto odds ratios (ORs) and 95% confidence intervals (CIs). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation method. The primary safety and efficacy outcome measures were stroke or death rate at 30 days and ipsilateral stroke at 1 year (including ipsilateral stroke and death rate at 30 days), respectively. Perioperative stroke, ipsilateral stroke, myocardial infarction (MI), and cranial nerve injury (CNI) were all secondary outcome measures. The systematic review of the literature identified nine randomized controlled trials reporting on 3709 patients allocated into CEA (n = 1479) or CAS (n = 2230). Stroke or death rate at 30 days was significantly higher for CAS (64/2176 [2.94%]) compared with CEA (27/1431 [1.89%]; OR, 1.57; 95% CI, 1.01-2.44; P = .044), with low level of heterogeneity beyond chance (I 2  = 0%). Also, stroke rate at 30 days was significantly higher for CAS (63/2176 [2.90%]) than for CEA (26/1431 [1.82%]; OR, 1.63; 95% CI, 1.04-2.54; P = .032; I 2  = 0%). MI at 30 days was nonsignificantly lower for CAS (12/1815 [0.66%]) compared with CEA (16/1070 [1.50%]; OR, 0.53; 95% CI, 0.24-1.14; P = .105; I 2  = 0%); however, CNI at 30 days was significantly lower for CAS (2/1794 [0.11%]) than for CEA (33/1061 [3.21%]; OR, 0.13; 95% CI, 0.07-0.26; P < .00001; I 2  = 0%). Regarding the long-term outcome of stroke or death rate at 30 days plus ipsilateral stroke during follow-up, this was significantly higher for CAS (79/2173 [3.64%]) than for CEA (35/1430 [2.45%]; OR, 1.51; 95% CI, 1.02-2.24; P = .04; I 2  = 0%). Quality of evidence for all stroke outcomes was graded moderate. Among patients with asymptomatic stenosis undergoing carotid intervention, there is moderate-quality evidence to suggest that CEA had significantly lower 30-day stroke and also stroke or death rates compared with CAS at the cost of higher CNI and nonsignificantly higher MI rates. The long-term efficacy of CEA in ipsilateral stroke prevention, taking into account perioperative stroke and death, was preserved during follow-up. There is an urgent need for high-quality research before a firm recommendation is made that CAS is inferior or not to CEA. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Role of the oxytocin system in amygdala subregions in the regulation of social interest in male and female rats.

PubMed

Dumais, Kelly M; Alonso, Andrea G; Bredewold, Remco; Veenema, Alexa H

2016-08-25

We previously found that oxytocin (OT) receptor (OTR) binding density in the medial amygdala (MeA) correlated positively with social interest (i.e., the motivation to investigate a conspecific) in male rats, while OTR binding density in the central amygdala (CeA) correlated negatively with social interest in female rats. Here, we determined the causal involvement of OTR in the MeA and CeA in the sex-specific regulation of social interest in adult rats by injecting an OTR antagonist (5ng/0.5μl/side) or OT (100pg/0.5μl/side) before the social interest test (4-min same-sex juvenile exposure). OTR blockade in the CeA decreased social interest in males but not females, while all other treatments had no behavioral effect. To further explore the sex-specific involvement of the OT system in the CeA in social interest, we used in vivo microdialysis to determine possible sex differences in endogenous OT release in the CeA during social interest. Interestingly, males and females showed similar levels of extracellular OT release at baseline and during social interest, suggesting that factors other than local OT release mediate the sex-specific role of CeA-OTR in social interest. Moreover, we found a positive correlation between CeA-OT release and social investigation time in females. This was further reflected by reduced CeA-OT release during social interest in females that expressed low compared to high social interest. We discuss the possibility that this reduction in OT release may be a consequence, rather than a cause, of exposure to a social stimulus. Overall, our findings show for the first time that extracellular OT release in the CeA is similar between males and females and that OTR in the CeA plays a causal role in the regulation of social interest toward juvenile conspecifics in males. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325).

PubMed

Dehing-Oberije, Cary; Aerts, Hugo; Yu, Shipeng; De Ruysscher, Dirk; Menheere, Paul; Hilvo, Mika; van der Weide, Hiska; Rao, Bharat; Lambin, Philippe

2011-10-01

Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival. Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52). The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively. The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6. Copyright © 2011 Elsevier Inc. All rights reserved.

Using graphene-based plasmonic nanocomposites to quench energy from quantum dots for signal-on photoelectrochemical aptasensing.

PubMed

Zeng, Xianxiang; Ma, Shishi; Bao, Jianchun; Tu, Wenwen; Dai, Zhihui

2013-12-17

On the basis of the absorption and emission spectra overlap, an enhanced resonance energy transfer caused by excition-plasmon resonance between reduced graphene oxide (RGO)-Au nanoparticles (AuNPs) and CdTe quantum dots (QDs) was obtained. With the synergy of AuNPs and RGO as a planelike energy acceptor, it resulted in the enhancement of energy transfer between excited CdTe QDs and RGO-AuNPs nanocomposites. Upon the novel sandwichlike structure formed via DNA hybridization, the exciton produced in CdTe QDs was annihilated. A damped photocurrent was obtained, which was acted as the background signal for the development of a universal photoelectrochemical (PEC) platform. With the use of carcinoembryonic antigen (CEA) as a model which bonded to its specific aptamer and destroyed the sandwichlike structure, the energy transfer efficiency was lowered, leading to PEC response augment. Thus a signal-on PEC aptasensor was constructed. Under 470 nm irradiation at -0.05 V, the PEC aptasensor for CEA determination exhibited a linear range from 0.001 to 2.0 ng mL(-1) with a detection limit of 0.47 pg mL(-1) at a signal-to-noise ratio of 3 and was satisfactory for clinical sample detection. Since different aptamers can specifically bind to different target molecules, the designed strategy has an expansive application for the construction of versatile PEC platforms.

Systematic follow-up after curative surgery for colorectal cancer in Norway: a population-based audit of effectiveness, costs, and compliance.

PubMed

Körner, Hartwig; Söreide, Kjetil; Stokkeland, Pål J; Söreide, Jon Arne

2005-03-01

In this study, we analyzed the Norwegian guidelines for systematic follow-up after curative colorectal cancer surgery in a large single institution. Three hundred fourteen consecutive unselected patients undergoing curative surgery for colorectal cancer between 1996 and 1999 were studied with regard to asymptomatic curable recurrence, compliance with the program, and cost. Follow-up included carcinoembryonic antigen (CEA) interval measurements, colonoscopy, ultrasonography of the liver, and radiography of the chest. In 194 (62%) of the patients, follow-up was conducted according to the Norwegian guidelines. Twenty-one patients (11%) were operated on for curable recurrence, and 18 patients (9%) were disease free after curative surgery for recurrence at evaluation. Four metachronous tumors (2%) were found. CEA interval measurement had to be made most frequently (534 tests needed) to detect one asymptomatic curable recurrence. Follow-up program did not influence cancer-specific survival. Overall compliance with the surveillance program was 66%, being lowest for colonoscopy (55%) and highest for ultrasonography of the liver (85%). The total program cost was 228,117 euro (US 280,994 dollars), translating into 20,530 euro (US 25,289 dollars) for one surviving patient after surgery for recurrence. The total diagnosis yield with regard to disease-free survival after surgery for recurrence was 9%. Compliance was moderate. Whether the continuing implementation of such program and cost are justified should be debated.

An ultrasensitive luminol cathodic electrochemiluminescence immunosensor based on glucose oxidase and nanocomposites: graphene-carbon nanotubes and gold-platinum alloy.

PubMed

Jiang, Xinya; Chai, Yaqin; Yuan, Ruo; Cao, Yaling; Chen, Yingfeng; Wang, Haijun; Gan, Xianxue

2013-06-14

In the present study, a novel and ultrasensitive electrochemiluminescence (ECL) immunosensor based on luminol cathodic ECL was fabricated by using Au nanoparticles and Pt nanoparticles (nano-AuPt) electrodeposited on graphene-carbon nanotubes nanocomposite as platform for the detection of carcinoembryonic antigen (CEA). For this introduced immunosensor, graphene (GR) and single wall carbon nanotubes (CNTs) dispersed in chitosan (Chi-GR-CNTs) were firstly decorated on the bare gold electrode (GE) surface. Then nano-AuPt were electrodeposited (DpAu-Pt) on the Chi-GR-CNTs modified electrode. Subsequently, glucose oxidase (GOD) was employed to block the non-specific sites of electrode surface. When glucose was present in the working buffer solution, GOD immediately catalyzed the oxidation of glucose to in situ generate hydrogen peroxide (H2O2), which could subsequently promote the oxidation of luminol with an amplified cathodic ECL signal. The proposed immunosensor was performed at low potential (-0.1 to 0.4V) and low concentration of luminol. The CEA was determined in the range of 0.1 pg mL(-1) to 40 ng mL(-1) with a limit of detection down to 0.03 pg mL(-1) (SN(-1)=3). Moreover, with excellent sensitivity, selectivity, stability and simplicity, the as-proposed luminol-based ECL immunosensor provided great potential in clinical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Fabrication of highly catalytic silver nanoclusters/graphene oxide nanocomposite as nanotag for sensitive electrochemical immunoassay.

PubMed

Wang, Jiamian; Wang, Xiuyun; Wu, Shuo; Song, Jie; Zhao, Yanqiu; Ge, Yanqiu; Meng, Changgong

2016-02-04

Silver nanoclusters and graphene oxide nanocomposite (AgNCs/GRO) is synthesized and functionalized with detection antibody for highly sensitive electrochemical sensing of carcinoembryonic antigen (CEA), a model tumor marker involved in many cancers. AgNCs with large surface area and abundant amount of low-coordinated sites are synthesized with DNA as template and exhibit high catalytic activity towards the electrochemical reduction of H2O2. GRO is employed to assemble with AgNCs because it has large specific surface area, super electronic conductivity and strong π-π stacking interaction with the hydrophobic bases of DNA, which can further improve the catalytic ability of the AgNCs. Using AgNCs/GRO as signal amplification tag, an enzyme-free electrochemical immunosensing protocol is designed for the highly sensitive detection of CEA on the capture antibody functionalized immunosensing interface. Under optimal conditions, the designed immunosensor exhibits a wide linear range from 0.1 pg mL(-1) to 100 ng mL(-1) and a low limit of detection of 0.037 pg mL(-1). Practical sample analysis reveals the sensor has good accuracy and reproducibility, indicating the great application prospective of the AgNCs/GRO in fabricating highly sensitive immunosensors, which can be extended to the detection of various kinds of low abundance disease related proteins. Copyright © 2015 Elsevier B.V. All rights reserved.

A SPR biosensor based on signal amplification using antibody-QD conjugates for quantitative determination of multiple tumor markers

PubMed Central

Wang, Huan; Wang, Xiaomei; Wang, Jue; Fu, Weiling; Yao, Chunyan

2016-01-01

The detection of tumor markers is very important in early cancer diagnosis; however, tumor markers are usually present at very low concentrations, especially in the early stages of tumor development. Surface plasmon resonance (SPR) is widely used to detect biomolecular interactions; it has inherent advantages of being high-throughput, real-time, and label-free technique. However, its sensitivity needs essential improvement for practical applications. In this study, we developed a signal amplification strategy using antibody-quantum dot (QD) conjugates for the sensitive and quantitative detection of α-fetoprotein (AFP), carcinoembryonic antigen (CEA) and cytokeratin fragment 21-1 (CYFRA 21-1) in clinical samples. The use of a dual signal amplification strategy using AuNP-antibody and antibody-QD conjugates increased the signal amplification by 50-folds. The constructed SPR biosensor showed a detection limit as low as 0.1 ng/mL for AFP, CEA, and CYFRA 21-1. Moreover, the results obtained using this SPR biosensor were consistent with those obtained using the electrochemiluminescence method. Thus, the constructed SPR biosensor provides a highly sensitive and specific approach for the detection of tumor markers. This SPR biosensor can be expected to be readily applied for the detection of other tumor markers and can offer a potentially powerful solution for tumor screening. PMID:27615417

The U.S. Forest Service's analysis of cumulative effects to wildlife: A study of legal standards, current practice, and ongoing challenges on a National Forest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schultz, Courtney A., E-mail: courtney.schultz@colostate.edu

Cumulative effects analysis (CEA) allows natural resource managers to understand the status of resources in historical context, learn from past management actions, and adapt future activities accordingly. U.S. federal agencies are required to complete CEA as part of environmental impact assessment under the National Environmental Policy Act (NEPA). Past research on CEA as part of NEPA has identified significant deficiencies in CEA practice, suggested methodologies for handling difficult aspects of CEA, and analyzed the rise in litigation over CEA in U.S. courts. This article provides a review of the literature and legal standards related to CEA as it is donemore » under NEPA and then examines current practice on a U.S. National Forest, utilizing qualitative methods in order to provide a detailed understanding of current approaches to CEA. Research objectives were to understand current practice, investigate ongoing challenges, and identify impediments to improvement. Methods included a systematic review of a set of NEPA documents and semi-structured interviews with practitioners, scientists, and members of the public. Findings indicate that the primary challenges associated with CEA include: issues of both geographic and temporal scale of analysis, confusion over the purpose of the requirement, the lack of monitoring data, and problems coordinating and disseminating data. Improved monitoring strategies and programmatic analyses could support improved CEA practice.« less

Effect of desipramine and citalopram treatment on forced swimming test-induced changes in cocaine- and amphetamine-regulated transcript (CART) immunoreactivity in mice.

PubMed

Chung, Sung; Kim, Hee Jeong; Kim, Hyun Ju; Choi, Sun Hye; Kim, Jin Wook; Kim, Jeong Min; Shin, Kyung Ho

2014-05-01

Recent study demonstrates antidepressant-like effect of cocaine- and amphetamine-regulated transcript (CART) in the forced swimming test (FST), but less is known about whether antidepressant treatments alter levels of CART immunoreactivity (CART-IR) in the FST. To explore this possibility, we assessed the treatment effects of desipramine and citalopram, which inhibit the reuptake of norepinephrine and serotonin into the presynaptic terminals, respectively, on changes in levels of CART-IR before and after the test swim in mouse brain. Levels of CART-IR in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), and hypothalamic paraventricular nucleus (PVN) were significantly increased before the test swim by desipramine and citalopram treatments. This increase in CART-IR in the AcbSh, dBNST, and PVN before the test swim remained elevated by desipramine treatment after the test swim, but this increase in these brain areas returned to near control levels after test swim by citalopram treatment. Citalopram, but not desipramine, treatment increased levels of CART-IR in the central nucleus of the amygdala (CeA) and the locus ceruleus (LC) before the test swim, and this increase was returned to control levels after the test swim in the CeA, but not in the LC. These results suggest common and distinct regulation of CART by desipramine and citalopram treatments in the FST and raise the possibility that CART in the AcbSh, dBNST, and CeA may be involved in antidepressant-like effect in the FST.

Identification of Serum Periostin as a Potential Diagnostic and Prognostic Marker for Colorectal Cancer.

PubMed

Dong, Dong; Zhang, Lufang; Jia, Li; Ji, Wei; Wang, Zhiyong; Ren, Li; Niu, Ruifang; Zhou, Yunli

2018-06-01

Periostin (POSTN) plays an important role in numerous cancers, especially in gastrointestinal malignancy. The objective of this study was to investigate the diagnostic and prognostic role of serum POSTN in colorectal cancer (CRC). Serum periostin, together with CEA, CA19.9, CA72.4, and CA242 levels were measured in samples from 108 patients with CRC and 56 healthy controls, and their correlation with clinical characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses were used to evaluate diagnostic and prognostic significance. Serum POSTN levels were significantly higher in patients with CRC compared with healthy controls (p < 0.0001) and associated with clinical stages (p < 0.001). ROC analysis revealed that POSTN was a biomarker comparable to CEA, CA19.9, and CA72.4 to distinguish all CRC from healthy controls (AUC = 0.75). Moreover, POSTN retained its diagnostic ability for CEA-negative (AUC = 0.69) and CA19.9-negative CRC patients (AUC = 0.71). Survival analysis revealed that patients with lower serum POSTN had longer overall survival than those with high serum POSTN (p = 0.0146). Serum POSTN might be a novel diagnostic and prognostic biomarker for patients with CRC.

Regulation of gene expression in plasmid ColE1: delayed expression of the kil gene.

PubMed Central

Zhang, S P; Yan, L F; Zubay, G

1988-01-01

cea, imm, and kil are a cluster of three functionally related genes of the plasmid ColE1. The cea and kil genes are in the same inducible operon, with transcription being initiated from a promoter adjacent to the cea gene. The imm gene is located between the cea and kil genes, but it is transcribed in the opposite direction. Complementary interaction between the imm mRNA and the anti-imm sequences in the middle of the cea-kil transcript causes a pronounced delay in expression of the kil gene when the cea-kil operon is induced. A segment in the overlapping region between the cea and imm genes causes delayed expression of the kil gene in the absence of imm gene transcription. This delay effect increases the yields of colicin synthesized in induced cells. Images PMID:3142845

Linkages between childhood emotional abuse and marital satisfaction: The mediating role of empathic accuracy for hostile emotions

PubMed Central

Maneta, E.K.; Cohen, S.; Schulz, M.S.; Waldinger, R.J.

2014-01-01

Research linking childhood emotional abuse (CEA) and adult marital satisfaction has focused on individuals without sufficient attention to couple processes. Less attention has also been paid to the effects of CEA on the ability to read other’s emotions, and how this may be related to satisfaction in intimate relationships. In this study, 156 couples reported on histories of CEA, marital satisfaction and empathic accuracy of their partners’ positive and hostile emotions during discussion of conflicts in their relationships. Actor-Partner Interdependence Modeling was used to examine links between CEA and marital satisfaction, with empathic accuracy as a potential mediator. Both men’s and women’s CEA histories were linked not only with their own lower marital satisfaction but also with their partners’ lower satisfaction. Empathic accuracy for hostile emotions mediated the link between women’s CEA and their satisfaction and their partners’ satisfaction in the relationship. Findings suggest that a history of CEA is associated with difficulties with empathic accuracy, and that empathic inaccuracy in part mediates the association between CEA and adult marital dissatisfaction. PMID:25151303

Linkages between childhood emotional abuse and marital satisfaction: The mediating role of empathic accuracy for hostile emotions.

PubMed

Maneta, E K; Cohen, S; Schulz, M S; Waldinger, R J

2015-06-01

Research linking childhood emotional abuse (CEA) and adult marital satisfaction has focused on individuals without sufficient attention to couple processes. Less attention has also been paid to the effects of CEA on the ability to read other's emotions, and how this may be related to satisfaction in intimate relationships. In this study, 156 couples reported on histories of CEA, marital satisfaction and empathic accuracy of their partners' positive and hostile emotions during discussion of conflicts in their relationships. Actor-Partner Interdependence Modeling was used to examine links between CEA and marital satisfaction, with empathic accuracy as a potential mediator. Both men's and women's CEA histories were linked not only with their own lower marital satisfaction but also with their partners' lower satisfaction. Empathic accuracy for hostile emotions mediated the link between women's CEA and their satisfaction and their partners' satisfaction in the relationship. Findings suggest that a history of CEA is associated with difficulties with empathic accuracy, and that empathic inaccuracy in part mediates the association between CEA and adult marital dissatisfaction. Copyright © 2014 Elsevier Ltd. All rights reserved.

cea-kil operon of the ColE1 plasmid.

PubMed Central

Sabik, J F; Suit, J L; Luria, S E

1983-01-01

We isolated a series of Tn5 transposon insertion mutants and chemically induced mutants with mutations in the region of the ColE1 plasmid that includes the cea (colicin) and imm (immunity) genes. Bacterial cells harboring each of the mutant plasmids were tested for their response to the colicin-inducing agent mitomycin C. All insertion mutations within the cea gene failed to bring about cell killing after mitomycin C treatment. A cea- amber mutation exerted a polar effect on killing by mitomycin C. Two insertions beyond the cea gene but within or near the imm gene also prevented the lethal response to mitomycin C. These findings suggest the presence in the ColE1 plasmid of an operon containing the cea and kil genes whose product is needed for mitomycin C-induced lethality. Bacteria carrying ColE1 plasmids with Tn5 inserted within the cea gene produced serologically cross-reacting fragments of the colicin E1 molecule, the lengths of which were proportional to the distance between the insertion and the promoter end of the cea gene. Images PMID:6298187

Hidden Costs: the ethics of cost-effectiveness analyses for health interventions in resource-limited settings

PubMed Central

Rutstein, Sarah E.; Price, Joan T.; Rosenberg, Nora E.; Rennie, Stuart M.; Biddle, Andrea K.; Miller, William C.

2017-01-01

Cost-effectiveness analysis (CEA) is an increasingly appealing tool for evaluating and comparing health-related interventions in resource-limited settings. The goal is to inform decision-makers regarding the health benefits and associated costs of alternative interventions, helping guide allocation of limited resources by prioritizing interventions that offer the most health for the least money. Although only one component of a more complex decision-making process, CEAs influence the distribution of healthcare resources, directly influencing morbidity and mortality for the world’s most vulnerable populations. However, CEA-associated measures are frequently setting-specific valuations, and CEA outcomes may violate ethical principles of equity and distributive justice. We examine the assumptions and analytical tools used in CEAs that may conflict with societal values. We then evaluate contextual features unique to resource-limited settings, including the source of health-state utilities and disability weights; implications of CEA thresholds in light of economic uncertainty; and the role of external donors. Finally, we explore opportunities to help align interpretation of CEA outcomes with values and budgetary constraints in resource-limited settings. The ethical implications of CEAs in resource-limited settings are vast. It is imperative that CEA outcome summary measures and implementation thresholds adequately reflect societal values and ethical priorities in resource-limited settings. PMID:27141969

Hidden costs: The ethics of cost-effectiveness analyses for health interventions in resource-limited settings.

PubMed

Rutstein, Sarah E; Price, Joan T; Rosenberg, Nora E; Rennie, Stuart M; Biddle, Andrea K; Miller, William C

2017-10-01

Cost-effectiveness analysis (CEA) is an increasingly appealing tool for evaluating and comparing health-related interventions in resource-limited settings. The goal is to inform decision-makers regarding the health benefits and associated costs of alternative interventions, helping guide allocation of limited resources by prioritising interventions that offer the most health for the least money. Although only one component of a more complex decision-making process, CEAs influence the distribution of health-care resources, directly influencing morbidity and mortality for the world's most vulnerable populations. However, CEA-associated measures are frequently setting-specific valuations, and CEA outcomes may violate ethical principles of equity and distributive justice. We examine the assumptions and analytical tools used in CEAs that may conflict with societal values. We then evaluate contextual features unique to resource-limited settings, including the source of health-state utilities and disability weights, implications of CEA thresholds in light of economic uncertainty, and the role of external donors. Finally, we explore opportunities to help align interpretation of CEA outcomes with values and budgetary constraints in resource-limited settings. The ethical implications of CEAs in resource-limited settings are vast. It is imperative that CEA outcome summary measures and implementation thresholds adequately reflect societal values and ethical priorities in resource-limited settings.

Age-dependent effects of carotid endarterectomy or stenting on cognitive performance.

PubMed

Wasser, Katrin; Hildebrandt, Helmut; Gröschel, Sonja; Stojanovic, Tomislav; Schmidt, Holger; Gröschel, Klaus; Pilgram-Pastor, Sara M; Knauth, Michael; Kastrup, Andreas

2012-11-01

Although evidence is accumulating that age modifies the risk of carotid angioplasty and stenting (CAS) versus endarterectomy (CEA) for patients with significant carotid stenosis, the impact of age on cognition after either CEA or CAS remains unclear. In this study, we analyzed the effects of age on cognitive performance after either CEA or CAS using a comprehensive neuropsychological test battery with parallel test forms and a control group to exclude a learning effect. The neuropsychological outcomes after revascularization were determined in 19 CAS and 27 CEA patients with severe carotid stenosis. The patients were subdivided according to their median age (<68 years and ≥68 years); 27 healthy subjects served as a control group. In all patients clinical examinations, MRI scans and a neuropsychological test battery that assessed four major cognitive domains were performed immediately before, within 72 h, and 3 months after CEA or CAS. While patients <68 years of age showed no significant cognitive alteration after either CEA or CAS, a significant cognitive decline was observed in patients ≥68 years in both treatment groups (p = 0.001). Notably, this cognitive deterioration persisted in patients after CEA, whereas it was only transient in patients treated with CAS. These results demonstrate an age-dependent effect of CEA and CAS on cognitive functions. In contrast to the recently observed increased clinical complication rates in older subjects after CAS compared with CEA, CEA appears to be associated with a greater, persistent decline in cognitive performance than CAS in this subgroup of patients.

Relationship between red blood cell distribution width, bilirubin, and clinical characteristics of patients with gastric cancer.

PubMed

Wei, T-T; Wang, L-L; Yin, J-R; Liu, Y-T; Qin, B-D; Li, J-Y; Yin, X; Zhou, L; Zhong, R-Q

2017-10-01

Red blood cell distribution width (RDW) and bilirubin have been proved to be prognostic factors for various types of cancer. However, their prognostic value in patients with gastric cancer (GC) remains largely unknown. To verify whether RDW and bilirubin are prognostic factors for patients with GC, we performed a cross-sectional study to analyze the relationship between RDW, bilirubin, and the clinical characteristics of patients with GC. Medical records of all newly diagnosed and pathologically proved patients with GC admitted to Changzheng Hospital between January 2016 and July 2016 were retrospectively reviewed. The relationship between RDW, bilirubin, and the clinical characteristics of patients with GC was analyzed. A total of 144 patients with GC were enrolled. Patients with GC had significantly higher RDW than healthy controls, even after adjusting for hemoglobin, while total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were significantly decreased. Furthermore, RDW and bilirubin were significantly correlated with tumor stage, as well as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Our study indicated that RDW and bilirubin could be potential prognostic factors for patients of GC. © 2017 John Wiley & Sons Ltd.

A systematic review on the quality, validity and usefulness of current cost-effectiveness studies for treatments of neovascular age-related macular degeneration.

PubMed

Elshout, Mari; Webers, Carroll A B; van der Reis, Margriet I; Schouten, Jan S A G

2018-06-04

Ophthalmologists increasingly depend on new drugs to advance their treatment options. These options are limited by restraints on reimbursements for new and expensive drugs. These restraints are put in place through health policy decisions based on cost-effectiveness analyses (CEA). Cost-effectiveness analyses need to be valid and of good quality to support correct decisions to create new treatment opportunities. In this study, we report the quality, validity and usefulness of CEAs for therapies for nAMD. A systematic review in PubMed, EMBASE and Cochrane was performed to include CEAs. Quality and validity assessment was based on current general quality criteria and on elements that are specific to the field of ophthalmology. Forty-eight CEAs were included in the review. Forty-four CEAs did not meet four basic model quality and validity criteria specific to CEAs in the field of ophthalmology (both eyes analysed instead of one; a time horizon extending beyond 4 years; extrapolating VA and treatment intervals beyond trial data realistically; and including the costs of low-vision). Four CEAs aligned with the quality and validity criteria. In two of these CEAs bevacizumab as-needed (PRN) was more cost-effective than bevacizumab monthly; aflibercept (VIEW); or ranibizumab monthly or PRN. In two CEAs, ranibizumab (PRN or treat and extent) was dominant over aflibercept. In two other CEAs, aflibercept was either more cost-effective or dominant over ranibizumab monthly or PRN. Two of the CEAs of sufficient quality and validity show that bevacizumab PRN is the most cost-effective treatment. Comparing ranibizumab and aflibercept, either treatment can be more cost-effective depending on the assumptions used for drug prices and treatment frequencies. The majority of the published CEAs are of insufficient quality and validity. They wrongly inform decision-makers at the cost of opportunities for ophthalmologists to treat patients. As such, they may negatively influence overall patient outcomes and societal costs. For future ophthalmic treatments, CEAs need to be improved and only published when they are of sufficient quality and validity. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Contralateral occlusion is not a clinically important reason for choosing carotid artery stenting for patients with significant carotid artery stenosis.

PubMed

Brewster, Luke P; Beaulieu, Robert; Kasirajan, Karthik; Corriere, Matthew A; Ricotta, Joseph J; Patel, Siddharth; Dodson, Thomas F

2012-11-01

Contralateral carotid artery occlusion by itself carries an increased risk of stroke. Carotid endarterectomy (CEA) in the presence of contralateral carotid artery occlusion has high reported rates of perioperative morbidity and mortality. Our objective was to determine if there is a clinical benefit to patients who receive carotid artery stenting (CAS) compared to CEA in the presence of contralateral carotid artery occlusion. We conducted a retrospective medical chart review over a 4.5-year institutional experience of persons with contralateral carotid artery occlusion and ipsilateral carotid artery stenosis who underwent CAS or CEA. The main outcome measures were 30-day cardiac, stroke, and mortality rate, and midterm mortality. Of a total of 713 patients treated for carotid artery stenosis during this time period, 57 had contralateral occlusion (~8%). Thirty-nine of these patients were treated with CAS, and 18 with CEA. The most common indications for CAS were prior neck surgery (18), contralateral internal carotid occlusion (nine), and prior neck radiation (seven). The average age was 70 ± 8.5 for CEA and 66.7 ± 9.3 for CAS (P = .20). Both groups were predominantly men (CEA 12 of 18; CAS 28 of 39; P = .76), with similar prevalence of symptomatic lesions (CEA 8 of 18, CAS 20 of 39; P = .77). Two patients died within 30 days in the CAS group (5%). No deaths occurred within 30 days in the CEA group (P = .50); the mortality rate for CAS and CEA combined was 3.5%. No perioperative strokes or myocardial infarction occurred in either group. Two transient ischemic attacks occurred after CAS. At mean follow-up of 29.4 ± 16 months (CEA) and 28 ± 14.4 months (CAS; range, 1.5-48.5 months), seven deaths occurred in the CAS group and one in the CEA group (17.9% vs 5.5%; P = .40). There were two reinterventions in the CAS group for in-stent restenosis and there were no reoperations in the CEA group. Although CEA and CAS can both be performed with good perioperative results and acceptable midterm mortality, the observed outcomes do not support use of contralateral carotid artery occlusion as a selection criterion for CAS over CEA in the absence of other indications. Copyright © 2012 Society for Vascular Surgery. All rights reserved.

Activation of the Jasmonic Acid Pathway by Depletion of the Hydroperoxide Lyase OsHPL3 Reveals Crosstalk between the HPL and AOS Branches of the Oxylipin Pathway in Rice

PubMed Central

Tang, Jiuyou; Wang, Weihong; Zhang, Fengxia; Wang, Guodong; Chu, Jinfang; Yan, Cunyu; Wang, Taoqing; Chu, Chengcai; Li, Chuanyou

2012-01-01

The allene oxide synthase (AOS) and hydroperoxide lyase (HPL) branches of the oxylipin pathway, which underlie the production of jasmonates and aldehydes, respectively, function in plant responses to a range of stresses. Regulatory crosstalk has been proposed to exist between these two signaling branches; however, there is no direct evidence of this. Here, we identified and characterized a jasmonic acid (JA) overproduction mutant, cea62, by screening a rice T-DNA insertion mutant library for lineages that constitutively express the AOS gene. Map-based cloning was used to identify the underlying gene as hydroperoxide lyase OsHPL3. HPL3 expression and the enzyme activity of its product, (E)-2-hexenal, were depleted in the cea62 mutant, which resulted in the dramatic overproduction of JA, the activation of JA signaling, and the emergence of the lesion mimic phenotype. A time-course analysis of lesion formation and of the induction of defense responsive genes in the cea62 mutant revealed that the activation of JA biosynthesis and signaling in cea62 was regulated in a developmental manner, as was OsHPL3 activity in the wild-type plant. Microarray analysis showed that the JA-governed defense response was greatly activated in cea62 and this plant exhibited enhanced resistance to the T1 strain of the bacterial blight pathogen Xanthomonasoryzaepvoryzae (Xoo). The wounding response was attenuated in cea62 plants during the early stages of development, but partially recovered when JA levels were elevated during the later stages. In contrast, the wounding response was not altered during the different developmental stages of wild-type plants. These findings suggest that these two branches of the oxylipin pathway exhibit crosstalk with regards to biosynthesis and signaling and cooperate with each other to function in diverse stress responses. PMID:23209649

The preparation of ethylenediamine-modified fluorescent carbon dots and their use in imaging of cells.

PubMed

Dong, Wei; Zhou, Siqi; Dong, Yan; Wang, Jingwen; Ge, Xin; Sui, Lili

2015-09-01

In this work, fluorescent carbon dots (CDs) were synthesized using a hydrothermal method with glucose as the carbon source and were surface-modified with ethylenediamine. The properties of as-prepared CDs were analyzed by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), ultraviolet-visible light (UV/vis) absorption and fluorescent spectra. Furthermore, CDs conjugated with mouse anti-(human carcinoembryonic antigen) (CEA) monoclonal antibody were successful employed in the biolabeling and fluorescent imaging of human gastric carcinoma cells. In addition, the cytotoxicity of CDs was also tested using human gastric carcinoma cells. There was no apparent cytotoxicity on human gastric carcinoma cells. These results suggest the potential application of the as-prepared CDs in bioimaging and related fields. Copyright © 2015 John Wiley & Sons, Ltd.

Imaging of colorectal carcinoma with radiolabeled antibodies.

PubMed

Goldenberg, D M; Goldenberg, H; Sharkey, R M; Lee, R E; Higgenbotham-Ford, E; Horowitz, J A; Hall, T C; Pinsky, C M; Hansen, H J

1989-10-01

Colorectal cancer has been the tumor type most frequently studied with radiolabeled antibodies. Among the various antibodies, a majority of patients with colorectal cancer have received xenogeneic polyclonal or monoclonal antibodies against carcino-embryonic antigen. This review summarizes the current status of colorectal cancer imaging with radiolabeled antibodies, ie, radioimmunodetection (RAID), and examines the published studies involving carcinoembryonic antigen (CEA) antibodies and 17-1A, 19-9, and B72.3, and other monoclonal antibodies. In order to better address the issue of the current and future clinical usefulness of this emerging technology, particular attention is given to the protocols, methods, and results of the published studies. Despite differences in study parameters, antibodies and forms, labels, administration routes and doses, and scanning instruments and methods, it has been found that (1) almost no adverse reactions have been evident; (2) antibody fragments are preferred over whole immunoglobulin G reagents because they achieve higher tumor-to-background ratios earlier, thus reducing or precluding the need for dual-isotope subtraction methods or long delays before imaging; (3) use of antibody fragments, including the monovalent Fab' form, permits imaging with short-lived radionuclides of excellent photon properties, such as 123I and 99mTc; (4) circulating antigens against which the imaging antibody is directed can complex with the injected antibody, but such complexes have not prevented successful RAID; (5) patients with high serum titers of the appropriate antigen target usually have higher rates of positive RAID; (6) patients who are seronegative for the tumor antigen being studied can have positive RAID findings, which can represent the detection of occult lesions; (7) single photon emission computed tomography appears to provide better image resolution than planar scanning; (8) regardless of the sensitivity reported in any particular study, almost all investigators have observed the disclosure of occult neoplasms by RAID; and (9) RAID, a more functional test of usually high specificity, can complement other radiological methods, such as computed tomography scans, which are limited to structural information.

MATERNAL TRAUMA AFFECTS PRENATAL MENTAL HEALTH AND INFANT STRESS REGULATION AMONG PALESTINIAN DYADS.

PubMed

Isosävi, Sanna; Diab, Safwat Y; Kangaslampi, Samuli; Qouta, Samir; Kankaanpää, Saija; Puura, Kaija; Punamäki, Raija-Leena

2017-09-01

We examined how diverse and cumulated traumatic experiences predicted maternal prenatal mental health and infant stress regulation in war conditions and whether maternal mental health mediated the association between trauma and infant stress regulation. Participants were 511 Palestinian mothers from the Gaza Strip who reported exposure to current war trauma (WT), past childhood emotional (CEA) and physical abuse, socioeconomic status (SES), prenatal mental health problems (posttraumatic stress disorder and depression symptoms), and perceived stress during their secondtrimester of pregnancy as well as infant stress regulation at 4 months. While all trauma types were associated with high levels of prenatal symptoms, CEA had the most wide-ranging effects and was uniquely associated with depression symptoms. Concerning infant stress regulation, mothers' CEA predicted negative affectivity, but only among mothers with low WT. Against hypothesis, the effects of maternal trauma on infant stress regulation were not mediated by mental health symptoms. Mothers' higher SES was associated with better infant stress regulation whereas infant prematurity and male sex predisposed for difficulties. Our findings suggest that maternal childhood abuse, especially CEA, should be a central treatment target among war-exposed families. Cumulated psychosocial stressors might increase the risk for transgenerational problems. © 2017 Michigan Association for Infant Mental Health.

Human-Robot Cooperation with Commands Embedded in Actions

NASA Astrophysics Data System (ADS)

Kobayashi, Kazuki; Yamada, Seiji

In this paper, we first propose a novel interaction model, CEA (Commands Embedded in Actions). It can explain the way how some existing systems reduce the work-load of their user. We next extend the CEA and build ECEA (Extended CEA) model. The ECEA enables robots to achieve more complicated tasks. On this extension, we employ ACS (Action Coding System) which can describe segmented human acts and clarifies the relationship between user's actions and robot's actions in a task. The ACS utilizes the CEA's strong point which enables a user to send a command to a robot by his/her natural action for the task. The instance of the ECEA led by using the ACS is a temporal extension which has the user keep a final state of a previous his/her action. We apply the temporal extension of the ECEA for a sweeping task. The high-level task, a cooperative task between the user and the robot can be realized. The robot with simple reactive behavior can sweep the region of under an object when the user picks up the object. In addition, we measure user's cognitive loads on the ECEA and a traditional method, DCM (Direct Commanding Method) in the sweeping task, and compare between them. The results show that the ECEA has a lower cognitive load than the DCM significantly.

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

PubMed

Hege, Kristen M; Bergsland, Emily K; Fisher, George A; Nemunaitis, John J; Warren, Robert S; McArthur, James G; Lin, Andy A; Schlom, Jeffrey; June, Carl H; Sherwin, Stephen A

2017-01-01

T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 10 10 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72. Fourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111 Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed. These findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity.

Acute sleep deprivation preconditions the heart against ischemia/ reperfusion injury: the role of central GABA-A receptors

PubMed Central

Parsa, Hoda; Imani, Alireza; Faghihi, Mahdieh; Riahi, Esmail; Badavi, Mohammad; Shakoori, Abbas; Rastegar, Tayebeh; Aghajani, Marjan; Rajani, Sulail Fatima

2017-01-01

Objective(s): Central γ-aminobutyric acid (GABA) neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD) affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI), and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA) by assessing nitric oxide (NO) and oxidative stress. Materials and Methods: The CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist) administration. All animals underwent 30 min of coronary occlusion (ischemia), followed by 2 hr reperfusion (IR). The five experimental groups (n=12) included are as follows: IR: received saline; BIC+IR: received Bicuculline; MLP+IR: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD+IR: underwent ASD in an aquarium with multiple small platforms; and BIC+ASD+IR: received bicuculline prior to ASD. Results: Bicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS) gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BIC+ASD+IR as compared to the ASD+IR group. Conclusion: Blockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production. PMID:29299201

Acute sleep deprivation preconditions the heart against ischemia/ reperfusion injury: the role of central GABA-A receptors.

PubMed

Parsa, Hoda; Imani, Alireza; Faghihi, Mahdieh; Riahi, Esmail; Badavi, Mohammad; Shakoori, Abbas; Rastegar, Tayebeh; Aghajani, Marjan; Rajani, Sulail Fatima

2017-11-01

Central γ-aminobutyric acid (GABA) neurotransmission modulates cardiovascular functions and sleep. Acute sleep deprivation (ASD) affects functions of various body organs via different mechanisms. Here, we evaluated the effect of ASD on cardiac ischemia/reperfusion injury (IRI), and studied the role of GABA-A receptor inhibition in central nucleus of amygdala (CeA) by assessing nitric oxide (NO) and oxidative stress. The CeA in sixty male Wistar rats was cannulated for saline or bicuculline (GABA-A receptor antagonist) administration. All animals underwent 30 min of coronary occlusion (ischemia), followed by 2 hr reperfusion (IR). The five experimental groups (n=12) included are as follows: IR: received saline; BIC+IR: received Bicuculline; MLP+IR: received saline, followed by the placement of animals in an aquarium with multiple large platforms; ASD+IR: underwent ASD in an aquarium with multiple small platforms; and BIC+ASD+IR: received bicuculline prior to ASD. Bicuculline administration increased the malondialdehyde levels and infarct size, and decreased the NO metabolites levels and endothelial nitric oxide synthase (eNOS) gene expression in infarcted and non-infarcted areas in comparison to IR group. ASD reduced malondialdehyde levels and infarct size and increased NO metabolites, corticosterone levels and eNOS expression in infarcted and non-infarcted areas as compared to the IR group. Levels of malondialdehyde were increased while levels of NO metabolites, corticosterone and eNOS expression in infarcted and non-infarcted areas were reduced in the BIC+ASD+IR as compared to the ASD+IR group. Blockade of GABA-A receptors in the CeA abolishes ASD-induced cardioprotection by suppressing oxidative stress and NO production.

Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine.

PubMed

Warlow, Shelley M; Robinson, Mike J F; Berridge, Kent C

2017-08-30

Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target. SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central nucleus of amygdala (CeA) optogenetic stimulation with one option for earning intravenous cocaine makes that option almost the exclusive focus of intense pursuit and consumption. CeA stimulation also elevated the effort cost rats were willing to pay for cocaine and made associated cues become intensely attractive. However, we also show that CeA laser had no reinforcing properties at all when given alone for the same rats. Therefore, CeA laser pairing makes its associated cocaine option and cues become powerfully attractive in a nearly addictive fashion. Copyright © 2017 the authors 0270-6474/17/378330-19$15.00/0.

Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine

PubMed Central

2017-01-01

Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target. SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central nucleus of amygdala (CeA) optogenetic stimulation with one option for earning intravenous cocaine makes that option almost the exclusive focus of intense pursuit and consumption. CeA stimulation also elevated the effort cost rats were willing to pay for cocaine and made associated cues become intensely attractive. However, we also show that CeA laser had no reinforcing properties at all when given alone for the same rats. Therefore, CeA laser pairing makes its associated cocaine option and cues become powerfully attractive in a nearly addictive fashion. PMID:28751460

Developing appropriate methods for cost-effectiveness analysis of cluster randomized trials.

PubMed

Gomes, Manuel; Ng, Edmond S-W; Grieve, Richard; Nixon, Richard; Carpenter, James; Thompson, Simon G

2012-01-01

Cost-effectiveness analyses (CEAs) may use data from cluster randomized trials (CRTs), where the unit of randomization is the cluster, not the individual. However, most studies use analytical methods that ignore clustering. This article compares alternative statistical methods for accommodating clustering in CEAs of CRTs. Our simulation study compared the performance of statistical methods for CEAs of CRTs with 2 treatment arms. The study considered a method that ignored clustering--seemingly unrelated regression (SUR) without a robust standard error (SE)--and 4 methods that recognized clustering--SUR and generalized estimating equations (GEEs), both with robust SE, a "2-stage" nonparametric bootstrap (TSB) with shrinkage correction, and a multilevel model (MLM). The base case assumed CRTs with moderate numbers of balanced clusters (20 per arm) and normally distributed costs. Other scenarios included CRTs with few clusters, imbalanced cluster sizes, and skewed costs. Performance was reported as bias, root mean squared error (rMSE), and confidence interval (CI) coverage for estimating incremental net benefits (INBs). We also compared the methods in a case study. Each method reported low levels of bias. Without the robust SE, SUR gave poor CI coverage (base case: 0.89 v. nominal level: 0.95). The MLM and TSB performed well in each scenario (CI coverage, 0.92-0.95). With few clusters, the GEE and SUR (with robust SE) had coverage below 0.90. In the case study, the mean INBs were similar across all methods, but ignoring clustering underestimated statistical uncertainty and the value of further research. MLMs and the TSB are appropriate analytical methods for CEAs of CRTs with the characteristics described. SUR and GEE are not recommended for studies with few clusters.

Radioimmunoassay of tumor markers in serum of patients with renal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cordoni-Voutsas, M.; Glaubitt, D.; Wagner, W.

1984-01-01

Having noted an increased serum level of TPA and CEA in patients with renal carcinoma the authors extended these studies by using a larger number of tumor markers. In 15 patients (11 men and 4 women after menopause) aged 33 to 74 years who had renal carcinoma, among them 3 with tumor metastases, the serum concentration of TPA, CA 12-5, CEA, AFP, ferritin, prolactin, ..beta..-HCG, and ..beta../sub 2/-microglobulin was measured by radioimmunoassay. Monoclonal antibodies were used in the determination of serum CA 12-5 and CEA. In all patients surgical treatment, irradiation, or cytostatic therapy had not been performed. In serummore » the normal range was exceeded by TPA in 7 patients, CA 12-5 in 3, CEA and AFP in one each, ferritin in 12, prolactin in 2, and ..beta../sub 2/-microglobulin in 10 patients. In one man serum prolactin was reduced. Serum ..beta..-HCG was normal in all patients. According to these results serum ferritin, TPA, and ..beta../sub 2/-microglobulin are of great value as tumor markers in patients with renal carcinoma. In several patients the increase of serum ..beta../sub 2/-microglobulin may be ascribed partly to deterioration of renal function. As no consistent patterns of tumor markers in serum were observed it is recommended to determine several tumor markers and not only one of them during the follow-up of patients. Radioimmunoassays for measuring the serum level of tumor markers, especially ferritin, TPA, and ..beta../sub 2/-microglobulin, may considerably assist in the management of patients with renal carcinoma by providing early information about tumor recurrence or metastases.« less

Optogenetic activation of the central amygdala generates addiction-like preference for reward.

PubMed

Tom, Rebecca L; Ahuja, Aarit; Maniates, Hannah; Freeland, Charlotte M; Robinson, Mike J F

2018-05-23

Drug and behavioural addictions are characterized by an intense and focused pursuit of a single reward above all others. Pursuit of the addictive reward is often compulsively sought despite adverse consequences and better alternative outcomes. Here, we explored the ability of the central amygdala (CeA) to powerfully bias choice, causing specific rewards to be almost compulsively preferred. Rats were trained on an operant choice task in which they could choose to respond on either of the two levers to receive a sucrose reward, one of which was paired with optogenetic stimulation of the CeA using channelrhodopsin-2 (ChR2). Rats developed an almost exclusive preference for the laser-paired reward over the otherwise equal unpaired reward. We found that this preference for stimulation-paired reward persists even when a much larger sucrose reward is offered as an alternative (contingency management) or when this preferred reward is paired with adverse consequences such as progressively larger electric foot shock, time delays or effort requirements. We also report that when challenged with foot shock, a small proportion of these animals (≈20%) retained an exclusive laser-paired reward preference, whereas others began to seek the alternate reward when the shock reached high levels. Lastly, we confirmed that optogenetic CeA stimulation was not independently rewarding if delivered in the absence of a paired sucrose reward. These results suggest a role for the CeA in focusing motivation and desire to excessive levels, generating addiction-like behaviour that persists in the face of more rewarding alternatives and adverse consequences. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Developing Appropriate Methods for Cost-Effectiveness Analysis of Cluster Randomized Trials

PubMed Central

Gomes, Manuel; Ng, Edmond S.-W.; Nixon, Richard; Carpenter, James; Thompson, Simon G.

2012-01-01

Aim. Cost-effectiveness analyses (CEAs) may use data from cluster randomized trials (CRTs), where the unit of randomization is the cluster, not the individual. However, most studies use analytical methods that ignore clustering. This article compares alternative statistical methods for accommodating clustering in CEAs of CRTs. Methods. Our simulation study compared the performance of statistical methods for CEAs of CRTs with 2 treatment arms. The study considered a method that ignored clustering—seemingly unrelated regression (SUR) without a robust standard error (SE)—and 4 methods that recognized clustering—SUR and generalized estimating equations (GEEs), both with robust SE, a “2-stage” nonparametric bootstrap (TSB) with shrinkage correction, and a multilevel model (MLM). The base case assumed CRTs with moderate numbers of balanced clusters (20 per arm) and normally distributed costs. Other scenarios included CRTs with few clusters, imbalanced cluster sizes, and skewed costs. Performance was reported as bias, root mean squared error (rMSE), and confidence interval (CI) coverage for estimating incremental net benefits (INBs). We also compared the methods in a case study. Results. Each method reported low levels of bias. Without the robust SE, SUR gave poor CI coverage (base case: 0.89 v. nominal level: 0.95). The MLM and TSB performed well in each scenario (CI coverage, 0.92–0.95). With few clusters, the GEE and SUR (with robust SE) had coverage below 0.90. In the case study, the mean INBs were similar across all methods, but ignoring clustering underestimated statistical uncertainty and the value of further research. Conclusions. MLMs and the TSB are appropriate analytical methods for CEAs of CRTs with the characteristics described. SUR and GEE are not recommended for studies with few clusters. PMID:22016450

Cost-effectiveness Analysis Appraisal and Application: An Emergency Medicine Perspective.

PubMed

April, Michael D; Murray, Brian P

2017-06-01

Cost-effectiveness is an important goal for emergency care delivery. The many diagnostic, treatment, and disposition decisions made in the emergency department (ED) have a significant impact upon healthcare resource utilization. Cost-effectiveness analysis (CEA) is an analytic tool to optimize these resource allocation decisions through the systematic comparison of costs and effects of alternative healthcare decisions. Yet few emergency medicine leaders and policymakers have any formal training in CEA methodology. This paper provides an introduction to the interpretation and use of CEA with a focus on application to emergency medicine problems and settings. It applies a previously published CEA to the hypothetical case of a patient presenting to the ED with chest pain who requires risk stratification. This paper uses a widely cited checklist to appraise the CEA. This checklist serves as a vehicle for presenting basic CEA terminology and concepts. General topics of focus include measurement of costs and outcomes, incremental analysis, and sensitivity analysis. Integrated throughout the paper are recommendations for good CEA practice with emphasis on the guidelines published by the U.S. Panel on Cost-Effectiveness in Health and Medicine. Unique challenges for emergency medicine CEAs discussed include the projection of long-term outcomes from emergent interventions, costing ED services, and applying study results to diverse patient populations across various ED settings. The discussion also includes an overview of the limitations inherent in applying CEA results to clinical practice to include the lack of incorporation of noncost considerations in CEA (e.g., ethics). After reading this article, emergency medicine leaders and researchers will have an enhanced understanding of the basics of CEA critical appraisal and application. The paper concludes with an overview of economic evaluation resources for readers interested in conducting ED-based economic evaluation studies. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Stroke/Death Rates Following Carotid Artery Stenting and Carotid Endarterectomy in Contemporary Administrative Dataset Registries: A Systematic Review.

PubMed

Paraskevas, K I; Kalmykov, E L; Naylor, A R

2016-01-01

Randomised trials have reported higher stroke/death rates after carotid artery stenting (CAS) versus carotid endarterectomy (CEA). Despite this, the 2011 American Heart Association (AHA) guidelines expanded CAS indications, partly because of the Carotid Revascularization Endarterectomy versus Stenting Trial, but also because of improving outcomes in industry sponsored CAS Registries. The aim of this systematic review was: (i) to compare stroke/death rates after CAS/CEA in contemporary dataset registries, (ii) to examine whether published stroke/death rates after CAS fall within AHA thresholds, and, (iii) to see if there had been a decline (over time) in procedural risk after CAS/CEA. PubMed/Medline, Embase, and Cochrane databases were systematically searched according to the recommendations of the PRISMA statement from January 1, 2008 until February 23, 2015 for administrative dataset registries reporting outcomes after both CEA and CAS. Twenty-one registries reported outcomes involving more than 1,500,000 procedures. Stroke/death after CAS was significantly higher than after CEA in 11/21 registries (52%) involving "average risk for CEA" asymptomatic patients and in 11/18 registries (61%) involving "average risk for CEA" symptomatic patients. In another five registries, CAS was associated with higher stroke/death rates than CEA for both symptomatic and asymptomatic patients, but formal statistical comparison was not reported. CAS was associated with stroke/death rates that exceeded risk thresholds recommended by the AHA in 9/21 registries (43%) involving "average risk for CEA" asymptomatic patients and in 13/18 registries (72%) involving "average risk for CEA" symptomatic patients. In 5/18 registries (28%), the procedural risk after CAS in "average risk" symptomatic patients exceeded 10%. Data from contemporary administrative dataset registries suggest that stroke/death rates following CAS remain significantly higher than after CEA and often exceed accepted AHA thresholds. There was no evidence of a sustained decline in procedural risk after CAS. Copyright © 2015 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Application of the cultured epidermal autograft "JACE(®") for treatment of severe burns: Results of a 6-year multicenter surveillance in Japan.

PubMed

Matsumura, Hajime; Matsushima, Asako; Ueyama, Masashi; Kumagai, Norio

2016-06-01

In the 1970s, Green et al. developed a method that involved culturing keratinocyte sheets and used for treatment of burns. Since then, the take rate of cultured epidermal autograft (CEA) onto fascia, granulation tissue, or allografts has been extensively reported, while that on an artificial dermis in a large case series is not. Moreover, the contribution of CEA to patient survival has not been analyzed in a multicenter study. We conducted a 6-year multicenter surveillance on the application of the CEA "JACE(®") for treatment of burns >30% total body surface area (TBSA) across 118 Japanese hospitals. This surveillance included 216 patients and 718 graft sites for efficacy analysis. The CEA take rate at 4 weeks after grafting was evaluated, and safety was monitored until 52 weeks. In addition, the survival curve obtained in this study and the data obtained from the Tokyo Burn Unit Association (TBUA) were compared. The mean CEA take rates at week 4 were 66% (sites) and 68% (patients), and the rate on the artificial dermis was 65% for 226 sites. CEA application combined with wide split-thickness auto or patch autograft increased the CEA take rate. On comparison with the data obtained from the TBUA, which included data on individuals with burns of the same severity, CEA application was found to contribute to patient survival until 7 weeks after burn. We reported the take rate of CEA based on a 6-year multicenter surveillance. From our results, we found that the application of CEA is a useful treatment for the patients with extensive burns. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

AT1 receptor blockade in the central nucleus of the amygdala attenuates the effects of muscimol on sodium and water intake.

PubMed

Hu, B; Qiao, H; Sun, B; Jia, R; Fan, Y; Wang, N; Lu, B; Yan, J Q

2015-10-29

The blockade of the central nucleus of the amygdala (CeA) with the GABAA receptor agonist muscimol significantly reduces hypertonic NaCl and water intake by sodium-depleted rats. In the present study we investigated the effects of previous injection of losartan, an angiotensin II type-1 (AT1) receptor antagonist, into the CeA on 0.3M NaCl and water intake reduced by muscimol bilaterally injected into the same areas in rats submitted to water deprivation-partial rehydration (WD-PR) and in rats treated with the diuretic furosemide (FURO). Male Sprague-Dawley rats with stainless steel cannulas bilaterally implanted into the CeA were used. Bilateral injections of muscimol (0.2 nmol/0.5 μl, n=8 rats/group) into the CeA in WD-PR-treated rats reduced 0.3M NaCl intake and water intake, and pre-treatment of the CeA with losartan (50 μg/0.5 μl) reversed the inhibitory effect of muscimol. The negative effect of muscimol on sodium and water intake could also be blocked by pretreatment with losartan microinjected into the CeA in rats given FURO (n=8 rats/group). However, bilateral injections of losartan (50 μg/0.5 μl) alone into the CeA did not affect the NaCl or water intake. These results suggest that the deactivation of CeA facilitatory mechanisms by muscimol injection into the CeA is promoted by endogenous angiotensin II acting on AT1 receptors in the CeA, which prevents rats from ingesting large amounts of hypertonic NaCl and water. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Activation of corticotropin-releasing factor receptors from the basolateral or central amygdala increases the tonic immobility response in guinea pigs: an innate fear behavior.

PubMed

Donatti, Alberto Ferreira; Leite-Panissi, Christie Ramos Andrade

2011-11-20

The tonic immobility (TI) behavior is an innate response associated with extreme threat situations such as a predator attack. Several studies have provided evidence suggesting an important role for corticotropin-releasing factor (CRF) in the regulation of the endocrine system, defensive behaviors and behavioral responses to stress. TI has been shown to be positively correlated with the basal plasma levels of corticosterone. CRF receptors and neurons that are immunoreactive to CRF are found in many cerebral regions, especially in the amygdaloid complex. Previous reports have demonstrated the involvement of the basolateral amygdaloid (BLA) and central amygdaloid (CeA) nuclei in the TI response. In this study, we evaluated the CRF system of the BLA and the CeA in the modulation of the TI response in guinea pigs. The activation of CRF receptors in the BLA and in the CeA promoted an increase in the TI response. In contrast, the inhibition of these receptors via alpha-helical-CRF(9-41) decreased the duration of the TI response. Moreover, neither the activation nor inhibition of CRF receptors in the BLA or the CeA altered spontaneous motor activity in the open-field test. These data suggest that the activation of the CRF receptors in the BLA or the CeA probably potentiates fear and anxiety, which may be one of the factors that promote an increase in the TI behavior. Therefore, these data support the role of the CRF system in the control of emotional responses, particularly in the modulation of innate fear. Copyright © 2011 Elsevier B.V. All rights reserved.

Gender Differences in Treatment of Severe Carotid Stenosis After TIA

PubMed Central

Poisson, Sharon N.; Johnston, S. Claiborne; Sidney, Stephen; Klingman, Jeffrey G.; Nguyen-Huynh, Mai N.

2010-01-01

Background and Purpose Gender differences in carotid endarterectomy (CEA) rates after transient ischemic attack (TIA) are not well studied, though some reports suggest that eligible men are more likely to have CEA than women after stroke. Methods We retrospectively identified all patients diagnosed with TIA and ≥70% carotid stenosis on ultrasound in 2003-2004 from 19 emergency departments. Medical records were abstracted for clinical data, 90-day follow-up events including stroke, cardiovascular events or death, CEA within 6 months, and post-operative 30-day outcomes. We assessed gender as a predictor of CEA and its complications, adjusting for demographic and clinical variables, as well as time to CEA between groups. Results Of 299 patients identified, 47% were women. Women were older with higher presenting SBP and less likely to smoke or to have CAD or diabetes. Fewer women (36.4%) had CEA than men (53.8%) (p=0.004). Reasons for withholding surgical treatment were similar in women and men, and there were no differences in follow-up stroke, CV event, postoperative complications or death. Time to CEA was also significantly delayed in women. Conclusions Women with severe carotid stenosis and recent TIA are less likely to undergo CEA than men, and surgeries are more delayed. PMID:20651270

The Exploration of Peptide Biomarkers in Malignant Pleural Effusion of Lung Cancer Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry

PubMed Central

Xu, Jing; Xu, Bin; Tang, Chuanhao; Li, Xiaoyan; Qin, Haifeng; Wang, Weixia; Wang, Hong; Wang, Zhongyuan; Li, Liangliang; Li, Zhihua; Gao, Hongjun

2017-01-01

Background. Diagnoses of malignant pleural effusion (MPE) are a crucial problem in clinics. In our study, we compared the peptide profiles of MPE and tuberculosis pleural effusion (TPE) to investigate the value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in diagnosis of MPE. Material and Methods. The 46 MPE and 32 TPE were randomly assigned to training set and validation set. Peptides were isolated by weak cation exchange magnetic beads and peaks in the m/z range of 800–10000 Da were analyzed. Comparing the peptide profile between 30 MPE and 22 TPE samples in training set by ClinProTools software, we screened the specific biomarkers and established a MALDI-TOF-MS classification of MPE. Finally, the other 16 MPE and 10 TPE were included to verify the model. We additionally determined carcinoembryonic antigen (CEA) in MPE and TPE samples using electrochemiluminescent immunoassay method. Results. Five peptide peaks (917.37 Da, 4469.39 Da, 1466.5 Da, 4585.21 Da, and 3216.87 Da) were selected to separate MPE and TPE by MALDI-TOF-MS. The sensitivity, specificity, and accuracy of the classification were 93.75%, 100%, and 96.15%, respectively, after blinded test. The sensitivity of CEA was significantly lower than MALDI-TOF-MS classification (P = 0.035). Conclusions. The results indicate MALDI-TOF-MS is a potential method for diagnosing MPE. PMID:28386154

The Exploration of Peptide Biomarkers in Malignant Pleural Effusion of Lung Cancer Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry.

PubMed

Xu, Jing; Xu, Bin; Tang, Chuanhao; Li, Xiaoyan; Qin, Haifeng; Wang, Weixia; Wang, Hong; Wang, Zhongyuan; Li, Liangliang; Li, Zhihua; Gao, Hongjun; He, Kun; Liu, Xiaoqing

2017-01-01

Background . Diagnoses of malignant pleural effusion (MPE) are a crucial problem in clinics. In our study, we compared the peptide profiles of MPE and tuberculosis pleural effusion (TPE) to investigate the value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in diagnosis of MPE. Material and Methods . The 46 MPE and 32 TPE were randomly assigned to training set and validation set. Peptides were isolated by weak cation exchange magnetic beads and peaks in the m / z range of 800-10000 Da were analyzed. Comparing the peptide profile between 30 MPE and 22 TPE samples in training set by ClinProTools software, we screened the specific biomarkers and established a MALDI-TOF-MS classification of MPE. Finally, the other 16 MPE and 10 TPE were included to verify the model. We additionally determined carcinoembryonic antigen (CEA) in MPE and TPE samples using electrochemiluminescent immunoassay method. Results . Five peptide peaks (917.37 Da, 4469.39 Da, 1466.5 Da, 4585.21 Da, and 3216.87 Da) were selected to separate MPE and TPE by MALDI-TOF-MS. The sensitivity, specificity, and accuracy of the classification were 93.75%, 100%, and 96.15%, respectively, after blinded test. The sensitivity of CEA was significantly lower than MALDI-TOF-MS classification ( P = 0.035). Conclusions . The results indicate MALDI-TOF-MS is a potential method for diagnosing MPE.

Predicting malignant and tuberculous pleural effusions through demographics and pleural fluid analysis of patients.

PubMed

Valdés, Luis; San-José, Esther; Ferreiro, Lucía; Golpe, Antonio; González-Barcala, Francisco-Javier; Toubes, María E; Rodríguez-Álvarez, María X; Álvarez-Dobaño, José M; Rodríguez-Núñez, Nuria; Rábade, Carlos; Gude, Francisco

2015-04-01

The differential diagnosis of malignant and tuberculous pleural effusion is frequently difficult. The aim of our study is to determine the discrimination value of demographic parameters and different biological markers in pleural fluid. In pleural fluid obtained from 106 patients with tuberculous, 250 with malignant and 218 with miscellaneous pleural effusion, clinical and analytical parameters were analysed, applying polytomous regression analysis and the receiver operating characteristic (ROC) curves. The three groups could be differentiated using the measured markers. Age, tumour necrosing factor-alpha, lactate dehydrogenase (LDH), adenosine deaminase (ADA), C-reactive protein (CRP) and carcinoembryonic antigen (CEA) were significant predictors for discriminating tuberculous from malignant pleural effusions; nucleated cells, lymphocytes, cholesterol, LDH, ADA, CRP, CEA and CA15.3 distinguish between malignant and miscellaneous pleural effusions. The ROC areas (95% confidence interval) were, 0.973 (0.953, 0.992) for tuberculous, 0.922 (0.900, 0.943) for miscellaneous, and 0.927 (0.907, 0.948) for malignant pleural effusion. The polytomous model correctly classified a significantly high proportion of patients with tuberculosis (85.8%) and cancer (81.6%). The incorrect classification rate was 17.8%, which increased to 19.5% in the correction using bootstrap. The results obtained to estimate the probability of tuberculous and malignant pleural effusion confirm that this model achieves a high diagnostic accuracy. This model should be applied to determine which patients with a pleural effusion of unknown origin would not benefit from further invasive procedures. © 2014 John Wiley & Sons Ltd.

Clinical Trials with Oncolytic Measles Virus: Current Status and Future Prospects.

PubMed

Msaouel, Pavlos; Opyrchal, Mateusz; Dispenzieri, Angela; Peng, Kah Whye; Federspiel, Mark J; Russell, Stephen J; Galanis, Evanthia

2018-01-01

Attenuated Edmonston lineage measles virus (MV-Edm) vaccine strains can preferentially infect and lyse a wide variety of cancer cells. Oncolytic MV-Edm derivatives are genetically engineered to express the human carcinoembryonic antigen (MV-CEA virus) or the human sodium iodide symporter (MV-NIS virus) and are currently being tested in clinical trials against ovarian cancer, glioblastoma multiforme, multiple myeloma, mesothelioma, head and neck cancer, breast cancer and malignant peripheral nerve sheath tumors. This review describes the basic and preclinical data that facilitated the clinical translation of MV-Edm strains, and summarizes the clinical results of this oncolytic platform to date. Furthermore, we discuss the latest clinically relevant MV-Edm vector developments and creative strategies for future translational steps. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

PubMed

Metildi, Cristina A; Kaushal, Sharmeela; Luiken, George A; Talamini, Mark A; Hoffman, Robert M; Bouvet, Michael

2014-04-01

The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.

Influence of bioactive sulfated polysaccharide-protein complexes on hepatocarcinogenesis, angiogenesis and immunomodulatory activities.

PubMed

Matloub, Azza A; Aglan, Hadeer A; Mohamed El Souda, Sahar Salah; Aboutabl, Mona Elsayed; Maghraby, Amany Sayed; Ahmed, Hanaa H

2016-12-01

To explore the in vivo anticancer, anti-angiogenesis and immunomodulatory efficacies of the bioactive polysaccharide isolated from cold aqueous extract of Jania rubens (JCEM) and Pterocladia capillacea (PCEM) as well as hot aqueous extract of Enteromorpha intestinalis (EHEM) against hepatocellular carcinoma rat model (HCC) and to study their chemical composition. The sugars and amino acids composition of the bioactive polysaccharides of JCEM, PCEM and EHEM were determined using gas liquid chromatography and amino acid analyzer, respectively. These polysaccharide extracts (20 mg/kg b.wt. for 5 weeks) were assessed on hepatocarcinogenesis in rats and α-fetoprotein (AFP), carcinoembryonic antigen (CEA), glypican-3 (GPC-3), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) and Ig G levels were evaluated. The GLC analysis of JCEM, PCEM and EHEM polysaccharide revealed the presence of 10, 9 and 10 sugars, in addition the amino acid analyzer enable identification of 16, 15 and 15 amino acids, respectively. These polysaccharide extracts of JCEM, PCEM and EHEM produced significant decrease in serum AFP, CEA, GPC-3, HGF and VEGF compared with untreated HCC group. JCEM, PCEM and EHEM had an immunostimulatory responses by increasing the IgG levels as compared by naïve value (1.23, 1.53 and 1.17 folds), respectively. The bioactive polysaccharides in HCC induced rats improved the humoral immune response. The photomicrographs of liver tissue sections of the groups of HCC treated with polysaccharide extracts of Jania rubens and Enteromorpha intestinalis showed intact histological structure. Moreover, fractions HE1, HE4, HE7 obtained from polysaccharide of EHEM showed moderate cytotoxic activity against HepG2 in vitro with IC 50 73.1, 42.6, 76.2 μg/mL. However, fractions of PCEM and JCEM show no or weak cytotoxicity against HepG2 in vitro where the cytotoxic activity of their crude polysaccharide extract proved synergetic effect. The pronounced antitumor activity of sulfated polysaccharide-protein complexes of JCEM and EHEM is due to direct cytotoxic activity, anti-hepatocarcinogenesis, and anti-angiogenesis. In addition, JCEM, PCEM and EHEM had an immunostimulatory response and improved the humoral immune response in HCC induced rats. Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Pathologic response after preoperative therapy predicts prognosis of Chinese colorectal cancer patients with liver metastases.

PubMed

Wang, Yun; Yuan, Yun-Fei; Lin, Hao-Cheng; Li, Bin-Kui; Wang, Feng-Hua; Wang, Zhi-Qiang; Ding, Pei-Rong; Chen, Gong; Wu, Xiao-Jun; Lu, Zhen-Hai; Pan, Zhi-Zhong; Wan, De-Sen; Sun, Peng; Yan, Shu-Mei; Xu, Rui-Hua; Li, Yu-Hong

2017-10-02

Pathologic response is evaluated according to the extent of tumor regression and is used to estimate the efficacy of preoperative treatment. Several studies have reported the association between the pathologic response and clinical outcomes of colorectal cancer patients with liver metastases who underwent hepatectomy. However, to date, no data from Chinese patients have been reported. In this study, we aimed to evaluate the association between the pathologic response to pre-hepatectomy chemotherapy and prognosis in a cohort of Chinese patients. In this retrospective study, we analyzed the data of 380 liver metastases in 159 patients. The pathologic response was evaluated according to the tumor regression grade (TRG). The prognostic role of pathologic response in recurrence-free survival (RFS) and overall survival (OS) was assessed using Kaplan-Meier curves with the log-rank test and multivariate Cox models. Factors that had potential influence on pathologic response were also analyzed using multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests. Patients whose tumors achieved pathologic response after preoperative chemotherapy had significant longer RFS and OS than patients whose tumor had no pathologic response to chemotherapy (median RFS: 9.9 vs. 6.5 months, P = 0.009; median OS: 40.7 vs. 28.1 months, P = 0.040). Multivariate logistic regression and Kruskal-Wallis/Mann-Whitney U tests showed that metastases with small diameter, metastases from the left-side primary tumors, and metastases from patients receiving long-duration chemotherapy had higher pathologic response rates than their control metastases (all P < 0.05). A decrease in the serum carcinoembryonic antigen (CEA) level after preoperative chemotherapy predicted an increased pathologic response rate (P < 0.05). Although the application of targeted therapy did not significantly influence TRG scores of all cases of metastases, the addition of cetuximab to chemotherapy resulted in a higher pathologic response rate when combined with irinotecan-based regimens rather than with oxaliplatin-based regimens. We found that the evaluation of pathologic response may predict the prognosis of Chinese colorectal cancer patients with liver metastases after preoperative chemotherapy. Small tumor diameter, long-duration chemotherapy, left primary tumor, and decreased serum CEA level after chemotherapy are associated with increased pathologic response rates.

The Physiology of Fear: Reconceptualizing the Role of the Central Amygdala in Fear Learning

PubMed Central

Keifer, Orion P.; Hurt, Robert C.; Ressler, Kerry J.

2015-01-01

The historically understood role of the central amygdala (CeA) in fear learning is to serve as a passive output station for processing and plasticity that occurs elsewhere in the brain. However, recent research has suggested that the CeA may play a more dynamic role in fear learning. In particular, there is growing evidence that the CeA is a site of plasticity and memory formation, and that its activity is subject to tight regulation. The following review examines the evidence for these three main roles of the CeA as they relate to fear learning. The classical role of the CeA as a routing station to fear effector brain structures like the periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the hypothalamus will be briefly reviewed, but specific emphasis is placed on recent literature suggesting that the CeA 1) has an important role in the plasticity underlying fear learning, 2) is involved in regulation of other amygdala subnuclei, and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss the parallels of human and mouse CeA involvement in fear disorders and fear conditioning, respectively. PMID:26328883

Cerebral hyperperfusion following carotid endarterectomy: diagnostic utility of intraoperative transcranial Doppler ultrasonography compared with single-photon emission computed tomography study.

PubMed

Ogasawara, Kuniaki; Inoue, Takashi; Kobayashi, Masakazu; Endo, Hidehoko; Yoshida, Kenji; Fukuda, Takeshi; Terasaki, Kazunori; Ogawa, Akira

2005-02-01

Cerebral hyperperfusion syndrome is a rare but serious complication of carotid endarterectomy (CEA). The aim of the present study was to determine whether intraoperative blood flow velocity (BFV) monitoring in the middle cerebral artery (MCA) by using transcranial Doppler ultrasonography (TCD) could be used as a reliable technique to detect cerebral hyperperfusion following CEA by comparing findings with those of brain single photon emission CT (SPECT). Intraoperative BFV monitoring was attempted in 67 patients undergoing CEA for treatment of ipsilateral internal carotid artery (ICA) stenosis (> or =70%). Cerebral blood flow (CBF) was also assessed using SPECT, which was performed before and immediately after CEA. Intraoperative BFV monitoring was achieved in 60 patients. Of the 60 patients, post-CEA hyperperfusion (CBF increase > or =100%, compared with preoperative values) was observed in six patients. The sensitivity, specificity, and positive predictive value of the BFV increases immediately after declamping of the ICA for detecting post-CEA hyperperfusion was 100%, 94% and 67%, respectively, with a cut-off point 2.0-fold that of preclamping BFV. The sensitivity and specificity of the BFV increases at the end of the procedure for detecting post-CEA hyperperfusion were 100% for both parameters, with cut-off points of 2.0- to 2.2-fold BFV of preclamping value. Hyperperfusion syndrome developed in two patients with post-CEA hyperperfusion, but intracerebral hemorrhage did not occur. In one of these two patients, BFV monitoring was not possible because of failure to obtain an adequate bone window. Intraoperative MCA BFV monitoring by using TCD is a less reliable method to detect cerebral hyperperfusion following CEA than postoperative MCA BFV monitoring, provided adequate monitoring can be achieved.

Kappa Opioid Receptor-Mediated Dysregulation of GABAergic Transmission in the Central Amygdala in Cocaine Addiction

PubMed Central

Kallupi, Marsida; Wee, Sunmee; Edwards, Scott; Whitfield, Tim W.; Oleata, Christopher S.; Luu, George; Schmeichel, Brooke E.; Koob, George F.; Roberto, Marisa

2013-01-01

Background Studies have demonstrated an enhanced dynorphin/kappa-opioid receptor (KOR) system following repeated cocaine exposure, but few reports have focused on neuroadaptations within the central amygdala (CeA). Methods We identified KOR-related physiological changes in the CeA following escalation of cocaine self-administration in rats. We used in vitro slice electrophysiological (intracellular and whole-cell recordings) methods to assess whether differential cocaine access in either 1h (short access, ShA) or 6h (long access, LgA) sessions induced plasticity at CeA GABAergic synapses, or altered the sensitivity of these synapses to KOR agonism (U50488) or antagonism (nor-BNI). We then determined the functional effects of CeA KOR blockade in cocaine-related behaviors. Results Baseline evoked GABAergic transmission was enhanced in the CeA from ShA and LgA rats compared to cocaine-naïve rats. Acute cocaine (1 uM) application significantly decreased GABA release in all groups (naïve, ShA, and LgA rats). Application of U50488 (1 uM) significantly decreased GABAergic transmission in the CeA from naïve rats, but increased it in LgA rats. Conversely, nor-BNI (200 nM) significantly increased GABAergic transmission in the CeA from naïve rats, but decreased it in LgA rats. Nor-BNI did not alter the acute cocaine-induced inhibition of GABAergic responses. Finally, CeA microinfusion of nor-BNI blocked cocaine-induced locomotor sensitization and attenuated the heightened anxiety-like behavior observed during withdrawal from chronic cocaine exposure in the defensive burying paradigm. Conclusion Together these data demonstrate that CeA dynorphin/KOR systems are dysregulated following excessive cocaine exposure and suggest KOR antagonism as a viable therapeutic strategy for cocaine addiction. PMID:23751206

Multicenter experience on eversion versus conventional carotid endarterectomy in symptomatic carotid artery stenosis: observations from the Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE-1) trial.

PubMed

Demirel, Serdar; Attigah, Nicolas; Bruijnen, Hans; Ringleb, Peter; Eckstein, Hans-Henning; Fraedrich, Gustav; Böckler, Dittmar

2012-07-01

Carotid endarterectomy (CEA) is beneficial in patients with symptomatic carotid artery stenosis. However, randomized trials have not provided evidence concerning the optimal CEA technique, conventional or eversion. The outcome of 563 patients within the surgical randomization arm of the Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE-1) trial was analyzed by surgical technique subgroups: eversion endarterectomy versus conventional endarterectomy with patch angioplasty. The primary end point was ipsilateral stroke or death within 30 days after surgery. Secondary outcome events included perioperative adverse events and the 2-year risk of restenosis, stroke, and death. Both groups were similar in terms of demographic and other baseline clinical variables. Shunt frequency was higher in the conventional CEA group (65% versus 17%; P<0.0001). The risk of ipsilateral stroke or death within 30 days after surgery was significantly greater with eversion CEA (9% versus 3%; P=0.005). There were no statistically significant differences in the rate of perioperative secondary outcome events with the exception of a significantly higher risk of intraoperative ipsilateral stroke rate in the eversion CEA group (4% versus 0.3%; P=0.0035). The 2-year risk of ipsilateral stroke occurring after 30 days was significantly higher in the conventional CEA group (2.9% versus 0%; P=0.017). In patients with symptomatic carotid artery stenosis, conventional CEA appears to be associated with better periprocedural neurological outcome than eversion CEA. Eversion CEA, however, may be more effective for long-term prevention of ipsilateral stroke. These findings should be interpreted with caution noting the limitations of the post hoc, nonrandomized nature of the analysis.

Highly sensitive detection of multiple tumor markers for lung cancer using gold nanoparticle probes and microarrays.

PubMed

Gao, Wanlei; Wang, Wentao; Yao, Shihua; Wu, Shan; Zhang, Honglian; Zhang, Jishen; Jing, Fengxiang; Mao, Hongju; Jin, Qinghui; Cong, Hui; Jia, Chunping; Zhang, Guojun; Zhao, Jianlong

2017-03-15

Assay of multiple serum tumor markers such as carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen (CYFRA21-1), and neuron specific enolase (NSE), is important for the early diagnosis of lung cancer. Dickkopf-1 (DKK1), a novel serological and histochemical biomarker, was recently reported to be preferentially expressed in lung cancer. Four target proteins were sandwiched by capture antibodies attached to microarrays and detection antibodies carried on modified gold nanoparticles. Optical signals generated by the sandwich structures were amplified by gold deposition with HAuCl 4 and H 2 O 2 , and were observable by microscopy or the naked eye. The four tumor markers were subsequently measured in 106 lung cancer patients and 42 healthy persons. The assay was capable of detecting multiple biomarkers in serum sample at concentration of <1 ng mL -1 in 1 h. Combined detection of the four tumor markers highly improved the sensitivity (to 87.74%) for diagnosis of lung cancer compared with sensitivity of single markers. A rapid, highly sensitive co-detection method for multiple biomarkers based on gold nanoparticles and microarrays was developed. In clinical use, it would be expected to improve the early diagnosis of lung cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

[A case of gastric metastasis and carcinomatous peritonitis of breast cancer with improved QOL by stent implantation and gemcitabine].

PubMed

Mukaibashi, Tomoe; Kojima, Izumi; Yamanaka, Ayumi; Nishiyama, Sachiko; Yamanaka, Takashi; Nakayama, Hirotaka; Matsuura, Hitoshi; Matsuzu, Kenichi; Inaba, Masaaki; Yoshida, Akira; Shimizu, Satoru

2013-08-01

A 73-year-old woman had undergone mastectomy for left breast cancer. One year later, bone metastasis was detected. After 7 years, the patient experienced epigastric discomfort, and gastrointestinal endoscopy showed stenosis of the pylorus and enlarged gastric folds. Stomach cancer was suspected at first, but gastric metastasis of breast cancer was diagnosed on the basis of endoscopic reexamination and computed tomography(CT)images. The patient could not drink water, and therefore, gastrointestinal stenting was performed, which facilitated ingestion to some extent. However, at the same time, an elevated serum carcinoembryonic antigen(CEA)level and jaundice were observed. Therefore, biliary tract stenosis due to carcinomatous peritonitis was diagnosed. We attempted to treat the jaundice with endoscopic retrograde cholangiopancreatography( ERCP)or percutaneous transhepatic cholangiography(PTCD), but the treatment was not successful, and an increase in ascites was noted. Accordingly, gemcitabine was administered as systemic therapy. As a result, ascites decreased and jaundice improved. Patients with gastric metastasis of breast cancer have poor quality of life(QOL)because of difficulties in ingestion or vomiting, and poor prognoses, because of frequent concurrent carcinomatous peritonitis. We experienced a case of gastric metastasis and carcinomatous peritonitis, and were able to improve the patient's QOL by gastrointestinal stenting and gemcitabine administration.

DNA Methylation Analysis of the SHOX2 and RASSF1A Panel in Bronchoalveolar Lavage Fluid for Lung Cancer Diagnosis

PubMed Central

Zhang, Chenzi; Yu, Wenjun; Wang, Lin; Zhao, Mingna; Guo, Qiaomei; Lv, Shaogang; Hu, Xiaomeng; Lou, Jiatao

2017-01-01

Introduction: Currently the majority of lung cancer patients are diagnosed as advanced diseases for no sensitive and specific biomarkers exist, noninvasive biomarkers with high sensitivity and specificity are urgently needed in lung cancer diagnosis. Bronchoscopy is a standard procedure of the diagnostic work-up of patients with suspected lung cancer despite of the limited diagnostic accuracy. Besides, epigenetic changes through DNA methylation play an important role in tumorigenesis. Thus, we examined the aberrant methylation of the SHOX2 and RASSF1A in bronchoalveolar lavage fluid (BALF) in comparing with conventional cytology examination and serum CEA in order to evaluate the new diagnostic method. Patients and Methods: BALF and serum samples were collected from 322 patients at the time of diagnosis, 284 of them were pathologically confirmed lung cancer, 35 were benign lung diseases and 3 were malignancies in other systems. For all of the 322 patients, the methylation status of the SHOX2 and RASSF1A gene were detected by a new RT-PCR platform and then confirmed by sanger sequencing. Serum CEA were detected using electrochemiluminescence immunoassay. Results: Profiling data showed the consistency of RT-PCR and sanger sequencing in detecting the methylation of the SHOX2 and RASSF1A. Besides, the combination of SHOX2 and RASSF1A methylation in BALF yielded a diagnostic sensitivity of 81.0% and specificity of 97.4%. When compared with established cytology examination (sensitivity: 68.3%, specificity: 97.4%) and serum biomarker carcinoembryonic antigen (CEA) (sensitivity: 30.6%, specificity: 100.0%), the SHOX2 and RASSF1A methylation panel showed the highest diagnostic efficiency. Notably, the combination of cytology and the SHOX2 and RASSF1A methylation panel could significantly improve the diagnostic efficacy. Conclusion: The methylation analysis of the SHOX2 and RASSF1A panel in BALF with RT-PCR achieved a satisfactory sensitivity and specificity in lung cancer diagnosis, especially in an early stage. It could be used as a promising noninvasive biomarker for auxiliary diagnosis of lung cancer. PMID:29151944

Engineering a Single Chain Fv Antibody to αvβ6 Integrin using the Specificity-Determining Loop of a Foot-and-Mouth Disease Virus

PubMed Central

Kogelberg, Heide; Tolner, Berend; Thomas, Gareth J.; Di Cara, Danielle; Minogue, Shane; Ramesh, Bala; Sodha, Serena; Marsh, Dan; Lowdell, Mark W.; Meyer, Tim; Begent, Richard H.J.; Hart, Ian; Marshall, John F; Chester, Kerry

2010-01-01

Summary The αvβ6 integrin is a promising target for cancer therapy. Its expression is up-regulated de novo on many types of carcinoma where it may activate transforming growth factor-β1 and transforming growth factor-β3, interact with the specific extracellular matrix proteins and promote migration and invasion of tumour cells. The viral protein 1 (VP1) coat protein of the O1 British field strain serotype of foot-and-mouth disease virus is a high-affinity ligand for αvβ6, and we recently reported that a peptide derived from VP1 exhibited αvβ6-specific binding in vitro and in vivo. We hypothesized that this peptide could confer binding specificity of an antibody to αvβ6. A 17-mer peptide of VP1 was inserted into the complementary-determining region H3 loop of MFE-23, a murine single-chain Fv (scFv) antibody reactive with carcinoembryonic antigen (CEA). The resultant scFv (B6-1) bound to αvβ6 but retained residual reactivity with CEA. This was eliminated by point mutation (Y100bP) in the variable heavy-chain domain to create an scFv (B6-2) that was as structurally stable as MFE-23 and reacted specifically with αvβ6 but not α5β1, αvβ3, αvβ5, αvβ8 or CEA. B6-2 was internalized into αvβ6-expressing cells and inhibited αvβ6-dependent migration of carcinoma cells. B6-2 was subsequently humanized. The humanized form (B6-3) was obtained as a non-covalent dimer from secretion in Pichia pastoris (115 mg/l) and was a potent inhibitor of αvβ6-mediated cell adhesion. Thus, we have used a rational stepwise approach to create a humanized scFv with therapeutic potential to block αvβ6-mediated cancer cell invasion or to deliver and internalize toxins specifically to αvβ6-expressing tumours. PMID:18656482

Cost-effectiveness modelling in diagnostic imaging: a stepwise approach.

PubMed

Sailer, Anna M; van Zwam, Wim H; Wildberger, Joachim E; Grutters, Janneke P C

2015-12-01

Diagnostic imaging (DI) is the fastest growing sector in medical expenditures and takes a central role in medical decision-making. The increasing number of various and new imaging technologies induces a growing demand for cost-effectiveness analysis (CEA) in imaging technology assessment. In this article we provide a comprehensive framework of direct and indirect effects that should be considered for CEA in DI, suitable for all imaging modalities. We describe and explain the methodology of decision analytic modelling in six steps aiming to transfer theory of CEA to clinical research by demonstrating key principles of CEA in a practical approach. We thereby provide radiologists with an introduction to the tools necessary to perform and interpret CEA as part of their research and clinical practice. • DI influences medical decision making, affecting both costs and health outcome. • This article provides a comprehensive framework for CEA in DI. • A six-step methodology for conducting and interpreting cost-effectiveness modelling is proposed.

Influence of Preoperative Risk Factors on Outcome After Carotid Endarterectomy

PubMed Central

Sternbergh, W. Charles; Money, Samuel R.

2003-01-01

As supported by level 1 multicenter randomized trial data, carotid endarterectomy (CEA) has a very low risk of perioperative morbidity and excellent durability, and provides significant long-term reductions of the risk of stroke. At Ochsner, our 1.1% risk of major stroke or death after CEA (n=366) is a demonstration of the safety of this procedure in experienced hands. This treatment modality continues to be the gold standard for most patients with carotid artery occlusive disease. Almost half of these patients treated with CEA were considered “high-risk” as defined by ineligibility for past or present randomized carotid trials. Importantly, these “high-risk” patients had outcomes that were not statistically different from “low-risk” trial-eligible patients. Thus, evidence-based decision-making does not support the routine use of investigational carotid stenting in “high-risk” trial-ineligible patients. However, carotid stenting is clearly a valuable alternative for selected patients. Our challenge is to precisely define which patients will most benefit from medical, surgical, or catheter-based therapy for carotid artery occlusive disease. PMID:22470252

First experience using cultured epidermal autografts in Taiwan for burn victims of the Formosa Fun Coast Water Park explosion, as part of Japanese medical assistance.

PubMed

Matsumura, Hajime; Harunari, Nobuyuki; Ikeda, Hiroto

2016-05-01

On June 27, 2015, a flammable starch-based powder exploded at Formosa Fun Coast in Taipei, Taiwan, injuring 499 people, and more than 200 people were in critical condition with severe burns. Although a cultured epidermal autograft (CEA) was not approved or used in clinical practice, the Taiwan Food and Drug Administration requested a Japanese CEA manufacturer to donate CEA for the burn victims as part of international medical assistance. The authors cooperated in this project and participated in the patient selection, wound bed management for CEA, and technical assistance for CEA use. Here, we provide an overview of the project. Nine patients were enrolled, and two patients were excluded from the skin biopsy; seven skin biopsies were collected approximately 1 month after the disaster. The average TBSA% burned was 81.0%, and the mean age was 20.1 years. CEA was grafted in five patients; wound closure had been obtained in one patient, and one patient was severely ill at the time of grafting. The CEA was combined with a wide split auto mesh graft or patch graft. The mean re-epithelization rate at 4 weeks after the grafting was 84.2% by patient, and all of the patients survived. Although this project had many obstacles to overcome, CEA grafting was successful and contributed to wound closure and survival. Copyright © 2015 Elsevier Ltd and ISBI. All rights reserved.

TU-CD-BRB-09: Prediction of Chemo-Radiation Outcome for Rectal Cancer Based On Radiomics of Tumor Clinical Characteristics and Multi-Parametric MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nie, K; Yue, N; Shi, L

2015-06-15

Purpose: To evaluate the tumor clinical characteristics and quantitative multi-parametric MR imaging features for prediction of response to chemo-radiation treatment (CRT) in locally advanced rectal cancer (LARC). Methods: Forty-three consecutive patients (59.7±6.9 years, from 09/2013 – 06/2014) receiving neoadjuvant CRT followed by surgery were enrolled. All underwent MRI including anatomical T1/T2, Dynamic Contrast Enhanced (DCE)-MRI and Diffusion-Weighted MRI (DWI) prior to the treatment. A total of 151 quantitative features, including morphology/Gray Level Co-occurrence Matrix (GLCM) texture from T1/T2, enhancement kinetics and the voxelized distribution from DCE-MRI, apparent diffusion coefficient (ADC) from DWI, along with clinical information (carcinoembryonic antigen CEA level,more » TNM staging etc.), were extracted for each patient. Response groups were separated based on down-staging, good response and pathological complete response (pCR) status. Logistic regression analysis (LRA) was used to select the best predictors to classify different groups and the predictive performance were calculated using receiver operating characteristic (ROC) analysis. Results: Individual imaging category or clinical charateristics might yield certain level of power in assessing the response. However, the combined model outperformed than any category alone in prediction. With selected features as Volume, GLCM AutoCorrelation (T2), MaxEnhancementProbability (DCE-MRI), and MeanADC (DWI), the down-staging prediciton accuracy (area under the ROC curve, AUC) could be 0.95, better than individual tumor metrics with AUC from 0.53–0.85. While for the pCR prediction, the best set included CEA (clinical charateristics), Homogeneity (DCE-MRI) and MeanADC (DWI) with an AUC of 0.89, more favorable compared to conventional tumor metrics with an AUC ranging from 0.511–0.79. Conclusion: Through a systematic analysis of multi-parametric MR imaging features, we are able to build models with improved predictive value over conventional imaging or clinical metrics. This is encouraging, suggesting the wealth of imaging radiomics should be further explored to help tailor the treatment into the era of personalized medicine. This work is supported by the National Science Foundation of China (NSFC Grant No. 81201091), National High Technology Research and Development Program of China (863 program, Grant No. 2015AA020917), and Fund Project for Excellent Abroad Scholar Personnel in Science and Technology.« less

[Clinical and neurophysiological aspects of severe forms of autism in children].

PubMed

Simashkova, N V; Iakupova, L P; Bashina, V M

2006-01-01

The aim of the study was to elucidate fundamentals for the phenomenon of universality of childhood autism by comparison of clinical and neurophysiological features of its severest forms--children endogenous autism (CEA) and Rett's syndrome (RS). Each group included 20 patients. Both groups were similar by age-at-disease-onset, clinical appearances during the disease course and dynamics of psychopathological syndromes. The theta-rhythm is common for CEA and RS at the disease stage with marked signs of disease acuity, autism, regress and, therefore, may be regarded as a marker of severity and development delay. The universality of autism phenomenon in its severe forms was confirmed both at the clinical and neurophysiological levels.

Two-Level Weld-Material Homogenization for Efficient Computational Analysis of Welded Structure Blast-Survivability

NASA Astrophysics Data System (ADS)

Grujicic, M.; Arakere, G.; Hariharan, A.; Pandurangan, B.

2012-06-01

The introduction of newer joining technologies like the so-called friction-stir welding (FSW) into automotive engineering entails the knowledge of the joint-material microstructure and properties. Since, the development of vehicles (including military vehicles capable of surviving blast and ballistic impacts) nowadays involves extensive use of the computational engineering analyses (CEA), robust high-fidelity material models are needed for the FSW joints. A two-level material-homogenization procedure is proposed and utilized in this study to help manage computational cost and computer storage requirements for such CEAs. The method utilizes experimental (microstructure, microhardness, tensile testing, and x-ray diffraction) data to construct: (a) the material model for each weld zone and (b) the material model for the entire weld. The procedure is validated by comparing its predictions with the predictions of more detailed but more costly computational analyses.

Generalized cost-effectiveness analysis for national-level priority-setting in the health sector

PubMed Central

Hutubessy, Raymond; Chisholm, Dan; Edejer, Tessa Tan-Torres

2003-01-01

Cost-effectiveness analysis (CEA) is potentially an important aid to public health decision-making but, with some notable exceptions, its use and impact at the level of individual countries is limited. A number of potential reasons may account for this, among them technical shortcomings associated with the generation of current economic evidence, political expediency, social preferences and systemic barriers to implementation. As a form of sectoral CEA, Generalized CEA sets out to overcome a number of these barriers to the appropriate use of cost-effectiveness information at the regional and country level. Its application via WHO-CHOICE provides a new economic evidence base, as well as underlying methodological developments, concerning the cost-effectiveness of a range of health interventions for leading causes of, and risk factors for, disease. The estimated sub-regional costs and effects of different interventions provided by WHO-CHOICE can readily be tailored to the specific context of individual countries, for example by adjustment to the quantity and unit prices of intervention inputs (costs) or the coverage, efficacy and adherence rates of interventions (effectiveness). The potential usefulness of this information for health policy and planning is in assessing if current intervention strategies represent an efficient use of scarce resources, and which of the potential additional interventions that are not yet implemented, or not implemented fully, should be given priority on the grounds of cost-effectiveness. Health policy-makers and programme managers can use results from WHO-CHOICE as a valuable input into the planning and prioritization of services at national level, as well as a starting point for additional analyses of the trade-off between the efficiency of interventions in producing health and their impact on other key outcomes such as reducing inequalities and improving the health of the poor. PMID:14687420

Generalized cost-effectiveness analysis for national-level priority-setting in the health sector.

PubMed

Hutubessy, Raymond; Chisholm, Dan; Edejer, Tessa Tan-Torres

2003-12-19

Cost-effectiveness analysis (CEA) is potentially an important aid to public health decision-making but, with some notable exceptions, its use and impact at the level of individual countries is limited. A number of potential reasons may account for this, among them technical shortcomings associated with the generation of current economic evidence, political expediency, social preferences and systemic barriers to implementation. As a form of sectoral CEA, Generalized CEA sets out to overcome a number of these barriers to the appropriate use of cost-effectiveness information at the regional and country level. Its application via WHO-CHOICE provides a new economic evidence base, as well as underlying methodological developments, concerning the cost-effectiveness of a range of health interventions for leading causes of, and risk factors for, disease.The estimated sub-regional costs and effects of different interventions provided by WHO-CHOICE can readily be tailored to the specific context of individual countries, for example by adjustment to the quantity and unit prices of intervention inputs (costs) or the coverage, efficacy and adherence rates of interventions (effectiveness). The potential usefulness of this information for health policy and planning is in assessing if current intervention strategies represent an efficient use of scarce resources, and which of the potential additional interventions that are not yet implemented, or not implemented fully, should be given priority on the grounds of cost-effectiveness.Health policy-makers and programme managers can use results from WHO-CHOICE as a valuable input into the planning and prioritization of services at national level, as well as a starting point for additional analyses of the trade-off between the efficiency of interventions in producing health and their impact on other key outcomes such as reducing inequalities and improving the health of the poor.

Aberrant histone deacetylase2-mediated histone modifications and synaptic plasticity in the amygdala predisposes to anxiety and alcoholism.

PubMed

Moonat, Sachin; Sakharkar, Amul J; Zhang, Huaibo; Tang, Lei; Pandey, Subhash C

2013-04-15

Epigenetic mechanisms have been implicated in psychiatric disorders, including alcohol dependence. However, the epigenetic basis and role of specific histone deacetylase (HDAC) isoforms in the genetic predisposition to anxiety and alcoholism is unknown. We measured amygdaloid HDAC activity, levels of HDAC isoforms, and histone H3 acetylation in selectively bred alcohol-preferring (P) and -nonpreferring (NP) rats. We employed HDAC2 small interfering RNA infusion into the central nucleus of amygdala (CeA) of P rats to determine the causal role of HDAC2 in anxiety-like and alcohol-drinking behaviors. Chromatin immunoprecipitation analysis was performed to examine the histone acetylation status of brain-derived neurotrophic factor (Bdnf) and activity-regulated cytoskeleton associated protein (Arc) genes. Golgi-Cox staining was performed to measure dendritic spine density. We found that P rats innately display higher nuclear HDAC activity and HDAC2 but not HDAC 1, 3, 4, 5, and 6 protein levels and lower acetylation of H3-K9 but not H3-K14, in the CeA and medial nucleus of amygdala compared with NP rats. Acute ethanol exposure decreased amygdaloid HDAC activity and HDAC2 protein levels, increased global and gene (Bdnf and Arc)-specific histone acetylation, and attenuated anxiety-like behaviors in P rats but had no effects in NP rats. The HDAC2 knockdown in the CeA attenuated anxiety-like behaviors and voluntary alcohol but not sucrose consumption in P rats and increased histone acetylation of Bdnf and Arc with a resultant increase in protein levels that correlated with increased dendritic spine density. These novel data demonstrate the role of HDAC2-mediated epigenetic mechanisms in anxiety and alcoholism. Published by Elsevier Inc.

Comparison of carotid endarterectomy and stenting in real world practice using a regional quality improvement registry

PubMed Central

Nolan, Brian W.; De Martino, Randall R.; Goodney, Philip P.; Schanzer, Andres; Stone, David H.; Butzel, David; Kwolek, Christopher J.; Cronenwett, Jack L.

2013-01-01

Objective Carotid artery stenting (CAS) vs endarterectomy (CEA) remains controversial and has been the topic of recent randomized controlled trials. The purpose of this study was to compare the practice and outcomes of CAS and CEA in a real world setting. Methods This is a retrospective analysis of 7649 CEA and 430 CAS performed at 17 centers from 2003 to 2010 within the Vascular Study Group of New England (VSGNE). The primary outcome measures were (1) any in-hospital stroke or death and (2) any stroke, death, or myocardial infarction (MI). Patients undergoing CEA in conjunction with cardiac surgery were excluded. Multivariate logistic regression was performed to identify predictors of stroke or death in patients undergoing CAS. Results CEA was performed in 17 centers by 111 surgeons, while CAS was performed in 6 centers by 30 surgeons and 8 interventionalists. Patient characteristics varied by procedure. Patients undergoing CAS had a higher prevalence of coronary artery disease, congestive heart failure, diabetes, and prior ipsilateral CEA. Embolic protection was used in 97% of CAS. Shunts were used in 48% and patches in 86% of CEA. The overall in-hospital stroke or death rate was higher among patients undergoing CAS (2.3% vs 1.1%; P = .03). Overall stroke, death, or MI (2.8% CAS vs 2.1% CEA; P = .32) were not different. Asymptomatic patients had similar rates of stroke or death (CAS 0.73% vs CEA 0.89%; P = .78) and stroke, death, or MI (CAS 1.1% vs CEA 1.8%; P = .40). Symptomatic patients undergoing CAS had higher rates of stroke or death (5.1% vs 1.6%; P = .001), and stroke, death, or MI (5.8% vs 2.7%; P = .02). By multivariate analysis, major stroke (odds ratio, 4.5; 95% confidence interval [CI], 1.9–10.8), minor stroke (2.7; CI, 1.5–4.8), prior ipsilateral CEA (3.2, CI, 1.7–6.1), age >80 (2.1; CI, 1.3–3.4), hypertension (2.6; CI, 1.0–6.3), and a history of chronic obstructive pulmonary disease (1.6; CI, 1.0–2.4) were predictors of stroke or death in patients undergoing carotid revascularization. Conclusions In our regional vascular surgical practices, the overall outcomes of CAS and CEA are similar for asymptomatic patients. However, symptomatic patients treated with CAS are at a higher risk for stroke or death. (J Vasc Surg 2012;56:990-6.) PMID:22579135

Amygdala c-Fos induction corresponds to unconditioned and conditioned aversive stimuli but not to freezing.

PubMed

Holahan, Matthew R; White, Norman M

2004-06-04

These experiments examined the relationship between freezing and c-Fos expression in the amygdala. In Experiment 1 freezing was elevated during a period immediately following shock in rats that remained in the shock context, but not in rats that were moved to a different, neutral context. The two groups showed equally elevated c-Fos levels in both the central (CeA) and lateral (LA) nuclei. In Experiment 2 rats were shocked in one compartment (paired) and not shocked in another, distinct compartment (unpaired). Rats re-exposed to the paired compartment 24h later froze more than rats exposed to the unpaired compartment, and rats in both groups froze more than un-shocked rats. c-Fos protein expression in CeA, LA and basolateral (BLA) nucleus was elevated in the rats exposed to the paired compartment but not in rats exposed to the unpaired compartment. Thus, c-Fos expression was induced by exposure to both unconditioned and conditioned stimuli, although it is unclear if the same cell population was activated in both cases. Neither case of c-Fos expression coincided with the occurrence of freezing. c-Fos expression may represent neural activity in LA and CeA produced by exposure to unconditioned cues and activity in BLA, LA and CeA produced by conditioned cues. This activity may contribute to an aversive affective state (or "fear"). Behaviors promoted by this state, such as freezing, may be mediated in other brain areas, or by other neurons in the amygdala.

76 FR 41375 - Retail Foreign Exchange Transactions

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-14

... retail customers. The rule also describes various requirements with which national banks, Federal... section 2(c)(2)(B)(i)(I) of the CEA with a retail customer \\5\\ except pursuant to a rule or regulation of... the CEA. \\3\\ The CEA defines ``financial institution'' as including ``a depository institution (as...

Identity and relatedness as mediators between child emotional abuse and adult couple adjustment in women.

PubMed

Bigras, Noémie; Godbout, Natacha; Hébert, Martine; Runtz, Marsha; Daspe, Marie-Ève

2015-12-01

The empirical literature indicates that childhood emotional abuse (CEA) produces long lasting impairments in interpersonal relatedness and identity, often referred to as self-capacities. CEA has also been shown to negatively impact couple functioning. This study examined the role of identity and interpersonal conflicts in mediating the relationship between CEA and women's report of couple adjustment among 184 French Canadian women from the general population. Path analysis revealed that CEA was related to poorer couple adjustment through its impact on dysfunctional self-capacities and the experience of greater conflicts in relationships. Findings highlight the importance of assessing CEA to better explain couple adjustment in women with relationship difficulties and provide potential intervention targets based on the self-capacities framework. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Sensitivity, specificity and prognostic value of CEA in colorectal cancer: results of a Tunisian series and literature review].

PubMed

Bel Hadj Hmida, Y; Tahri, N; Sellami, A; Yangui, N; Jlidi, R; Beyrouti, M I; Krichen, M S; Masmoudi, H

2001-01-01

In order to determine the sensitivity of CEA in the diagnosis of colo-rectal carcinoma, we studied a series of 48 patients with colo-rectal carcinoma (1992-1996). The sensitivity was at 52% with a reference value of 5 ng/ml and 68.7% for a reference value of 2.5 ng/ml. With a reference value of 5 ng/ml, the sensitivity of CEA was at 37% only for patients with colo-rectal carcinoma at Dukes B stage, 66.6% for patients at stage C and 75% for patients at stage D. The dosage of CEA was carried out with a sandwich immunoenzymatic technique in tube. There is no statistic significant correlation between the pre-operative rate of CEA and the localisation of the tumor and its histologic type; in contrast, it was significantly correlated with the ganglionnary metastasis. A significant relationship between the pre-operative rate of CEA and the Dukes stage was found for a reference value of 10 ng/ml but not for a reference value of 5 ng/ml. We calculated the specificity of the CEA for the cancers of colon and rectum which was at 76.98% with a reference value of 5 ng/ml and 86% with a reference value of 10 ng/ml.

The Physiology of Fear: Reconceptualizing the Role of the Central Amygdala in Fear Learning.

PubMed

Keifer, Orion P; Hurt, Robert C; Ressler, Kerry J; Marvar, Paul J

2015-09-01

The historically understood role of the central amygdala (CeA) in fear learning is to serve as a passive output station for processing and plasticity that occurs elsewhere in the brain. However, recent research has suggested that the CeA may play a more dynamic role in fear learning. In particular, there is growing evidence that the CeA is a site of plasticity and memory formation, and that its activity is subject to tight regulation. The following review examines the evidence for these three main roles of the CeA as they relate to fear learning. The classical role of the CeA as a routing station to fear effector brain structures like the periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the hypothalamus will be briefly reviewed, but specific emphasis is placed on recent literature suggesting that the CeA 1) has an important role in the plasticity underlying fear learning, 2) is involved in regulation of other amygdala subnuclei, and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss the parallels of human and mouse CeA involvement in fear disorders and fear conditioning, respectively. ©2015 Int. Union Physiol. Sci./Am. Physiol. Soc.

Risk factor analysis of new brain lesions associated with carotid endarterectmy.

PubMed

Lee, Jae Hoon; Suh, Bo Yang

2014-01-01

Carotid endarterectomy (CEA) is the standard treatment for carotid artery stenosis. New brain ischemia is a major concern associated with CEA and diffusion weighted imaging (DWI) is a good imaging modality for detecting early ischemic brain lesions. We aimed to investigate the surgical complications and identify the potential risk factors for the incidence of new brain lesions (NBL) on DWI after CEA. From January 2006 to November 2011, 94 patients who had been studied by magnetic resonance imaging including DWI within 1 week after CEA were included in this study. Data were retrospectively investigated by review of vascular registry protocol. Seven clinical variables and three procedural variables were analyzed as risk factors for NBL after CEA. The incidence of periprocedural NBL on DWI was 27.7%. There were no fatal complications, such as ipsilateral disabling stroke, myocardial infarction or mortality. A significantly higher incidence of NBL was found in ulcer positive patients as opposed to ulcer negative patients (P = 0.029). The incidence of NBL after operation was significantly higher in patients treated with conventional technique than with eversion technique (P = 0.042). Our data shows CEA has acceptable periprocedural complication rates and the existence of ulcerative plaque and conventional technique of endarterectomy are high risk factors for NBL development after CEA.

A Systematic Review of the Level of Evidence in Economic Evaluations of Medical Devices: The Example of Vertebroplasty and Kyphoplasty.

PubMed

Martelli, Nicolas; Devaux, Capucine; van den Brink, Hélène; Pineau, Judith; Prognon, Patrice; Borget, Isabelle

2015-01-01

Economic evaluations are far less frequently reported for medical devices than for drugs. In addition, little is known about the quality of existing economic evaluations, particularly for innovative devices, such as those used in vertebroplasty and kyphoplasty. To assess the level of evidence provided by the available economic evaluations for vertebroplasty and kyphoplasty. A systematic review of articles in English or French listed in the MEDLINE, PASCAL, COCHRANE and National Health Service Economic Evaluation databases, with limits on publication date (up to the date of the review, March 2014). We included only economic evaluations of vertebroplasty or kyphoplasty. Editorial and methodological articles were excluded. Data were extracted from articles by two authors working independently and using two analysis grids to measure the quality of economic evaluations. Twenty-one studies met our inclusion criteria. All were published between 2008 and 2014. Eighteen (86%) were full economic evaluations. Cost-effectiveness analysis (CEA) was the most frequent type of economic evaluation, and was present in 11 (52%) studies. Only three CEAs complied fully with the British Medical Journal checklist. The quality of the data sources used in the 21 studies was high, but the CEAs conforming to methodological guidelines did not use high-quality data sources for all components of the analysis. This systematic review shows that the level of evidence in economic evaluations of vertebroplasty and kyphoplasty is low, despite the recent publication of a large number of studies. This finding highlights the challenges to be faced to improve the quality of economic evaluations of medical devices.

Biomarkers for early detection of pancreatic cancer — EDRN Public Portal

Cancer.gov

Background: The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools. Methods: Sixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Results: The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively correlated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected 1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone. Conclusions: Most biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combination offered some advantage of CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis, however further study will be needed to fully define the implications of these findings.

Selective bispecific T cell recruiting antibody and antitumor activity of adoptive T cell transfer.

PubMed

Kobold, Sebastian; Steffen, Julius; Chaloupka, Michael; Grassmann, Simon; Henkel, Jonas; Castoldi, Raffaella; Zeng, Yi; Chmielewski, Markus; Schmollinger, Jan C; Schnurr, Max; Rothenfußer, Simon; Schendel, Dolores J; Abken, Hinrich; Sustmann, Claudio; Niederfellner, Gerhard; Klein, Christian; Bourquin, Carole; Endres, Stefan

2015-01-01

One bottleneck for adoptive T cell therapy (ACT) is recruitment of T cells into tumors. We hypothesized that combining tumor-specific T cells, modified with a marker antigen and a bispecific antibody (BiAb) that selectively recognizes transduced T cells and tumor cells would improve T cell recruitment to tumors and enhance therapeutic efficacy. SV40 T antigen-specific T cells from T cell receptor (TCR)-I-transgenic mice were transduced with a truncated human epidermal growth factor receptor (EGFR) as a marker protein. Targeting and killing by combined ACT and anti-EGFR-anti-EpCAM BiAb therapy was analyzed in C57Bl/6 mice (n = six to 12 per group) carrying subcutaneous tumors of the murine gastric cancer cell line GC8 (SV40(+) and EpCAM(+)). Anti-EGFR x anti-c-Met BiAb was used for targeting of human tumor-specific T cells to c-Met(+) human tumor cell lines. Differences between experimental conditions were analyzed using the Student's t test, and differences in tumor growth with two-way analysis of variance. Overall survival was analyzed by log-rank test. All statistical tests were two-sided. The BiAb linked EGFR-transduced T cells to tumor cells and enhanced tumor cell lysis. In vivo, the combination of ACT and Biab produced increased T cell infiltration of tumors, retarded tumor growth, and prolonged survival compared with ACT with a control antibody (median survival 95 vs 75 days, P < .001). In human cells, this strategy enhanced recruitment of human EGFR-transduced T cells to immobilized c-Met and recognition of tyrosinase(+) melanoma cells by TCR-, as well as of CEA(+) colon cancer cells by chimeric antigen receptor (CAR)-modified T cells. BiAb recruitment of tumor-specific T cells transduced with a marker antigen to tumor cells may enhance efficacy of ACT. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Short-Term Results of Carotid Endarterectomy and Stenting After the Introduction of Carotid Magnetic Resonance Imaging: A Single-Institution Retrospective Study.

PubMed

Fukumitsu, Ryu; Yoshida, Kazumichi; Kurosaki, Yoshitaka; Torihashi, Koichi; Sadamasa, Nobutake; Koyanagi, Masaomi; Narumi, Osamu; Sato, Tsukasa; Chin, Masaki; Handa, Akira; Yamagata, Sen; Miyamoto, Susumu

2017-05-01

Although carotid artery stenting (CAS) has been gaining popularity as an alternative to carotid endarterectomy (CEA), perioperative stroke rate following contemporary CAS remains significantly higher than stroke rate after CEA. The purpose of this study was to assess perioperative (within 30 days) therapeutic results in patients with carotid stenosis (CS) after introduction of preoperative carotid magnetic resonance imaging plaque evaluation in a single center performing both CEA and CAS. Based on prospectively collected data for patients with CS who were scheduled for carotid revascularization, retrospective analysis was conducted of 295 consecutive patients with CS. An intervention was selected after consideration of periprocedural risks for both CEA and CAS. Concerning risk factors for CAS, results of magnetic resonance imaging plaque evaluation were emphasized with a view toward reducing embolic complications. CAS was performed in 114 patients, and CEA was performed in 181 patients. Comparing baseline characteristics of the 295 patients, age, T1 signal intensity of plaque, symptomatic CS, urgent intervention, and diabetes mellitus differed significantly between CAS and CEA groups. Among patients who underwent CAS, new hyperintense lesions on diffusion-weighted imaging were confirmed in 47 patients. New hyperintense lesions on diffusion-weighted imaging were recognized in 21.4% of patients who underwent CEA (n = 39), significantly less frequent than in patients who underwent CAS. The overall short-term outcome of CEA and CAS is acceptable. Preoperative carotid magnetic resonance imaging evaluation of plaque might contribute to low rates of ischemic complications in CAS. Copyright © 2017 Elsevier Inc. All rights reserved.

NMDA receptor adjusted co-administration of ecstasy and cannabinoid receptor-1 agonist in the amygdala via stimulation of BDNF/Trk-B/CREB pathway in adult male rats.

PubMed

Ashabi, Ghorbangol; Sadat-Shirazi, Mitra-Sadat; Khalifeh, Solmaz; Elhampour, Laleh; Zarrindast, Mohammad-Reza

2017-04-01

Consumption of cannabinoid receptor-1 (CB-1) agonist such as cannabis is widely taken in 3,4- methylenedioxymethamphetamine (MDMA) or ecstasy users; it has been hypothesized that co-consumption of CB-1 agonist might protect neurons against MDMA toxicity. N-methyl-d-aspartate (NMDA) receptors regulate neuronal plasticity and firing rate in the brain through Tyrosine-kinase B (Trk-B) activation. The molecular and electrophysiological association among NMDA and MDMA/Arachidonylcyclopropylamide (ACPA, a selective CB-1 receptor agonist) co-consumption was not well-known. Here, neuronal spontaneous activity, Brain-derived neurotrophic factor (BDNF), Trk-B and cAMP response element binding protein (CREB) phosphorylation levels were recognized in ACPA and MDMA co-injected rats. Besides, we proved the role of NMDA receptor on MDMA and ACPA combination on neuronal spontaneous activity and Trk-B/BDNF pathway in the central amygdala (CeA). Male rats were anesthetized with intra-peritoneal injections of urethane; MDMA, D-2-amino-5-phosphonopentanoate (D-AP5, NMDA receptor antagonist) were injected into CeA. ACPA was administrated by intra-cerebroventricular injection. Thirty minutes following injections, neuronal firing rate was recorded from CeA. Two hours after drug injection, amygdala was collected from brain for molecular evaluations. Single administration of MDMA and/or ACPA reduced firing rates compared with sham group in the CeA dose-dependently. Injection of D-AP5, ACPA and MDMA reduced firing rate compared with sham group (P<0.001). Interestingly, injection of ACPA+MDMA enhanced BDNF, Trk-B and CREB phosphorylation compared with MDMA groups. D-AP5, ACPA and MDMA co-injection decreased BDNF, Trk-B and CREB phosphorylation levels compared with ACPA+MDMA in the amygdala (P<0.01). Probably, NMDA receptors are involved in the protective role of acute MDMA+ACPA co-injection via BDNF/Trk-B/CREB pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

1-D grating based SPR biosensor for the detection of lung cancer biomarkers using Vroman effect

NASA Astrophysics Data System (ADS)

Teotia, Pradeep Kumar; Kaler, R. S.

2018-01-01

Grating based surface plasmon resonance waveguide biosensor have been reported for the detection of lung cancer biomarkers using Vroman effect. The proposed grating based multilayered biosensor is designed with high detection accuracy for Epidermal growth factor receptor (EGFR) and also analysed to show high detection accuracy with acceptable sensitivity for both cancer biomarkers. The introduction of periodic grating with multilayer metals generates a good resonance that make it possible for early detection of cancerous cells. Using finite difference time domain method, it is observed wavelength of biosensor get red-shifted on variations of the refractive index due to the presence of both the cancerous bio-markers. The reported detection accuracy and sensitivity of proposed biosensor is quite acceptable for both lung cancer biomarkers i.e. Carcinoembryonic antigen (CEA) and Epidermal growth factor receptor (EGFR) which further offer us label free early detection of lung cancer using these biomarkers.

Conceptual and methodological challenges to integrating SEA and cumulative effects assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gunn, Jill, E-mail: jill.gunn@usask.c; Noble, Bram F.

The constraints to assessing and managing cumulative environmental effects in the context of project-based environmental assessment are well documented, and the potential benefits of a more strategic approach to cumulative effects assessment (CEA) are well argued; however, such benefits have yet to be clearly demonstrated in practice. While it is widely assumed that cumulative effects are best addressed in a strategic context, there has been little investigation as to whether CEA and strategic environmental assessment (SEA) are a 'good fit' - conceptually or methodologically. This paper identifies a number of conceptual and methodological challenges to the integration of CEA andmore » SEA. Based on results of interviews with international experts and practitioners, this paper demonstrates that: definitions and conceptualizations of CEA are typically weak in practice; approaches to effects aggregation vary widely; a systems perspective lacks in both SEA and CEA; the multifarious nature of SEA complicates CEA; tiering arrangements between SEA and project-based assessment are limited to non-existing; and the relationship of SEA to regional planning remains unclear.« less

Using carbon nanotubes-gold nanocomposites to quench energy from pinnate titanium dioxide nanorods array for signal-on photoelectrochemical aptasensing.

PubMed

Deng, Wenping; Shen, Lei; Wang, Xiu; Yang, Chunlei; Yu, Jinghua; Yan, Mei; Song, Xianrang

2016-08-15

On the basis of the absorption and emission spectra overlap, an enhanced resonance energy transfer caused by excition-plasmon resonance between carbon nanotubes-gold nanoparticles (CNTs-Au) and pinnate titanium dioxide nanorods array (P-TiO2 NA) was obtained. Three-dimensional single crystalline P-TiO2 were prepared successfully on fluorine-doped tin oxide conducting glass (FTO glass), and its optical absorption properties and photoelectrochemical (PEC) properties were investigated. With the synergy of CNTs-Au as energy acceptor, it resulted in the enhancement of energy transfer between excited P-TiO2 NA and CNTs-Au. Upon the novel sandwichlike structure formed via DNA hybridization, the exciton produced in P-TiO2 NA was annihilated and a damped photocurrent was obtained. With the use of carcinoembryonic antigen (CEA) as a model which bonded to its specific aptamer and destroyed the sandwichlike structure, the energy transfer efficiency was lowered, leading to PEC response augment. Thus a signal-on PEC aptasensor was constructed. Under the optimal conditions, the PEC aptasensor for CEA determination exhibited a linear range from 0.001 to 2.5ngmL(-1) with a detection limit of 0.39pgmL(-1) and was satisfactory for clinical sample detection. Furthermore, the proposed aptasensor shows satisfying performance, such as easy preparation, rapid detection and so on. Moreover, since different aptamer can specifically bind to different target molecules, the designed strategy has an expansive application for the construction of versatile PEC platforms. Copyright © 2016 Elsevier B.V. All rights reserved.

Co-Expansion of Cytokine-Induced Killer Cells and Vγ9Vδ2 T Cells for CAR T-Cell Therapy

PubMed Central

Chen, Can; Tan, Wee-Kiat; Chi, Zhixia; Xu, Xue-Hu; Wang, Shu

2016-01-01

Gamma delta (γδ) T cells and cytokine-induced killer (CIK) cells, which are a heterogeneous population of T lymphocytes and natural killer T (NKT) cells, have been separately expanded ex vivo and shown to be capable of targeting and mediating cytotoxicity against various tumor cells in a major histocompatibility complex-unrestricted manner. However, the co-expansion and co-administration of these immune cells have not been explored. In this study we describe an efficient method to expand simultaneously both CIK and Vγ9Vδ2 T cells, termed as CIKZ cells, from human peripheral blood mononuclear cells (PBMCs) using Zometa, interferon-gamma (IFN-γ), interleukin 2 (IL-2), anti-CD3 antibody and engineered K562 feeder cells expressing CD64, CD137L and CD86. A 21-day culture of PBMCs with this method yielded nearly 20,000-fold expansion of CIKZ cells with γδ T cells making up over 20% of the expanded population. The expanded CIKZ cells exhibited antitumor cytotoxicity and could be modified to express anti-CD19 chimeric antigen receptor (CAR), anti-CEA CAR, and anti-HER2 CAR to enhance their specificity and cytotoxicity against CD19-, CEA-, or HER2-positive tumor cells. The tumor inhibitory activity of anti-CD19 CAR-modified CIKZ cells was further demonstrated in vivo in a Raji tumor mouse model. The findings herein substantiate the feasibility of co-expanding CIK and γδ cells for adoptive cellular immunotherapy applications such as CAR T-cell therapy against cancer. PMID:27598655

Nanoporous Glass Integrated in Volumetric Bar-Chart Chip for Point-of-Care Diagnostics of Non-Small Cell Lung Cancer.

PubMed

Li, Ying; Xuan, Jie; Song, Yujun; Qi, Wenjin; He, Bangshun; Wang, Ping; Qin, Lidong

2016-01-26

Point-of-care (POC) testing has the potential to enable rapid, low-cost, and large-scale screening. POC detection of a multiplexed biomarker panel can facilitate the early diagnosis of non-small cell lung cancer (NSCLC) and, thus, may allow for more timely surgical intervention for life-saving treatment. Herein, we report the nanoporous glass (NPG) integrated volumetric bar-chart chip (V-Chip) for POC detection of the three NSCLC biomarkers CEA, CYFRA 21-1, and SCCA, by the naked eye. The 3D nanostructures in the NPG membrane efficiently increase the number of binding sites for antibodies and decrease the diffusion distance between antibody and antigen, enabling the low detection limit and rapid analysis time of the NPG-V-Chip. We utilized the NPG-V-Chip to test the NSCLC biomarker panel and found that the limit of detection can reach 50 pg/mL (10-fold improvement over the original V-Chip), and the total assay time can be decreased from 4 to 0.5 h. We then detected CEA in 21 serum samples from patients with common cancers, and the on-chip results showed good correlation with the clinical results. We further assayed 10 lung cancer samples using the device and confirmed the results obtained using conventional ELISA methods. In summary, the NPG-V-Chip platform has the ability of multiplex, low detection limit, low cost, lack of need for accessory equipment, and rapid analysis time, which may render the V-Chip a useful platform for quantitative POC detection in resource-limited settings and personalized diagnostics.

Electrochemiluminescence of luminol enhanced by the synergetic catalysis of hemin and silver nanoparticles for sensitive protein detection.

PubMed

Jiang, Xinya; Chai, Yaqin; Wang, Haijun; Yuan, Ruo

2014-04-15

A novel and ultrasensitive electrochemiluminescence (ECL) immunosensor, which was based on the amplifying ECL of luminol by hemin-reduced graphene oxide (hemin-rGO) and Ag nanoparticles (AgNPs) decorated reduced graphene oxide (Ag-rGO), was constructed for the detection of carcinoembryonic antigen (CEA). For this proposed sandwich-type ECL immunosensor, Au nanoparticles electrodeposited (DpAu) onto hemin-rGO (DpAu/hemin-rGO) constructed the base of the immunosensor. DpAu had outstanding electrical conductivity to promote the electron transfer at the electrode interface and had good biocompatibility to load large amounts of primary antibody (Ab1), which provided an excellent platform for this immunosensor. Moreover, AgNPs and glucose oxidase (GOD) functionalized graphene labeled secondary antibody (Ag-rGO-Ab2-GOD) was designed as the signal probe for the sandwiched immunosensor. Not only did the hemin-rGO improve the electron transfer of the electrode surface, but hemin also further amplified the ECL signal of luminol in the presence of hydrogen peroxide (H2O2). With the aid of Ag-rGO-Ab2-GOD, enhanced signal was obtained by in situ generation of H2O2 and catalysis of AgNPs to ECL reaction of the luminol-H2O2 system. The as-prepared ECL immunosensor exhibited excellent analytical property for the detection of CEA in the range from 0.1 pg mL(-1) to 160 ng mL(-1) with a detection limit of 0.03 pg mL(-1) (SN(-1)=3). © 2013 Published by Elsevier B.V.

PREFACE: Nanosafe 2012: International Conferences on Safe Production and Use of Nanomaterials

NASA Astrophysics Data System (ADS)

Tardif, François

2013-04-01

Welcome from the organizers The rapidly developing field of nanotechnology opens up many exciting opportunities and benefits for new materials with significantly improved properties as well as some revolutionary applications in the fields of energy, environment, medicine, etc. These new materials potentially pave the way to considerable innovations in many industries of the 21st century although associated risks must be perfectly under control for workers, consumers and the environment. So, one can easily understand why Nanosafety is now considered as a specific new scientific area, gaining in importance and maturity every day. Following the successful outcome of the two past international conferences on the safe production and use of nanomaterials: Nanosafe 2008 and 2010, the organizing committee has the pleasure of welcoming again to Grenoble some of the most famous specialists of the field in the world. In addition to the standard issues addressed in previous nanosafe conferences such as Toxicology, Eco-toxicology, Expology, Detection, Life Cycle Analysis, Regulation and Standardization, new topics of great interest will be dealt with this year, concerning Governance and practical Risk Management for OSH experts and Societal issues. In order to enhance the exchanges and conviviality three debates werw organized around Nano Governance, Toxicology and Ethics. We hope that you will appreciate this new Nanosafe edition like the previous ones. This is your Nanosafe conference, please enjoy. The Nanosafe conference organisers François Tardif and Frédéric Shuster Management Vanessa Gaultier Francois TardifFrederic ShusterVanessa Gaultier François TardifFrédéric Shuster Vanessa Gaultier Local Organizing Committee Vanessa GAULTIER (CEA) François TARDIF (CEA) Dominique BAGUET (CEA) Frédédric SHUSTER (CEA) Yves SICARD (CEA) Catherine DURAND (CEA) Didier MOLKO (MINATEC) International Scientific Committee Chair: Frédéric SCHUSTER (CEA, FR) François TARDIF (CEA, FR) Co-chair: Georgios KATALAGARIANAKIS (EC, BE) Mélanie AUFFAN (CEREGE, FR) Jorge BOCZKOWSKI (INSERM, FR) Jean-Yves BOTTERO (CEREGE, FR) Jacques BOUILLARD (INERIS, FR) Derk BROUWER (TNO, NL) Marie CARRIERE (CEA, FR) Claude EMOND (U. MONTREAL, CA) Cassandra ENGEMAN (UCSB, USA) Eric GAFFET (CNRS, FR) François GENSDARMES (IRSN, FR) Alexei GRINBAUM (CEA, FR) Antje GROBE (U.STUTTGART, DE) Peter HOET (KUL, BE) Eric QUEMENEUR (CEA, FR) Olivier LE BIHAN (INERIS, FR) Robert MUIR (NANEUM, UK) Tinh NGUYEN (NIST, USA) Bernd NOWACK (EMPA, CH) Günter OBERDÖRSTER (U. ROCHESTER, USA) David PUI (U. MINNESOTA, USA) Michael RIEDIKER (IST, CH) Yves SAMSON (CEA, FR) Ken TAKEDA (U. TOKYO, JP) Olivier WITSCHGER (INRS, FR) The PDF contains a list of sponsor logos, the conference programme and planning documents.

Clinical results of carotid artery stenting versus carotid endarterectomy

PubMed Central

Akinci, Tuba; Derle, Eda; Kibaroğlu, Seda; Harman, Ali; Kural, Feride; Cınar, Pınar; Kilinc, Munire; Akay, Hakki T.; Can, Ufuk; Benli, Ulku S.

2016-01-01

Objective: To review our results of carotid artery stenting (CAS) and carotid endarterectomy (CEA). Methods: We evaluated the medical records of patients undergoing carotid artery revascularization procedure, between 2001 and 2013 in Baskent University Hospital, Ankara, Turkey. Carotid artery stenting or CEA procedures were performed in patients with asymptomatic carotid stenosis (≥70%) or symptomatic stenosis (≥50%). Demographic data, procedural details, and clinical outcomes were recorded. Primary outcome measures were in 30-day stroke/transient ischemic attacks (TIA)/amaurosis fugax or death. Secondary outcome measures were nerve injury, bleeding complications, length of stay in hospital, stroke, restenosis (ICA patency), and all-cause death during long-term follow-up. Results: One hundred ninety-four CEA and 115 CAS procedures were performed for symptomatic and/or asymptomatic carotid artery stenosis. There is no significant differences 30-day mortality and neurologic morbidity between CAS (13%) and CEA procedures (7.7%). Length of stay in hospital were significantly longer in CEA group (p=0.001). In the post-procedural follow up, only in symptomatic patients, restenosis rate was higher in the CEA group (p=.045). The other endpoints did not differ significantly. Conclusions: Endovascular stent treatment of carotid artery atherosclerotic disease is an alternative for vascular surgery, especially for patients that are high risk for standard CEA. The increasing experience, development of cerebral protection systems and new treatment protocols increases CAS feasibility. PMID:27744460

Carotid Endarterectomy: Current Concepts and Practice Patterns

PubMed Central

Saha, Sibu P.; Saha, Subhajit; Vyas, Krishna S.

2015-01-01

Background Stroke is the number one cause of disability and third leading cause of death among adults in the United States. A major cause of stroke is carotid artery stenosis (CAS) caused by atherosclerotic plaques. Randomized trials have varying results regarding the equivalence and perioperative complication rates of stents versus carotid endarterectomy (CEA) in the management of CAS. Objectives We review the evidence for the current management of CAS and describe the current concepts and practice patterns of CEA. Methods A literature search was conducted using PubMed to identify relevant studies regarding CEA and stenting for the management of CAS. Results The introduction of CAS has led to a decrease in the percentage of CEA and an increase in the number of CAS procedures performed in the context of all revascularization procedures. However, the efficacy of stents in patients with symptomatic CAS remains unclear because of varying results among randomized trials, but the perioperative complication rates exceed those found after CEA. Conclusions Vascular surgeons are uniquely positioned to treat carotid artery disease through medical therapy, CEA, and stenting. Although data from randomized trials differ, it is important for surgeons to make clinical decisions based on the patient. We believe that CAS can be adopted with low complication rate in a selected subgroup of patients, but CEA should remain the standard of care. This current evidence should be incorporated into practice of the modern vascular surgeon. PMID:26417192

Costs and cost-effectiveness of carotid stenting versus endarterectomy for patients at standard surgical risk: results from the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST).

PubMed

Vilain, Katherine R; Magnuson, Elizabeth A; Li, Haiyan; Clark, Wayne M; Begg, Richard J; Sam, Albert D; Sternbergh, W Charles; Weaver, Fred A; Gray, William A; Voeks, Jenifer H; Brott, Thomas G; Cohen, David J

2012-09-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite end point between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for health care policy and treatment guidelines. We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health use scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. Although initial procedural costs were $1025/patient higher with CAS, postprocedure costs and physician costs were lower such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15 055 versus $14 816; mean difference, $239/patient; 95% CI for difference, -$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50 000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00004732.

Costs and Cost-Effectiveness of Carotid Stenting versus Endarterectomy for Patients at Standard Surgical Risk: Results from the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST)

PubMed Central

Vilain, Katherine R.; Magnuson, Elizabeth A.; Li, Haiyan; Clark, Wayne M.; Begg, Richard J.; Sam, Albert D.; Sternbergh, W. Charles; Weaver, Fred A.; Gray, William A.; Voeks, Jenifer H.; Brott, Thomas G.; Cohen, David J.

2012-01-01

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated similar rates of the primary composite endpoint between carotid artery stenting (CAS) and carotid endarterectomy (CEA), although the risk of stroke was higher with CAS, and the risk of myocardial infarction (MI) was higher with CEA. Given the large number of patients who are candidates for these procedures, an understanding of their relative cost and cost-effectiveness may have important implications for healthcare policy and treatment guidelines. Methods We performed a formal economic evaluation alongside the CREST trial. Costs were estimated from all trial participants over the first year of follow-up using a combination of resource use data and hospital billing data. Patient-level health utility scores were obtained using data from the SF-36. We then used a Markov disease-simulation model calibrated to the CREST results to project 10-year costs and quality-adjusted life expectancy for the 2 treatment groups. Results Although initial procedural costs were $1025/patient higher with CAS, post-procedure costs and physician costs were lower, such that total costs for the index hospitalization were similar for the CAS and CEA groups ($15,055 versus $14,816; mean difference $239/patient, 95% CI for difference, −$297 to $775). Neither follow-up costs after discharge nor total 1-year costs differed significantly. For the CREST population, model-based projections over a 10-year time horizon demonstrated that CAS would result in a mean incremental cost of $524/patient and a reduction in quality-adjusted life expectancy of 0.008 years compared with CEA. Probabilistic sensitivity analysis demonstrated that CEA was economically attractive at an incremental cost-effectiveness threshold of $50,000/quality-adjusted life-year gained in 54% of samples, whereas CAS was economically attractive in 46%. Conclusions Despite slightly lower in-trial costs and lower rates of stroke with CEA compared with CAS, projected 10-year outcomes from this controlled clinical trial demonstrate only trivial differences in overall healthcare costs and quality-adjusted life expectancy between the 2 strategies. If the CREST results can be replicated in clinical practice, these findings suggest that factors other than cost-effectiveness should be considered when deciding between treatment options for carotid artery stenosis in patients at standard risk for surgical complications. PMID:22821614

Nociceptin/orphanin FQ decreases glutamate transmission and blocks ethanol-induced effects in the central amygdala of naive and ethanol-dependent rats.

PubMed

Kallupi, Marsida; Varodayan, Florence P; Oleata, Christopher S; Correia, Diego; Luu, George; Roberto, Marisa

2014-04-01

The central nucleus of the amygdala (CeA) mediates several addiction-related processes and nociceptin/orphanin FQ (nociceptin) regulates ethanol intake and anxiety-like behaviors. Glutamatergic synapses, in the CeA and throughout the brain, are very sensitive to ethanol and contribute to alcohol reinforcement, tolerance, and dependence. Previously, we reported that in the rat CeA, acute and chronic ethanol exposures significantly decrease glutamate transmission by both pre- and postsynaptic actions. In this study, using electrophysiological techniques in an in vitro CeA slice preparation, we investigated the effects of nociceptin on glutamatergic transmission and its interaction with acute ethanol in naive and ethanol-dependent rats. We found that nociceptin (100-1000 nM) diminished basal-evoked compound glutamatergic receptor-mediated excitatory postsynaptic potentials (EPSPs) and spontaneous and miniature EPSCs (s/mEPSCs) by mainly decreasing glutamate release in the CeA of naive rats. Notably, nociceptin blocked the inhibition induced by acute ethanol (44 mM) and ethanol blocked the nociceptin-induced inhibition of evoked EPSPs in CeA neurons of naive rats. In neurons from chronic ethanol-treated (ethanol-dependent) rats, the nociceptin-induced inhibition of evoked EPSP amplitude was not significantly different from that in naive rats. Application of [Nphe1]Nociceptin(1-13)NH2, a nociceptin receptor (NOP) antagonist, revealed tonic inhibitory activity of NOP on evoked CeA glutamatergic transmission only in ethanol-dependent rats. The antagonist also blocked nociceptin-induced decreases in glutamatergic responses, but did not affect ethanol-induced decreases in evoked EPSP amplitude. Taken together, these studies implicate a potential role for the nociceptin system in regulating glutamatergic transmission and a complex interaction with ethanol at CeA glutamatergic synapses.

Visual Aids for Improving Patient Decision Making in Severe Symptomatic Carotid Stenosis.

PubMed

Fridman, Sebastian; Saposnik, Gustavo; Sposato, Luciano A

2017-12-01

Because of the large amount of information to process and the limited time of a clinical consult, choosing between carotid endarterectomy (CEA) and carotid angioplasty with stenting (CAS) can be confusing for patients with severe symptomatic internal carotid stenosis (ICA). We aim to develop a visual aid tool to help clinicians and patients in the decision-making process of selecting between CEA and CAS. Based on pooled analysis from randomized controlled trials including patients with symptomatic and severe ICA (SSICA), we generated visual plots comparing CEA with CAS for 3 prespecified postprocedural time points: (1) any stroke or death at 4 months, and (2) any stroke or death in the first 30 days and ipsilateral stroke thereafter at 5 years and (3) at 10 years. A total of 4574 participants (2393 assigned to CAS, and 2361 to CEA) were included in the analyses. For every 100 patients with SSICA, 6 would develop any stroke or death in the CEA group compared with 9 undergoing CAS at 4 months (hazard ratio [HR] 1.53; 95%CI 1.20-1.95). At 5 years, 7 patients in the CEA group would develop any periprocedural stroke or death and ipsilateral stroke thereafter versus 12 undergoing CAS (HR 1.72; 95%CI 1.24-2.39), compared with 10 patients in the CEA and 13 in the CAS groups at 10 years (HR 1.17; 95%CI 0.82-1.66). Visual aids presented in this study could potentially help patients with severe symptomatic internal carotid stenosis to better weigh the risks and benefits of CEA versus CAS as a function of time, allowing for the prioritization of personal preferences, and should be prospectively assessed. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Effects of unilatral- and bilateral inhibition of rostral ventral tegmental area and central nucleus of amygdala on morphine-induced place conditioning in male Wistar rat.

PubMed

Mohammadian, Zahra; Sahraei, Hedayat; Meftahi, Gholam Hossein; Ali-Beik, Hengameh

2017-03-01

The rostral ventral tegmental area (VTAR) and central nucleus of amygdala (CeA) are considered the main regions for induction of psychological dependence on abused drugs, such as morphine. The main aim of this study was to investigate the transient inhibition of each right and left side as well as both sides of the VTAR and the CeA by lidocaine (2%) on morphine reward properties using the conditioned place preference (CPP) method. Male Wistar rats (250±20 g) 7 days after recovery from surgery and cannulation were conditioned to morphine (7.5 mg/kg) in CPP apparatus. Five minutes before morphine injection in conditioning phase, lidocaine was administered either uni- or bilaterally into the VTAR (0.25 μL/site) or CeA (0.5 μL/site). The results revealed that lidocaine administration into the left side, but not the right side of the VTAR and the CeA reduced morphine CPP significantly. The reduction was potentiated when lidocaine was injected into both sides of the VTAR and the CeA. The number of compartment crossings was reduced when lidocaine was injected into both sides of the VTAR and the CeA as well as the left side. Rearing was reduced when lidocaine was injected into the right, but not the left side of the VTAR. Sniffing and rearing increased when animals received lidocaine in the right side and reduced in the group that received lidocaine in the left side of the CeA. It was concluded that the right and the left side of VTAR and the CeA play different roles in morphine-induced activity and reward. © 2016 John Wiley & Sons Australia, Ltd.

Deep brain stimulation in the central nucleus of the amygdala decreases 'wanting' and 'liking' of food rewards.

PubMed

Ross, Shani E; Lehmann Levin, Emily; Itoga, Christy A; Schoen, Chelsea B; Selmane, Romeissa; Aldridge, J Wayne

2016-10-01

We investigated the potential of deep brain stimulation (DBS) in the central nucleus of the amygdala (CeA) in rats to modulate functional reward mechanisms. The CeA is the major output of the amygdala with direct connections to the hypothalamus and gustatory brainstem, and indirect connections with the nucleus accumbens. Further, the CeA has been shown to be involved in learning, emotional integration, reward processing, and regulation of feeding. We hypothesized that DBS, which is used to treat movement disorders and other brain dysfunctions, might block reward motivation. In rats performing a lever-pressing task to obtain sugar pellet rewards, we stimulated the CeA and control structures, and compared stimulation parameters. During CeA stimulation, animals stopped working for rewards and rejected freely available rewards. Taste reactivity testing during DBS exposed aversive reactions to normally liked sucrose tastes and even more aversive taste reactions to normally disliked quinine tastes. Interestingly, given the opportunity, animals implanted in the CeA would self-stimulate with 500 ms trains of stimulation at the same frequency and current parameters as continuous stimulation that would stop reward acquisition. Neural recordings during DBS showed that CeA neurons were still active and uncovered inhibitory-excitatory patterns after each stimulus pulse indicating possible entrainment of the neural firing with DBS. In summary, DBS modulation of CeA may effectively usurp normal neural activity patterns to create an 'information lesion' that not only decreased motivational 'wanting' of food rewards, but also blocked 'liking' of rewards. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Carotid endarterectomy: the change in practice over 11 years in a stroke centre.

PubMed

Tse, Gabrielle T W; Kilkenny, Monique F; Bladin, Chris; Grigg, Michael; Dewey, Helen M

2017-11-13

Recent research evidence has impacted the practice of carotid endarterectomy (CEA). We aim to characterize changes in the practice and outcome of CEA over time in a single large-volume stroke centre. All patients who underwent CEA from 2004 to 2014 and carotid angioplasty and stenting (CAS) from 2003 to 2008 at an Australian metropolitan tertiary stroke centre hospital were included. Clinical data were analysed to identify time trends in choice of intervention, patient selection, preoperative imaging utilization, surgical timing and outcome. There were 510 CEAs performed during 2004-2014 and 95 CASs during 2003-2008. The proportion of patients undergoing CEA compared to CAS increased from 60% to 90% from 2004 to 2008 (P < 0.001). CAS patients were more likely to have cardiac co-morbidities. From 2004 to 2014, the proportion of CEA patients aged ≥80 years increased (P = 0.001) and the proportion of asymptomatic patients decreased (P = 0.003) over time. Median time from symptom onset to surgery decreased from 52 days (Q1: 25, Q3: 74) in 2004 to 8 days (Q1: 5, Q3: 37) in 2014 (P < 0.001). Use of preoperative ultrasonography decreased whilst CT angiography and the number of imaging modalities applied to each patient increased over time (P < 0.001). Overall, 5.9% of CEAs were complicated by death, stroke or acute myocardial infarction with no significant change over time. The trends in CEA practice at our centre align with international trends and guidelines. This study provides a representative indicator of Australian hospital practice, and illustrates how evidence from research is translated into clinical care. © 2017 Royal Australasian College of Surgeons.

Use of number needed to treat in cost-effectiveness analyses.

PubMed

Garg, Vishvas; Shen, Xian; Cheng, Yan; Nawarskas, James J; Raisch, Dennis W

2013-03-01

To review the use of number needed to treat (NNT) and/or number needed to harm (NNH) values to determine their relevance in helping clinicians evaluate cost-effectiveness analyses (CEAs). PubMed and EconLit were searched from 1966 to September 2012. Reviews, editorials, non-English-language articles, and articles that did not report NNT/NNH or cost-effectiveness ratios were excluded. CEA studies reporting cost per life-year gained, per quality-adjusted life-year (QALY), or other cost per effectiveness measure were included. Full texts of all included articles were reviewed for study information, including type of journal, impact factor of the journal, focus of study, data source, publication year, how NNT/NNH values were reported, and outcome measures. A total of 188 studies were initially identified, with 69 meeting our inclusion criteria. Most were published in clinician-practice-focused journals (78.3%) while 5.8% were in policy-focused journals, and 15.9% in health-economics-focused journals. The majority (72.4%) of the articles were published in high-impact journals (impact factor >3.0). Many articles focused on either disease treatment (40.5%) or disease prevention (40.5%). Forty-eight percent reported NNT as a part of the CEA ratio per event. Most (53.6%) articles used data from literature reviews, while 24.6% used data from randomized clinical trials, and 20.3% used data from observational studies. In addition, 10% of the studies implemented modeling to perform CEA. CEA studies sometimes include NNT ratios. Although it has several limitations, clinicians often use NNT for decision-making, so including NNT information alongside CEA findings may help clinicians better understand and apply CEA results. Further research is needed to assess how NNT/NNH might meaningfully be incorporated into CEA publications.

Glutamatergic transmission in the central nucleus of the amygdala is selectively altered in Marchigian Sardinian alcohol-preferring rats: alcohol and CRF effects

PubMed Central

Herman, Melissa A.; Varodayan, Florence P.; Oleata, Christopher S.; Luu, George; Kirson, Dean; Heilig, Markus; Ciccocioppo, Roberto; Roberto, Marisa

2015-01-01

The CRF system of the central nucleus of the amygdala (CeA) is important for the processing of anxiety, stress, and effects of acute and chronic ethanol. We previously reported that ethanol decreases evoked glutamate transmission in the CeA of Sprague Dawley rats and that ethanol dependence alters glutamate release in the CeA. Here, we examined the effects of ethanol, CRF and a CRF1 receptor antagonist on spontaneous and evoked glutamatergic transmission in CeA neurons from Wistar and Marchigian Sardinian Preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and characterized by heightened activity of the CRF1 system. Basal spontaneous and evoked glutamate transmission in CeA neurons from msP rats was increased compared to Wistar rats. Ethanol had divergent effects, either increasing or decreasing spontaneous glutamate release in the CeA of Wistar rats. This bidirectional effect was retained in msP rats, but the magnitude of the ethanol-induced increase in glutamate release was significantly smaller. The inhibitory effect of ethanol on evoked glutamatergic transmission was similar in both strains. CRF also either increased or decreased spontaneous glutamate release in CeA neurons of Wistar rats, however, in msP rats CRF only increased glutamate release. The inhibitory effect of CRF on evoked glutamatergic transmission was also lost in neurons from msP rats. A CRF1 antagonist produced only minor effects on spontaneous glutamate transmission, which were consistent across strains, and no effects on evoked glutamate transmission. These results demonstrate that the genetically altered CRF system of msP rats results in alterations in spontaneous and stimulated glutamate signaling in the CeA that may contribute to both the anxiety and drinking behavioral phenotypes. PMID:26519902

The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts

PubMed Central

Kadayifci, Abdurrahman; Al-Haddad, Mohammad; Atar, Mustafa; Dewitt, John M.; Forcione, David G.; Sherman, Stuart; Casey, Brenna W.; Fernandez-del Castillo, Carlos; Schmidt, C. Max; Pitman, Martha B.; Brugge, William R.

2016-01-01

Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100 % and 93.2 %), but low sensitivity (48.3 % and 56.3 %) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8 %) and AUC (0.84) significantly compared to KRAS (65.3 % and 0.74) or CEA (65.8 % and 0.74) alone, but only in the clinical cohort (P < 0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73 % vs. 37 %, P = 0.001). The negative predictive value of KRAS mutation was 77.6 % in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use. PMID:27092317

Comparison of Ablation Predictions for Carbonaceous Materials Using CEA and JANAF-Based Species Thermodynamics

NASA Technical Reports Server (NTRS)

Milos, Frank S.

2011-01-01

In most previous work at NASA Ames Research Center, ablation predictions for carbonaceous materials were obtained using a species thermodynamics database developed by Aerotherm Corporation. This database is derived mostly from the JANAF thermochemical tables. However, the CEA thermodynamics database, also used by NASA, is considered more up to date. In this work, the FIAT code was modified to use CEA-based curve fits for species thermodynamics, then analyses using both the JANAF and CEA thermodynamics were performed for carbon and carbon phenolic materials over a range of test conditions. The ablation predictions are comparable at lower heat fluxes where the dominant mechanism is carbon oxidation. However, the predictions begin to diverge in the sublimation regime, with the CEA model predicting lower recession. The disagreement is more significant for carbon phenolic than for carbon, and this difference is attributed to hydrocarbon species that may contribute to the ablation rate.

The Central Amygdala Projection to the Substantia Nigra Reflects Prediction Error Information in Appetitive Conditioning

ERIC Educational Resources Information Center

Lee, Hongjoo J.; Gallagher, Michela; Holland, Peter C.

2010-01-01

The central amygdala nucleus (CeA) plays a critical role in cognitive processes beyond fear conditioning. For example, intact CeA function is essential for enhancing attention to conditioned stimuli (CSs). Furthermore, this enhanced attention depends on the CeA's connections to the nigrostriatal system. In the current study, we examined the role…

Aeroacoustics research in Europe: The CEAS-ASC report on 2016 highlights

NASA Astrophysics Data System (ADS)

Wilson, Alexander G.

2018-08-01

The Council of European Aerospace Societies (CEAS) Aeroacoustics Specialists Committee (ASC) supports and promotes the interests of the scientific and industrial aeroacoustics community on the European scale, and European aeronautics activities internationally. Each year, the committee highlights several of the research and development projects in Europe. This paper is the 2016 issue of this collection of Aeroacoustic Highlights, compiled from contributions submitted to the CEAS-ASC. The contributions are classified under three main headings; Aircraft and Turbomachinery Noise, Experimental and Numerical Methods and Further Applications of Aeroacoustics. A concise summary of the CEAS-ASC workshop held in Southampton, England, in September 2016 is also included in this report.

Cost effectiveness analysis for nursing research.

PubMed

Bensink, Mark E; Eaton, Linda H; Morrison, Megan L; Cook, Wendy A; Curtis, R Randall; Gordon, Deborah B; Kundu, Anjana; Doorenbos, Ardith Z

2013-01-01

With ever-increasing pressure to reduce costs and increase quality, nurses are faced with the challenge of producing evidence that their interventions and care provide value. Cost effectiveness analysis (CEA) is a tool that can be used to provide this evidence by comparative evaluation of the costs and consequences of two or more alternatives. The aim of this article is to introduce the essential components of CEA to nurses and nurse researchers with the protocol of a recently funded cluster randomized controlled trial as an example. This article provides (a) a description of the main concepts and key steps in CEA and (b) a summary of the background and objectives of a CEA designed to evaluate a nursing-led pain and symptom management intervention in rural communities compared with the current usual care. As the example highlights, incorporating CEA into nursing research studies is feasible. The burden of the additional data collection required is offset by quantitative evidence of the given intervention's cost and impact using humanistic and economic outcomes. At a time when U.S. healthcare is moving toward accountable care, the information provided by CEA will be an important additional component of the evidence produced by nursing research.

[Treatment Strategy and Results of Carotid Endarterectomy in Chronic Renal Failure Patients].

PubMed

Murahashi, Takeo; Kamiyama, Kenji; Osato, Toshiaki; Watanabe, Toshiichi; Ogino, Tatsuya; Sugio, Hironori; Endo, Hideki; Takahira, Kazuki; Shindo, Koichiro; Takahashi, Shuhei; Nakamura, Hirohiko

2017-02-01

The number of patients receiving chronic dialysis treatment in Japan currently exceeds 300,000 people. Few reports have described carotid endarterectomy(CEA)for chronic renal failure patients because of the unacceptable rate of perioperative stroke and other morbidities. A strategy for and treatment results of CEA for chronic renal failure patients in our hospital are described herein. The present study included 6 patients who underwent CEA while receiving dialysis treatment between April 2011 and November 2014. Dialysis treatment was initiated due to diabetes in 4 patients and renal sclerosis in 2 patients. All the patients were men, with a mean age of 74.0 years. Two patients were symptomatic, and four were asymptomatic. In all the patients, heart vascular lesions and arteriosclerosis risk factors were present. Postoperatively, pneumonia transient cranial neuropathy, heart failure, and pneumonia in 1 case required extensive treatment. However, by the time of discharge from hospital, no cases had deteriorated compared with their pre-CEA state. The modified Rankin scale score on discharge was 0-2 for all the patients. CEA can be performed safely in patients receiving dialysis, but further operative procedures and careful postoperative management are likely to be needed for patients with CEA who are receiving dialysis.

Systematic preoperative coronary angiography and stenting improves postoperative results of carotid endarterectomy in patients with asymptomatic coronary artery disease: a randomised controlled trial.

PubMed

Illuminati, G; Ricco, J-B; Greco, C; Mangieri, E; Calio', F; Ceccanei, G; Pacilè, M A; Schiariti, M; Tanzilli, G; Barillà, F; Paravati, V; Mazzesi, G; Miraldi, F; Tritapepe, L

2010-02-01

To evaluate the usefulness of systematic coronary angiography followed, if needed, by coronary artery angioplasty (percutaneous coronary intervention (PCI)) on the incidence of cardiac ischaemic events after carotid endarterectomy (CEA) in patients without evidence of coronary artery disease (CAD). From January 2005 to December 2008, 426 patients, candidates for CEA, with no history of CAD and with normal cardiac ultrasound and electrocardiography (ECG), were randomised into two groups. In group A (n=216) all the patients had coronary angiography performed before CEA. In group B, all the patients had CEA without previous coronary angiography. In group A, 66 patients presenting significant coronary artery lesions at angiography received PCI before CEA. They subsequently underwent surgery under aspirin (100 mg day(-1)) and clopidogrel (75 mg day(-1)). CEA was performed within a median delay of 4 days after PCI (range: 1-8 days). Risk factors, indications for CEA and surgical techniques were comparable in both groups (p>0.05). The primary combined endpoint of the study was the incidence of postoperative myocardial ischaemic events combined with the incidence of complications of coronary angiography. Secondary endpoints were death and stroke rates after CEA and incidence of cervical haematoma. Postoperative mortality was 0% in group A and 0.9% in group B (p=0.24). One postoperative stroke (0.5%) occurred in group A, and two (0.9%) in group B (p=0.62). No postoperative myocardial event was observed in group A, whereas nine ischaemic events were observed in group B, including one fatal myocardial infarction (p=0.01). Binary logistic regression analysis demonstrated that preoperative coronary angiography was the only independent variable that predicted the occurrence of postoperative coronary ischaemia after CEA. The odds ratio for coronary angiography (group A) indicated that when holding all other variables constant, a patient having preoperative coronary angiography before carotid surgery was 4 times less likely to have a cardiac ischaemic event after carotid surgery. No complications related to coronary angiography were observed and no cervical haematomas occurred in patients undergoing surgery under aspirin and clopidogrel in this study. Systematic preoperative coronary angiography, possibly followed by PCI, significantly reduces the incidence of postoperative myocardial events after CEA in patients without clinical evidence of CAD. Copyright (c) 2009 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

SONOlysis in prevention of Brain InfaRctions During Internal carotid Endarterectomy (SONOBIRDIE) trial - study protocol for a randomized controlled trial.

PubMed

Hrbáč, Tomáš; Netuka, David; Beneš, Vladimír; Nosáľ, Vladimír; Kešnerová, Petra; Tomek, Aleš; Fadrná, Táňa; Beneš, Vladimír; Fiedler, Jiří; Přibáň, Vladimír; Brozman, Miroslav; Langová, Kateřina; Herzig, Roman; Školoudík, David

2017-01-17

Carotid endarterectomy (CEA) is a beneficial procedure for selected patients with an internal carotid artery (ICA) stenosis. Surgical risk of CEA varies from between 2 and 15%. The aim of the study is to demonstrate the safety and effectiveness of sonolysis (continual transcranial Doppler monitoring, TCD) using a 2-MHz diagnostic probe with maximal diagnostic energy on the reduction of the incidence of stroke, transient ischemic attack (TIA) and brain infarction detected using magnetic resonance imaging (MRI) by the activation of the endogenous fibrinolytic system during CEA. Design: a multicenter, randomized, double-blind, sham-controlled trial. international, multicenter trial for patients with at least 70% symptomatic or asymptomatic ICA stenosis undergoing CEA. patients with symptomatic or asymptomatic ICA stenosis of at least 70% are candidates for CEA; a sufficient temporal bone window for TCD; aged 40-85 years, functionally independent; provision of signed informed consent. Randomization: consecutive patients will be assigned to the sonolysis or control (sham procedure) group by computer-generated 1:1 randomization. Prestudy calculations showed that a minimum of 704 patients in each group is needed to reach a significant difference with an alpha value of 0.05 (two-tailed) and a beta value of 0.8 assuming that 10% would be lost to follow-up or refuse to participate in the study (estimated 39 endpoints). the primary endpoint is the incidence of stroke or TIA during 30 days after CEA and the incidence of new ischemic lesions on brain MRI performed 24 h after CEA in the sonolysis and control groups. Secondary endpoints are occurrence of death, any stroke, or myocardial infarction within 30 days, changes in cognitive functions 1 year post procedure related to pretreatment scores, and number of new lesions and occurrence of new lesions ≥0.5 mL on post-procedural brain MRI. descriptive statistics and linear/logistic multiple regression models will be performed. Clinical relevance will be measured as relative risk reduction, absolute risk reduction and the number needed to treat. Reduction of the periprocedural complications of CEA using sonolysis as a widely available and cheap method may significantly increase the safety of CEA and extend the indication criteria for CEA. ClinicalTrials.gov, NCT02398734 . Registered on 20 March 2015.

CESAR5.3: Isotopic depletion for Research and Testing Reactor decommissioning

NASA Astrophysics Data System (ADS)

Ritter, Guillaume; Eschbach, Romain; Girieud, Richard; Soulard, Maxime

2018-05-01

CESAR stands in French for "simplified depletion applied to reprocessing". The current version is now number 5.3 as it started 30 years ago from a long lasting cooperation with ORANO, co-owner of the code with CEA. This computer code can characterize several types of nuclear fuel assemblies, from the most regular PWR power plants to the most unexpected gas cooled and graphite moderated old timer research facility. Each type of fuel can also include numerous ranges of compositions like UOX, MOX, LEU or HEU. Such versatility comes from a broad catalog of cross section libraries, each corresponding to a specific reactor and fuel matrix design. CESAR goes beyond fuel characterization and can also provide an evaluation of structural materials activation. The cross-sections libraries are generated using the most refined assembly or core level transport code calculation schemes (CEA APOLLO2 or ERANOS), based on the European JEFF3.1.1 nuclear data base. Each new CESAR self shielded cross section library benefits all most recent CEA recommendations as for deterministic physics options. Resulting cross sections are organized as a function of burn up and initial fuel enrichment which allows to condensate this costly process into a series of Legendre polynomials. The final outcome is a fast, accurate and compact CESAR cross section library. Each library is fully validated, against a stochastic transport code (CEA TRIPOLI 4) if needed and against a reference depletion code (CEA DARWIN). Using CESAR does not require any of the neutron physics expertise implemented into cross section libraries generation. It is based on top quality nuclear data (JEFF3.1.1 for ˜400 isotopes) and includes up to date Bateman equation solving algorithms. However, defining a CESAR computation case can be very straightforward. Most results are only 3 steps away from any beginner's ambition: Initial composition, in core depletion and pool decay scenario. On top of a simple utilization architecture, CESAR includes a portable Graphical User Interface which can be broadly deployed in R&D or industrial facilities. Aging facilities currently face decommissioning and dismantling issues. This way to the end of the nuclear fuel cycle requires a careful assessment of source terms in the fuel, core structures and all parts of a facility that must be disposed of with "industrial nuclear" constraints. In that perspective, several CESAR cross section libraries were constructed for early CEA Research and Testing Reactors (RTR's). The aim of this paper is to describe how CESAR operates and how it can be used to help these facilities care for waste disposal, nuclear materials transport or basic safety cases. The test case will be based on the PHEBUS Facility located at CEA - Cadarache.

5-HT2C Receptor Knockdown in the Amygdala Inhibits Neuropathic-Pain-Related Plasticity and Behaviors.

PubMed

Ji, Guangchen; Zhang, Wei; Mahimainathan, Lenin; Narasimhan, Madhusudhanan; Kiritoshi, Takaki; Fan, Xiuzhen; Wang, Jigong; Green, Thomas A; Neugebauer, Volker

2017-02-08

Neuroplasticity in the amygdala drives pain-related behaviors. The central nucleus (CeA) serves major amygdala output functions and can generate emotional-affective behaviors and modulate nocifensive responses. The CeA receives excitatory and inhibitory inputs from the basolateral nucleus (BLA) and serotonin receptor subtype 5-HT 2C R in the BLA, but not CeA, has been implicated anxiogenic behaviors and anxiety disorders. Here, we tested the hypothesis that 5-HT 2C R in the BLA plays a critical role in CeA plasticity and neuropathic pain behaviors in the rat spinal nerve ligation (SNL) model. Local 5-HT 2C R knockdown in the BLA with stereotaxic injection of 5-HT 2C R shRNA AAV vector decreased vocalizations and anxiety- and depression-like behaviors and increased sensory thresholds of SNL rats, but had no effect in sham controls. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that 5-HT 2C R knockdown blocked the increase in neuronal activity (increased responsiveness, irregular spike firing, and increased burst activity) in SNL rats. At the synaptic level, 5-HT 2C R knockdown blocked the increase in excitatory transmission from BLA to CeA recorded in brain slices from SNL rats using whole-cell patch-clamp conditions. Inhibitory transmission was decreased by 5-HT 2C R knockdown in control and SNL conditions to a similar degree. The findings can be explained by immunohistochemical data showing increased expression of 5-HT 2C R in non-GABAergic BLA cells in SNL rats. The results suggest that increased 5-HT 2C R in the BLA contributes to neuropathic-pain-related amygdala plasticity by driving synaptic excitation of CeA neurons. As a rescue strategy, 5-HT 2C R knockdown in the BLA inhibits neuropathic-pain-related behaviors. SIGNIFICANCE STATEMENT Neuroplasticity in the amygdala has emerged as an important pain mechanism. This study identifies a novel target and rescue strategy to control abnormally enhanced amygdala activity in an animal model of neuropathic pain. Specifically, an integrative approach of gene transfer, systems and brain slice electrophysiology, behavior, and immunohistochemistry was used to advance the novel concept that serotonin receptor subtype 5-HT 2C contributes critically to the imbalance between excitatory and inhibitory drive of amygdala output neurons. Local viral vector-mediated 5-HT 2C R knockdown in the amygdala normalizes the imbalance, decreases neuronal activity, and inhibits neuropathic-pain-related behaviors. The study provides valuable insight into serotonin receptor (dys)function in a limbic brain area. Copyright © 2017 the authors 0270-6474/17/371378-16$15.00/0.

Impact of repeated asenapine treatment on FosB/ΔFosB expression in neurons of the rat central nucleus of the amygdala: colocalization with corticoliberine (CRH) and effect of an unpredictable mild stress preconditioning.

PubMed

Majercikova, Z; Kiss, A

2015-04-01

FosB/ΔFosB expression in the central amygdalar nucleus (CeA) in response to repeated asenapine (ASE) treatment (an atypical antipsychotic used for the treatment of schizophrenia) was studied in normal rats and rats preconditioned with chronic unpredictable variable mild stress (CMS). The goal of this study was to reveal whether repeated ASE treatment for 14 days may: 1) induce FosB/ΔFosB expression in the amygdala, 2) activate CRH-synthesizing neurons in the CeA, and 3) interfere with 21 days lasting concomitant CMS preconditioning. Four groups of animals were studied: controls and ASE-, CMS-, and CMS+ASE-treated ones. CMS consisted of the restrain, social isolation, crowding, swimming, and cold and lasted 21 days. The ASE and CMS+ASE groups were from the 7th day of the experiment treated with ASE (0.3 mg/kg, subcutaneously - s.c.) twice a day, i.e. together for 14 days. Controls and CMS groups were treated with saline (300 µl/rat, s.c.) twice a day for 14 days. All the animals were sacrificed on the 22nd day, i.e. 16-18 hours after the last treatments. Single FosB/ΔFosB, FosB/ΔFosB colocalizations with CRH, and CRH immunolabeled perikarya were investigated in the CeA using a combined light and fluorescent immunohistochemistry. The distribution aspect of the black FosB/ΔFosB profiles was homogeneous over the whole CeA and no significant differences in the number of FosB/ΔFosB profiles between the individual groups of the rats really occurred. The level of colocalization pattern of FosB/ΔFosB in CRH perikarya was also very similar between the individual groups and in each case it reached approximately 10% of double-labeling. No differences were also seen in the number of CRH immunolabeled perikarya. The density of CRH nerve projections within the CeA was very alike in the individual groups of animals investigated. The study provides a new anatomical/functional finding about the lack of the stimulatory effect of the repeated ASE treatment on the expression of FosB/ΔFosB, FosB/ΔFosB/CRH colocalizations, and CRH immunolabeled perikarya number in the CeA. In addition, CMS preconditioning itself neither stimulated nor inhibited FosB/ΔFosB expression, nor altered the impact of ASE on the activity of CRH neurons in the CeA.

Post-traumatic stress avoidance is attenuated by corticosterone and associated with brain levels of steroid receptor co-activator-1 in rats.

PubMed

Whitaker, Annie M; Farooq, Muhammad A; Edwards, Scott; Gilpin, Nicholas W

2016-01-01

Individuals with post-traumatic stress disorder (PTSD) avoid trauma-related stimuli and exhibit blunted hypothalamic-pituitary-adrenal (HPA) axis activation at the time of stress. Our rodent model of stress mimics the avoidance symptom cluster of PTSD. Rats are classified as "Avoiders" or "Non-Avoiders" post-stress based on the avoidance of a predator-odor paired context. Previously, we found Avoiders exhibit an attenuated HPA stress response to predator odor. We hypothesized that corticosterone administration before stress would reduce the magnitude and incidence of stress-paired context avoidance. Furthermore, we also predicted that Avoiders would exhibit altered expression of glucocorticoid receptor (GR) signaling machinery elements, including steroid receptor co-activator (SRC)-1. Male Wistar rats (n = 16) were pretreated with corticosterone (25 mg/kg) or saline and exposed to predator-odor stress paired with a context and tested for avoidance 24 h later. A second group of corticosterone-naïve rats (n = 24) were stressed (or not), indexed for avoidance 24 h later, and killed 48 h post-odor exposure to measure phosphorylated GR, FKBP51 and SRC-1 levels in the paraventricular nucleus (PVN), central amygdala (CeA) and ventral hippocampus (VH), all brain sites that highly express GRs and regulate HPA function. Corticosterone pretreatment reduced the magnitude and incidence of avoidance. In Avoiders, predator-odor exposure led to lower SRC-1 expression in the PVN and CeA, and higher SRC-1 expression in the VH. SRC-1 expression in PVN, CeA and VH was predicted by prior avoidance behavior. Hence, a blunted HPA stress response may contribute to stress-induced neuroadaptations in central SRC-1 levels and behavioral dysfunction in Avoider rats.

A Systematic Review of the Level of Evidence in Economic Evaluations of Medical Devices: The Example of Vertebroplasty and Kyphoplasty

PubMed Central

van den Brink, Hélène; Pineau, Judith; Prognon, Patrice; Borget, Isabelle

2015-01-01

Context Economic evaluations are far less frequently reported for medical devices than for drugs. In addition, little is known about the quality of existing economic evaluations, particularly for innovative devices, such as those used in vertebroplasty and kyphoplasty. Objective To assess the level of evidence provided by the available economic evaluations for vertebroplasty and kyphoplasty. Data Sources A systematic review of articles in English or French listed in the MEDLINE, PASCAL, COCHRANE and National Health Service Economic Evaluation databases, with limits on publication date (up to the date of the review, March 2014). Study Selection We included only economic evaluations of vertebroplasty or kyphoplasty. Editorial and methodological articles were excluded. Data Extraction Data were extracted from articles by two authors working independently and using two analysis grids to measure the quality of economic evaluations. Data Synthesis Twenty-one studies met our inclusion criteria. All were published between 2008 and 2014. Eighteen (86%) were full economic evaluations. Cost-effectiveness analysis (CEA) was the most frequent type of economic evaluation, and was present in 11 (52%) studies. Only three CEAs complied fully with the British Medical Journal checklist. The quality of the data sources used in the 21 studies was high, but the CEAs conforming to methodological guidelines did not use high-quality data sources for all components of the analysis. Conclusions This systematic review shows that the level of evidence in economic evaluations of vertebroplasty and kyphoplasty is low, despite the recent publication of a large number of studies. This finding highlights the challenges to be faced to improve the quality of economic evaluations of medical devices. PMID:26661078

Prediagnostic Serum Biomarkers as Early Detection Tools for Pancreatic Cancer in a Large Prospective Cohort Study

PubMed Central

Nolen, Brian M.; Brand, Randall E.; Prosser, Denise; Velikokhatnaya, Liudmila; Allen, Peter J.; Zeh, Herbert J.; Grizzle, William E.; Lomakin, Aleksey; Lokshin, Anna E.

2014-01-01

Background The clinical management of pancreatic cancer is severely hampered by the absence of effective screening tools. Methods Sixty-seven biomarkers were evaluated in prediagnostic sera obtained from cases of pancreatic cancer enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Results The panel of CA 19-9, OPN, and OPG, identified in a prior retrospective study, was not effective. CA 19-9, CEA, NSE, bHCG, CEACAM1 and PRL were significantly altered in sera obtained from cases greater than 1 year prior to diagnosis. Levels of CA 19-9, CA 125, CEA, PRL, and IL-8 were negatively associated with time to diagnosis. A training/validation study using alternate halves of the PLCO set failed to identify a biomarker panel with significantly improved performance over CA 19-9 alone. When the entire PLCO set was used for training at a specificity (SP) of 95%, a panel of CA 19-9, CEA, and Cyfra 21-1 provided significantly elevated sensitivity (SN) levels of 32.4% and 29.7% in samples collected <1 and >1 year prior to diagnosis, respectively, compared to SN levels of 25.7% and 17.2% for CA 19-9 alone. Conclusions Most biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection. PMID:24747429

Literature review of cranial nerve injuries during carotid endarterectomy.

PubMed

Sajid, M S; Vijaynagar, B; Singh, P; Hamilton, G

2007-01-01

In the recent prospective randomised trials on carotid endarterectomy (CEA), the incidence of cranial nerve injuries (CNI) are reported to be higher than in previously published studies. The objective of this study is to review the incidence of post CEA cranial nerve injury and to discover whether it has changed in the last 25 years after many innovations in vascular surgery. Generic terms including carotid endarterectomy, cranial nerve injuries, post CEA complications and cranial nerve deficit after neck surgery were used to search a variety of electronic databases. Based on selection criteria, decisions regarding inclusion and exclusion of primary studies were made. The incidence of CNI before and after 1995 was compared. We found 31 eligible studies from the literature. Patients who underwent CEA through any approach were included in the study. All patients had cranial nerves examined both before and after surgery. The total number of patients who had CEA before 1995 was 3521 with 10.6% CNI (352 patients) and after 1995, 7324 patients underwent CEA with 8.3% CNI (614 patients). Cranial nerves XII, X and VII were most commonly involved (rarely IX and XI). Statistical analysis showed that the incidence of CNI has decreased (X(2) = 5.89 + 0.74 = 6.63 => p-value = 0.0100). CNI is still a significant postoperative complication of carotid endarterectomy. Despite increasing use of CEA, the incidence of CNI has decreased probably because of increased awareness of the possibility of cranial nerve damage.

The once and future application of cost-effectiveness analysis.

PubMed

Berger, M L

1999-09-01

Cost-effectiveness analysis (CEA) is used by payers to make coverage decisions, by providers to make formulary decisions, and by large purchasers/employers and policymakers to choose health care performance measures. However, it continues to be poorly utilized in the marketplace because of overriding financial imperatives to control costs and a low apparent willingness to pay for quality. There is no obvious relationship between the cost-effectiveness of life-saving interventions and their application. Health care decision makers consider financial impact, safety, and effectiveness before cost-effectiveness. WHY IS CEA NOT MORE WIDELY APPLIED? Most health care providers have a short-term parochial financial perspective, whereas CEA takes a long-term view that captures all costs, benefits, and hazards, regardless of to whom they accrue. In addition, a history of poor standardization of methods, unrealistic expectations that CEA could answer fundamental ethical and political issues, and society's failure to accept the need for allocating scarce resources more judiciously, have contributed to relatively little use of the method by decision makers. HOW WILL CEA FIND GREATER UTILITY IN THE FUTURE? As decision makers take a longer-term view and understand that CEA can provide a quantitative perspective on important resource allocation decisions, including the distributional consequences of alternative choices, CEA is likely to find greater use. However, it must be embedded within a framework that promotes confidence in the social justice of health care decision making through ongoing dialogue about how the value of health and health care are defined.

Modern medical treatment with or without carotid endarterectomy for severe asymptomatic carotid atherosclerosis.

PubMed

Kolos, Igor; Troitskiy, Alexandr; Balakhonova, Tatiana; Shariya, Merab; Skrypnik, Denis; Tvorogova, Tatiana; Deev, Alexandr; Boytsov, Sergey

2015-10-01

This study assessed the value of modern medical treatment (MMT) with and without carotid endarterectomy (CEA) in patients with asymptomatic severe carotid artery stenosis. We conducted a randomized trial involving 55 patients with 70% to 79% carotid stenosis at three Russian centers. Between 2009 and 2013, 31 patients were randomized to undergo CEA with MMT (CEA group) and 24 to receive MMT alone. The primary end point was nonfatal ipsilateral stroke or death from any cause during a follow-up period of 5.0 years. The secondary end point was any nonfatal stroke, carotid revascularization, or death from any cause during follow-up. The trial was stopped after a median follow-up of 3.3 years (maximum, 5.0 years). There were two primary events in the CEA group and nine events in the MMT group. The 3.3-year cumulative primary event rates were 6.5% in the CEA group and 37.5% in the MMT group (hazard ratio for the MMT group, 5.06; 95% confidence interval, 1.53-16.79; P = .008). The 3.3-year cumulative secondary end point was 12.9% in the CEA group and 50.0% in the MMT group (hazard ratio for the MMT group, 4.23; 95% confidence interval, 1.55-11.53; P = .0048). CEA as an initial management strategy could reduce the risk of death and major cerebrovascular events when added to MMT. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Assessing the quality of online information for patients with carotid disease.

PubMed

Keogh, C J; McHugh, S M; Clarke Moloney, M; Hannigan, A; Healy, D A; Burke, P E; Kavanagh, E G; Grace, P A; Walsh, S R

2014-01-01

Controversy exists relating to carotid endarterectomy (CEA) versus carotid artery stenting (CAS). We aimed to assess the quality of online patient information relating to both. The Google search engine was searched for "carotid endarterectomy" and "carotid stenting". The first 50 webpages returned were assessed. The Gunning Fog Index (GFI) and Flesch Reading Ease Score (FRES) were calculated to assess readability. The LIDA tool (Minervation Ltd., Oxford, U.K.) was used to assess accessibility, usability and reliability. 20% (n = 10) of the webpages returned for CEA were from peer reviewed sources with 34% (n = 17) posted by hospitals or health services. Comparatively, for CAS, 40% (n = 20) were peer reviewed with 16% (n = 8) posted by hospitals or health services. GFI and FRES scores indicated webpages for both CEA and CAS had poor general readability. Webpages for CEA were easier to read than those for CAS (mean FRES difference of 6.7 (95% CI 0.51 to 12.93, p = 0.03). Median LIDA scores demonstrated acceptable reliability, accessibility and usability of information for both CEA and CAS webpages. The more readable webpages were not associated with higher LIDA scores for either CEA or CAS webpages. Webpages providing information on carotid disease management must be made more readable. Online information currently available to patients regarding CAS is more difficult to read and comprehend than CEA. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Carotid Artery Stenting Trials: Conduct, Results, Critique, and Current Recommendations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macdonald, Sumaira, E-mail: sumaira.macdonald@nuth.nhs.uk

2012-02-15

The carotid stenting trialists have demonstrated persistence and determination in comparing an evolving technique, carotid artery stenting (CAS), against a mature and exacting standard for carotid revascularisation, carotid endarterectomy (CEA). This review focuses on their endeavours. A total of 12 1-on-1 randomised trials comparing CAS and CEA have been reported; 6 of these can be considered major, and 5 of these reflect (in part) current CAS standards of practice and form the basis of this review. At least 18 meta-analyses seeking to compare CAS and CEA exist. These are limited by the quality and heterogeneity of the data informing themmore » (e.g., five trials were stopped prematurely such that they collectively failed to reach recruitment target by >4000 patients). The Carotid Stenting Trialists' Collaboration Publication represents a prespecified meta-analysis of European trials that were sufficiently similar to allow valid conclusions to be drawn; these trials and conclusions will be explored. When the rate of myocardial infarction (MI) is rigorously assessed, CAS and CEA are equivalent for the composite end point of stroke/death and MI, with more minor strokes for CAS and more MIs for CEA. These outcomes have a discrepant impact on quality of life and subsequent mortality. The all-stroke death outcomes for patients <70 years old are equivalent, with more minor strokes occurring in the elderly during CAS than CEA. There are significantly more severe haematomas and cranial nerve injuries after CEA. The influence of experience on outcome cannot be underestimated.« less

CAP4K Teacher Tour: Aligning State-Level Support with Classroom-Level Needs

ERIC Educational Resources Information Center

Colorado Department of Education, 2009

2009-01-01

In January 2009, the Colorado Department of Education (CDE) and the Colorado Education Association (CEA) initiated a 13-city teacher tour to engage teachers in a statewide discussion about CAP4K, its relevance to practice, its impact on teaching and learning and the kind of help that teachers would find useful for classroom implementation. Between…

The value of innovation under value-based pricing.

PubMed

Moreno, Santiago G; Ray, Joshua A

2016-01-01

The role of cost-effectiveness analysis (CEA) in incentivizing innovation is controversial. Critics of CEA argue that its use for pricing purposes disregards the 'value of innovation' reflected in new drug development, whereas supporters of CEA highlight that the value of innovation is already accounted for. Our objective in this article is to outline the limitations of the conventional CEA approach, while proposing an alternative method of evaluation that captures the value of innovation more accurately. The adoption of a new drug benefits present and future patients (with cost implications) for as long as the drug is part of clinical practice. Incidence patients and off-patent prices are identified as two key missing features preventing the conventional CEA approach from capturing 1) benefit to future patients and 2) future savings from off-patent prices. The proposed CEA approach incorporates these two features to derive the total lifetime value of an innovative drug (i.e., the value of innovation). The conventional CEA approach tends to underestimate the value of innovative drugs by disregarding the benefit to future patients and savings from off-patent prices. As a result, innovative drugs are underpriced, only allowing manufacturers to capture approximately 15% of the total value of innovation during the patent protection period. In addition to including the incidence population and off-patent price, the alternative approach proposes pricing new drugs by first negotiating the share of value of innovation to be appropriated by the manufacturer (>15%?) and payer (<85%?), in order to then identify the drug price that satisfies this condition. We argue for a modification to the conventional CEA approach that integrates the total lifetime value of innovative drugs into CEA, by taking into account off-patent pricing and future patients. The proposed approach derives a price that allows manufacturers to capture an agreed share of this value, thereby incentivizing innovation, while supporting health-care systems to pursue dynamic allocative efficiency. However, the long-term sustainability of health-care systems must be assessed before this proposal is adopted by policy makers.

The value of innovation under value-based pricing

PubMed Central

Moreno, Santiago G.; Ray, Joshua A.

2016-01-01

Objective The role of cost-effectiveness analysis (CEA) in incentivizing innovation is controversial. Critics of CEA argue that its use for pricing purposes disregards the ‘value of innovation’ reflected in new drug development, whereas supporters of CEA highlight that the value of innovation is already accounted for. Our objective in this article is to outline the limitations of the conventional CEA approach, while proposing an alternative method of evaluation that captures the value of innovation more accurately. Method The adoption of a new drug benefits present and future patients (with cost implications) for as long as the drug is part of clinical practice. Incidence patients and off-patent prices are identified as two key missing features preventing the conventional CEA approach from capturing 1) benefit to future patients and 2) future savings from off-patent prices. The proposed CEA approach incorporates these two features to derive the total lifetime value of an innovative drug (i.e., the value of innovation). Results The conventional CEA approach tends to underestimate the value of innovative drugs by disregarding the benefit to future patients and savings from off-patent prices. As a result, innovative drugs are underpriced, only allowing manufacturers to capture approximately 15% of the total value of innovation during the patent protection period. In addition to including the incidence population and off-patent price, the alternative approach proposes pricing new drugs by first negotiating the share of value of innovation to be appropriated by the manufacturer (>15%?) and payer (<85%?), in order to then identify the drug price that satisfies this condition. Conclusion We argue for a modification to the conventional CEA approach that integrates the total lifetime value of innovative drugs into CEA, by taking into account off-patent pricing and future patients. The proposed approach derives a price that allows manufacturers to capture an agreed share of this value, thereby incentivizing innovation, while supporting health-care systems to pursue dynamic allocative efficiency. However, the long-term sustainability of health-care systems must be assessed before this proposal is adopted by policy makers. PMID:27123192

Cost-Effectiveness Research in Neurosurgery: We Can and We Must.

PubMed

Stein, Sherman C

2018-01-05

Rapid advancement of medical and surgical therapies, coupled with the recent preoccupation with limiting healthcare costs, makes a collision of the 2 objectives imminent. This article explains the value of cost-effectiveness analysis (CEA) in reconciling the 2 competing goals, and provides a brief introduction to evidence-based CEA techniques. The historical role of CEA in determining whether new neurosurgical strategies provide value for cost is summarized briefly, as are the limitations of the technique. Finally, the unique ability of the neurosurgical community to provide input to the CEA process is emphasized, as are the potential risks of leaving these important decisions in the hands of others. Copyright © 2018 by the Congress of Neurological Surgeons.

Internal carotid artery rupture caused by carotid shunt insertion

PubMed Central

Illuminati, Giulio; Caliò, Francesco G.; Pizzardi, Giulia; Vietri, Francesco

2015-01-01

Introduction Shunting is a well-accepted method of maintaining cerebral perfusion during carotid endarterectomy (CEA). Nonetheless, shunt insertion may lead to complications including arterial dissection, embolization, and thrombosis. We present a complication of shunt insertion consisting of arterial wall rupture, not reported previously. Presentation of case A 78-year-old woman underwent CEA combined with coronary artery bypass grafting (CABG). At the time of shunt insertion an arterial rupture at the distal tip of the shunt was detected and was repaired via a small saphenous vein patch. Eversion CEA and subsequent CABG completed the procedure whose postoperative course was uneventful. Discussion Shunting during combined CEA-CABG may be advisable to assure cerebral protection from possible hypoperfusion due to potential hemodynamic instability of patients with severe coronary artery disease. Awareness and prompt management of possible shunt-related complications, including the newly reported one, may contribute to limiting their harmful effect. Conclusion Arterial wall rupture is a possible, previously not reported, shunt-related complication to be aware of when performing CEA. PMID:26255001

Safety of carotid endarterectomy while on clopidogrel (Plavix). Clinical article.

PubMed

Wait, Scott D; Abla, Adib A; Killory, Brendan D; Starke, Robert M; Spetzler, Robert F; Nakaji, Peter

2010-10-01

Many patients undergoing carotid endarterectomy (CEA) regularly take clopidogrel, a permanent platelet inhibitor. The authors sought to determine whether taking clopidogrel in the period before CEA leads to more bleeding or other complications. The authors performed a retrospective, institutional review board–approved review of 182 consecutive patients who underwent CEA. Clinical, radiographic, and surgical data were gleaned from hospital and clinic records. Analysis was based on the presence or absence of clopidogrel in patients undergoing CEA and was performed twice by considering clopidogrel use within 8 days and within 5 days of surgery to define the groups. Taking clopidogrel within 8 days before surgery resulted in no statistical increase in any measure of morbidity or death. Taking clopidogrel within 5 days was associated with a small but significant increase in operative blood loss and conservatively managed postoperative neck swelling. No measure of permanent morbidity or death was increased in either clopidogrel group. Findings in this study support the safety of preoperative clopidogrel in patients undergoing CEA.

[Hydrogel microchip as a tool for studying exosomes in human serum].

PubMed

Butvilovskaya, V I; Tikhonov, A A; Savvateeva, E N; Ragimov, A A; Salimov, E L; Voloshin, S A; Sidorov, D V; Chernichenko, M A; Polyakov, A P; Filushin, M M; Tsybulskaya, M V; Rubina, A Yu

2017-01-01

Exosomes are cell-derived vesicles that are secreted by both normal and cancer cells. Over the last decade, a few studies have revealed that exosomes cross talk and/or influence major tumor-related pathways such as angiogenesis and metastasis involving many cell types within the tumor microenvironment. The protein composition of the membrane of an exosome reflects that of the membrane of the cell of origin. Because of this, tumor-derived exosomes differ from exosomes that are derived from normal cells. The detection of tumor exosomes and analysis of their molecular composition hold promise for diagnosis and prognosis of cancer. Here, we present hydrogel microarrays (biochips), which contain a panel of immobilized antibodies that recognize tetraspanins (CD9, CD63, CD81) and prognostic markers for colorectal cancer (A33, CD147). These biochips make it possible to analyze the surface proteins of either isolated exosomes or exosomes that are present in the serum samples without isolation. These biochips were successfully used to analyze the surface proteins of exosomes from serum that was collected from a colorectal cancer patient and healthy donor. Biochip-guided immunofluorescent analysis of the exosomes has made it possible for us to detect the A33 antigen and CD147 in the serum sample of the colorectal cancer patient with normal levels of CEA and CA19-9.

Improvement in Cerebral and Ocular Hemodynamics Early after Carotid Endarterectomy in Patients of Severe Carotid Artery Stenosis with or without Contralateral Carotid Occlusion.

PubMed

Wang, Jian; Wang, Weici; Jin, Bi; Zhang, Yanrong; Xu, Ping; Xiang, Feixiang; Zheng, Yi; Chen, Juan; Sheng, Shi; Ouyang, Chenxi; Li, Yiqing

2016-01-01

Purpose. To investigate the alternation in cerebral and ocular blood flow velocity (BFV) in patients of carotid stenosis (CS) with or without contralateral carotid occlusion (CO) early after carotid endarterectomy (CEA). Patients and Methods. Nineteen patients underwent CEA for ≥50% CS. Fourteen patients had the unilateral CS, and five patients had the ipsilateral CS and the contralateral CO. Transcranial Doppler (TCD) and Color Doppler Imaging (CDI) were performed before and early after CEA. Results. In patients with unilateral CS, significant improvements in BFV were observed in anterior cerebral artery (ACA) and middle cerebral artery (MCA) on the ipsilateral side after CEA. In patients of ipsilateral CS and contralateral CO, significant improvements in BFV were observed in the ACA and MCA not only on the ipsilateral side but also on the contralateral side postoperatively. The ipsilateral ophthalmic artery (OA) retrograde flows in two patients were recovered to anterograde direction following CEA. The BFV in short posterior ciliary artery (SPCA) of the ipsilateral side significantly increased postoperatively irrespective of the presence of contralateral CO. Conclusions. CEA improved cerebral anterior circulation hemodynamics especially in patients of unilateral CS and contralateral CO, normalized the OA reverse flow, and increased the blood perfusion of SPCA.

The zebrafish maternal-effect gene cellular atoll encodes the centriolar component sas-6 and defects in its paternal function promote whole genome duplication.

PubMed

Yabe, Taijiro; Ge, Xiaoyan; Pelegri, Francisco

2007-12-01

A female-sterile zebrafish maternal-effect mutation in cellular atoll (cea) results in defects in the initiation of cell division starting at the second cell division cycle. This phenomenon is caused by defects in centrosome duplication, which in turn affect the formation of a bipolar spindle. We show that cea encodes the centriolar coiled-coil protein Sas-6, and that zebrafish Cea/Sas-6 protein localizes to centrosomes. cea also has a genetic paternal contribution, which when mutated results in an arrested first cell division followed by normal cleavage. Our data supports the idea that, in zebrafish, paternally inherited centrosomes are required for the first cell division while maternally derived factors are required for centrosomal duplication and cell divisions in subsequent cell cycles. DNA synthesis ensues in the absence of centrosome duplication, and the one-cycle delay in the first cell division caused by cea mutant sperm leads to whole genome duplication. We discuss the potential implications of these findings with regards to the origin of polyploidization in animal species. In addition, the uncoupling of developmental time and cell division count caused by the cea mutation suggests the presence of a time window, normally corresponding to the first two cell cycles, which is permissive for germ plasm recruitment.

Comparative Review of the Treatment Methodologies of Carotid Stenosis

PubMed Central

Bae, Coney; Szuchmacher, Mauricio; Chang, John B.

2015-01-01

The treatment of carotid stenosis entails three methodologies, namely, medical management, carotid angioplasty and stenting (CAS), as well as carotid endarterectomy (CEA). The North American Symptomatic Carotid Endarterectomy Trial (NASCET) and European Carotid Surgery Trial (ECST) have shown that symptomatic carotid stenosis greater than 70% is best treated with CEA. In asymptomatic patients with carotid stenosis greater than 60%, CEA was more beneficial than treatment with aspirin alone according to the Asymptomatic Carotid Atherosclerosis (ACAS) and Asymptomatic Carotid Stenosis Trial (ACST) trials. When CAS is compared with CEA, the CREST resulted in similar rates of ipsilateral stroke and death rates regardless of symptoms. However, CAS not only increased adverse effects in women, it also amplified stroke rates and death in elderly patients compared with CEA. CAS can maximize its utility in treating focal restenosis after CEA and patients with overwhelming cardiac risk or prior neck irradiation. When performing CEA, using a patch was equated to a more durable result than primary closure, whereas eversion technique is a new methodology deserving a spotlight. Comparing the three major treatment strategies of carotid stenosis has intrinsic drawbacks, as most trials are outdated and they vary in their premises, definitions, and study designs. With the newly codified best medical management including antiplatelet therapies with aspirin and clopidogrel, statin, antihypertensive agents, strict diabetes control, smoking cessation, and life style change, the current trials may demonstrate that asymptomatic carotid stenosis is best treated with best medical therapy. The ongoing trials will illuminate and reshape the treatment paradigm for symptomatic and asymptomatic carotid stenosis. PMID:26417191

Utility of serum Aspergillus-galactomannan antigen to evaluate the risk of severe acute exacerbation in chronic obstructive pulmonary disease

PubMed Central

Yoshimura, Katsuhiro; Inoue, Yusuke; Nishimoto, Koji; Karayama, Masato; Furuhashi, Kazuki; Enomoto, Noriyuki; Nakamura, Yutaro; Inui, Naoki; Yokomura, Koushi; Imokawa, Shiro; Suda, Takafumi

2018-01-01

Background Recent studies have shown that the microbiome, namely Aspergillus species, play a previously unrecognized role in both stable and exacerbated chronic obstructive pulmonary disease (COPD). Galactomannan is a major component of the Aspergillus cell wall that has been widely used as a diagnostic marker. Objectives To explore whether serum levels of Aspergillus-galactomannan antigen could be used to evaluate the risk of severe acute exacerbation of COPD (AE-COPD). Methods We measured the Aspergillus-galactomannan antigen levels of 191 patients with stable COPD, and examined its clinical relevance including AE-COPD. Results There were 77 (40.3%) patients who were positive for serum Aspergillus-galactomannan antigen (≥0.5). High Aspergillus-galactomannan antigen level (≥0.7) was associated with older age and presence of bronchiectasis and cysts on computed tomography images. Compared to patients with low Aspergillus-galactomannan antigen level (<0.7), patients with high Aspergillus-galactomannan antigen level had significantly higher incidence of severe AE-COPD (P = 0.0039, Gray’s test) and respiratory-related mortality (P = 0.0176, log-rank test). Multivariate analysis showed that high Aspergillus-galactomannan antigen level was independently associated with severe AE-COPD (hazard ratio, 2.162; 95% confidence interval, 1.267−3.692; P = 0.005). Conclusion Serum Aspergillus-galactomannan antigen was detected in patients with COPD, and elevated serum Aspergillus-galactomannan antigen was associated with severe AE-COPD. PMID:29870550

Cost-effectiveness analyses in orthopaedic sports medicine: a systematic review.

PubMed

Nwachukwu, Benedict U; Schairer, William W; Bernstein, Jaime L; Dodwell, Emily R; Marx, Robert G; Allen, Answorth A

2015-06-01

As increasing attention is paid to the cost of health care delivered in the United States (US), cost-effectiveness analyses (CEAs) are gaining in popularity. Reviews of the CEA literature have been performed in other areas of medicine, including some subspecialties within orthopaedics. Demonstrating the value of medical procedures is of utmost importance, yet very little is known about the overall quality and findings of CEAs in sports medicine. To identify and summarize CEA studies in orthopaedic sports medicine and to grade the quality of the available literature. Systematic review. A systematic review of the literature was performed to compile findings and grade the methodological quality of US-based CEA studies in sports medicine. The Quality of Health Economic Studies (QHES) instrument and the checklist by the US Panel on Cost-effectiveness in Health and Medicine were used to assess study quality. One-sided Fisher exact testing was performed to analyze the predictors of high-quality CEAs. Twelve studies met inclusion criteria. Five studies examined anterior cruciate ligament reconstruction, 3 studies examined rotator cuff repair, 2 examined autologous chondrocyte implantation, 1 study examined hip arthroscopic surgery, and 1 study examined the operative management of shoulder dislocations. Based on study findings, operative intervention in sports medicine is highly cost-effective. The quality of published evidence is good, with a mean quality score of 81.8 (range, 70-94). There is a trend toward higher quality in more recent publications. No significant predictor of high-quality evidence was found. The CEA literature in sports medicine is good; however, there is a paucity of studies, and the available evidence is focused on a few procedures. More work needs to be conducted to quantify the cost-effectiveness of different techniques and procedures within sports medicine. The QHES tool may be useful for the evaluation of future CEAs. © 2014 The Author(s).

Carotid bypass: a safe and durable solution for recurrent carotid stenosis.

PubMed

Spinelli, Francesco; Martelli, Eugenio; Stilo, Francesco; Pipitò, Narayana; Benedetto, Filippo; Spinelli, Domenico; Squillaci, Domenico; De Caridi, Giovanni; Barillà, David

2014-07-01

The long-term results of carotid artery stenting (CAS) for post-carotid endarterectomy (CEA) restenosis are disappointing (4-year patency rates: ∼75%). Since 1988, our group has offered carotid bypass (CB) as an alternative to redo CEA and later also to CAS in this setting. The aim of this retrospective study was to investigate early and late outcomes associated with CB in this population. Data were collected from patients treated with CB in the year 2000-2012 for significant/symptomatic post-CEA restenosis (or intra-stent restenosis [ISR] after CAS for post-CEA restenosis). All patients had good life expectancy. CB was performed under loco-regional anesthesia. With the aid of sequential vessel clamping, the graft (great saphenous vein [GSV] or polytetrafluoroethylene) was anastomosed with the common carotid artery (side-to-end) and the distal internal carotid artery (end-to-side). Patients were followed with clinical and duplex scan assessments at 1, 3, and 6 months and yearly thereafter. The study population comprised 21 patients (mean age 67.3 years; 17 men). CB was performed for post-CEA restenosis (or ISR after CAS for post-CEA restenosis, n=3) 51.2 months (mean) after the previous operation. GSV grafts were used in half of the cases (n=11; 52.4%); temporary shunting was used in 4 (19%) patients. Intraoperative complications (none fatal) occurred in 4 (19%) patients (3 transient peripheral nerve injuries, 1 cervical hematoma). During follow-up (mean 64.8 months), there were no neurologic complications or restenoses. Overall mortality was 33.3% (6 deaths from acute myocardial infarctions, 1 from a ruptured abdominal aortic aneurysm). For post-CEA restenosis (or ISR after CAS for post-CEA restenosis), CB offers superior long-term patency rates than CAS (or redo angioplasty) and an acceptable risk of cranial nerve damage. Copyright © 2014 Elsevier Inc. All rights reserved.

Measurement of the center edge angle and determination of the Severin classification using digital radiography, computer-assisted measurement tools, and a Severin algorithm: intraobserver and interobserver reliability revisited.

PubMed

Carroll, Kristen L; Murray, Kathleen A; MacLeod, Lynne M; Hennessey, Theresa A; Woiczik, Marcella R; Roach, James W

2011-06-01

Numerous studies underscore the poor intraobserver and interobserver reliability of both the center edge angle (CEA) and the Severin classification using plain film measurements. In this study, experienced observers applied a computer-assisted measurement program to determine the CEA in digital pelvic radiographs of adults who had been previously treated for dysplasia of the hip (DDH). Using a teaching aid/algorithm of the Severin classification, the observers then assigned a Severin rating to these hips. Intraobserver and interobserver errors were then calculated on both the CEA measurements and the Severin classifications. Four pediatric orthopaedic surgeons and 1 pediatric radiologist calculated the CEAs using the OrthoView TM planning system and then determined the Severin classification on 41 blinded digital pelvic radiographs. The radiographs were evaluated by each examiner twice, with evaluations separated by 2 months. All examiners reviewed a Severin classification algorithm before making their Severin assignments. The intraobserver and interobserver reliability for both the CEA and the Severin classification were calculated using the interclass correlation coefficients and Cohen and Fleiss κ scores, respectively. The intraobserver and interobserver reliability for CEA measurement was moderate to almost perfect. When we separated the Severin classification into 3 clinically relevant groups of good (Severin I and II), dysplastic (Severin III), and poor (Severin IV and above), our interobserver reliability neared almost perfect. The Severin classification is an extremely useful and oft-used radiographic measure for the success of DDH treatment. Our research found digital radiography, computer-aided measurement tools, the use of a Severin algorithm, and separating the Severin classification into 3 clinically relevant groups significantly increased the intraobserver and interobserver reliability of both the CEA and Severin classification. This finding will assist future studies using the CEA and Severin classification in the radiographic assessment of DDH treatment outcomes.

When is critical care medicine cost-effective? A systematic review of the cost-effectiveness literature.

PubMed

Talmor, Daniel; Shapiro, Nathan; Greenberg, Dan; Stone, Patricia W; Neumann, Peter J

2006-11-01

Receiving care in an intensive care unit can greatly influence patients' survival and quality of life. Such treatments can, however, be extremely resource intensive. Therefore, it is increasingly important to understand the costs and consequences associated with interventions aimed at reducing mortality and morbidity of critically ill patients. Cost-effectiveness analyses (CEAs) have become increasingly common to aid decisions about the allocation of scarce healthcare resources. To identify published original CEAs presenting cost/quality-adjusted life year or cost/life-year ratios for treatments used in intensive care units, to summarize the results in an accessible format, and to identify areas in critical care medicine that merit further economic evaluation. We conducted a systematic search of the English-language literature for original CEAs of critical care interventions published from 1993 through 2003. We collected data on the target population, therapy or program, study results, analytic methods employed, and the cost-effectiveness ratios presented. We identified 19 CEAs published through 2003 with 48 cost-effectiveness ratios pertaining to treatment of severe sepsis, acute respiratory failure, and general critical care interventions. These ratios ranged from cost saving to 958,423 US dollars/quality-adjusted life year and from 1,150 to 575,054 US dollars/life year gained. Many studies reported favorable cost-effectiveness profiles (i.e., below 50,000 US dollars/life year or quality-adjusted life year). Specific interventions such as activated protein C for patients with severe sepsis have been shown to provide good value for money. However, overall there is a paucity of CEA literature on the management of the critically ill, and further high-quality CEA is needed. In particular, research should focus on costly interventions such as 24-hr intensivist availability, early goal-directed therapy, and renal replacement therapy. Recent guidelines for the conduct of CEAs in critical care may increase the number and improve the quality of future CEAs.

Unusual clinical manifestation of pheochromocytoma in a MEN2A patient.

PubMed

Guerrieri, M; Filipponi, S; Arnaldi, G; Giovagnetti, M; Lezoche, E; Mantero, F; Taccaliti, A

2002-01-01

A case of unusual clinical manifestation of pheochromocytoma in a type 2A multiple endocrine neoplasia (MEN2A) patient is presented. A 27-year-old man affected by MEN2A syndrome, complaining of anxiety and depression, was admitted in our Division. Past medical history included a total thyroidectomy for medullary carcinoma in 1985, and left adrenalectomy for pheochromocytoma in 1994. Blood pressure was 130/ 85 mmHg without orthostatic hypotension and pulse rate was 72 beats/min. Laboratory data revealed thyroid hormones and carcinoembryonic antigen (CEA) in the normal range and high basal serum calcitonin levels (158 pg/ml). Plasma catecholamines and vanillylmandelic acid resulted in normal levels but epinephrine/norepinephrine ratio was elevated (0.65). The glucagon stimulation test showed positive clinical and biochemical response. Magnetic resonance imaging (MRI) and meta-iodobenzylguanidine (MIBG) scintiscan confirmed the presence of bilateral adrenal masses. Bilateral adrenalectomy by laparoscopic anterior approach was performed. Histology was consistent with adrenal pheochromocytomas. After surgical approach, psychiatric findings disappeared and did not recur at follow-up in spite of no medication for two years. In conclusion, bilateral pheochromocytoma is more frequent in MEN2A syndrome and probably understimated if the follow-up is not prolonged. In these cases clinical features are often aspecific and basal hormonal data may be normal in a great number of patients. Therefore long-term observation is justified in these patients. Pheochromocytoma was described as the "great mimic" for the numerous subjective manifestations. Differential diagnosis among typical features of neuropsychiatric disorders and pheochromocytoma must be considered.

Short-term results of a randomized trial examining timing of carotid endarterectomy in patients with severe asymptomatic unilateral carotid stenosis undergoing coronary artery bypass grafting.

PubMed

Illuminati, Giulio; Ricco, Jean-Baptiste; Caliò, Francesco; Pacilè, Maria Antonietta; Miraldi, Fabio; Frati, Giacomo; Macrina, Francesco; Toscano, Michele

2011-10-01

This study evaluated the timing of carotid endarterectomy (CEA) in the prevention of stroke in patients with asymptomatic carotid stenosis >70% receiving a coronary artery bypass graft (CABG). From January 2004 to December 2009, 185 patients with unilateral asymptomatic carotid artery stenosis >70%, candidates for CABG, were randomized into two groups. In group A, 94 patients received a CABG with previous or simultaneous CEA. In group B, 91 patients underwent CABG, followed by CEA. All patients underwent preoperative helical computed tomography scans, excluding significant atheroma of the ascending aorta or aortic arch. Baseline characteristics of the patients, type of coronary artery lesion, and preoperative myocardial function were comparable in the two groups. In group A, all patients underwent CEA under general anesthesia with the systematic use of a carotid shunt, and 79 patients had a combined procedure and 15 underwent CEA a few days before CABG. In group B, all patients underwent CEA, 1 to 3 months after CABG, also under general anesthesia and with systematic carotid shunting. Two patients (one in each group) died of cardiac failure in the postoperative period. Operative mortality was 1.0% in group A and 1.1% in group B (P = .98). No strokes occurred in group A vs seven ipsilateral ischemic strokes in group B, including three immediate postoperative strokes and four late strokes, at 39, 50, 58, and 66 days, after CABG. These late strokes occurred in patients for whom CEA was further delayed due to an incomplete sternal wound healing or because of completion of a cardiac rehabilitation program. The 90-day stroke and death rate was 1.0% (one of 94) in group A and 8.8% (eight of 91) in group B (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.01-0.91; P = .02). Logistic regression analysis showed that only delayed CEA (OR, 14.2; 95% CI, 1.32-152.0; P = .03) and duration of cardiopulmonary bypass (OR, 1.06; 95% CI, 1.02-1.11; P = .004) reliably predicted stroke or death at 90 days. This study suggests that previous or simultaneous CEA in patients with unilateral severe asymptomatic carotid stenosis undergoing CABG could prevent stroke better than delayed CEA, without increasing the overall surgical risk. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Does the sequence of pulmonary vasculature ligation have any oncological impact during an anatomical lung resection for non-small-cell lung cancer?

PubMed

Toufektzian, Levon; Attia, Rizwan; Polydorou, Nicolaos; Veres, Lukacs

2015-02-01

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was 'in patients with primary lung carcinoma, does the sequence of pulmonary vasculature ligation during anatomical lung resection influence the oncological outcomes?' A total of 48 papers were found using the reported search, of which 7 represented the best evidence to answer the question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Among six prospective studies included, five of them randomized patients to either pulmonary vein or artery occlusion first during anatomical lung resection, while one study was retrospective. Two reports did not find any difference between pulmonary vein and artery occlusion first during long-term follow-up in terms of either disease recurrence (51 vs 53%, P = 0.7), or 5-year overall survival (54 vs 50%, P = 0.82). One report did not find any difference with regard to circulating tumour cells either after thoracotomy (5.0 vs 3.9, P = 0.4), or after the completion of lobectomy (38.0 vs 70.0, P = 0.23). One report found a higher expression of CD44v6 (P = 0.008) and CK19 (P = 0.05) in patients undergoing pulmonary arterial occlusion first. One report found that pulmonary vein occlusion before that of the pulmonary arterial branches has a favourable outcome on circulating carcino-embryonic antigen (CEA) mRNA in the peripheral blood, while another one did not find a significant difference in circulating levels of CEA mRNA (P = 0.075) and CK19 mRNA (P = 0.086) with either method. Another study reported no correlation between circulating pin1 mRNA levels in peripheral blood after the completion of the resection and the sequence of ligation of pulmonary vessels (9.95 ± 0.91 vs 14.71 ± 1.64, P > 0.05). Based on the two studies assessing the long-term outcome of patients with primary lung cancer undergoing anatomical curative resection, the sequence of ligation of pulmonary vessels does not seem to influence the oncological outcomes or survival. However, the other studies focusing on the influence of these techniques on circulating tumour cells or their molecular products report conflicting results the clinical consequences of which cannot be predicted. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

[Comparison of blood pressure profiles with flunitrazepam/fentanyl/nitrous oxide vs cervical epidural anesthesia in surgery of the carotid artery].

PubMed

Pluskwa, F; Bonnet, F; Abhay, K; Touboul, C; Rey, B; Marcandoro, J; Becquemin, J B

1989-01-01

A study was carried out to compare the evolution of arterial blood pressure during carotid endarterectomy performed under either general anaesthesia (GA) or cervical epidural anaesthesia (CEA). 20 patients were randomly assigned to two equal groups. In the CEA group, 15 ml of 0.375% bupivacaine and 150 micrograms fentanyl were injected into the epidural space at C7-D1 level. In the GA group, patients were anaesthetized with 0.2 mg.kg-1 flunitrazepam and 5 micrograms.kg-1 fentanyl; intubation was carried out using 0.08 mg.kg-1 vecuronium, and the patients were ventilated with a mixture of nitrous oxide and oxygen (50% of each). Further injections, every 30 min, of 2 micrograms.kg-1 fentanyl were given to the patients in group GA. Blood pressure was monitored continuously, up to 4 h postoperatively, with a radial arterial catheter. Per- or postoperative hypertension was defined as a rise in systolic arterial blood pressure (Pasys) over 180 mmHg for greater than 3 min; this was treated with 20 mg nifedipine intranasally (group CEA) or 100 micrograms fentanyl with 0.5 mg flunitrazepam with or without nifedipine (group GA). Per- or postoperative hypotension was defined as a fall in Pasys below 100 mmHg and or a 30% fall in mean arterial blood pressure for greater than 3 min; this was treated, in both groups, with an intravenous bolus of 3 mg ephedrine. Patients in group CEA experienced more frequent episodes of peroperative hypertension (8/2; p less than 0.02) and postoperative hypotension (5/1) than group GA.(ABSTRACT TRUNCATED AT 250 WORDS)

Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection.

PubMed

Kolitz-Domb, Michal; Grinberg, Igor; Corem-Salkmon, Enav; Margel, Shlomo

2014-08-12

The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer owing to the negligible absorption and autofluorescence of water and other intrinsic biomolecules in this region. The main aim of the present study is to synthesize and characterize novel NIR fluorescent nanoparticles based on proteinoid and PLLA for early detection of colon tumors. The present study describes the synthesis of new proteinoid-PLLA copolymer and the preparation of NIR fluorescent nanoparticles for use in diagnostic detection of colon cancer. These fluorescent nanoparticles were prepared by a self-assembly process in the presence of the NIR dye indocyanine green (ICG), a FDA-approved NIR fluorescent dye. Anti-carcinoembryonic antigen antibody (anti-CEA), a specific tumor targeting ligand, was covalently conjugated to the P(EF-PLLA) nanoparticles through the surface carboxylate groups using the carbodiimide activation method. The P(EF-PLLA) nanoparticles are stable in different conditions, no leakage of the encapsulated dye into PBS containing 4% HSA was detected. The encapsulation of the NIR fluorescent dye within the P(EF-PLLA) nanoparticles improves significantly the photostability of the dye. The fluorescent nanoparticles are non-toxic, and the biodistribution study in a mouse model showed they evacuate from the body over 24 h. Specific colon tumor detection in a chicken embryo model and a mouse model was demonstrated for anti-CEA-conjugated NIR fluorescent P(EF-PLLA) nanoparticles. The results of this study suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent P(EF-PLLA) nanoparticles over colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs such as paclitaxel and/or doxorubicin, within these biodegradable NIR fluorescent P(EF-PLLA) nanoparticles, for both detection and therapy of colon cancer.

Engineering of near IR fluorescent albumin nanoparticles for in vivo detection of colon cancer.

PubMed

Cohen, Sarit; Margel, Shlomo

2012-08-14

The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer because water and other intrinsic biomolecules display negligible absorption or autofluorescence in this region. Novel fluorescent nanoparticles with potential to improve neoplasm detection sensitivity may prove to be a valuable tool in early detection of colon tumors. The present study describes the synthesis and use of NIR fluorescent albumin nanoparticles as a diagnostic tool for detection of colon cancer. These fluorescent nanoparticles were prepared by a precipitation process of human serum albumin (HSA) in aqueous solution in the presence of a carboxylic acid derivative of the NIR dye IR-783 (CANIR). Tumor-targeting ligands such as peanut agglutinin (PNA), anti-carcinoembryonic antigen antibodies (anti-CEA) and tumor associated glycoprotein-72 monoclonal antibodies (anti-TAG-72) were covalently conjugated to the albumin nanoparticles via the surface carboxylate groups by using the carbodiimide activation method. Leakage of the encapsulated dye into PBS containing 4% HSA or human bowel juice was not detected. This study also demonstrates that the encapsulation of the NIR fluorescent dye within the HSA nanoparticles reduces the photobleaching of the dye significantly. Specific colon tumor detection in a mouse model was demonstrated for PNA, anti-CEA and anti-TAG-72 conjugated NIR fluorescent HSA nanoparticles. These bioactive NIR fluorescent albumin nanoparticles also detected invisible tumors that were revealed as pathological only subsequent to histological analysis. These results may suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent nanoparticles over regular colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs, such as paclitaxel and doxorubicin, within these biodegradable NIR fluorescent HSA nanoparticles, in order to use them for both detection as well as therapy of colon cancer and others.

The Human Cytomegalovirus-Specific UL1 Gene Encodes a Late-Phase Glycoprotein Incorporated in the Virion Envelope

PubMed Central

Shikhagaie, Medya; Mercé-Maldonado, Eva; Isern, Elena; Muntasell, Aura; Albà, M. Mar; López-Botet, Miguel; Hengel, Hartmut

2012-01-01

We have investigated the previously uncharacterized human cytomegalovirus (HCMV) UL1 open reading frame (ORF), a member of the rapidly evolving HCMV RL11 family. UL1 is HCMV specific; the absence of UL1 in chimpanzee cytomegalovirus (CCMV) and sequence analysis studies suggest that UL1 may have originated by the duplication of an ancestor gene from the RL11-TRL cluster (TRL11, TRL12, and TRL13). Sequence similarity searches against human immunoglobulin (Ig)-containing proteins revealed that HCMV pUL1 shows significant similarity to the cellular carcinoembryonic antigen-related (CEA) protein family N-terminal Ig domain, which is responsible for CEA ligand recognition. Northern blot analysis revealed that UL1 is transcribed during the late phase of the viral replication cycle in both fibroblast-adapted and endotheliotropic strains of HCMV. We characterized the protein encoded by hemagglutinin (HA)-tagged UL1 in the AD169-derived HB5 background. UL1 is expressed as a 224-amino-acid type I transmembrane glycoprotein which becomes detectable at 48 h postinfection. In infected human fibroblasts, pUL1 colocalized at the cytoplasmic site of virion assembly and secondary envelopment together with TGN-46, a marker for the trans-Golgi network, and viral structural proteins, including the envelope glycoprotein gB and the tegument phosphoprotein pp28. Furthermore, analyses of highly purified AD169 UL1-HA epitope-tagged virions revealed that pUL1 is a novel constituent of the HCMV envelope. Importantly, the deletion of UL1 in HCMV TB40/E resulted in reduced growth in a cell type-specific manner, suggesting that pUL1 may be implicated in regulating HCMV cell tropism. PMID:22345456

Hypoxia-inducible bidirectional shRNA expression vector delivery using PEI/chitosan-TBA copolymers for colorectal Cancer gene therapy.

PubMed

Javan, Bita; Atyabi, Fatemeh; Shahbazi, Majid

2018-06-01

This investigation was conducted to construct a hypoxia/colorectal dual-specific bidirectional short hairpin RNA (shRNA) expression vector and to transfect it into the colon cancer cell line HT-29 with PEI/chitosan-TBA nanoparticles for the simultaneous knock down of β-catenin and Bcl-2 under hypoxia. To construct a pRNA-bipHRE-CEA vector, the carcinoma embryonic antigen (CEA) promoter designed in two directions and the vascular endothelial growth factor (VEGF) enhancer were inserted between two promoters for hypoxic cancer specific gene expression. To confirm the therapeutic effect of the dual-specific vector, β-catenin and Bcl-2 shRNAs were inserted downstream of each promoter. The physicochemical properties, the cytotoxicity, and the transfection efficiency of these PEI/chitosan-TBA nanoparticles were investigated. In addition, the antitumor effects of the designed vector on the expression of β-catenin and Bcl-2, cell cycle distribution, and apoptosis were investigated in vitro. The silencing effect of the hypoxia-response shRNA expression vector was relatively low (18%-25%) under normoxia, whereas it was significantly increased to approximately 50%-60% in the HT-29 cell line. Moreover, the cancer cells showed significant G0/G1 arrest and increased apoptosis due to gene silencing under hypoxia. Furthermore, MTS assay, fluorescence microscopy images, and flow cytometry analyses confirmed that the PEI/chitosan-TBA blend system provided effective transfection with low cytotoxicity. This novel hypoxia-responsive shRNA expression vector may be useful for RNA interference (RNAi)-based cancer gene therapy in hypoxic colorectal tumors. Moreover, the PEI/chitosan-TBA copolymer might be a promising gene carrier for use in gene transfer in vivo. Copyright © 2018. Published by Elsevier Inc.

Caspase-3 activity, response to chemotherapy and clinical outcome in patients with colon cancer.

PubMed

de Oca, Javier; Azuara, Daniel; Sanchez-Santos, Raquel; Navarro, Matilde; Capella, Gabriel; Moreno, Victor; Sola, Anna; Hotter, Georgina; Biondo, Sebastiano; Osorio, Alfonso; Martí-Ragué, Joan; Rafecas, Antoni

2008-01-01

The prognostic value of the degree of apoptosis in colorectal cancer is controversial. This study evaluates the putative clinical usefulness of measuring caspase-3 activity as a prognostic factor in colonic cancer patients receiving 5-fluoracil adjuvant chemotherapy. We evaluated caspase-3-like protease activity in tumours and in normal colon tissue. Specimens were studied from 54 patients. These patients had either stage III cancer (Dukes stage C) or high-risk stage II cancer (Dukes stage B2 with invasion of adjacent organs, lymphatic or vascular infiltration or carcinoembryonic antigen [CEA] >5). Median follow-up was 73 months. Univariate analysis was performed previously to explore the relation of different variables (age, sex, preoperative CEA, tumour size, Dukes stage, vascular invasion, lymphatic invasion, caspase-3 activity in tumour and caspase-3 activity in normal mucosa) as prognostic factors of tumour recurrence after chemotherapy treatment. Subsequently, a multivariate Cox regression model was performed. Median values of caspase-3 activity in tumours were more than twice those in normal mucosa (88.1 vs 40.6 U, p=0.001), showing a statistically significant correlation (r=0.34). Significant prognostic factors of recurrence in multivariate analysis were: male sex (odds ratio, OR=3.53 [1.13-10.90], p=0.02), age (OR=1.09 [1.01-1.18], p=0.03), Dukes stage (OR=1.93 [1.01-3.70]), caspase-3 activity in normal mucosa (OR=1.02 [1.01-1.04], p=0.017) and caspase-3 activity in tumour (OR=1.02 [1.01-1.03], p=0.013). Low caspase-3 activity in the normal mucosa and tumour are independent prognostic factors of tumour recurrence in patients receiving adjuvant 5-fluoracil-based treatment in colon cancer, correlating with poor disease-free survival and higher recurrence rate.

Examining the cost-effectiveness of cancer screening promotion.

PubMed

Andersen, M Robyn; Urban, Nicole; Ramsey, Scott; Briss, Peter A

2004-09-01

Cost-effectiveness analyses (CEAs) can help to quantify the contribution of the promotion of a screening program to increased participation in screening. The cost-effectiveness (C/E) of screening promotion depends in large part on the endpoints of interest. At the most fundamental level, the C/E of a strategy for promoting screening would focus on the attendance rate, or cost per person screened, and the C/E would be influenced by the costs of promotion, as well as by the size and responsiveness of the target population. In addition, the costs of screening promotion (measured as the cost per additional participant in screening) can be included in a CEA estimate of the screening technology. In this case, depending on the efficacy of the screening test and the costs and influence of the promotion, the C/E of screening may improve or become poorer. In the current study, the authors reviewed the literature on the C/E of cancer screening promotion. The following lessons were learned regarding the C/E of screening and its promotion: 1) high-quality information on the C/E of screening is increasingly available; 2) cost-effective promotion of screening is dependent on cost-effective screening strategies; 3) quality-of-life effects may be important in assessing the overall C/E of screening programs; 4) research efforts aimed at identifying cost-effective approaches to screening promotion are useful but sparse; 5) C/E studies should be better incorporated into well designed effectiveness research efforts; 6) variations in C/E according to intervention characteristics, population characteristics, and context should be evaluated in greater depth; 7) the long-term effects of screening promotion are critical to assessing C/E; 8) the effects of promotion on costs of screening must be better understood; and 9) CEA must be interpreted in light of other information. The authors showed that CEA can be a valuable tool for understanding the merits of health promotion interventions and that CEA is particularly valuable in identifying screening strategies that might be promoted most cost-effectively.

Kappa opioid receptor antagonists: A possible new class of therapeutics for migraine prevention.

PubMed

Xie, Jennifer Y; De Felice, Milena; Kopruszinski, Caroline M; Eyde, Nathan; LaVigne, Justin; Remeniuk, Bethany; Hernandez, Pablo; Yue, Xu; Goshima, Naomi; Ossipov, Michael; King, Tamara; Streicher, John M; Navratilova, Edita; Dodick, David; Rosen, Hugh; Roberts, Ed; Porreca, Frank

2017-07-01

Background Stress is the most commonly reported migraine trigger. Dynorphin, an endogenous opioid peptide acting preferentially at kappa opioid receptors (KORs), is a key mediator of stress responses. The aim of this study was to use an injury-free rat model of functional cephalic pain with features of migraine and medication overuse headache (MOH) to test the possible preventive benefit of KOR blockade on stress-induced cephalic pain. Methods Following sumatriptan priming to model MOH, rats were hyper-responsive to environmental stress, demonstrating delayed cephalic and extracephalic allodynia and increased levels of CGRP in the jugular blood, consistent with commonly observed clinical outcomes during migraine. Nor-binaltorphimine (nor-BNI), a long-acting KOR antagonist or CYM51317, a novel short-acting KOR antagonist, were given systemically either during sumatriptan priming or immediately before environmental stress challenge. The effects of KOR blockade in the amygdala on stress-induced allodynia was determined by administration of nor-BNI into the right or left central nucleus of the amygdala (CeA). Results KOR blockade prevented both stress-induced allodynia and increased plasma CGRP. Stress increased dynorphin content and phosphorylated KOR in both the left and right CeA in sumatriptan-primed rats. However, KOR blockade only in the right CeA prevented stress-induced cephalic allodynia as well as extracephalic allodynia, measured in either the right or left hindpaws. U69,593, a KOR agonist, given into the right, but not the left, CeA, produced allodynia selectively in sumatriptan-primed rats. Both stress and U69,593-induced allodynia were prevented by right CeA U0126, a mitogen-activated protein kinase inhibitor, presumably acting downstream of KOR. Conclusions Our data reveal a novel lateralized KOR circuit that mediated stress-induced cutaneous allodynia and increased plasma CGRP in an injury-free model of functional cephalic pain with features of migraine and medication overuse headache. Selective, small molecule, orally available, and reversible KOR antagonists are currently in development and may represent a novel class of preventive therapeutics for migraine.

Comparison of the CEAS and Williams-type barley yield models for North Dakota and Minnesota

NASA Technical Reports Server (NTRS)

Leduc, S. (Principal Investigator)

1982-01-01

The CEAS and Williams type models were compared based on specified selection criteria which includes a ten year bootstrap test (1970-1979). Based on this, the models were quite comparable; however, the CEAS model was slightly better overall. The Williams type model seemed better for the 1974 estimates. Because that year spring wheat yield was particularly low, the Williams type model should not be excluded from further consideration.

Future costs in cost effectiveness analysis.

PubMed

Lee, Robert H

2008-07-01

This paper resolves several controversies in CEA. Generalizing [Garber, A.M., Phelps, C.E., 1997. Economic foundations of cost-effectiveness analysis. Journal of Health Economics 16 (1), 1-31], the paper shows accounting for unrelated future costs distorts decision making. After replicating [Meltzer, D., 1997. Accounting for future costs in medical cost-effectiveness analysis. Journal of Health Economics 16 (1), 33-64] quite different conclusion that unrelated future costs should be included in CEA, the paper shows that Meltzer's findings result from modeling the budget constraint as an annuity, which is problematic. The paper also shows that related costs should be included in CEA. This holds for a variety of models, including a health maximization model. CEA should treat costs in the manner recommended by Garber and Phelps.

Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala Is Required for Alcohol Dependence.

PubMed

de Guglielmo, Giordano; Crawford, Elena; Kim, Sarah; Vendruscolo, Leandro F; Hope, Bruce T; Brennan, Molly; Cole, Maury; Koob, George F; George, Olivier

2016-09-07

Abstinence from alcohol is associated with the recruitment of neurons in the central nucleus of the amygdala (CeA) in nondependent rats that binge drink alcohol and in alcohol-dependent rats. However, whether the recruitment of this neuronal ensemble in the CeA is causally related to excessive alcohol drinking or if it represents a consequence of excessive drinking remains unknown. We tested the hypothesis that the recruitment of a neuronal ensemble in the CeA during abstinence is required for excessive alcohol drinking in nondependent rats that binge drink alcohol and in alcohol-dependent rats. We found that inactivation of the CeA neuronal ensemble during abstinence significantly decreased alcohol drinking in both groups. In nondependent rats, the decrease in alcohol intake was transient and returned to normal the day after the injection. In dependent rats, inactivation of the neuronal ensemble with Daun02 produced a long-term decrease in alcohol drinking. Moreover, we observed a significant reduction of somatic withdrawal signs in dependent animals that were injected with Daun02 in the CeA. These results indicate that the recruitment of a neuronal ensemble in the CeA during abstinence from alcohol is causally related to excessive alcohol drinking in alcohol-dependent rats, whereas a similar neuronal ensemble only partially contributed to alcohol-binge-like drinking in nondependent rats. These results identify a critical neurobiological mechanism that may be required for the transition to alcohol dependence, suggesting that focusing on the neuronal ensemble in the CeA may lead to a better understanding of the etiology of alcohol use disorders and improve medication development. Alcohol dependence recruits neurons in the central nucleus of the amygdala (CeA). Here, we found that inactivation of a specific dependence-induced neuronal ensemble in the CeA reversed excessive alcohol drinking and somatic signs of alcohol dependence in rats. These results identify a critical neurobiological mechanism that is required for alcohol dependence, suggesting that targeting dependence neuronal ensembles may lead to a better understanding of the etiology of alcohol use disorders, with implications for diagnosis, prevention, and treatment. Copyright © 2016 the authors 0270-6474/16/369446-08$15.00/0.

Should patients with asymptomatic significant carotid stenosis undergo simultaneous carotid and cardiac surgery?

PubMed Central

Ogutu, Peter; Werner, Raphael; Oertel, Frank; Beyer, Michael

2014-01-01

A best evidence topic in cardiovascular surgery was written according to a structured protocol. The question addressed was whether patients with severe asymptomatic carotid and coronary artery diseases should undergo simultaneous carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG). A total of 624 papers were found using the reported search, of which 20 represent the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study results of these papers are tabulated. Previous cohort studies showed mixed results, while advocating for the necessity of a randomized controlled trial (RCT). A recent RCT showed that patients undergoing prophylactic or simultaneous CEA + CABG had lower rates of stroke (0%) compared with delayed CEA 1–3 months after CABG (7.7%), without significant perioperative mortality difference. This study included patients with unilateral severe (>70%) asymptomatic carotid stenosis requiring CABG. An earlier partly randomized trial also showed better outcomes for patients undergoing simultaneous procedures (P = 0.045). Interestingly, systematic reviews previously failed to show compelling evidence supporting prophylactic CEA. This could be partly due to the fact that these reviews collectively analyse different cohort qualities. Neurological studies have, however, shown reduced cognitive and phonetic quality and function in patients with unilateral and bilateral asymptomatic carotid artery stenosis. Twenty-one RCTs comparing lone carotid artery stenting (CAS) and CEA informed the American Heart Association guidelines, which declared CAS comparable with CEA for symptomatic and asymptomatic carotid stenosis (CS). However, the risk of death/stroke for CAS alone is double that for CEA alone in the acute phase following onset of symptoms, while CEA alone is associated with a doubled risk of myocardial infarction. There is, however, no significant difference for combined 30-day risk of death/stroke/myocardial infarction. Outcomes of hybrid or simultaneous CAS/CABG procedures show comparable results, albeit from rather small cohorts. While current evidence leans towards simultaneous CEA/CABG, the emergence of hybrid operating theatres in various institutions may allow larger cohorts with subsequent significant data on simultaneous CAS/CABG. A randomized controlled trial comparing both approaches would be crucial in informing future updates of existing guidelines. PMID:24368551

Using Real-World Data in Health Technology Assessment (HTA) Practice: A Comparative Study of Five HTA Agencies.

PubMed

Makady, Amr; van Veelen, Ard; Jonsson, Páll; Moseley, Owen; D'Andon, Anne; de Boer, Anthonius; Hillege, Hans; Klungel, Olaf; Goettsch, Wim

2018-03-01

Reimbursement decisions are conventionally based on evidence from randomised controlled trials (RCTs), which often have high internal validity but low external validity. Real-world data (RWD) may provide complimentary evidence for relative effectiveness assessments (REAs) and cost-effectiveness assessments (CEAs). This study examines whether RWD is incorporated in health technology assessment (HTA) of melanoma drugs by European HTA agencies, as well as differences in RWD use between agencies and across time. HTA reports published between 1 January 2011 and 31 December 2016 were retrieved from websites of agencies representing five jurisdictions: England [National Institute for Health and Care Excellence (NICE)], Scotland [Scottish Medicines Consortium (SMC)], France [Haute Autorité de santé (HAS)], Germany [Institute for Quality and Efficacy in Healthcare (IQWiG)] and The Netherlands [Zorginstituut Nederland (ZIN)]. A standardized data extraction form was used to extract information on RWD inclusion for both REAs and CEAs. Overall, 52 reports were retrieved, all of which contained REAs; CEAs were present in 25 of the reports. RWD was included in 28 of the 52 REAs (54%), mainly to estimate melanoma prevalence, and in 22 of the 25 (88%) CEAs, mainly to extrapolate long-term effectiveness and/or identify drug-related costs. Differences emerged between agencies regarding RWD use in REAs; the ZIN and IQWiG cited RWD for evidence on prevalence, whereas the NICE, SMC and HAS additionally cited RWD use for drug effectiveness. No visible trend for RWD use in REAs and CEAs over time was observed. In general, RWD inclusion was higher in CEAs than REAs, and was mostly used to estimate melanoma prevalence in REAs or to predict long-term effectiveness in CEAs. Differences emerged between agencies' use of RWD; however, no visible trends for RWD use over time were observed.

Looking up, down, and sideways: Reconceiving cumulative effects assessment as a mindset

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sinclair, A. John, E-mail: jsincla@umanitoba.ca; Doelle, Meinhard, E-mail: mdoelle@dal.ca; Duinker, Peter N., E-mail: peter.duinker@dal.ca

Despite all the effort that has gone into defining, researching and establishing best practices for cumulative effects assessment (CEA), understanding remains weak and practice wanting. At one extreme of implementation, CEA can be described as merely an irritant to the completion of a project-specific environmental assessment (EA). At the other extreme, the conceptual view is that all effects in EA should be deemed cumulative unless demonstrated otherwise. Our purpose here is to consider how we might reconceive CEA as a mindset that is at the heart of absolutely every assessment of valued ecosystem component (VEC) to ensure that we understandmore » the relative contributions of various stressors and can decide when cumulative effects may foreclose future activities due to impacts on VECs. Conceptually, we ground the CEA mindset in the context of three lenses that must all be functioning and working together for the mindset to be operative: a technical lens; a law and policy lens; and a participatory lens. Our arguments are based on a review of the CEA, strategic effects assessment (SEA) and regional effects assessment literatures, an examination and consideration of Canadian EA and SEA case practice, and our combined professional experiences. Through using the Bay of Fundy in Canada as a case example, we establish the concept of the CEA mindset and an approach for moving forward with implementation. - Highlights: • Conceptualization of cumulative effects assessment as a mindset. • Elaboration of technical, law and policy and participation lenses critical to CEA • Coordination and integration of cumulative effects for valued ecosystem components • Application in Bay of Fundy ecosystem and terrestrial watershed.« less

Analgesic Effects of Duloxetine on Formalin-Induced Hyperalgesia and Its Underlying Mechanisms in the CeA

PubMed Central

Zhang, Lie; Yin, Jun-Bin; Hu, Wei; Zhao, Wen-Jun; Fan, Qing-Rong; Qiu, Zhi-Chun; He, Ming-Jie; Ding, Tan; Sun, Yan; Kaye, Alan D.; Wang, En-Ren

2018-01-01

In rodents, the amygdala has been proposed to serve as a key center for the nociceptive perception. Previous studies have shown that extracellular signal-regulated kinase (ERK) signaling cascade in the central nucleus of amygdala (CeA) played a functional role in inflammation-induced peripheral hypersensitivity. Duloxetine (DUL), a serotonin and noradrenaline reuptake inhibitor, produced analgesia on formalin-induced spontaneous pain behaviors. However, it is still unclear whether single DUL pretreatment influences formalin-induced hypersensitivity and what is the underlying mechanism. In the current study, we revealed that systemic pretreatment with DUL not only dose-dependently suppressed the spontaneous pain behaviors, but also relieved mechanical and thermal hypersensitivity induced by formalin hindpaw injection. Consistent with the analgesic effects of DUL on the pain behaviors, the expressions of Fos and pERK that were used to check the neuronal activities in the spinal cord and CeA were also dose-dependently reduced following DUL pretreatment. Meanwhile, no emotional aversive behaviors were observed at 24 h after formalin injection. The concentration of 5-HT in the CeA was correlated with the dose of DUL in a positive manner at 24 h after formalin injection. Direct injecting 5-HT into the CeA suppressed both the spontaneous pain behaviors and hyperalgesia induced by formalin injection. However, DUL did not have protective effects on the formalin-induced edema of hindpaw. In sum, the activation of CeA neurons may account for the transition from acute pain to long-term hyperalgesia after formalin injection. DUL may produce potent analgesic effects on the hyperalgesia and decrease the expressions of p-ERK through increasing the concentration of serotonin in the CeA. PMID:29692727

Analgesic Effects of Duloxetine on Formalin-Induced Hyperalgesia and Its Underlying Mechanisms in the CeA.

PubMed

Zhang, Lie; Yin, Jun-Bin; Hu, Wei; Zhao, Wen-Jun; Fan, Qing-Rong; Qiu, Zhi-Chun; He, Ming-Jie; Ding, Tan; Sun, Yan; Kaye, Alan D; Wang, En-Ren

2018-01-01

In rodents, the amygdala has been proposed to serve as a key center for the nociceptive perception. Previous studies have shown that extracellular signal-regulated kinase (ERK) signaling cascade in the central nucleus of amygdala (CeA) played a functional role in inflammation-induced peripheral hypersensitivity. Duloxetine (DUL), a serotonin and noradrenaline reuptake inhibitor, produced analgesia on formalin-induced spontaneous pain behaviors. However, it is still unclear whether single DUL pretreatment influences formalin-induced hypersensitivity and what is the underlying mechanism. In the current study, we revealed that systemic pretreatment with DUL not only dose-dependently suppressed the spontaneous pain behaviors, but also relieved mechanical and thermal hypersensitivity induced by formalin hindpaw injection. Consistent with the analgesic effects of DUL on the pain behaviors, the expressions of Fos and pERK that were used to check the neuronal activities in the spinal cord and CeA were also dose-dependently reduced following DUL pretreatment. Meanwhile, no emotional aversive behaviors were observed at 24 h after formalin injection. The concentration of 5-HT in the CeA was correlated with the dose of DUL in a positive manner at 24 h after formalin injection. Direct injecting 5-HT into the CeA suppressed both the spontaneous pain behaviors and hyperalgesia induced by formalin injection. However, DUL did not have protective effects on the formalin-induced edema of hindpaw. In sum, the activation of CeA neurons may account for the transition from acute pain to long-term hyperalgesia after formalin injection. DUL may produce potent analgesic effects on the hyperalgesia and decrease the expressions of p-ERK through increasing the concentration of serotonin in the CeA.