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Sample records for potential tumor marker

  1. Tumor Markers

    MedlinePlus

    ... types: Germ cell tumors, lymphoma, leukemia, melanoma, and neuroblastoma Tissue analyzed: Blood How used: To assess stage, ... NSE) Cancer types: Small cell lung cancer and neuroblastoma Tissue analyzed: Blood How used: To help in ...

  2. 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.

  3. Serum tumor markers.

    PubMed

    Perkins, Greg L; Slater, Evan D; Sanders, Georganne K; Prichard, John G

    2003-09-15

    Monoclonal antibodies are used to detect serum antigens associated with specific malignancies. These tumor markers are most useful for monitoring response to therapy and detecting early relapse. With the exception of prostate-specific antigen (PSA), tumor markers do not have sufficient sensitivity or specificity for use in screening. Cancer antigen (CA) 27.29 most frequently is used to follow response to therapy in patients with metastatic breast cancer. Carcinoembryonic antigen is used to detect relapse of colorectal cancer, and CA 19-9 may be helpful in establishing the nature of pancreatic masses. CA 125 is useful for evaluating pelvic masses in postmenopausal women, monitoring response to therapy in women with ovarian cancer, and detecting recurrence of this malignancy. Alpha-fetoprotein (AFP), a marker for hepatocellular carcinoma, sometimes is used to screen highly selected populations and to assess hepatic masses in patients at particular risk for developing hepatic malignancy. Testing for the beta subunit of human chorionic gonadotropin (beta-hCG) is an integral part of the diagnosis and management of gestational trophoblastic disease. Combined AFP and beta-hCG testing is an essential adjunct in the evaluation and treatment of nonseminomatous germ cell tumors, and in monitoring the response to therapy. AFP and beta-hCG also may be useful in evaluating potential origins of poorly differentiated metastatic cancer. PSA is used to screen for prostate cancer, detect recurrence of the malignancy, and evaluate specific syndromes of adenocarcinoma of unknown primary.

  4. Diagnostic potential in prostate cancer of a panel of urinary molecular tumor markers.

    PubMed

    Talesa, Vincenzo N; Antognelli, Cinzia; Del Buono, Chiara; Stracci, Fabrizio; Serva, Maria R; Cottini, Emanuele; Mearini, Ettore

    2009-01-01

    Prostate cancer (PCa) is a heterogeneous, multifactorial and multifocal disease. Therefore, the search for a combination of assays using a panel of tumor markers is fundamental for a more precise and reliable diagnosis. In the present study we investigated the diagnostic value of five different genes, associated with PCa carcinogenesis, encoding for prostate-specific membrane antigen (PSMA), serine protease Hepsin, PCa antigen 3 (PCA3), UDP-N-acetyl-alpha-D-galatosamine transferase (GalNAC-T3) and prostate-specific antigen (PSA). Forty-four patients, with previously untreated, histologically verified PCa and forty-six patients with benign prostatic hyperplasia (BPH) were enrolled in this study. Absolute concentration of the transcript levels of each gene was calculated by quantitative Real-Time PCR analysis in urine sediments of men suffering from PCa or BPH after prostatic massage. The diagnostic value of a concomitant examination of these markers was evaluated by logistic regression analysis. We demonstrated that the diagnostic potential of the combined urinary PSA and PSMA level was significantly better than that of each singularly considered marker, including total serum PSA, the present gold standard test for PCa diagnosis.

  5. Absence of the Epithelial Glycocalyx As Potential Tumor Marker for the Early Detection of Colorectal Cancer

    PubMed Central

    Ramaker, Katrin; Bade, Steffen; Röckendorf, Niels; Meckelein, Barbara; Vollmer, Ekkehard; Schultz, Holger; Fröschle, Günter-Willi; Frey, Andreas

    2016-01-01

    Detection of cancer at an early stage is pivotal for successful treatment and long term survival, yet early diagnosis requires sensitive and specific markers that can be easily detected by screening procedures. Differences in the surface structure of tumor and healthy cells, if sufficiently pronounced and discernible, may serve that purpose. We analyzed the luminal surface of healthy and neoplastic human colorectal tissues for the presence and architecture of the glycocalyx—a dense network of highly glycosylated proteins—using transmission electron microscopy. The ultrastructural analyses showed that 93% of healthy mucosae were covered by an intact glycocalyx. Contrarily, on over 90% of the surface of neoplastic cells the glycocalyx was absent. The sensitivity and specificity of our marker “absence of a glycocalyx” are excellent, being 91% (83–96%) and 96% (89–99%) for adenocarcinomas and 94% (73–100%) and 92% (85–97%) for precancerous polyps (means and 95% confidence intervals). Using a cell culture model we could demonstrate that a particulate probe targeting a cell surface receptor usually concealed beneath the glycocalyx can bind selectively to glycocalyx-free areas of a tumor cell layer. We propose that the absence of a glycocalyx may serve as novel type of tumor marker. If the absence of the glycocalyx can be detected e.g. via binding of imaging probes to non-shielded surface receptors of anomalously differentiated cells, this tumor marker could be used to enable early diagnosis of colorectal cancer. PMID:28033349

  6. Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers.

    PubMed

    Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

    2016-03-17

    The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c-d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors.

  7. Assessment of Environmental and Hereditary Influence on Development of Pituitary Tumors Using Dermatoglyphic Traits and Their Potential as Screening Markers

    PubMed Central

    Gradiser, Marina; Matovinovic Osvatic, Martina; Dilber, Dario; Bilic-Curcic, Ines

    2016-01-01

    The aim of this study was to assess environmental and hereditary influence on development of pituitary tumors using dermatoglyphic traits. The study was performed on 126 patients of both genders with pituitary tumors (60 non-functional and 66 functional pituitary tumor patients) in comparison to the control group of 400 phenotypically healthy individuals. Statistical analysis of quantitative and qualitative traits of digito-palmar dermatoglyphics was performed, and hormonal status was determined according to the standard protocols. Although we did not find markers that could specifically distinguish functional from non-functional tumors, we have found markers predisposing to the development of tumors in general (a small number of ridges between triradius of both hands, a smaller number of ridges between the triradius of c–d rc R), those for endocrine dysfunction (increased number of arches and reduced number of whorls, difference of pattern distribution in the I3 and I4 interdigital space), and some that could potentially be attributed to patients suffering from pituitary tumors (small number of ridges for variables FRR 5, smaller number of ridges in the FRL 4 of both hands and difference of pattern distribution at thenar of I1 and I2 interdigital space). The usage of dermatoglyphic traits as markers of predisposition of pituitary tumor development could facilitate the earlier detection of patients in addition to standard methods, and possibly earlier treatment and higher survival rate. Finally, our results are consistent with the hypothesis about multifactorial nature of pituitary tumor etiology comprised of both gene instability and environmental factors. PMID:26999178

  8. Molecular signature of salivary gland tumors: potential use as diagnostic and prognostic marker.

    PubMed

    Fonseca, Felipe Paiva; Sena Filho, Marcondes; Altemani, Albina; Speight, Paul M; Vargas, Pablo Agustin

    2016-02-01

    Salivary gland tumors are a highly heterogeneous group of lesions with diverse microscopic appearances and variable clinical behavior. The use of clinical and histological parameters to predict patient prognosis and survival rates has been of limited utility, and the search for new biomarkers that could not only aid in a better understanding of their pathogenesis but also be reliable auxiliaries for prognostic determination and useful diagnostic tools has been performed in the last decades with very exciting results. Hence, gene rearrangements such as CRTC1-MAML2 in mucoepidermoid carcinomas have shown excellent specificity, and more than that, it has been strongly correlated with low-grade tumors and consequently with an increased survival rate and better prognosis of patients affected by neoplasms carrying this translocation. Moreover, MYB-NFIB and EWSR1-ATF1 gene fusions were shown to be specifically found in cases of adenoid cystic carcinomas and hyalinizing clear cell carcinomas, respectively, in the context of salivary gland tumors, becoming reliable diagnostic tools for these entities and potential therapeutic targets for future therapeutic protocols. Finally, the identification of ETV6-NTRK3 in cases previously diagnosed as uncommon acinic cell carcinomas, cystadenocarcinomas, and adenocarcinomas not otherwise specified led to the characterization of a completely new and now widely accepted entity, including, therefore, mammary analogue secretory carcinoma in the list of well-recognized salivary gland carcinomas. Thus, further molecular investigations of salivary gland tumors are warranted, and the recognition of other genetic abnormalities can lead to the acknowledgment of new entities and the acquirement of reliable biomarkers.

  9. Association of FOXM1 expression with tumor histology and prognosis in Wilms tumor: Potential for a new prognostic marker

    PubMed Central

    Apelt, Nadja; Hubertus, Jochen; Mayr, Doris; Graf, Norbert; Furtwängler, Rhoikos; Von Schweinitz, Dietrich; Kappler, Roland

    2016-01-01

    Wilms tumor (WT) is the most common pediatric renal malignancy. A recent ontogenic model suggests that undifferentiated tumor state, and hence poor prognosis, in WT is determined by stabilization of β-catenin in the nucleus. Forkhead box M1 (FOXM1) is a downstream component of the Wnt pathway and promotes nuclear localization of β-catenin. As elevation of FOXM1 gene expression is prognostic in various types of malignancy, we hypothesized that high FOXM1 expression in WT is associated with undifferentiated histology and thus poor prognosis. In the current study, the expression of FOXM1 mRNA was determined in 46 WT specimens and 11 renal tissue controls from patients undergoing tumor nephrectomy, and these data were assessed with regard to clinicopathological parameters. The results demonstrated an upregulation of FOXM1 in WT by 10-fold compared to normal tissue. Expression differed significantly between controls and tumors of intermediate- and high-risk histopathology (P<0.001, Kruskal-Wallis), and distinguished normal tissue from tumors of good and adverse clinical outcome (P<0.001, Kruskal-Wallis). Notably, FOXM1 expression was significantly lower (P=0.009) in patients that received preoperative doxorubicin. These results suggest that FOXM1 may serve as a companion diagnostic factor for doxorubicin-based therapies in WT. PMID:27698870

  10. Markers of bile duct tumors

    PubMed Central

    Malaguarnera, Giulia; Giordano, Maria; Paladina, Isabella; Rando, Alessandra; Uccello, Mario; Basile, Francesco; Biondi, Antonio; Carnazzo, Santo; Alessandria, Innocenza; Mazzarino, Clorinda

    2011-01-01

    Biliary tract carcinomas are relatively rare, representing less than 1% of cancers. However, their incidence has increased in Japan and in industrialized countries like the USA. Biliary tract tumors have a poor prognosis and a high mortality rate because they are usually detected late in the course of the disease; therapeutic treatment options are often limited and of minimal utility. Recent studies have shown the importance of serum and molecular markers in the diagnosis and follow up of biliary tract tumors. This review aims to introduce the main features of the most important serum and molecular markers of biliary tree tumors. Some considerable tumor markers are cancer antigen 125, carbohydrate antigen 19-9, carcinoembryonic antigen, chromogranin A, mucin 1, mucin 5, alpha-fetoprotein, claudins and cytokeratins. PMID:21528090

  11. Quantum dots based potential-resolution dual-targets electrochemiluminescent immunosensor for subtype of tumor marker and its serological evaluation.

    PubMed

    Liu, Xuan; Jiang, Hui; Fang, Yuan; Zhao, Wei; Wang, Nianyue; Zang, Guizhen

    2015-09-15

    The identification of subtypes of known tumor markers is of great importance for clinical diagnosis but still a great challenge in novel detection methodologies with simple operation and acceptable sensitivity. This work for the first time reported a quantum dots (QDs) based potential-resolved electrochemiluminescent (ECL) immunosensor to realize simultaneous detection of dual targets. Because of different surface microstructures, dimercaptosuccinic acid stabilized CdTe (DMSA-CdTe) QDs and TiO2 nanoparticles-glutathione stabilized CdTe (TiO2-GSH-CdTe) QDs composites showed a large difference of ECL peak potential (∼360 mV), which provided an access for potential-resolution detection. The ECL emission on indium tin oxide electrodes showed consistent strength during the cyclic scan, and intensity data were collected at -0.89 V and -1.25 V (vs Ag/AgCl) for DMSA-CdTe QDs and TiO2-GSH-CdTe QDs composites, respectively. The interface modification procedures of immunosensor construction were characterized by atomic force microscopy. The portion of Lens culinaris lectin affiliated isoform of alpha fetoprotein (AFP), AFP-L3%, in total AFP, is recently a novel criteria showing even higher sensitivity and specificity than AFP at the early stage of cancer. Combined with the enzyme cyclic amplification strategy, linear ranges for AFP-L3 and AFP dual-targets detection were 3.24 pg mL(-1)-32.4 ng mL(-1) and 1.0 pg mL(-1)-20 ng mL(-1), with limits of detection of 3.24 pg mL(-1) and 1.0 pg mL(-1), respectively. Compared with clinical detection data, the calculated portion of AFP-L3% by as-prepared immunosensor showed acceptable accuracy. These results open a new avenue for facile and rapid multiple-components detection based on the nano-ECL technique and provide a new clinical diagnosis platform for HCC.

  12. Molecular characterization of circumventricular organs and third ventricle ependyma in the rat: potential markers for periventricular tumors.

    PubMed

    Szathmari, Alexandru; Champier, Jacques; Ghersi-Egea, Jean-François; Jouvet, Anne; Watrin, Chantal; Wierinckx, Anne; Fèvre Montange, Michelle

    2013-02-01

    Circumventricular organs (CVOs) are specialized ventricular structures around the third and fourth ventricles of the brain. In humans, these structures are present during the fetal period and some become vestigial after birth. Some of these organs, such as the pineal gland (PG), subcommissural organ (SCO), and organum vasculosum of the lamina terminalis, might be the sites of origin of periventricular tumors, notably pineal parenchymal tumors, papillary tumor of the pineal region and chordoid glioma. In contrast to the situation in humans, CVOs are present in the adult rat and can be dissected by laser capture microdissection (LCM). In this study, we used LCM and microarrays to analyze the transcriptomes of three CVOs, the SCO, the subfornical organ (SFO), and the PG and the third ventricle ependyma in the adult rat, in order to better characterize these organs at the molecular level. Several genes were expressed only, or mainly, in one of these structures, for example, Erbb2 and Col11a1 in the ependyma, Epcam and Claudin-3 (CLDN3) in the SCO, Ren1 and Slc22a3 in the SFO and Tph, Aanat and Asmt in the PG. The expression of these genes in periventricular tumors should be examined as evidence for a possible origin from the CVOs. Furthermore, we performed an immunohistochemical study of CLDN3, a membrane protein involved in forming cellular tight junctions and found that CLDN3 expression was restricted to the apical pole of ependymocytes in the SCO. This microarray study provides new evidence regarding the possible origin of some rare periventricular tumors.

  13. MR spectroscopy of intracranial tuberculomas: A singlet peak at 3.8 ppm as potential marker to differentiate them from malignant tumors

    PubMed Central

    Alfaro, David; Martinot, Carlos; Fayed, Nicolas; Gaskill-Shipley, Mary

    2015-01-01

    Purpose The diagnosis of intracranial tuberculomas is often challenging. Our purpose is to describe the most common metabolic patterns of tuberculomas by MR spectroscopy (MRS) with emphasis on potential specific markers. Methods Single-voxel MRS short echo time was performed in 13 cases of tuberculomas proven by histology and/or response to anti-mycobacterial therapy. For comparison MRS was also performed in 19 biopsy-proven malignant tumors (13 high-grade gliomas and six metastasis). Presence of metabolic peaks was assessed visually and categorical variables between groups were compared using chi-square. Metabolite ratios were compared using Mann-Whitney test and diagnostic accuracy of the metabolite ratios was compared using receiver-operating characteristic (ROC) curves analysis. Results Spectroscopic peaks representing lipids and glutamate/glutamine (Glx) as well as a peak at ∼3.8 ppm were well defined in 77% (10/13), 77% (10/13) and 69% (nine of 13) of tuberculomas, respectively. Lipid and Glx peaks were also present in most of the malignant lesions, 79% (15/19) and 74% (14/19) respectively. However, a peak at ∼3.8 ppm was present in only 10% (two of 19) of the tumor cases (p < 0.001). Higher Cho/Cr and mI/Cr ratios helped discriminate malignant lesions with an area under the ROC curve of 0.86 (SE: 0.078, p < 0.002, CI: 0.7–1) and 0.8 (SE: 0.1, p < 0.009, CI: 0.6–1), respectively. Threshold values between 1.7–1.9 for Cho/Cr and 0.8–0.9 for mI/Cr provided high specificity (91% for both metabolites) and adequate sensitivity (75% and 80%, respectively) for discrimination of malignant lesions. Conclusion A singlet peak at ∼3.8 ppm is present in the majority of tuberculomas and absent in most malignant tumors, potentially a marker to differentiate these lesions. The assignment of the peak is difficult from our analysis; however, guanidinoacetate (Gua) is a possibility. Higher Cho/Cr and mI/Cr ratios should favor malignant lesions

  14. Age-Specific Gene Expression Signatures for Breast Tumors and Cross-Species Conserved Potential Cancer Progression Markers in Young Women

    PubMed Central

    Colak, Dilek; Nofal, Asmaa; AlBakheet, AlBandary; Nirmal, Maimoona; Jeprel, Hatim; Eldali, Abdelmoneim; AL-Tweigeri, Taher; Tulbah, Asma; Ajarim, Dahish; Malik, Osama Al; Kaya, Namik; Park, Ben H.; Bin Amer, Suad M.

    2013-01-01

    Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross

  15. Serum tumor markers in pediatric osteosarcoma: a summary review

    PubMed Central

    2012-01-01

    Osteosarcoma is the most common primary high-grade bone tumor in both adolescents and children. Early tumor detection is key to ensuring effective treatment. Serum marker discovery and validation for pediatric osteosarcoma has accelerated in recent years, coincident with an evolving understanding of molecules and their complex interactions, and the compelling need for improved pediatric osteosarcoma outcome measures in clinical trials. This review gives a short overview of serological markers for pediatric osteosarcoma, and highlights advances in pediatric osteosarcoma-related marker research within the past year. Studies in the past year involving serum markers in patients with pediatric osteosarcoma can be assigned to one of four categories, i.e., new approaches and new markers, exploratory studies in specialized disease subsets, large cross-sectional validation studies, and longitudinal studies, with and without an intervention. Most of the studies have examined the association of a serum marker with some aspect of the natural history of pediatric osteosarcoma. As illustrated by the many studies reviewed, several serum markers are emerging that show a credible association with disease modification. The expanding pool of informative osteosarcoma-related markers is expected to impact development of therapeutics for pediatric osteosarcoma positively and, it is hoped, ultimately clinical care. Combinations of serum markers of natural immunity, thyroid hormone homeostasis, and bone tumorigenesis may be undertaken together in patients with pediatric osteosarcoma. These serum markers in combination may do better. The potential effect of an intrinsic dynamic balance of tumor angiogenesis residing within a single hormone (tri-iodothyronine) is an attractive concept for regulation of vascularization in pediatric osteosarcoma. PMID:22587902

  16. Expression of Von Willebrand factor, an endothelial cell marker, is up-regulated by angiogenesis factors: a potential method for objective assessment of tumor angiogenesis.

    PubMed

    Zanetta, L; Marcus, S G; Vasile, J; Dobryansky, M; Cohen, H; Eng, K; Shamamian, P; Mignatti, P

    2000-01-15

    von Willebrand factor (vWF), a glycoprotein produced uniquely by endothelial cells and megakaryocytes, is routinely used to identify vessels in tissue sections. Vessel density in tumor specimens, as determined by immuno-histochemical staining for vWF or other endothelial cell markers, is a negative prognostic factor for many solid tumors. vWF is heterogeneously distributed throughout the vasculature, transcriptional control in response to the tissue microenvironment being responsible for local variations in endothelial cell levels of vWF. Here, we report that fibroblast growth factor-2 and vascular endothelial growth factor, potent angiogenesis inducers expressed in a variety of tumors, up-regulate expression of vWF mRNA and protein in cultured endothelial cells with a synergistic effect. Our data support the measurement of vWF mRNA in tumors to detect activated endothelium or angiogenesis. For this purpose, we developed a semi-quantitative RT-PCR for vWF mRNA. Preliminary results obtained with specimens from colon carcinoma and the corresponding normal colonic mucosa showed higher vWF mRNA levels in most tumors than in their normal counterparts. The differences in vWF mRNA levels were much larger than the differences in vessel counts between a tumor and the corresponding normal mucosa, indicating that high vWF mRNA levels in tumors may indeed be an early sign of activation of the endothelium. The rapidity, objectivity, sensitivity and specificity of this technique make it suitable for routine clinical application to identify aggressive, highly angiogenic tumors.

  17. Role of tumor markers and circulating tumors cells in the management of breast cancer.

    PubMed

    Saad, Ayman; Abraham, Jame

    2008-06-01

    Along with various imaging modalities, serologic tumor markers such as CA 15-3 and CA 27.29 have been used for decades to monitor treatment response in patients with metastatic breast cancer (MBC). Despite the frequent use of these markers, they lack high sensitivity and specificity for breast cancer progression. The prognostic significance of these markers remains indeterminate because of the conflicting outcome of many clinical trials. The circulating tumor cell (CTC) test has recently been studied in clinical trials in patients with MBC. Some of the studies showed that high levels of CTCs are correlated with poor survival in MBC. An intergroup trial is underway to determine the implication of changing treatment based on the CTC level. This article will discuss the current data on these markers, with special emphasis on the CTC test. The potential clinical utility of these markers will also be discussed.

  18. Neuroendocrine marker expression in thyroid epithelial tumors.

    PubMed

    Satoh, F; Umemura, S; Yasuda, M; Osamura, R Y

    2001-01-01

    Tissue sections from 50 cases with thyroid tumors, composed of 11 follicular adenomas, 10 follicular carcinomas, 14 papillary carcinomas, 10 anaplastic carcinomas, and 5 medullary carcinomas, were immunohistochemically analyzed for representative neuroendocrine markers. Immunoexpression ratios of these neuroendocrine markers were as follows: Follicular adenomas, neuron-specific enolase (NSE)63.6%, synaptophysin (SynP) 45.5%, Leu7 27.3%, NCAM 45.5%, chromogranin A (CgA) 0%, SNAP25 0%; follicular carcinomas, NSE 90.0%, SynP 80.0%, Leu7 80.0%, NCAM 0%, CgA 0%, SNAP25 0%; papillary carcinomas, NSE 85.7%, SynP 78.6%, Leu7 100%, NCAM 7.0%, CgA 0%, SNAP25.0%; anaplastic carcinomas, NSE 10.0%, SynP 0%, Leu7 0%, NCAM 0%, CgA 0%, SNAP25 0%; medullary carcinomas, NSE 100%, SynP100%, Leu7 80.0%, NCAM 40.0%, CgA 100%, SNAP25 100%. The two follicular carcinomas, which were morphologically characterized by "insular" (or "alveolar") arrangements, showed distinct immunoexpression of NSE and SynP at the same time. By in situ hybridization (ISH), expression of mRNA for NSE was confirmed in cases with marked immunoexpression of NSE. Although no endocrine granules were found, our results suggested that a specific type of follicular carcinoma, i.e., insular variant, may be immaturely neuroendocrine-differentiated.

  19. Interstitial Inorganic Phosphate as a Tumor Microenvironment Marker for Tumor Progression

    PubMed Central

    Bobko, Andrey A.; Eubank, Timothy D.; Driesschaert, Benoit; Dhimitruka, Ilirian; Evans, Jason; Mohammad, Rahman; Tchekneva, Elena E.; Dikov, Mikhail M.; Khramtsov, Valery V.

    2017-01-01

    Noninvasive in vivo assessment of chemical tumor microenvironment (TME) parameters such as oxygen (pO2), extracellular acidosis (pHe), and concentration of interstitial inorganic phosphate (Pi) may provide unique insights into biological processes in solid tumors. In this work, we employ a recently developed multifunctional trityl paramagnetic probe and electron paramagnetic resonance (EPR) technique for in vivo concurrent assessment of these TME parameters in various mouse models of cancer. While the data support the existence of hypoxic and acidic regions in TME, the most dramatic differences, about 2-fold higher concentrations in tumors vs. normal tissues, were observed for interstitial Pi - the only parameter that also allowed for discrimination between non-metastatic and highly metastatic tumors. Correlation analysis between [Pi], pO2, pHe and tumor volumes reveal an association of high [Pi] with changes in tumor metabolism and supports different mechanisms of protons and Pi accumulation in TME. Our data identifies interstitial inorganic phosphate as a new TME marker for tumor progression. Pi association with tumor metabolism, buffer-mediated proton transport, and a requirement of high phosphorus content for the rapid growth in the “growth rate hypothesis” may underline its potential role in tumorigenesis and tumor progression. PMID:28117423

  20. Gene markers in brain tumors: what the epileptologist should know.

    PubMed

    Ostrom, Quinn; Cohen, Mark L; Ondracek, Annie; Sloan, Andrew; Barnholtz-Sloan, Jill

    2013-12-01

    Gene markers or biomarkers can be used for diagnostic or prognostic purposes for all different types of complex disease, including brain tumors. Prognostic markers can be useful to explain differences not only in overall survival but also in response to treatment and for development of targeted therapies. Multiple genes with specific types of alterations have now been identified that are associated with improved response to chemotherapy and radiotherapy, such as O(6)-methylguanine methyltranferase (MGMT) or loss of chromosomes 1p and/or 19q. Other alterations have been identified that are associated with improved overall survival, such as mutations in isocitrate dehydrogenase 1 (IDH1) and/or isocitrate dehydrogenase 2 (IDH2) or having the glioma CpG island DNA methylator phenotype (G-CIMP). There are many biomarkers that may have relevance in brain tumor-associated epilepsy that do not respond to treatment. Given the rapidly changing landscape of high throughput "omics" technologies, there is significant potential for gaining further knowledge via integration of multiple different types of high genome-wide data. This knowledge can be translated into improved therapies and clinical outcomes for patients with brain tumors.

  1. Activated macrophages containing tumor marker in colon carcinoma: immunohistochemical proof of a concept.

    PubMed

    Faber, T J E; Japink, D; Leers, M P G; Sosef, M N; von Meyenfeldt, M F; Nap, M

    2012-04-01

    The presence of carcinoembryonic antigen (CEA)-containing activated macrophages has been demonstrated in peripheral blood from patients with colorectal carcinoma. Macrophages migrate from the circulation into the tissue, phagocytose debris, and return to the bloodstream. Hence it seems likely that activated macrophages containing tumor debris, i.e., tumor marker, are present in the stroma of colorectal carcinoma. After phagocytosis, they could follow a hematogenic or lymphogenic route to the peripheral blood. The aim of this study is to assess the presence of tumor marker-containing activated macrophages in the stroma of colon carcinoma and in regional lymph nodes. From 10 cases of colon carcinoma, samples of tumor tissue and metastasis-free lymph nodes were cut in serial sections and stained for CD68 to identify macrophages and for CEA, cytokeratin, or M30 presence. Slides were digitalised and visually inspected using two monitors, comparing the CD68 stain to the tumor marker stain to evaluate the presence of tumor marker-positive macrophages. Macrophages containing tumor marker could be identified in tumor stroma and in metastasis-free regional lymph nodes. The distribution varied for the different markers, CEA-positive macrophages being most abundant. The presence of macrophages containing tumor marker in the tumor stroma and lymph nodes from patients with colon carcinoma could be confirmed in this series using serial immunohistochemistry. This finding supports the concept of activated macrophages, after phagocytosing cell debris, being transported or migrating through the lymphatic system. These results support the potential of tumor marker-containing macrophages to serve as a marker for diagnosis and follow-up of colon cancer patients.

  2. Suprabasin as a novel tumor endothelial cell marker

    PubMed Central

    Alam, Mohammad T; Nagao-Kitamoto, Hiroko; Ohga, Noritaka; Akiyama, Kosuke; Maishi, Nako; Kawamoto, Taisuke; Shinohara, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2014-01-01

    Recent studies have reported that stromal cells contribute to tumor progression. We previously demonstrated that tumor endothelial cells (TEC) characteristics were different from those of normal endothelial cells (NEC). Furthermore, we performed gene profile analysis in TEC and NEC, revealing that suprabasin (SBSN) was upregulated in TEC compared with NEC. However, its role in TEC is still unknown. Here we showed that SBSN expression was higher in isolated human and mouse TEC than in NEC. SBSN knockdown inhibited the migration and tube formation ability of TEC. We also showed that the AKT pathway was a downstream factor of SBSN. These findings suggest that SBSN is involved in the angiogenic potential of TEC and may be a novel TEC marker. PMID:25283635

  3. [Considerations in rational use of tumor markers in breast carcinoma].

    PubMed

    Crombach, G

    1998-04-22

    The objective of this review is to determine clinical practical guidelines for the use of serum tumor markers in the care of breast cancer patients outside of clinical trials. Mucin antigens (CA 15-3, MCA, CA 549) and CEA are established markers in breast cancer. Owing to their low sensitivity, none of these markers can be recommended for screening, diagnosis or staging. During follow-up, increasing marker levels may indicate recurrence 3-6 months earlier than clinical and radiological examinations in about 40-50% of patients. However, the clinical benefit of this lead-time is not established. Tumor markers are able to monitor response to treatment in 70-80% of patients with metastatic breast cancer. However, paradoxical changes of the markers especially in the beginning of treatment, the insufficient concordance with tumor activity in 20-30% of the women, and the lack of curative therapy regimens limit the prospective clinical use of the markers in the individual patient. Therefore, marker changes require confirmation by radiological methods in most cases. The present data are insufficient to recommend routine use of tumor markers alone for monitoring breast cancer patients after primary treatment or during palliative therapy. However, in the absence of readily measurable disease (e. g. bone metastases) continuously increasing marker levels may be used to indicate treatment failure. If high-dose chemotherapy in metastatic breast cancer renders to be effective, the clinical impact of tumor markers will increase considerably. Until that time, the analytical performance and the sensitivity of the established marker assays should be improved, and the clinical role of newer marker tests (TPS, CA 27.29) should be evaluated.

  4. Potential Markers in Cardiac Hypertrophy?

    PubMed

    Malinowski, Bartosz; Fulgheri, Gabriele; Wicinski, Michal; Grzesk, Elzbieta; Odrowaz-Sypniewska, Grazyna; Grześk, Grzegorz; Darwish, Nasser

    2012-07-01

    Cardiomyopathies are diagnosed based on medical history of patient (symptoms and family history), physical examination, results of echocardiogram and in some situations additionally ECG or chest-X-ray results. Currently used non-invasive diagnostic methods, could be complemented by biochemical tests. In this review some emerging potential biomarkers such as: osteopontin, ST-2 receptor, osteoprotegerin, neopterin, urocortins, growth differentiation factor 15 and urotensin II are described. In current article human and non human investigations have been reviewed, since rat is most commonly used model in experimental cardiology and gives important foundations to clinical knowledge.

  5. Serum tumor markers in patients with breast cancer.

    PubMed

    Lumachi, Franco; Basso, Stefano M M

    2004-10-01

    Several serum tumor markers have been investigated in patients with breast cancer for assessing outcome, predicting recurrence and monitoring the therapeutic response. There is a general consensus concerning their limited application in diagnosing malignancy; however, serum tumor markers can be considered for the early detection of recurrence. The most effective markers for this indication are cancer antigens (CA)15-3 and 27.29, and c-erbB-2, although their efficacy in establishing disease progression has not been determined to date. In terms of evaluating prognosis and predicting response to therapy, only the expression of c-erbB-2 has clinical evidence. To conclude, at present, no serum tumor marker is cost effective, and none can be used with confidence in the decision making regarding breast cancer patients.

  6. Standardization of tumor markers - priorities identified through external quality assessment.

    PubMed

    Sturgeon, Catharine

    2016-01-01

    Tumor markers are often heterogeneous substances that may be present in elevated concentrations in the serum of cancer patients. Typically measured by immunoassay, they contribute to clinical management, particularly in screening, case-finding, prognostic assessment, and post-treatment monitoring. Data both from external quality assessment (EQA) schemes and clinical studies demonstrate significant variation in tumor marker results obtained for the same specimen using different methods. Between-method between-laboratory coefficients of variation (CV) reported by EQA schemes generally reflect the complexity of the measurand, ranging from <5% for the structurally relatively simple α-fetoprotein (AFP) to >25% for the complex mucinous cancer antigen 19-9 (CA19-9). Improving the standardization of tumor marker measurements is particularly important for three reasons. The primary use of tumor markers is in monitoring cancer patients over long periods of time. Clinical interpretation of trends may consequently be affected if results are obtained in different laboratories using different methods or if a laboratory has to change method. Differences in results may have major implications for adoption of area-wide decision cut-offs and make implementation of these difficult. Method-related differences also make it difficult to compare clinical studies. Improving comparability of tumor marker results requires broad international agreement about which molecular forms of the measurand have clinical utility, identifying and adopting pure molecular forms as calibrants, and defining antibody specificities for their optimal detection. These aims have been achieved to varying extents for the most frequently measured serum tumor markers as described in this paper.

  7. Real-time tumor tracking using implanted positron emission markers: concept and simulation study.

    PubMed

    Xu, Tong; Wong, Jerry T; Shikhaliev, Polad M; Ducote, Justin L; Al-Ghazi, Muthana S; Molloi, Sabee

    2006-07-01

    16% (84Rb). In addition, four markers (labeled with 124I) inside a 30 cm diameter water phantom were simulated to evaluate the feasibility of the multimarker localization algorithm. Localization was considered successful if a marker was localized to within 2 mm from its true location. The success rate of marker localization was found to depend on the number of annihilation events used and the error in the initial estimate of the marker position. By detecting 250 positron annihilation events from 4 markers (average of 62 events per marker), the marker success rates for initial errors of +/-5, +/-10, and +/-15 mm were 99.9%, 99.6%, and 92.4%, respectively. Moreover, the average localization error was 0.55 (+/-0.27) mm, which was independent of initial error. The computing time for localizing four markers was less than 20 ms (Pentium 4, 2.8 GHz processor, 512 MB memory). In conclusion, preliminary results demonstrate that the PeTrack technique can potentially provide real-time tumor tracking with low doses associated with the marker's activity. Furthermore, the small size of PeTrack markers is expected to facilitate implantation and reduce patient risk.

  8. Real-time tumor tracking using implanted positron emission markers: Concept and simulation study

    SciTech Connect

    Xu Tong; Wong, Jerry T.; Shikhaliev, Polad M.; Ducote, Justin L.; Al-Ghazi, Muthana S.; Molloi, Sabee

    2006-07-15

    % ({sup 124}I,{sup 74}As) to 16% ({sup 84}Rb). In addition, four markers (labeled with {sup 124}I) inside a 30 cm diameter water phantom were simulated to evaluate the feasibility of the multimarker localization algorithm. Localization was considered successful if a marker was localized to within 2 mm from its true location. The success rate of marker localization was found to depend on the number of annihilation events used and the error in the initial estimate of the marker position. By detecting 250 positron annihilation events from 4 markers (average of 62 events per marker), the marker success rates for initial errors of {+-}5, {+-}10, and {+-}15 mm were 99.9%, 99.6%, and 92.4%, respectively. Moreover, the average localization error was 0.55 ({+-}0.27) mm, which was independent of initial error. The computing time for localizing four markers was less than 20 ms (Pentium 4, 2.8 GHz processor, 512 MB memory). In conclusion, preliminary results demonstrate that the PeTrack technique can potentially provide real-time tumor tracking with low doses associated with the marker's activity. Furthermore, the small size of PeTrack markers is expected to facilitate implantation and reduce patient risk.

  9. REporting recommendations for tumor MARKer prognostic studies (REMARK).

    PubMed

    McShane, Lisa M; Altman, Douglas G; Sauerbrei, Willi; Taube, Sheila E; Gion, Massimo; Clark, Gary M

    2006-11-01

    Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, pre-planned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

  10. Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

    PubMed Central

    Banin Hirata, Bruna Karina; Oda, Julie Massayo Maeda; Losi Guembarovski, Roberta; Ariza, Carolina Batista; de Oliveira, Carlos Eduardo Coral; Watanabe, Maria Angelica Ehara

    2014-01-01

    Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity. PMID:24591761

  11. Tumor markers used in monitoring the tumor recurrence in patients with colorectal cancer

    PubMed Central

    BURZ, CLAUDIA; AZIZ, BEN YOUSSEF MOHAMED; BĂLĂCESCU, LOREDANA; LELUŢIU, LUMINIŢA; BUIGA, RAREŞ; SAMASCA, GABRIEL; IRIMIE, ALEXANDRU; LISENCU, COSMIN

    2016-01-01

    Background and aims The aim of this study was to investigate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) correlated with some tissue molecules as predictive markers for recurrence in colon cancer. Methods A total of 30 patients diagnosed with colon cancer stage II or III who underwent optimal surgery were enrolled in study. Tumor markers CEA and CA 19-9 were determined before surgery. Tumor samples were prepared using tissue microarray kit (TMA) then stained for different cellular markers (Ki 67, HER2, BCL2, CD56, CD4, CD8) and analyzed using Inforatio programme for quantitative determination. All patients received standard adjuvant treatment, which consisted of eight cycles chemotherapy type XELOX. The patients were followed up for 3 years. Results Upon 3 years follow-up, 67% of patients developed tumor relapse, the most common site of metastasis being the liver. No correlations were observed between either serum or tissue tumor markers and the risk of tumor relapse. Conclusion Over 50% of patients with colon cancer who had optimal treatment developed metastasis. No statistically significant predictive value for investigated molecules was found. Future studies are needed to confirm the use of molecular markers in monitoring patients with colorectal cancer PMID:27547057

  12. Classic tumor markers in gastric cancer. Current standards and limitations.

    PubMed

    Căinap, Călin; Nagy, Viorica; Gherman, Alexandra; Cetean, Sanziana; Laszlo, Istvan; Constantin, Anne-Marie; Căinap, Simona

    2015-01-01

    The progress made in the last few years made available a large amount of information that needs to be integrated and ordered by oncologists. Tumor markers are one of the pieces that physicians need to fit into the bigger puzzle. This article will detail the most frequent etiologies for the surges in the carcinoembryonic antigen (CEA), cancer-related antigen 72-4 (CA 72-4), cancer-related antigen 19-9 (CA 19-9) serum levels and their indications. Although tumor markers are an invaluable asset to medical practice, their role in screening, diagnosis and oncologic treatment remains poorly standardized. Ongoing or future clinical trials will shed light on pending problems.

  13. Variation of tumoral marker after radiofrequency ablation of pancreatic adenocarcinoma

    PubMed Central

    Barbi, Emilio; Girelli, Roberto; Tinazzi Martini, Paolo; De Robertis, Riccardo; Ciaravino, Valentina; Salvia, Roberto; Butturini, Giovanni; Frigerio, Isabella; Milazzo, Teresa; Crosara, Stefano; Paiella, Salvatore; Pederzoli, Paolo; Bassi, Claudio

    2016-01-01

    Background To evaluate the correlation between variations of CA 19.9 blood levels and the entity of necrosis at CT after radiofrequency ablation (RFA) of unresectable pancreatic adenocarcinoma. Methods In this study, from June 2010 to February 2014, patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure were included. All these patients underwent RFA. CT study was performed 1 week after RFA. The dosage of CA 19.9 levels was performed 1 month after RFA. Features of necrosis at CT, as mean entity, density and necrosis percentages compared to the original lesion, were evaluated and compared by using t-test with CA 19.9 blood levels variations after RFA procedure. Results In this study were included 51 patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure and with CT study and CA 19.9 available for analysis. After the procedure, CA 19.9 blood levels reduced in 24/51 (47%), remained stable in 10/51 (20%) and increased in 17/51 (33%). In patients with CA 19.9 levels reduced, the tumor marker were reduced less than 20% in 4/24 (17%) and more than 20% in 20/24 (83%); instead the tumor marker were reduced less than 30% in 8/24 (33%) and more than 30% in 16/24 (67%). At CT scan necrotic area density difference was not statistically significant. Also there was no statistically significant difference among the mean area, the mean volume and the mean ablation volume in percentage related to the treated tumor among the three different groups of patients divided depending on the CA 19.9 blood levels. But a tendency to a statistically significant difference was found in comparing the mean percentage of ablation volume between two subgroups of patients with a decrease of CA 19.9 levels with less or more than 20% reduction of tumor markers and between two subgroups with less or more than

  14. Potential markers of oxidative stress in stroke.

    PubMed

    Cherubini, Antonio; Ruggiero, Carmelinda; Polidori, M Cristina; Mecocci, Patrizia

    2005-10-01

    Free radical production is increased in ischemic and hemorrhagic stroke, leading to oxidative stress that contributes to brain damage. The measurement of oxidative stress in stroke would be extremely important for a better understanding of its pathophysiology and for identifying subgroups of patients that might receive targeted therapeutic intervention. Since direct measurement of free radicals and oxidized molecules in the brain is difficult in humans, several biological substances have been investigated as potential peripheral markers. Among lipid peroxidation products, malondialdehyde, despite its relevant methodological limitations, is correlated with the size of ischemic stroke and clinical outcome, while F2-isoprostanes appear to be promising, but they have not been adequately evaluated. 8-Hydroxy-2-deoxyguanosine has been extensively investigated as markers of oxidative DNA damage but no study has been done in stroke patients. Also enzymatic and nonenzymatic antioxidants have been proposed as indirect markers. Among them ascorbic acid, alpha-tocopherol, uric acid, and superoxide dismutase are related to brain damage and clinical outcome. After a critical evaluation of the literature, we conclude that, while an ideal biomarker is not yet available, the balance between antioxidants and by-products of oxidative stress in the organism might be the best approach for the evaluation of oxidative stress in stroke patients.

  15. Tumor markers in breast cancer- European Group on Tumor Markers recommendations.

    PubMed

    Molina, Rafael; Barak, Vivian; van Dalen, Arie; Duffy, Michael J; Einarsson, Roland; Gion, Massimo; Goike, Helenka; Lamerz, Rolf; Nap, Marius; Sölétormos, György; Stieber, Petra

    2005-01-01

    Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins (CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin (trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy.

  16. Alternative fiducial markers for Vero real-time tumor tracking radiotherapy: A phantom study

    NASA Astrophysics Data System (ADS)

    Park, Shin-Hyung; Kim, Jae-Chul; Kim, Sung Joon

    2016-12-01

    The objective of this study was to investigate the feasibility of potential fiducial markers consisting of various materials in a Vero real-time tumor-tracking (RTTT) system. In order to determine the applicability of fiducial markers for the Vero RTTT system, we tested various markers consisting of 8 kinds of material (titanium, stainless steel, high-carbon steel, pure steel, copper, silver, tantalum, and gold) with various diameters ranging from 0.3 mm to 1.6 mm and a length of 5 mm. Additionally, a commercial gold coil marker (Visicoil™, IBA dosimetry, Schwarzenbruck, Germany) of diameter 0.5 mm and length 1 cm was included for evaluation. The radiologic visibility on kV fluoroscopy/kV CT scan images of the fiducial markers was evaluated. The detectability on the RTTT system was tested using a two-dimensional moving phantom (Brainlab AG, Feldkirchen, Germany), producing sinusoidal motion. The target center's accuracy was evaluated by calculating the deviation of the position of a metal sphere from the center on the dose profile. Dose profiles were measured using Gafchromic EBT2 films (International Specialty Products, NJ, USA). All markers were visible on kV fluoroscopy/kV CT while markers with atomic number ≥ 25.7 were detectable on the Vero RTTT system. All the detected markers showed excellent geometric accuracy.

  17. Biomarkers Discovery for Colorectal Cancer: A Review on Tumor Endothelial Markers as Perspective Candidates

    PubMed Central

    2016-01-01

    Colorectal cancer (CRC) is the third most common cancer in the world. The early detection of CRC, during the promotion/progression stages, is an enormous challenge for a successful outcome and remains a fundamental problem in clinical approach. Despite the continuous advancement in diagnostic and therapeutic methods, there is a need for discovery of sensitive and specific, noninvasive biomarkers. Tumor endothelial markers (TEMs) are associated with tumor-specific angiogenesis and are potentially useful to discriminate between tumor and normal endothelium. The most promising TEMs for oncogenic signaling in CRC appeared to be the TEM1, TEM5, TEM7, and TEM8. Overexpression of TEMs especially TEM1, TEM7, and TEM8 in colorectal tumor tissue compared to healthy tissue suggests their role in tumor blood vessels formation. Thus TEMs appear to be perspective candidates for early detection, monitoring, and treatment of CRC patients. This review provides an update on recent data on tumor endothelial markers and their possible use as biomarkers for screening, diagnosis, and therapy of colorectal cancer patients. PMID:27965519

  18. Detection of tumor markers with ProteinChip technology.

    PubMed

    Wiesner, Andreas

    2004-02-01

    The early diagnosis of cancer at a curable stage is crucial for the successful treatment of this disease. Most of the currently used tumor assays appear too late and rely on single biomarkers with high false-negative and/or false-positive rates. As an additional burden for the patient, the traditional assays often require biopsy material instead of less invasively taken samples like serum. With the hope for more reliable DNA- and RNA-based screening tools, the research activities of the past 20 years have focused on the genomic characteristics of cancer cells. But, up to now, the output from this strategy has been disappointingly low and the disillusionment is paired with a return to proteins as the real key players in all physiological and pathological processes. Meanwhile, comparative protein profiling is generally acknowledged as a promising way for the detection of specific and predictive protein patterns reflecting certain stages of cancer without dependency on single markers. To meet the new technological demands, the ProteinChip Biomarker System was developed for the Expression Difference Mapping analysis of several hundreds of samples per day on a single, uncomplicated platform; with software support for the construction of multi-marker predictive models. The Interaction Discovery Mapping platform is introduced as the next methodical step for investigations about protein binding partners of possible importance in diagnosis and therapy. This review summarizes the current state in cancer diagnosis, provides an introduction into the ProteinChip technology, and gives an update on publications and research collaborations in SELDI-based tumor marker discovery.

  19. Mena, a new available marker in tumors of salivary glands?

    PubMed

    Gurzu, S; Krause, M; Ember, I; Azamfirei, L; Gobel, G; Feher, K; Jung, I

    2012-02-07

    Mena (mammalian Ena) is an actin regulatory protein involved in cell motility and adhesion. Based on its potential role in malignant transformation revealed in other organs, we analyzed the Mena expression in normal salivary glands (SG) and salivary tumors. Mena expression was determined in normal SG (n=10) and also benign (n=20) and malignant (n=35) lesions of SG. For the immunohistochemical staining we used the anti-Mena antibody. All normal SG and the benign lesions (10 pleomorphic adenomas, 10 Warthin's tumors) were Mena negative. Salivary duct carcinomas (n=5), carcinomas in pleomorphic adenoma (n=5), acinic cell carcinomas (n=5), squamous cell carcinomas (n=10) and high-grade mucoepidermoid carcinomas (n=2) were positive. The lymphomas (n=5) and low-grade mucoepidermoid carcinomas (n=1) were Mena negative. In one case the lymphoblastic cells stained positive for Mena. Some of the endothelial cells, in the peritumoral vessels, were Mena positive. To the best of our knowledge, this is the first study in the literature about Mena expression in salivary tumors. Our study suggests that Mena protein seems to play a role in malignant transformation and its intensity is correlated with the type and grade of tumor and also with vascular invasion. Its positivity in endothelial cells may suggest its potential role in tumor angiogenesis.

  20. [Tumor markers in the diagnosis of pancreatic cancer].

    PubMed

    Cappelli, G; Paladini, S; D'Agata, A

    1999-01-01

    The difficulty in an early diagnosis of pancreatic cancer is in the absence of early symptoms due to lower limit of detection of the actual imaging techniques. Clinical symptoms like weight loss, abdominal pain and jaundice indicate an advanced cancer stage. Today 50% of pancreatic tumors are diagnosed in advanced metastatic stage and only 20-30% show resectable cancer. Ultrasound and determination of a mucine like antigen as CA 19-9, CA 50 and CA 195 seem to allow an earlier diagnosis with a higher rate of resective surgery and a prolonged survival for these patients. The mucines are high molecular weight glycoproteins consistent of a backbone protein to which oligosaccarides are attached. The linkage of carbohydrate to the peptide is termed O-glycosidic and involves the hydroxylic groups of serine or threonine with N-acetylglucosamine. Only the backbone proteins are genetically determined (genes MUC). The gangliosides are the same or derivative of Lewis antigen. CA 19-9, CA 50 and CA 195 are assays directed to different epitopes probably present on the same mucinous antigen. These epitopes are not present in different mucines as CA 15-3, CA 125 and TAG 72. Recently other two mucines are emploied CA 242 and CAM 17.1 but they are not better than CA 19-9. The use of a "triplet" of tumor markers as CA 19-9, CA 125 and CEA is the best diagnostic tool for cancer of pancreas in an "integrated" use with ultrasonographic evaluation of the lesion. CA 19-9 permits differential diagnosis from neuroendocrine tumor or pancreatitis, the values of CA 125 and CEA are useful in the evaluation of the stage, resectability and prognosis of pancreatic cancer. The recent use of CA19-9 for the evaluation of radiochemotherapy in preoperative management of the patient is a mode of a well known application of tumor markers in a kinetic evaluation of the tumor for the radicality of therapy, follow-up, recurrence and the effectiveness of the palliative therapy.

  1. Prognostic value of preoperative serum tumor markers in gastric cancer

    PubMed Central

    Huang, Ze-Bo; Zhou, Xin; Xu, Jun; Du, Yi-Ping; Zhu, Wei; Wang, Jian; Shu, Yong-Qian; Liu, Ping

    2014-01-01

    AIM: To evaluate the prognostic value of preoperative carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19-9, and CA50 in patients undergoing D2 resection. METHODS: We evaluated 363 patients with gastric cancer who underwent gastrectomy at our hospital from January 2006 to December 2009. Blood samples were obtained from each patient within 1 wk before surgery. The cut-off values for serum CEA, CA19-9, and CA50 were 5 ng/mL, 37 U/mL, and 20 U/mL, respectively. The correlation between preoperative tumor marker levels and prognosis was studied by means of univariate and multivariate analyses. RESULTS: The preoperative serum positive rates of CEA, CA19-9 and CA50 were 24.0%, 18.9% and 24.5%, respectively. The positivity rate of serum CEA was significantly correlated with age (P < 0.001), sex (P = 0.022), tumor size (P = 0.007) and depth of invasion (P = 0.018); CA19-9 with tumor size (P = 0.042) and lymph node metastasis (P < 0.001); and CA50 only with lymph node metastasis (P = 0.001). In multivariate analysis, tumor size, T category, N category, vascular or neural invasion, and adjuvant chemotherapy were independent prognostic factors for overall survival. CA19-9 had an independent prognostic significance in patients without adjuvant chemotherapy (P = 0.027). CONCLUSION: Preoperative serum CEA, CA19-9 and CA50 are prognostic in patients with gastric cancer. Only CA19-9 is an independent prognostic factor after surgery without adjuvant chemotherapy. PMID:24829865

  2. A discrimination index for selecting markers of tumor growth dynamic across multiple cancer studies with a cure fraction.

    PubMed

    Rouam, Sigrid; Broët, Philippe

    2013-08-01

    To identify genomic markers with consistent effect on tumor dynamics across multiple cancer series, discrimination indices based on proportional hazards models can be used since they do not depend heavily on the sample size. However, the underlying assumption of proportionality of the hazards does not always hold, especially when the studied population is a mixture of cured and uncured patients, like in early-stage cancers. We propose a novel index that quantifies the capability of a genomic marker to separate uncured patients, according to their time-to-event outcomes. It allows to identify genomic markers characterizing tumor growth dynamic across multiple studies. Simulation results show that our index performs better than classical indices based on the Cox model. It is neither affected by the sample size nor the cure rate fraction. In a cross-study of early-stage breast cancers, the index allows to select genomic markers with a potential consistent effect on tumor growth dynamics.

  3. Potential Prognostic Markers for Human Prostate Cancer

    DTIC Science & Technology

    2001-03-01

    such as proliferation, differentiation and assay [15]. TGF[3 may be produced by metastatic motility. Upregulation of growth factor synthesis or prostate...via mod- ronment include neuroendocrine cells. These cells ulation of tumor cell receptor expression. Control of can secrete bombesin, a gastrin ...controls, indicating that addition ofT015 accelerates tumor expansion. TIl15 synthesis triggered a dramatic increase in cell motility, boosting serum

  4. Molecular beacon imaging of tumor marker gene expression in pancreatic cancer cells.

    PubMed

    Yang, Lily; Cao, Zehong; Lin, Yiming; Wood, William C; Staley, Charles A

    2005-05-01

    We have developed a fluorescence imaging-based approach to detect expression of tumor marker genes in pancreatic cancer cells using molecular beacons (MBs). MBs are short hairpin oligonucleotide probes that bind to specific oligonucleotide sequences and produce fluorescent signals. MBs targeting transcripts of two tumor marker genes, mutant K-ras and survivin, were synthesized and their specificity in detection of the expression of those genes in pancreatic cancer cells was examined. We found that K-ras MBs differentially bind to mutant K-ras mRNAs, resulting in strong fluorescent signals in pancreatic cancer cells with specific mutant K-ras genes but not in normal cells or cancer cells expressing either wild type or a different mutation of the K-ras gene. Additionally, MBs targeting survivin mRNA produced a bright fluorescent signal specifically in pancreatic cancer cells. We also demonstrated that MBs labeled with different fluorophores could detect survivin and mutant K-ras mRNAs simultaneously in single cancer cells. Furthermore, we showed that survivin and K-ras MBs have a high specificity in identifying cancer cells on frozen sections of pancreatic cancer tissues. In conclusion, molecular beacon-based imaging of expression of tumor marker genes has potential for the development of novel approaches for the detection of pancreatic cancer cells.

  5. Production of immunoreactive calcitonin and some other tumor markers by established human carcinoma cell lines.

    PubMed

    Ichiki, S; Kuroki, M; Matsunaga, A; Kuroki, M; Matsuoka, Y

    1986-03-01

    Out of seven human carcinoma cell lines (M7609, CCK-81, FCC-1, RPMI#4788, QGP-1, HLC-1, and KNS-62), 4 cell lines were found to produce immunoreactive calcitonin (ICT), a potential tumor marker for various malignancies. During a 7-day culture, 1.4 X 10(5) QGP-1, RPMI#4788, HLC-1, and KNS-62 cells secreted 7,000 pg, 500 pg, 400 pg, and 400 pg of ICT in the medium, respectively. The production of ICT by QGP-1 cells was increased by addition of pentagastrin or calcium gluconate. Three different components of ICT (peak I, molecular weight greater than 40,000; peak II, 14,000-18,000; peak III, 3,400) were detected by gel filtration of the QGP-1 spent medium. In a competitive inhibition-type radioimmunoassay of serial dilutions of each ICT component, peak III component showed very similar immunoreactivity to synthetic calcitonin. However, the other two components gave clearly different immunoreactivities from the peak III component and showed very similar immunoreactivities to each other. All the cell lines were further screened for synthesis of 7 other tumor markers, carcinoembryonic antigen, nonspecific cross-reacting antigen, CA19-9, tissue polypeptide antigen, alpha-fetoprotein, beta 2-microglobulin and ferritin. Every cell line produced 2 to 6 markers concomitantly, and various combinations of positive markers were found among the cell lines.

  6. Use of preoperative FLAIR MRI and ependymal proximity of tumor enhancement as surrogate markers of brain tumor origin.

    PubMed

    Smith, Timothy R; Hulou, M Maher; Abecassis, Josh; Das, Sunit; Chandler, James P

    2015-09-01

    Neural stem cells proliferate in the subventricular zone and give rise to progeny that differentiate and migrate throughout the brain. We aimed to test the hypothesis that glioma behavior and grade may correlate with the identity of the tumor cell of origin. We evaluated three preoperative radiographic features (fluid attenuated inversion recovery [FLAIR] MRI characteristics, tumor proximity to ventricular ependyma, and subependymal representation) as surrogate markers of tumor origin using a retrospective cohort design. The medical records of 228 patients who underwent surgical resection of a glioma from January 2004 to August 2008 were reviewed. Average patient age was 54.5 years (standard deviation [SD] 15.3) with a male predominance (62.9%). World Health Organization glioma grades amongst the cohort were Grade IV (71.6%), Grade III (21.3%) and Grade II (7.1%). Mean survival was 11.2 months (SD 10.5) with a mean follow up of 12.8 months (SD 11.3). Glioma tumor grade was significantly correlated to FLAIR signal proximity to the ependymal surface (p<0.01) and inversely with proximity of tumor mass to the ependyma (p<0.01). The mean distance of tumor-associated FLAIR signal from the ependymal surface for glioblastoma multiforme (GBM) was 1.2mm (SD 3.3) compared to 4.8 (SD 6.5) for anaplastic astrocytomas and 6.6mm (SD 6.7; p<0.01) for low grade gliomas. Conversely, the mean distance of the enhancing tumor mass from the ependyma for GBM was 7.3mm (SD 9.4), Grade III glioma 2.3mm (SD 4.9), and Grade II glioma 3.8mm (SD 6.8; p<0.05). These findings suggest that higher grade gliomas might arise from less differentiated neuroepithelial cells in the subventricular zone that possess greater migratory potential.

  7. Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

    PubMed Central

    Diaz-Cano, Salvador J.

    2012-01-01

    Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma), mechanisms of intercellular transference of genetic information (exosomes), and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning. PMID:22408433

  8. Comparison of loss of heterozygosity patterns between ovarian tumors of low malignant potential and malignant ovarian tumors

    SciTech Connect

    Crawford, E.C.; Miller, D.M.; Finley, W.H.

    1994-09-01

    Ovarian tumors of low malignant potential (LMP) represent a pathologic subtype of ovarian tumor that possess many features common to malignant tumors including epithelial stratification, increased mitotic activity and atypical cellularity. These tumors, however, do not invade the ovarian stroma and have a much improved patient prognosis. Utilizing dinucleotide repeats, loss of heterozygosity (LOH) studies were performed on a total of 12 ovarian tumors of LMP in 5 regions found to have significant levels of LOH in malignant ovarian tumors. The regions chosen for study were 3p, 6q, 11p, 17p and 17q. LOH could be demonstrated in malignant ovarian tumors in loci from 3p, 11p and both chromosomal arms of 17 when compared to normal tissue from the same patient. Loss in malignant tumors was more common in loci mapped to 3p21 and to 11p15. OH was not noted in any samples for a repeat in the TP53 gene even though flanking markers on 17p were lost in 1 patient with a malignant tumor. Loss was not demonstrated in any of the loci examined from 6q in malignant ovarian tumors. LOH was not demonstrated in any of the 39 loci examined from any of the five chromosomal regions in the ovarian tumors of LMP. Cytogenetic analyses of these LMP tumors were consistent with lack of involvement in these chromosomal regions. These data suggest the mechanism of tumorigenesis is different in tumors of LMP from that in malignant ovarian tumors.

  9. Stability of Markers Used for Real-Time Tumor Tracking After Percutaneous Intrapulmonary Placement

    SciTech Connect

    Voort van Zyp, Noelle C. van der; Hoogeman, Mischa S.; Water, Steven van de; Levendag, Peter C.; Holt, Bronno van der; Heijmen, Ben J.M.; Nuyttens, Joost J.

    2011-11-01

    Purpose: To determine the stability of markers used for real-time tumor tracking after percutaneous intrapulmonary placement. Methods and Materials: A total of 42 patients with 44 lesions, 111 markers, and {>=}2 repeat computed tomography (CT) scans were studied. The tumor on the repeat CT scans was registered with the tumor on the planning CT scan. Next, the three-dimensional marker coordinates were determined on the planning CT scan and repeat CT scans. Marker stability was analyzed by the displacement of the markers and the displacement of the center of mass (COM) of the marker configurations. In addition, we assessed the reliability of using the intermarker distance as a check for displacements in the COM of the marker configurations. Results: The median marker displacement was 1.3 mm (range, 0.1-53.6). The marker displacement was >5 mm in 12% of the markers and >10 mm in 5% of the markers. The causes of marker displacement >5 mm included marker migration (2 of 13) and target volume changes (5 of 13). Nonsynchronous tumor and marker movement during breathing might have been responsible for the displacements >5 mm in the other 6 of 13 markers. The median displacement in the COM of the marker configurations was 1.0 mm (range, 0.1-23.3). Displacements in the COM of the marker configurations of {>=}2.0 mm were detected by changes in the intermarker distance of >1.5 mm in 96% of the treatment fractions. Conclusion: The median marker displacement was small (1.3 mm). Nevertheless, displacements >5 mm occurred in 12% of the markers. Therefore, we recommend the implantation of multiple markers because multiple markers will enable a quick and reliable check of marker displacement by determining the change in the intermarker distance. A displacement in the COM of the marker configuration of {>=}2.0 mm was almost always detected (96%) by a change in the distance between the markers of >1.5 mm. This enabled the displaced marker to be disabled, such that tumor localization

  10. 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

  11. Clinically Meaningful Use of Blood Tumor Markers in Oncology

    PubMed Central

    Pagliaro, Lance

    2016-01-01

    Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs) were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. However, recent research has shown superior performance using a combination of multiple TMs as a panel for assessment, or as part of validated algorithms that also incorporate other clinical factors. In addition, newer TMs have been discovered that have an increased sensitivity and specificity profile for defined malignancies. The aim of this review is to provide a concise overview of the appropriate uses of both traditional and newer TMs and their roles in diagnosis, prognosis, and the monitoring of patients in current clinical practice. We also look at the future direction of TMs and their integration with other diagnostic modalities and other emerging serum based biomarkers, such as circulating nucleic acids, to ultimately advance diagnostic performance and improve patient management. PMID:28042579

  12. Hybrid hydrogel photonic barcodes for multiplex detection of tumor markers.

    PubMed

    Xu, Yueshuang; Zhang, Xiaoping; Luan, Chengxin; Wang, Huan; Chen, Baoan; Zhao, Yuanjin

    2017-01-15

    Barcodes-based suspension array have for demonstrated values in multiplex assay of tumor markers. Photonic barcodes which are encoded by their characteristic reflection peaks are the important supports for suspension array due to their stable code, low fluorescent background and high surface-volume ratio. Attempts to develop this technology tend to improve the function of the photonic barcodes. Here, we present a new type of hybrid hydrogel photonic barcodes for efficient multiplex assays. This photonic barcodes are hybrid inverse opal hydrogel composed of poly(ethylene glycol) diacrylate (PEG-DA) and agarose. The polymerized PEG-DA hydrogel could guarantee the stabilities of the inverse opal structure and its resultant code, while the agarose could offer active chemical groups for the probe immobilization and homogeneous water surrounding for the bioassay. In addition, the interconnected pores inverse opal structure could provide channels for biomolecules diffusing and reaction into the voids of barcodes. These features imparted the hybrid hydrogel photonic barcodes with limits of detection (LOD) of 0.78ng/mL for carcinoembryonic antigen (CEA) and 0.21ng/mL for α-fetoprotein (AFP), respectively. It was also demonstrated that the proposed barcodes showed acceptable accuracy and detection reproducibility, and the results were in acceptable agreement with those from common clinic method for the detections of practical clinical samples. Thus, our technique provides a new platform for simultaneous multiplex immunoassay.

  13. Is Bax/Bcl-2 Ratio Considered as a Prognostic Marker with Age and Tumor Location in Colorectal Cancer?

    PubMed Central

    Khodapasand, Ehsan; Jafarzadeh, Narges; Farrokhi, Farid; Kamalidehghan, Behnam; Houshmand, Massoud

    2015-01-01

    Background: Bax and Bcl-2 are the major members of Bcl-2 family whose play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction. Therefore, the balance between pro- and anti-apoptotic members of this family can determine the cellular fate. Methods: In this study, the relative level of mRNA expression of Bax and Bcl-2 genes was determined using RNA extraction, cDNA synthesis and RT-qPCR technique from 22 tumoral tissues and adjacent non-tumoral tissues from adenocarcinoma colorectal cancer. Results: The potential prognostic and predictive significance of Bax and Bcl-2 gene expression and Bax/Bcl-2 ratio were demonstrated in colorectal cancer. The significant correlation between qPCR data and different clinicopathologic parameters of colorectal carcinoma, including age, gender, tumor size, tumor stage, tumor location, and tumor differentiation was also examined. Interestingly, no significant correlation was seen between Bax and Bcl-2 expressions and clinicopathological parameters of colorectal cancer. However, Bax/Bcl-2 ratio was statistically correlated with age and tumor location. Patients with age above 50 showed decreased levels of Bax/Bcl-2 ratio. Moreover, the Bax/Bcl-2 ratio was significantly lower in tumors resected from colon compared to sigmoid colon, rectosigmoid and rectum tumors. Conclusion: This study indicates a significant correlation between age and tumor location with Bax/Bcl-2 expression ratio, suggesting predictive value as a potential molecular marker of colorectal cancer. PMID:25864810

  14. Hair shaft miRNA-221 levels as a new tumor marker of malignant melanoma.

    PubMed

    Inada, Taisuke; Fukushima, Satoshi; Murai, Masayuki; Jinnin, Masatoshi; Miyashita, Azusa; Nakahara, Satoshi; Yamashita, Junji; Aoi, Jun; Masuguchi, Shinichi; Ihn, Hironobu

    2015-02-01

    miRNA-221 (miR-221) is known to be abnormally expressed in many human cancers. The serum levels of miR-221 have been reported as a tumor marker for malignant melanoma (MM). We hypothesized that the hair shaft miR-221 levels may be increased in patients with MM. We therefore assessed the possibility that hair shaft miR-221 levels could be a marker for MM. The hair shaft miR-221 levels were significantly higher in patients with MM than controls. The rates of increased hair shaft miR-221 levels above the cut-off value were comparable to those of serum 5-S-CD, which is a tumor marker commonly used for MM. Measurements of the hair shaft miR-221 levels could have potential clinical value in the detection of MM. This is the first report investigating the hair shaft levels of an miRNA in patients with MM. Our investigations offer new insight into the relationship between miR-221 and MM, and may provide a new, non-invasive way to screen for melanoma.

  15. The Role of Human Chorionic Gonadotropin as Tumor Marker: Biochemical and Clinical Aspects.

    PubMed

    Sisinni, Lorenza; Landriscina, Matteo

    2015-01-01

    Tumor markers are biological substances that are produced/released mainly by malignant tumor cells, enter the circulation in detectable amounts and are potential indicators of the presence of a tumor. The most useful biochemical markers are the tumor-specific molecules, i.e., receptors, enzymes, hormones, growth factors or biological response modifiers that are specifically produced by tumor cells and not, or minimally, by the normal counterpart (Richard et al. Principles and practice of gynecologic oncology. Wolters Kluwer Health, Philadelphia, 2009). Based on their specificity and sensitivity in each malignancy, biomarkers are used for screening, diagnosis, disease monitoring and therapeutic response assessment in clinical management of cancer patients.This chapter is focused on human chorionic gonadotropin (hCG), a hormone with a variety of functions and widely used as a tumor biomarker in selected tumors. Indeed, hCG is expressed by both trophoblastic and non-trophoblastic human malignancies and plays a role in cell transformation, angiogenesis, metastatization, and immune escape, all process central to cancer progression. Of note, hCG testing is crucial for the clinical management of placental trophoblastic malignancies and germ cell tumors of the testis and the ovary. Furthermore, the production of hCG by tumor cells is accompanied by varying degrees of release of the free subunits into the circulation, and this is relevant for the management of cancer patients (Triozzi PL, Stevens VC, Oncol Rep 6(1):7-17, 1999).The name chorionic gonadotropin was conceived: chorion derives from the latin chordate meaning afterbirth, gonadotropin indicates that the hormone is a gonadotropic molecule, acting on the ovaries and promoting steroid production (Cole LA, Int J Endocrinol Metab 9(2):335-352, 2011). The function, the mechanism of action and the interaction between hCG and its receptor continue to be the subject of intensive investigation, even though many issues about

  16. Modeling Pancreatic Tumor Motion Using 4-Dimensional Computed Tomography and Surrogate Markers

    SciTech Connect

    Huguet, Florence; Yorke, Ellen D.; Davidson, Margaret; Zhang, Zhigang; Jackson, Andrew; Mageras, Gig S.; Wu, Abraham J.; Goodman, Karyn A.

    2015-03-01

    Purpose: To assess intrafractional positional variations of pancreatic tumors using 4-dimensional computed tomography (4D-CT), their impact on gross tumor volume (GTV) coverage, the reliability of biliary stent, fiducial seeds, and the real-time position management (RPM) external marker as tumor surrogates for setup of respiratory gated treatment, and to build a correlative model of tumor motion. Methods and Materials: We analyzed the respiration-correlated 4D-CT images acquired during simulation of 36 patients with either a biliary stent (n=16) or implanted fiducials (n=20) who were treated with RPM respiratory gated intensity modulated radiation therapy for locally advanced pancreatic cancer. Respiratory displacement relative to end-exhalation was measured for the GTV, the biliary stent, or fiducial seeds, and the RPM marker. The results were compared between the full respiratory cycle and the gating interval. Linear mixed model was used to assess the correlation of GTV motion with the potential surrogate markers. Results: The average ± SD GTV excursions were 0.3 ± 0.2 cm in the left-right direction, 0.6 ± 0.3 cm in the anterior-posterior direction, and 1.3 ± 0.7 cm in the superior-inferior direction. Gating around end-exhalation reduced GTV motion by 46% to 60%. D95% was at least the prescribed 56 Gy in 76% of patients. GTV displacement was associated with the RPM marker, the biliary stent, and the fiducial seeds. The correlation was better with fiducial seeds and with biliary stent. Conclusions: Respiratory gating reduced the margin necessary for radiation therapy for pancreatic tumors. GTV motion was well correlated with biliary stent or fiducial seed displacements, validating their use as surrogates for daily assessment of GTV position during treatment. A patient-specific internal target volume based on 4D-CT is recommended both for gated and not-gated treatment; otherwise, our model can be used to predict the degree of GTV motion.

  17. Mortality and Embolic Potential of Cardiac Tumors

    PubMed Central

    Dias, Ricardo Ribeiro; Fernandes, Fábio; Ramires, Félix José Alvarez; Mady, Charles; Albuquerque, Cícero Piva; Jatene, Fábio Biscegli

    2014-01-01

    Background Cardiac tumors are rare, mostly benign with high embolic potential. Objectives To correlate the histological type of cardiac masses with their embolic potential, implantation site and long term follow up in patients undergoing surgery. Methods Between January 1986 and December 2011, we retrospectively analyzed 185 consecutive patients who underwent excision of intracardiac mass (119 females, mean age 48±20 years). In 145 patients, the left atrium was the origin site. 72% were asymptomatic and prior embolization was often observed (19.8%). The diagnosis was established by echocardiography, magnetic resonance and histological examination. Results Most tumors were located in the left side of the heart. Myxoma was the most common (72.6%), followed by fibromas (6.9%), thrombi (6.4%) and sarcomas (6.4%). Ranging from 0.6cm to 15cm (mean 4.6 ± 2.5cm) 37 (19.8%) patients had prior embolization, stroke 10.2%, coronary 4.8%, peripheral 4.3% 5.4% of hospital death, with a predominance of malignant tumors (40% p < 0.0001). The histological type was a predictor of mortality (rhabdomyomas and sarcomas p = 0.002) and embolic event (sarcoma, lipoma and fibroelastoma p = 0.006), but not recurrence. Tumor size, atrial fibrillation, cavity and valve impairment were not associated with the embolic event. During follow-up (mean 80±63 months), there were 2 deaths (1.1%) and two recurrences 1 and 11 years after the operation, to the same cavity. Conclusion Most tumors were located in the left side of the heart. The histological type was predictor of death and preoperative embolic event, while the implantation site carries no relation with mortality or to embolic event. PMID:25029470

  18. Analysis of Marker-Defined HNSCC Subpopulations Reveals a Dynamic Regulation of Tumor Initiating Properties

    PubMed Central

    Bragado, Paloma; Estrada, Yeriel; Sosa, Maria Soledad; Avivar-Valderas, Alvaro; Cannan, David; Genden, Eric; Teng, Marita; Ranganathan, Aparna C.; Wen, Huei-Chi; Kapoor, Avnish; Bernstein, Emily; Aguirre-Ghiso, Julio A.

    2012-01-01

    Head and neck squamous carcinoma (HNSCC) tumors carry dismal long-term prognosis and the role of tumor initiating cells (TICs) in this cancer is unclear. We investigated in HNSCC xenografts whether specific tumor subpopulations contributed to tumor growth. We used a CFSE-based label retentions assay, CD49f (α6-integrin) surface levels and aldehyde dehydrogenase (ALDH) activity to profile HNSCC subpopulations. The tumorigenic potential of marker-positive and -negative subpopulations was tested in nude (Balb/c nu/nu) and NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice and chicken embryo chorioallantoic membrane (CAM) assays. Here we identified in HEp3, SQ20b and FaDu HNSCC xenografts a subpopulation of G0/G1-arrested slow-cycling CD49fhigh/ALDH1A1high/H3K4/K27me3low subpopulation (CD49f+) of tumor cells. A strikingly similar CD49fhigh/H3K27me3low subpopulation is also present in primary human HNSCC tumors and metastases. While only sorted CD49fhigh/ALDHhigh, label retaining cells (LRC) proliferated immediately in vivo, with time the CD49flow/ALDHlow, non-LRC (NLRC) tumor cell subpopulations were also able to regain tumorigenic capacity; this was linked to restoration of CD49fhigh/ALDHhigh, label retaining cells. In addition, CD49f is required for HEp3 cell tumorigenicity and to maintain low levels of H3K4/K27me3. CD49f+ cells also displayed reduced expression of the histone-lysine N-methyltransferase EZH2 and ERK1/2phosphorylation. This suggests that although transiently quiescent, their unique chromatin structure is poised for rapid transcriptional activation. CD49f− cells can “reprogram” and also achieve this state eventually. We propose that in HNSCC tumors, epigenetic mechanisms likely driven by CD49f signaling dynamically regulate HNSCC xenograft phenotypic heterogeneity. This allows multiple tumor cell subpopulations to drive tumor growth suggesting that their dynamic nature renders them a “moving target” and their eradication might require more

  19. Quantum-dot-tagged photonic crystal beads for multiplex detection of tumor markers.

    PubMed

    Li, Juan; Wang, Huan; Dong, Shujun; Zhu, Peizhi; Diao, Guowang; Yang, Zhanjun

    2014-12-04

    Novel quantum-dot-tagged photonic crystal beads were fabricated for multiplex detection of tumor markers via self-assembly of quantum dot-embedded polystyrene nanospheres into photonic crystal beads through a microfluidic device.

  20. Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications.

    PubMed

    Papagiorgis, Petros Christakis

    2016-05-01

    Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.

  1. Tumor markers in clinical practice: a review focusing on common solid cancers.

    PubMed

    Duffy, Michael J

    2013-01-01

    Tumor markers are playing an increasingly important role in cancer detection and management. These laboratory-based tests are potentially useful in screening for early malignancy, aiding cancer diagnosis, determining prognosis, surveillance following curative surgery for cancer, up front predicting drug response or resistance, and monitoring therapy in advanced disease. Clinically useful markers include fecal occult blood testing in screening for early colorectal cancer, carcinoembryonic antigen in the management of patients with colorectal cancer, both α-fetoprotein and human chorionic gonadotrophin in the management of patients with non-seminomatous germ cell tumors, CA 125 for monitoring therapy in patients with ovarian cancer, estrogen receptors for predicting response to hormone therapy in breast cancer, human epidermal growth factor receptor 2 for the identification of women with breast cancer likely to respond to trastuzumab (Herceptin) and KRAS mutational status for identifying patients with advanced colorectal cancer likely to benefit from treatment with the anti-epidermal growth factor receptor antibodies, cetuximab and panitumumab. Although widely used, the value of prostate-specific antigen screening in reducing mortality from prostate cancer is unclear.

  2. KIT is an independent prognostic marker for pancreatic endocrine tumors: a finding derived from analysis of islet cell differentiation markers.

    PubMed

    Zhang, Lizhi; Smyrk, Thomas C; Oliveira, Andre M; Lohse, Christine M; Zhang, Shuya; Johnson, Michele R; Lloyd, Ricardo V

    2009-10-01

    Prediction of the biologic behavior of pancreatic endocrine tumor (PET) without local invasion or metastasis is often difficult. The 2004 World Health Organization (WHO) classification uses size, angioinvasion, mitotic activity, and Ki-67 index as prognostic criteria. Recently, cytokeratin 19 (CK19) was shown to be another prognostic marker, but the mechanism by which CK19 predicts prognosis is unknown. As CK19 is the first cytokeratin expressed in all epithelial cells in fetal pancreas, we sought to test expression of other markers of islet cell differentiation including KIT, Pdx-1, Pax4, and Pax6 in PET and correlation of these markers with clinical behavior. Clinical information and histology was reviewed in 97 PETs. All tumors were classified according to WHO criteria and a tumor, node, and metastases stage system. Immunohistochemistry was performed using antibodies to Ki-67, KIT, CK19, Pdx-1, Pax4, and Pax6. Associations of clinicopathologic and immunohistochemical features with prognosis were evaluated using Cox proportional hazards regression models. WHO and tumor, node, and metastases classifications, mitotic counts and Ki-67 labeling, infiltrative border, necrosis, perineural invasion, extrapancreatic extension, tumor size, and positive CK19 and KIT expression were significantly associated with death from disease in a univariate setting. In multivariate analysis, only WHO criteria and KIT expression were shown to be independent. An immunohistochemical classification system was derived from a combination of KIT and CK19 expression: low risk (KIT-/CK19-), intermediate risk (KIT-/CK19+), and high risk (KIT+/CK19+). Survival, metastases, and recurrence of PET were significantly different among the 3 groups. These results indicate that KIT is a new and independent prognostic marker for PETs. The classification system derived from KIT and CK19 was able to predict clinical behavior of PET.

  3. Hyperpolarized 13C MR Markers of Renal Tumor Aggressiveness

    DTIC Science & Technology

    2014-10-01

    lactate in the media. We observed three fold higher rate of lactate secreted into the media by the ccRCC tissue compared to the normal kidney (figure...imaging sequences with higher spatial resolution as well as sensitivity to generate contrast between the mouse kidney and the tumor grafts. This will...signal in the tumor grafts compared to the high background signal arising from the mouse kidney , several optimizations were explored, such as diffusion

  4. Recognition of Transmembrane Protein 39A as a Tumor-Specific Marker in Brain Tumor

    PubMed Central

    Park, Jisoo; Lee, Hyunji; Tran, Quangdon; Mun, Kisun; Kim, Dohoon; Hong, Youngeun; Kwon, So Hee; Brazil, Derek; Park, Jongsun; Kim, Seon-Hwan

    2017-01-01

    Transmembrane protein 39A (TMEM39A) belongs to the TMEM39 family. TMEM39A gene is a susceptibility locus for multiple sclerosis. In addition, TMEM39A seems to be implicated in systemic lupus erythematosus. However, any possible involvement of TMEM39A in cancer remains largely unknown. In the present report, we provide evidence that TMEM39A may play a role in brain tumors. Western blotting using an anti-TMEM39A antibody indicated that TMEM39A was overexpressed in glioblastoma cell lines, including U87-MG and U251-MG. Deep-sequencing transcriptomic profiling of U87-MG and U251-MG cells revealed that TMEM39A transcripts were upregulated in such cells compared with those of the cerebral cortex. Confocal microscopic analysis of U251-MG cells stained with anti-TMEM39A antibody showed that TMEM39A was located in dot-like structures lying close to the nucleus. TMEM39A probably located to mitochondria or to endosomes. Immunohistochemical analysis of glioma tissue specimens indicated that TMEM39A was markedly upregulated in such samples. Bioinformatic analysis of the Rembrandt knowledge base also supported upregulation of TMEM39A mRNA levels in glioma patients. Together, the results afford strong evidence that TMEM39A is upregulated in glioma cell lines and glioma tissue specimens. Therefore, TMEM39A may serve as a novel diagnostic marker of, and a therapeutic target for, gliomas and other cancers. PMID:28133515

  5. Chromogranin A – unspecific neuroendocrine marker. Clinical utility and potential diagnostic pitfalls

    PubMed Central

    Czarnywojtek, Agata; Fischbach, Jakub; Bączyk, Maciej; Ziemnicka, Katarzyna; Wrotkowska, Elżbieta; Gryczyńska, Maria; Ruchała, Marek

    2016-01-01

    Chromogranin A, despite a number of limitations, is still the most valuable marker of neuroendocrine tumors (NETs). Granins belong to the family of acidic proteins that constitute a major component of secretory granules of various endocrine and neuroendocrine cells, which are components of both the classical endocrine glands and the diffuse neuroendocrine system. These cells are a potential source of transformation into neuroendocrine tumors. The awareness of potential causes influencing the false results of its concentrations simplifies diagnosis and treatment. One of the disadvantages of this marker is its non-specificity and the existence of a number of pathological processes leading to an increase in its concentration, which often results in confusion and diagnostic difficulties. The molecular structure is characterized by a number of sites susceptible to the proteolytic activity of enzymes, resulting in the formation of a number of biologically active peptides. Presumably they act as precursors of active proteins. Chromogranin expression correlates with the amount of secretory vesicles in neuroendocrine cells. The peptide chain during biochemical changes becomes a precursor of biologically active proteins with a wide range of activities. There are a number of commercially available kits for the determination of chromogranin A, which differ in methodology. We present the evaluation of chromogranin A as a marker of neuroendocrine tumors in clinical practice and the possible factors that may affect the outcome of its concentration. PMID:26925113

  6. Magic roundabout, a tumor endothelial marker: expression and signaling.

    PubMed

    Seth, Pankaj; Lin, Yanfeng; Hanai, Jun-ichi; Shivalingappa, Venkatesha; Duyao, Mabel P; Sukhatme, Vikas P

    2005-07-01

    Molecular signals that guide blood vessels to specific paths are not fully deciphered, but are thought to be similar to signals that mediate neuronal guidance. These cues are not only critical for normal blood vessel development, but may also play a major role in tumor angiogenesis. In this study, we have demonstrated the tumor endothelial specific expression of a Robo family member, magic roundabout (MRB), functionally characterized its role in endothelial cell migration and defined a signaling pathway that might mediate this function. We show that MRB is differentially over-expressed in tumor endothelial cells versus normal adult endothelial cells in numerous solid tumors. Moreover, over-expression of MRB in endothelial cells activates MRB in a ligand-independent fashion, and activation of MRB via Slit2, a putative ligand, results in inhibition of VEGF and FGF induced migration. We also demonstrate that MRB induced inhibition of endothelial migration is partially mediated by the Ras-Raf-Mek-Erk signaling pathway. We therefore hypothesize that expression of MRB is involved in regulating the migration of endothelial cells during tumor angiogenesis.

  7. Quantification of plasma exosome is a potential prognostic marker for esophageal squamous cell carcinoma.

    PubMed

    Matsumoto, Yasunori; Kano, Masayuki; Akutsu, Yasunori; Hanari, Naoyuki; Hoshino, Isamu; Murakami, Kentaro; Usui, Akihiro; Suito, Hiroshi; Takahashi, Masahiko; Otsuka, Ryota; Xin, Hu; Komatsu, Aki; Iida, Keiko; Matsubara, Hisahiro

    2016-11-01

    Exosomes play important roles in cancer progression. Although its contents (e.g., proteins and microRNAs) have been focused on in cancer research, particularly as potential diagnostic markers, the exosome behavior and methods for exosome quantification remain unclear. In the present study, we analyzed the tumor-derived exosome behavior and assessed the quantification of exosomes in patient plasma as a biomarker for esophageal squamous cell carcinoma (ESCC). A CD63-GFP expressing human ESCC cell line (TE2-CD63-GFP) was made by transfection, and mouse subcutaneous tumor models were established. Fluorescence imaging was performed on tumors and plasma exosomes harvested from mice. GFP-positive small vesicles were confirmed in the plasma obtained from TE2-CD63-GFP tumor-bearing mice. Patient plasma was collected in Chiba University Hospital (n=86). Exosomes were extracted from 100 µl of the plasma and quantified by acetylcholinesterase (AChE) activity. The relationship between exosome quantification and the patient clinical characteristics was assessed. The quantification of exosomes isolated from the patient plasma revealed that esophageal cancer patients (n=66) expressed higher exosome levels than non-malignant patients (n=20) (P=0.0002). Although there was no correlation between the tumor progression and the exosome levels, exosome number was the independent prognostic marker and low levels of exosome predicted a poor prognosis (P=0.03). In conclusion, exosome levels may be useful as an independent prognostic factor for ESCC patients.

  8. Molecular predictive markers in tumors of the gastrointestinal tract

    PubMed Central

    Papadopoulou, Eirini; Metaxa-Mariatou, Vasiliki; Tsaousis, Georgios; Tsoulos, Nikolaos; Tsirigoti, Angeliki; Efstathiadou, Chrisoula; Apessos, Angela; Agiannitopoulos, Konstantinos; Pepe, Georgia; Bourkoula, Eugenia; Nasioulas, George

    2016-01-01

    Gastrointestinal malignancies are among the leading causes of cancer-related deaths worldwide. Like all human malignancies they are characterized by accumulation of mutations which lead to inactivation of tumor suppressor genes or activation of oncogenes. Advances in Molecular Biology techniques have allowed for more accurate analysis of tumors’ genetic profiling using new breakthrough technologies such as next generation sequencing (NGS), leading to the development of targeted therapeutical approaches based upon biomarker-selection. During the last 10 years tremendous advances in the development of targeted therapies for patients with advanced cancer have been made, thus various targeted agents, associated with predictive biomarkers, have been developed or are in development for the treatment of patients with gastrointestinal cancer patients. This review summarizes the advances in the field of molecular biomarkers in tumors of the gastrointestinal tract, with focus on the available NGS platforms that enable comprehensive tumor molecular profile analysis. PMID:27895815

  9. Sox10 – A marker for not only Schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue. A systematic analysis of 5134 tumors

    PubMed Central

    Miettinen, Markku; McCue, Peter A.; Sarlomo-Rikala, Maarit; Biernat, Wojciech; Czapiewski, Piotr; Kopczynski, Janusz; Thompson, Lester D.; Lasota, Jerzy; Wang, Zengfeng; Fetsch, John F.

    2015-01-01

    Sox10 transcription factor is expressed in Schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. Additionally, it has been reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 express-ion in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30–70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the GI-tract and metastatic melanoma, and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, PEComa, and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell type breast cancers, were only rarely positive but included rare squamous carcinomas of head and neck and pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors. PMID:25724000

  10. Optimal surface marker locations for tumor motion estimation in lung cancer radiotherapy

    NASA Astrophysics Data System (ADS)

    Dong, Bin; Jiang Graves, Yan; Jia, Xun; Jiang, Steve B.

    2012-12-01

    Using fiducial markers on the patient’s body surface to predict the tumor location is a widely used approach in lung cancer radiotherapy. The purpose of this work is to propose an algorithm that automatically identifies a sparse set of locations on the patient’s surface with the optimal prediction power for the tumor motion. In our algorithm, it is assumed that there is a linear relationship between the surface marker motion and the tumor motion. The sparse selection of markers on the external surface and the linear relationship between the marker motion and the internal tumor motion are represented by a prediction matrix. Such a matrix is determined by solving an optimization problem, where the objective function contains a sparsity term that penalizes the number of markers chosen on the patient’s surface. Bregman iteration is used to solve the proposed optimization problem. The performance of our algorithm has been tested on realistic clinical data of four lung cancer patients. Thoracic 4DCT scans with ten phases are used for the study. On a reference phase, a grid of points are casted on the patient’s surfaces (except for the patient’s back) and propagated to other phases via deformable image registration of the corresponding CT images. Tumor locations at each phase are also manually delineated. We use nine out of ten phases of the 4DCT images to identify a small group of surface markers that are mostly correlated with the motion of the tumor and find the prediction matrix at the same time. The tenth phase is then used to test the accuracy of the prediction. It is found that on average six to seven surface markers are necessary to predict tumor locations with a 3D error of about 1 mm. It is also found that the selected marker locations lie closely in those areas where surface point motion has a large amplitude and a high correlation with the tumor motion. Our method can automatically select sparse locations on the patient’s external surface and

  11. Identifying molecular markers for the sensitive detection of residual atypical teratoid rhabdoid tumor cells.

    PubMed

    Vu-Han, Tu-Lan; Frühwald, Michael C; Hasselblatt, Martin; Kerl, Kornelius; Nagel, Inga; Obser, Tobias; Oyen, Florian; Siebert, Reiner; Schneppenheim, Reinhard

    2014-09-01

    Atypical teratoid rhabdoid tumor (AT/RT), a rare and highly malignant tumor entity of the central nervous system that presents in early childhood, has a poor prognosis. AT/RTs are characterized by biallelic inactivating mutations of the gene SMARCB1 in 98% of patients; these mutations may serve as molecular markers for residual tumor cell detection in liquid biopsies. We developed a marker-specific method to detect residual AT/RT cells. Seven of 150 patient samples were selected, each with a histological and genetically ascertained diagnosis of AT/RT. Tumor tissue was either formalin fixed or fresh frozen. DNA was extracted from the patients' peripheral blood leukocytes (PBL) and cerebrospinal fluid (CSF). Multiplex ligation-dependent probe amplification, DNA sequencing, and fluorescence in situ hybridization were used to characterize the tumors' mutations. Residual tumor cell detection used mutation-specific primers and real-time PCR. The detection limit for the residual tumor cell search was 1-18%, depending on the quality of the template provided. The residual tumor cell search in PBL and CSF was negative for all seven patients. The SMARCB1 region of chromosome 22 is prone to DNA double-strand breaks. The individual breakpoints and breakpoint-specific PCR offer the option to detect minimal residual tumor cells in CSF or blood. Even if we did not detect minimal residual tumor cells in the investigated material, proof of principle for this method was confirmed.

  12. Metanephrine neuroendocrine tumor marker detection by SERS using Au nanoparticle/Au film sandwich architecture.

    PubMed

    Boca, Sanda; Farcau, Cosmin; Baia, Monica; Astilean, Simion

    2016-02-01

    Neuroendocrine tumors, such as pheochromocytoma or paraganglioma, are dangerous tumors that constitute a potential threat for a large number of patients. Currently, the biochemical diagnosis of neuroendocrine tumors is based on measurement of the direct secretory products of the adrenomedullary-sympathetic system or of their metabolites, such as catecholamines or their metanephrine derivatives, from plasma or urine. The techniques used for analysis of plasma free metanephrines, i.e. high-performance liquid chromatography or high-performance liquid chromatography coupled with mass-spectrometry are technically-demanding and time consuming, which limit their availability. Here we demonstrate a simple, fast and low-cost method for detecting metanephrine by Surface Enhanced Raman Scattering (SERS). The protocol consists in using evaporation-induced self-assembly of gold (Au) nanoparticles incubated with the analyte, on planar gold films. The assembly process produces regions with a dense distribution of both inter-particle gaps and particle-film gaps. Finite-difference time-domain simulations confirm that both kinds of gaps are locations of enhanced electromagnetic fields resulting from inter-particle and particle-film plasmonic coupling, useful for SERS amplification. Metanephrine vibrational bands assignment was performed according to density functional theory calculations. Metanephrine metabolite was detected in liquid at concentration levels lower than previously reported for other similar metabolites. The obtained results demonstrate that the Au nanoparticle/Au film exhibits noticeable SERS amplification of the adsorbed metabolite and can be used in the design of efficient, stable SERS-active substrates for the detection and identification of specific tumor markers.

  13. Tumor cell differentiation by marker free fluorescence microscopy

    NASA Astrophysics Data System (ADS)

    Schneckenburger, Herbert; Weber, Petra; Wagner, Michael; Brantsch, Marco; Biller, Philipp; Kioschis, Petra; Kessler, Waltraud

    2011-02-01

    Autofluorescence and Raman spectra, images and decay kinetics of U251-MG glioblastoma cells prior and after activation of tumor suppressor genes are compared. While phase contrast images and fluorescence patterns of the tumor (control) cells and the less malignant cells are similar, differences can be deduced from autofluorescence spectra and decay times. In particular, upon excitation around 375nm, the fluorescence ratio of the protein bound and the free coenzyme NADH depends on the state of malignancy. Slight differences are also observed in Raman spectra of these cell lines, in particular at wave numbers around 970 cm-1. While larger numbers of fluorescence and Raman spectra are evaluated by the method of multivariate data analysis, additional information is obtained from spectral images and fluorescence lifetime images (FLIM).

  14. Molecular Markers for Novel Therapeutic Strategies in Pancreatic Endocrine Tumors

    PubMed Central

    Gilbert, Judith A.; Adhikari, Laura J.; Lloyd, Ricardo V.; Halfdanarson, Thorvardur R.; Muders, Michael H.; Ames, Matthew M.

    2012-01-01

    Objectives Pancreatic endocrine tumors (PETs) share numerous features with gastrointestinal neuroendocrine (carcinoid) tumors. Targets of novel therapeutic strategies previously assessed in carcinoid tumors were analyzed in PETs (44 cases). Methods Activating mutations in EGFR, KIT, and PDGFRA, and non-response mutations in KRAS, were evaluated. Copy number of EGFR and HER-2/neu was quantified by fluorescence in situ hybridization. Expression of EGFR, PDGFRA, VEGFR1, TGFBR1, Hsp90, SSTR2A, SSTR5, IGF1R, mTOR, and MGMT was measured immunohistochemically. Results Elevated EGFR copy number was found in 38% of cases, but no KRAS non-response mutations. VEGFR1, TGFBR1, PDGFRA, SSTR5, SSTR2A, and IGF1R exhibited the highest levels of expression in the largest percentages of PETs. Anticancer drugs BMS-754807 (selective for IGF1R/IR), 17-(allylamino)-17-demethoxygeldanamycin (17-AAG, targeting Hsp90), and axitinib (directed toward VEGFR1–3/PDGFRA-B/KIT) induced growth inhibition of human QGP-1 PET cells with IC50 values (nM) of 273, 723, and 743, respectively. At growth-inhibiting concentrations, BMS-754807 inhibited IGF1R phosphorylation; 17-AAG induced loss of EGFR, IGF1R, and VEGFR2; and axitinib increased p21Waf1/Cip1(CDKN1A) expression without inhibiting VEGFR2 phosphorylation. Conclusions Results encourage further research into multi-drug strategies incorporating inhibitors targeting IGF1R or Hsp90 and into studies of axitinib combined with conventional chemotherapeutics toxic to tumor cells in persistent growth arrest. PMID:23211371

  15. Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

    SciTech Connect

    Ohta, Kengo Shimohira, Masashi; Sasaki, Shigeru Iwata, Hiromitsu Nishikawa, Hiroko Ogino, Hiroyuki Hara, Masaki; Hashizume, Takuya Shibamoto, Yuta

    2015-10-15

    PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors.

  16. Radioimmunoassay of tumor markers in serum of patients with renal carcinoma

    SciTech Connect

    Cordoni-Voutsas, M.; Glaubitt, D.; Wagner, W.; Lichtenberg, T.

    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 serum 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.

  17. Volatile compounds as potential defective coffee beans' markers.

    PubMed

    Toci, Aline T; Farah, Adriana

    2008-06-01

    Although Brazil is the largest raw coffee producer and exporter in the world, a large amount of its Arabica coffee production is considered inappropriate for exportation. This by-product of coffee industry is called PVA due to the presence of black (P), green (V) and sour (A) defective beans, which are known to contribute considerably for cup quality decrease. Data on the volatile composition of Brazilian defective coffee beans are scarce. In this study, we evaluated the volatile composition of defective coffee beans (two lots) compared to good quality beans from the respective lots. Potential defective beans' markers were identified. In the raw samples, 2-methylpyrazine and 2-furylmethanol acetate were identified only in black-immature beans and butyrolactone only in sour beans, while benzaldehyde and 2,3,5,6-tetramethylpyrazine showed to be potential markers of defective beans in general. In the roasted PVA beans, pyrazine, 2,3-butanediol meso, 2-methyl-5-(1-propenyl)pyrazine, hexanoic acid, 4-ethyl-guayacol and isopropyl p-cresol sulfide also showed to be potential defective coffee beans' markers.

  18. Therapeutic potential of bacteria against solid tumors.

    PubMed

    Hatzikirou, Haralampos; Lopez Alfonso, Juan Carlos; Leschner, Sara; Weiss, Siegfried; Meyer-Hermann, Michael

    2017-02-15

    Intentional bacterial infections can produce efficacious anti-tumor responses in mice, rats, dogs and humans. However, low overall success rates and intense side-effects prevent such approaches from being employed clinically. In this work, we titered bacteria and/or the pro-inflammatory cytokine TNF-α in a set of established murine models of cancer. To interpret the experiments conducted, we considered and calibrated a tumor-effector cell recruitment model under the influence of functional tumor-associated vasculature. In this model, bacterial infections and TNF-α enhanced immune activity and altered vascularization in the tumor bed. Information to predict bacterial therapy outcomes was provided by pre-treatment tumor size and the underlying immune recruitment dynamics. Notably, increasing bacterial loads did not necessarily produce better long-term tumor control, suggesting that tumor sizes affected optimal bacterial loads. Short-term treatment responses were favored by high concentrations of effector cells post-injection, such as induced by higher bacterial loads, but in the longer term did not correlate with an effective restoration of immune surveillance. Overall, our findings suggested that a combination of intermediate bacterial loads with low levels TNF-α administration could enable more favorable outcomes elicited by bacterial infections in tumor-bearing subjects.

  19. The effect of artificial neural network model combined with six tumor markers in auxiliary diagnosis of lung cancer.

    PubMed

    Feng, Feifei; Wu, Yiming; Wu, Yongjun; Nie, Guangjin; Ni, Ran

    2012-10-01

    To evaluate the diagnosis potential of artificial neural network (ANN) model combined with six tumor markers in auxiliary diagnosis of lung cancer, to differentiate lung cancer from lung benign disease, normal control, and gastrointestinal cancers. Serum carcino-embryonic antigen (CEA), gastrin, neurone specific enolase (NSE), sialic acid (SA), Cu/Zn, Ca were measured through different experimental procedures in 117 lung cancer patients, 93 lung benign disease patients, 111 normal control, 47 gastric cancer patients, 50 patients with colon cancer and 50 esophagus cancer patients, 19 parameters of basic information were surveyed among lung cancer, lung benign disease and normal control, then developed and evaluated ANN models to distinguish lung cancer. Using the ANN model with the six serum tumor markers and 19 parameters to distinguish lung cancer from benign lung disease and healthy people, the sensitivity was 98.3%, the specificity was 99.5% and the accuracy was 96.9%. Another three ANN models with the six serum tumor markers were employed to differentiate lung cancer from three gastrointestinal cancers, the sensitivity, specificity and accuracy of distinguishing lung cancer from gastric cancer by the ANN model of lung cancer-gastric cancer were 100%, 83.3% and 93.5%, respectively; The sensitivity, specificity and accuracy of discriminating lung cancer by lung cancer-colon cancer ANN model were 90.0%, 90.0%, and 90.0%; And which were 86.7%, 84.6%, and 86.0%, respectively, by lung cancer-esophagus cancer ANN model. ANN model built with the six serum tumor markers could distinguish lung cancer, not only from lung benign disease and normal people, but also from three common gastrointestinal cancers. And our evidence indicates the ANN model maybe is an excellent and intelligent system to discriminate lung cancer.

  20. Identification of potential protein markers of noble rot infected grapes.

    PubMed

    Lorenzini, Marilinda; Millioni, Renato; Franchin, Cinzia; Zapparoli, Giacomo; Arrigoni, Giorgio; Simonato, Barbara

    2015-07-15

    The evaluation of Botrytis cinerea as noble rot on withered grapes is of great importance to predict the wine sensory/organoleptic properties and to manage the winemaking process of Amarone, a passito dry red wine. This report describes the first proteomic analysis of grapes infected by noble rot under withering conditions to identify possible markers of fungal infection. 2-D gel electrophoresis revealed that protein profiles of infected and not infected grape samples are significantly different in terms of number of spots and relative abundance. Protein identification by MS analysis allowed to identify only in infected berries proteins of B. cinerea that represent potential markers of the presence of the fungus in the withered grapes.

  1. Tumor interstitial fluid pressure as an early-response marker for anticancer therapeutics.

    PubMed

    Ferretti, Stephane; Allegrini, Peter R; Becquet, Mike M; McSheehy, Paul Mj

    2009-09-01

    Solid tumors have a raised interstitial fluid pressure (IFP) due to high vessel permeability, low lymphatic drainage, poor perfusion, and high cell density around the blood vessels. To investigate tumor IFP as an early-response biomarker, we have tested the effect of seven anticancer chemotherapeutics including cytotoxics and targeted cytostatics in 13 experimental tumor models. IFP was recorded with the wick-in-needle method. Models were either ectopic or orthotopic and included mouse and rat syngeneic as well as human xenografts in nude mice. The mean basal IFP was between 4.4 and 15.2mm Hg; IFP was lowest in human tumor xenografts and highest in rat syngeneic models. Where measured, basal IFP correlated positively with relative tumor blood volume (rTBV) determined by dynamic contrast-enhanced magnetic resonance imaging. Most chemotherapeutics sooner (2 or 3 days) or later (6 or 7 days) lowered tumor IFP significantly, and the cytotoxic patupilone caused the greatest decrease in IFP. In rat mammary orthotopic BN472 tumors, significant drug-induced decreases in IFP and rTBV correlated positively with each other for both patupilone and the cytostatic vatalanib. In the two orthotopic models studied, early decreases in IFP were significantly (P < or = .005) correlated with late changes in tumor volume. Thus, drug-induced decreases in tumor IFP are an early marker of response to therapy, which could aid clinical development.

  2. Interfractional Position Variation of Pancreatic Tumors Quantified Using Intratumoral Fiducial Markers and Daily Cone Beam Computed Tomography

    SciTech Connect

    Horst, Astrid van der; Wognum, Silvia; Dávila Fajardo, Raquel; Jong, Rianne de; Hooft, Jeanin E. van; Fockens, Paul; Tienhoven, Geertjan van; Bel, Arjan

    2013-09-01

    Purpose: The aim of this study was to quantify interfractional pancreatic position variation using fiducial markers visible on daily cone beam computed tomography (CBCT) scans. In addition, we analyzed possible migration of the markers to investigate their suitability for tumor localization. Methods and Materials: For 13 pancreatic cancer patients with implanted Visicoil markers, CBCT scans were obtained before 17 to 25 fractions (300 CBCTs in total). Image registration with the reference CT was used to determine the displacement of the 2 to 3 markers relative to bony anatomy and to each other. We analyzed the distance between marker pairs as a function of time to identify marker registration error (SD of linear fit residuals) and possible marker migration. For each patient, we determined the mean displacement of markers relative to the reference CT (systematic position error) and the spread in displacements (random position error). From this, we calculated the group systematic error, Σ, and group random error, σ. Results: Marker pair distances showed slight trends with time (range, −0.14 to 0.14 mm/day), possibly due to tissue deformation, but no shifts that would indicate marker migration. The mean SD of the fit residuals was 0.8 mm. We found large interfractional position variations, with for 116 of 300 (39%) fractions a 3-dimensional vector displacement of >10 mm. The spread in displacement varied significantly (P<.01) between patients, from a vector range of 9.1 mm to one of 24.6 mm. For the patient group, Σ was 3.8, 6.6, and 3.5 mm; and σ was 3.6, 4.7 and 2.5 mm, in left–right, superior–inferior, and anterior–posterior directions, respectively. Conclusions: We found large systematic displacements of the fiducial markers relative to bony anatomy, in addition to wide distributions of displacement. These results for interfractional position variation confirm the potential benefit of using fiducial markers rather than bony anatomy for daily online

  3. Senescence marker protein 30 (SMP30) serves as a potential prognostic indicator in hepatocellular carcinoma

    PubMed Central

    Mo, Zhijing; Zheng, Shunxin; Lv, Zhilue; Zhuang, Yuan; Lan, Xiuwan; Wang, Feng; Lu, Xiaoling; Zhao, Yongxiang; Zhou, Sufang

    2016-01-01

    Senescence marker protein 30 (SMP30) has been identified as a tumor-related molecule of hepatocellular carcinoma (HCC). Its clinical significance and underlying mechanisms in HCC tissues, however, remain largely unexplored. We have demonstrated a preferentially expressed SMP30 in normal liver using a tissue microarray. By employing real-time quantitative PCR, two tissue microarrays and Oncomine database analysis, we have also shown that the SMP30 in HCC tissues has significantly reduced when compared with that in paired adjacent non-tumor tissues (P = 0.0037). The reduced expression of SMP30 is very noticeably related to larger tumor size (P = 0.012), enhanced TNM (P = 0.009) and worse survival (P < 0.0001) in HCC patients. The analyses using Cox regression have indicated that the decreased SMP30 expression is an independent risk to the reduced overall survival rate of HCC patients (P = 0.001), and the down-regulation of SMP30 in HCC might be mediated by DNA methylation. Moreover, genes co-expressed with SMP30 may affect the prognosis through apoptotic process, biological adhesion and blood coagulation by PANTHER analyses. Our studies have indicated that the SMP30 may serve as a candidate of HCC clinical prognostic marker and a potential therapeutic target. PMID:27991558

  4. Immunomagnetic separation of tumor initiating cells by screening two surface markers

    PubMed Central

    Sun, Chen; Hsieh, Yuan-Pang; Ma, Sai; Geng, Shuo; Cao, Zhenning; Li, Liwu; Lu, Chang

    2017-01-01

    Isolating tumor initiating cells (TICs) often requires screening of multiple surface markers, sometimes with opposite preferences. This creates a challenge for using bead-based immunomagnetic separation (IMS) that typically enriches cells based on one abundant marker. Here, we propose a new strategy that allows isolation of CD44+/CD24− TICs by IMS involving both magnetic beads coated by anti-CD44 antibody and nonmagnetic beads coated by anti-CD24 antibody (referred to as two-bead IMS). Cells enriched with our approach showed significant enhancement in TIC marker expression (examined by flow cytometry) and improved tumorsphere formation efficiency. Our method will extend the application of IMS to cell subsets characterized by multiple markers. PMID:28074882

  5. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update.

    PubMed

    Duffy, M J; Lamerz, R; Haglund, C; Nicolini, A; Kalousová, M; Holubec, L; Sturgeon, C

    2014-06-01

    Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.

  6. Adenosine deaminase complexing protein (ADCP): a transformation sensitive protein with potentials of a cancer marker.

    PubMed

    Herbschleb-Voogt, E; Ten Kate, J; Meera Khan, P

    1983-01-01

    Several observations by independent investigators in the past have indicated that adenosine deaminase complexing protein (ADCP), present in considerable quantities in certain human tissues, was absent or decreased in the cancers originated from them. During the present study, electrophoretic analysis of adenosine deaminase (ADA) isozymes and radioimmunoassay for ADCP in the primary fibroblasts and the transformed as well as certain tumor derived cell lines have demonstrated that ADCP present in large quantities in the primary cells was absent or nearly absent in the transformed or tumor-derived cell lines. Though the mechanisms involved are not yet clear, the above observations indicate that ADCP has the potentials of a useful marker in the studies on transformed cells and cancer tissues.

  7. The comparison of nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) with Ki67 proliferation marker expression in common skin tumors.

    PubMed

    Zduniak, Krzysztof; Agrawal, Siddarth; Symonowicz, Krzysztof; Jurczyszyn, Kamil; Ziółkowski, Piotr

    2014-03-01

    Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) is a chromosomal protein of unknown function. Its amino acid composition and structure of its DNA binding domain resemble those of high mobility group A (HMGA) proteins which are associated with various malignancies. Since changes in expression of HMGA are considered as a marker of tumor progression, it is possible that similar changes in expression of NUCKS could be a useful tool in diagnosis of malignant skin tumors. To investigate this assumption we used specific antibodies against NUCKS for immunohistochemistry of squamous (SCC) and basal cell carcinoma (BCC) as well as keratoacanthoma (KA). We found high expression of NUCKS in nuclei of SCC and BCC cells which exceeded expression of the well-known proliferation marker Ki67. Expression of NUCKS in benign KA was much below that of malignant tumors. With the present study and based on our previous experience we would like to suggest the NUCKS protein as a novel proliferation marker for immunohistochemical evaluation of formalin-fixed and paraffin-embedded skin tumor specimens. We would like to emphasize that NUCKS abundance in malignant skin tumors is higher than that of the well-known proliferation marker Ki67, thus allowing more precise assessment of tumor proliferation potential.

  8. 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 HAuCl4 and H2O2, 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.

  9. Serum levels of GFAP and EGFR in primary and recurrent high-grade gliomas: correlation to tumor volume, molecular markers, and progression-free survival.

    PubMed

    Kiviniemi, Aida; Gardberg, Maria; Frantzén, Janek; Parkkola, Riitta; Vuorinen, Ville; Pesola, Marko; Minn, Heikki

    2015-09-01

    Our aim was to study the association of two potential serum biomarkers glial fibrillary acidic protein (GFAP) and epidermal growth factor receptor (EGFR) with prognostic markers such as IDH1 mutation, tumor burden, and survival in patients with high-grade gliomas (HGG). Additionally, our objective was to evaluate the potential of serum EGFR as a surrogate marker for EGFR status in the tumor. Pre-operative serum samples were prospectively collected from patients with primary (n = 17) or recurrent (n = 10) HGG. Serum GFAP and EGFR levels were determined by ELISA and studied for correlation with molecular markers including EGFR amplification, tumor volume in contrast-enhanced T1-weighted MRI, and progression-free survival (PFS). Pre-operative serum GFAP level of ≥0.014 ng/ml was 86 % sensitive and 85 % specific for the diagnosis of glioblastoma. High GFAP was related to the lack of IDH1 mutation (P = 0.016), high Ki67 proliferation index (P < 0.001), and poor PFS (HR 5.9, CI 1.2-29.9, P = 0.032). Serum GFAP correlated with enhancing tumor volume in primary (r = 0.64 P = 0.005), but also in recurrent HGGs (r = 0.76 P = 0.011). In contrast, serum EGFR levels did not differ between HGG patients and 13 healthy controls, and were not related to EGFR status in the tumor. We conclude that high serum GFAP associates with IDH1 mutation-negative HGG, and poor PFS. Correlation with tumor burden in recurrent HGG implicates the potential of serum GFAP for detection of tumor recurrence. Our results suggest that circulating EGFR is not derived from glioma cells and cannot be used as a marker for EGFR status in the tumor.

  10. Predictive and prognostic value of preoperative serum tumor markers in resectable adenosqamous lung carcinoma

    PubMed Central

    Yue, Dongsheng; Li, Kai; Jiang, Richeng

    2016-01-01

    Background Adenosquamous carcinoma is a rare and aggressive form of lung cancer. The prognostic and predictive value of preoperative serum tumor markers and frequency of EGFR mutations in adenosquamous lung carcinoma are unclear. Methods We retrospectively analyzed data and samples collected from 106 radically resected adenosquamous lung carcinoma patients with pathological stage I-IIIA between 2008 and 2013. Correlations between serum tumor marker levels and EGFR mutations as well as survival parameters were analyzed and prognostic factors were identified. Results Of the 106 adenosquamous lung carcinoma patients, 29 (27.4%) harbored EGFR mutations. By univariate analysis, advanced clinical stage (P = 0.009 for disease-free survival [DFS]; P = 0.046 for overall survival [OS]), larger tumor size (P = 0.001 for DFS; P = 0.002 for OS), regional lymph node metastasis (P = 0.024 for DFS; P = 0.030 for OS), higher NSE level (P = 0.002 for DFS; P < 0.001 for OS), and higher TMI (tumor marker index) (P = 0.009 for OS) were significantly correlated with a worse prognosis. By multivariate analysis, NSE (P = 0.014) was confirmed as independent predictor for DFS, while NSE (P = 0.001) and TMI (P = 0.038) were independent prognostic factors for OS. Conclusion Adenosquamous lung carcinoma is an aggressive malignancy with relatively high EGFR mutation frequency. Elevated preoperative NSE level and TMI are adverse predictive and prognostic indicators. PMID:27623437

  11. A comparative study of four serological tumor markers for the detection of breast cancer.

    PubMed

    Clinton, Shawn R; Beason, Kevin L; Bryant, Sabrina; Johnson, James T; Jackson, Margaret; Wilson, Cynthia; Holifield, Kay; Vincent, Charlton; Hall, Margot

    2003-01-01

    Breast cancer is currently the third most common cause of cancer in the world. Circulating tumor antigens are often used as a minimally invasive tool for noting breast cancer progression. The objective of this study was to compare four tumor antigens (CA 15-3, CA 27.29, alpha-fetoprotein [AFP], and carcinoembryonic antigen [CEA]) for their diagnostic efficacy in breast cancer patients. It was hypothesized that CA 15-3 would proved to be superior to CA 27.29, CEA, and AFP in assay performance. Tumor marker assays were performed according to the manufacturers' directions. Assays used in this study were CA 15-3 and CA 27.29 (Fujirebio Diagnostics/Centocor Inc.), AFP (Abbott Inc.), and CEA (Hybritech Inc.). A total of 554 patient samples were obtained from an area hospital, plus 200 healthy adult samples which were used for the determination of normal reference intervals. The patients included patients with no disease (184), with non-malignant disease (11), with breast cancer (87), and with other types of cancer (272). Diagnostic percent sensitivities for each marker were: CA 15-3 (63%), CA 27.29 (39%), CEA (22%), and AFP (22%). Diagnostic specificities for each marker were comparable, ranging from 80-88%. Analytical parameters were evaluated for the assays and compared favorably. We concluded that CA 15-3 was the best tumor antigen for use as a diagnostic aid and monitoring agent.

  12. Chondroitin sulfate proteoglycan CSPG4 as a novel hypoxia-sensitive marker in pancreatic tumors.

    PubMed

    Keleg, Shereen; Titov, Alexandr; Heller, Anette; Giese, Thomas; Tjaden, Christine; Ahmad, Sufian S; Gaida, Matthias M; Bauer, Andrea S; Werner, Jens; Giese, Nathalia A

    2014-01-01

    CSPG4 marks pericytes, undifferentiated precursors and tumor cells. We assessed whether the shed ectodomain of CSPG4 (sCSPG4) might circulate and reflect potential changes in CSPG4 tissue expression (pCSPG4) due to desmoplastic and malignant aberrations occurring in pancreatic tumors. Serum sCSPG4 was measured using ELISA in test (n = 83) and validation (n = 221) cohorts comprising donors (n = 11+26) and patients with chronic pancreatitis (n = 11+20) or neoplasms: benign (serous cystadenoma SCA, n = 13+20), premalignant (intraductal dysplastic IPMNs, n = 9+55), and malignant (IPMN-associated invasive carcinomas, n = 4+14; ductal adenocarcinomas, n = 35+86). Pancreatic pCSPG4 expression was evaluated using qRT-PCR (n = 139), western blot analysis and immunohistochemistry. sCSPG4 was found in circulation, but its level was significantly lower in pancreatic patients than in donors. Selective maintenance was observed in advanced IPMNs and PDACs and showed a nodal association while lacking prognostic relevance. Pancreatic pCSPG4 expression was preserved or elevated, whereby neoplastic cells lacked pCSPG4 or tended to overexpress without shedding. Extreme pancreatic overexpression, membranous exposure and tissue(high)/sera(low)-discordance highlighted stroma-poor benign cystic neoplasm. SCA is known to display hypoxic markers and coincide with von-Hippel-Lindau and Peutz-Jeghers syndromes, in which pVHL and LBK1 mutations affect hypoxic signaling pathways. In vitro testing confined pCSPG4 overexpression to normal mesenchymal but not epithelial cells, and a third of tested carcinoma cell lines; however, only the latter showed pCSPG4-responsiveness to chronic hypoxia. siRNA-based knockdowns failed to reduce the malignant potential of either normoxic or hypoxic cells. Thus, overexpression of the newly established conditional hypoxic indicator, CSPG4, is apparently non-pathogenic in pancreatic malignancies but might mark distinct

  13. Chondroitin Sulfate Proteoglycan CSPG4 as a Novel Hypoxia-Sensitive Marker in Pancreatic Tumors

    PubMed Central

    Keleg, Shereen; Titov, Alexandr; Heller, Anette; Giese, Thomas; Tjaden, Christine; Ahmad, Sufian S.; Gaida, Matthias M.; Bauer, Andrea S.; Werner, Jens; Giese, Nathalia A.

    2014-01-01

    CSPG4 marks pericytes, undifferentiated precursors and tumor cells. We assessed whether the shed ectodomain of CSPG4 (sCSPG4) might circulate and reflect potential changes in CSPG4 tissue expression (pCSPG4) due to desmoplastic and malignant aberrations occurring in pancreatic tumors. Serum sCSPG4 was measured using ELISA in test (n = 83) and validation (n = 221) cohorts comprising donors (n = 11+26) and patients with chronic pancreatitis (n = 11+20) or neoplasms: benign (serous cystadenoma SCA, n = 13+20), premalignant (intraductal dysplastic IPMNs, n = 9+55), and malignant (IPMN-associated invasive carcinomas, n = 4+14; ductal adenocarcinomas, n = 35+86). Pancreatic pCSPG4 expression was evaluated using qRT-PCR (n = 139), western blot analysis and immunohistochemistry. sCSPG4 was found in circulation, but its level was significantly lower in pancreatic patients than in donors. Selective maintenance was observed in advanced IPMNs and PDACs and showed a nodal association while lacking prognostic relevance. Pancreatic pCSPG4 expression was preserved or elevated, whereby neoplastic cells lacked pCSPG4 or tended to overexpress without shedding. Extreme pancreatic overexpression, membranous exposure and tissuehigh/seralow-discordance highlighted stroma-poor benign cystic neoplasm. SCA is known to display hypoxic markers and coincide with von-Hippel-Lindau and Peutz-Jeghers syndromes, in which pVHL and LBK1 mutations affect hypoxic signaling pathways. In vitro testing confined pCSPG4 overexpression to normal mesenchymal but not epithelial cells, and a third of tested carcinoma cell lines; however, only the latter showed pCSPG4-responsiveness to chronic hypoxia. siRNA-based knockdowns failed to reduce the malignant potential of either normoxic or hypoxic cells. Thus, overexpression of the newly established conditional hypoxic indicator, CSPG4, is apparently non-pathogenic in pancreatic malignancies but might mark distinct epithelial

  14. Potential role of BCL2 in the recurrence of uterine smooth muscle tumors of uncertain malignant potential.

    PubMed

    Conconi, Donatella; Chiappa, Valentina; Perego, Patrizia; Redaelli, Serena; Bovo, Giorgio; Lavitrano, Marialuisa; Milani, Rodolfo; Dalprà, Leda; Lissoni, Andrea Alberto

    2017-01-01

    Uterine smooth muscle tumors are the most common female genital tract neoplasms. While leiomyosarcoma has been studied at length, smooth muscle tumors of uncertain malignant potential (STUMPs) still have ambiguous and unresolved issues, with a risk of relapse and evolution largely undefined. We performed an array comparative genomic hybridization analysis on a primitive STUMP and its local recurrence, histologically diagnosed as undifferentiated sarcoma. To the best of our knowledge, our report is the first genomic study on primitive STUMPs and the different relapsed tumors. The results showed few copy number alterations shared between both samples and the high heterogeneity in the STUMP was apparently lost in the sarcoma. Surprisingly the STUMP presented an amplification of the BCL2 gene, not observed in the relapsed tumor. Additionally, fluorescence in situ hybridization and immunohistochemical staining were performed to confirm BCL2 amplification and expression in these samples and in two other cases of primitive STUMPs and their corresponding relapsed tumors. The presence of BCL2 in multiple copies and expression in the two primitive STUMPs and two relapsed tumors was confirmed. The marked amplification of the BCL2 gene present in the primitive STUMP and the multiple copies also observed in other cases, suggest its potential role as a marker of STUMP malignant potential and recurrence.

  15. Circulating tumor cells and miRNA as prognostic markers in neuroendocrine neoplasms.

    PubMed

    Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria Al

    2017-04-07

    The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs.

  16. Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer.

    PubMed

    Wang, Haiying; Molina, Julian; Jiang, John; Ferber, Matthew; Pruthi, Sandhya; Jatkoe, Timothy; Derecho, Carlo; Rajpurohit, Yashoda; Zheng, Jian; Wang, Yixin

    2013-11-01

    Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and

  17. Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer

    PubMed Central

    WANG, HAIYING; MOLINA, JULIAN; JIANG, JOHN; FERBER, MATTHEW; PRUTHI, SANDHYA; JATKOE, TIMOTHY; DERECHO, CARLO; RAJPUROHIT, YASHODA; ZHENG, JIAN; WANG, YIXIN

    2013-01-01

    Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and

  18. MAP17 and SGLT1 Protein Expression Levels as Prognostic Markers for Cervical Tumor Patient Survival

    PubMed Central

    Perez, Marco; Praena-Fernandez, Juan M.; Felipe-Abrio, Blanca; Lopez-Garcia, Maria A.; Lucena-Cacace, Antonio; Garcia, Angel; Lleonart, Matilde; Roncador, Guiovanna; Marin, Juan J.; Carnero, Amancio

    2013-01-01

    MAP17 is a membrane-associated protein that is overexpressed in human tumors. Because the expression of MAP17 increases reactive oxygen species (ROS) generation through SGLT1 in cancer cells, in the present work, we investigated whether MAP17 and/or SGLT1 might be markers for the activity of treatments involving oxidative stress, such as cisplatin or radiotherapy. First, we confirmed transcriptional alterations in genes involved in the oxidative stress induced by MAP17 expression in HeLa cervical tumor cells and found that Hela cells expressing MAP17 were more sensitive to therapies that induce ROS than were parental cells. Furthermore, MAP17 increased glucose uptake through SGLT receptors. We then analyzed MAP17 and SGLT1 expression levels in cervical tumors treated with cisplatin plus radiotherapy and correlated the expression levels with patient survival. MAP17 and SGLT1 were expressed in approximately 70% and 50% of cervical tumors of different types, respectively, but they were not expressed in adenoma tumors. Furthermore, there was a significant correlation between MAP17 and SGLT1 expression levels. High levels of either MAP17 or SGLT1 correlated with improved patient survival after treatment. However, the patients with high levels of both MAP17 and SGLT1 survived through the end of this study. Therefore, the combination of high MAP17 and SGLT1 levels is a marker for good prognosis in patients with cervical tumors after cisplatin plus radiotherapy treatment. These results also suggest that the use of MAP17 and SGLT1 markers may identify patients who are likely to exhibit a better response to treatments that boost oxidative stress in other cancer types. PMID:23418532

  19. New Strategies in Personalized Medicine for Solid Tumors: Molecular Markers and Clinical Trial Designs

    PubMed Central

    Jürgensmeier, Juliane M.; Eder, Joseph P.; Herbst, Roy S.

    2017-01-01

    The delineation of signaling pathways to understand tumor biology combined with the rapid development of technologies that allow broad molecular profiling and data analysis, has led to a new era of personalized medicine in oncology. Many academic institutions now routinely profile patients and discuss them in personalized medicine tumor boards before making treatment recommendations. Clinical trials initiated by pharmaceutical companies often require specific markers for enrollment or at least explore multiple options for future markers. In addition to the still small number of targeted agents that are approved for the therapy of patients with histological and molecularly defined tumors, there is a broad range of novel targeted agents in development that are undergoing clinical studies with companion profiling to determine the best responding patient population. While the present focus of profiling are genetic analyses, additional testing of RNA, protein and immune parameters are being developed and incorporated in clinical research and are likely to contribute significantly to future patient selection and treatment approaches. As the advances in tumor biology and human genetics have identified promising tumor targets, the ongoing clinical evaluation of novel agents will now need to show if the promise can be translated into benefit for patients. PMID:25183480

  20. CA19-9: A promising tumor marker for pancreatic carcinoma

    SciTech Connect

    Sakahara, H.; Endo, K.; Nakajima, K.; Hidaka, A.; Nakashima, T.; Ohta, H.; Torizuka, K.; Naito, A.; Suzuki, T.

    1984-01-01

    In order to evaluate CA19-9 as a tumor marker for pancreatic carcinoma (PC), serum levels of CA19-9 were compared with those of CEA and elastase-1 in 56 patients, consisted of 43 cases with histologically proven adenocarcinomas and 13 cases with chronic pancreatitis. Serum levels were determined by using RIA kit obtained from CIS, France (CA19-9 and CEA) and Abbot (elastase-1). CA19-9 gave the highest accuracy among tumor markers the authors have studied and serum levels were markedly elevated over 100U/ml in 30 (70%) cases with PC, whereas none in chronic pancreatitis. CA19-9 values were closely related to the tumor size and the presence or absence of metastsis on CT findings. Small tumors of less than 3cm in diameter, although the site of tumor was limited to the head of the pancreas, showed positive results in 2 out of 5 cases. Furthermore, CA19-9 was at a level of less than 22U/ml in 98 normal controls and was found to be elevated in only 4 (3%) out of 124 patients with benign diseases, including liver diseases, gastric ulcer, cholelithiasis, and so on. These results indicate that CA19-9 is much better in diagnosis and management of PC than is CEA.

  1. Macrophages associated with tumors as potential targets and therapeutic intermediates.

    PubMed

    Vinogradov, Serguei; Warren, Galya; Wei, Xin

    2014-04-01

    Tumor-associated macrophages (TAMs) form approximately 50% of tumor mass. TAMs were shown to promote tumor growth by suppressing immunocompetent cells, inducing neovascularization and supporting cancer stem cells. TAMs retain mobility in tumor mass, which can potentially be employed for better intratumoral biodistribution of nanocarriers and effective tumor growth inhibition. Due to the importance of TAMs, they are increasingly becoming principal targets of novel therapeutic approaches. In this review, we compare features of macrophages and TAMs that are essential for TAM-directed therapies, and illustrate the advantages of nanomedicine that are related to the preferential capture of nanocarriers by Mϕ in the process of drug delivery. We discuss recent efforts in reprogramming or inhibiting tumor-protecting properties of TAMs, and potential strategies to increase efficacy of conventional chemotherapy by combining with macrophage-associated delivery of nanodrugs.

  2. Macrophages associated with tumors as potential targets and therapeutic intermediates

    PubMed Central

    Vinogradov, Serguei; Warren, Galya; Wei, Xin

    2014-01-01

    Tumor-associated macrophages (TAMs) form approximately 50% of tumor mass. TAMs were shown to promote tumor growth by suppressing immunocompetent cells, inducing neovascularization and supporting cancer stem cells. TAMs retain mobility in tumor mass, which can potentially be employed for better intratumoral biodistribution of nanocarriers and effective tumor growth inhibition. Due to the importance of TAMs, they are increasingly becoming principal targets of novel therapeutic approaches. In this review, we compare features of macrophages and TAMs that are essential for TAM-directed therapies, and illustrate the advantages of nanomedicine that are related to the preferential capture of nanocarriers by Mφ in the process of drug delivery. We discuss recent efforts in reprogramming or inhibiting tumor-protecting properties of TAMs, and potential strategies to increase efficacy of conventional chemotherapy by combining with macrophage-associated delivery of nanodrugs. PMID:24827844

  3. Oxidized macrophage migration inhibitory factor is a potential new tissue marker and drug target in cancer

    PubMed Central

    Schinagl, Alexander; Thiele, Michael; Douillard, Patrice; Völkel, Dirk; Kenner, Lukas; Kazemi, Zahra; Freissmuth, Michael; Scheiflinger, Friedrich; Kerschbaumer, Randolf J.

    2016-01-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, which was shown to be upregulated in cancers and to exhibit tumor promoting properties. Unlike other cytokines, MIF is ubiquitously present in the circulation and tissue of healthy subjects. We recently described a previously unrecognized, disease-related isoform of MIF, designated oxMIF, which is present in the circulation of patients with different inflammatory diseases. In this article, we report that oxMIF is also linked to different solid tumors as it is specifically expressed in tumor tissue from patients with colorectal, pancreatic, ovarian and lung cancer. Furthermore, oxMIF can be specifically targeted by a subset of phage display-derived fully human, monoclonal anti-MIF antibodies (mAbs) that were shown to neutralize pro-tumorigenic activities of MIF in vivo. We further demonstrate that anti-oxMIF mAbs sensitize human cancer cell lines (LNCaP, PC3, A2780 and A2780ADR) to the action of cytotoxic drugs (mitoxantrone, cisplatin and doxorubicin) in vitro and in an A2780 xenograft mouse model of ovarian cancer. We conclude that oxMIF is the disease related isoform of MIF in solid tumors and a potential new diagnostic marker and drug target in cancer. PMID:27636991

  4. Distinct expression profile of stem cell markers, LGR5 and LGR6, in basaloid skin tumors.

    PubMed

    Jang, Bo Gun; Lee, Cheol; Kim, Hye Sung; Shin, Myung Soo; Cheon, Min Seok; Kim, Jae Wang; Kim, Woo Ho

    2017-03-01

    Mammalian epidermis, which is composed of hair follicles, sebaceous glands, and interfollicular epidermis, is maintained by discrete stem cells. In vivo lineage tracing demonstrated that murine LGR5 cells are mainly responsible for hair follicle regeneration whereas LGR6 cells generate sebaceous glands and interfollicular epidermis. However, little is known about their expression in the human skin tumors. In this study, we investigated the expression profile of LGR5 and LGR6 in a variety of human skin tumors including basaloid tumors with follicular differentiation (94 basal cell carcinomas, 18 trichoepitheliomas, 3 basaloid follicular hamartomas, and 12 pilomatricomas) and tumors with ductal differentiation (7 eccrine poromas, 8 hidradenomas, and 5 spiradenomas). LGR5 expression was highest in basal cell carcinomas (BCCs) followed by trichoepitheliomas (TEs) and basaloid follicular hamartomas. LGR6 had the same expression pattern as LGR5, even though its expression was lower. Interestingly, LGR6 expression was detected in stromal cells around the tumor and papillary mesenchymal bodies of TEs but not in stromal cells of BCCs, suggesting different characteristics of tumor-associated fibroblasts between TEs and BCCs. It was unexpected to find that pilomatricomas exclusively expressed LGR6, and its expression was limited to the basaloid cells. Notably, LGR6-positive cells were observed in sweat gland ductal cells in normal skin. This might explain, in part, the finding that LGR6 expression was relatively higher in basaloid tumors with ductal differentiation than in those with follicular differentiation. In particular, spiradenomas displayed the same distribution pattern of LGR6 as normal sweat glands, suggesting the possibility of LGR6-positive cells as tumor stem cells. In conclusion, we documented the different expression patterns of stem cell markers, LGR5 and LGR6 in various skin tumors. These data may provide important insights to understand the origin and

  5. Cell-free methylation markers with diagnostic and prognostic potential in hepatocellular carcinoma

    PubMed Central

    Lu, Chang-Yi; Chen, Shih-Ya; Peng, Hui-Ling; Kan, Pu-Yeh; Chang, Wan-Chi; Yen, Chia-Jui

    2017-01-01

    Hepatocellular carcinoma (HCC) is a highly malignant tumor with poor prognosis and high mortality. There is a dearth of effective early diagnostic tools, so liver resection surgery and liver transplantation are the only effective medical treatments. The most commonly used marker for HCC detection is serum alpha fetoprotein (AFP), which has low sensitivity and specificity. Because aberrant DNA methylation of genes and miRNAs occurs early in most cancers, we explored whether circulating methylation markers could be promising clinical tools for HCC diagnosis. Using a whole-genome approach, we identified many hyper-methylated miRNAs in HCC. Furthermore, three abnormally methylated genes and one miRNA were combined to establish a methylation predictive model and tested for its diagnostic and prognostic potential in HCC. Using plasma samples, the predictive model exhibited high sensitivity and specificity (> 80%) for HBV-related HCC. Most importantly, nearly 75% of patients who could not be diagnosed with AFP at 20 ng/mL were detected by this model. Further, the predictive model exhibited an exceedingly high ability to predict 5-year overall survival in HCC patients. These data demonstrate the high diagnostic and prognostic potential of methylation markers in the plasma of HCC patients. PMID:28031532

  6. Potential usefulness of biological markers in risk assessment

    SciTech Connect

    Perera, F.

    1987-12-01

    Substantial data have been generated during the last 5 years in experimental systems and human populations which shed light on the potential usefulness of biological markers in human cancer risk assessment. Following a brief review of overall progress to date in the biomonitoring of human populations, this paper turns to the growing body of data regarding carcinogen-DNA and protein adducts as illustrative markers of biologically effective dose of carcinogens. The data base illustrates considerable human interindividual variation in binding and the presence of significant background levels of adducts-both of which support the absence of human population thresholds for exposure to carcinogens. The contribution of adduct data to our understanding of the shape of low-dose-response curve and the reliability of interspecies extrapolation, as well as the relevance of adducts to cancer risk, are also discussed. Even though adducts can now be useful in hazard identification or qualitative risk assessment,more research is needed before they can serve as quantitative predictors of human cancer risk.

  7. Detection of multiple tumor markers using ultra-long carbon nanotube devices

    NASA Astrophysics Data System (ADS)

    So, Hye-Mi; Park, Dong-Won; Kim, Beom Soo; Kong, Ki-Jeong; Buh, Gyoung-Ho; Chang, Hyunju; Lee, Jeong-O.; Kong, Jing

    2008-03-01

    For the simultaneous detection of multiple tumor markers, we have fabricated ultra-long carbon nanotube sensors that can detect carcinoembryonic antigen (CEA) and prostate specific antigen (PSA), simultaneously. Ultra-long carbon nanotubes, several millimeters long, were grown by ethanol CVD, and fabricated as FET sensors by using conventional photolithography. To functionalize each segment of a single ultra-long nanotube device with multiple-tumor markers, we first functionalize the entire device with CDI-Tween 20 linking molecules, and then immobilized CEA and PSA antibodies using the microfluidic channel. The electrical conductance from CEA-antibody functionalized and PSA-antibody functionalized segment of a ultra-long carbon nanotube device was monitored simultaneously with Ag/AgCl reference electrode as a liquid gate. We will discuss the advantages of long-nanotube device in detail.

  8. Ulex europaeus I lectin as a marker for tumors derived from endothelial cells.

    PubMed

    Miettinen, M; Holthofer, H; Lehto, V P; Miettinen, A; Virtanen, I

    1983-01-01

    Some skin and soft tumors, which generally are assumed to be derived from endothelial cells or blood vessels, were characterized with fluorochrome-labeled Ulex europaeus I agglutinin (UEA I), recently shown to bind specifically to endothelial cells in various normal human tissues. The staining pattern was compared with that obtained with immunostaining using antibodies against factor-VIII-related antigen (FVIII-RAG), a known marker for endothelial cells. The results showed that UEA-I is a specific and a more sensitive marker for the endothelial cells in benign vascular lesions as compared with anti-FVIII-RAG. UEA-I also stained many neoplastic cells of endothelial sarcomas, which generally were negative for FVIII-RAG. Melanomas, anaplastic carcinomas, and other types of sarcomas were negative for both UEA-I and FVIII-RAG. The results suggest that UEA-I lectin is a specific and sensitive adjunct tool in demonstrating endothelial cells and endothelial derivation of human tumors.

  9. Lanthanide-doped luminescent nano-bioprobes for the detection of tumor markers

    NASA Astrophysics Data System (ADS)

    Chen, Zhuo; Zheng, Wei; Huang, Ping; Tu, Datao; Zhou, Shanyong; Huang, Mingdong; Chen, Xueyuan

    2015-02-01

    Sensitive and specific biodetection of tumor markers is essential for early-stage cancer diagnosis and therapy, and will ultimately increase the patient survival rate. As a new generation of luminescent bioprobes, lanthanide (Ln3+)-doped inorganic luminescent nanoparticles have attracted considerable interest for a variety of biomedical applications due to their superior physicochemical properties. In this feature article, we provide a brief overview of the most recent advances in the development of Ln3+-doped luminescent nano-bioprobes and their promising applications for in vitro detection of tumor markers with an emphasis on the establishment of state-of-the-art assay techniques, such as heterogeneous time-resolved (TR) luminescent bioassay, dissolution-enhanced luminescent bioassay, upconversion (UC) luminescent bioassay, homogeneous TR Förster resonance energy transfer (TR-FRET) and UC-FRET bioassays. Some future prospects and efforts towards this emerging field are also envisioned.

  10. Optoelectrofluidic sandwich immunoassays for detection of human tumor marker using surface-enhanced Raman scattering.

    PubMed

    Hwang, Hyundoo; Chon, Hyangah; Choo, Jaebum; Park, Je-Kyun

    2010-09-15

    A sandwich immunoassay is a powerful tool for identifying a specific substance in a biological sample. However, its heterogeneous strategy always requires repetitive liquid handlings and long processing time. Here an optoelectrofluidic immunoassay platform for simple, fast, and automated detection of human tumor marker based on surface-enhanced Raman scattering (SERS) has been developed. By using a conventional optoelectrofluidic device and a liquid crystal display module, simple and quantitative detection of human tumor marker, alpha-fetoprotein, in a ∼500 nL sample droplet has been automatically conducted with lower detection limit of about 0.1 ng/mL within 5 min. This study depicts the first practical application, for protein detection, of the optoelectrofluidic manipulation technology. This image-driven immunoassay platform opens a new way for simple, fast, automated, and highly sensitive detection of antigens.

  11. Ultrasensitive Luminescent In Vitro Detection for Tumor Markers Based on Inorganic Lanthanide Nano‐Bioprobes

    PubMed Central

    Zheng, Wei; Zhou, Shanyong; Xu, Jin; Liu, Yongsheng; Huang, Ping; Liu, Yan

    2016-01-01

    Ultrasensitive and accurate detection of tumor markers is of vital importance for the screening or diagnosis of cancers at their early stages and for monitoring cancer relapse after surgical resection. Inorganic lanthanide (Ln3+) nanoparticles (NPs), owing to their superior physicochemical characteristics, are regarded as a new generation of luminescent nano‐bioprobes in the field of cancer diagnosis and therapy. In this progress report, a focus is set on our recent efforts on the development of inorganic Ln3+‐NPs as efficient luminescent nano‐bioprobes for the ultrasensitive in vitro biodetection of tumor markers, with an emphasis on the dissolution‐enhanced luminescent bioassay (DELBA), an emerging technique recently developed toward practical medical applications. PMID:27980996

  12. Tumor Markers

    SciTech Connect

    Weller, Richard E.

    2000-04-18

    Veterinary oncology has seen tremendous growth since the first textbook devoted to the subject in the late 1970s. Cancer is usually at the top of the list when owners ask about health concerns for their pets (and it remains the leading cause of death among dogs and cats). The volume, Veterinary Oncology Secrets, joins others in the series by presenting in question and answer format the type of information so important to veterinary students, interns and residents, general practitioners, and specialists in a number of clinical fields.

  13. Dynamic studies of positron-emitting putative tumor marker /sup 132/Cs in mice show differential tumor and regional uptake

    SciTech Connect

    McKee, J.S.; Durocher, J.J.; Bose, R.; Gusdal, M.I.; Sharma, G.P.; Pinsky, C.; Gallop, D.

    1985-01-01

    Positron-emitting /sup 132/Cs (t1/2 = 6.47 days) was generated from stable /sup 133/CsCl via the /sup 133/Cs (p,pn) /sup 132/Cs reaction. BALB/c mice, bearing implanted MT296 mammary tumors, were given 4.6 mEq kg-1 of /sup 132/CsCl via a single intraperitoneal injection. Postinjection uptake of /sup 132/Cs into body regions was monitored in vivo with external detectors. Positron emission from the tumor region was continuously greater than that from the head, the numerical ratio of mean emission intensities being fourfold at 10 min postinjection. Tissues excised from these mice postmortem showed sequence of relative tissue cesium uptake rates to be kidney 1.8, small intestine 1.7, tumor 1.0, skin 0.75, liver 0.75, skeletal muscle 0.4, and brain 0.28. Comparative studies with multiple injections of stable cesium and rubidium showed this sequence to be ion-specific. These observations suggest that positron-emitting isotopes of cesium could provide useful markers for tumors of several tissues.

  14. Potential markers of the nutritional status in an experimental model.

    PubMed

    Feliu, M S; Slobodianik, N H

    2000-01-01

    The activity of adenine deaminase (ADA) and purine nucleoside phosphorylase (PNP) as potential nutritional markers was analyzed in an experimental model. Weanling Wistar rats were fed a protein-free diet ad libitum to obtain a severe degree of wasting. An age-matched control group received a stock diet. At the end of the experiment, body weight (BW) and thymus weight (TW) were determined. Activity of ADA and PNP was determined on thymocytes of protein-deprived and control rats; the results, expressed as micromoles of uric acid x 10(-1)/W (W = TW/BW(0.75)), were 17.0 +/- 2.6 versus 9.1 +/- 3.0 for ADA and 11.5 +/- 4.2 versus 3.9 +/- 1.0 for PNP (P < 0.01). These results suggest that the nutritional stress provoked by the administration of a protein-free diet from weaning onward affects the development of thymocytes. Moreover, the increase in the activity of ADA and PNP would be an alternative mechanism to avoid the accumulation of high levels of deoxynucleotides, which would be toxic for T lymphocytes. However, some investigators have observed an increase of ADA activity in human serum under some adverse conditions; for this reason and taking into account the present findings, it would be interesting to determine the relation between the activity of ADA and PNP in thymocytes and serum in experimental models to analyze and propose these biochemical parameters as potential and useful markers of nutritional status; it also would be interesting to test this relation in human studies.

  15. Immunohistochemistry as potential diagnostic pitfall in the most common solid tumors of children and adolescents.

    PubMed

    Magro, Gaetano; Longo, Francesca Romana; Angelico, Giuseppe; Spadola, Saveria; Amore, Flavia Francesca; Salvatorelli, Lucia

    2015-01-01

    Making a correct diagnosis when dealing with a small round blue cell tumor (SRBCT) of children and adolescents may be relatively straightforward if the tumor arises in the typical clinical setting and the classic pathologic features are all recognizable. However it is widely known that diagnostic difficulties may arise because of: (i) many tumors share overlapping morphological and/or immunohistochemical features; (ii) considerable clinical, pathologic, and immunohistochemical variations do exist; (iii) the increasing use of small biopsies in daily practice makes the diagnosis of these neoplasms more challenging. Accordingly, immunohistochemical analyses are currently mandatory in establishing the correct diagnosis. In this regard there is the need to identify more sensitive and specific immunomarkers useful in the distinction of the several tumor entities. Over the last decades, several markers, such as CD99, WT1 protein, desmin, myogenin, NB84, and INI1 have been identified, providing a considerable help in recognition of the most common solid tumors (ESW/pPNET, rhabdomyosarcoma, neuroblastoma, Wilms' tumor, desmoplastic small round cell tumor; malignant rhabdoid tumor) in children and adolescents. However, at the same time, their unusual, unexpected expression can result in a misinterpretation of the immunohistochemical results, especially by pathologists who are not familiar with oncologic pediatric pathology. Therefore the present review focuses on the potential immunohistochemical pitfalls which should be kept in mind by pathologists to prevent diagnostic errors when dealing with SRBCTs.

  16. Peptide Agonists of Vasopressin V2 Receptor Reduce Expression of Neuroendocrine Markers and Tumor Growth in Human Lung and Prostate Tumor Cells

    PubMed Central

    Pifano, Marina; Garona, Juan; Capobianco, Carla S.; Gonzalez, Nazareno; Alonso, Daniel F.; Ripoll, Giselle V.

    2017-01-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that express neuropeptides as synaptophysin, chromogranin A (CgA), and specific neuronal enolase (NSE), among others. Vasopressin (AVP) is a neuropeptide with an endocrine, paracrine, and autocrine effect in normal and pathological tissues. AVP receptors are present in human lung, breast, pancreatic, colorectal, and gastrointestinal tumors. While AVP V1 receptors are associated with stimulation of cellular proliferation, AVP V2 receptor (V2r) is related to antiproliferative effects. Desmopressin (dDAVP) is a synthetic analog of AVP that acts as a selective agonist for the V2r, which shows antitumor properties in breast and colorectal cancer models. Recently, we developed a derivative of dDAVP named [V4Q5]dDAVP, which presents higher antitumor effects in a breast cancer model compared to the parental compound. The goal of present work was to explore the antitumor properties of the V2r agonist dDAVP and its novel analog [V4Q5]dDAVP on aggressive human lung (NCI-H82) and prostate cancer (PC-3) cell lines with neuroendocrine (NE) characteristics. We study the presence of specific NE markers (CgA and NSE) and V2r expression in NCI-H82 and PC-3. Both cell lines express high levels of NE markers NSE and CgA but then incubation with dDAVP diminished expression levels of both markers. DDAVP and [V4Q5]dDAVP significantly reduced proliferation, doubling time, and migration in both tumor cell cultures. [V4Q5]dDAVP analog showed a higher cytostatic effect than dDAVP, on cellular proliferation in the NCI-H82 cell line. Silencing of V2r using small interfering RNA significantly attenuated the inhibitory effects of [V4Q5]dDAVP on NCI-H82 cell proliferation. We, preliminarily, explored the in vivo effect of dDAVP and [V4Q5]dDAVP on NCI-H82 small cell lung cancer xenografts. Treated tumors (0.3 μg kg−1, thrice a week) grew slower in comparison to vehicle-treated animals. In this work, we demonstrated

  17. Induction of short-term markers of tumor promotion by organic peroxides.

    PubMed

    Gimenez-Conti, I; Viaje, A; Chesner, J; Conti, C; Slaga, T J

    1991-04-01

    Experiments from different laboratories have shown that benzoyl peroxide (BzPo) and other organic peroxides are effective tumor promoters in the mouse skin two-stage carcinogenesis system. In the present paper we have studied the short-term effect of six other organic peroxides, which have not been previously assayed as skin tumor promoters. These compounds were chosen for their molecular diversity, the type of radical predicted to be formed, solubility and availability. The parameters evaluated in this study include a series of short-term markers of tumor promotion, hyperplasia, induction of dark basal keratinocytes and induction of ornithine decarboxylase activity. After single applications the biological activity of the compounds was: m-chloroperoxybenzoic acid greater than di-m-methylbenzoyl peroxide greater than dicumyl peroxide greater than O,O-t-butyl-O-(2-ethylhexyl)mono-peroxycarbonate greater than benzoyl peroxide greater than di-m-chlorobenzoyl peroxide greater than di-t-butyl peroxide greater than t-butyl hydroperoxide. After multiple applications, the order of activity of the compounds was: dicumyl peroxide greater than di-m-methyl-benzoyl peroxide greater than O,O-t-butyl-O-(2-ethylhexyl)monoperoxy carbonate greater than m-chloroperoxybenzoic acid greater than di-m-chlorobenzoyl peroxide greater than t-butyl hydroperoxide greater than benzoyl peroxide greater than di-t-butyl peroxide. The difference of activity among the different compounds did not seem to correlate directly with the chemical stability of the compound; it is more likely that the activity depends on different factors such as percutaneous absorption, metabolism, and the rate of free radical formation in vivo. The data presented here further support the association between free radicals and tumor promotion since all of the compounds, with the exception of one, were active in inducing the short-term markers of tumor promotion. It will also establish conditions for future tumor experiments.

  18. Exploring the intrinsic differences among breast tumor subtypes defined using immunohistochemistry markers based on the decision tree

    PubMed Central

    Li, Yang; Tang, Xu-Qing; Bai, Zhonghu; Dai, Xiaofeng

    2016-01-01

    Exploring the intrinsic differences among breast cancer subtypes is of crucial importance for precise diagnosis and therapeutic decision-making in diseases of high heterogeneity. The subtypes defined with several layers of information are related but not consistent, especially using immunohistochemistry markers and gene expression profiling. Here, we explored the intrinsic differences among the subtypes defined by the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 based on the decision tree. We identified 30 mRNAs and 7 miRNAs differentially expressed along the tree’s branches. The final signature panel contained 30 mRNAs, whose performance was validated using two public datasets based on 3 well-known classifiers. The network and pathway analysis were explored for feature genes, from which key molecules including FOXQ1 and SFRP1 were revealed to be densely connected with other molecules and participate in the validated metabolic pathways. Our study uncovered the differences among the four IHC-defined breast tumor subtypes at the mRNA and miRNA levels, presented a novel signature for breast tumor subtyping, and identified several key molecules potentially driving the heterogeneity of such tumors. The results help us further understand breast tumor heterogeneity, which could be availed in clinics. PMID:27786176

  19. A comparison of cancer stem cell markers and nonclassical major histocompatibility complex antigens in colorectal tumor and noncancerous tissues.

    PubMed

    Özgül Özdemir, Rabia Bilge; Özdemir, Alper Tunga; Oltulu, Fatih; Kurt, Kamile; Yiğittürk, Gürkan; Kırmaz, Cengiz

    2016-12-01

    Colorectal carcinoma (CRC) is one of the most fatal types of cancer in both women and men, and, unfortunately, patients are often diagnosed at an advanced stage. Cancer stem cells (CSCs) are associated with poor prognosis, metastasis, and recurrence, as well as chemotherapy and radiotherapy resistance. Therefore, different treatment alternatives are needed to facilitate the elimination of CSCs. One such approach is immunotherapy; however, tumor cells can evade immune cells by alteration of the expression patterns of human leukocyte antigens (HLA). In this study, we immunohistochemically investigated the expression patterns of CSC-specific markers CD44, CD133, Nanog, and Oct3/4, and immunosuppressive molecules HLA-G and -E in advanced CRC tumor tissues and noncancerous colon biopsies. We found significantly increased CD44, Nanog, Oct3/4, HLA-G, and HLA-E expression in the CRC tumor tissues compared with the noncancerous colon biopsies. These findings suggest that some tumor cells may be CSC-like and that the increased expression of HLA-G and HLA-E may be considered as an immune-evasive adaptation. Therefore, the nonclassical major histocompatibility complex class Ib antigens HLA-G and HLA-E may be potential targets in the elimination of CRC-CSCs. However, more detailed studies are required to support our findings.

  20. Down-regulation of tumor endothelial marker 8 suppresses cell proliferation mediated by ERK1/2 activity

    PubMed Central

    Cao, Chuangjie; Wang, Zhuo; Huang, Leilei; Bai, Lihong; Wang, Yuefeng; Liang, Yingjie; Dou, Chengyun; Wang, Liantang

    2016-01-01

    Tumor endothelial marker 8 (TEM8) was recently suggested as a putative anti-tumor target in several types of human cancer based on its selective overexpression in tumor versus normal endothelial cells. The objective of this study was to detect the potential functions of TEM8 in osteosarcoma. Overall, TEM8 was mainly located in cytoplasm and was up-regulated in osteosarcoma compared to benign bone lesions and adjacent non tumor tissue (ANT). High TEM8 expression group had a significant lower overall survival rate than that in the low TEM8 expression group. TEM8 knock-down by siRNA or shRNA results in significant reduction of osteosarcoma cell growth and proliferation both in vitro and in vivo. Ablation of TEM8 led to increasing of p21 and p27 and suppression of cyclin D1 mediated by Erk1/2 activity. These findings suggest that down-regulation of TEM8 play an important role in the inhibition of tumorigenesis and development of osteosarcoma. PMID:26996335

  1. Effect of HPV on tumor expression levels of the most commonly used markers in HNSCC.

    PubMed

    Polanska, Hana; Heger, Zbynek; Gumulec, Jaromir; Raudenska, Martina; Svobodova, Marketa; Balvan, Jan; Fojtu, Michaela; Binkova, Hana; Horakova, Zuzana; Kostrica, Rom; Adam, Vojtech; Kizek, Rene; Masarik, Michal

    2016-06-01

    Approximately 90 % of head and neck cancers are squamous cell carcinomas (HNSCC), and the overall 5-year survival rate is not higher than 50 %. There is much evidence that human papillomavirus (HPV) infection may influence the expression of commonly studied HNSCC markers. Our study was focused on the possible HPV-specificity of molecular markers that could be key players in important steps of cancerogenesis (MKI67, EGF, EGFR, BCL-2, BAX, FOS, JUN, TP53, MT1A, MT2A, VEGFA, FLT1, MMP2, MMP9, and POU5F). qRT-PCR analysis of these selected genes was performed on 74 biopsy samples of tumors from patients with histologically verified HNSCC (22 HPV-, 52 HPV+). Kaplan-Meier analysis was done to determine the relevance of these selected markers for HNSCC prognosis. In conclusion, our study confirms the impact of HPV infection on commonly studied HNSCC markers MT2A, MMP9, FLT1, VEGFA, and POU5F that were more highly expressed in HPV-negative HNSCC patients and also shows the relevance of studied markers in HPV-positive and HPV-negative HNSCC patients.

  2. Network analysis reveals potential markers for pediatric adrenocortical carcinoma

    PubMed Central

    Kulshrestha, Anurag; Suman, Shikha; Ranjan, Rakesh

    2016-01-01

    Pediatric adrenocortical carcinoma (ACC) is a rare malignancy with a poor outcome. Molecular mechanisms of pediatric ACC oncogenesis and advancement are not well understood. Accurate and timely diagnosis of the disease requires identification of new markers for pediatric ACC. Differentially expressed genes (DEGs) were identified from the gene expression profile of pediatric ACC and obtained from Gene Expression Omnibus. Gene Ontology functional and pathway enrichment analysis was implemented to recognize the functions of DEGs. A protein–protein interaction (PPI) and gene–gene functional interaction (GGI) network of DEGs was constructed. Hub gene detection and enrichment analysis of functional modules were performed. Furthermore, a gene regulatory network incorporating DEGs–microRNAs–transcription factors was constructed and analyzed. A total of 431 DEGs including 228 upregulated and 203 downregulated DEGs were screened. These genes were largely involved in cell cycle, steroid biosynthesis, and p53 signaling pathways. Upregulated genes, CDK1, CCNB1, CDC20, and BUB1B, were identified as the common hubs of PPI and GGI networks. All the four common hub genes were also part of modules of the PPI network. Moreover, all the four genes were also present in the largest module of GGI network. A gene regulatory network consisting of 82 microRNAs and 100 transcription factors was also constructed. CDK1, CCNB1, CDC20, and BUB1B may serve as potential biomarker of pediatric ACC and as potential targets for therapeutic approach, although experimental studies are required to authenticate our findings. PMID:27555782

  3. Electroretinography and Visual Evoked Potentials in Childhood Brain Tumor Survivors.

    PubMed

    Pietilä, Sari; Lenko, Hanna L; Oja, Sakari; Koivisto, Anna-Maija; Pietilä, Timo; Mäkipernaa, Anne

    2016-07-01

    This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment.

  4. ERG is a novel and reliable marker for endothelial cells in central nervous system tumors.

    PubMed

    Haber, Matthew A; Iranmahboob, Amir; Thomas, Cheddhi; Liu, Mengling; Najjar, Amanda; Zagzag, David

    2015-01-01

    ETS-related gene (ERG) is a transcription factor that has been linked to angiogenesis. Very little research has been done to assess ERG expression in central nervous system (CNS) tumors. We evaluated 57 CNS tumors, including glioblastomas (GBMs) and hemangioblastomas (HBs), as well as two arteriovenous malformations and four samples of normal brain tissue with immunohistochemistry using a specific ERG rabbit monoclonal antibody. In addition, immunostains for CD31, CD34, and α-smooth muscle actin (α-SMA) were performed on all samples. CD31 demonstrated variable and sometimes weak immunoreactivity for endothelial cells. Furthermore, in 1 case of a GBM, CD34 stained not only endothelial cells, but also tumor cells. In contrast, we observed that ERG was only expressed in the nuclei of endothelial cells, for example, in the hyperplastic vascular complexes that comprise the glomeruloid microvascular proliferation seen in GBMs. Conversely, α-SMA immunoreactivity was identified in the abluminal cells of these hyperplastic vessels. Quantitative evaluation with automated methodology and custom Matlab 2008b software was used to calculate percent staining of ERG in each case. We observed significantly higher quantitative expression of ERG in HBs than in other CNS tumors. Our results show that ERG is a novel, reliable, and specific marker for endothelial cells within CNS tumors that can be used to better study the process of neovascularization.

  5. GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker

    PubMed Central

    Carvalho, Kátia C; Cunha, Isabela W; Rocha, Rafael M; Ayala, Fernanda R; Cajaíba, Mariana M; Begnami, Maria D; Vilela, Rafael S; Paiva, Geise R; Andrade, Rodrigo G; Soares, Fernando A

    2011-01-01

    OBJECTIVE: To analyze glucose transporter 1 expression patterns in malignant tumors of various cell types and evaluate their diagnostic value by immunohistochemistry. INTRODUCTION: Glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans. Glucose transporter 1 is aberrantly expressed in several tumor types. Studies have implicated glucose transporter 1 expression as a prognostic and diagnostic marker in tumors, primarily in conjunction with positron emission tomography scan data. METHODS: Immunohistochemistry for glucose transporter 1 was performed in tissue microarray slides, comprising 1955 samples of malignant neoplasm from different cell types. RESULTS: Sarcomas, lymphomas, melanomas and hepatoblastomas did not express glucose transporter 1. Forty-seven per cent of prostate adenocarcinomas were positive, as were 29% of thyroid, 10% of gastric and 5% of breast adenocarcinomas. Thirty-six per cent of squamous cell carcinomas of the head and neck were positive, as were 42% of uterine cervix squamous cell carcinomas. Glioblastomas and retinoblastomas showed membranous glucose transporter 1 staining in 18.6% and 9.4% of all cases, respectively. Squamous cell carcinomas displayed membranous expression, whereas adenocarcinomas showed cytoplasmic glucose transporter 1 expression. CONCLUSION: Glucose transporter 1 showed variable expression in various tumor types. Its absence in sarcomas, melanomas, hepatoblastomas and lymphomas suggests that other glucose transporters mediate the glycolytic pathway in these tumors. The data suggest that glucose transporter 1 is a valuable immunohistochemical marker that can be used to identify patients for evaluation by positron emission tomography scan. The function of cytoplasmic glucose transporter 1 in adenocarcinomas must be further examined. PMID:21808860

  6. Evaluation of lipid-bound sialic acid (LSA) as a tumor marker.

    PubMed

    López Sáez, J J; Senra-Varela, A

    1995-01-01

    The objective of this study is the evaluation of serum levels of lipid-bound sialic acid (LSA) as a of marker cancer. This is a case-control study, and the levels of LSA were determined with blinded duplicates of cases and controls. Histologic verification of all cancer cases was used to confirm the diagnosis. The study included 135 patients with cancer (breast carcinoma, head and neck squamous cell carcinoma, lung cancer and gastrointestinal cancer) and 95 controls (57 normal subjects and 38 with chronic non-malignant diseases). Marker determination was done by the spectrophotometric procedure of Katopodis with resorcinol. The mean LSA level in the 57 healthy individuals was 15.09 mg/dl(95% C.I., 13.51-16.67), in the entire control group of 95 non-tumoral individuals it was 19.21 mg/dl (17.18-21.24), and in the 135 cancer patients it was 26.64 mg/dl (24.42-28.87). There was a statistically significant difference between patients with chronic non-tumoral diseases and healthy individuals (p < 0.001) and also between cancer patients and healthy individuals (p > 0.001), but not between cancer patients and patients with chronic non-tumoral diseases (p> 0.05). The mean LSA serum values related to tumor site were (mg/dl): breast cancer, 21.49; gastrointestinal tumors, 28.45; head and neck cancer, 28.61 and lung cancer, 32.54. The means according to clinical stage were: complete remission, 18.50 significantly higher than the healthy controls (p< 0.05); local disease, 23.50 (p < 0.01); locoregional disease, (p < 0.05); local disease, 23.50 (p < 0.01); locoregional disease, 27.21 (p < 0.001); metastatic disease, 34.49 (p < 0.001), and relapses, 20.87 (p< 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  7. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

    SciTech Connect

    Mashima, Hirosato; Ohno, Hideki; Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide

    2013-03-22

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.

  8. Molecular markers: a potential resource for ginger genetic diversity studies.

    PubMed

    Ismail, Nor Asiah; Rafii, M Y; Mahmud, T M M; Hanafi, M M; Miah, Gous

    2016-12-01

    Ginger is an economically important and valuable plant around the world. Ginger is used as a food, spice, condiment, medicine and ornament. There is available information on biochemical aspects of ginger, but few studies have been reported on its molecular aspects. The main objective of this review is to accumulate the available molecular marker information and its application in diverse ginger studies. This review article was prepared by combing material from published articles and our own research. Molecular markers allow the identification and characterization of plant genotypes through direct access to hereditary material. In crop species, molecular markers are applied in different aspects and are useful in breeding programs. In ginger, molecular markers are commonly used to identify genetic variation and classify the relatedness among varieties, accessions, and species. Consequently, it provides important input in determining resourceful management strategies for ginger improvement programs. Alternatively, a molecular marker could function as a harmonizing tool for documenting species. This review highlights the application of molecular markers (isozyme, RAPD, AFLP, SSR, ISSR and others such as RFLP, SCAR, NBS and SNP) in genetic diversity studies of ginger species. Some insights on the advantages of the markers are discussed. The detection of genetic variation among promising cultivars of ginger has significance for ginger improvement programs. This update of recent literature will help researchers and students select the appropriate molecular markers for ginger-related research.

  9. Oxidative Stress in COPD: Sources, Markers, and Potential Mechanisms

    PubMed Central

    McGuinness, Adam John Anthony; Sapey, Elizabeth

    2017-01-01

    Markers of oxidative stress are increased in chronic obstructive pulmonary disease (COPD) and reactive oxygen species (ROS) are able to alter biological molecules, signaling pathways and antioxidant molecule function, many of which have been implicated in the pathogenesis of COPD. However, the involvement of ROS in the development and progression of COPD is not proven. Here, we discuss the sources of ROS, and the defences that have evolved to protect against their harmful effects. We address the role that ROS may have in the development and progression of COPD, as well as current therapeutic attempts at limiting the damage they cause. Evidence has indicated that the function of several key cells appears altered in COPD patients, and expression levels of important oxidant and antioxidant molecules may be abnormal. Therapeutic trials attempting to restore equilibrium to these molecules have not impacted upon all facets of disease and whilst the theory behind ROS influence in COPD appears sound, current models testing relevant pathways to tissue damage are limited. The heterogeneity seen in COPD patients presents a challenge to our understanding, and further research is essential to identify potential targets and stratified COPD patient populations where ROS therapies may be maximally efficacious. PMID:28212273

  10. Oral keratinocyte stem/progenitor cells: specific markers, molecular signaling pathways and potential uses.

    PubMed

    Calenic, Bogdan; Greabu, Maria; Caruntu, Constantin; Tanase, Cristiana; Battino, Maurizio

    2015-10-01

    Oral keratinocyte stem cells reside in the basal layers of the oral epithelium, representing a minor population of cells with a great potential to self-renew and proliferate over the course of their lifetime. As a result of the potential uses of oral keratinocyte stem cells in regenerative medicine and the key roles they play in tissue homeostasis, inflammatory conditions, wound healing and tumor initiation and progression, intense scientific efforts are currently being undertaken to identify, separate and reprogram these cells. Although currently there is no specific marker that can characterize and isolate oral keratinocyte stem cells, several suggestions have been made. Thus, different stem/progenitor-cell subpopulations have been categorized based on combinations of positive and/or negative membrane-surface markers, which include integrins, clusters of differentiation and cytokeratins. Important advances have also been made in understanding the molecular pathways that govern processes such as self-renewal, differentiation, proliferation, wound healing and programmed cell death. A thorough understanding of stem-cell biology and the molecular players that govern cellular fate is paramount in the quest for using stem-cell-derived therapies in the treatment of various oral pathologies. The current review focuses on recent advances in understanding the molecular signaling pathways coordinating the behavior of these cells and in identifying suitable markers used for their isolation and characterization. Special emphasis will also be placed on the roles played by oral keratinocyte stem and progenitor cells in normal and diseased oral tissues and on their potential uses in the fields of general medicine and dentistry.

  11. Development and Evaluation of a Tumor Marker for Prostate Cancer — EDRN Public Portal

    Cancer.gov

    Major strides in the early detection, staging, monitoring, and risk stratification of men with prostate cancer have been realized over the last few decades. We have recently witnessed a reduction in the death rate for prostate cancer, stage migration with increased numbers of men with local/regional disease, and a greater understanding of the natural history of progression following recurrence. These advances, while not solely dependant on biomarkers, can be attributed to the discovery of Prostate Specific Antigen (PSA) in the late 1970's. In the wake of these discoveries, we still continue to unnecessarily biopsy men at risk for having prostate cancer to identify the 1:4 with the disease, understage men with presumed local disease, continue to lack an accurate method for staging which can direct treatment options for the individual patient and continue to poorly understand the tumor biology and kinetics of disease progression. Clearly, discovery of a new tumor marker and validation/clinical investigation of the markers are mandatory to advance our knowledge and direct the care of men with prostate cancer. With this research, we intend to evaluate the clinical, diagnostic, and prognostic accuracy of new and existing biomarkers on a prospective serum bank collected from men either participating in early detection programs or engaging in pre or post treatment situations. By increasing our clinical research and specimen collections we hope to further advance the staging and direction for treatment in men with prostate cancer. This study approaches patients scheduled for a prostate biopsy, patients visiting the Urology Outpatient Clinic with PSA elevation, patients scheduled for radical prostatectomy, prostate cancer patients with scheduled appointments in Radiation Oncology and men participating in early prostate cancer detection screenings. Subjects will be excluded from the study if: 1) Subjects have any mental impairment that would hinder the ability to provide

  12. Analytical and clinical evaluation of a new tumor marker in breast cancer: CA 27.29.

    PubMed

    Correale, M; Abbate, I; Gargano, G; Catino, A; Dragone, C D; Musci, M D; Serio, G; Paradiso, A; De Lena, M

    1992-01-01

    Evaluation of a radioimmunoassay for a new tumor marker, named CA 27.29, recently proposed for use in breast cancer patients, is reported in this study. After considering the analytical performance, the clinical study was directed to a control group of 66 apparently healthy subjects (Controls), a group of 25 women with benign breast disease (BBD) and a group of 164 breast cancer patients divided into primary before any treatment (M-), in follow-up with no evidence of disease (NED) and presence of metastases (M+). When compared to CA 15.3, our results showed similar sensitivity of both markers with a slightly lower specificity for CA 27.29. In some cases, however, CA 27.29 elevation appears earlier than CA 15.3 as a sign of metastases. We thus propose their associated use.

  13. SC-27CD13 REPRESENTS A NOVEL BRAIN TUMOR STEM CELL MARKER FOR GLIOBLASTOMA

    PubMed Central

    Reeve, Nathaniel; Markert, Tara; Oliva, Claudia; Griguer, Corinne

    2014-01-01

    Glioblastoma multiforme (GBM) is a very deadly and highly vascularized tumor, but targeting glioma angiogenesis by vascular endothelial growth factor inhibition has been minimally successful. Thus, understanding the molecular mechanisms that control glioma angiogenesis and progression could lead to significant new therapies. We previously described that mitochondrial DNA (mtDNA) depletion induces increased tumor angiogenesis, decreased mouse survival, increased resistance to chemotherapy, and an increase in CD133 (a well-known stem cell marker). Because glioma enriched with brain tumor stem cells (BTSCs) share similar properties with mtDNA depleted glioma cells, we hypothesize that genes up-regulated in mitochondrial depleted cells could be signature markers of BTSCs. Thus, mtDNA could be essential for the maintenance and expansion of BTSC populations. We ran an RT Profiler PCR array for angiogenesis on both U251 ρ° cells depleted of mtDNA and on the parental, isogenic U251 glioma cells. CD13 mRNA expression was increased 200 fold in ρ° cells over U251 cells. Using fluorescence-activated cell sorting and immunocytochemisty we found that CD13 is significantly increased in ρ° cells over U251 cells, and is not regulated by hypoxia (1% O2). Purification of the CD13+ population by magnetic-activated cell sorting revealed that these cells form neurospheres when cultured in Neurobasal (NB) medium. In addition, 60% of CD13+ cells were also CD133+ in NB medium, while only 10% of CD13+ cells were also CD133+ in DMEM/F-12 medium. These findings suggest CD13 may be a marker of cancer stem cells in GBM. Further elucidation of the molecular mechanisms controlling the expression of CD13 may reveal novel therapuetic targets capable of improving the treatment of GBM.

  14. Physiologic variations of serum tumor markers in gynecological malignancies during pregnancy: a systematic review

    PubMed Central

    2012-01-01

    Background Recent insights provide support for the treatment of cancer during pregnancy, a coincidence that poses both mother and fetus at risk. Our aim was to critically review studies on the physiologic variations during pregnancy, the most common tumor markers used in diagnosis and follow-up of gynecological cancers. Methods We conducted a systematic review of six tumor markers during normal pregnancy: carbohydrate antigen (CA) 15-3 (breast cancer); squamous cell carcinoma antigen (cervical cancer); and CA 125, anti-Müllerian hormone, inhibin B and lactate dehydrogenase (ovarian cancer). Results For CA 15-3, 3.3% to 20.0% of all measurements were above the cut-off (maximum 56 U/mL in the third trimester). Squamous cell carcinoma antigen values were above cut-off in 3.1% and 10.5% of the measurements (maximum 4.3 µg/L in the third trimester). Up to 35% of CA 125 levels were above cut-off: levels were highest in the first trimester, with a maximum value up to 550 U/mL. Inhibin B, anti-Müllerian hormone and lactate dehydrogenase levels were not elevated in maternal serum during normal pregnancy. Conclusion During normal pregnancy, tumor markers including CA 15.3, squamous cell carcinoma antigen and CA 125 can be elevated; inhibin B, anti-Müllerian hormone and lactate dehydrogenase levels remain below normal cut-off values. Knowledge of physiological variations during pregnancy can be clinically important when managing gynecological cancers in pregnant patients. PMID:22873292

  15. Inflammatory markers and risk of epithelial ovarian cancer by tumor subtypes: the EPIC cohort

    PubMed Central

    Ose, Jennifer; Schock, Helena; Tjonneland, Anne; Hansen, Louise; Overvad, Kim; Dossus, Laure; Clavel-Chapelon, Francoise; Baglietto, Laura; Boeing, Heiner; Trichopolou, Antonia; Benetou, Vassiliki; Lagiou, Pagona; Masala, Giovanna; Tagliabue, Giovanna; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; de Mesquita, H.Bas Bueno; Peeters, Petra H M; Onland-Moret, N Charlotte; Weiderpass, Elisabete; Gram, Inger T; Sánchez, Soledad; Obon-Santacana, Mireia; Sànchez-Pérez, Maria-José; Larrañaga, Nerea; Castaño, José María Huerta; Ardanaz, Eva; Brändstedt, Jenny; Lundin, Eva; Idahl, Annika; Travis, Ruth C; Khaw, Kay-Tee; Rinaldi, Sabina; Romieu, Isabelle; Merrit, Melissa A; Gunter, Marc J; Riboli, Elio; Kaaks, Rudolf; Fortner, Renée T

    2015-01-01

    Background Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. Methods We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), interleukin-6 (IL-6), and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n=1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. Results CRP and IL-6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 vs. CRP ≤1 mg/L was associated with higher overall EOC risk (OR=1.67 [1.03 - 2.70]). We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference: (e.g., IL-6: waist ≤80: ORlog2=0.97 [0.81 - 1.16]; waist >88: ORlog2=1.78 [1.28 - 2.48], pheterogeneity ≤0.01). Conclusions Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL-6 and CRP may be associated with EOC risk among women with higher adiposity. Impact Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu. PMID:25855626

  16. Role of miR-139 as a surrogate marker for tumor aggression in breast cancer.

    PubMed

    Dai, Hongyan; Gallagher, Dan; Schmitt, Sarah; Pessetto, Ziyan Y; Fan, Fang; Godwin, Andrew K; Tawfik, Ossama

    2017-03-01

    MicroRNAs are non-protein coding molecules that play a key role in oncogenesis, tumor progression, and metastasis in many types of malignancies including breast cancer. In the current study, we studied the expression of microRNA-139-5p (miR-139) in invasive ductal carcinoma (IDC) of the breast and correlated its expression with tumor grade, molecular subtype, hormonal status, human epidermal growth factor receptor 2 status, proliferation index, tumor size, lymph node status, patient's age, and overall survival in 74 IDC cases. In addition, we compared and correlated miR-139 expression in 18 paired serum and tissue samples from patients with IDC to assess its value as a serum marker. Our data showed that miR-139 was down-regulated in all tumor tissue samples compared with control. More pronounced down-regulation was seen in tumors that were higher grade, estrogen receptor negative, progesterone receptor negative, more proliferative, or larger in size (P < .05). Although not statistically significant, lower miR-139 level was frequently associated with human epidermal growth factor receptor 2 overexpression. In addition, significantly lower miR-139 tissue level was seen in patients who were deceased (P = .027), although older age (>50 years) and positive local nodal disease did not adversely affect miR-139 expression. In contrast, serum miR-139 profile of the patients appeared similar to that of normal control. In conclusion, our study demonstrated that down-regulation of miR-139 was associated with aggressive tumor behavior and disease progression in breast cancer. miR-139 may serve as a risk assessment biomarker in tailoring treatment options.

  17. Exosome levels in human body fluids: A tumor marker by themselves?

    PubMed

    Cappello, Francesco; Logozzi, Mariantonia; Campanella, Claudia; Bavisotto, Celeste Caruso; Marcilla, Antonio; Properzi, Francesca; Fais, Stefano

    2017-01-01

    Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can provide several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may themselves represent a predictive/diagnostic of tumors, discriminating cancer patients from healthy subjects. The aim of this review is to highlight these latest challenging findings to provide novel and groundbreaking ideas for successful tumor early diagnosis and follow-up.

  18. Reprint of "EXOSOME LEVELS IN HUMAN BODY FLUIDS: A TUMOR MARKER BY THEMSELVES?"

    PubMed

    Cappello, Francesco; Logozzi, Mariantonia; Campanella, Claudia; Bavisotto, Celeste Caruso; Marcilla, Antonio; Properzi, Francesca; Fais, Stefano

    2017-02-15

    Despite considerable research efforts, the finding of reliable tumor biomarkers remains challenging and unresolved. In recent years a novel diagnostic biomedical tool with high potential has been identified in extracellular nanovesicles or exosomes. They are released by the majority of the cells and contain detailed molecular information on the cell of origin including tumor hallmarks. Exosomes can be isolated from easy accessible body fluids, and most importantly, they can at once provide with several biomarkers, with different levels of specificity. Recent clinical evidence shows that the levels of exosomes released into body fluids may by themselves represent a predictive/diagnostic of tumors, discriminating cancer patients from healthy subjects. The aim of this review is to highlight these latest challenging findings to provide novel and groundbreaking ideas for successful tumor early diagnosis and follow-up.

  19. Serum cytokeratin 19 fragment 21-1 is a useful tumor marker for the assessment of extramammary Paget's disease.

    PubMed

    Kato, Junji; Sumikawa, Yasuyuki; Hida, Tokimasa; Kamiya, Takafumi; Horimoto, Kohei; Kamiya, Shiori; Sato, Sayuri; Takahashi, Hitomi; Sawada, Masahide; Yamashita, Toshiharu

    2017-02-02

    Cytokeratin 19 fragment 21-1 (CYFRA 21-1) has been used as a tumor marker for several malignancies. However, to date, no studies have assessed whether CYFRA 21-1 could be a useful marker for extramammary Paget's disease (EMPD). The present study aimed to evaluate the significance of CYFRA 21-1 as a serum tumor marker for EMPD progression. Concentrations of serum CYFRA 21-1 and carcinoembryonic antigen (CEA) in 13 cases of EMPD were measured prior to undergoing treatment at Sapporo Medical University Hospital from January 2014 to May 2016. Four of the 13 patients had lymph node metastases at diagnosis, but none had distant metastases. Immunohistochemistry indicated that all 13 primary tumors and four metastatic tumors in lymph nodes were positive for cytokeratin 19. Although none of the 13 patients showed high serum CEA levels, six patients (46.2%) had elevated serum CYFRA 21-1. Furthermore, CYFRA 21-1 was reduced in association with post-treatment tumor reduction in all six patients. Among these six patients, four developed recurrence and metastasis during the follow-up period. CYFRA 21-1 was re-elevated in all four of these patients; however, serum CEA was elevated only in the patient with distant metastasis. These results suggest that CYFRA 21-1 is more sensitive compared with CEA, and can be useful as a tumor marker for evaluating tumor progression and treatment efficacy in patients with EMPD.

  20. The cancer-retina antigen recoverin as a potential biomarker for renal tumors.

    PubMed

    Golovastova, Marina O; Tsoy, Larisa V; Bocharnikova, Anna V; Korolev, Dmitry O; Gancharova, Olga S; Alekseeva, Ekaterina A; Kuznetsova, Ekaterina B; Savvateeva, Lyudmila V; Skorikova, Elena E; Strelnikov, Vladimir V; Varshavsky, Vladimir A; Vinarov, Andrey Z; Nikolenko, Vladimir N; Glybochko, Peter V; Zernii, Evgeni Yu; Zamyatnin, Andrey A; Bazhin, Alexandr V; Philippov, Pavel P

    2016-07-01

    The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.

  1. Markers

    ERIC Educational Resources Information Center

    Healthy Schools Network, Inc., 2011

    2011-01-01

    Dry erase whiteboards come with toxic dry erase markers and toxic cleaning products. Dry erase markers labeled "nontoxic" are not free of toxic chemicals and can cause health problems. Children are especially vulnerable to environmental health hazards; moreover, schools commonly have problems with indoor air pollution, as they are more densely…

  2. Detection of the tumor marker mucine with a diode-laser-based evanescent wave sensor

    NASA Astrophysics Data System (ADS)

    Bock, Daniel; Kaul, Sepp; Loescher, Frank; Ruckstuhl, Thomas; Schulz, V.; Ueberfeld, J.; Seeger, Stefan

    1996-11-01

    Optical sensors based on the utilization of the evanescent field arising at the interface between two media in the case of total internal reflection are an excellent tool for the reduction of time consuming and complex chemical analysis. We developed a fiber-optic based set-up with visible diode lasers as excitation sources. As recognition element an optical fiber covered with a photopolymerized antibody monolayer was used. Beside the commercially available cyanine fluorescent dye Cy 5, newly developed fluorescent dyes in the red spectral region were coupled to antibodies. In order to test the set-up in a clinically relevant system the antibodies BM-2 and BM-7 were chosen. With this antibody system the tumor marker mucine in a sandwich immunoassay was investigated. This protein shows increased concentrations in serum and ascites in the case of breast cancer. The combination of semiconductor devices and ultrathin antibody layers together with an antibody system directed against mucine offers the possibility of an on-line detection of the tumor marker.

  3. HLA Class II Antigen Expression in Colorectal Carcinoma Tumors as a Favorable Prognostic Marker12

    PubMed Central

    Sconocchia, Giuseppe; Eppenberger-Castori, Serenella; Zlobec, Inti; Karamitopoulou, Eva; Arriga, Roberto; Coppola, Andrea; Caratelli, Sara; Spagnoli, Giulio Cesare; Lauro, Davide; Lugli, Alessandro; Han, Junyi; Iezzi, Giandomenica; Ferrone, Cristina; Ferlosio, Amedeo; Tornillo, Luigi; Droeser, Raoul; Rossi, Piero; Attanasio, Antonio; Ferrone, Soldano; Terracciano, Luigi

    2014-01-01

    The goal of this study was to determine the frequency of HLA class II antigen expression in colorectal carcinoma (CRC) tumors, its association with the clinical course of the disease, and the underlying mechanism(s). Two tissue microarrays constructed with 220 and 778 CRC tumors were stained with HLA-DR, DQ, and DP antigen-specific monoclonal antibody LGII-612.14, using the immunoperoxidase staining technique. The immunohistochemical staining results were correlated with the clinical course of the disease. The functional role of HLA class II antigens expressed on CRC cells was analyzed by investigating their in vitro interactions with immune cells. HLA class II antigens were expressed in about 25% of the 220 and 21% of the 778 tumors analyzed with an overall frequency of 23%. HLA class II antigens were detected in 19% of colorectal adenomas. Importantly, the percentage of stained cells and the staining intensity were significantly lower than those detected in CRC tumors. However, HLA class II antigen staining was weakly detected only in 5.4% of 37 normal mucosa tissues. HLA class II antigen expression was associated with a favorable clinical course of the disease. In vitro stimulation with interferon gamma (IFNγ) induced HLA class II antigen expression on two of the four CRC cell lines tested. HLA class II antigen expression on CRC cells triggered interleukin-1β (IL-1β) production by resting monocytes. HLA class II antigen expression in CRC tumors is a favorable prognostic marker. This association may reflect stimulation of IL-1β production by monocytes. PMID:24563618

  4. Grp94 in complexes with IgG is a soluble diagnostic marker of gastrointestinal tumors and displays immune-stimulating activity on peripheral blood immune cells

    PubMed Central

    Tramentozzi, Elisa; Ruli, Erlis; Angriman, Imerio; Bardini, Romeo; Campora, Michela; Guzzardo, Vincenza; Zamarchi, Rita; Rossi, Elisabetta; Rugge, Massimo; Finotti, Paola

    2016-01-01

    Glucose-regulated protein94 (Grp94), the most represented endoplasmic reticulum (ER)-resident heat shock protein (HSP), is a tumor antigen shared by different types of solid and hematological tumors. The tumor-specific feature of Grp94 is its translocation from the ER to the cell surface where it displays pro-oncogenic functions. This un-physiological location has important implications for both the tumor pathology and anti-tumor therapy. We wanted to address the question of whether Grp94 could be measured as liquid marker in cancer patients in order to make predictions of diagnostic and therapeutic relevance for the tumor. To this aim, we performed an in-depth investigation on patients with primary tumors of the gastrointestinal (GI) tract, using different methodological approaches to detect Grp94 in tumor tissues, plasma and peripheral blood mononuclear cells (PBMCs). Results indicate that Grp94 is not only the antigen highly expressed in any tumor tissue and in cells of tumor infiltrates, mostly B lymphocytes, but it is also found in the circulation. However, the only form in which Grp94 was detected in the plasma of any patients and in B lymphocytes induced to proliferate, was that of stable complexes with Immunoglobulin (Ig)G. Using a specific immune-enzyme assay to measure plasma Grp94-IgG complexes, we showed that Grp94-IgG complexes were significantly increased in cancer patients compared to healthy control subjects, serving as diagnostic tumor biomarker. Results also demonstrate that the stimulation of patient PBMCs with Grp94-IgG complexes led to an increased secretion of inflammatory cytokines that might drive a potentially beneficial anti-tumor effect. PMID:27662661

  5. Evaluation of molecular markers in canine mammary tumors: correlation with histological grading.

    PubMed

    Vinothini, G; Balachandran, C; Nagini, S

    2009-01-01

    The objective of this study was to evaluate molecular markers involved in mammary tumorigenesis in a canine model that mimics many essential elements of human breast cancer. Thirty mammary gland tumors and control tissues obtained from female dogs were included in the study. We analyzed changes in the expression of markers of hormone and receptor status (estradiol, estrogen receptor; ER and HER-2/neu), hormone metabolism (CYP1A1 and CYP1B1), cell proliferation and survival [proliferating cell nuclear antigen (PCNA), glutathione S-transferase-P (GST-P), nuclear factor-kappaB (NF-kappaB-p50, NF-kappaB-p65), phosphorylated-inhibitor of kappaB-alpha (p-IkappaB-alpha) and IkappaB], apoptosis (Bcl-2, Bax, caspases, Apaf-1, cytochrome-C, and PARP), invasion [matrix metalloproteinases-2 and -9 (MMP-2, MMP-9), tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), and reversion-inducing cysteine-rich protein with Kazal motifs (RECK)], angiogenesis [vascular endothelial growth factor (VEGF)], and epigenetics [DNA methyltransferase (Dnmt-1), histone deacetylase (HDAC-1)] by immunohistochemical localization and Western blot analysis and correlated these with histological grade. The present study provides evidence that increased expression of ER, HER-2/neu, estradiol, and its metabolizing enzymes, as well as proteins involved in cell proliferation, apoptosis evasion, invasion, and angiogenesis may confer a selective growth advantage to canine mammary tumors. To our knowledge this is the first report on the hallmark capabilities of canine mammary tumors, which lends credence to the view that the dog is a valuable model for human breast cancer studies.

  6. SU-E-J-23: An Accurate Algorithm to Match Imperfectly Matched Images for Lung Tumor Detection Without Markers

    SciTech Connect

    Rozario, T; Bereg, S; Chiu, T; Liu, H; Kearney, V; Jiang, L; Mao, W

    2014-06-01

    Purpose: In order to locate lung tumors on projection images without internal markers, digitally reconstructed radiograph (DRR) is created and compared with projection images. Since lung tumors always move and their locations change on projection images while they are static on DRRs, a special DRR (background DRR) is generated based on modified anatomy from which lung tumors are removed. In addition, global discrepancies exist between DRRs and projections due to their different image originations, scattering, and noises. This adversely affects comparison accuracy. A simple but efficient comparison algorithm is reported. Methods: This method divides global images into a matrix of small tiles and similarities will be evaluated by calculating normalized cross correlation (NCC) between corresponding tiles on projections and DRRs. The tile configuration (tile locations) will be automatically optimized to keep the tumor within a single tile which has bad matching with the corresponding DRR tile. A pixel based linear transformation will be determined by linear interpolations of tile transformation results obtained during tile matching. The DRR will be transformed to the projection image level and subtracted from it. The resulting subtracted image now contains only the tumor. A DRR of the tumor is registered to the subtracted image to locate the tumor. Results: This method has been successfully applied to kV fluoro images (about 1000 images) acquired on a Vero (Brainlab) for dynamic tumor tracking on phantom studies. Radiation opaque markers are implanted and used as ground truth for tumor positions. Although, other organs and bony structures introduce strong signals superimposed on tumors at some angles, this method accurately locates tumors on every projection over 12 gantry angles. The maximum error is less than 2.6 mm while the total average error is 1.0 mm. Conclusion: This algorithm is capable of detecting tumor without markers despite strong background signals.

  7. EST-SSR markers derived from an elite barley cultivar (Hordeum vulgare L. 'Morex'): polymorphism and genetic marker potential.

    PubMed

    Emebiri, Livinus C

    2009-08-01

    Microsatellites or simple sequence repeats have become the markers of choice for marker-assisted selection because of their low template DNA requirement, high reproducibility, and high level of polymorphism. This study investigated a new set of barley (Hordeum vulgare L.) EST-derived SSR markers designed to target gene sequences expressed during grain development, as they are more likely to be important in determining grain quality. The EST sequences (HVSMEh and HVSMEi) were derived from cDNA libraries of the elite six-rowed cultivar Morex, made from spikes harvested at 5 to 45 days after pollination. Approximately half of the 110 SSR markers derived from the ESTs were polymorphic in a panel of 8 diverse barley genotypes, with PIC values between 0.19 and 0.79. Twenty of the new markers were mapped to chromosomal locations using 2 doubled haploid populations. To demonstrate marker potential, quantitative trait locus (QTL) analyses were carried out with phenotypic data on wort beta-glucan content and beta-glucanase activity, two traits with a long history of genetic studies. Most of the EST-SSR markers mapped to within 10 cM of the cellulose synthase (HvCesA) and cellulose synthase-like (HvCslF) genes, which provides highly informative functional markers for tracking these genes in breeding programs. It was also observed that on any given chromosome, the QTL for beta-glucan content and beta-glucanase activity were rarely coincident but tended to occur in adjacent intervals along chromosomal regions, which agreed with their independent genetic basis; the adjacent localization may be important for coordination of cell wall degradation during germination and malting.

  8. The Late Positive Potential: A Neurophysiological Marker for Emotion Regulation in Children

    ERIC Educational Resources Information Center

    Dennis, Tracy A.; Hajcak, Greg

    2009-01-01

    Background: The ability to modulate emotional responses, or emotion regulation, is a key mechanism in the development of mood disruptions. Detection of a neural marker for emotion regulation thus has the potential to inform early detection and intervention for mood problems. One such neural marker may be the late positive potential (LPP), which is…

  9. Clinical Utility of Serum Homocysteine and Folate as Tumor Markers in Oral Squamous Cell Carcinoma - A Cross-Sectional Study

    PubMed Central

    Erugula, Sridhar Reddy; Danappanavar, Prasanna M.; Ealla, Kranti Kiran Reddy; Velidandla, Surekha; Manikya, Sangameshwar

    2016-01-01

    Introduction Oral Squamous Cell Carcinoma (OSCC) is a common malignancy involving head and neck. Identifying the markers of molecular levels or biochemical markers involving the various metabolic reactions associated with the initiation and biological behavior of individual tumors are very important in diagnosis and prognosis. Aim To measure and compare the levels of serum Homocysteine (Hcy) and serum folate in OSCC patients, smoking group and healthy subjects and also to assess the clinical utility of serum Hcy as a potential tumor marker in OSCC. Materials and Methods The study group comprised of 60 subjects, of whom 30 were classified as OSCC cases (GROUP I) and 15 were classified as smokers without OSCC (GROUP II). The control group included 15 healthy individuals without smoking habit (Group III). Hcy was measured with High Performance Liquid Chromatography (HPLC). Folate estimation was done by Chemiluminiscence Immuno Assay (CLIA). Comparison of mean Hcy and folate values among the groups was done using ANOVA with Post-Hoc Games Howell test. Gender was compared using Chi-square test. Comparison of mean age was using ANOVA with Post-Hoc Tukey’s test. Results The mean serum folate level in OSCC patients was 5.34ng/mL, 7.68ng/mL in smoking group and 10.99ng/mL in control group. There was a significant difference in the mean serum folate levels among the three study groups (p<0.001). The mean serum Hcy in OSCC patients was 23.58μmol/L, 17.46μmol/L, in smoking group and 10.76μmol/l in controls. There was a significant difference in the mean serum Hcy levels among the three study groups (p<0.001). Conclusion The present study found an interesting association with serum Hcy and folate levels in OSCC which could be useful as a biochemical “Tumor Marker” and thereby providing insights into the onset and progression of the disease. PMID:27891452

  10. Evaluation of Near Infrared Dyes as Markers of P-Glycoprotein Activity in Tumors

    PubMed Central

    Semenenko, Inessa; Portnoy, Emma; Aboukaoud, Mohammed; Guzy, Serge; Shmuel, Miriam; Itzhak, Gal; Eyal, Sara

    2016-01-01

    Aim: The multidrug resistance protein 1 (MDR1; P-glycoprotein) has been associated with efflux of chemotherapeutic agents from tumor cells and with poor patient prognosis. This study evaluated the feasibility of non-invasive, non-radioactive near infrared (NIR) imaging methodology for detection of MDR1 functional activity in tumors. Methods: Initial accumulation assays were conducted in MDR1-overexpressing MDCK cells (MDCK-MDR1) and control MDCK cells (MDCK-CT) using the NIR dyes indocyanine green (ICG), IR-783, IR-775, rhodamine 800, XenoLight DiR, and Genhance 750, at 0.4 μM–100 μM. ICG and IR-783 were also evaluated in HT-29 cells in which MDR1 overexpression was induced by colchicine (HT-29-MDR1) and their controls (HT-29-CT). In vivo optical imaging studies were conducted using immunodeficient mice bearing HT-29-CT and HT-29-MDR1 xenografts. Results: ICG’s emission intensity was 2.0- and 2.2-fold higher in control versus MDR1-overexpressing cells, in MDCK and HT-29 cell lines, respectively. The respective IR-783 control:MDR1 ratio was 1.4 in both MDCK and HT-29 cells. Optical imaging of mice bearing HT-29-CT and HT-29-MDR1 xenografts revealed a statistically non-significant, 1.7-fold difference (p > 0.05) in ICG emission intensity between control and MDR1 tumors. No such differences were observed with IR-783. Conclusion: ICG and IR-783 appear to be weak MDR1 substrates. In vivo, low sensitivity and high between-subject variability impair the ability to use the currently studied probes as markers of tumor MDR1 activity. The results suggest that, for future use of this technology, additional NIR probes should be screened as MDR1 substrates. PMID:27895581

  11. Circulating tumor DNA as an early marker of therapeutic response in patients with metastatic colorectal cancer

    PubMed Central

    Tie, J.; Kinde, I.; Wang, Y.; Wong, H. L.; Roebert, J.; Christie, M.; Tacey, M.; Wong, R.; Singh, M.; Karapetis, C. S.; Desai, J.; Tran, B.; Strausberg, R. L.; Diaz, L. A.; Papadopoulos, N.; Kinzler, K. W.; Vogelstein, B.; Gibbs, P.

    2015-01-01

    Background Early indicators of treatment response in metastatic colorectal cancer (mCRC) could conceivably be used to optimize treatment. We explored early changes in circulating tumor DNA (ctDNA) levels as a marker of therapeutic efficacy. Patients and methods This prospective study involved 53 mCRC patients receiving standard first-line chemotherapy. Both ctDNA and CEA were assessed in plasma collected before treatment, 3 days after treatment and before cycle 2. Computed tomography (CT) scans were carried out at baseline and 8–10 weeks and were centrally assessed using RECIST v1.1 criteria. Tumors were sequenced using a panel of 15 genes frequently mutated in mCRC to identify candidate mutations for ctDNA analysis. For each patient, one tumor mutation was selected to assess the presence and the level of ctDNA in plasma samples using a digital genomic assay termed Safe-SeqS. Results Candidate mutations for ctDNA analysis were identified in 52 (98.1%) of the tumors. These patient-specific candidate tissue mutations were detectable in the cell-free DNA from the plasma of 48 of these 52 patients (concordance 92.3%). Significant reductions in ctDNA (median 5.7-fold; P < 0.001) levels were observed before cycle 2, which correlated with CT responses at 8–10 weeks (odds ratio = 5.25 with a 10-fold ctDNA reduction; P = 0.016). Major reductions (≥10-fold) versus lesser reductions in ctDNA precycle 2 were associated with a trend for increased progression-free survival (median 14.7 versus 8.1 months; HR = 1.87; P = 0.266). Conclusions ctDNA is detectable in a high proportion of treatment naïve mCRC patients. Early changes in ctDNA during first-line chemotherapy predict the later radiologic response. PMID:25851626

  12. Tumor endothelial markers define novel subsets of cancer-specific circulating endothelial cells associated with antitumor efficacy

    PubMed Central

    Mehran, Reza; Nilsson, Monique; Khajavi, Mehrdad; Du, Zhiqiang; Cascone, Tina; Wu, Hua Kang; Cortes, Andrea; Xu, Li; Zurita, Amado; Schier, Robert; Riedel, Bernhard; El-Zein, Randa; Heymach, John V.

    2014-01-01

    Circulating endothelial cells (CEC) are derived from multiple sources including bone marrow (circulating endothelial progenitors [CEP]) and established vasculature (mature CEC). Although CEC have shown promise as a biomarker for cancer patients, their utility has been limited in part by the lack of specificity for tumor vasculature and the different non-malignant causes that can impact CEC. Tumor endothelial markers (TEM) are antigens enriched in tumor vs non-malignant endothelia. We hypothesized that TEMs may be detectable on CEC and that these circulating TEM+ endothelial cells (CTEC) may be a more specific marker for cancer and tumor response than standard CEC. We found that tumor-bearing mice had a relative increase in numbers of circulating CTEC, specifically with increased levels of TEM7 and TEM8 expression. Following treatment with various vascular targeting agents, we observed a decrease in CTEC that correlated with the reductions in tumor growth. We extended these findings to human clinical samples and observed that CTEC were present in esophageal cancer and non-small cell lung cancer (NSCLC) patients (N=40) and their levels decreased after surgical resection. These results demonstrate that CTEC are detectable in preclinical cancer models and cancer patients. Further, they suggest that CTEC offer a novel cancer-associated marker that may be useful as a blood-based surrogate for assessing the presence of tumor vasculature and antiangiogenic drug activity. PMID:24626092

  13. Thrombomodulin as a marker for vascular tumors. Comparative study with factor VIII and Ulex europaeus I lectin.

    PubMed

    Yonezawa, S; Maruyama, I; Sakae, K; Igata, A; Majerus, P W; Sato, E

    1987-10-01

    Thrombomodulin (TM) is a newly described endothelial cell-associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. Various vascular tumors were characterized with immunoperoxidase staining with the use of a polyclonal anti-TM serum. The staining patterns of TM were compared with those of Factor VIII-related antigen (FVIII-RAG) and Ulex europaeus agglutinin-I (UEA-I), which have been used as markers for endothelial cells. The results showed that TM is a specific and a highly sensitive marker for angiosarcomas in comparison with FVIII-RAG or UEA-I. In contrast, UEA-I is more sensitive for benign vascular tumors than TM or FVIII-RAG. The other mesenchymal tumors of nonvascular origin showed negative staining for three endothelial markers. These results indicate that TM is a new specific and sensitive tool for the diagnosis of angiosarcomas.

  14. Immunoassay for tumor markers in human serum based on Si nanoparticles and SiC@Ag SERS-active substrate.

    PubMed

    Zhou, Lu; Zhou, Jun; Feng, Zhao; Wang, Fuyan; Xie, Shushen; Bu, Shizhong

    2016-04-21

    Based on a sandwich structure consisting of nano-Si immune probes and a SiC@Ag SERS-active immune substrate, a kind of ultra-sensitive immunoassay protocol is presented to detect tumor markers in human serum. The nano-Si immune probes were prepared by immobilizing the detecting antibodies onto the surfaces of SiO2-coated Si nanoparticles (NPs) which were modified with 3-(aminopropyl)trimethoxysilane, and the SiC@Ag SERS-active immune substrates were prepared by immobilizing the captured antibodies on Ag film sputtered on SiC sandpaper. To the best of our knowledge, it is the first time that Si NPs are directly used as Raman tags in an immunoassay strategy. And, the SiC@Ag SERS-active substrates exhibit excellent surface enhanced Raman scattering (SERS) performances with an enhancement factor of ∼10(5), owing to the plasmonic effect of the Ag film on the rough surface of the SiC sandpaper. In our experiments, the sandwich immunoassay structure has been successfully applied to detect prostate specific antigen (PSA), α-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9) in a human serum sample and the limit of detections are as low as 1.79 fg mL(-1), 0.46 fg mL(-1) and 1.3 × 10(-3) U mL(-1), respectively. It reveals that the proposed immunoassay protocol has demonstrated a high sensitivity for tumor markers in human serum and a potential practicability in biosensing and clinical diagnostics.

  15. External quality control results for hormones, tumor markers and CRP testing.

    PubMed

    Tatsumi, N; Kawano, K; Takubo, T; Nakamura, H; Tsuda, I

    1999-01-01

    Most hormones, tumor markers, C-reactive protein, and rheumatoid factor (RF) are measured immunologically. Immunological methods based on the antigen-antibody reaction have certain specific problems, including their principle of determination, character of antibodies used, reaction conditions, and others. Free thyroxine (FT4) and thyroid stimulating hormone (TSH), as well as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate antigen, carcinoantigen 19-9 (CA 19-9), and CA 125 are very commonly measured in the routine medical laboratory. Authentic materials can be obtained for hormones and CRP, and efforts to improve quality control and standardization have been made for years. Results of surveillance for FT4, TSH, and AFP were not poor, but inter-laboratory differences for CEA, CA 19-9, and RF were not insignificant.

  16. Intracellular TCR-signaling pathway: novel markers for lymphoma diagnosis and potential therapeutic targets.

    PubMed

    Agostinelli, Claudio; Rizvi, Hasan; Paterson, Jennifer; Shende, Vishvesh; Akarca, Ayse U; Agostini, Elena; Fuligni, Fabio; Righi, Simona; Spagnolo, Sebastiano; Piccaluga, Pier Paolo; Clark, Edward A; Pileri, Stefano A; Marafioti, Teresa

    2014-10-01

    Despite the immunologic functions of T-cell receptor signaling molecules being extensively investigated, their potential as immunohistochemical markers has been poorly explored. With this background, we evaluated the expression of 5 intracellular proteins-GADS, DOK2, SKAP55, ITK, and PKCα-involved in T-cell receptor signaling in normal and neoplastic hematologic tissue samples, using antibodies raised against fixation-resistant epitopes of the 5 molecules. All 5 antibodies were associated with normal T-cell differentiation. GADS, DOK2, SKAP55, and ITK turned out to be T-cell lineage-specific markers in the setting of lymphoid and myeloid precursor neoplasms but showed differential expression in peripheral T-cell lymphoma (PTCL) subtypes, being detected in PTCL/not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma but negative in anaplastic large cell lymphoma (ALCL). Peripheral B-cell lymphomas were consistently negative for ITK, with occasional cases showing expression of DOK2 and SKAP55, and a proportion (47%) of hairy cell leukemias were GADS. Notably, PKCα highlighted a defective antigen in both PTCL/NOS (6%) and angioimmunoblastic T-cell lymphoma (10%), mostly negative in ALCL, and was aberrantly expressed in classical Hodgkin lymphoma (65%), Burkitt lymphoma (48%), and plasma cell myeloma (48%). In conclusion, all five molecules evaluated play a role in T-cell differentiation in normal and neoplastic tissues. They can be applied confidently to routine sections contributing primarily to assignment of T-lineage differentiation in the setting of hematopoietic precursor neoplasms (GADS/DOK2/SKAP55/ITK) and for the differential diagnosis between ALCL and PTCL/NOS (GADS/DOK2/SKAP55/ITK) or classical Hodgkin lymphoma (PKCα). Finally, association with specific tumor subtypes may have therapeutic potential.

  17. Tumor markers and oncogene expression in thyroid cancer using biochemical and immunohistochemical studies.

    PubMed

    Hashimoto, T; Matsubara, F; Mizukami, Y; Miyazaki, I; Michigishi, T; Yanaihara, N

    1990-04-01

    In 111 thyroid cancer patients consisting of 89 papillary carcinomas, 17 follicular carcinomas, 2 medullary carcinomas, 1 squamous cell carcinoma and 2 malignant lymphomas, the levels of 12 tumor markers, including thyroglobulin (Tg), were measured in the serum by radioimmunoassay and radioimmunoassay related methods. Serum levels of Tg were elevated in 58.6%, those of CA-M26 in 15.7%, CA 19-9 in 5.3%, CT in 3.6%, NSE in 3.6%, CA 15-3 in 2.6%, CA 125 in 2.6%, CEA in 0.9%, CA-M 29 in 0%, ferritin in 0%, SCC in 0% and AFP in 0% of cases. Among the patients, there was a case of thyroid carcinoma secreting thyroglobulin and CA 19-9, both of whose titer decreased after surgery. Immunohistochemical studies were carried out on 57 of the above mentioned patients plus 6 anaplastic carcinomas, 15 adenomas, 5 adenomatous goiters, 6 Hashimoto's thyroiditis, 15 Graves' disease and 15 normal subjects. CA 19-9 was positive in 58% of the papillary carcinomas, EGF in 73% of papillary carcinomas, 67% of anaplastic carcinomas, and 33% of follicular carcinomas, while EGF-R was found in 73% of the papillary carcinomas, and 33% of the follicular carcinomas. Enhanced expression of ras p 21 oncogene and (c-myc oncogene) was demonstrated in 100% (100%) of anaplastic carcinomas, in 100% (67%) of follicular carcinomas and in 63% (90%) of papillary carcinomas. Our results indicate that a better tumor marker is required and more extensive molecular oncology research should be pursued.

  18. Centrosome Amplification: A Potential Marker of Breast Cancer Agressiveness

    DTIC Science & Technology

    2006-07-01

    generation of aneuploid cancer cells (25, 26). Inhibition of centrosome reduplication depends on the balance between oncogene and tumor suppressor...suppressor p53 preserves the stability of the genome by inhibiting centrosome reduplication . The ability of p53 in preventing centrosome... reduplication in the absence of DNA replication is linked to over-expression of the cdk inhibitor p21, inhibition of cyclin/cdk2 activity and consequent

  19. Potential immunological markers for diagnosis and therapeutic assessment of toxocariasis.

    PubMed

    Rubinsky-Elefant, Guita; Hoshino-Shimizu, Sumie; Jacob, Cristina Miuki Abe; Sanchez, Maria Carmen Arroyo; Ferreira, Antonio Walter

    2011-01-01

    In human toxocariasis, there are few approaches using immunological markers for diagnosis and therapeutic assessment. An immunoblot (IB) assay using excretory-secretory Toxocara canis antigen was standardized for monitoring IgG, IgE and IgA antibodies in 27 children with toxocariasis (23 visceral, three mixed visceral and ocular, and one ocular form) for 22-116 months after chemotherapy. IB sensitivity was 100% for IgG antibodies to bands of molecular weight 29-38, 48-54, 95-116, 121-162, >205 kDa, 80.8% for IgE to 29-38, 48-54, 95-121, > 205 kDa, and 65.4% for IgA to 29-38, 48-54, 81-93 kDa. Candidates for diagnostic markers should be IgG antibodies to bands of low molecular weight (29-38 and 48-54 kDa). One group of patients presented the same antibody reactivity to all bands throughout the follow-up study; in the other group, antibodies decayed partially or completely to some or all bands, but these changes were not correlated with time after chemotherapy. Candidates for monitoring patients after chemotherapy may be IgG antibodies to > 205 kDa fractions, IgA to 29-38, 48-54, 81-93 kDa and IgE to 95-121 kDa. Further identification of antigen epitopes related to these markers will allow the development of sensitive and specific immunoassays for the diagnosis and therapeutic assessment of toxocariasis.

  20. Immunohistochemical Markers of Soft Tissue Tumors: Pathologic Diagnosis, Genetic Contributions, and Therapeutic Options

    PubMed Central

    Parham, David M

    2015-01-01

    After ~30 years of widespread usage, immunohistochemistry (IHC) has become a standard method of diagnosis for surgical pathology. Because of the plethora of diagnoses and often subtle nature of diagnostic criteria, IHC finds particular utility in soft tissue tumors. The use of progressively small amounts of tissue for diagnosis highlights the importance of this method. The sensitivity and crispness of IHC stains have progressively improved with the advent of new techniques. Traditionally, IHC detects cell-typic markers that characterize cell phenotypes, such as chromogranin for neuroectodermal tissue, myogenin for skeletal muscle, and cytokeratin for epithelium. However, the advent of genetic discoveries have led to IHC testing for detection of fusion gene products or overexpressed oncogenes associated with deletions and mutations. Proliferation-based markers such as Ki-67 can also be used for prognosis and grading, but more standardization is needed. Development of monoclonal antibody-based pharmaceuticals, such as imatinib or crizotinib, holds the promise of tailored anticancer therapy. IHC thus has assumed importance not only for diagnosis but also for guidance of personalized medicine. PMID:26549970

  1. Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF-{kappa}B

    SciTech Connect

    Takahashi, Nozomi Kilsdonk, Jeroen W.J. van; Ostendorf, Benedikt; Smeets, Ruben; Bruggeman, Sophia W.M.; Alonso, Angel; Loo, Fons van de; Schneider, Matthias; Berg, Wim B. van den; Swart, Guido W.M.

    2008-09-26

    Nucleoporin 88 kDa (Nup88) is a tumor marker, overexpressed in various types of cancer. In Drosophila Nup88 (mbo) was reported to selectively mediate the nucleocytoplasmic transport of NF-{kappa}B, an ubiquitous transcription factor involved in immune responses, apoptosis, and cancer. We addressed the function of Nup88 in mammalian cells. Selective depletion of Nup88 by small interfering RNA (siRNA) inhibited NF-{kappa}B-dependent reporter gene activation and the nuclear translocation of NF-{kappa}B without affecting the upstream activation pathway in NIH3T3 cells. In contrast, nuclear translocation of glucocorticoid receptor was not reduced by the depletion of Nup88. In metastatic melanoma cells overexpressing Nup88, constitutive activation of NF-{kappa}B was found both in nucleus and cytoplasm. Nup88 depletion in these cells reduced TNF-induced nuclear accumulation of NF-{kappa}B subunits. We conclude that Nup88 regulates the activity of NF-{kappa}B at the level of nucleocytoplasmic transport. Overexpression of Nup88 in tumor cells may, thus be involved in the constitutive NF-{kappa}B activation.

  2. Oncocytic variant of malignant gastrointestinal neuroectodermal tumor: a potential diagnostic pitfall.

    PubMed

    Boland, Jennifer M; Folpe, Andrew L

    2016-11-01

    Malignant gastrointestinal neuroectodermal tumor (MGNET) is a very rare, aggressive malignant neoplasm that may occur in any location in the gastrointestinal tract. Malignant gastrointestinal neuroectodermal tumors typically consist of sheet-like to pseudopapillary proliferation of primitive-appearing epithelioid cells with a moderate amount of lightly eosinophilic cytoplasm, round nuclei and small nucleoli, often in association with osteoclast-like giant cells. By immunohistochemistry, these tumors show expression of S100 protein and SOX10, in the absence of expression of more specific melanocytic markers (eg, HMB45, Melan A). Genetically, malignant gastrointestinal neuroectodermal tumors are characterized by rearrangements of the EWSR1 or FUS genes with CREB1 or ATF1. We report a case of gastric malignant gastrointestinal neuroectodermal tumor occurring in a 46-year-old woman and showing striking oncocytic cytoplasmic change, a previously undescribed potential diagnostic pitfall. An initial needle biopsy showed large, eosinophilic cells with S100 protein and SOX10 expression and lacking expression of KIT, DOG1, Melan A, keratin, chromogranin, or smooth muscle actin, and was interpreted as representing a granular cell tumor. The subsequent excision specimen showed similar-appearing areas, but also contained small more primitive-appearing areas, lacking oncocytic change and having high nuclear grade and brisk mitotic activity. This resection specimen was initially diagnosed as a malignant granular cell tumor. However subsequent gene expression profiling studies showed an EWSR1-ATF1 fusion, confirmed with fluorescence in situ hybridization for EWSR1, and a final diagnosis of MGNET with oncocytic change was made. This case highlights a previously undescribed pitfall in the diagnosis of MGNET, oncocytic change, and suggests that MGNET should be included in the differential diagnosis for unusual oncocytic neoplasms of the gastrointestinal tract.

  3. Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

    PubMed Central

    Klinger, Neil V.

    2016-01-01

    Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin's ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors. PMID:27807473

  4. Tumor endothelial marker 8 expression levels in dendritic cell-based cancer vaccines are related to clinical outcome.

    PubMed

    Venanzi, Franco Maria; Petrini, Massimiliano; Fiammenghi, Laura; Bolli, Elisabetta; Granato, Anna Maria; Ridolfi, Laura; Gabrielli, Federica; Barucca, Alessandra; Concetti, Antonio; Ridolfi, Ruggero; Riccobon, Angela

    2010-01-01

    Previous studies have shown that tumor endothelial markers (TEMs 1-9) are up modulated in immunosuppressive, pro-angiogenic dendritic cells (DCs) found in tumor microenvironments. We recently reported that monocyte-derived DCs used for vaccination trials may accumulate high levels of TEM8 gene transcripts. Here, we investigate whether TEM8 expression in DC preparations represents a specific tumor-associated change of potential clinical relevance. TEM8 expression at the mRNA and protein level was evaluated by quantitative real-time RT-PCR and cytofluorimetric analysis in human clinical grade DCs utilized for the therapeutic vaccination of 17 advanced cancer patients (13 melanoma and 4 renal cell carcinoma). The analyses revealed that DCs from patients markedly differ in their ability to up-modulate TEM8. Indeed, mDCs from eight non-progressing patients [median overall survival (OS) = 32 months, all positive to the delayed-type hypersensitivity test (DTH)], had similar TEM8 mRNA expression levels [mDCs vs. immature iDCs; mean fold increase (mfi) = 1.97] to those found in healthy donors (mfi = 2.7). Conversely, mDCs from nine progressing patients (OS < 5 months, all but one with negative DTH) showed an increase in TEM8 mRNA levels (mfi = 12.88, p = 0.0018). The present observations suggest that TEM8 expression levels in DC-based therapeutic vaccines would allow the selection of a subgroup of patients who are most likely to benefit from therapeutic vaccination.

  5. Down's syndrome-associated single minded gene as a novel tumor marker.

    PubMed

    Deyoung, Maurice Phil; Scheurle, Daniela; Damania, Hema; Zylberberg, Claudia; Narayanan, Ramaswamy

    2002-01-01

    The Cancer Genome Anatomy Project (CGAP) database has thousands of Expressed Sequence Tags encompassing both known and novel genes. Bioinformatics of the CGAP database led to the prediction that Single Minded Gene (sim2) could be specific to colon tumors. The sim2 gene is located in a minimum region of the chromosome 21 often implicated in trisomia called Down's Syndrome Critical Region. To date, the sim proteins have not been shown to be involved in cancer. Intrigued by the possible association of a Down's syndrome-related gene to solid tumors, efforts were undertaken to validate the expression specificity. The sim2 isoform (sim2-short-form, sim2-s) expression was seen in carcinomas of colon, pancreas and prostate, but not in corresponding normal tissues. Stage-specific expression of the sim2-s protein was seen in normal matched paraffin sections of the colon tumors. In a matched set of tissues of Benign Prostatic Hyperplasia (BPH) and prostate carcinomas, sim2-s expression was detected in the BPH. The expression specificity of sim2-s in select solid tumors offers both diagnostic and therapeutic potential and warrants additional study.

  6. Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model

    SciTech Connect

    Fokas, Emmanouil; Haenze, Joerg; Kamlah, Florentine; Eul, Bastian G.; Lang, Nico; Keil, Boris; Heverhagen, Johannes T.; Engenhart-Cabillic, Rita; An Hanxiang; Rose, Frank

    2010-08-01

    Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas after IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.

  7. Immunohistochemical expression of SALL4 in hepatocellular carcinoma, a potential pitfall in the differential diagnosis of yolk sac tumors.

    PubMed

    Gonzalez-Roibon, Nilda; Katz, Betina; Chaux, Alcides; Sharma, Rajni; Munari, Enrico; Faraj, Sheila F; Illei, Peter B; Torbenson, Michael; Netto, George J

    2013-07-01

    SALL4 is a transcription factor that serves as a marker of yolk sac tumor. Yolk sac tumor and hepatocellular carcinoma share histologic, serologic, and immunohistochemical features. Previous studies have shown lack of SALL4 expression in hepatocellular carcinoma, suggesting utility in this differential diagnosis. Sixty-nine samples of hepatocellular carcinoma were retrieved from surgical pathology archives and used to construct 9 tissue microarrays. A germ cell tumor tissue microarray containing 10 yolk sac tumors was used for comparison. Extent, intensity, and pattern of nuclear SALL4 expression were assessed in each spot. Mean percentage of expression was calculated for each tumor and used during analysis. Optimal discriminatory extent of expression cutoff was determined by receiver operating characteristic curve analysis. Other potential discriminatory markers including Hep Par1 were also evaluated. Forty-six percent (32/69) of hepatocellular carcinoma and all yolk sac tumors revealed at least focal expression of SALL4. A unique punctuate/clumped pattern of nuclear staining was present in 94% (30/32) of hepatocellular carcinoma, whereas all yolk sac tumors displayed a diffuse finely granular nuclear staining pattern. A 25% extent of SALL4 expression cutoff was found to be optimal for the distinction of yolk sac tumor from hepatocellular carcinoma yielding a sensitivity of 100%, specificity of 92.8%, and a positive predictive value of 66.6% for yolk sac tumor diagnosis. The addition of Hep Par1 increased the specificity (99%) and positive predictive value (90%). This is the first report of SALL4 expression in hepatocellular carcinoma. Our finding should be taken into consideration in the differential diagnosis of hepatocellular carcinoma and yolk sac tumor. The unique punctuate/clumped pattern seen in hepatocellular carcinoma cases could be of further discriminatory value.

  8. Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression.

    PubMed

    Putluri, Nagireddy; Shojaie, Ali; Vasu, Vihas T; Vareed, Shaiju K; Nalluri, Srilatha; Putluri, Vasanta; Thangjam, Gagan Singh; Panzitt, Katrin; Tallman, Christopher T; Butler, Charles; Sana, Theodore R; Fischer, Steven M; Sica, Gabriel; Brat, Daniel J; Shi, Huidong; Palapattu, Ganesh S; Lotan, Yair; Weizer, Alon Z; Terris, Martha K; Shariat, Shahrokh F; Michailidis, George; Sreekumar, Arun

    2011-12-15

    Although alterations in xenobiotic metabolism are considered causal in the development of bladder cancer, the precise mechanisms involved are poorly understood. In this study, we used high-throughput mass spectrometry to measure over 2,000 compounds in 58 clinical specimens, identifying 35 metabolites which exhibited significant changes in bladder cancer. This metabolic signature distinguished both normal and benign bladder from bladder cancer. Exploratory analyses of this metabolomic signature in urine showed promise in distinguishing bladder cancer from controls and also nonmuscle from muscle-invasive bladder cancer. Subsequent enrichment-based bioprocess mapping revealed alterations in phase I/II metabolism and suggested a possible role for DNA methylation in perturbing xenobiotic metabolism in bladder cancer. In particular, we validated tumor-associated hypermethylation in the cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1B1 (CYP1B1) promoters of bladder cancer tissues by bisulfite sequence analysis and methylation-specific PCR and also by in vitro treatment of T-24 bladder cancer cell line with the DNA demethylating agent 5-aza-2'-deoxycytidine. Furthermore, we showed that expression of CYP1A1 and CYP1B1 was reduced significantly in an independent cohort of bladder cancer specimens compared with matched benign adjacent tissues. In summary, our findings identified candidate diagnostic and prognostic markers and highlighted mechanisms associated with the silencing of xenobiotic metabolism. The metabolomic signature we describe offers potential as a urinary biomarker for early detection and staging of bladder cancer, highlighting the utility of evaluating metabolomic profiles of cancer to gain insights into bioprocesses perturbed during tumor development and progression.

  9. Comparison of breast cancer to healthy control tissue discovers novel markers with potential for prognosis and early detection.

    PubMed

    Schummer, Michèl; Green, Ann; Beatty, J David; Karlan, Beth Y; Karlan, Scott; Gross, Jenny; Thornton, Sean; McIntosh, Martin; Urban, Nicole

    2010-02-09

    This study was initiated to identify biomarkers with potential value for the early detection of poor-outcome breast cancer. Two sets of well-characterized tissues were utilized: one from breast cancer patients with favorable vs. poor outcome and the other from healthy women undergoing reduction mammaplasty. Over 46 differentially expressed genes were identified from a large list of potential targets by a) mining publicly available expression data (identifying 134 genes for quantitative PCR) and b) utilizing a commercial PCR array. Three genes show elevated expression in cancers with poor outcome and low expression in all other tissues, warranting further investigation as potential blood markers for early detection of cancers with poor outcome. Twelve genes showed lower expression in cancers with poor outcome than in cancers with favorable outcome but no differential expression between aggressive cancers and most healthy controls. These genes are more likely to be useful as prognostic tissue markers than as serum markers for early detection of aggressive disease. As a secondary finding was that, when histologically normal breast tissue was removed from a distant site in a breast with cancer, 7 of 38 specimens displayed a cancer-like expression profile, while the remaining 31 were genetically similar to the reduction mammaplasty control group. This finding suggests that some regions of ipsilateral histologically 'normal' breast tissue are predisposed to becoming malignant and that normal-appearing tissue with malignant signature might warrant treatment to prevent new primary tumors.

  10. Identification of potential genetic markers for improved growth rate in channel catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Identification of genetic polymorphism associated with muscle growth would improve selection efficiency of channel catfish broodstock. Because faster growth is typically associated with increased food intake, factors involved in food intake regulation may serve as potential gene markers for selecti...

  11. Taming Tumor Glycolysis and Potential Implications for Immunotherapy

    PubMed Central

    Ganapathy-Kanniappan, Shanmugasundaram

    2017-01-01

    Immune evasion and deregulation of energy metabolism play a pivotal role in cancer progression. Besides the coincidence in their historical documentation and concurrent recognition as hallmarks of cancer, both immune evasion and metabolic deregulation may be functionally linked as well. For example, the metabolic phenotype, particularly tumor glycolysis (aerobic glycolysis), impacts the tumor microenvironment (TME), which in turn acts as a major barrier for successful targeting of cancer by antitumor immune cells and other therapeutics. Similarly, in the light of recent research, it has been known that some of the immune sensitive antigens that are downregulated in cancer may also be restored or induced by cellular/metabolic stress. For instance, cancer cells downregulate the cell surface ligands such as MHC class I chain-related (MIC) protein-(A/B) that are normally upregulated in disease/pathological conditions. Noteworthy, the MHC class I chain-related protein A and B (MIC-A/B) are recognized by natural killer (NK) cells for immune elimination. Interestingly, MIC-A/B is stress inducible as demonstrated by oxidative stress and other cellular-stress factors. Consequently, stimulation of metabolic stress has also been shown to sensitize cancer cells to NK cell-mediated cytotoxicity. Taken together, data from recent reports imply that dysregulation of tumor glycolysis could facilitate induction of immune sensitive surface ligands leading to increased efficacy of antitumor immunotherapeutics. Nonetheless, dysregulated tumor glycolysis may also impact the TME and alter it from acidic, low pH into a therapeutically desirable TME that can enhance the effective infiltration of antitumor immune cells. In this mini-review, targeting tumor glycolysis has been discussed to evaluate its potential implications to enhance and/or facilitate anticancer immunity. PMID:28348977

  12. Potential of epigenetic therapies in the management of solid tumors

    PubMed Central

    Valdespino, Victor; Valdespino, Patricia M

    2015-01-01

    Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s) more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and undertaking new cancer epigenetic-therapy clinical trails. PMID:26346546

  13. Stock-still behavior: a potential developmental marker.

    PubMed

    Sherkow, Susan P; Weinstein, Lissa; Kamens, Sarah R; Megyes, Matthew; Tishman, Lynn P; Williams, Cheryl

    2008-01-01

    During the course of a pilot study of toddlers' behavior and play, the experimenters observed a previously undocumented behavior. This behavior now labeled "stock-still" behavior, was noted at the age of 17.5 months and consisted of the toddlers' standing motionless at or near the doorway of a nursery when previously they had marched, seemingly intrepid, into the room on their own. A prospective study of eight children was undertaken to test the hypothesis that this behavior reliably occurs at a set time during the child's development. Analysis of videotape footage determined that the behavior did not occur as an isolated event but instead was part of a series of one to six individual events within a window spanning two to eight weeks, during a discrete period of time from ages 15.5 months to 18.5 months. It was hypothesized that this behavior may be a developmental marker of the moment when a toddler cognitively and affectively registers the differences between "inside" and "outside," self and other and inner space and outer space. This developmental step is manifested behaviorally as the child's ability to inhibit her responses to previously compelling external stimuli. This hypothesis, as well as its limitations, is herein discussed, and additional clarifying observations are suggested.

  14. Human mammaglobin: a superior marker for reverse-transcriptase PCR in detecting circulating tumor cells in breast cancer patients.

    PubMed

    Li, GuangLiang; Zhang, Jing; Jin, KeTao; He, KuiFeng; Wang, HaoHao; Lu, HaiQi; Teng, LiSong

    2011-04-01

    Breast cancer is the most frequent cancer in women in the USA and the second most common cause of death in females who develop cancer. Recently, the detection of circulating tumor cells has emerged as a promising tool for monitoring the progression of clinically occult micrometastases in breast cancer patients. Sensitive molecular techniques, primarily based upon the reverse-transcriptase PCR, using various molecules as markers, have been developed to detect circulating tumor cells. Among those molecules, human mammaglobin mRNA has been found to be the most specific marker for the hematogenous spread of breast cancer cells. In this article, we review the current knowledge regarding the use of reverse-transcriptase PCR for detecting human mammaglobin mRNA as a biomarker for circulating tumor cells in breast cancer patients, and evaluate the clinical implications of human mammaglobin since it was first isolated in 1996.

  15. Carbon nanoparticle-enhanced immunoelectrochemical detection for protein tumor marker with cadmium sulfide biotracers.

    PubMed

    Ho, Ja-an Annie; Lin, Yeh-Chun; Wang, Li-Sheng; Hwang, Kuo-Chu; Chou, Pi-Tai

    2009-02-15

    We have developed a sensitive electrochemical immunoassay system for the detection of a protein tumor marker, carcinoembryonic antigen (CEA), that is based on a carbon nanoparticle (CNP)/poly(ethylene imine) (PEI)-modified screen-printed graphite electrode (CNP-PEI/SPGE) covered with anti-CEA antibodies. The signal amplification strategy--using CdS nanocrystals as biotracers and CNPs to enhance electron transfer--improves the sensitivity and detection limit for CEA, suggesting that this system holds promise for development into a point-of-care or disposable home-care self-diagnostic tool. This biosensor is based on a sandwich complex immunoassay, which we assembled from sequential layers of the anti-CEA antibody (alphaCEA) on CNP-PEI/SPGE, the CEA sample, and the CdS nanocrystal quantum dots (QDs) sensitized with alphaCEA (alphaCEA-CdS QD). We used square wave anodic stripping voltammetry (SWASV) to amplify the signal current response obtained from the dissolved alphaCEA-CdS QDs. The calibration curve for CEA concentration was linear in the range of 0.032-10 ng/mL; the detection limit (estimated as the mean of the blank sample plus three times the standard deviation obtained on the blank sample) was 32 pg/mL (equivalent to 160 fg in a 5 microL sample). This method is suitably precise and sensitive to function as a means of determining urinary CEA, which is a better marker than serum CEA for the early detection of urothelial carcinoma.

  16. Identification of novel tumor markers in prostate, colon and breast cancer by unbiased methylation profiling.

    PubMed

    Chung, Woonbok; Kwabi-Addo, Bernard; Ittmann, Michael; Jelinek, Jaroslav; Shen, Lanlan; Yu, Yinhua; Issa, Jean-Pierre J

    2008-04-30

    DNA hypermethylation is a common epigenetic abnormality in cancer and may serve as a useful marker to clone cancer-related genes as well as a marker of clinical disease activity. To identify CpG islands methylated in prostate cancer, we used methylated CpG island amplification (MCA) coupled with representational difference analysis (RDA) on prostate cancer cell lines. We isolated 34 clones that corresponded to promoter CpG islands, including 5 reported targets of hypermethylation in cancer. We confirmed the data for 17 CpG islands by COBRA and/or pyrosequencing. All 17 genes were methylated in at least 2 cell lines of a 21-cancer cell line panel containing prostate cancer, colon cancer, leukemia, and breast cancer. Based on methylation in primary tumors compared to normal adjacent tissues, NKX2-5, CLSTN1, SPOCK2, SLC16A12, DPYS and NSE1 are candidate biomarkers for prostate cancer (methylation range 50%-85%). The combination of NSE1 or SPOCK2 hypermethylation showed a sensitivity of 80% and specificity of 95% in differentiating cancer from normal. Similarly NKX2-5, SPOCK2, SLC16A12, DPYS and GALR2 are candidate biomarkers for colon cancer (methylation range 60%-95%) and GALR2 hypermethylation showed a sensitivity of 85% and specificity of 95%. Finally, SLC16A12, GALR2, TOX, SPOCK2, EGFR5 and DPYS are candidate biomarkers for breast cancer (methylation range 33%-79%) with the combination of EGFR5 or TOX hypermethylation showing a sensitivity of 92% and specificity of 92%. Expression analysis for eight genes that had the most hypermethylation confirmed the methylation associated silencing and reactivation with 5-aza-2'-deoxycytidine treatment. Our data identify new targets of transcriptional silencing in cancer, and provide new biomarkers that could be useful in screening for prostate cancer and other cancers.

  17. Evaluation of prognostic markers for canine mast cell tumors treated with vinblastine and prednisone

    PubMed Central

    Webster, Joshua D; Yuzbasiyan-Gurkan, Vilma; Thamm, Douglas H; Hamilton, Elizabeth; Kiupel, Matti

    2008-01-01

    Background Canine cutaneous mast cell tumor (MCT) is a common neoplastic disease associated with a variable biologic behavior. Surgery remains the primary treatment for canine MCT; however, radiation therapy (RT) and chemotherapy are commonly used to treat aggressive MCT. The goals of this study were to evaluate the prognostic utility of histologic grade, c-KIT mutations, KIT staining patterns, and the proliferation markers Ki67 and AgNORs in dogs postoperatively treated with vinblastine and prednisone +/- RT, and to compare the outcome of dogs treated with post-operative chemotherapy +/- RT to that of a prognostically matched group treated with surgery alone. Associations between prognostic markers and survival were evaluated. Disease-free intervals (DFI) and overall survival times (OS) of dogs with similar pretreatment prognostic indices postoperatively treated with chemotherapy were compared to dogs treated with surgery alone. Results Histologic grade 3 MCTs, MCTs with c-KIT mutations, MCTs with increased cytoplasmic KIT, and MCTs with increased Ki67 and AgNOR values were associated with decreased DFI and OS. Dogs with histologic grade 3 MCT had significantly increased DFI and OS when treated with chemotherapy vs. surgery alone. Although not statistically significant due to small sample sizes, MCTs with c-KIT mutations had increased DFI and OS when treated with chemotherapy vs. surgery alone. Conclusion and clinical importance This study confirms the prognostic value of histologic grade, c-KIT mutations, KIT staining patterns, and proliferation analyses for canine MCT. Additionally, the results of this study further define the benefit of postoperative vinblastine and prednisone for histologic grade 3 MCTs. PMID:18700956

  18. Potential Role of Methylation Marker in Glioma Supporting Clinical Decisions

    PubMed Central

    Roszkowski, Krzysztof; Furtak, Jacek; Zurawski, Bogdan; Szylberg, Tadeusz; Lewandowska, Marzena A.

    2016-01-01

    The IDH1/2 gene mutations, ATRX loss/mutation, 1p/19q status, and MGMT promoter methylation are increasingly used as prognostic or predictive biomarkers of gliomas. However, the effect of their combination on radiation therapy outcome is discussable. Previously, we demonstrated that the IDH1 c.G395A; p.R132H mutation was associated with longer survival in grade II astrocytoma and GBM (Glioblastoma). Here we analyzed the MGMT promoter methylation status in patients with a known mutation status in codon 132 of IDH1, followed by clinical and genetic data analysis based on the two statuses. After a subtotal tumor resection, the patients were treated using IMRT (Intensity-Modulated Radiation Therapy) with 6 MeV photons. The total dose was: 54 Gy for astrocytoma II, 60 Gy for astrocytoma III, 60 Gy for glioblastoma, 2 Gy per day, with 24 h intervals, five days per week. The patients with MGMT promoter methylation and IDH1 somatic mutation (OS = 40 months) had a better prognosis than those with MGMT methylation alone (OS = 18 months). In patients with astrocytoma anaplasticum (n = 7) with the IDH1 p.R132H mutation and hypermethylated MGMT, the prognosis was particularly favorable (median OS = 47 months). In patients with astrocytoma II meeting the above criteria, the prognosis was also better than in those not meeting those criteria. The IDH1 mutation appears more relevant for the prognosis than MGMT methylation. The IDH1 p.R132H mutation combined with MGMT hypermethylation seems to be the most advantageous for treatment success. Patients not meeting those criteria may require more aggressive treatments. PMID:27834917

  19. Non-Invasive Markers of Tumor Growth, Metastases, and Sensitivity to Anti-Neoplastic Therapy

    DTIC Science & Technology

    2009-01-01

    Public Release; Distribution Unlimited 13 . SUPPLEMENTARY NOTES 14. ABSTRACT The goals of this application are to develop methods to non...The data suggest that lactate is a potential surrogate for measuring tumor hypoxia in this model. 13 Table 1 Average lactate concentration...Lactate (mM/L) Avg # voxels Lactate (mM/L) Avg # voxels I 110-265 0 7 0 1 0 6 II 478-649 1.53 13 1.79 3 1.46 10 III 1035-1207 4.78 17 6.95

  20. Plasma DCLK1 is a marker of hepatocellular carcinoma (HCC): Targeting DCLK1 prevents HCC tumor xenograft growth via a microRNA-dependent mechanism

    PubMed Central

    May, Randal; Qu, Dongfeng; Ali, Naushad; Fazili, Javid; Weygant, Nathaniel; Chandrakesan, Parthasarathy; Ding, Kai; Lightfoot, Stanley A.; Houchen, Courtney W.

    2015-01-01

    Tumor stem cell marker Doublecortin-like kinase1 (DCLK1) is upregulated in several solid tumors. The role of DCLK1 in hepatocellular carcinoma (HCC) is unclear. We immunostained tissues from human livers with HCC, cirrhosis controls (CC), and non-cirrhosis controls (NCC) for DCLK1. Western blot and ELISA analyses for DCLK1 were performed with stored plasma samples. We observed increased immunoreactive DCLK1 in epithelia and stroma in HCC and CCs compared with NCCs, and observed a marked increase in plasma DCLK1 from patients with HCC compared with CC and NCC. Analysis of the Cancer Genome Atlas’ HCC dataset revealed that DCLK1 is overexpressed in HCC tumors relative to adjacent normal tissues. High DCLK1-expressing cells had more epithelial-mesenchymal transition (EMT). Various tumor suppressor miRNAs were also downregulated in HCC tumors. We evaluated the effects of DCLK1 knockdown on Huh7.5-derived tumor xenograft growth. This was associated with growth arrest and a marked downregulation of cMYC, and EMT transcription factors ZEB1, ZEB2, SNAIL, and SLUG via let-7a and miR-200 miRNA-dependent mechanisms. Furthermore, upregulation of miR-143/145, a corresponding decrease in pluripotency factors OCT4, NANOG, KLF4, and LIN28, and a reduction of let-7a, miR-143/145, and miR-200-specific luciferase activity was observed. These findings suggest that the detection of elevated plasma DCLK1 may provide a cost-effective, less invasive tool for confirmation of clinical signs of cirrhosis, and a potential companion diagnostic marker for patients with cirrhosis and HCC. Our results support evaluating DCLK1 as a biomarker for detection and as a therapeutic target for eradicating HCC. PMID:26468984

  1. Hypoxia in human colorectal adenocarcinoma: Comparison between extrinsic and potential intrinsic hypoxia markers

    SciTech Connect

    Goethals, Laurence; Debucquoy, Annelies; Perneel, Christiaan; Geboes, Karel; Ectors, Nadine; De Schutter, Harlinde; Penninckx, Freddy; McBride, William H.; Begg, Adrian C.; Haustermans, Karin M. . E-mail: karin.haustermans@uzleuven.be

    2006-05-01

    Purpose: To detect and quantify hypoxia in colorectal adenocarcinomas by use of pimonidazole and iododeoxyuridine (IdUrd) as extrinsic markers and carbonic anhydrase IX (CA IX), microvessel density (MVD), epidermal growth-factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as intrinsic markers of hypoxia. Methods and Material: Twenty patients with an adenocarcinoma of the left colon and rectum treated by primary surgery were injected with pimonidazole and IdUrd. Serial sections of tumor biopsies were single stained for VEGF, EGFR, Ki67, and double stained for blood vessels in combination with either pimonidazole, IdUrd, or CA IX. Percentage of expression was scored as well as colocalization of pimonidazole with CA IX. Results: The median percentage of hypoxia, as judged by pimonidazole staining, was 16.7% (range, 0-52.4%). The expression of pimonidazole correlated inversely with the total MVD and endothelial cord MVD (R = -0.55, p = 0.01; R = -0.47, p = 0.04). Good colocalization was found between pimonidazole and CA IX in only 30% of tumors, with no correlation overall between pimonidazole and CA IX, VEGF, or EGFR or between the different intrinsic markers. Cells around some vessels (0.08-11%) were negative for IdUrd but positive for Ki 67, which indicated their lack of perfusion at the time of injection. Conclusion: Chronic and acute hypoxic regions are present in colorectal tumors, as shown by pimonidazole and IdUrd staining. Only in a minority of tumors did an association exist between the areas stained by pimonidazole and those positive for CA IX. Pimonidazole also did not correlate with expression of other putative intrinsic hypoxia markers (VEGF, EGFR)

  2. Endosomal recycling regulates Anthrax Toxin Receptor 1/Tumor Endothelial Marker 8-dependent cell spreading.

    PubMed

    Gu, Jingsheng; Faundez, Victor; Werner, Erica

    2010-07-15

    Mechanisms for receptor-mediated anthrax toxin internalization and delivery to the cytosol are well understood. However, far less is known about the fate followed by anthrax toxin receptors prior and after cell exposure to the toxin. We report that Anthrax Toxin Receptor 1/Tumor Endothelial Marker 8 (TEM8) localized at steady state in Rab11a-positive and transferrin receptor-containing recycling endosomes. TEM8 followed a slow constitutive recycling route of approximately 30min as determined by pulsed surface biotinylation and chase experiments. A Rab11a dominant negative mutant and Myosin Vb tail expression impaired TEM8 recycling by sequestering TEM8 in intracellular compartments. Sequestration of TEM8 in intracellular compartments with monensin coincided with increased TEM8 association with a multi-protein complex isolated with antibodies against transferrin receptor. Addition of the cell-binding component of anthrax toxin, Protective Antigen, reduced TEM8 half-life from 7 to 3 hours, without preventing receptor recycling. Pharmacological and molecular perturbation of recycling endosome function using monensin, dominant negative Rab11a, or myosin Vb tail, reduced PA binding efficiency and TEM8-dependent cell spreading on PA-coated surfaces without affecting toxin delivery to the cytosol. These results indicate that the intracellular fate of TEM8 differentially affect its cell adhesion and cell intoxication functions.

  3. Clinical Significance of Serum IL-12 Level in Patients with Early Breast Carcinoma and Its Correlation with Other Tumor Markers

    PubMed Central

    Youssef, Samar Samir; Mohammad, Manal Moussa; Ezz-El-Arab, Lobna R.

    2015-01-01

    AIM: To investigate the diagnostic significance of Interleukin 12 (IL-12) in breast cancer (BC) and its correlation with other tumor markers including cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and MMP9/TIMP1 ratio. METHODS: Serum levels of IL-12, tumor markers, and hormone receptors were measured in 92 BC and 56 benign lesion patients versus 40 healthy subjects. Clinical stage, tumor size, lymph node metastasis, grade, and histological type were recorded. RESULTS: BC patients have lower IL-12, but higher CA 15.3 and CEA than control group. High levels of serum IL-12 were associated with lymph node positivity and progesterone receptor negativity. IL-12 was significant lower in invasive ductal carcinoma (IDC) compared to non IDC histological type. IL-12 was higher in patients with higher stage and grade but the difference was not statistically significant. IL-12 correlates negatively with MMP9/TIMP1 ratio. CONCLUSION: IL-12 is less specific than CEA for screening early BC, but its correlation with tumor aggressiveness and progression markers may have a prognostic value. PMID:27275301

  4. May Sonic Hedgehog proteins be markers for malignancy in uterine smooth muscle tumors?

    PubMed

    Garcia, Natalia; Bozzini, Nilo; Baiocchi, Glauco; da Cunha, Isabela Werneck; Maciel, Gustavo Arantes; Soares Junior, José Maria; Soares, Fernando Augusto; Baracat, Edmund Chada; Carvalho, Katia Candido

    2016-04-01

    Several studies have demonstrated that the Sonic Hedgehog signaling pathway (SHH) plays an important role in tumorigenesis and cellular differentiation. We analyzed the protein expression of SHH pathway components and evaluated whether their profile could be useful for the diagnosis, prognosis, or prediction of the risk of malignancy for uterine smooth muscle tumors (USMTs). A total of 176 samples (20 myometrium, 119 variants of leiomyoma, and 37 leiomyosarcoma) were evaluated for the protein expression of the SHH signaling components, HHIP1 (SHH inhibitor), and BMP4 (SHH target) by immunohistochemistry. Western blot analysis was performed to verify the specificity of the antibodies. We grouped leiomyoma samples into conventional leiomyomas and unusual leiomyomas that comprise atypical, cellular, mitotically active leiomyomas and uterine smooth muscle tumors of uncertain malignant potential. Immunohistochemical analysis showed that SMO, SUFU, GLI1, GLI3, and BMP4 expression gradually increased depending on to the histologic tissue type. The protein expression of SMO, SUFU, and GLI1 was increased in unusual leiomyoma and leiomyosarcoma samples compared to normal myometrium. The inhibitor HHIP1 showed higher expression in myometrium, whereas only negative or basal expression of SMO, SUFU, GLI1, and GLI3 was detected in these samples. Strong expression of SHH was associated with poorer overall survival. Our data suggest that the expression of SHH proteins can be useful for evaluating the potential risk of malignancy for USMTs. Moreover, GLI1 and SMO may serve as future therapeutic targets for women with USMTs.

  5. 2D/4D marker-free tumor tracking using 4D CBCT as the reference image.

    PubMed

    Wang, Mengjiao; Sharp, Gregory C; Rit, Simon; Delmon, Vivien; Wang, Guangzhi

    2014-05-07

    Tumor motion caused by respiration is an important issue in image-guided radiotherapy. A 2D/4D matching method between 4D volumes derived from cone beam computed tomography (CBCT) and 2D fluoroscopic images was implemented to track the tumor motion without the use of implanted markers. In this method, firstly, 3DCBCT and phase-rebinned 4DCBCT are reconstructed from cone beam acquisition. Secondly, 4DCBCT volumes and a streak-free 3DCBCT volume are combined to improve the image quality of the digitally reconstructed radiographs (DRRs). Finally, the 2D/4D matching problem is converted into a 2D/2D matching between incoming projections and DRR images from each phase of the 4DCBCT. The diaphragm is used as a target surrogate for matching instead of using the tumor position directly. This relies on the assumption that if a patient has the same breathing phase and diaphragm position as the reference 4DCBCT, then the tumor position is the same. From the matching results, the phase information, diaphragm position and tumor position at the time of each incoming projection acquisition can be derived. The accuracy of this method was verified using 16 candidate datasets, representing lung and liver applications and one-minute and two-minute acquisitions. The criteria for the eligibility of datasets were described: 11 eligible datasets were selected to verify the accuracy of diaphragm tracking, and one eligible dataset was chosen to verify the accuracy of tumor tracking. The diaphragm matching accuracy was 1.88 ± 1.35 mm in the isocenter plane and the 2D tumor tracking accuracy was 2.13 ± 1.26 mm in the isocenter plane. These features make this method feasible for real-time marker-free tumor motion tracking purposes.

  6. High Infiltration of Polarized CD163+ Tumor-Associated Macrophages Correlates with Aberrant Expressions of CSCs Markers, and Predicts Prognosis in Patients with Recurrent Gastric Cancer

    PubMed Central

    Zhang, Wei-jie; Zhou, Zhi-hua; Guo, Ming; Yang, Liu-qing; Xu, Yuan-yuan; Pang, Tao-hong; Gao, Shan-ting; Xu, Xin-yun; Sun, Qi; Feng, Min; Wang, Hao; Lu, Chun-lei; Wu, Guo-zhong; Guan, Wen-xian; Xu, Gui-fang

    2017-01-01

    Background: As the most predominant tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) are associated with poor outcome in multiple solid cancers and play important roles in cancer progression. Cancer stem cells (CSCs) may account for metastasis and recurrence after cancer therapy. However, the association between TAMs and CSCs is not clarified in gastric cancer (GC). The aim of the present study was to evaluate the effects of TAMs on CSCs in GC and find out the risk factors to predict recurrence and prognosis. Material and methods: This study included consecutive 236 patients with histologically confirmed primary GC. TAMs marker CD163 and CSCs-related proteins were detected by immunohistochemistry (IHC) in GC tissues and their prognostic values were all investigated. Results: High expression of CD163+ TAMs was found in patents with aggressive characteristics, especially for patents with recurrence. There existed a significant correlation between high expression of CD163 and CSCs-related markers in GC tissues. In patients with recurrence, high-expression of CD163 TAMs was an independent worse prognostic factor. Conclusion: High infiltration of TAMs was related to aggressive behavior, associated with aberrant expression of CSC markers, and an independent worse prognostic factor in GC. Targeting TAMs may be a potential treatment strategy for GC, including patients with recurrence. PMID:28261336

  7. Quantitative Assessment of Tumor Associated Macrophages in Head and Neck Squamous Cell Carcinoma Using CD68 Marker: An Immunohistochemical Study

    PubMed Central

    Bagul, Neeta; Roy, Souparna; Ganjre, Anjali; Meher, Aishwarya; Singh, Pratibha

    2016-01-01

    Introduction Oral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers in India. Clear evidence regarding inflammation being an etiological factor of cancer was found only in the last few decades. A major inflammatory component in the tumor tissue is Tumor-Associated Macrophages (TAMs). The CD68 antibody is a marker for staining TAMs. Aim The aim of this study is to quantify the macrophage count in healthy oral mucosa and OSCC and comparing TAMs in different histopathological grades of OSCC immunohistochemically. Materials and Methods Thirty archival specimens of OSCC patients and 10 healthy biopsy samples were collected. Immunohistochemical staining was done using a CD68 marker. Statistical analysis was done using Kruskal-Wallis ANOVA and Mann-Whitney U test. Results Comparing CD68 expression in various study groups showed a significant difference (p=0.000). The pair-wise analysis showed different grades of OSCC, which differed significantly for CD68 expression from the normal oral mucosa. Conclusion The most significant cells present in tumor stroma are TAMs, which remain in close proximity to neoplastic cells and interact with them via several chemical mediators, which may serve to increase the invasiveness of the malignant epithelium. Dense infiltration of TAMs adjacent to tumor cells and islands vividly implies their role in tumor progression. PMID:27190959

  8. Evaluation of Lumipulse® G1200 for the measurement of six tumor markers: Comparison with AIA® 2000.

    PubMed

    de Rancher, Marie-Aude Robert; Oudart, Jean-Baptiste; Maquart, François-Xavier; Monboisse, Jean Claude; Ramont, Laurent

    2016-11-01

    Tumor marker assays are daily practiced, for screening and follow up of cancers. Interassay precision is an important parameter for the interpretation of the kinetics of the markers, in order to conclude to the efficiency or failure of treatment. The aim of this study was to compare two automated Immunoassay analyzers, Lumipulse® G1200 and AIA® 2000. Both analyzers used an immunoassay system but with different antibodies. Six tumor markers commonly used were studied: AFP, PSA, CA 19-9, CA 15-3, CA 125 and CEA. 253 samples have been collected over a period of one month and analyzed by both analyzers. Regression of Passing-Badblock and Bland-Altman diagram were used to analyze the results for AFP (n=36), PSA (n=39), CA-125 (n=40), CA 15-3 (n=40), CA 19-9 (n=46) and CEA (n=52) were performed. Analytical performances of Lumipulse® G1200 highlighted the good inter-run and intra-run precision of the analyzer. We obtained a good correlation coefficient between Lumipulse G1200® and AIA 2000®, >0.96 for most markers except CA 19-9 which provided a correlation coefficient significantly lower than that obtained with other markers. The concordance for all markers was >94% except for CA 19-9 (83.7%). This study showed a good correlation between the two analyzers and, therefore, a transfer from one analyzer to the other is possible for the different markers studied. However, we found here the classical difficulty to transfer this type of analysis, due to the absence of method standardization. This difficulty was particularly illustrated by CA19-9.

  9. Acne - a potential skin marker of internal disease.

    PubMed

    Pace, Joseph L

    2015-01-01

    Polycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in adult women. Hyperandrogenism is the crux of the pathogenesis of both acne and hirsutism, the most frequent clinical presentations of the syndrome. The chronic anovulation that may occur, often but not always associated with enlarged cystic ovaries, has long been recognized as an important feature of PCOS. In recent years major changes have occurred with regard to PCOS: Although management of the common cutaneous manifestations, mainly acne, hirsutism, alopecia, and acanthosis nigricans, remains strictly within the realm of daily dermatologic practice, the pendulum is shifting toward greater awareness of the longer-term systemic implications of PCOS, with emphasis on the unique opportunity and privileged position of the dermatologist to diagnose this potentially serious problem at an early stage, when effective long-term treatment can be instituted. Patients need to be advised that PCOS cannot be cured but can be controlled. Management should involve a multidisciplinary team with emphasis on lifestyle change, insulin sensitizing agents, androgen blockers, and attention to specific cutaneous manifestations.

  10. WE-AB-303-03: A Scheme for Real-Time, Marker-Less and Low-Dose Tumor Tracking Using Scattering Imaging: Monte Carlo Simulation Study

    SciTech Connect

    Yan, H; Medin, P; Jiang, S; Jia, X

    2015-06-15

    Purpose: In-treatment tumor localization is critical for the management of tumor motion in lung cancer radiotherapy. Conventional tumor-tracking methods using a kV or MV x-ray projection has limited contrast. To facilitate real-time, marker-less and low-dose in-treatment image tumor tracking, we propose a novel scheme using Compton scatter imaging. This study reports Monte Carlo (MC) simulations on this scheme for the purpose of proof-of-principle. Methods: A slit x-ray beam along the patient superior-inferior (SI) direction is directed to the patient, intersecting the patient lung at a 2D plane containing majority part of the tumor motion trajectory. X-ray photons are scattered due to Compton effect from this plane, which are spatially collimated by, e.g., a pinhole, on one side of the plane and then captured by a detector behind it. The captured image, after correcting for x-ray attenuation and scatter angle variation, reflects the electron density, which allows visualization of the instantaneous anatomy on this plane. We performed MC studies on a phantom and a patient case for the initial test of this proposed method. Results: In the phantom case, the contrast-resolution calculated using tumor/lung as foreground/background for kV fluoroscopy, cone-beam CT, and scattering image were 0.0625, 0.6993, and 0.5290, respectively. In the patient case, tumor motion can be clearly observed in the scatter images. Compared to fluoroscopy, scattering imaging also significantly reduced imaging dose because of its narrower beam design. Conclusion: MC simulation studies demonstrated the potential of the proposed scheme in terms of capturing the instantaneous anatomy of a patient on a 2D plane. Clear visualization of the tumor will probably facilitate ‘marker-less’ and ‘real-time’ tumor tracking with low imaging dose. NIH (1R01CA154747-01, 1R21CA178787-01A1 and 1R21EB017978-01A1)

  11. IDENTIFYING POTENTIAL MARKERS OF THE SUN'S GIANT CONVECTIVE SCALE

    SciTech Connect

    McIntosh, Scott W.; Wang, Xin; Leamon, Robert J.; Scherrer, Philip H.

    2014-04-01

    Line-of-sight magnetograms from the Helioseismic and Magnetic Imager (HMI) of the Solar Dynamics Observatory (SDO) are analyzed using a diagnostic known as the magnetic range of influence (MRoI). The MRoI is a measure of the length over which a photospheric magnetogram is balanced and so its application gives the user a sense of the connective length scales in the outer solar atmosphere. The MRoI maps and histograms inferred from the SDO/HMI magnetograms primarily exhibit four scales: a scale of a few megameters that can be associated with granulation, a scale of a few tens of megameters that can be associated with super-granulation, a scale of many hundreds to thousands of megameters that can be associated with coronal holes and active regions, and a hitherto unnoticed scale that ranges from 100 to 250 Mm. We infer that this final scale is an imprint of the (rotationally driven) giant convective scale on photospheric magnetism. This scale appears in MRoI maps as well-defined, spatially distributed concentrations that we have dubbed ''g-nodes''. Furthermore, using coronal observations from the Atmospheric Imaging Assembly on SDO, we see that the vicinity of these g-nodes appears to be a preferred location for the formation of extreme-ultraviolet (and likely X-Ray) brightpoints. These observations and straightforward diagnostics offer the potential of a near real-time mapping of the Sun's largest convective scale, a scale that possibly reaches to the very bottom of the convective zone.

  12. Tumor markers for diagnosis, monitoring of recurrence and prognosis in patients with upper gastrointestinal tract cancer.

    PubMed

    Jing, Jie-Xian; Wang, Yan; Xu, Xiao-Qin; Sun, Ting; Tian, Bao-Guo; Du, Li-Li; Zhao, Xian-Wen; Han, Cun-Zhi

    2014-01-01

    To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05). Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levels of CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasis and recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperative CA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combined detection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.

  13. Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

    SciTech Connect

    Roman, Nicholas O.; Shepherd, Wes; Mukhopadhyay, Nitai; Hugo, Geoffrey D.; Weiss, Elisabeth

    2012-08-01

    Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy-based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

  14. Microfluidic, marker-free isolation of circulating tumor cells from blood samples

    PubMed Central

    Karabacak, Nezihi Murat; Spuhler, Philipp S; Fachin, Fabio; Lim, Eugene J; Pai, Vincent; Ozkumur, Emre; Martel, Joseph M; Kojic, Nikola; Smith, Kyle; Chen, Pin-i; Yang, Jennifer; Hwang, Henry; Morgan, Bailey; Trautwein, Julie; Barber, Thomas A; Stott, Shannon L; Maheswaran, Shyamala; Kapur, Ravi; Haber, Daniel A; Toner, Mehmet

    2014-01-01

    The ability to isolate and analyze rare circulating tumor cells (CTCs) has the potential to further our understanding of cancer metastasis and enhance the care of cancer patients. In this protocol, we describe the procedure for isolating rare CTCs from blood samples by using tumor antigen–independent microfluidic CTC-iChip technology. The CTC-iChip uses deterministic lateral displacement, inertial focusing and magnetophoresis to sort up to 107 cells/s. By using two-stage magnetophoresis and depletion antibodies against leukocytes, we achieve 3.8-log depletion of white blood cells and a 97% yield of rare cells with a sample processing rate of 8 ml of whole blood/h. The CTC-iChip is compatible with standard cytopathological and RNA-based characterization methods. This protocol describes device production, assembly, blood sample preparation, system setup and the CTC isolation process. Sorting 8 ml of blood sample requires 2 h including setup time, and chip production requires 2–5 d. PMID:24577360

  15. Microfluidic, marker-free isolation of circulating tumor cells from blood samples.

    PubMed

    Karabacak, Nezihi Murat; Spuhler, Philipp S; Fachin, Fabio; Lim, Eugene J; Pai, Vincent; Ozkumur, Emre; Martel, Joseph M; Kojic, Nikola; Smith, Kyle; Chen, Pin-i; Yang, Jennifer; Hwang, Henry; Morgan, Bailey; Trautwein, Julie; Barber, Thomas A; Stott, Shannon L; Maheswaran, Shyamala; Kapur, Ravi; Haber, Daniel A; Toner, Mehmet

    2014-03-01

    The ability to isolate and analyze rare circulating tumor cells (CTCs) has the potential to further our understanding of cancer metastasis and enhance the care of cancer patients. In this protocol, we describe the procedure for isolating rare CTCs from blood samples by using tumor antigen-independent microfluidic CTC-iChip technology. The CTC-iChip uses deterministic lateral displacement, inertial focusing and magnetophoresis to sort up to 10⁷ cells/s. By using two-stage magnetophoresis and depletion antibodies against leukocytes, we achieve 3.8-log depletion of white blood cells and a 97% yield of rare cells with a sample processing rate of 8 ml of whole blood/h. The CTC-iChip is compatible with standard cytopathological and RNA-based characterization methods. This protocol describes device production, assembly, blood sample preparation, system setup and the CTC isolation process. Sorting 8 ml of blood sample requires 2 h including setup time, and chip production requires 2-5 d.

  16. Label-free detection of tumor markers in a colon carcinoma tumor progression model by confocal Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Scalfi-Happ, Claudia; Rück, Angelika; Udart, Martin; Hauser, Carmen; Dürr, Christine; Kriebel, Martin

    2013-06-01

    Living colon carcinoma cells were investigated by confocal Raman microspectroscopy. An in vitro model of tumor progression was established. Evaluation of data sets by cluster analysis reveals that lipid bodies might be a valuable diagnostic parameter for early carcinogenesis.

  17. A multiplexed marker-based algorithm for diagnosis of carcinoma of unknown primary using circulating tumor cells

    PubMed Central

    Yang, Zhaohai; Dicker, David T.; Holder, Sheldon L.; Lim, Bora; Harouaka, Ramdane; Zheng, Si-Yang; Drabick, Joseph J.; Lamparella, Nicholas E.; Truica, Cristina I.; El-Deiry, Wafik S.

    2016-01-01

    Real-time, single-cell multiplex immunophenotyping of circulating tumor cells (CTCs) is hypothesized to inform diagnosis of tissue of origin in patients with carcinoma of unknown primary (CUP). In 20 to 50% of CUP patients, the primary site remains unidentified, presenting a challenge for clinicians in diagnosis and treatment. We developed a post-CellSearch CTC assay using multiplexed Q-dot or DyLight conjugated antibodies with the goal of detecting multiple markers in single cells within a CTC population. We adapted our approach to size-based CTC enrichment protocols for capturing CTCs and subsequent immunofluorescence (IF) using a minimal set of markers to predict the primary sites for common metastatic tumors. The carcinomas are characterized with cytokeratin 7 (CK7), cytokeratin 20 (CK20), thyroid transcription factor 1 (TTF-1), estrogen receptor (ER) or prostate-specific antigen (PSA. IF has been optimized in cultured tumor cells with individual antibodies, then with conjugated antibodies to form a multiplex antibody set. With IF, we evaluated antibodies specific to these 5 markers in lung, breast, colorectal, and prostate cancer cell lines and blood from metastatic prostate and breast cancer patients. This advanced technology provides a noninvasive, diagnostic blood test as an adjunct to routine tissue biopsy. Its further implementation requires prospective clinical testing. PMID:26695546

  18. Lycopersicon esculentum lectin: an effective and versatile endothelial marker of normal and tumoral blood vessels in the central nervous system.

    PubMed

    Mazzetti, S; Frigerio, S; Gelati, M; Salmaggi, A; Vitellaro-Zuccarello, L

    2004-01-01

    The binding of Lycopersicon esculentum lectin (LEA) to the vascular endothelium was studied in the central nervous system of rat, mouse and guinea pig at different developmental ages, and in a gliosarcoma model. Our observations showed that LEA consistently stained the entire vascular tree in the spinal cord and in the brain of all animal species at all developmental ages investigated. In the tumor model, the staining of the vascular network was very reproducible, enabled an easy identification of vascular profiles and displayed a higher efficiency when compared to two other commonly used vascular marker (EHS laminin and PECAM-1). Moreover, our results showed that LEA staining was comparable in both vibratome and paraffin sections and could be easily combined with other markers in double labeling experiments. These observations indicate that LEA staining may represent an effective and versatile endothelial marker for the study of the vasculature of the central nervous system in different animal species and experimental conditions.

  19. An investigation of the potential of DIP-STR markers for DNA mixture analyses.

    PubMed

    Cereda, G; Biedermann, A; Hall, D; Taroni, F

    2014-07-01

    The genetic characterization of unbalanced mixed stains remains an important area where improvement is imperative. In fact, using the standard tools of forensic DNA profiling (i.e., STR markers), the profile of the minor contributor in mixed DNA stains cannot be successfully detected if its quantitative share of DNA is less than 10% of the mixed trace. This is due to the fact that the major contributor's profile "masks" that of the minor contributor. Besides known remedies to this problem, such as Y-STR analysis, a new compound genetic marker that consists of a Deletion/Insertion Polymorphism (DIP) linked to a Short Tandem Repeat (STR) polymorphism, has recently been developed and proposed. These novel markers are called DIP-STR markers. This paper compares, from a statistical and forensic perspective, the potential usefulness of these novel DIP-STR markers (i) with traditional STR markers in cases of moderately unbalanced mixtures, and (ii) with Y-STR markers in cases of female-male mixtures. This is done through a comparison of the distribution of 100,000 likelihood ratio values obtained using each method on simulated mixtures. This procedure is performed assuming, in turn, the prosecution's and the defence's point of view.

  20. Cyst fluid NB/70K concentration and leukocyte esterase: two new markers for differentiating pancreatic serous tumors from pseudocysts.

    PubMed

    Yong, W H; Southern, J F; Pins, M R; Warshaw, A L; Compton, C C; Lewandrowski, K B

    1995-05-01

    Cystic lesions of the pancreas include inflammatory pseudocysts, serous cystadenomas, and mucinous tumors, some of which are malignant. Preoperative clinical and radiological parameters are unreliable and may result in incorrect diagnosis and inappropriate treatment. Cyst fluid analysis for cytology, viscosity, carcino-embryonic antigen, CA 72-4, and CA 15-3 will distinguish mucinous from nonmucinous lesions and usually help in determining malignancy. Currently, there is no reliable method to differentiate inflammatory pseudocysts from serous cystadenomas. This distinction is important because the treatment of these two lesions is different; pseudocysts are either observed or drained, whereas serous tumors are usually resected. The tumor marker NB/70K was measured in aspirated cyst fluid from 13 inflammatory pseudocysts and 11 serous cystadenomas by a commercial immunoassay. Leukocyte esterase was measured using Chemstrip SG urine test strips and amylase and lipase on a routine chemistry analyzer. The cyst fluid NB/70K concentration was significantly higher in pseudocysts (mean, 555 U/ml; range, 42-1,926 U/ml) than in serous cystadenomas (mean, 12 U/ml; range 0-130 U/ml) and this difference was significant (p < 0.0002). Leukocyte esterase was detected in 7 of 11 pseudocysts but was absent in 10 of 10 serous tumors (p = 0.002). Amylase and lipase values were generally higher in pseudocysts but these markers were unreliable due to marked outliers. Cyst fluid NB/70K and leukocyte esterase are promising markers to help differentiate pseudocysts from serous tumors on percutaneous aspirates. When combined with previously reported cyst fluid parameters (amylase, lipase, cytology, and amylase isoenzymes), these two cystic lesions can be reliably distinguished.

  1. Mutations in p53 as potential molecular markers for human breast cancer

    SciTech Connect

    Runnebaum, I.B.; Nagarajan, M.; Bowman, M.; Soto, D.; Sukumar, S. )

    1991-12-01

    Based on the high incidence of loss of heterozygosity for loci on chromosome 17p in the vicinity of the p53 locus in human breast tumors. The authors investigated the frequency and effects of mutations in the p53 tumor suppressor gene in mammary neoplasia. They examined the p53 gene in 20 breast cancer cell lines and 59 primary breast tumors. Northern blot analysis, immunoprecipitation, and nucleotide sequencing analysis revealed aberrant mRNA expression, over-expression of protein, and point mutations in the p53 gene in 50% of the cell line tested. A multiplex PCR assay was developed to search for deletions in the p53 genomic locus. Multiplex PCR of genomic DNA showed that up to 36% of primary tumors contained aberrations in the p53 locus. Mutations in exons 5-9 of the p53 gene were found in 10 out of 59 (17%) of the primary tumors studied by single-stranded conformation polymorphism analysis. They conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene. Correlated to disease status, p53 gene mutations could prove to be a valuable marker for diagnosis and/or prognosis of breast neoplasia.

  2. Is CRX protein a useful marker in differential diagnosis of tumors of the pineal region?

    PubMed

    Manila, Antonelli; Mariangela, Novello; Libero, Lauriola; Francesca, Gianno; Romana, Buttarelli Francesca; Felice, Giangaspero

    2014-01-01

    The cone-rod homeobox (CRX) is a gene that belongs to the member of the orthodenticle homeobox (Otx) family, with important function in development and differentiation of retinal and pineal cells. Moreover, CRX appears to be specifically expressed in pineal tumors and retinoblastomas. We performed an immunohistochemical study on 91 pediatric and adult central nervous system tumors, plus 2 normal brain samples. Our results demonstrated that CRX is expressed not only in pineal parenchymal tumors and retinoblastoma, but also in a some medulloblastomas and supratentorial primitive neuroectodermal tumors. None of the glial tumors screened were positive for CRX. In conclusion, CRX could be useful in surgical neuropathology for the differential diagnosis of pineal region tumors, in particular to discriminate pineal tumors from glial tumors.

  3. A method of surface marker location optimization for tumor motion estimation in lung stereotactic body radiation therapy

    SciTech Connect

    Lu, Bo Park, Justin C.; Fan, Qiyong; Kahler, Darren; Liu, Chihray; Chen, Yunmei

    2015-01-15

    Purpose: Accurately localizing lung tumor localization is essential for high-precision radiation therapy techniques such as stereotactic body radiation therapy (SBRT). Since direct monitoring of tumor motion is not always achievable due to the limitation of imaging modalities for treatment guidance, placement of fiducial markers on the patient’s body surface to act as a surrogate for tumor position prediction is a practical alternative for tracking lung tumor motion during SBRT treatments. In this work, the authors propose an innovative and robust model to solve the multimarker position optimization problem. The model is able to overcome the major drawbacks of the sparse optimization approach (SOA) model. Methods: The principle-component-analysis (PCA) method was employed as the framework to build the authors’ statistical prediction model. The method can be divided into two stages. The first stage is to build the surrogate tumor matrix and calculate its eigenvalues and associated eigenvectors. The second stage is to determine the “best represented” columns of the eigenvector matrix obtained from stage one and subsequently acquire the optimal marker positions as well as numbers. Using 4-dimensional CT (4DCT) and breath hold CT imaging data, the PCA method was compared to the SOA method with respect to calculation time, average prediction accuracy, prediction stability, noise resistance, marker position consistency, and marker distribution. Results: The PCA and SOA methods which were both tested were on all 11 patients for a total of 130 cases including 4DCT and breath-hold CT scenarios. The maximum calculation time for the PCA method was less than 1 s with 64 752 surface points, whereas the average calculation time for the SOA method was over 12 min with 400 surface points. Overall, the tumor center position prediction errors were comparable between the two methods, and all were less than 1.5 mm. However, for the extreme scenarios (breath hold), the

  4. Synthetic-fuel plants: potential tumor risks to public health.

    PubMed

    Moskowitz, P D; Morris, S C; Fischer, H; Thode, H C; Hamilton, L D

    1985-09-01

    This article quantifies potential public health risks from tumor-producing pollutants emitted from two synthetic-fuel plants (direct liquefaction--Exxon Donor Solvent: and indirect liquefaction--Lurgi Fischer-Tropsch) located at a representative site in the eastern United States. In these analyses gaseous and aqueous waste streams were characterized; exposures via inhalation, terrestrial and aquatic food chains, and drinking water supplies were modeled. Analysis suggested that emissions of "polycyclic aromatic hydrocarbons," "aromatic amines," "neutral N, O, S heterocyclics," "nitriles," and "other trace elements" pose the largest quantifiable risks to public health. Data and analysis for these pollutant categories should be refined to more accurately match compound-specific estimated exposure levels with tumorigenic potency estimates. Before these results are used for regulatory purposes, more detailed analysis for selected pollutant classes are needed, and more sophisticated aquatic exposure models must be developed. Also, differences in geographic scales among the environmental transport models used need to be rectified.

  5. Multiplexed sandwich immunoassays using flow-injection electrochemiluminescence with designed substrate spatial-resolved technique for detection of tumor markers.

    PubMed

    Zhang, Yan; Liu, Weiyan; Ge, Shenguang; Yan, Mei; Wang, Shaowei; Yu, Jinghua; Li, Nianqiang; Song, Xianrang

    2013-03-15

    Convenient sensor array for simultaneous multi-analyte testing was increasingly needed in clinical diagnosis. A novel electrochemiluminescence (ECL) immunosensor array for the sequential detection of multiple tumor markers was developed by site-selectively immobilizing multiple antigens on different electrodes. Disposable indium tin oxide (ITO) glass array was employed as detection platform. With a sandwich-type immunoassay format, the amount of carbon dots coated silica (SiO(2)@C-dots) labeled antibodies increased with the increment of antigens in the samples. The ECL signal from different immunosensors was collected in turn by a photomultiplier (PMT) with the aid of a home-made potential transformer equiped with a home-made multiplexed-switch. Using carcino embryonic antigen (CEA), prostate specific antigen (PSA) and α-fetoprotein (α-AFP) as model analytes, the proposed immunoassay exhibited excellent precision and sensitivity. For all three analytes, the relative standard deviations (RSDs) for six times detection were lower than 7.1% and the detection limits were in the range of 0.003-0.006 ng mL(-1). The results for real sample analysis demonstrated that the newly constructed immunosensor array provided a rapid, simple, simultaneous multi-analyte immunoassay with high throughput, cost-effective and sufficiently low detection limits for clinical applications. Importantly, the novel individually addressable immunosensor array for multi-analyte immunoassay by introducing the ECL readout mechanism with the aid of the home-made potential transformer and multiplexed-switch could be a useful supplement to commercial assay methods in clinical chemistry.

  6. Small renal masses: The molecular markers associated with outcome of patients with kidney tumors 7 cm or less

    NASA Astrophysics Data System (ADS)

    Spirina, L. V.; Usynin, Y. A.; Kondakova, I. V.; Yurmazov, Z. A.; Slonimskaya, E. M.; Pikalova, L. V.

    2016-08-01

    The investigation of molecular mechanisms of tumor cell behavior in small renal masses is required to achieve the better cancer survival. The aim of the study is to find molecular markers associated with outcome of patients with kidney tumors 7 cm or less. A homogenous group of 20 patients T1N0M0-1 (mean age 57.6 ± 2.2 years) with kidney cancer was selected for the present analysis. The content of transcription and growth factors was determined by ELISA. The levels of AKT-mTOR signaling pathway components were measured by Western blotting analysis. The molecular markers associated with unfavorable outcome of patients with kidney tumors 7 cm or less were high levels of NF-kB p50, NF-kB p65, HIF-1, HIF-2, VEGF and CAIX. AKT activation with PTEN loss also correlated with the unfavorable outcome of kidney cancer patients with tumor size 7 cm or less. It is observed that the biological features of kidney cancer could predict the outcome of patients.

  7. Senescence marker protein 30 (SMP30)/regucalcin (RGN) expression decreases with aging, acute liver injuries and tumors in zebrafish

    SciTech Connect

    Fujisawa, Koichi; Terai, Shuji; Hirose, Yoshikazu; Takami, Taro; Yamamoto, Naoki; Sakaida, Isao

    2011-10-22

    Highlights: {yields} Zebrafish SMP30/RGN mRNA expression decreases with aging. {yields} Decreased expression was observed in liver tumors as compared to the surrounding area. {yields} SMP30/RGN is important for liver proliferation and tumorigenesis. -- Abstract: Senescence marker protein 30 (SMP30)/regucalcin (RGN) is known to be related to aging, hepatocyte proliferation and tumorigenesis. However, expression and function of non-mammalian SMP30/RGN is poorly understood. We found that zebrafish SMP30/RGN mRNA expression decreases with aging, partial hepatectomy and thioacetamide-induced acute liver injury. SMP30/RGN expression was also greatly decreased in a zebrafish liver cell line. In addition, we induced liver tumors in adult zebrafish by administering diethylnitrosamine. Decreased expression was observed in foci, hepatocellular carcinomas, cholangiocellular carcinomas and mixed tumors as compared to the surrounding area. We thus showed the importance of SMP30/RGN in liver proliferation and tumorigenesis.

  8. False positive tumor markers: elevation in patients with breast cancer on FAC-type chemotherapy and correlation with the development of hand-foot syndrome.

    PubMed

    Tyshler, L B; Longton, G M; Ellis, G K; Livingston, R B

    1996-01-01

    Breast cancer patients on dose-intensive chemotherapy often have elevated tumor markers during the course of treatment. Our objective was to estimate the incidence of a "false positive" tumor marker screen and to determine whether hand-foot epithelial damage was correlated. Data from 53 patients with high risk primary breast cancer who had undergone adjuvant or neoadjuvant 5FU-containing chemotherapy (FAC or FAC plus G-CSF) for 3 to 12 months were reviewed. The relationship between tumor marker elevation and disease recurrence, regimen intensity, and the occurrence of hand-foot syndrome was examined. Thirty-three of the 53 patients had elevated tumor markers in the absence of recurrent disease. The false positive rate was higher in patients who underwent FAC plus G-CSF chemotherapy than in patients who underwent FAC chemotherapy (92% vs 55%, p = .01). A false positive marker screen was associated with the occurrence of hand-foot syndrome even when the effect of regimen was accounted for by stratification (p = .01). Tumor marker screening of breast cancer patients on this type of adjuvant chemotherapy has poor specificity for recurrent malignancy. These data suggest tumor marker elevation may be an indicator of epithelial toxicity during chemotherapy, manifested clinically as hand-foot syndrome.

  9. The effects of tumor location on diagnostic criteria for canine malignant peripheral nerve sheath tumors (MPNSTs) and the markers for distinction between canine MPNSTs and canine perivascular wall tumors.

    PubMed

    Suzuki, S; Uchida, K; Nakayama, H

    2014-07-01

    Canine malignant peripheral nerve sheath tumors (MPNSTs) occur not only in the peripheral nervous system (PNS) but also in soft tissue and various organs (non-PNS). The most important diagnostic criterion is proof of peripheral nerve sheath origin. This is difficult in non-PNS MPNSTs, and its differential diagnosis is challenging. Canine perivascular wall tumors (PWTs) also commonly arise in soft tissue. Their histopathological features are quite similar to those of canine MPNSTs, making their differential diagnosis challenging. To elucidate whether the morphological features are applicable to diagnose non-PNS MPNSTs and to demonstrate useful markers for distinction between canine MPNSTs and PWTs, the authors examined 30 canine MPNSTs and 31 PWTs immunohistochemically for S100, nestin, NGFR, Olig2, claudin-1, CD57, PRX, α-SMA, desmin, and calponin. Among canine MPNSTs, the PNS tumors displayed significantly higher S100 and Olig2 expression than the non-PNS tumors. The expression levels of the other markers did not differ significantly, suggesting that the same morphological diagnostic criteria are applicable regardless of their location. The PWT cells displayed significantly weaker immunoreactivity than MPNSTs to markers used except α-SMA and desmin. Cluster analysis sorted most canine MPNSTs and PWTs into 2 distinctly different clusters, whereas 3 MPNSTs and 6 PWTs were assigned to the opposing cluster. These 3 MPNSTs were negative for almost all markers, while these 6 PWTs were positive for only neuronal markers. In particular, NGFR and Olig2 were almost negative in the rest of PWT cases. These findings suggest that NGFR and Olig2 are useful to distinguish these 2 tumors.

  10. Evaluation of Tumor Shape Variability in Head-and-Neck Cancer Patients Over the Course of Radiation Therapy Using Implanted Gold Markers

    SciTech Connect

    Hamming-Vrieze, Olga; Kranen, Simon Robert van; Beek, Suzanne van; Heemsbergen, Wilma; Herk, Marcel van; Brekel, Michiel Wilhelmus Maria van den; Sonke, Jan-Jakob; Rasch, Coenraad Robert Nico

    2012-10-01

    Purpose: This study quantifies tumor shape variability in head-and-neck cancer patients during radiation therapy using implanted markers. Methods and Materials: Twenty-seven patients with oropharyngeal tumors treated with (chemo)radiation were included. Helical gold markers (0.35 Multiplication-Sign 2 mm, 3-10/patient, average 6) were implanted around the tumor. Markers were identified on planning computed tomography (CT) and daily cone beam CT (CBCT). After bony anatomy registration, the daily vector length on CBCT in reference to the planning CT and daily marker movement perpendicular to the gross tumor volume (GTV) surface at planning CT (d{sub normal}) of each marker were analyzed. Time trends were assessed with linear regression of the {sub markers}. In 2 patients, 2 markers were implanted in normal tissue to evaluate migration by measuring intermarker distances. Results: Marker implantation was feasible without complications. Three-dimensional vectors (4827 measurements, mean 0.23 cm, interquartile ratio 0.24 cm) were highest in base of tongue sublocalization (P<.001) and bulky tumors (vectors exceeded 0.5 cm in 5.7% [0-20 mL], 12.0% [21-40 mL], and 21.7% [{>=}41 mL], respectively [P<.001] of measurements). The measured inward time trend in 11/27 patients correlated with the visual observed marker pattern. In patients with an outward trend (5/27) or no trend (11/27), visual observation showed predominantly an inhomogeneous pattern. Remarkably, in 6 patients, outward marker movement was observed in the posterior pharyngeal wall. The difference in distance between normal tissue markers (1 SD) was 0.05-0.06 cm without time trend, indicating that implanted markers did not migrate. Conclusions: During head-and-neck radiation therapy, normal tissue markers remained stable. Changes in position of tumor markers depended on sublocalization and tumor volume. Large differences in marker patterns between patients as well as within patients were observed

  11. Comparison of the value of PCNA and Ki-67 as markers of cell proliferation in ameloblastic tumor

    PubMed Central

    Mosqueda-Taylor, Adalberto; Molina-Frechero, Nelly; Mori-Estevez, Ana D.; Sánchez-Acuña, Guillermo

    2013-01-01

    Objectives: The aim of this study was to compare among PCNAand Ki-67 as the most reliable immunohistochemical marker for evaluating cell proliferation in ameloblastic tumors. Study Design: Observational, retrospective, and descriptive study of a large series of ameloblastic tumors, composed of 161 ameloblastomas and four ameloblastic carcinomas, to determine and compare PCNA and Ki-67 expression using immunohistochemistry techniques. Results: When analyzing Ki-67 positivity, the desmoplastic ameloblastoma demonstrated a significantly lower proliferation rate (1.9%) compared with the solid/multicystic and unicystic ameloblastomas and ameloblastic carcinomas (p<0.05), whereas the ameloblastic carcinomas displayed a significantly higher rate compared with all of the other ameloblastomas (48.7%) (p<0.05). When analyzing cell proliferation with PCNA, we found significant differences only between the ameloblastic carcinomas (93.3%) and the desmoplastic ameloblastomas (p<0.05). When differences between the immunopositivity for PCNA and Ki-67 were compared, the percentages were higher for PCNA in all types of ameloblastomas and ameloblastic carcinomas. In all cases, the percentages were greater than 80%, whereas the immunopositivity for Ki-67 was significantly lower; for example, the ameloblastic carcinoma expressed the highest positivity and only reached 48.7%, compared to 93.3% when we used PCNA. Conclusions: In the present study, when we used the proliferation cell marker Ki-67, the percentages of positivity were more specific and varied among the different types of ameloblastomas, suggesting that Ki-67 is a more specific marker for the proliferation of ameloblastic tumor cells. Key words:Ameloblastomas, ameloblastic carcinoma, PCNA, Ki-67, cell proliferation markers. PMID:23229269

  12. Identification of vascular breast tumor markers by laser capture microdissection and label-free LC-MS.

    PubMed

    Hill, Jennifer J; Tremblay, Tammy-Lynn; Pen, Ally; Li, Jie; Robotham, Anna C; Lenferink, Anne E G; Wang, Edwin; O'Connor-McCourt, Maureen; Kelly, John F

    2011-05-06

    Blood vessels in tumors frequently show abnormal characteristics, such as tortuous morphology or leakiness, but very little is known about protein expression in tumor vessels. In this study, we have used laser capture microdissection (LCM) to isolate microvessels from clinical samples of invasive ductal carcinoma (IDC), the most common form of malignant breast cancer, and from patient-matched adjacent nonmalignant tissue. This approach eliminates many of the problems associated with the heterogeneity of clinical tumor tissues by controlling for differences in protein expression between both individual patients and different cell types. Proteins from the microvessels were trypsinized and the resulting peptides were quantified by a label-free nanoLC-MS method. A total of 86 proteins were identified that are overexpressed in tumor vessels relative to vessels isolated from the adjacent nonmalignant tissue. These proteins include well-known breast tumor markers such as Periostin and Tenascin C but also proteins with lesser-known or emerging roles in breast cancer and tumor angiogenesis (i.e., Serpin H1, Clic-1, and Transgelin 2). We also identified 40 proteins that were relatively under-expressed in IDC tumor vessels, including several components of the basement membrane whose lower expression could be responsible for weakening tumor vessels. Lastly, we show that a subset of 29 proteins, derived from our list of differentially expressed proteins, is able to predict survival in three publicly available clinical breast cancer microarray data sets, which suggests that this subset of proteins likely plays a functional role in cancer progression and outcome.

  13. Changes in the tumor marker concentration in female patients with hyper-, eu-, and hypothyroidism.

    PubMed

    Hashimoto, T; Matsubara, F

    1989-12-01

    The levels of 6 circulating tumor markers were evaluated in a total of 131 female subjects with altered thyroid states; 36 normal subjects, 46 hyperthyroid patients with Graves' disease, and 49 primary hypothyroid patients. The mean CEA concentration was observed to be significantly higher (p less than 0.02) in hypothyroid patients than in normal and hyperthyroid patients (1.1 +/- 0.1 ng/ml, 0.8 +/- 0.1 ng/ml and 0.8 +/- 0.1 ng/ml, respectively). Similarly, the mean serum CA 125 concentration in hypothyroid patients was higher (p less than 0.02) than in normal and hyperthyroid patients (13.0 +/- 2.6 U/ml, 7.6 +/- 1.1 U/ml and 5.5 +/- 0.8 U/ml, respectively), and the mean serum CA 15-3 concentration in hypothyroid patients was significantly higher than in normal subjects (p less than 0.01) and hyperthyroid patients (p less than 0.001) (16.2 +/- 0.9 U/ml, 13.9 +/- 0.6 U/ml and 10.6 +/- 0.5 U/ml, respectively). No statistical difference was found in mean CA 19-9 in the three subject groups. AFP in the hypothyroid patients (3.6 +/- 0.3 ng/ml) was significantly higher (p less than 0.05) than in normal subjects (2.6 +/- 0.2 ng/ml) and hyperthyroid patients (1.7 +/- 0.2 ng/ml) (p less than 0.01). On the other hand, serum ferritin was low in the hypothyroid patients (65.9 8.0 ng/ml) and significantly increased (69.1 +/- 9.0 ng/ml) (p less than 0.02) with the normalization of thyroid function. In hyperthyroidism, serum ferritin (70.2 +/- 7.0 ng/ml) was significantly higher than in the hypothyroid patients (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. SIRT1 induces tumor invasion by targeting epithelial mesenchymal transition-related pathway and is a prognostic marker in triple negative breast cancer.

    PubMed

    Jin, Min-Sun; Hyun, Chang Lim; Park, In Ae; Kim, Ji Young; Chung, Yul Ri; Im, Seock-Ah; Lee, Kyung-Hun; Moon, Hyeong-Gon; Ryu, Han Suk

    2016-04-01

    Absence of therapeutic targets poses a critical hurdle in improving prognosis for patients with triple negative breast cancer (TNBC). We evaluated interaction between SIRT1 and epithelial mesenchymal transition (EMT)-associated proteins as well as the role of combined protein expression as a predictor of lymph node metastasis and clinical outcome in TNBC through in vivo and vitro studies. Three hundred nineteen patients diagnosed with TNBC were chosen, immunohistochemical staining for SIRT1 and EMT-related markers' expression was performed on tissue microarrays, and in vitro experiments with each of the three human TNBC cell lines were carried out. The cohort was reclassified according to the use of adjuvant chemotherapy, tumor size, and AJCC stage to analyze the prognostic role of SIRT1 and EMT-related proteins' expression considering different therapeutic modalities and AJCC stages. Combination of four proteins including SIRT1 and three EMT-related proteins was revealed to be a statistically significant independent predictor of lymph node metastasis in the tumor size cohort as well as in the total patient population. Upon Cox regression analysis, increased expression level of the combined proteins correlated with decreased disease-free survival in the total patients as well as those who received adjuvant chemotherapy and those who had early stage breast cancer. In additional in vitro experiments, inhibition of SIRT1 expression with small interfering RNA (siRNA) suppressed tumor invasion in three different TNBC cell lines, and altered expression levels of EMT-related proteins following SIRT1 gene inhibition were identified on western blotting and fluorescence activated cell sorting (FACS) analysis; on the other hand, no change in expression levels of the cell cycle-related factors was observed. Our analysis showed the potential role of SIRT1 in association with EMT-related factors on tumor invasion, metastasis, and disease-free survival in TNBC, SIRT1, and

  15. Cancer vaccines: harnessing the potential of anti-tumor immunity.

    PubMed

    Suckow, Mark A

    2013-10-01

    Although the presence of cancer suggests failure of the immune system to protect against development of tumors, the possibility that immunity can be redirected and focused to generate an anti-tumor response offers great translational possibility. The key to this is identifying antigens likely to be present in any given tumor and functionally critical to tumor survival and growth. Such tumor-associated antigens (TAAs) are varied and optimally should be absent from normal tissue. Of particular interest are TAAs associated with the tumor stroma, as immunity directed against the stroma may restrict the ability of the tumor to grow and metastasize. Important to directing the immune system toward an effect anti-tumor response is the understanding of how TAAs are processed and how the tumor is able to evade immune elimination. The process of immunoediting happens in response to the selective pressure that the immune system places upon tumor cell populations and allows for emergence of tumor cells capable of escaping immune destruction. Efforts to harness the immune system for clinical application has been aided by vaccines based on purified recombinant protein or nucleic acid TAAs. For example, a vaccine for canine melanoma has been developed and approved based on immunization with DNA components of tyrosinase, a glycoprotein essential to melanin synthesis. The performance of cancer vaccines has been aided in some cases when supplemented with immunostimulatory molecules such as interleukin 2 or a novel extracellular matrix vaccine adjuvant. Vaccines with the broadest menu of antigenic targets may be those most likely to succeed against cancer. For this reason, tissue vaccines produced from harvested tumor material may offer significant benefit. With several cancer vaccines on the veterinary and human markets, efforts to understand basic tumor immunology are soon to yield great dividends.

  16. Potential use of radiolabelled porphyrins for tumor scanning

    SciTech Connect

    Thaller, R.A.; Lyster, D.M.; Dolphin, D.

    1983-01-01

    Fe-TMPI, Fe-TCP and protohemins showed high initial uptake using tissue culture techniques with mouse tumor cells (P815). However, the tumor uptake in the in vivo model was poor. Of the radionuclides investigated, iron labelled to TMPI demonstrated the best uptake by tumor in vitro. As has been previously demonstrated, the unnatural meso-arylporphyrin derivatives showed better uptake than did naturally occurring porphyrins and their derivatives.

  17. Podoplanin is a novel myoepithelial cell marker in pleomorphic adenoma and other salivary gland tumors with myoepithelial differentiation.

    PubMed

    Tsuneki, Masayuki; Maruyama, Satoshi; Yamazaki, Manabu; Essa, Ahmed; Abé, Tatsuya; Babkair, Hamzah Ali; Ahsan, Md Shahidul; Cheng, Jun; Saku, Takashi

    2013-03-01

    The expression of podoplanin, one of the representative immunohistochemical markers for lymphatic endothelium, is upregulated in various kinds of cancers. Based on our previous studies, we have developed a hypothesis that podoplanin plays a role in cell adhesion via its association with extracellular matrix (ECM). Since salivary pleomorphic adenoma is histologically characterized by its ECM-enriched stroma, we firstly wanted to explore the expression modes of podoplanin in pleomorphic adenoma and related salivary tumors by immunohistochemistry. In normal salivary gland, podoplanin was specifically localized in myoepithelial cells, which were also positively labeled by antibodies against P63, of the intercalated duct as well as acini. In pleomorphic adenoma, podoplanin was colocalized with P63 and CD44 in basal cells of glandular structures as well as in stellate/spindle cells in myxochondroid matrices, where perlecan and hyaluronic acid were enriched. The expression of podoplanin was confirmed at both protein and mRNA levels in pleomorphic adenoma cell systems (SM-AP1 and SM-AP4) by using immunofluorescence, western blotting, and reverse transcription polymerase chain reaction. Podoplanin was localized on the cell border as well as in the external periphery of the cells. Moreover, podoplanin expression was also confirmed in tumor cells with myoepithelial differentiation in myoepithelioma and intraductal papilloma. The results indicate that podoplanin can be regarded as a novel myoepithelial marker in salivary gland tumors and suggest that podoplanin's communication with ECM molecules is essential to phenotypic differentiation to myoepithelial cells.

  18. ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer

    PubMed Central

    Hou, Pingfu; Zhang, Zhe; Zhang, Yafei; Wang, Weimin; Sun, Guixiang; Xu, Lichun; Zhou, Jianwei; Bai, Jin; Zheng, Junnian

    2016-01-01

    ING4, a potential tumor suppressor, is implicated in cell cycle arrest, apoptosis, cell migration and angiogenesis. Here, we investigated the clinical value of ING4 and its impact on angiogenesis in colorectal cancer (CRC). In this study, we found that ING4 expression was significantly reduced in CRC tissues versus paired normal colon tissues. Moreover, low ING4 expression was significantly associated with increased lymph node metastasis, advanced TNM stage and poor overall survival. Multivariate Cox regression analysis showed that ING4 expression was an independent favourable prognostic factor for CRC (hazard ratio = 0.45, P = 0.001). In addition, we found that ING4 strongly inhibited CRC angiogenesis by suppressing Sp1 expression and transcriptional activity through ubiquitin degradation and down-regulating the expressions of Sp1 downstream pro-angiogenic genes, MMP-2 and COX-2. Moreover, ING4 might inhibit phosphorylation activity of cyclin/CDK2 complexes to trigger Sp1 degradation by inducing p21 expression in despite of p53 status. Our findings imply that reduced ING4 expression in CRC resulted in increased angiogenesis and contributed to CRC metastasis and poor prognosis. Restoration of ING4 may be a novel strategy for the treatment of metastatic CRC. PMID:27806345

  19. New perspective on molecular markers as promising therapeutic targets in germ cell tumors

    PubMed Central

    Chieffi, Paolo

    2016-01-01

    Summary Testicular germ cell tumors (TGCTs) are the most frequent solid malignant tumors in men 20–40 years of age and the most frequent cause of death from solid tumors in this age group. TGCTs comprise two major histologic groups: seminomas and non-seminomas germ cell tumors (NSGCTs). NSGCTs can be further divided into embryonal carcinoma, Teratoma, yolk sac tumor, and choriocarcinoma. Seminomas and NSGCTs present significant differences in clinical features, therapy, and prognosis, and both show characteristics of the Primordial Germ Cells (PGCs). Many discovered biomarkers including HMGA1, GPR30, Aurora-B, estrogen receptor β, and others have given further advantages to discriminate between histological subgroups and could represent useful therapeutic targets. PMID:27195201

  20. Complement component 7 (C7), a potential tumor suppressor, is correlated with tumor progression and prognosis

    PubMed Central

    Pan, Xiaodan; Chen, Kaiyan; Zhang, Nan; Jin, Jiaoyue; Wu, Junzhou; Feng, Jianguo; Yu, Herbert; Jin, Hongchuan; Su, Dan

    2016-01-01

    Our previous study found copy number variation of chromosome fragment 5p13.1-13.3 might involve in the progression of ovarian cancer. In the current study, the alteration was validated and complement component 7 (C7), located on 5p13.1, was identified. To further explore the clinical value of C7 in tumors, 156 malignant, 22 borderline, 33 benign and 24 normal ovarian tissues, as well as 173 non-small cell lung cancer (NSCLC) tissues along with corresponding adjacent and normal tissues from the tissue bank of Zhejiang Cancer Hospital were collected. The expression of C7 was analyzed using reverse transcriptase quantitative polymerase chain reaction. As a result, the C7 expression displayed a gradual downward trend in normal, benign, borderline and malignant ovarian tissues, and the decreased expression of C7 was correlative to poor differentiation in patients with ovarian cancer. Interestingly, a similar change of expression of C7 was found in normal, adjacent and malignant tissues in patients with NSCLC, and low expression of C7 was associated with worse grade and advanced clinical stage. Both results from this cohort and the public database indicated that NSCLC patients with low expression of C7 had a worse outcome. Furthermore, multivariate cox regression analysis showed NSCLC patients with low C7 had a 3.09 or 5.65-fold higher risk for relapse or death than those with high C7 respectively, suggesting C7 was an independent prognostic predictor for prognoses of patients with NSCLC. Additionally, overexpression of C7 inhibited colony formation of NSCLC cells, which hints C7 might be a potential tumor suppressor. PMID:27852032

  1. Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro

    PubMed Central

    Chhor, Vibol; Le Charpentier, Tifenn; Lebon, Sophie; Oré, Marie-Virgine; Celador, Idoia Lara; Josserand, Julien; Degos, Vincent; Jacotot, Etienne; Hagberg, Henrik; Sävman, Karin; Mallard, Carina; Gressens, Pierre; Fleiss, Bobbi

    2013-01-01

    Microglia mediate multiple facets of neuroinflammation, including cytotoxicity, repair, regeneration, and immunosuppression due to their ability to acquire diverse activation states, or phenotypes. Modulation of microglial phenotype is an appealing neurotherapeutic strategy but a comprehensive study of classical and more novel microglial phenotypic markers in vitro is lacking. The aim of this study was to outline the temporal expression of a battery of phenotype markers from polarised microglia to generate an in vitro tool for screening the immunomodulatory potential of novel compounds. We characterised expression of thirty-one macrophage/microglial phenotype markers in primary microglia over time (4, 12, 36, and 72 h), using RT-qPCR or multiplex protein assay. Firstly, we selected Interleukin-4 (IL-4) and lipopolysaccharide (LPS) as the strongest M1–M2 polarising stimuli, from six stimuli tested. At each time point, markers useful to identify that microglia were M1 included iNOS, Cox-2 and IL-6 and a loss of M2a markers. Markers useful for quantifying M2b-immunomodulatory microglia included, increased IL-1RA and SOCS3 and for M2a-repair and regeneration, included increased arginase-1, and a loss of the M1 and M2b markers were discriminatory. Additional markers were regulated at fewer time points, but are still likely important to monitor when assessing the immunomodulatory potential of novel therapies. Further, to facilitate identification of how novel immunomodulatory treatments alter the functional affects of microglia, we characterised how the soluble products from polarised microglia affected the type and rate of neuronal death; M1/2b induced increasing and M2a-induced decreasing neuronal loss. We also assessed any effects of prior activation state, to provide a way to identify how a novel compound may alter phenotype depending on the stage of injury/insult progression. We identified generally that a prior M1/2b reduced the ability of microglia to switch to

  2. Molecular trophic markers in marine food webs and their potential use for coral ecology.

    PubMed

    Leal, Miguel Costa; Ferrier-Pagès, Christine

    2016-10-01

    Notable advances in ecological genomics have been driven by high-throughput sequencing technology and taxonomically broad sequence repositories that allow us to accurately assess species interactions with great taxonomic resolution. The use of DNA as a marker for ingested food is particularly relevant to address predator-prey interactions and disentangle complex marine food webs. DNA-based methods benefit from reductionist molecular approaches to address ecosystem scale processes, such as community structure and energy flow across trophic levels, among others. Here we review how molecular trophic markers have been used to better understand trophic interactions in the marine environment and their advantages and limitations. We focus on animal groups where research has been focused, such as marine mammals, seabirds, fishes, pelagic invertebrates and benthic invertebrates, and use case studies to illustrate how DNA-based methods unraveled food-web interactions. The potential of molecular trophic markers for disentangling the complex trophic ecology of corals is also discussed.

  3. Combination of miR-21 with Circulating Tumor Cells Markers Improve Diagnostic Specificity of Metastatic Breast Cancer.

    PubMed

    Yang, Xingwang; Wang, Xiaoming; Shen, Hongyan; Deng, Rong; Xue, Kecheng

    2015-09-01

    Circulating miR-21 is upregulated in breast cancer. However, correlation of miR-21 expression with clinic pathologic characteristics remains questionable. In this study, we investigate whether combination of circulation miR-21 with circulating tumor cells (CTCs) marker (EpCAM, MUS1, HER2) could improve diagnostic specificity of metastatic breast cancer. Total 223 breast cancer patients were included. 89 % patients were associated with upregulation of miR-21 compared with health control. 20 % patients were detected for CTCs marker positive. For higher specificity purpose, triple marker positive samples were selected as true CTCs positive, which only occupied 59.5 % of total metastatic breast cancer patients. Specificity of detection of CTCs was 96.7 %. Furthermore, 59.5 % metastatic breast cancer patients were shown both abnormal miR-21 and true CTCs positive according to distribution of true CTCs positive and abnormal miR-21; Combination of miR-21 and CTCs was increased specificity of metastatic detection to 100 %. Our findings suggested that combination of miR-21 with CTCs marker could be used for better diagnosis of metastatic breast cancer in the future.

  4. The Simultaneous Elevation of Oxidative Stress Markers and Wilms' Tumor 1 Gene during the Progression of Myelodysplastic Syndrome

    PubMed Central

    Shimizu, Naomi; Hasunuma, Hidekazu; Watanabe, Yasuhiro; Matsuzawa, Yasuo; Iwashita, Youichi; Tatsuno, Ichiro; Yokota, Hiromitsu

    2016-01-01

    Oxidative stress is closely related to iron overload in myelodysplastic syndrome (MDS) and induces DNA damage. We evaluated the oxidative stress markers derivatives of reactive oxidative metabolites (dROM) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) during azacitidine treatment in an MDS patient. Simultaneous with an increase in the expression of Wilms' Tumor 1 (WT1) gene in the peripheral blood, the serum dROM level was elevated, and this increase was observed earlier than the increases in ferritin and 8-OHdG. Throughout the clinical course, dROM and 8-OHdG correlated significantly with WT1 and with ferritin, suggesting that changes in the oxidative stress marker levels reflect not only iron overload but also disease progression of MDS. PMID:27980269

  5. Optimum location of external markers using feature selection algorithms for real-time tumor tracking in external-beam radiotherapy: a virtual phantom study.

    PubMed

    Nankali, Saber; Esmaili Torshabi, Ahmad; Samadi Miandoab, Payam; Baghizadeh, Amin

    2016-01-08

    In external-beam radiotherapy, using external markers is one of the most reliable tools to predict tumor position, in clinical applications. The main challenge in this approach is tumor motion tracking with highest accuracy that depends heavily on external markers location, and this issue is the objective of this study. Four commercially available feature selection algorithms entitled 1) Correlation-based Feature Selection, 2) Classifier, 3) Principal Components, and 4) Relief were proposed to find optimum location of external markers in combination with two "Genetic" and "Ranker" searching procedures. The performance of these algorithms has been evaluated using four-dimensional extended cardiac-torso anthropomorphic phantom. Six tumors in lung, three tumors in liver, and 49 points on the thorax surface were taken into account to simulate internal and external motions, respectively. The root mean square error of an adaptive neuro-fuzzy inference system (ANFIS) as prediction model was considered as metric for quantitatively evaluating the performance of proposed feature selection algorithms. To do this, the thorax surface region was divided into nine smaller segments and predefined tumors motion was predicted by ANFIS using external motion data of given markers at each small segment, separately. Our comparative results showed that all feature selection algorithms can reasonably select specific external markers from those segments where the root mean square error of the ANFIS model is minimum. Moreover, the performance accuracy of proposed feature selection algorithms was compared, separately. For this, each tumor motion was predicted using motion data of those external markers selected by each feature selection algorithm. Duncan statistical test, followed by F-test, on final results reflected that all proposed feature selection algorithms have the same performance accuracy for lung tumors. But for liver tumors, a correlation-based feature selection algorithm, in

  6. Oxystressed tumor microenvironment potentiates epithelial to mesenchymal transition and alters cellular bioenergetics towards cancer progression.

    PubMed

    Sridaran, Dhivya; Ramamoorthi, Ganesan; MahaboobKhan, Rasool; Kumpati, Premkumar

    2016-10-01

    During tumorigenesis, cancer cells generate complex, unresolved interactions with the surrounding oxystressed cellular milieu called tumor microenvironment (TM) that favors spread of cancer to other body parts. This dissemination of cancer cells from the primary tumor site is the main clinical challenge in cancer treatment. In addition, the significance of enhanced oxidative stress in TM during cancer progression still remains elusive. Thus, the present study was performed to investigate the molecular and cytoskeletal alterations in breast cancer cells associated with oxystressed TM that potentiates metastasis. Our results showed that depending on the extent of oxidative stress in TM, cancer cells exhibited enhanced migration and survival with reduction of chemosensitivity. Corresponding ultrastructural analysis showed radical cytoskeletal modifications that reorganize cell-cell interactions fostering transition of epithelial cells to mesenchymal morphology (EMT) marking metastasis, which was reversed upon antioxidant treatment. Decreased E-cadherin and increased vimentin, Twist1/2 expression corroborated the initiation of EMT in oxystressed TM-influenced cells. Further evaluation of cellular energetics demonstrated significant metabolic reprogramming with inclination towards glucose or external glutamine from TM as energy source depending on the breast cancer cell type. These observations prove the elemental role of oxystressed TM in cancer progression, initiating EMT and metabolic reprogramming. Further cell-type specific metabolomic analysis would unravel the alternate mechanisms in cancer progression for effective therapeutic intervention. Graphical abstract Schematic representation of the study and proposed mechanism of oxystressed TM influenced cancer progression. Cancer cells exhibit a close association with tumor microenvironment (TM), and oxystressed TM enhances cancer cell migration and survival and reduces chemosensitivity. Oxystressed TM induces dynamic

  7. DNMTs as potential therapeutic targets in high-risk pediatric embryonal brain tumors.

    PubMed

    Sin-Chan, Patrick; Huang, Annie

    2014-10-01

    Malignant brain tumors, which are the leading cause of cancer-related morbidity and mortality in children, span a wide spectrum of diseases with distinct clinical phenotypes but may share remarkably similar morphologic features. Until recently, few molecular markers of childhood brain tumors have been identified, which has limited therapeutic advances. Recent global genomic studies have enabled robust molecular classification of childhood brain tumors and the identification and consolidation of rare, seemingly disparate clinical entities. It is now increasingly evident that deregulation of epigenetic processes contributes substantially to heterogeneity in tumor phenotypes and comprise significant drivers of cancer initiation and progression. Specifically, DNA hypermethylation and silencing of critical tumor suppressor genes by DNA methyltransferases (DNMT) has emerged as an important and fundamental mechanism in brain tumor pathogenesis. These observations have been underscored by the recent discovery of TTYH1-C19MC gene fusions in an aggressive pediatric embryonal brain tumor, which results in deregulation and increased expression of a neural-specific DNMT3B isoform in C19MC-associated brain tumors. Our observations that pharmacological inhibitors of DNMTs and histone deacetylases significantly inhibit growth of cells derived from C19MC-associated tumors indicate targeting of epigenomic modifiers as a novel therapeutic approach for these highly treatment-resistant tumors.

  8. Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

    PubMed Central

    Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

    2011-01-01

    Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

  9. Caveolin-1 and cancer metabolism in the tumor microenvironment: markers, models, and mechanisms.

    PubMed

    Sotgia, Federica; Martinez-Outschoorn, Ubaldo E; Howell, Anthony; Pestell, Richard G; Pavlides, Stephanos; Lisanti, Michael P

    2012-01-01

    Caveolins are a family of membrane-bound scaffolding proteins that compartmentalize and negatively regulate signal transduction. Recent studies have implicated a loss of caveolin-1 (Cav-1) expression in the pathogenesis of human cancers. Loss of Cav-1 expression in cancer-associated fibroblasts results in an activated tumor microenvironment, thereby driving early tumor recurrence, metastasis, and poor clinical outcome in breast and prostate cancers. We describe various paracrine signaling mechanism(s) by which the loss of stromal Cav-1 promotes tumor progression, including fibrosis, extracellular matrix remodeling, and the metabolic/catabolic reprogramming of cancer-associated fibroblast, to fuel the growth of adjacent tumor cells. It appears that oxidative stress is the root cause of initiation of the loss of stromal Cav-1 via autophagy, which provides further impetus for the use of antioxidants in anticancer therapy. Finally, we discuss the functional role of Cav-1 in epithelial cancer cells.

  10. Antibodies elicited by the first non-viral prophylactic cancer vaccine show tumor-specificity and immunotherapeutic potential

    PubMed Central

    Lohmueller, Jason J.; Sato, Shuji; Popova, Lana; Chu, Isabel M.; Tucker, Meghan A.; Barberena, Roberto; Innocenti, Gregory M.; Cudic, Mare; Ham, James D.; Cheung, Wan Cheung; Polakiewicz, Roberto D.; Finn, Olivera J.

    2016-01-01

    MUC1 is a shared tumor antigen expressed on >80% of human cancers. We completed the first prophylactic cancer vaccine clinical trial based on a non-viral antigen, MUC1, in healthy individuals at-risk for colon cancer. This trial provided a unique source of potentially effective and safe immunotherapeutic drugs, fully-human antibodies affinity-matured in a healthy host to a tumor antigen. We purified, cloned, and characterized 13 IgGs specific for several tumor-associated MUC1 epitopes with a wide range of binding affinities. These antibodies bind hypoglycosylated MUC1 on human cancer cell lines and tumor tissues but show no reactivity against fully-glycosylated MUC1 on normal cells and tissues. We found that several antibodies activate complement-mediated cytotoxicity and that T cells carrying chimeric antigen receptors with the antibody variable regions kill MUC1+ target cells, express activation markers, and produce interferon gamma. Fully-human and tumor-specific, these antibodies are candidates for further testing and development as immunotherapeutic drugs. PMID:27545199

  11. Differential expression of nucleostemin, a stem cell marker, and its variants in different types of brain tumors.

    PubMed

    Malakootian, Mahshid; Mowla, Seyed Javad; Saberi, Hooshang; Asadi, Malek Hossein; Atlasi, Yaser; Shafaroudi, Afsaneh Malekzadeh

    2010-09-01

    Nucleostemin (NS) is implicated in the control of stem and cancer cell proliferation. In the present study, we have examined the expression of NS and its spliced variants in various brain tumors. Total RNA was extracted from 59 brain tumor samples, and the expression of different NS spliced variants was measured by semi-quantitative RT-PCR. The subcellular distribution of NS protein in brain tumors was further examined by immunohistochemistry. Furthermore, to decipher the potential involvement of NS in brain tumorogenesis, its expression was knocked-down by means of RNA interference (RNAi) in two malignant glioma (U-87MG and A172), one astrocytoma (1321N1) and one medulloblastoma (DAOY) cell lines. The alterations in cell-cycle progression of the treated cells were then analyzed by flow cytometry. Our data revealed that NS and its variants are widely expressed in different types of brain tumors. Among the NS spliced variants, variant "1" and variant "3" were detected in the majority of tumor samples, whereas variant "2" was only detectable in few samples. Moreover, the intensity of the expression was correlated with the grade of the tumors (P < 0.05). Accordingly, the expression was much higher in glial tumors compared to that of meningiomas. As expected, a nucleolar/nucleoplasmic localization of NS protein was observed in the examined tumor samples. RNAi results revealed a significant reduction of NS expression along with a moderate blockade of the cell cycle in G(2)/M and S phases of NS-siRNA treated cells. All in all, our data suggest a potential role for NS in tumorogenesis of brain cancers.

  12. Naphthalocyanine-complexes as potential photosensitizers for PDT of tumors

    NASA Astrophysics Data System (ADS)

    Shopova, Maria; Woehrle, Dieter; Mantareva, Vanya; Mueller, Silke

    1999-07-01

    In the present paper information about the synthesis and results on the pharmacokinetic and experimental photodynamic therapy (PDT) of naphthalocyanines are given. The photodynamic activity of differently substituted zinc(II)- and silicon(IV)-naphthalocyanines using liposomes or Cremophor EL as drug-delivery systems is shown on different tumor models. For the evaluation of the phototherapeutic effect different assessment criteria were used, including light and electron microscope observations. The main conclusions which can be arrived at on the basis of our findings are the following: silicon(IV)-naphthalocyanine seems to be not a very effective tumor sensitizer, especially in the treatment o pigmented melanoma, while zinc(II)-naphthalocyanines appear to be very promising for PDT of tumors. Their selective targeting and slow clearance from tumor tissue, fast clearance from skin and pronounced phototherapeutic effect on different tumor models and especially at melanotic tumors, even after application of low drug doses, make this group of photosensitizers very attractive for successful PDT of cancer.

  13. Plasmodium falciparum kelch 13: a potential molecular marker for tackling artemisinin-resistant malaria parasites.

    PubMed

    Mita, Toshihiro; Tachibana, Shin-Ichiro; Hashimoto, Muneaki; Hirai, Makoto

    2016-01-01

    Although artemisinin combination therapies have been deployed as a first-line treatment for uncomplicated malaria in almost all endemic countries, artemisinin-resistant parasites have emerged and have gradually spread across the Greater Mekong subregions. There is growing concern that the resistant parasites may migrate to or emerge indigenously in sub-Saharan Africa, which might provoke a global increase in malaria-associated morbidity and mortality. Therefore, development of molecular markers that enable identification of artemisinin resistance with high sensitivity is urgently required to combat this issue. In 2014, a potential artemisinin-resistance responsible gene, Plasmodium falciparum kelch13, was discovered. Here, we review the genetic features of P. falciparum kelch13 and discuss its related resistant mechanisms and potential as a molecular marker.

  14. Sperm midpiece apoptotic markers: impact on fertilizing potential in in vitro fertilization and intracytoplasmic sperm injection.

    PubMed

    Talarczyk-Desole, Joanna; Kotwicka, Małgorzata; Jendraszak, Magdalena; Pawelczyk, Leszek; Murawski, Marek; Jędrzejczak, Piotr

    2016-04-01

    The aim of this study was to investigate the relationship between apoptotic markers present in human spermatozoa, namely phosphatidylserine translocation (PST) from the inner to the outer layer of the cytomembrane and the active form of caspase-3 (c3) versus the fertilizing potential of male gametes in conventional in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) models. A total of 116 male patients treated with their partners for infertility underwent basic semen analysis and an assessment of the presence of PST and the active c3 in sperm using flow cytometry. Forty patients underwent IVF, group A, while 76 patients underwent ICSI, group B. The fertilizing potential of the gametes was measured as the percentage of oocytes with pronuclei present after either procedure. PST and active c3 were identified in vital gametes, mainly in the midpiece area. Concentration, motility, morphology, and viability of spermatozoa strongly negatively correlated with both markers. In group A, a negative correlation between both markers and the success rate of conventional IVF was observed (r = -0.4, p = 0.04 for PST; r = -0.4, p = 0.02 for active c3, respectively). In group B, the success rate of ICSI did not correlate with either marker (r = -0.2, p = 0.85 for PST and r = 0.1, p = 0.51 for active c3). The two apoptotic markers localized in the sperm midpiece area may affect their function not only by decreasing basic andrologic parameters but also by reducing the probability of conception. Therefore, analysis of PST and active c3 in the sperm of patients undergoing infertility treatment should be recommended.

  15. A comparison of oral and intravenous pimonidazole in canine tumors using intravenous CCI-103F as a control hypoxia marker

    SciTech Connect

    Kleiter, Miriam M.; Thrall, Donald E.; Malarkey, David E.; Ji Xiaoshen; Lee, David Y.W.; Chou, S.-C.; Raleigh, James A. . E-mail: james_raleigh@med.unc.edu

    2006-02-01

    Purpose: Pimonidazole HCl is widely used in immunohistochemical analyses of hypoxia in normal and malignant tissues. The present study investigates oral administration as a means of minimizing invasiveness. Methods and Materials: Twelve dogs with confirmed malignancy received 0.5 g/m{sup 2} of pimonidazole HCl: 6 by mouth and 6 by i.v. infusion. All dogs received i.v. CCI-103F as a control. Plasma levels of pimonidazole, pimonidazole N-oxide, and CCI-103F were measured. Tumor biopsies were formalin fixed, paraffin embedded, sectioned, immunostained, and analyzed for pimonidazole and CCI-103F binding. pH dependence for pimonidazole and CCI-103F binding was studied in vitro. Results: Pimonidazole and CCI-103F binding in carcinomas and sarcomas was strongly correlated for both oral and i.v. pimonidazole HCl (r {sup 2} = 0.97). On average, the extent of pimonidazole binding exceeded that for CCI-103F by a factor of approximately 1.2, with the factor ranging from 1.0 to 1.65. Binding of both markers was pH dependent, but pimonidazole binding was greater at all values of pH. Conclusions: Oral pimonidazole HCl is effective as a hypoxia marker in spontaneously arising canine tumors. Selective cellular uptake and concomitant higher levels of binding in regions of hypoxia at the high end of pH gradients might account for the greater extent of pimonidazole binding.

  16. Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers.

    PubMed

    Armstrong, Andrew J; Marengo, Matthew S; Oltean, Sebastian; Kemeny, Gabor; Bitting, Rhonda L; Turnbull, James D; Herold, Christina I; Marcom, Paul K; George, Daniel J; Garcia-Blanco, Mariano A

    2011-08-01

    During cancer progression, malignant cells undergo epithelial-mesenchymal transitions (EMT) and mesenchymal-epithelial transitions (MET) as part of a broad invasion and metastasis program. We previously observed MET events among lung metastases in a preclinical model of prostate adenocarcinoma that suggested a relationship between epithelial plasticity and metastatic spread. We thus sought to translate these findings into clinical evidence by examining the existence of EMT in circulating tumor cells (CTC) from patients with progressive metastatic solid tumors, with a focus on men with castration-resistant prostate cancer (CRPC) and women with metastatic breast cancer. We showed that the majority (> 80%) of these CTCs in patients with metastatic CRPC coexpress epithelial proteins such as epithelial cell adhesion molecule (EpCAM), cytokeratins (CK), and E-cadherin, with mesenchymal proteins including vimentin, N-cadherin and O-cadherin, and the stem cell marker CD133. Equally, we found that more than 75% of CTCs from women with metastatic breast cancer coexpress CK, vimentin, and N-cadherin. The existence and high frequency of these CTCs coexpressing epithelial, mesenchymal, and stem cell markers in patients with progressive metastases has important implications for the application and interpretation of approved methods to detect CTCs.

  17. Unique metabolic features of pancreatic cancer stroma: relevance to the tumor compartment, prognosis, and invasive potential

    PubMed Central

    Knudsen, Erik S.; Balaji, Uthra; Freinkman, Elizaveta; McCue, Peter; Witkiewicz, Agnieszka K.

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The aggressiveness and therapeutic recalcitrance of this malignancy has been attributed to multiple factors including the influence of an active desmoplastic stroma. How the stromal microenvironment of PDAC contributes to the fatal nature of this disease is not well defined. In the analysis of clinical specimens, we observed diverse expression of the hypoxic marker carbonic anhydrase IX and the lactate transporter MCT4 in the stromal compartment. These stromal features were associated with the epithelial to mesenchymal phenotype in PDAC tumor cells, and with shorter patient survival. Cultured cancer-associated fibroblasts (CAFs) derived from primary PDAC exhibited a high basal level of hypoxia inducible factor 1a (HIF1α) that was both required and sufficient to modulate the expression of MCT4. This event was associated with increased transcription and protein synthesis of HIF1α in CAFs relative to PDAC cell lines, while surprisingly the protein turnover rate was equivalent. CAFs utilized glucose predominantly for glycolytic intermediates, whereas glutamine was the preferred metabolite for the TCA cycle. Unlike PDAC cell lines, CAFs were resistant to glucose withdrawal but sensitive to glutamine depletion. Consistent with the lack of reliance on glucose, CAFs could survive the acute depletion of MCT4. In co-culture and xenograft studies CAFs stimulated the invasive potential and metastatic spread of PDAC cell lines through a mechanism dependent on HIF1α and MCT4. Together, these data indicate that stromal metabolic features influence PDAC tumor cells to promote invasiveness and metastatic potential and associate with poor outcome in patients with PDAC. PMID:27623078

  18. New Mechanisms of Tumor-Associated Macrophages on Promoting Tumor Progression: Recent Research Advances and Potential Targets for Tumor Immunotherapy

    PubMed Central

    He, Shulin; Hou, Wei

    2016-01-01

    The majority of basic and clinical studies have shown a protumor function of tumor-associated macrophages (TAMs), which represent a large proportion of matrix cells. TAMs promote tumorigenesis, and their number is related to the malignancy degree and poor prognosis of many kinds of tumors. Macrophage plasticity makes it possible to change the tumor microenvironment and remodel antitumor immunity during cancer immunotherapy. Increasing numbers of studies have revealed the effects of TAMs on the tumor microenvironment, for example, via promotion of tumor growth and tumorigenesis and through an increase in the number of cancer stem cells or via facilitation of angiogenesis, lymphangiogenesis, and metastasis. Investigators also proposed tumor-immunological treatments targeting TAMs by inhibiting TAM recruitment and differentiation, by regulating TAM polarization, and by blocking factors and pathways associated with the protumor function of TAMs. This comprehensive review presents recent research on TAMs in relation to prediction of poor outcomes, remodeling of the tumor immune microenvironment, and immunological targeted therapies. PMID:27975071

  19. Characterization of carbonic anhydrase IX (CA IX) as an endogenous marker of chronic hypoxia in live human tumor cells

    SciTech Connect

    Vordermark, Dirk . E-mail: vordermark_d@klinik.uni-wuerzburg.de; Kaffer, Anja; Riedl, Susanne; Katzer, Astrid; Flentje, Michael

    2005-03-15

    Purpose: Published clinical studies provide conflicting data regarding the prognostic significance of carbonic anhydrase IX (CA IX) overexpression as an endogenous marker of tumor hypoxia and its comparability with other methods of hypoxia detection. We performed a systematic analysis of CA IX protein levels under various in vitro conditions of tumor hypoxia in HT 1080 human fibrosarcoma and FaDu human pharyngeal carcinoma cells. Because sorting of live CA IX positive cells from tumors provides a tool to study the radiosensitivity of chronically hypoxic cells, we modified and tested a CA IX flow cytometry protocol on mixed hypoxic/aerobic suspensions of HT 1080 and FaDu cells. Methods and materials: HT 1080 and FaDu cells were treated with up to 24 h of in vitro hypoxia and up to 96 h of reoxygenation. To test the effect of nonhypoxic stimuli, glucose and serum availability, pH and cell density were modified. CA IX protein was quantified in Western blots of whole-cell lysates. Mixed suspensions with known percentages of hypoxic cells were prepared for CA IX flow cytometry. The same mixtures were assayed for clonogenic survival after 10 Gy. Results: Hypoxia-induced CA IX protein expression was seen after >6 h at {<=}5% O{sub 2}, and protein was stable over 96 h of reoxygenation in both cell lines. Glucose deprivation abolished the hypoxic CA IX response, and high cell density caused CA IX induction under aerobic conditions. Measured percentages of CA IX-positive cells in mixtures closely reflected known percentages of hypoxic cells in HT 1080 and were associated with radioresistance of mixtures after 10 Gy. Conclusion: CA IX is a stable marker of current or previous chronic hypoxia but influenced by nonhypoxic stimuli. Except the time course of accumulation, all properties of this marker resembled our previous findings for hypoxia-inducible factor-1{alpha}. A modified flow cytometry protocol provided good separability of CA IX-negative and -positive cells in vitro

  20. Molecular Markers in Low-Grade Glioma-Toward Tumor Reclassification.

    PubMed

    Olar, Adriana; Sulman, Erik P

    2015-07-01

    Low-grade diffuse gliomas are a heterogeneous group of primary glial brain tumors with highly variable survival. Currently, patients with low-grade diffuse gliomas are stratified into risk subgroups by subjective histopathologic criteria with significant interobserver variability. Several key molecular signatures have emerged as diagnostic, prognostic, and predictor biomarkers for tumor classification and patient risk stratification. In this review, we discuss the effect of the most critical molecular alterations described in diffuse (IDH1/2, 1p/19q codeletion, ATRX, TERT, CIC, and FUBP1) and circumscribed (BRAF-KIAA1549, BRAF(V600E), and C11orf95-RELA fusion) gliomas. These molecular features reflect tumor heterogeneity and have specific associations with patient outcome that determine appropriate patient management. This has led to an important, fundamental shift toward developing a molecular classification of World Health Organization grade II-III diffuse glioma.

  1. Serial lumbar and ventricular cerebrospinal fluid biochemical marker measurements in patients with leptomeningeal metastases from solid and hematological tumors.

    PubMed

    Twijnstra, A; Ongerboer de Visser, B W; van Zanten, A P; Hart, A A; Nooyen, W J

    1989-05-01

    This study presents results of investigations of lumbar and ventricular cerebrospinal fluid (CSF) biochemical markers (Beta-glucuronidase (B-gluc), Beta-2-microglobulin (B2-m), and carcinoembrionic antigen (CEA] in 28 patients with five different tumor types with leptomeningeal metastasis diagnosed by CSF cytology and/or autopsy. All received methotrexate and radiotherapy at some stage. Decadron or other symptomatic treatments were not used. Measurements of the concentrations of B-gluc, B2-m and CEA were evaluated with the aim of correlating the results of these measurements to site of disease, of monitoring response and early relapse of leptomeningeal disease, and of establishing the duration of survival. In almost all our patients the results of ventricular CSF B-gluc, B2-m and CEA measurements were lower than those obtained from lumbar CSF. The markers did not correlate with site of disease or CSF cytology. A clear relationship was found between pretreatment lumbar CSF B2-m and CEA levels, response to therapy and survival. The markers are also useful for monitoring response. The findings of this study indicate that B2-m and CEA levels have a prognostic value with regard to response to therapy and time of survival.

  2. Tumor necrosis factor beta NcoI polymorphism is associated with inflammatory and metabolic markers in multiple sclerosis patients.

    PubMed

    Kallaur, Ana Paula; Oliveira, Sayonara Rangel; Simão, Andréa Name Colado; de Almeida, Elaine Regina Delicato; Morimoto, Helena Kaminami; Alfieri, Daniela Frizon; Pereira, Wildea Lice de Carvalho Jennings; Borelli, Sueli Donizete; Kaimen-Maciel, Damácio Ramon; Maes, Michael; Reiche, Edna Maria Vissoci

    2014-11-15

    To evaluate the association between the tumor necrosis factor beta (TNF-β) NcoI polymorphism and inflammatory and metabolic markers in patients with multiple sclerosis (MS) patients and the association of these markers with disease disability, a 782 base-pair fragment of the TNF-β gene was amplified from genomic DNA and digested with the NcoI restriction enzyme. The serum levels of numerous cytokines (IL-1β, IL-12, IL-6, TNF-α, IFN-γ, IL-4, IL-10, and IL-17) serum lipid levels, plasma insulin levels, and the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) levels were evaluated in 123 female and 43 male patients with MS. Females carrying the TNFB2/B2 genotype presented with decreased IL-4 and IL-10 levels and increased TNF-α, glucose, insulin, and HOMA-IR levels; moreover, there were positive correlations between EDSS and glucose and between EDSS and HOMA-IR in these females. Males carrying the TNFB2/B2 genotype exhibited increased levels of TNF-α, IFN-γ, and IL-17 (p=0.0326) and decreased levels of IL-4, IL-10, insulin, and HOMA-IR; there was a positive correlation between EDSS and TNF-α levels. The TNFB2/B2 genotype of TNF-β NcoI polymorphism was associated with increased inflammatory and metabolic markers and this association was different according to sex of MS patients.

  3. MicroRNA-222 Expression as a Predictive Marker for Tumor Progression in Hormone Receptor-Positive Breast Cancer

    PubMed Central

    Han, Song-Hee; Kim, Hyun Jeong; Gwak, Jae Moon; Kim, Mimi; Chung, Yul Ri

    2017-01-01

    Purpose The microRNA-221/222 (miR-221/222) gene cluster has been reported to be associated with the promotion of epithelial-mesenchymal transition (EMT), downregulation of estrogen receptor-α, and tamoxifen resistance in breast cancer. We studied the expression of miR-222 in human breast cancer samples to analyze its relationship with clinicopathologic features of the tumor, including estrogen receptor status, expression of EMT markers, and clinical outcomes. Methods Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-222 in 197 invasive breast cancers. Expression of EMT markers (vimentin, smooth muscle actin, osteonectin, N-cadherin, and E-cadherin) was evaluated using immunohistochemistry. Results High miR-222 levels were associated with high T stage, high histologic grade, high Ki-67 proliferation index, and HER2 gene amplification. Its expression was significantly higher in the luminal B and human epidermal growth factor receptor 2-positive (HER2+) subtypes than in the luminal A and triple-negative subtypes. In the hormone receptor-positive subgroup, there was a significant negative correlation between miR-222 and estrogen receptor expression, and miR-222 expression was associated with EMT marker expression. In the group as a whole, high miR-222 expression was not associated with clinical outcome. However, subgroup analyses by hormone receptor status revealed that high miR-222 expression was a poor prognostic factor in the hormone receptor-positive subgroup, but not in the hormone receptor-negative subgroup. Conclusion This study showed that miR-222 is associated with down-regulation of the estrogen receptor, EMT, and tumor progression in hormone receptor-positive breast cancer, indicating that miR-222 might be associated with endocrine therapy resistance and poor clinical outcome in hormone receptor-positive breast cancer. PMID:28382093

  4. Harnessing the potential of epigenetic therapy to target solid tumors

    PubMed Central

    Ahuja, Nita; Easwaran, Hariharan; Baylin, Stephen B.

    2014-01-01

    Epigenetic therapies may play a prominent role in the future management of solid tumors. This possibility is based on the clinical efficacy of existing drugs in treating defined hematopoietic neoplasms, paired with promising new data from preclinical and clinical studies that examined these agents in solid tumors. We suggest that current drugs may represent a targeted therapeutic approach for reprogramming solid tumor cells, a strategy that must be pursued in concert with the explosion in knowledge about the molecular underpinnings of normal and cancer epigenomes. We hypothesize that understanding targeted proteins in the context of their enzymatic and scaffolding functions and in terms of their interactions in complexes with proteins that are targets of new drugs under development defines the future of epigenetic therapies for cancer. PMID:24382390

  5. Sharks: a potential source of antiangiogenic factors and tumor treatments.

    PubMed

    Cho, Jung; Kim, Young

    2002-12-01

    Since angiogenesis is a key feature of tumor growth, inhibiting this process is one way to treat cancer. Cartilage is a natural source of material with strong antiangiogenic activity. This report reviews knowledge of the anticancer properties of shark cartilage and clinical information on drugs such as neovastat and squalamine. Because their entire endoskeleton is composed of cartilage, sharks are thought to be an ideal source of angiogenic and tumor growth inhibitors. Shark cartilage extract has shown antiangiogenic and antitumor activities in animals and humans. The oral administration of cartilage extract was efficacious in reducing angiogenesis. Purified antiangiogenic factors from shark cartilage, such as U-995 and neovastat (AE-941), also showed antiangiogenic and antitumor activity. AE-941 is under phase III clinical investigation. Squalamine, a low molecular weight aminosterol, showed strong antitumor activity when combined with chemotherapeutic materials. The angiogenic tissue inhibitor of metalloprotease 3 (TIMP-3) and tumor suppressor protein (snm23) genes from shark cartilage were cloned and characterized.

  6. Diagnostic potential of tumor DNA from ovarian cyst fluid

    PubMed Central

    Wang, Yuxuan; Sundfeldt, Karin; Mateoiu, Constantina; Shih, Ie-Ming; Kurman, Robert J; Schaefer, Joy; Silliman, Natalie; Kinde, Isaac; Springer, Simeon; Foote, Michael; Kristjansdottir, Björg; James, Nathan; Kinzler, Kenneth W; Papadopoulos, Nickolas; Diaz, Luis A; Vogelstein, Bert

    2016-01-01

    We determined whether the mutations found in ovarian cancers could be identified in the patients' ovarian cyst fluids. Tumor-specific mutations were detectable in the cyst fluids of 19 of 23 (83%) borderline tumors, 10 of 13 (77%) type I cancers, and 18 of 18 (100%) type II cancers. In contrast, no mutations were found in the cyst fluids of 18 patients with benign tumors or non-neoplastic cysts. Though large, prospective studies are needed to demonstrate the safety and clinical utility of this approach, our results suggest that the genetic evaluation of cyst fluids might be able to inform the management of the large number of women with these lesions. DOI: http://dx.doi.org/10.7554/eLife.15175.001 PMID:27421040

  7. Potential of palladium-109-labeled antimelanoma monoclonal antibody for tumor therapy

    SciTech Connect

    Fawwaz, R.A.; Wang, T.S.T.; Srivastava, S.C.; Rosen, J.M.; Ferrone, S.; Hardy, M.A.; Alderson, P.O.

    1984-07-01

    Palladium-109, a beta-emitting radionuclide, was chelated to the monoclonal antibody 225.28S to the high molecular weight antigen associated with human melanoma. Injection of the radiolabeled monoclonal antibody into nude mice bearing human melanoma resulted in significant accumulation of the radiolabel in the tumors: 19% injected dose/g; 38:1 and 61:1 tumor-to-blood ratios at 24 and 48 hr, respectively. The localization of the radiolabeled antibody in liver and kidney also was high, but appreciably lower than that achieved in tumor. These results suggest Pd-109-labeled monoclonal antibody to tumor-associated antigens may have potential applications in tumor immunotherapy.

  8. Circulating tumor cells expressing cancer stem cell marker CD44 as a diagnostic biomarker in patients with gastric cancer

    PubMed Central

    Watanabe, Toru; Okumura, Tomoyuki; Hirano, Katsuhisa; Yamaguchi, Tetsuji; Sekine, Shinichi; Nagata, Takuya; Tsukada, Kazuhiro

    2017-01-01

    Epithelial cell adhesion molecule (EpCAM) is a marker for circulating tumor cells (CTCs) in various types of cancer, while cluster of differentiation 44 (CD44) is a marker for gastric cancer (GC) stem cells. To evaluate the clinical significance of CD44+ CTCs in patients with GC in the present study, the number of EpCAM+CD44+ and EpCAM+CD44− cells were detected in the peripheral blood of 26 GC patients and 12 healthy volunteers using flow cytometry. The number (mean ± standard deviation) of EpCAM+CD44+ cells in the GC patients and healthy volunteers was 69.9±52.0 and 0.91±2.10, respectively (P=0.0001), while that of EpCAM+CD44− cells was 59.1±88.0 and 9.83±9.91, respectively (P=0.0313). The sensitivity and specificity of EpCAM+CD44+ cell detection for the identification of GC patients were 92.3 and 100%, respectively. By contrast, the values of EpCAM+CD44− cell detection were 76.9 and 83.3%, respectively. The number of EpCAM+CD44+ cells in the GC patients was correlated with the disease stage (P=0.0423), the depth of the tumor (P=0.0314) and venous invasion (P=0.0184) in the resected tumor specimens, while the number of EpCAM+CD44− cells did not correlate with any clinicopathological factors. The number of EpCAM+CD44+ cells significantly decreased following surgical resection of the tumor or induction of systemic chemotherapy. Additionally, atypical cells with a high nuclear to cytoplasmic ratio were morphologically detected in the sorted EpCAM+CD44+ cells. These results suggested that CD44+ CTCs, but not CD44− CTCs, reflect the malignant status of the primary tumor in patients with GC, providing a candidate biomarker for diagnosis and treatment response. PMID:28123556

  9. Proinflammatory and Anti-Inflammatory Cytokines Mediated by NF-κB Factor as Prognostic Markers in Mammary Tumors

    PubMed Central

    Martins, Gustavo Rodrigues; Gelaleti, Gabriela Bottaro; Moschetta, Marina Gobbe; Maschio-Signorini, Larissa Bazela; Zuccari, Debora Ap. Pires de Campos

    2016-01-01

    Inflammation results in the production of cytokines, such as interleukin- (IL-) 4 and IL-10 with immunosuppressive properties or IL-6 and TNF-α with procarcinogenic activity. Furthermore, NF-κB is the major link between inflammation and tumorigenesis. This study verified the interaction between active inflammatory cytokines in the tumor microenvironment and serum of female dogs with mammary tumors and their correlation with the clinicopathological characteristics and overall survival. Measurement of gene expression was performed by qPCR and protein levels by ELISA/Luminex. High gene and protein expression levels of NF-κB, IL-6, and TNF-α were found in association with characteristics that reflect worse prognosis and a negative correlation between TNF-α protein expression and survival time was observed (p < 0.05). In contrast, high gene and protein expression levels of IL-4 and IL-10 were associated with characteristics of better prognosis and an increased level of IL-4 and a longer survival time of animals were obtained (p < 0.05). In addition, there was a positive correlation between TNF-α and IL-6 expression in association with NF-κB. The results show a significant correlation of these cytokines with tumor development, associated with NF-κB expression and cytokines promodulation, showing that these biological factors could be used as predictive and prognostic markers in breast cancer. PMID:26989335

  10. Lipocalin 2 (LCN2) is a promising target for cholangiocarcinoma treatment and bile LCN2 level is a potential cholangiocarcinoma diagnostic marker

    PubMed Central

    Chiang, Kun-Chun; Yeh, Ta-Sen; Wu, Ren-Chin; Pang, Jong-Hwei S.; Cheng, Chi-Tung; Wang, Shang-Yu; Juang, Horng-Heng; Yeh, Chun-Nan

    2016-01-01

    Cholangiocarcinoma (CCA) is a devastating disease due to resistance to traditional chemotherapies and radiotherapies. New therapeutic strategies against CCA are urgently needed. This study investigated the role of lipocalin-2 (LCN2) in human cholangiocarcinoma as a potential therapeutic target and diagnostic marker. So far, the role of LCN2 in cancer is still controversial and studies regarding the role of LCN2 in CCA are limited. LCN2 knockdown inhibited CCA cell growth in vitro and in vivo through induction of cell cycle arrest at G0/G1 phases and decreased metastatic potential due to repression of epithelial-mesenchymal transition (EMT). Overexpression of LCN2 in CCA cells increased cell metastatic potential. We showed for the first time that the N-myc downstream regulated gene 1 (NDRG1) and NDRG2, known as tumor suppressor genes, are negatively regulated by LCN2 in CCA cells. LCN2 concentration in bile was higher in patients with CCA than that in patients with gallstones, with a cutoff value of 20.08 ng/ml making this a potential diagnostic marker. Higher LCN2 expression was associated with worse survival in patients with CCA. LCN2 is a promising target for CCA treatment and bile LCN2 level is a potential diagnostic marker for CCA. PMID:27782193

  11. Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

    PubMed Central

    Pusparajah, Priyia; Lee, Learn-Han; Abdul Kadir, Khalid

    2016-01-01

    Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed. PMID:27313539

  12. Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

    PubMed

    Pusparajah, Priyia; Lee, Learn-Han; Abdul Kadir, Khalid

    2016-01-01

    Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed.

  13. Potential of Gene Therapy for the Treatment of Pituitary Tumors

    PubMed Central

    Goya, R G.; Sarkar, D.K.; Brown, O.A.; Hereñú, C.B.

    2010-01-01

    Pituitary adenomas constitute the most frequent neuroendocrine pathology, comprising up to 15% of primary intracranial tumors. Current therapies for pituitary tumors include surgery and radiotherapy, as well as pharmacological approaches for some types. Although all of these approaches have shown a significant degree of success, they are not devoid of unwanted side effects, and in most cases do not offer a permanent cure. Gene therapy—the transfer of genetic material for therapeutic purposes—has undergone an explosive development in the last few years. Within this context, the development of gene therapy approaches for the treatment of pituitary tumors emerges as a promising area of research. We begin by presenting a brief account of the genesis of prolactinomas, with particular emphasis on how estradiol induces prolactinomas in animals. In so doing, we discuss the role of each of the recently discovered growth inhibitory and growth stimulatory substances and their interactions in estrogen action. We also evaluate the cell-cell communication that may govern these growth factor interactions and subsequently promote the growth and survival of prolactinomas. Current research efforts to implement gene therapy in pituitary tumors include the treatment of experimental prolactinomas or somatomammotropic tumors with adenoviral vector-mediated transfer of the suicide gene for the herpes simplex type 1 (HSV1) thymidine kinase, which converts the prodrug ganciclovir into a toxic metabolite. In some cases, the suicide transgene has been placed under the control of pituitary cell-type specific promoters, like the human prolactin or human growth hormone promoters. Also, regulatable adenoviral vector systems are being assessed in gene therapy approaches for experimental pituitary tumors. In a different type of approach, an adenoviral vector, encoding the human retinoblastoma suppressor oncogene, has been successfully used to rescue the phenotype of spontaneous pituitary

  14. Analysis of potential markers for detection of submicroscopic lymph node metastases in breast cancer

    PubMed Central

    Merrie, A E H; Yun, K; Gunn, J; Phillips, L V; McCall, J L

    1999-01-01

    We have developed sensitive assays for cytokeratin (K) 8, 16, 19, stromelysin 3 (ST3), MUC1 and maspin mRNAs using reverse transcription polymerase chain reaction (RT-PCR) and used these to assess lymph node status in patients undergoing surgery for breast cancer. In addition the RT-PCR assays were tested against lymph nodes from non-cancer patients to determine their specificity. Despite high sensitivity RT-PCR assays for K8, K16, K19, ST3 and maspin were not found to be useful as markers of submicroscopic disease as transcripts of these genes were detected in the great majority of control lymph nodes tested. Expression of MUC1 was also not found to be useful as it was both insensitive and non-specific. The importance of assessing potential markers against an adequately sized control population is demonstrated, as failure to do so can lead to erroneous conclusions. © 1999 Cancer Research Campaign PMID:10471055

  15. Mitosis Is a Source of Potential Markers for Screening and Survival and Therapeutic Targets in Cervical Cancer

    PubMed Central

    Espinosa, Ana María; Alfaro, Ana; Roman-Basaure, Edgar; Guardado-Estrada, Mariano; Palma, Ícela; Serralde, Cyntia; Medina, Ingrid; Juárez, Eligia; Bermúdez, Miriam; Márquez, Edna; Borges-Ibáñez, Manuel; Muñoz-Cortez, Sergio; Alcántara-Vázquez, Avissai; Alonso, Patricia; Curiel-Valdez, José; Kofman, Susana; Villegas, Nicolas; Berumen, Jaime

    2013-01-01

    The effect of preventive human papillomavirus (HPV) vaccination on the reduction of the cervical cancer (CC) burden will not be known for 30 years. Therefore, it’s still necessary to improve the procedures for CC screening and treatment. The objective of this study was to identify and characterize cellular targets that could be considered potential markers for screening or therapeutic targets. A pyramidal strategy was used. Initially the expression of 8,638 genes was compared between 43 HPV16-positive CCs and 12 healthy cervical epitheliums using microarrays. A total of 997 genes were deregulated, and 21 genes that showed the greatest deregulation were validated using qRT-PCR. The 6 most upregulated genes (CCNB2, CDC20, PRC1, SYCP2, NUSAP1, CDKN3) belong to the mitosis pathway. They were further explored in 29 low-grade cervical intraepithelial neoplasias (CIN1) and 21 high-grade CIN (CIN2/3) to investigate whether they could differentiate CC and CIN2/3 (CIN2+) from CIN1 and controls. CCNB2, PRC1, and SYCP2 were mostly associated with CC and CDC20, NUSAP1, and CDKN3 were also associated with CIN2/3. The sensitivity and specificity of CDKN3 and NUSAP1 to detect CIN2+ was approximately 90%. The proteins encoded by all 6 genes were shown upregulated in CC by immunohistochemistry. The association of these markers with survival was investigated in 42 CC patients followed up for at least 42 months. Only CDKN3 was associated with poor survival and it was independent from clinical stage (HR = 5.9, 95%CI = 1.4–23.8, p = 0.01). CDKN3 and NUSAP1 may be potential targets for the development of screening methods. Nevertheless, further studies with larger samples are needed to define the optimal sensitivity and specificity. Inhibition of mitosis is a well-known strategy to combat cancers. Therefore, CDKN3 may be not only a screening and survival marker but a potential therapeutic target in CC. However, whether it’s indispensable for tumor growth remains to be

  16. Investigation of in vivo potential of scorpion venom against skin tumorigenesis in mice via targeting markers associated with cancer development

    PubMed Central

    Al Asmari, Abdulrahman K; Khan, Abdul Quaiyoom

    2016-01-01

    Cancer is the leading cause of morbidity and mortality all over the world in spite of the advances made in its management. In this study, we investigated the in vivo anti-tumorigenic potential of the venom obtained from a medically important scorpion species Leiurus quinquestriatus on chemically induced skin cancer in mice. Animals were divided into five groups, with 13 animals in each group. All the treatments were given topically on the shaved dorsal surface of the skin. Animals in Group 1 received vehicle only (0.2 mL acetone). Moreover, 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol per mouse) was applied to all the animals in the remaining four groups. After 1 week, different concentrations of venom (17.5 μg, 35 μg, and 52.5 μg per animal) were applied to each animal in the Groups III–V. Thirty minutes after the application of venom, croton oil was applied on the same position where venom was administered to the animals of Groups III–V. Animals in Group II were treated as the positive control (without venom) and received croton oil as in Groups III–V. The findings of this study revealed that venom extract of L. quinquestriatus inhibits DMBA + croton oil-induced mouse skin tumor incidence and tumor multiplicity. Venom treatment also decreased the expression of proinflammatory cytokines. Immunohistochemistry results showed a downregulation of the expression of molecular markers such as Ki-67, nuclear factor kappa-B, cyclooxygenase-2, B-cell lymphoma-2, and vascular endothelial growth factor, in venom-treated animals. Our findings suggest that the venom of L. quinquestriatus possesses in vivo anticancer potential and may be used in the development of anticancer molecules. PMID:27799739

  17. Systematic analysis of 18F-FDG PET and metabolism, proliferation and hypoxia markers for classification of head and neck tumors

    PubMed Central

    2014-01-01

    Background Quantification of molecular cell processes is important for prognostication and treatment individualization of head and neck cancer (HNC). However, individual tumor comparison can show discord in upregulation similarities when analyzing multiple biological mechanisms. Elaborate tumor characterization, integrating multiple pathways reflecting intrinsic and microenvironmental properties, may be beneficial to group most uniform tumors for treatment modification schemes. The goal of this study was to systematically analyze if immunohistochemical (IHC) assessment of molecular markers, involved in treatment resistance, and 18F-FDG PET parameters could accurately distinguish separate HNC tumors. Methods Several imaging parameters and texture features for 18F-FDG small-animal PET and immunohistochemical markers related to metabolism, hypoxia, proliferation and tumor blood perfusion were assessed within groups of BALB/c nu/nu mice xenografted with 14 human HNC models. Classification methods were used to predict tumor line based on sets of parameters. Results We found that 18F-FDG PET could not differentiate between the tumor lines. On the contrary, combined IHC parameters could accurately allocate individual tumors to the correct model. From 9 analyzed IHC parameters, a cluster of 6 random parameters already classified 70.3% correctly. Combining all PET/IHC characteristics resulted in the highest tumor line classification accuracy (81.0%; cross validation 82.0%), which was just 2.2% higher (p = 5.2×10-32) than the performance of the IHC parameter/feature based model. Conclusions With a select set of IHC markers representing cellular processes of metabolism, proliferation, hypoxia and perfusion, one can reliably distinguish between HNC tumor lines. Addition of 18F-FDG PET improves classification accuracy of IHC to a significant yet minor degree. These results may form a basis for development of tumor characterization models for treatment allocation purposes

  18. Inverse Relationship between Tumor Proliferation Markers and Connexin Expression in a Malignant Cardiac Tumor Originating from Mesenchymal Stem Cell Engineered Tissue in a Rat in vivo Model

    PubMed Central

    Spath, Cathleen; Schlegel, Franziska; Leontyev, Sergey; Mohr, Friedrich-Wilhelm; Dhein, Stefan

    2013-01-01

    Background: Recently, we demonstrated the beneficial effects of engineered heart tissues for the treatment of dilated cardiomyopathy in rats. For further development of this technique we started to produce engineered tissue (ET) from mesenchymal stem cells. Interestingly, we observed a malignant tumor invading the heart with an inverse relationship between proliferation markers and connexin expression. Methods: Commercial CD54+/CD90+/CD34−/CD45− bone marrow derived mesenchymal rat stem cells (cBM-MSC), characterized were used for production of mesenchymal stem-cell-ET (MSC-ET) by suspending them in a collagen I, matrigel-mixture and cultivating for 14 days with electrical stimulation. Three MSC-ET were implanted around the beating heart of adult rats for days. Another three MSC-ET were produced from freshly isolated rat bone marrow derived stem cells (sBM-MSC). Results: Three weeks after implantation of the MSC-ETs the hearts were surgically excised. While in 5/6 cases the ET was clearly distinguishable and was found as a ring containing mostly connective tissue around the heart, in 1/6 the heart was completely surrounded by a huge, undifferentiated, pleomorphic tumor originating from the cMSC-ET (cBM-MSC), classified as a high grade malignant sarcoma. Quantitatively we found a clear inverse relationship between cardiac connexin expression (Cx43, Cx40, or Cx45) and increased Ki-67 expression (Cx43: p < 0.0001, Cx45: p < 0.03, Cx40: p < 0.014). At the tumor-heart border there were significantly more Ki-67 positive cells (p = 0.001), and only 2% Cx45 and Ki-67-expressing cells, while the other connexins were nearly completely absent (p < 0.0001). Conclusion and Hypothesis: These observations strongly suggest the hypothesis, that invasive tumor growth is accompanied by reduction in connexins. This implicates that gap junction communication between tumor and normal tissue is reduced or absent, which could mean that growth and differentiation

  19. Predictive potential of photoacoustic spectroscopy in breast tumor detection based on xenograft serum profiles

    NASA Astrophysics Data System (ADS)

    Priya, Mallika; Chandra, Subhas; Rao, Bola Sadashiva Satish; Ray, Satadru; Mahato, Krishna Kishore

    2015-02-01

    Breast cancer is the second most common cancer all over the world. Heterogeneity in breast cancer makes it a difficult task to detect with the existing serum markers at an early stage. With an aim to detect the disease early at the pre-malignant level, MCF-7 cells xenografts were developed using female nude mice and blood serum were extracted on days 0th, 10th, 15th & 20th post tumor cells injection (N=12 for each time point). Photoacoustic spectra were recorded on the serum samples at 281nm pulsed laser excitations. A total of 144 time domain spectra were recorded from 48 serum samples belonging to 4 different time points. These spectra were then converted into frequency domain (0-1250kHz) using MATLAB algorithms. Subsequently, seven features (mean, median, mode, variance, standard deviation, area under the curve & spectral residuals after 10th degree polynomial fit) were extracted from them and used for PCA. Further, using the first three Principal components (PCs) of the data, Linear Discriminate Analysis has been carried out. The performance of the analysis showed 82.64% accuracy in predicting various time points under study. Further, frequency-region wise analysis was also performed on the data and found 95 - 203.13 kHz region most suitable for the discrimination among the 4 time points. The analysis provided a clear discrimination in most of the spectral features under study suggesting that the photoacoustic technique has the potential to be a diagnostic tool for early detection of breast tumor development

  20. Computerized method for estimation of the location of a lung tumor on EPID cine images without implanted markers in stereotactic body radiotherapy

    NASA Astrophysics Data System (ADS)

    Arimura, H.; Egashira, Y.; Shioyama, Y.; Nakamura, K.; Yoshidome, S.; Anai, S.; Nomoto, S.; Honda, H.; Toyofuku, F.; Higashida, Y.; Onizuka, Y.; Terashima, H.

    2009-02-01

    The purpose of this study was to develop a computerized method for estimation of the location of a lung tumor in cine images on an electronic portal imaging device (EPID) without implanted markers during stereotactic body radiotherapy (SBRT). Each tumor region was segmented in the first EPID cine image, i.e., reference portal image, based on a multiple-gray level thresholding technique and a region growing technique, and then the image including the tumor region was cropped as a 'tumor template' image. The tumor location was determined as the position in which the tumor template image took the maximum cross-correlation value within each consecutive portal image, which was acquired in cine mode on the EPID in treatment. EPID images with 512 × 384 pixels (pixel size: 0.56 mm) were acquired at a sampling rate of 0.5 frame s-1 by using energies of 4, 6 or 10 MV on linear accelerators. We applied our proposed method to EPID cine images (226 frames) of 12 clinical cases (ages: 51-83, mean: 72) with a non-small cell lung cancer. As a result, the average location error between tumor points obtained by our method and the manual method was 1.47 ± 0.60 mm. This preliminary study suggests that our method based on the tumor template matching technique might be feasible for tracking the location of a lung tumor without implanted markers in SBRT.

  1. Specific markers, micro-environmental anomalies and tropism: opportunities for gold nanorods targeting of tumors in laser-induced hyperthermia

    NASA Astrophysics Data System (ADS)

    Tatini, Francesca; Ratto, Fulvio; Centi, Sonia; Landini, Ida; Nobili, Stefania; Witort, Ewa; Fusi, Franco; Capaccioli, Sergio; Mini, Enrico; Pini, Roberto

    2014-03-01

    Gold nanorods (GNRs) are optimal contrast agents for near-infrared (NIR) laser-induced photothermal ablation of cancer. Selective targeting of cancer cells can be pursued by attaching specific molecules on the particles surface or by the use of cellular vectors loaded with GNRs. We performed and tested various targeting approaches by means of GNRs functionalization with (i) antibodies against Cancer-Antigen-125 (CA-125), (ii) inhibitors of the carbonic anhydrase 9 (CA9) and (iii) by the use of macrophages as cellular vectors. GNRs with a NIR absorption band at 810 nm were synthesized and PEGylated. For GNRs functionalization the targets of choice were CA-125, the most widely used biomarker for ovarian cancer, and CA9, overexpressed by hypoxic cells which are often located within the tumor mass. In the case of cellular vectors, to be used as Trojan horses naturally able to reach tumor areas, the surface of PEG-GNRs was modified to achieve unspecific interactions with macrophage membranes. In all cases the cellular uptake was evaluated by silver staining and cell viability was assessed by MTT test. Then tests of laser-induced GNRs-mediated hyperthermia were performed in various cell cultures illuminating with an 810 nm diode laser (CW, 0,5-4 W/cm2 power density, 1-10 min exposure time) and cell death was evaluated. Each targeting strategy we tested may be used alone or in combination, to maximize the tumor loading and therefore the efficiency of the laser treatment. Moreover, a multiple approach could help when the tumor variability interferes with the targeting directed to a single marker.

  2. Prognostic Significance of the Metabolic Marker Hexokinase-2 in Various Solid Tumors: A Meta-Analysis

    PubMed Central

    Liu, Yulin; Wu, Ke; Shi, Liang; Xiang, Fan; Tao, Kaixiong; Wang, Guobin

    2016-01-01

    Objective Recently, numerous studies have reported that hexokinase-2 (HK2) is aberrantly expressed in cancer, indicating that HK2 plays a pivotal role in the development and progression of cancer. However, its prognostic significance in solid tumor remains unclear. Accordingly, we performed a meta-analysis to assess the prognostic value of HK2 in solid tumor. Methods Eligible studies were identified using PubMed, Embase, and Web of Science databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) were estimated with random effects or fixed effects models, respectively. Subgroup analysis was also performed according to patients’ ethnicities, tumor types, detection methods, and analysis types. Results Data from 21 included studies with 2532 patients were summarized. HK2 overexpression was significantly associated with worse OS (pooled HR = 1.90, 95% CI = 1.51–2.38, p < 0.001) and PFS (pooled HR = 2.91, 95% CI = 2.02–4.22, p < 0.001) in solid tumor. As to a specific form of cancer, the negative effect of HK2 on OS was observed in hepatocellular carcinoma (pooled HR = 2.06, 95% CI = 1.67–2.54, p < 0.001), gastric cancer (pooled HR = 1.72, 95% CI = 1.09–2.71, p = 0.020), colorectal cancer (pooled HR = 2.89, 95% CI = 1.62–5.16, p < 0.001), but not in pancreatic cancer (pooled HR = 1.13, 95% CI = 0.28–4.66, p = 0.864). No publication bias was found in the included studies for OS (Begg’s test, p = 0.325; Egger’s test, p = 0.441). Conclusion In this meta-analysis, we identified that elevated HK2 expression was significantly associated with shorter OS and PFS in patients with solid tumor, but the association varies according to cancer type. PMID:27824926

  3. Leptomeningeal carcinomatosis as only pathological finding at FDG-PET/CT in case of tumor marker elevation in breast cancer.

    PubMed

    Grande, Maria Luz Dominguez; Rayo, Juan Ignacio; Serrano, Justo; Infante, Jose Rafael; Garcia, Lucia; Duran, Carmen; Gomez-Caminero, Felipe

    2014-01-01

    Leptomeningeal carcinomatosis is an infrequent disease and although its treatment is palliative, earlier diagnosis will lead to prolonged survival and improve functional outcome. Whole-body FDG-PET allows the entire spinal cord to be examined noninvasively, so close attention should be paid to the spinal canal, since these lesions can easily be mistaken for physiologic uptake, sometimes there is no clinical suspicion and may occur without concurrent active cancer. We present a female patient with a history of carcinoma of the breast, who presented an elevation of serum tumor marker CA 15-3. An FDG-PET/CT study only revealed multiple abnormal uptake at the vertebral foramen at thoracic and lumbosacral regions suggesting leptomeningeal metastases that were confirmed by MRI and cerebrospinal fluid cytology.

  4. Prognostic Value of Invasion, Markers of Proliferation, and Classification of Giant Pituitary Tumors, in a Georeferred Cohort in Brazil of 50 Patients, with a Long-Term Postoperative Follow-Up

    PubMed Central

    de Magalhães, Albino Verçosa

    2016-01-01

    Although some pituitary adenomas may have an aggressive behavior, the vast majority are benign. There are still controversies about predictive factors regarding the biological behavior of these particular tumors. This study evaluated potential markers of invasion and proliferation compared to current classification patterns and epidemiogeographical parameters. The study included 50 patients, operated on for tumors greater than 30 mm, with a mean postoperative follow-up of 15.2 ± 4.8 years. Pituitary magnetic resonance was used to evaluate regrowth, invasion, and extension to adjacent tissue. Three tissue biomarkers were analyzed: p53, Ki-67, and c-erbB2. Tumors were classified according to a combination of histological and radiological features, ranging from noninvasive and nonproliferative (grade 1A) to invasive-proliferative (grade 2B). Tumors grades 2A and 2B represented 42% and 52%, respectively. Ki-67 (p = 0.23) and c-erbB2 (p = 0.71) had no significant relation to tumor progression status. P53 (p = 0.003), parasellar invasion (p = 0.03), and classification, grade 2B (p = 0.01), were associated with worse clinical outcome. Parasellar invasion prevails as strong predictive factor of tumor recurrence. Severe suprasellar extension should be considered as invasion parameter and could impact prognosis. No environmental factors or geographical cluster were associated with tumor behavior. PMID:27635138

  5. Simultaneous immobilization of glucose oxidase on the surface and cavity of hollow gold nanospheres as labels for highly sensitive electrochemical immunoassay of tumor marker.

    PubMed

    Song, Zhongju; Yuan, Ruo; Chai, Yaqin; Jiang, Wen; Su, Huilan; Che, Xin; Ran, Xiaoqi

    2011-01-15

    A novel tracer, glucose oxidase (GOD)-functionalized hollow gold nanospheres encapsulating glucose oxidase (Au(shell)@GOD), was designed to label the ferrocenemonocarboxylic-grafted secondary antibodies (Fc@Ab(2)) for highly sensitive detection of tumor marker using carboxyl group functionalized multiwall carbon nanotubes as platform. Initially, Au(shell)@GOD was synthesized specially by reverse micelle approach, and then the labeling of antibody and the preparation of GOD-functionalized Au(shell)@GOD were performed by one-pot assembly of Fc@Ab(2) and GOD on the surface of Au(shell)@GOD. The ferrocene used to label antibodies acted as a mediator of electron transfer between GOD and electrode surface. The high-content glucose oxidase in the tracer (on the surface and in the cavity) could significantly amplify the amperometric signal for sandwich-type immunoassay. Using carcinoembryonic antigen (CEA) as model analyte, the designed tracer showed linear range from 0.02 to 5.0 ng mL(-1) with the detection limit down to 6.7 pg mL(-1). The assay results of serum samples with the proposed method were in an acceptable agreement with the reference values. The new protocol showed acceptable stability and reproducibility, high sensitivity, and good precision, which could provide a promising potential for clinical screening and diagnosis of tumor disease.

  6. Functionalization of Carbon Nanomaterial Surface by Doxorubicin and Antibodies to Tumor Markers

    NASA Astrophysics Data System (ADS)

    Perepelytsina, Olena M.; Yakymchuk, Olena M.; Sydorenko, Mychailo V.; Bakalinska, Olga N.; Bloisi, Francesco; Vicari, Luciano Rosario Maria

    2016-06-01

    The actual task of oncology is effective treatment of cancer while causing a minimum harm to the patient. The appearance of polymer nanomaterials and technologies launched new applications and approaches of delivery and release of anticancer drugs. The goal of work was to test ultra dispersed diamonds (UDDs) and onion-like carbon (OLCs) as new vehicles for delivery of antitumor drug (doxorubicin (DOX)) and specific antibodies to tumor receptors. Stable compounds of UDDs and OLCs with DOX were obtained. As results of work, an effectiveness of functionalization was 2.94 % w/ w for OLC-DOX and 2.98 % w/ w for UDD-DOX. Also, there was demonstrated that UDD-DOX and OLC-DOX constructs had dose-dependent cytotoxic effect on tumor cells in the presence of trypsin. The survival of adenocarcinoma cells reduced from 52 to 28 % in case of incubation with the UDD-DOX in concentrations from 8.4-2.5 to 670-20 μg/ml and from 72 to 30 % after incubation with OLC-DOX. Simultaneously, antibodies to epidermal growth factor maintained 75 % of the functional activity and specificity after matrix-assisted pulsed laser evaporation deposition. Thus, the conclusion has been made about the prospects of selected new methods and approaches for creating an antitumor agent with capabilities targeted delivery of drugs.

  7. Ligand-independent assembly of purified soluble magic roundabout (Robo4), a tumor-specific endothelial marker.

    PubMed

    Yoshikawa, Mai; Mukai, Yohei; Okada, Yoshiaki; Yoshioka, Yasuo; Tsunoda, Shin-Ichi; Tsutsumi, Yasuo; Okada, Naoki; Aird, William C; Doi, Takefumi; Nakagawa, Shinsaku

    2008-09-01

    Magic roundabout (Robo4) is the fourth recently identified member of the roundabout receptor family. Robo4 is predominantly expressed in embryonic or tumor vascular endothelium and is considered important for vascular development and as a candidate tumor endothelial marker. Much remains unknown about the Robo4 molecule, however, such as its ligands, structure, and the details of its function. Thus, we aimed to establish an expression and purification method for obtaining soluble recombinant human Robo4 (shRobo4) and mouse Robo4 (smRobo4) for use in Robo4 characterization studies. In this work, we expressed the extracellular domain of hRobo4 and mRobo4 in mammalian 293F cells and purified them by two-step chromatography. Based on gel-filtration chromatography and Blue Native polyacrylamide gel electrophoresis, these purified proteins exist as multimers. The shRobo4 and smRobo4 we obtained will be useful in advanced studies to determine the importance of multimerization, identify the ligands, and elucidate the ligand-receptor interactions and Robo4-mediated signaling. The results of these studies will help to elucidate the role of Robo4 in angiogenesis and perhaps eventually contribute to the development of novel vessel-targeting therapies.

  8. Phosphoproteomic profiling of tumor tissues identifies HSP27 Ser82 phosphorylation as a robust marker of early ischemia

    PubMed Central

    Zahari, Muhammad Saddiq; Wu, Xinyan; Pinto, Sneha M.; Nirujogi, Raja Sekhar; Kim, Min-Sik; Fetics, Barry; Philip, Mathew; Barnes, Sheri R.; Godfrey, Beverly; Gabrielson, Edward; Nevo, Erez; Pandey, Akhilesh

    2015-01-01

    Delays between tissue collection and tissue fixation result in ischemia and ischemia-associated changes in protein phosphorylation levels, which can misguide the examination of signaling pathway status. To identify a biomarker that serves as a reliable indicator of ischemic changes that tumor tissues undergo, we subjected harvested xenograft tumors to room temperature for 0, 2, 10 and 30 minutes before freezing in liquid nitrogen. Multiplex TMT-labeling was conducted to achieve precise quantitation, followed by TiO2 phosphopeptide enrichment and high resolution mass spectrometry profiling. LC-MS/MS analyses revealed phosphorylation level changes of a number of phosphosites in the ischemic samples. The phosphorylation of one of these sites, S82 of the heat shock protein 27 kDa (HSP27), was especially abundant and consistently upregulated in tissues with delays in freezing as short as 2 minutes. In order to eliminate effects of ischemia, we employed a novel cryogenic biopsy device which begins freezing tissues in situ before they are excised. Using this device, we showed that the upregulation of phosphorylation of S82 on HSP27 was abrogated. We thus demonstrate that our cryogenic biopsy device can eliminate ischemia-induced phosphoproteome alterations, and measurements of S82 on HSP27 can be used as a robust marker of ischemia in tissues. PMID:26329039

  9. Smoking-related DNA adducts as potential diagnostic markers of lung cancer: new perspectives.

    PubMed

    Grigoryeva, E S; Kokova, D A; Gratchev, A N; Cherdyntsev, E S; Buldakov, M A; Kzhyshkowska, J G; Cherdyntseva, N V

    2015-03-01

    In recent years, the new direction such as identification of informative circulating markers reflecting molecular genetic changes in the DNA of tumor cells was actively developed. Smoking-related DNA adducts are very promising research area, since they indicate high pathogenetic importance in the lung carcinogenesis and can be identified in biological samples with high accuracy and reliability using highly sensitive mass spectrometry methods (TOF/TOF, TOF/MS, MS/MS). The appearance of DNA adducts in blood or tissues is the result of the interaction of carcinogenic factors, such as tobacco constituents, and the body reaction which is determined by individual characteristics of metabolic and repair systems. So, DNA adducts may be considered as a cumulative mirror of heterogeneous response of different individuals to smoking carcinogens, which finally could determine the risk for lung cancer. This review is devoted to analysis of the role of DNA adducts in lung carcinogenesis in order to demonstrate their usefulness as cancer associated markers. Currently, there are some serious limitations impeding the widespread use of DNA adducts as cancer biomarkers, due to failure of standardization of mass spectrometry analysis in order to correctly measure the adduct level in each individual. However, it is known that all DNA adducts are immunogenic, their accumulation over some threshold concentration leads to the appearance of long-living autoantibodies. Thus, detection of an informative pattern of autoantibodies against DNA adducts using innovative multiplex ELISA immunoassay may be a promising approach to find lung cancer at an early stage in high-risk groups (smokers, manufacturing workers, urban dwellers).

  10. Chondrogenic potential of subpopulations of cells expressing mesenchymal stem cell markers derived from human synovial membranes.

    PubMed

    Arufe, M C; De la Fuente, A; Fuentes, I; de Toro, F J; Blanco, F J

    2010-11-01

    In this study we analyzed the chondrogenic potential of subpopulations of mesenchymal stem cells (MSCs) derived from human synovial membranes enriched for CD73, CD106, and CD271 markers. Subpopulations of human synovial membrane MSCs enriched for CD73, CD106, and CD271 markers were isolated using a cytometry sorter and characterized by flow cytometry for MSC markers. The expression of Sox9, Nanog, and Runx2 genes by these cells was measured by reverse transcriptase-polymerase chain reaction. The chondrogenesis of each subpopulation was assessed by culturing the cells in a defined medium to produce spontaneous spheroid formation and differentiation towards chondrocyte-like cells. The examination of the spheroids by histological and immunohistochemical analyses for collagen type II (COL2), aggrecan, collagen type I (COL1), metalloprotease 13 (MMP13), and collagen type X (COLX) levels were performed to assess their chondrogenesis capacity. The adipogenesis and osteogenesis potential of each subpopulation was determined using commercial media; the resulting cells were stained with oil red O or red alizarin to test the degree of differentiation. The subpopulations had different profiles of cells positive for the MSC markers CD44, CD69, CD73, CD90, and CD105 and showed different expression levels of the genes Sox9, Nanog, and Runx2 involved in chondrogenesis, undifferentiation, and osteoblastogenesis, respectively. Immunohistochemical analysis demonstrated that COL1, COL2, COLX, MMP13, and aggrecan were expressed in the spheroids as soon as 14 days of culture. The CD271(+) subpopulation expressed the highest levels of COL2 staining compared to the other subpopulations. CD105 and Runx2 were shown by immunohistochemistry and genetic analysis to have significantly higher expression CD271(+) subpopulation than the other subpopulations. Spheroids formed from CD271-enriched and CD73-enriched MSCs from normal human synovial membranes mimic the native cartilage extracellular

  11. Epigenetic silencing of tumor suppressor genes: Paradigms, puzzles, and potential.

    PubMed

    Kazanets, Anna; Shorstova, Tatiana; Hilmi, Khalid; Marques, Maud; Witcher, Michael

    2016-04-01

    Cancer constitutes a set of diseases with heterogeneous molecular pathologies. However, there are a number of universal aberrations common to all cancers, one of these being the epigenetic silencing of tumor suppressor genes (TSGs). The silencing of TSGs is thought to be an early, driving event in the oncogenic process. With this in consideration, great efforts have been made to develop small molecules aimed at the restoration of TSGs in order to limit tumor cell proliferation and survival. However, the molecular forces that drive the broad epigenetic reprogramming and transcriptional repression of these genes remain ill-defined. Undoubtedly, understanding the molecular underpinnings of transcriptionally silenced TSGs will aid us in our ability to reactivate these key anti-cancer targets. Here, we describe what we consider to be the five most logical molecular mechanisms that may account for this widely observed phenomenon: 1) ablation of transcription factor binding, 2) overexpression of DNA methyltransferases, 3) disruption of CTCF binding, 4) elevation of EZH2 activity, 5) aberrant expression of long non-coding RNAs. The strengths and weaknesses of each proposed mechanism is highlighted, followed by an overview of clinical efforts to target these processes.

  12. Leukocytosis after routine cranial surgery: A potential marker for brain damage in intracranial surgery

    PubMed Central

    Agrawal, Deepak; Kurwale, Nilesh; Sharma, Bhawani Shankar

    2016-01-01

    Aims and Objectives: Leukocytosis after intracranial surgery may create concern about possible infection, especially when associated with fever. Knowledge of the expected degree of leukocytosis after surgery would assist in the interpretation of leukocytosis. It was hypothesized that the degree of leukocytosis after intracranial surgery correlated with the extent of brain damage inflicted during the surgery. Materials and Methods: In this prospective study conducted over 6 months, consecutive patients undergoing either elective resections of brain tumors (having significant collateral brain damage) or aneurysm clipping (with minimal collateral brain damage) were studied. Total blood leukocyte count was checked daily in the morning for the first five postoperative days in both the groups. The mean of the leukocyte count ratio (postoperative leukocyte count/preoperative leukocyte count) on each day was calculated for each group. Results: There were 76 patients, 46 in the test group and 30 controls. Both groups were well matched in age, sex, duration of surgery, and intraoperative fluid balance. The mean leukocyte count ratio on POD1 in the tumor group was significantly higher (1.87) as compared to 1.1 in the aneurysm group (P = 0.001). This difference in the leukocyte count ratio between the groups was maintained on the second and third postoperative days, with decreasing level of significance after the third day. Conclusions: This study shows that intraoperative brain injury is associated with leukocytosis in the immediate postoperative period. This can assist in the interpretation of leukocytosis after intracranial surgeries and could be a quantitative marker for brain injury in patients undergoing intracranial surgery. PMID:27057215

  13. Tumor-targeting bacterial therapy: A potential treatment for oral cancer (Review)

    PubMed Central

    LIU, SAI; XU, XIAOPING; ZENG, XIN; LI, LONGJIANG; CHEN, QIANMING; LI, JING

    2014-01-01

    Certain obligate or facultative anaerobic bacteria, which exhibit an inherent ability to colonize solid tumors in vivo, may be used in tumor targeting. As genetically manipulated bacteria may actively and specifically penetrate into the tumor tissue, bacterial therapy is becoming a promising approach in the treatment of tumors. However, to the best of our knowledge, no reports have been published thus far regarding the bacterial treatment of oral cancer, one of the most common types of cancer worldwide. In this review, the progress in the understanding of bacterial strategies used in tumor-targeted therapy is discussed and particular bacterial strains that may have great therapeutic potential in oral squamous cell carcinoma (OSCC) tumor-targeted therapy are predicted as determined by previous studies. PMID:25364397

  14. Heterogeneity of isozyme expression in tumor cells does not correlate with metastatic potential.

    PubMed

    Aukerman, S L; Siciliano, M J; Fidler, I J

    1986-01-01

    The major purpose of these studies was to determine whether the expression of isozymes by tumor cells was heterogeneous among tumor cell subpopulations within a neoplasm and whether expression of one or another isozyme correlated with metastatic potential of tumor cells. The expression levels of 40 isozymes were determined in 56 cell lines, many of them clonal, from nine different murine and human tumors. The enzymes chosen for study are involved in nucleotide, carbohydrate and pentose phosphate metabolism, and as such are indicators of the general metabolic and differentiational status of the cell. The tumors studied included two murine and two human malignant melanomas, four murine fibrosarcomas, and one human prostatic adenocarcinoma. The lines isolated from these tumors consisted of cells that are tumorigenic non-metastatic, tumorigenic low metastatic and tumorigenic highly metastatic. Clonally derived cell lines from a given tumor differed in their expression of a number of different isozymes, including adenosine deaminase, creatine phosphokinase-B and lactate dehydrogenase. Different patterns of isozyme expression were observed among different tumor types as well as between tumors of the same type; however, there were no differences in isozyme expression for any enzyme tested that correlated with metastatic ability of tumor cells.

  15. Androgen receptor is a potential novel prognostic marker and oncogenic target in osteosarcoma with dependence on CDK11

    PubMed Central

    Liao, Yunfei; Sassi, Slim; Halvorsen, Stefan; Feng, Yong; Shen, Jacson; Gao, Yan; Cote, Gregory; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng

    2017-01-01

    Osteosarcoma is the most common bone cancer in children and adolescents. Previously, we have found that cyclin-dependent kinase 11 (CDK11) signaling was essential for osteosarcoma cell growth and survival. Subsequently, CDK11 siRNA gene targeting, expression profiling, and network reconstruction of differentially expressed genes were performed between CDK11 knock down and wild type osteosarcoma cells. Reconstructed network of the differentially expressed genes pointed to the AR as key to CDK11 signaling in osteosarcoma. CDK11 increased transcriptional activation of AR gene in osteosarcoma cell lines. AR protein was highly expressed in various osteosarcoma cell lines and patient tumor tissues. Tissue microarray analysis showed that the disease-free survival rate for patients with high-expression of AR was significantly shorter than for patients with low-expression of AR. In addition, AR gene expression knockdown via siRNA greatly inhibited cell growth and viability. Similar results were found in osteosarcoma cells treated with AR inhibitor. These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment. PMID:28262798

  16. MFAP5 and TNNC1: Potential markers for predicting occult cervical lymphatic metastasis and prognosis in early stage tongue cancer.

    PubMed

    Yang, Xi; Wu, Kailiu; Li, Siyi; Hu, Longwei; Han, Jing; Zhu, Dongwang; Tian, Xuerui; Liu, Wei; Tian, Zhen; Zhong, Laiping; Yan, Ming; Zhang, Chenping; Zhang, Zhiyuan

    2017-01-10

    The purpose of this study is to identify candidate genes that could predict prognosis of early-stage tongue squamous cell carcinoma (TSCC) and its occult cervical lymphatic metastasis by large-scale gene expression profiling. Tumor tissue and matched normal mucosa samples were collected from patients with TSCC and analyzed with Affymetrix HTA2.0 high-density oligonucleotide array. Differentially expressed genes in TSCC with cervical lymph node metastasis (CLNM) were further analyzed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes for their functions and related pathways. A total of 107 differentially expressed genes (p < 0.05) were identified by microarray in TSCC samples with CLNM (n = 6) compared to those without CLNM (n = 6). Genes involved in the cell-matrix adherens junction and migration function including MFAP5, TNNC1, MGP, FBFBP1 and FBXO32 were selected and validated by RT-PCR in TSCC samples (n = 32). Of the five genes, MFAP5 and TNCC1 expressions were further validated by immohistochemistry (n = 61). The significant positive correlation between MFAP5 and TNNC1 expression (p<0.001) was observed. Notably, over-expression of MFAP5 and TNNC1 were correlated with CLNM, metastasis relapse-free survival and overall survival. Our findings indicated that MFAP5 and TNNC1 may be potential markers for predicting occult cervical lymphatic metastasis and prognosis of oral tongue carcinoma.

  17. Assessment of Tumor Radioresponsiveness and Metastatic Potential by Dynamic Contrast-Enhanced Magnetic Resonance Imaging

    SciTech Connect

    Ovrebo, Kirsti Marie; Gulliksrud, Kristine; Mathiesen, Berit; Rofstad, Einar K.

    2011-09-01

    Purpose: It has been suggested that gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may provide clinically useful biomarkers for personalized cancer treatment. In this preclinical study, we investigated the potential of DCE-MRI as a noninvasive method for assessing the radioresponsiveness and metastatic potential of tumors. Methods and Materials: R-18 melanoma xenografts growing in BALB/c nu/nu mice were used as experimental tumor models. Fifty tumors were subjected to DCE-MRI, and parametric images of K{sup trans} (the volume transfer constant of Gd-DTPA) and v{sub e} (the fractional distribution volume of Gd-DTPA) were produced by pharmacokinetic analysis of the DCE-MRI series. The tumors were irradiated after the DCE-MRI, either with a single dose of 10 Gy for detection of radiobiological hypoxia (30 tumors) or with five fractions of 4 Gy in 48 h for assessment of radioresponsiveness (20 tumors). The host mice were then euthanized and examined for lymph node metastases, and the primary tumors were resected for measurement of cell survival in vitro. Results: Tumors with hypoxic cells showed significantly lower K{sup trans} values than tumors without significant hypoxia (p < 0.0001, n = 30), and K{sup trans} decreased with increasing cell surviving fraction for tumors given fractionated radiation treatment (p < 0.0001, n = 20). Tumors in metastasis-positive mice had significantly lower K{sup trans} values than tumors in metastasis-negative mice (p < 0.0001, n = 50). Significant correlations between v{sub e} and tumor hypoxia, radioresponsiveness, or metastatic potential could not be detected. Conclusions: R-18 tumors with low K{sup trans} values are likely to be resistant to radiation treatment and have a high probability of developing lymph node metastases. The general validity of these observations should be investigated further by studying preclinical tumor models with biological

  18. Protein O-fucosyltransferase 1: a potential diagnostic marker and therapeutic target for human oral cancer.

    PubMed

    Yokota, Satoshi; Ogawara, Katsunori; Kimura, Ryota; Shimizu, Fumie; Baba, Takao; Minakawa, Yasuyuki; Higo, Morihiro; Kasamatsu, Atsushi; Endo-Sakamoto, Yosuke; Shiiba, Masashi; Tanzawa, Hideki; Uzawa, Katsuhiro

    2013-12-01

    Protein O-fucosyltransferase 1 (POFUT1) is the enzyme that adds O-fucose through O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cellular surface and secreted proteins. Our previous study using microarray technology showed that significant upregulation of POFUT1 occurs in oral squamous cell carcinoma (OSCC)-derived cell lines compared to human normal oral keratinocytes. The aim of the present study was to examine the status of POFUT1 mRNA and protein expression in OSCC-derived cell lines and human primary OSCCs. POFUT1 mRNA was upregulated significantly (P<0.05 for both comparisons) in five OSCC-derived cell lines and primary OSCCs using quantitative reverse transcriptase-polymerase chain reaction. Immunohistochemistry data indicated that POFUT1 protein expression levels were consistent with mRNA expression status in OSCC-derived cell lines and primary OSCCs. Furthermore, POFUT1 expression status was correlated significantly (P=0.048) with the primary tumor size. The proliferation of POFUT1 knockdown cells was inhibited significantly compared with that of control cells. These results indicated that POFUT1 expression can contribute to cancer progression and that POFUT1 may serve as a diagnostic marker and a therapeutic target for OSCCs.

  19. Sequence-related amplified polymorphism (SRAP) markers: A potential resource for studies in plant molecular biology1

    PubMed Central

    Robarts, Daniel W. H.; Wolfe, Andrea D.

    2014-01-01

    In the past few decades, many investigations in the field of plant biology have employed selectively neutral, multilocus, dominant markers such as inter-simple sequence repeat (ISSR), random-amplified polymorphic DNA (RAPD), and amplified fragment length polymorphism (AFLP) to address hypotheses at lower taxonomic levels. More recently, sequence-related amplified polymorphism (SRAP) markers have been developed, which are used to amplify coding regions of DNA with primers targeting open reading frames. These markers have proven to be robust and highly variable, on par with AFLP, and are attained through a significantly less technically demanding process. SRAP markers have been used primarily for agronomic and horticultural purposes, developing quantitative trait loci in advanced hybrids and assessing genetic diversity of large germplasm collections. Here, we suggest that SRAP markers should be employed for research addressing hypotheses in plant systematics, biogeography, conservation, ecology, and beyond. We provide an overview of the SRAP literature to date, review descriptive statistics of SRAP markers in a subset of 171 publications, and present relevant case studies to demonstrate the applicability of SRAP markers to the diverse field of plant biology. Results of these selected works indicate that SRAP markers have the potential to enhance the current suite of molecular tools in a diversity of fields by providing an easy-to-use, highly variable marker with inherent biological significance. PMID:25202637

  20. Early Detection of Ovarian Cancer by Molecular Targeted Ultrasound Imaging Together with Serum Markers of Tumor-Associated Nuclear Change and Angiogenesis

    DTIC Science & Technology

    2013-10-01

    ultrasound molecular imaging agents enhances signal intensity and detection of OVCA’ was examined in specific aim 1 described in Year-1 report...improved the detection of OVCA at early stage. This improvement in OVCA detectability was due to the enhanced ultrasound imaging signal intensity ...Molecular Targeted Ultrasound Imaging Together with Serum Markers of Tumor-Associated Nuclear Change and Angiogenesis PRINCIPAL

  1. 18F-fludrodeoxyglucose maximal standardized uptake value and metabolic tumor burden are associated with major chemotherapy-related tumor markers in NSCLC patients

    PubMed Central

    Bai, Lu; Guo, Chihua; Wang, Jiansheng; Liu, Xiang; Li, Yang; Li, Miao; Guo, Youmin; Duan, Xiaoyi

    2016-01-01

    Objective Metabolic activity and tumor burden are significant for prognosis and metastasis of non-small cell lung cancer (NSCLC), including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Chemotherapy resistance is a great challenge for treating NSCLC patients and is also closely related with several biomarkers such as epidermal growth factor receptor (EGFR), p53, and excision repair cross-complementing group 1 protein (ERCC1). Our purpose was to determine the correlation between positron emission tomography/computed tomography (PET/CT) parameters and tumor markers-related chemotherapy resistance in NSCLC. Methods Forty-six NSCLC chemotherapy-naïve patients were enrolled. The SUVmax, MTV, and TLG were calculated by PET/CT imaging, and expression of EGFR, p53, and ERCC1 were analyzed by immunohistochemistry on tissues. SUVmax, MTV, and TLG compared for their performance in predicting the expression of EGFR, p53, and ERCC1 were illustrated with statistical analysis. Results SUVmax was significantly correlated with p53 expression (P=0.001), and MTV and TLG were significantly associated with ERCC1 (P=0.000; P=0.000). Furthermore, multiple stepwise regression analysis revealed that SUVmax was the primary predictor for p53, MTV and TLG was the primary predictor for ERCC1. SUVmax had a sensitivity of 91% and specificity of 50% for the detection of p53 positive. The sensitivities of MTV and TLG were 83% and 80%, and specificities were 69% and 75% for the detection of ERCC1 positive, respectively. When we suggested p53 or ERCC1 positive, the cutoff value of SUVmax, MTV, and TLG were 7.68, 23.62, and 129.65 cm3, respectively. Conclusion SUVmax, MTV, and TLG were closely associated with p53 and ERCC1’ expressions. Therefore, 18F-fludrodeoxyglucose PET/CT could be a new way of predicting p53 or ERCC1-related chemotherapy effect in NSCLC patients with more convenience. PMID:27789962

  2. Trehalose as an indicator of desiccation stress in Drosophila melanogaster larvae: A potential marker of anhydrobiosis

    SciTech Connect

    Thorat, Leena J.; Gaikwad, Sushama M.; Nath, Bimalendu B.

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer First report confirming anhydrobiosis in Drosophila melanogaster larvae. Black-Right-Pointing-Pointer Trehalose synthesis and accumulation in larvae that hydrolyzed on rehydration. Black-Right-Pointing-Pointer Trehalose synthesis in concert with the enzymes involved in trehalose metabolism. Black-Right-Pointing-Pointer Inhibition of trehalose hydrolysis in presence of a specific trehalase inhibitor. Black-Right-Pointing-Pointer Trehalose proposed as a reliable marker for biomonitoring of climate change studies. -- Abstract: In the current scenario of global climate change, desiccation is considered as one of the major environmental stressors for the biota exposed to altered levels of ambient temperature and humidity. Drosophila melanogaster, a cosmopolitan terrestrial insect has been chosen as a humidity-sensitive bioindicator model for the present study since its habitat undergoes frequent stochastic and/or seasonally aggravated dehydration regimes. We report here for the first time the occurrence of anhydrobiosis in D. melanogaster larvae by subjecting them to desiccation stress under laboratory conditions. Larvae desiccated for ten hours at <5% relative humidity could enter anhydrobiosis and could revive upon rehydration followed by resumption of active metabolism. As revealed by FTIR and HPLC analyzes, our findings strongly indicated the synthesis and accumulation of trehalose in the desiccating larvae. Biochemical measurements pointed out the desiccation-responsive trehalose metabolic pathway that was found to be coordinated in concert with the enzymes trehalose 6-phosphate synthase and trehalase. Further, an inhibitor-based experimental approach using deoxynojirimycin, a specific trehalase inhibitor, demonstrated the pivotal role of trehalose in larval anhydrobiosis of D. melanogaster. We therefore propose trehalose as a potential marker for the assessment of anhydrobiosis in Drosophila. The present findings thus add

  3. HER3 Expression Is a Marker of Tumor Progression in Premalignant Lesions of the Gastroesophageal Junction

    PubMed Central

    Zhang, Paul J.; Furth, Emma E.; Ginsberg, Gregory G.; McMillan, Matthew T.; Datta, Jashodeep; Czerniecki, Brian J.; Roses, Robert E.

    2016-01-01

    Overexpression of receptor tyrosine kinases (RTK), including members of the HER family, has prognostic and therapeutic significance in invasive esophagogastric carcinoma. RTK expression in premalignant gastroesophageal lesions has not been extensively explored. Formalin-fixed paraffin-embedded tissue samples of esophageal biopsy specimens from 73 patients with Barrett’s esophagus with either low-grade dysplasia (LGD) (n = 32) or high-grade dysplasia (HGD) (n = 59) were analyzed for HER1, HER2, HER3 and CMET expression by immunohistochemistry (IHC). Immunophenotype was correlated with histologic and clinical features. High-grade dysplasia (HGD) was associated with overexpression of HER1 (20.7% vs. 3.1%, p = 0.023), HER2 (5.3% vs. 0.0%, p = 0.187) and HER3 (47.4% vs. 9.4%, p<0.001) compared to low-grade dysplasia (LGD). There was a significant association of HER2 (20.0% vs. 2.1%, p = 0.022) and HER3 (80.0% vs. 40.4%, p = 0.023) overexpression in HGD lesions associated with foci of invasive carcinoma compared to those without invasive foci. Overexpression of CMET was observed in 42.9% of specimens, was increasingly observed with HGD compared to LGD (58.3% vs. 36.7%, p = 0.200), and was most often co-expressed with HER3 (62.5% of HER3-positive specimens vs. 38.2% of HER3-negative specimens, p = 0.212). In summary, HER3 is frequently overexpressed in high-grade dysplastic lesions of the gastroesophageal junction and may be a marker of invasive progression. These data provide rationale for targeting HER2 and HER3 pathways in an early disease setting to prevent disease progression. PMID:27559738

  4. Potential role of the glycolytic oscillator in acute hypoxia in tumors

    NASA Astrophysics Data System (ADS)

    Che Fru, Leonard; Adamson, Erin B.; Campos, David D.; Fain, Sean B.; Jacques, Steven L.; van der Kogel, Albert J.; Nickel, Kwang P.; Song, Chihwa; Kimple, Randall J.; Kissick, Michael W.

    2015-12-01

    Tumor acute hypoxia has a dynamic component that is also, at least partially, coherent. Using blood oxygen level dependent magnetic resonance imaging, we observed coherent oscillations in hemoglobin saturation dynamics in cell line xenograft models of head and neck squamous cell carcinoma. We posit a well-established biochemical nonlinear oscillatory mechanism called the glycolytic oscillator as a potential cause of the coherent oscillations in tumors. These data suggest that metabolic changes within individual tumor cells may affect the local tumor microenvironment including oxygen availability and therefore radiosensitivity. These individual cells can synchronize the oscillations in patches of similar intermediate glucose levels. These alterations have potentially important implications for radiation therapy and are a potential target for optimizing the cancer response to radiation.

  5. MYBL2 is an independent prognostic marker that has tumor-promoting functions in colorectal cancer

    PubMed Central

    Ren, Fei; Wang, Lisha; Shen, Xiaohan; Xiao, Xiuying; Liu, Zebing; Wei, Ping; Wang, Yiqin; Qi, Peng; Shen, Chen; Sheng, Weiqi; Du, Xiang

    2015-01-01

    The MYBL2 gene plays an important role in the genesis and progression of tumors; however, few studies to date have defined the role of this gene in colorectal cancer (CRC). The aim of this study was to determine the relationship between MYBL2 and the prognosis of patients with CRC and to determine the possible effect of MYBL2 on colorectal carcinogenesis. Solid CRC tissues (n=180) preserved with RNAlater were collected to examine the mRNA levels of MYBL2 by real-time quantitative PCR (RT-qPCR). Formalin-fixed, paraffin-embedded (FFPE) blocks of CRC tissues (n=97) and adjacent noncancerous tissues (ANCTs, n=104) were obtained to detect MYBL2 protein levels by immunohistochemistry (IHC). siRNA was used to downregulate MYBL2 expression in the SW480 cell line to detect changes in proliferation, cell cycle progression, apoptosis, migration and invasion. The protein levels of MYBL2 were significantly higher in CRC tissues compared with ANCTs (P<0.05). Kaplan-Meier survival curves indicated that disease-free survival (DFS) was significantly worse in CRC patients in whom MYBL2 was overexpressed (at both the mRNA and protein levels) compared with patients not overexpressing MYBL2. Cox multivariate analysis revealed MYBL2 overexpression as an independent prognostic factor for poor patient survival. In addition, siRNA downregulation of MYBL2 suppressed SW480 cell proliferation, delayed cell cycle progression and induced apoptosis; however, changes in cell migration were minor. Western blot analysis demonstrated an association between MYBL2 expression and that of MMP9, Vimentin, and E-cadherin. MYBL2 is overexpressed in CRC and may therefore play an important role in tumourigenesis. PMID:26101717

  6. Tumor deposits: markers of poor prognosis in patients with locally advanced rectal cancer following neoadjuvant chemoradiotherapy

    PubMed Central

    Zhang, Lu-Ning; Xiao, Wei-Wei; Xi, Shao-Yan; OuYang, Pu-Yun; You, Kai-Yun; Zeng, Zhi-Fan; Ding, Pei-Rong; Zhang, Hui-Zhong; Pan, Zhi-Zhong; Xu, Rui-Hua; Gao, Yuan-Hong

    2016-01-01

    Background Tumor deposits (TDs) were reported to be poor prognoses in colorectal carcinoma, but the significance in locally advanced rectal cancer (LARC) (T3-4/N+) following neoadjuvant chemoradiotherapy (neo-CRT) and surgery is unclear. Since adjuvant chemotherapy showed no benefit for LARC following neo-CRT, it is of great value to investigate whether TDs can identify the subgroup of patients who may benefit from adjuvant chemotherapy. Methods Between 2004 and 2012, 310 LARC patients following neo-CRT and surgery were retrospectively reviewed. Overall survival (OS), disease-free survival (DFS), distant metastasis free survival (DMFS) and local recurrence free survival (LRFS) were evaluated by Kaplan-Meier method, log-rank test and Cox models. Results TDs-positive patients showed adverse OS, DFS and DMFS (all P≤0.001), but not LRFS (P = 0.273). In multivariate analysis, TDs continued to be associated with poor OS (HR = 2.44, 95% CI 1.32-4.4, P = 0.004) and DFS (HR = 1.99, 95% CI 1.21-3.27, P = 0.007), but not DMFS (HR = 1.77, 95% CI 0.97-3.20, P = 0.061) or LRFS (HR = 1.85, 95% CI 0.58-5.85, P = 0.298). Among TDs-positive patients, adjuvant chemotherapy significantly improved OS (P = 0.045) and DMFS (P = 0.026), but not DFS (P = 0.127) or LRFS (P = 0.862). Conclusions TDs are predictive of poor survival in LARC after neo-CRT. Fortunately, TDs-positive patients appear to benefit from adjuvant chemotherapy. PMID:26695441

  7. Marine-continental tephra correlations (Pantelleria, Italy, and Ionian Basin): the potential for Mediterranean marker horizons

    NASA Astrophysics Data System (ADS)

    Jordan, Nina

    2016-04-01

    Palaeo-environmental records from marine and terrestrial archives in the Mediterranean show broad-scale and millennial-scale climatic changes. Synchronising these records requires robust chronological control which may be achieved using isochronous tephra marker horizons. These need to be widespread and sufficiently unique in chemistry to be distinguished from each other. Pantelleria volcano, Italy, satisfies these criteria, with eruptions blanketing the Mediterranean Sea and being distinct from every other volcano in the region. This peralkaline volcano is already well-known for its 46 ka marker horizon (Y-6) but there is potential for extending correlations further back in time. Until recently, correlations were limited by scarce onshore glass data and few sediment cores covering sufficiently long time periods to compare with Pantelleria's >200 ka explosive volcanic history. Building on recent work that has established a detailed onshore stratigraphy, glass data are presented from Pantelleria and site 964 of ODP leg 160 which is situated ~400 km downwind from the volcano. New correlations can be established and previous suggestions are discussed in the light of this new data, representing a significant step forward in confident marine-continental tephra correlations.

  8. Assessment of eccentric exercise-induced oxidative stress using oxidation-reduction potential markers.

    PubMed

    Stagos, Dimitrios; Goutzourelas, Nikolaos; Ntontou, Amalia-Maria; Kafantaris, Ioannis; Deli, Chariklia K; Poulios, Athanasios; Jamurtas, Athanasios Z; Bar-Or, David; Kouretas, Dimitrios

    2015-01-01

    The aim of the present study was to investigate the use of static (sORP) and capacity ORP (cORP) oxidation-reduction potential markers as measured by the RedoxSYS Diagnostic System in plasma, for assessing eccentric exercise-induced oxidative stress. Nineteen volunteers performed eccentric exercise with the knee extensors. Blood was collected before, immediately after exercise, and 24, 48, and 72 h after exercise. Moreover, common redox biomarkers were measured, which were protein carbonyls, thiobarbituric acid-reactive substances, total antioxidant capacity in plasma, and catalase activity and glutathione levels in erythrocytes. When the participants were examined as one group, there were not significant differences in any marker after exercise. However, in 11 participants there was a high increase in cORP after exercise, while in 8 participants there was a high decrease. Thus, the participants were divided in low cORP group exhibiting significant decrease in cORP after exercise and in high cORP group exhibiting significant increase. Moreover, only in the low cORP group there was a significant increase in lipid peroxidation after exercise suggesting induction of oxidative stress. The results suggested that high decreases in cORP values after exercise may indicate induction of oxidative stress by eccentric exercise, while high increases in cORP values after exercise may indicate no existence of oxidative stress.

  9. Identification of Meflin as a Potential Marker for Mesenchymal Stromal Cells

    PubMed Central

    Maeda, Keiko; Enomoto, Atsushi; Hara, Akitoshi; Asai, Naoya; Kobayashi, Takeshi; Horinouchi, Asuka; Maruyama, Shoichi; Ishikawa, Yuichi; Nishiyama, Takahiro; Kiyoi, Hitoshi; Kato, Takuya; Ando, Kenju; Weng, Liang; Mii, Shinji; Asai, Masato; Mizutani, Yasuyuki; Watanabe, Osamu; Hirooka, Yoshiki; Goto, Hidemi; Takahashi, Masahide

    2016-01-01

    Bone marrow-derived mesenchymal stromal cells (BM-MSCs) in culture are derived from BM stromal cells or skeletal stem cells. Whereas MSCs have been exploited in clinical medicine, the identification of MSC-specific markers has been limited. Here, we report that a cell surface and secreted protein, Meflin, is expressed in cultured MSCs, fibroblasts and pericytes, but not other types of cells including epithelial, endothelial and smooth muscle cells. In vivo, Meflin is expressed by immature osteoblasts and chondroblasts. In addition, Meflin is found on stromal cells distributed throughout the BM, and on pericytes and perivascular cells in multiple organs. Meflin maintains the undifferentiated state of cultured MSCs and is downregulated upon their differentiation, consistent with the observation that Meflin-deficient mice exhibit increased number of osteoblasts and accelerated bone development. In the bone and BM, Meflin is more highly expressed in primitive stromal cells that express platelet-derived growth factor receptor α and Sca-1 than the Sca-1-negative adipo-osteogenic progenitors, which create a niche for hematopoiesis. Those results are consistent with a decrease in the number of clonogenic colony-forming unit-fibroblasts within the BM of Meflin-deficient mice. These preliminary data suggest that Meflin is a potential marker for cultured MSCs and their source cells in vivo. PMID:26924503

  10. Evaluation of DNA methylation markers and their potential to predict human aging.

    PubMed

    Soares Bispo Santos Silva, Deborah; Antunes, Joana; Balamurugan, Kuppareddi; Duncan, George; Sampaio Alho, Clarice; McCord, Bruce

    2015-08-01

    We present epigenetic methylation data for two genetic loci, GRIA2, and NPTX2, which were tested for prediction of age from different donors of biofluids. We analyzed 44 saliva samples and 23 blood samples from volunteers with ages ranging from 5 to 72 years. DNA was extracted and bisulfite modified using commercial kits. Specific primers were used for amplification and methylation profiles were determined by pyrosequencing. Methylation data from both markers and their relationship with age were determined using linear regression analysis, which indicates a positive correlation between methylation and age. Older individuals tend to have increased methylation in both markers compared to younger individuals and this trend was more pronounced in the GRIA2 locus when compared to NPTX2. The epigenetic predicted age, calculated using a GRIA2 regression analysis model, was strongly correlated to chronological age (R(2) = 0.801), with an average difference of 6.9 years between estimated and observed ages. When using a NPTX2 regression model, we observed a lower correlation between predicted and chronological age (R(2) = 0.654), with an average difference of 9.2 years. These data indicate these loci can be used as a novel tool for age prediction with potential applications in many areas, including clinical and forensic investigations.

  11. Mucosal-Associated Invariant T Cell Is a Potential Marker to Distinguish Fibromyalgia Syndrome from Arthritis

    PubMed Central

    Konno, Takahiko; Wakao, Rika; Fujita, Hiroko; Fujita, Hiroyoshi

    2015-01-01

    Background Fibromyalgia (FM) is defined as a widely distributed pain. While many rheumatologists and pain physicians have considered it to be a pain disorder, psychiatry, psychology, and general medicine have deemed it to be a syndrome (FMS) or psychosomatic disorder. The lack of concrete structural and/or pathological evidence has made patients suffer prejudice that FMS is a medically unexplained symptom, implying inauthenticity. Furthermore, FMS often exhibits comorbidity with rheumatoid arthritis (RA) or spondyloarthritis (SpA), both of which show similar indications. In this study, disease specific biomarkers were sought in blood samples from patients to facilitate objective diagnoses of FMS, and distinguish it from RA and SpA. Methods Peripheral blood mononuclear cells (PBMCs) from patients and healthy donors (HD) were subjected to multicolor flow cytometric analysis. The percentage of mucosal-associated invariant T (MAIT) cells in PBMCs and the mean fluorescent intensity (MFI) of cell surface antigen expression in MAIT cells were analyzed. Results There was a decrease in the MAIT cell population in FMS, RA, and SpA compared with HD. Among the cell surface antigens in MAIT cells, three chemokine receptors, CCR4, CCR7, and CXCR1, a natural killer (NK) receptor, NKp80, a signaling lymphocyte associated molecule (SLAM) family, CD150, a degrunulation marker, CD107a, and a coreceptor, CD8β emerged as potential biomarkers for FMS to distinguish from HD. Additionally, a memory marker, CD44 and an inflammatory chemokine receptor, CXCR1 appeared possible markers for RA, while a homeostatic chemokine receptor, CXCR4 deserved for SpA to differentiate from FMS. Furthermore, the drug treatment interruption resulted in alternation of the expression of CCR4, CCR5, CXCR4, CD27, CD28, inducible costimulatory molecule (ICOS), CD127 (IL-7 receptor α), CD94, NKp80, an activation marker, CD69, an integrin family member, CD49d, and a dipeptidase, CD26, in FMS. Conclusions

  12. A nomogram composed of clinicopathologic features and preoperative serum tumor markers to predict lymph node metastasis in early gastric cancer patients

    PubMed Central

    Li, Xue; Zhu, Chen-Jing; Wang, Yi-Gao; Chen, Xiao-Long; Zhang, Wei-Han; Chen, Xin-Zu; Yang, Kun; Liu, Kai; Zhang, Bo; Chen, Zhi-Xin; Chen, Jia-Ping; Zhou, Zong-Guang; Hu, Jian-Kun

    2016-01-01

    Predicting lymph node metastasis (LNM) accurately is of great importance to formulate optimal treatment strategies preoperatively for patients with early gastric cancer (EGC). This study aimed to explore risk factors that predict the presence of LNM in EGC. A total of 697 patients underwent gastrectomy enrolled in this study, were divided into training and validation set, and the relationship between LNM and other clinicopathologic features, preoperative serum combined tumor markers (CEA, CA19-9, CA125) were evaluated. Risk factors for LNM were identified using logistic regression analysis, and a nomogram was created by R program to predict the possibility of LNM in training set, while receiver operating characteristic (ROC) analysis was applied to assess the predictive value of the nomogram model in validation set. Consequently, LNM was significantly associated with tumor size, macroscopic type, differentiation type, ulcerative findings, lymphovascular invasion, depth of invasion and combined tumor marker. In multivariate logistic regression analysis, factors including of tumor size, differentiation type, ulcerative findings, lymphovascular invasion, depth of invasion and combined tumor marker were demonstrated to be independent risk factors for LNM. Moreover, a predictive nomogram with these independent factors for LNM in EGC patients was constructed, and ROC curve demonstrated a good discrimination ability with the AUC of 0.847 (95% CI: 0.789-0.923), which was significantly larger than those produced in previous studies. Therefore, including of these tumor markers which could be convenient and feasible to obtain from the serum preoperatively, the nomogram could effectively predict the incidence of LNM for EGC patients. PMID:27449100

  13. A genome-wide study of allelic imbalance in human testicular germ cell tumors using microsatellite markers.

    PubMed

    Bergthorsson, Jon Thor; Agnarsson, Bjarni Agnar; Gudbjartsson, Tomas; Magnusson, Kjartan; Thoroddsen, Asgeir; Palsson, Birgir; Bjornsson, Johannes; Stefansson, Kari; Gulcher, Jeffrey; Einarsson, Gudmundur Vikar; Amundadottir, Laufey Thora; Barkardottir, Rosa Bjork

    2006-01-01

    Testicular germ cell tumors (TGCT) arise by multistep carcinogenesis pathways involving selective losses and gains of chromosome material. To locate cancer genes underlying this selection, we performed a genome-wide study of allelic imbalance (AI) in 32 tumors, using 710 microsatellite markers. The highest prevalence of AI was found at 12p, in line with previous studies finding consistent gain of the region in TGCTs. High frequency of AI was also observed at chromosome arms 4p, 9q, 10p, 11q, 11p, 13q, 16q, 18p, and 22q. Within 39 candidate regions identified by mapping of smallest regions of overlap (SROs), the highest frequency of AI was at 12p11.21 approximately p11.22 (62%), 12p12.1 approximately p13.1 (53%), 12p13.1 approximately p13.2 (53%), 11q14.1 approximately q14.2 (53%), 11p13 approximately p14.3 (47%), 9q21.13 approximately q21.32 (47%), and 4p15.1 approximately p15.2 (44%). Two genes known to be involved in cancer reside in these regions, ETV6 at 12p13.2 (TEL oncogene) and WT1 at 11p13. We also found a significant association (P = 0.02) between AI at 10q21.1 approximately q22.2 and higher clinical stage. This study contributes to the ongoing search for genes involved in transformation of germ cells and provides a useful reference point to previous studies using cytogenetic techniques to map chromosome changes in TGCTs.

  14. Neck circumference as a potential marker of metabolic syndrome among college students1

    PubMed Central

    Pereira, Dayse Christina Rodrigues; de Araújo, Márcio Flávio Moura; de Freitas, Roberto Wagner Júnior Freire; Teixeira, Carla Regina de Souza; Zanetti, Maria Lúcia; Damasceno, Marta Maria Coelho

    2014-01-01

    OBJECTIVE: to relate neck circumference with metabolic syndrome and its criteria among college students. METHOD: cross-sectional study conducted with 702 college students in Fortaleza, CE, Brazil from September 2010 to June 2011. Socio-demographic data, waist circumference and neck circumference were collected together with blood pressure, fasting blood sugar, triglyceride levels, and HDL-C. RESULTS: 1.7% of the studied sample presented metabolic syndrome. Of these, 58.3% presented altered neck circumference (p<0.006). As neck circumference decreases, pressure levels improve (p<0.001). Additionally, college students with high fasting blood sugar (p=0.003) and high triglyceride levels (p<0.001) presented higher values of neck circumference. CONCLUSION: neck circumference is a potential predictive marker in the detection of metabolic syndrome and its components among college students. PMID:25591092

  15. Analysis of Molecular Markers by Anatomic Tumor Site in Stage III Colon Carcinomas from Adjuvant Chemotherapy Trial NCCTG N0147 (Alliance)

    PubMed Central

    Sinicrope, Frank A.; Mahoney, Michelle R.; Yoon, Harry H.; Smyrk, Thomas C.; Thibodeau, Stephen N.; Goldberg, Richard M.; Nelson, Garth D.; Sargent, Daniel J.; Alberts, Steven R.

    2015-01-01

    PURPOSE To determine the frequency and prognostic association of molecular markers by anatomic tumor site in patients with stage III colon carcinomas. Experimental Design In a randomized trial of adjuvant FOLFOX + cetuximab, BRAFV600E and KRAS (exon 2) mutations and DNA mismatch repair (MMR) proteins were analyzed in tumors (N=3,018) in relationship to tumor location including subsite. Cox models were used to assess clinical outcome including overall survival (OS). RESULTS KRAS codon 12 mutations were most frequent at the splenic flexure and cecum; codon 13 mutations were evenly distributed. BRAF mutation frequency sharply increased from transverse colon to cecum in parallel with deficient (d) MMR. Non-mutated BRAF or KRAS tumors progressively decreased from sigmoid to transverse (all p<0.0001). Significantly poorer OS was found for mutant KRAS in distal [HR, 1.98 (1.49–2.63); p<.0001] vs proximal [1.25 (0.97–1.60), p=.079] cancers. BRAF status and outcome were not significantly associated with tumor site. Proximal vs distal dMMR tumors had significantly better outcome. An interaction test was significant for tumor site by KRAS (padjusted=.043) and MMR (padjusted=.010) for OS. Significant prognostic differences for biomarkers by tumor site were maintained in the FOLFOX arm. Tumor site was independently prognostic with a stepwise improvement from cecum to sigmoid (OS: padjusted=0.001). CONCLUSIONS Mutations in BRAF or KRAS codon 12 were enriched in proximal cancers whereas non-mutated BRAF/KRAS were increased in distal tumors. Significant differences in outcome for KRAS mutations and dMMR were found by tumor site, indicating that their interpretation should occur in the context of tumor location. PMID:26187617

  16. An immature B cell population from peripheral blood serves as surrogate marker for monitoring tumor angiogenesis and anti-angiogenic therapy in mouse models.

    PubMed

    Fagiani, Ernesta; Bill, Ruben; Pisarsky, Laura; Ivanek, Robert; Rüegg, Curzio; Christofori, Gerhard

    2015-07-01

    Tumor growth depends on the formation of new blood vessels (tumor angiogenesis) either from preexisting vessels or by the recruitment of bone marrow-derived cells. Despite encouraging results obtained with preclinical cancer models, the therapeutic targeting of tumor angiogenesis has thus far failed to deliver an enduring clinical response in cancer patients. One major obstacle for improving anti-angiogenic therapy is the lack of validated biomarkers, which allow patient stratification for suitable treatment and a rapid assessment of therapy response. Toward these goals, we have employed several mouse models of tumor angiogenesis to identify cell populations circulating in their blood that correlated with the extent of tumor angiogenesis and therapy response. Flow cytometry analyses of different combinations of cell surface markers that define subsets of bone marrow-derived cells were performed on peripheral blood mononuclear cells from tumor-bearing and healthy mice. We identified one cell population, CD45(dim)VEGFR1(-)CD31(low), that was increased in levels during active tumor angiogenesis in a variety of transgenic and syngeneic transplantation mouse models of cancer. Treatment with various anti-angiogenic drugs did not affect CD45(dim)VEGFR1(-)CD31(low) cells in healthy mice, whereas in tumor-bearing mice, a consistent reduction in their levels was observed. Gene expression profiling of CD45(dim)VEGFR1(-)CD31(low) cells characterized these cells as an immature B cell population. These immature B cells were then directly validated as surrogate marker for tumor angiogenesis and of pharmacologic responses to anti-angiogenic therapies in various mouse models of cancer.

  17. Towards tumor immunodiagnostics

    PubMed Central

    Kotoula, Vassiliki

    2016-01-01

    Immunodiagnostic markers applicable on tissue or cytologic material may be prognostic or predictive of response to immunomodulatory drugs and may also be classified according to whether they are cell-specific or tumor-tissue-specific. Cell-specific markers are evaluated under the microscope as (I) morphological, corresponding to the assessment of tumor infiltrating immune cells on routine hematoxylin & eosin (H&E) sections; and (II) immunophenotypic, including the immunohistochemical (IHC) assessment of markers characteristic for tumor infiltrating immune cells. Tumor-tissue-specific markers are assessed in tissue extracts that may be enriched in neoplastic cells but almost inevitably also contain stromal and immune cells infiltrating the tumor. Such markers include (I) immune-response-related gene expression profiles, and (II) tumor genotype characteristics, as recently assessed with large-scale genotyping methods, usually next generation sequencing (NGS) applications. Herein, we discuss the biological nature of immunodiagnostic markers, their potential clinical relevance and the shortcomings that have, as yet, prevented their clinical application. PMID:27563650

  18. Parental potentiation of vocalization as a marker for filial bonds in infant animals.

    PubMed

    Shair, Harry N

    2014-12-01

    Maternal and paternal potentiation of vocalization are two parts of a promising model of early life social bonds that has been and can be a useful tool in research. Most mammalian infants vocalize when isolated. Interactions with adult females just before isolation have been found to increase vocalizations in several species. Interactions with littermates and other social stimuli do not. In guinea pigs and pigs, the response is specific to the dam. In rats and octagon degus, an unrelated adult female from the colony is sufficient. The presence of an intact adult male in the test chamber with dam-reared pups evokes behavioral inhibition, a fear response. Previous exposure to the male in the home cage, biparental rearing, dramatically transforms the response of the pup. The pup treats the adult male as it does its dam, including potentiation of vocalization during a subsequent isolation. This article outlines the methods, advantages, and disadvantages of parental potentiation as a research tool, as well as a brief review of the evidence supporting its use as a marker for filial attachment. Future research directions are outlined.

  19. Transcriptome sequencing of HER2-positive breast cancer stem cells identifies potential prognostic marker.

    PubMed

    Lei, Bo; Zhang, Xian-Yu; Zhou, Jia-Peng; Mu, Guan-Nan; Li, Yi-Wen; Zhang, You-Xue; Pang, Da

    2016-11-01

    In cancer stem cell theory, breast cancer stem cells (BCSCs) are postulated to be the root cause of recurrence and metastasis in breast cancer. Discovery of new biomarkers and development of BCSC-targeted therapy are practical issues that urgently need to be addressed in the clinic. However, few breast cancer stem cell targets are known. Given that there are few BCSCs, performing transcriptome sequencing on them thus far has not been possible. With the emergence of single-cell sequencing technology, we have now undertaken such a study. We prepared single-cell suspensions, which were sorted using flow cytometry from breast tumor tissue and adjacent normal breast tissue from two HER2-positive patients. We obtained BCSCs, breast cancer cells, mammary cells, and CD44(+) mammary cells. Transcriptome sequencing was then performed on these four cell types. Using bioinformatics, we identified 404 differentially expressed BCSC genes from the HER2-positive tumors and preliminary explored transcriptome characteristics of BCSCs. Finally, by querying a public database, we found that CA12 was a novel prognostic biomarker in HER2-positive breast cancer, which also had prognostic value in all breast cancer types. In conclusion, our results suggest that CA12 may be associated with BCSCs, especially HER2-positive BCSCs, and is a potential novel therapeutic target and biomarker.

  20. Primary Intraosseous Smooth Muscle Tumor of Uncertain Malignant Potential: Original Report and Molecular Characterization

    PubMed Central

    Kropp, Lauren; Siegal, Gene P.; Frampton, Garrett M.; Rodriguez, Michael G.; McKee, Svetlana; Conry, Robert M.

    2016-01-01

    We report the first case of primary intraosseous smooth muscle tumor of uncertain malignant potential (STUMP) which is analogous to borderline malignant uterine smooth muscle tumors so designated. The tumor presented in the femur of an otherwise healthy 30-year-old woman. Over a 3-year period, the patient underwent 11 biopsies or resections and 2 cytologic procedures. Multiple pathologists reviewed the histologic material including musculoskeletal pathologists but could not reach a definitive diagnosis. However, metastases eventually developed and were rapidly progressive and responsive to gemcitabine and docetaxel. Molecular characterization and ultrastructural analysis was consistent with smooth muscle origin, and amplification of unmutated chromosome 12p and 12q segments appears to be the major genomic driver of this tumor. Primary intraosseous STUMP is thought to be genetically related to leiomyosarcoma of bone, but likely representing an earlier stage of carcinogenesis. Wide excision and aggressive follow-up is warranted for this potentially life-threatening neoplasm. PMID:27994831

  1. Realizing the Translational Potential of Telomere Length Variation as a Tissue-Based Prognostic Marker for Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    Telomere Length Variation as a Tissue- Based Prognostic Marker for Prostate Cancer PRINCIPAL INVESTIGATOR: Elizabeth A. Platz CONTRACTING...Translational Potential of Telomere Length Variation as a Tissue- Based Prognostic Marker for Prostate Cancer 5b. GRANT NUMBER W81XWH-12-1-0545 5c...combination of telomere length variability in prostate cancer cells and short telomere length in cancer -associated stromal cells is an independent

  2. Multiplatform molecular profiling identifies potentially targetable biomarkers in malignant phyllodes tumors of the breast.

    PubMed

    Gatalica, Zoran; Vranic, Semir; Ghazalpour, Anatole; Xiu, Joanne; Ocal, Idris Tolgay; McGill, John; Bender, Ryan P; Discianno, Erin; Schlum, Aaron; Sanati, Souzan; Palazzo, Juan; Reddy, Sandeep; Pockaj, Barbara

    2016-01-12

    Malignant phyllodes tumor is a rare breast malignancy with sarcomatous overgrowth and with limited effective treatment options for recurrent and metastatic cases. Recent clinical trials indicated a potential for anti-angiogenic, anti-EGFR and immunotherapeutic approaches for patients with sarcomas, which led us to investigate these and other targetable pathways in malignant phyllodes tumor of the breast. Thirty-six malignant phyllodes tumors (including 8 metastatic tumors with two cases having matched primary and metastatic tumors) were profiled using gene sequencing, gene copy number analysis, whole genome expression, and protein expression. Whole genome expression analysis demonstrated consistent over-expression of genes involved in angiogenesis including VEGFA, Angiopoietin-2, VCAM1, PDGFRA, and PTTG1. EGFR protein overexpression was observed in 26/27 (96%) of cases with amplification of the EGFR gene in 8/24 (33%) cases. Two EGFR mutations were identified including EGFRvIII and a presumed pathogenic V774M mutation, respectively. The most common pathogenic mutations included TP53 (50%) and PIK3CA (15%). Cases with matched primary and metastatic tumors harbored identical mutations in both sites (PIK3CA/KRAS and RB1 gene mutations, respectively). Tumor expression of PD-L1 immunoregulatory protein was observed in 3/22 (14%) of cases. Overexpression of molecular biomarkers of increased angiogenesis, EGFR and immune checkpoints provides novel targeted therapy options in malignant phyllodes tumors of the breast.

  3. Autoantibodies to Ca2+ binding protein Calnuc is a potential marker in colon cancer detection.

    PubMed

    Chen, Yao; Lin, Ping; Qiu, Suimin; Peng, Xuan-Xian; Looi, Koksun; Farquhar, Marilyn Gist; Zhang, Jian-Ying

    2007-05-01

    Calnuc is a calcium (Ca2+) binding protein found in both Golgi and cytoplasm, and it may play a role in G protein- and Ca2+-regulated signal transduction events. This study was designed to investigate the possibility of whether Calnuc protein might be a tumor-associated antigen (TAA) that induces autoantibody response in human cancers, and to evaluate the feasibility of the Calnuc antigen-antibody system as a marker in cancer detection. Purified full-length recombinant Calnuc protein was used as an antigen in enzyme-linked immunoassay and Western blotting for the detection of autoantibodies in cancers. Sera from 447 patients with 9 different types of cancer were analyzed. Although the frequency of autoantibody to Calnuc was found to be 4.7% in total groups of cancer, it was not significantly different to that of normal individuals (1.2%). However, the frequency of autoantibody to Calnuc in colon cancer (11.5%) was significantly higher than that in normal individuals (1.2%). The expression analysis of Calnuc in multiple colon cancer tissues by immunohistochemistry on tissue array further confirmed the high specificity of Calnuc in colon cancer. Of 69 colon cancer tissue specimens examined, 41 tissues (59.4%) overexpressed Calnuc, while normal colon tissues did not show any expression of Calnuc. The subcellular distribution analysis of Calnuc examined by subcellular fractionation and immunofluorescence indicates that Calnuc is a membrane associated protein and mostly distributed in Golgi, which is consistent with previous reports. With adding Calnuc into a TAA array (including p53, c-myc, cyclin B1, cyclin D1), the cumulative frequency of antibody to multiple TAAs in colon cancer was raised to 65.4% which is significantly higher than the cumulative frequency in normal individuals (6.1%). This indicates that a mini-array of multiple TAAs which includes Calnuc might provide a novel non-invasive approach to enhance antibody detection for colon cancer diagnosis.

  4. Combined Evaluation of AFP, CA15-3, CA125, CA19-9, and CEA Tumor Markers in Patients with Hepatitis B and C

    PubMed Central

    ASSMAR, Mehdi; YEGANEH, Sara; MANSOURGHANAEI, Fariborz; AMIRMOZAFARI, Nour

    2016-01-01

    Background: This study aimed to determine the role of tumor markers AFP, CA15-3, CA125, CA19-9 and CEA in patients with hepatitis B and C. Methods: This descriptive cross-sectional study was performed from Oct 2012 to Oct 2014. Serum samples of 129 patients with hepatitis B and C referred to Guilan Liver and Digestive Disease Research Center in Rasht, Iran were collected and checked for the existence of the listed tumor markers by ELISA. Results: No increase in serum levels of tumor marker CA19-9, CEA and CA15-3 were seen in patients with hepatitis (P>0.05). In patients with hepatitis B, increase in CA125 were observed (P=0.03). In hepatitis C patients, there was an increase in AFP levels (P=0.03). Conclusion: The levels of AFP and CA125 markers were high in hepatitis C and hepatitis B, respectively. However, the increased levels were not seen is malignancy. Due to the small sample size, further study is necessary to find the reasons of the increase. PMID:28053931

  5. Mechanistic study of IR-780 dye as a potential tumor targeting and drug delivery agent.

    PubMed

    Zhang, Erlong; Luo, Shenglin; Tan, Xu; Shi, Chunmeng

    2014-01-01

    IR-780 iodide, a near-infrared fluorescent heptamethine dye, has been recently characterized to exhibit preferential accumulation property in the mitochondria of tumor cells. In this study, we investigated the possible mechanisms for its tumor selective activity and its potential as a drug delivery carrier. Results showed that the energy-dependent uptake of IR-780 iodide into the mitochondria of tumor cells was affected by glycolysis and plasma membrane potential. Moreover, OATP1B3 subtype of organic anion transporter peptides (OATPs) may play a dominant role in the transportation of IR-780 iodide into tumor cells, while cellular endocytosis, mitochondrial membrane potential and the ATP-binding cassette transporters did not show significant influence to its accumulation. We further evaluated the potential of IR-780 iodide as a drug delivery carrier by covalent conjugation of IR-780 with nitrogen mustard (IR-780NM). In vivo imaging showed that IR-780NM remained the tumor targeting property, indicating that IR-780 iodide could be potentially applied as a drug delivery agent for cancer targeted imaging and therapy.

  6. CD14/TLR4 priming potentially recalibrates and exerts anti-tumor efficacy in tumor associated macrophages in a mouse model of pancreatic carcinoma

    PubMed Central

    Prakash, Hridayesh; Nadella, Vinod; Singh, Sandhya; Schmitz-Winnenthal, Hubertus

    2016-01-01

    Pancreatic cancer is the fourth major cause of cancer related deaths in the world and 5 year survival is below 5%. Among various tumor directed therapies, stimulation of Toll-like receptors (TLR) has shown promising effects in various tumor models. However, pancreatic cancer cells frequently express these receptors themselves and their stimulation (TLR 2 and/or 4 particularly) within tumor microenvironment is known to potentially enhance tumor cell proliferation and cancer progression. Consistent stimulation of tumor associated macrophages (TAMs), in particular with tumor derived TLR ligand within the tumor microenvironment promotes cancer related inflammation, which is sterile, non-immunogenic and carcinogenic in nature. In view of this, recalibrating of TAM has the potential to induce immunogenic inflammation. Consistent with this, we provide experimental evidence for the first time in this study that priming of TAMs with TLR4 ligend (LPS) alone or in combination with IFN-γ not only recalibrates pancreatic tumor cells induced M2 polarization, but also confers anti-tumor potential in TAMs. Most interestingly, reduced tumor growth in macrophage depleted animals suggests that macrophage directed approaches are important for the management of pancreatic tumors. PMID:27511884

  7. Evaluation of a targeted nanobubble ultrasound contrast agent for potential tumor imaging

    NASA Astrophysics Data System (ADS)

    Li, Chunfang; Shen, Chunxu; Liu, Haijuan; Wu, Kaizhi; Zhou, Qibing; Ding, Mingyue

    2015-03-01

    Targeted nanobubbles have been reported to improve the contrast effect of ultrasound imaging due to the enhanced permeation and retention effects at tumor vascular leaks. In this work, the contrast enhancement abilities and the tumor targeting potential of a self-made VEGFR2-targeted nanobubble ultrasound contrast agent was evaluated in-vitro and in-vivo. Size distribution and zeta potential were assessed. Then the contrast-enhanced ultrasound imaging of the VEGFR2 targeted nanobubbles were evaluated with a custom-made experimental apparatus and in normal Wistar rats. Finally, the in-vivo tumor-targeting ability was evaluated on nude mice with subcutaneous tumor. The results showed that the target nanobubbles had uniform distribution with the average diameter of 208.1 nm, polydispersity index (PDI) of 0.411, and zeta potential of -13.21 mV. Significant contrast enhancement was observed in both in-vitro and in-vivo ultrasound imaging, demonstrating that the self-made target nanobubbles can enhance the contrast effect of ultrasound imaging efficiently. Targeted tumor imaging showed less promising result, due to the fact that the targeted nanobubbles arriving and permeating through tumor vessels were not many enough to produce significant enhancement. Future work will focus on exploring new imaging algorithm which is sensitive to targeted nanobubbles, so as to correctly detect the contrast agent, particularly at a low bubble concentration.

  8. The potentiation of radiation response on murine tumor by fludarabine phosphate.

    PubMed

    Kim, J H; Alfieri, A A; Kim, S H; Fuks, Z

    1986-04-01

    Fludarabine phosphate is a synthetic analog of beta-arabinofuranosyl adenine (beta-ara-A), an anti-viral agent. Since beta-ara-A has been shown to be an effective inhibitor of potentially lethal damage (PLD) repair in cell culture system but ineffective in in vivo tumors, we carried out experiments to determine whether fludarabine phosphate which is not inactivated by adenosine deaminase potentiates the radiation effects on in vivo murine tumor. The combined effects of single acute fludarabine phosphate (600 mg/kg) and single dose of X-irradiation (20 Gy) on Meth-A fibrosarcomas in BALB/c mice produced more than 90% tumor control, while the radiation alone resulted in less than 10% tumor control. The radiosensitizing effect by fludarabine phosphate was higher when the drug was administered immediately prior to X-irradiation. The dose modifying factor of fludarabine phosphate is estimated to be 1.6 at 400 mg/kg. Experiments with fractionated irradiation and fludarabine phosphate similarly showed a high rate of tumor control. The present study suggests that inhibitors of PLD repair including several antiviral agents may have potential utility in the treatment of some radioresistant human tumors by radiotherapy.

  9. 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.

  10. Telangiectases in Scleroderma: A Potential Clinical Marker of Pulmonary Arterial Hypertension

    PubMed Central

    Shah, Ami A.; Wigley, Fredrick M.; Hummers, Laura K.

    2012-01-01

    Objective Clinical markers are needed to identify scleroderma patients at risk for pulmonary arterial hypertension (PAH) since early therapy may improve survival. We investigated whether increased numbers of telangiectases in scleroderma associate with measures of pulmonary vascular disease. Methods One hundred forty-seven consecutive adult patients with scleroderma were enrolled in this cross-sectional study and scored for the presence of matted telangiectases on 11 body areas. Per body area, telangiectases were scored as 0 if none were present, 1 if there were fewer than 10 telangiectases, and 2 if 10 or more telangiectases were counted. Linear regression analysis was performed to assess the association between right ventricular systolic pressure (RVSP) and telangiectasia score, adjusted for age, race, smoking status, scleroderma subtype, disease duration, and autoantibody status. Logistic regression analysis was performed with PAH by right-heart catheterization (RHC) as the dependent variable. Results The mean telangiectasia score was 6.0 (SD 4.5, range 0–20). RVSP and telangiectasia score were positively correlated (r = 0.271, p = 0.001). The mean RVSP increased by 10.9 mm Hg for every 10-point increase in telangiectasia score (95% CI 3.6–18.3 mm Hg, p = 0.004), adjusted for potential confounders. The adjusted relative odds of PAH by RHC were 12.4 for patients with a 10-point increase in telangiectasia score (95% CI 1.78–85.9, p = 0.01). Conclusion Increased numbers of telangiectases strongly associate with the presence of pulmonary vascular disease. Telangiectases may be a clinical marker of more widespread aberrant microvascular disease in scleroderma. PMID:19955048

  11. PLC-β2 is modulated by low oxygen availability in breast tumor cells and plays a phenotype dependent role in their hypoxia-related malignant potential.

    PubMed

    Brugnoli, Federica; Grassilli, Silvia; Al-Qassab, Yasamin; Capitani, Silvano; Bertagnolo, Valeria

    2016-12-01

    Limited oxygen availability plays a critical role in the malignant progression of breast cancer by orchestrating a complex modulation of the gene transcription largely dependent on the tumor phenotype. Invasive breast tumors belonging to different molecular subtypes are characterized by over-expression of PLC-β2, whose amount positively correlates with the malignant evolution of breast neoplasia and supports the invasive potential of breast tumor cells. Here we report that hypoxia modulates the expression of PLC-β2 in breast tumor cells in a phenotype-related manner, since a decrease of the protein was observed in the BT-474 and MCF7 cell lines while an increase was revealed in MDA-MB-231 cells as a consequence of low oxygen availability. Under hypoxia, the down-modulation of PLC-β2 was mainly correlated with the decrease of the EMT marker E-cadherin in the BT-474 cells and with the up-regulation of the stem cell marker CD133 in MCF7 cells. The increase of PLC-β2 induced by low oxygen in MDA-MB-231 cells supports the hypoxia-related reorganization of actin cytoskeleton and sustains invasion capability. In all examined cell lines, but with an opposite role in the ER-positive and ER-negative cells, PLC-β2 was involved in the hypoxia-induced increase of HIF-1α, known to affect both EMT and CD133 expression. Our data include PLC-β2 in the complex and interconnected signaling pathways induced by low oxygen availability in breast tumor cells and suggest that the forced modulation of PLC-β2 programmed on the basis of tumor phenotype may prevent the malignant progression of breast neoplasia as a consequence of intra-tumoral hypoxia. © 2016 Wiley Periodicals, Inc.

  12. Molecular markers and imaging tools to identify malignant potential in Barrett's esophagus

    PubMed Central

    Bennett, Michael; Mashimo, Hiroshi

    2014-01-01

    Due to its rapidly rising incidence and high mortality, esophageal adenocarcinoma is a major public health concern, particularly in Western countries. The steps involved in the progression from its predisposing condition, gastroesophageal reflux disease, to its premalignant disorder, Barrett’s esophagus, and to cancer, are incompletely understood. Current screening and surveillance methods are limited by the lack of population-wide utility, incomplete sampling of standard biopsies, and subjectivity of evaluation. Advances in endoscopic ablation have raised the hope of effective therapy for eradication of high-risk Barrett’s lesions, but improvements are needed in determining when to apply this treatment and how to follow patients clinically. Researchers have evaluated numerous potential molecular biomarkers with the goal of detecting dysplasia, with varying degrees of success. The combination of biomarker panels with epidemiologic risk factors to yield clinical risk scoring systems is promising. New approaches to sample tissue may also be combined with these biomarkers for less invasive screening and surveillance. The development of novel endoscopic imaging tools in recent years has the potential to markedly improve detection of small foci of dysplasia in vivo. Current and future efforts will aim to determine the combination of markers and imaging modalities that will most effectively improve the rate of early detection of high-risk lesions in Barrett’s esophagus. PMID:25400987

  13. Gene expression profiling of craniofacial fibrous dysplasia reveals ADAMTS2 overexpression as a potential marker.

    PubMed

    Zhou, Shang-Hui; Yang, Wen-Jun; Liu, Sheng-Wen; Li, Jiang; Zhang, Chun-Ye; Zhu, Yun; Zhang, Chen-Ping

    2014-01-01

    Fibrous dysplasia (FD) as an abnormal bone growth is one of the common fibro-osseous leasions (FOL) in oral and maxillofacial region, however, its etiology still remains unclear. Here, we performed gene expression profiling of FD using microarray analysis to explore the key molecule events in FD development, and develop potential diagnostic markers or therapeutic targets for FD. We found that 1,881 genes exhibited differential expression with more than two-fold changes in FD compared to normal bone tissues, including 1,200 upregulated genes and 681 downregulated genes. Pathway analysis indicated that obviously activated pathways are Ribosome and ECM-receptor interaction pathways; downregulated pathways are "Hepatitis C" and "cancer" signaling pathways. We further validated the expression of ADAMTS2, one of most differentiated expressed genes, by Immunohistochemistry (IHC) in 40 of FD cases. Results showed that ADAMTS2 was significantly overexpressed in FD tissues, but rarely expressed in normal bone tissues, suggesting that ADAMTS2 could be a potential biomarker for FD. Thus, this study uncovered differentially expressed candidate genes in FD, which provides pilot data for understanding FD pathogenesis, and developing novel biomarkers for diagnosis and targeting of FD.

  14. S100B is a potential disease activity marker in non-segmental vitiligo.

    PubMed

    Speeckaert, Reinhart; Voet, Sofie; Hoste, Esther; van Geel, Nanja

    2017-02-14

    Vitiligo is a chronic skin condition characterized by progressive depigmentation of the skin. S100B is a damage-associated molecular pattern (DAMP) protein expressed in melanocytes, which has been proposed as a marker of melanocyte cytotoxicity. While the use of S100B as a biomarker in melanoma is well established, its association with vitiligo activity has not yet been investigated. Here, we show that S100B serum levels were significantly increased in patients with active non-segmental vitiligo and strongly correlated with the affected body surface area. Prospective follow-up showed a predictive value of serum S100B levels on disease progression. In vitro experiments using repeated freeze-thaw procedures demonstrated an intracellular upregulation of S100B in normal and vitiligo melanocytes prior to an extensive release in the environment. This phenomenon may explain the increased S100B serum values in the active phase of vitiligo. In a monobenzone-induced vitiligo mouse model we could show the potential of S100B inhibition as a therapeutic strategy in vitiligo. In conclusion, this report demonstrates the possible use of S100B as a biomarker for disease activity in vitiligo. Our data suggest that this DAMP protein could play a substantial role in the pathogenesis of vitiligo and may be a potential new target for treatment.

  15. Chemotherapy stimulates syndecan-1 shedding: A potentially negative effect of treatment that may promote tumor relapse

    PubMed Central

    Ramani, Vishnu C.; Sanderson, Ralph D.

    2015-01-01

    In patients with multiple myeloma, the heparan sulfate proteoglycan syndecan-1 (CD138) is shed from the surface of tumor cells and accumulates in the serum and within the extracellular matrix of the bone marrow where it promotes tumor growth and metastasis. In the present study we discovered that commonly used anti-myeloma drugs stimulate syndecan-1 shedding both in vitro and in animals bearing myeloma tumors. Enhanced shedding is accompanied by increased syndecan-1 synthesis prior to drug induced tumor cell death. Addition of a caspase inhibitor blocks the drug-induced shedding of syndecan-1 in vitro indicating that shedding is linked to the onset of apoptosis. ADAMs inhibitors or siRNA targeting ADAMs blocked drug-induced shedding suggesting that up regulation or activation of ADAMs is responsible for cleaving syndecan-1 from the tumor cell surface. These results reveal that myeloma chemotherapy stimulates synthesis and shedding of syndecan-1, a potentially negative side effect that may lead to accumulation of high levels of syndecan-1 to establish a microenvironment that nurtures relapse and promotes tumor progression. Interestingly, we also found that chemotherapeutic drugs stimulated syndecan-1 shedding from pancreatic cancer cells as well, indicating that drug-induced shedding of syndecan-1 may occur in many cancer types. Overall, our results indicate that use of metalloproteinase inhibitors (to inhibit syndecan-1 shedding) in combination with chemotherapy may represent a novel therapeutic strategy to prevent re-establishment of a microenvironment conducive for tumor relapse. PMID:24145151

  16. The Network of Epithelial-mesenchymal transition: potential new targets for tumor resistance

    PubMed Central

    Nantajit, Danupon; Lin, Dong; Li, Jian Jian

    2014-01-01

    Purpose In multiple cell metazoans, the ability of polarized epithelial cells to convert to motile mesenchymal cells in order to relocate to another location is governed by a unique process termed epithelial-mesenchymal transition (EMT). While being an essential process of cellular plasticity for normal tissue and organ developments, EMT is found to be involved in an array of malignant phenotypes of tumor cells including proliferation and invasion, angiogenesis, stemness of cancer cells and resistance to chemo-radiotherapy. Although EMT is being extensively studied and demonstrated to play a key role in tumor metastasis and in sustaining tumor hallmarks, there is a lack of clear picture of the overall EMT signaling network, wavering the potential clinical trials targeting EMT. Methods In this review, we highlight the potential key therapeutic targets of EMT linked with tumor aggressiveness, hypoxia, angiogenesis and cancer stem cells, emphasizing on an emerging EMT-associated NF-κB/HER2/STAT3 pathway in radioresistance of breast cancer stem cells. Results Further definition of cancer stem cell repopulation due to EMT-controlled tumor microenvironment will help to understand how tumors exploit the EMT mechanisms for their survival and expansion advantages. Conclusions The knowledge of EMT will offer more effective targets in clinical trials to treat therapy-resistant metastatic lesions. PMID:25270087

  17. Anabolic potential of bone mineral in human periosteal fibroblasts using steroid markers of healing.

    PubMed

    Suchak, A; Soory, M

    2013-05-01

    A deproteinized natural cancellous bone mineral (B) was studied in a cell culture model for its anabolic potential using two radiolabelled steroid substrates, 14C-testosterone (14C-T) and 14C-4-androstenedione (14C-4-A) independently; in the presence or absence of the anti-androgen finasteride (F) and minocycline (M). Culture medium was assayed for the biologically active metabolite 5 alpha-dihydrotestosterone (DHT) a marker of regenerative potential and wound healing. Confluent monolayer cultures of human periosteal fibroblasts were incubated in Eagle's minimum essential medium with each of the substrates 14C-T and 14C-4-A. Incubations were performed with previously established optimal concentrations of B5 (milligrams/ml), M25 (μg/ml) and F5 (μg/ml) alone and in combination (n=6) for 24h. The eluent was solvent extracted with ethyl acetate (2 ml x 2) and subjected to TLC in a benzene/acetone solvent system (4:1 v/v) for separation of metabolites; they were quantified using a radioisotope scanner. The yield of DHT was increased over controls in response to B and M with both substrates 14C-T and 14C-4-A by 1.7, 1.8-fold and 1.7, 1.6-fold respectively (n=6; p<0.001; one way ANOVA). Combined incubations of B and M resulted in similar yields. F inhibited DHT yields with both radiolabelled substrates by 2-3-fold (n=6; p<0.001) which was overcome by a combined incubation of F+B to values similar to those of controls (p<0.01). Documented pro-anabolic effects of minocycline were applicable as a standard for confirmation of responses to B. Significant increases in yields of DHT in response to B and M with both substrates indicate their anabolic potential in periosteal fibroblasts with implications for wound healing.

  18. Methylomics analysis identifies ZNF671 as an epigenetically repressed novel tumor suppressor and a potential non-invasive biomarker for the detection of urothelial carcinoma

    PubMed Central

    Hsieh, Hsiao-Yen; Jou, Yeong-Chin; Lin, Chang-Te; Tsai, Ming-Hsuan; Huang, Wen-Yu; Wang, Yi-Ting; Lin, Ru-Inn; Chen, Szu-Shan; Tung, Chun-Liang; Wu, Shu-Fen; Chang, De-Ching; Shen, Cheng-Huang; Hsu, Cheng-Da

    2015-01-01

    The molecular mechanism underlying the lethal phenomenon of urothelial carcinoma (UC) tumor recurrence remains unresolved. Here, by methylation microarray, we identified promoter methylation of the zinc-finger protein gene, ZNF671 in bladder UC tumor tissue samples, a finding that was independently validated by bisulphite pyrosequencing in cell lines and tissue samples. Subsequent assays including treatment with epigenetic depressive agents and in vitro methylation showed ZNF671 methylation to result in its transcriptional repression. ZNF671 re-expression in UC cell lines, via ectopic expression, inhibited tumor growth and invasion, in possible conjunction with downregulation of cancer stem cell markers (c-KIT, NANOG, OCT4). Clinically, high ZNF671 methylation in UC tumor tissues (n=96; 63 bladder, 33 upper urinary tract) associated with tumor grade and poor locoregional disease-free survival. Quantitative MSP analysis in a training (n=97) and test (n=61) sets of voided urine samples from bladder UC patients revealed a sensitivity and specificity of 42%-48% and 89%-92.8%, respectively, for UC cancer detection. Moreover, combining DNA methylation of ZNF671 and 2 other genes (IRF8 and sFRP1) further increased the sensitivity to 96.2%, suggesting a possible three-gene UC biomarker. In summary, ZNF671, an epigenetically silenced novel tumor suppressor, represents a potential predictor for UC relapse and non-invasive biomarker that could assist in UC clinical decision-making. PMID:26320192

  19. ADAMTS6 suppresses tumor progression via the ERK signaling pathway and serves as a prognostic marker in human breast cancer

    PubMed Central

    Xie, Keqi; Wang, Zhu; Wang, Yanping; Zheng, Hong

    2016-01-01

    A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family is involved in tumor development. However, how ADAMTS6 influences cancer remains unknown. We investigated the biological function and clinical implications of ADAMTs6 in breast cancer (BC). Its functional significance in BC cell lines was confirmed by ADAMTs6 overexpression or downregulation both in vitro and in vivo studies. Enhanced ADAMTS6 expression suppressed cell migration, invasion, and tumorigenesis, whereas knockdown promoted these characteristics. The extracellular signal-regulated kinase (ERK) pathway was partially involved in ADAMTS6-mediated inhibition of BC development, and miR-221-3p was identified as a predicted target for ADAMTS6. Results from the luciferase assay confirmed that miR-221-3p directly inhibited ADAMTS6 expression by binding its 3′-untranslated region. In addition, immunohistochemistry data from specimens from 182 BC patients showed that high ADAMTS6 expression was significantly correlated with favorable disease-free survival (DFS, p = 0.045). Subgroup analysis of patients with ER positive, PR positive or HER-2 negative tumors revealed that high ADAMTS6 expression more strongly extended DFS compared to low expression (p = 0.004, p = 0.009, p = 0.017). Multivariate analyses confirmed that ADAMTS6 expression was an independent risk factor for DFS (p = 0.011). Together, these data demonstrate that ADAMTS6 inhibits tumor development by regulating the ERK pathway via binding of miR-221-3p. Thus, its expression may be a potential prognostic biomarker for BC. PMID:27542224

  20. ERN1 and ALPK1 inhibit differentiation of bi-potential tumor-initiating cells in human breast cancer

    PubMed Central

    Strietz, Juliane; Stepputtis, Stella S.; Vannier, Corinne; Kim, Mihee M.; Castro, David J.; Au, Qingyan; Boerries, Melanie; Busch, Hauke; Aza-Blanc, Pedro; Heynen-Genel, Susanne; Bronsert, Peter; Kuster, Bernhard; Stickeler, Elmar; Brabletz, Thomas; Oshima, Robert G.; Maurer, Jochen

    2016-01-01

    Cancers are heterogeneous by nature. While traditional oncology screens commonly use a single endpoint of cell viability, altering the phenotype of tumor-initiating cells may reveal alternative targets that regulate cellular growth by processes other than apoptosis or cell division. We evaluated the impact of knocking down expression of 420 kinases in bi-lineage triple-negative breast cancer (TNBC) cells that express characteristics of both myoepithelial and luminal cells. Knockdown of ERN1 or ALPK1 induces bi-lineage MDA-MB-468 cells to lose the myoepithelial marker keratin 5 but not the luminal markers keratin 8 and GATA3. In addition, these cells exhibit increased β-casein production. These changes are associated with decreased proliferation and clonogenicity in spheroid cultures and anchorage-independent growth assays. Confirmation of these assays was completed in vivo, where ERN1- or ALPK1-deficient TNBC cells are less tumorigenic. Finally, treatment with K252a, a kinase inhibitor active on ERN1, similarly impairs anchorage-independent growth of multiple breast cancer cell lines. This study supports the strategy to identify new molecular targets for types of cancer driven by cells that retain some capacity for normal differentiation to a non-tumorigenic phenotype. ERN1 and ALPK1 are potential targets for therapeutic development. PMID:27829216

  1. 4-1BB Agonists: Multi-Potent Potentiators of Tumor Immunity

    PubMed Central

    Bartkowiak, Todd; Curran, Michael A.

    2015-01-01

    Immunotherapy is a rapidly expanding field of oncology aimed at targeting, not the tumor itself, but the immune system combating the cancerous lesion. Of the many approaches currently under study to boost anti-tumor immune responses; modulation of immune co-receptors on lymphocytes in the tumor microenvironment has thus far proven to be the most effective. Antibody blockade of the T cell co-inhibitory receptor cytotoxic T lymphocyte antigen-4 (CTLA-4) has become the first FDA approved immune checkpoint blockade; however, tumor infiltrating lymphocytes express a diverse array of additional stimulatory and inhibitory co-receptors, which can be targeted to boost tumor immunity. Among these, the co-stimulatory receptor 4-1BB (CD137/TNFSF9) possesses an unequaled capacity for both activation and pro-inflammatory polarization of anti-tumor lymphocytes. While functional studies of 4-1BB have focused on its prominent role in augmenting cytotoxic CD8 T cells, 4-1BB can also modulate the activity of CD4 T cells, B cells, natural killer cells, monocytes, macrophages, and dendritic cells. 4-1BB’s expression on both T cells and antigen presenting cells, coupled with its capacity to promote survival, expansion, and enhanced effector function of activated T cells, has made it an alluring target for tumor immunotherapy. In contrast to immune checkpoint blocking antibodies, 4-1BB agonists can both potentiate anti-tumor and anti-viral immunity, while at the same time ameliorating autoimmune disease. Despite this, 4-1BB agonists can trigger high grade liver inflammation which has slowed their clinical development. In this review, we discuss how the underlying immunobiology of 4-1BB activation suggests the potential for therapeutically synergistic combination strategies in which immune adverse events can be minimized. PMID:26106583

  2. Neutrophils with protumor potential could efficiently suppress tumor growth after cytokine priming and in presence of normal NK cells.

    PubMed

    Sun, Rui; Luo, Jing; Li, Dong; Shu, Yu; Luo, Chao; Wang, Shan-Shan; Qin, Jian; Zhang, Gui-Mei; Feng, Zuo-Hua

    2014-12-30

    In tumor-bearing state, the function of neutrophils is converted from tumor-suppressing to tumor-promoting. Here we report that priming with IFN-γ and TNF-α could convert the potential of neutrophils from tumor-promoting to tumor-suppressing. The neutrophils with protumor potential have not lost their responsiveness to IFN-γ and TNF-α. After priming with IFN-γ and TNF-α, the potential of the neutrophils to express Bv8 and Mmp9 genes was reduced. Conversely, the tumor-promotional neutrophils recovered the expression of Rab27a and Trail, resumed the activation levels of PI3K and p38 MAPK pathways in response to stimuli, and expressed higher levels of IL-18 and NK-activating ligands such as RAE-1, MULT-1, and H60. Therefore, the anti-tumor function of the neutrophils was augmented, including the cytotoxicity to tumor cells, the capability of degranulation, and the capacity to activate NK cells. Since the function of NK cells is impaired in tumor-bearing state, the administration of normal NK cells could significantly augment the efficiency of tumor therapy based on neutrophil priming. These findings highlight the reversibility of neutrophil function in tumor-bearing state, and suggest that neutrophil priming by IFN-γ/TNF-α might be a potential approach to eliminate residual tumor cells in comprehensive strategy for tumor therapy.

  3. Identification and evaluation of potential forensic marker proteins in vaginal fluid by liquid chromatography/mass spectrometry.

    PubMed

    Igoh, Akihisa; Doi, Yusuke; Sakurada, Koichi

    2015-09-01

    Vaginal fluid is one of the most common body fluids found at crime scenes. Discriminating vaginal fluid from other body fluids is important in forensic science; however, few potential protein markers have been reported to date. Proteomic methods for identifying protein markers have gained attention, although few reports have applied this technology to forensic protein markers. Therefore, to identify characteristic vaginal proteins, we examined various body fluids (nasal secretions, saliva, urine, semen, vaginal fluids, and sweat) using liquid chromatography/electrospray ionization time-of-flight mass spectrometry and peptide mass fingerprinting. We identified three components (average molecular mass values 17,237 ± 2, 18,063 ± 2, and 15,075 ± 1) detectable only in vaginal samples: two human small proline-rich protein 3 (SPRR3) isoforms and a human fatty acid-binding protein 5 (FABP5) with an acetylated (+42) N-terminal region lacking the initiator methionine residue (-131). Using ELISA, these yielded markedly high average values in vaginal fluids. The mass spectra of these proteins were not detected in infant saliva but were detected in the vaginal fluid throughout the menstrual cycle. The results of forensic analysis (detection limit, mixed body fluid samples, casework samples, and blind samples) suggest that these proteins are potential forensic markers. In conclusion, high SPRR3 and FABP5 expression levels, which may be used as potential markers for vaginal fluid identification in forensic science, were detected in vaginal fluids from healthy adults.

  4. Effects of inhibitors of radiation-induced potentially lethal damage repair on chemotherapy in murine tumors

    SciTech Connect

    Nakatsugawa, S.; Sugahara, T.

    1982-09-01

    Enhancement of various antitumor drugs effects by inhibitors of radiation-induced potentially lethal damage (PLD) repair was studied in three murine tumors (EMT-6, RIF-1 and SQ-1). In EMT-6 tumors, PLD repair inhibitors, 3'-deoxyguanosine (3'dG) and 7904 (a derivative of 3'-deoxyadenosine) showed a marked enhancement of tumor growth inhibition by anticancerous drugs (FT-207 (a derivative of 5-FU), bleomycin, Ara-C, ACNU). However, the effects of mitomycin-C and vincristine were not potentiated by the inhibitors. In SQ-1 carcinomas, another repair inhibitor, ara-A (1-..beta..-D-arabinofuranosyladenine) (32 mg/kg) potentiated the effect of ACNU. In RIF-1 sarcomas, in which a low PLD repair function has been reported after ionizing radiation exposure, the potentiation was not so marked as in EMT-6 or SQ-1 tumors. Thus, as a possibility, the potentiation by inhibitors of radiation-induced PLD repair might be a result of the inhibition of chemical-induced PLD repair. The study of this field may contribute to the improvement of cancer treatment not only by radiotherapy but also by chemotherapy.

  5. Pairwise diversity and tMRCA as potential markers for HIV infection recency

    PubMed Central

    Moyo, Sikhulile; Wilkinson, Eduan; Vandormael, Alain; Wang, Rui; Weng, Jia; Kotokwe, Kenanao P.; Gaseitsiwe, Simani; Musonda, Rosemary; Makhema, Joseph; Essex, Max; Engelbrecht, Susan; de Oliveira, Tulio; Novitsky, Vladimir

    2017-01-01

    Abstract Intrahost human immunodeficiency virus (HIV)-1 diversity increases linearly over time. We assessed the extent to which mean pairwise distances and the time to the most recent common ancestor (tMRCA) inferred from intrahost HIV-1C env sequences were associated with the estimated time of HIV infection. Data from a primary HIV-1C infection study in Botswana were used for this analysis (N = 42). A total of 2540 HIV-1C env gp120 variable loop region 1 to conserved region 5 (V1C5) of the HIV-1 envelope gp120 viral sequences were generated by single genome amplification and sequencing, with an average of 61 viral sequences per participant and 11 sequences per time point per participant. Raw pairwise distances were calculated for each time point and participant using the ape package in R software. The tMRCA was estimated using phylogenetic inference implemented in Bayesian Evolutionary Analysis by Sampling Trees v1.8.2. Pairwise distances and tMRCA were significantly associated with the estimated time since HIV infection (both P < 0.001). Taking into account multiplicity of HIV infection strengthened these associations. HIV-1C env-based pairwise distances and tMRCA can be used as potential markers for HIV recency. However, the tMRCA estimates demonstrated no advantage over the pairwise distances estimates. PMID:28178146

  6. Assessment of volatile profile as potential marker of chilling injury of basil leaves during postharvest storage.

    PubMed

    Cozzolino, Rosaria; Pace, Bernardo; Cefola, Maria; Martignetti, Antonella; Stocchero, Matteo; Fratianni, Florinda; Nazzaro, Filomena; De Giulio, Beatrice

    2016-12-15

    The volatile profile of three sweet basil cultivars, "Italico a foglia larga", "Cammeo" and "Italiano classico", packaged in air at 4 or 12°C until 9days, was monitored by solid phase microextraction with GC-MS. Chilling injury (CI) score and electrolyte leakage were also assessed. In total, 71 volatile organic compounds (VOCs) were identified in the headspace of basil samples. A preliminary principal component analysis highlighted the dominant effect of the cultivar on VOCs profiles. Data analysis by post-transformation of projection to latent structures regression (ptPLS2) clarified the role played by time and temperature of storage. Temperature influenced the emission of volatiles during storage, with much lower total volatile emissions at 4°C compared to 12°C. Finally, a ptPLS2 regression model performed on VOCs and the two CI parameters allowed selection of 10 metabolites inversely correlated to both CI parameters, which can be considered potential markers of CI in basil leaves.

  7. Increased nuclear ?-catenin expression in oral potentially malignant lesions: A marker of epithelial dysplasia

    PubMed Central

    Rojas-Alcayaga, Gonzalo; Maturana, Andrea; Aitken, Juan-Pablo; Rojas, Carolina; Ortega, Ana-Verónica

    2015-01-01

    Background Deregulation of ?-catenin is associated with malignant transformation; however, its relationship with potentially malignant and malignant oral processes is not fully understood. The aim of this study was to determine and compare the nuclear ?-catenin expression in oral dysplasia and oral squamous cell carcinoma (OSCC). Material and Methods Cross sectional study. Immunodetection of ?-catenin was performed on 72 samples, with the following distribution: 21 mild dysplasia, 12 moderate dysplasia, severe dysplasia 3, 36 OSCC including 19 well differentiated, 15 moderately differentiated and 2 poorly differentiated. Through microscopic observation the number of positive cells per 1000 epithelial cells was counted. For the statistical analysis, the Kruskal Wallis test was used. Results Nuclear expression of ?-catenin was observed in all samples with severe and moderate dysplasia, with a median of 267.5, in comparison to mild dysplasia whose median was 103.75. Only 10 samples (27.7%) with OSCC showed nuclear expression, with statistically significant differences between groups (p < 0.05). Conclusions Our results are consistent with most of the reports which show increased presence of ?-catenin in severe and moderate dysplasia compared to mild dysplasia; however the expression of nuclear ?-catenin decreased after starting the invasive neoplastic process. This suggests a role for this protein in the progression of dysplasia and early malignant transformation to OSCC. Immunodetection of ?-catenin could be a possible immune marker in the detection of oral dysplasia. Key words:Oral squamous cell carcinoma (OSCC), ?-catenin, oral dysplasia. PMID:26241451

  8. Cytoglobin: a potential marker for adipogenic differentiation in preadipocytes in vitro.

    PubMed

    Doğan, Ayşegül; Demirci, Selami; Kıratlı, Binnur; Şahin, Fikrettin

    2017-02-01

    Obesity, mainly characterized by the excess fat storage, is a global health problem resulting in serious morbidity and mortality. Identification of molecular mechanisms in adipogenic differentiation pathway might lead to development of new strategies for diagnosis, prevention and therapy of obesity and associated diseases. Discovery of new genes and proteins in the differentiation pathway could help to understand the key specific regulators of the adipogenesis. Cytoglobin (Cygb), identified as a new globin family member protein, is expressed in various tissues. Although its interaction with oxygen and nitric oxide indicates the potential role in antioxidant pathways, the exact role remains unclear. In the current study, expression level of Cygb was determined in proliferating and differentiating 3T3-F442A cells by gene expression and protein expression analysis. Results revealed that Cygb expression up-regulated in differentiated cells in parallel with adipogenic differentiation markers; PPARγ, CEBPα and FABP4 expressions. Besides, Cygb overexpression in preadipocytes contributed to the adipogenic differentiation as verified by detection of higher lipid droplets and increased PPARγ, CEBPα and FABP4 expressions with respect to control cells. These findings will shed light on the unknown roles of Cygb in adipogenesis and obesity.

  9. Plasma DNA integrity index as a potential molecular diagnostic marker for breast cancer.

    PubMed

    Kamel, Azza M; Teama, Salwa; Fawzy, Amal; El Deftar, Mervat

    2016-06-01

    Plasma DNA integrity index is increased in various malignancies including breast cancer, the most common cancer in women worldwide; early detection is crucial for successful treatment. Current screening methods fail to detect many cases of breast cancer at an early stage. In this study, we evaluated the level of plasma DNA integrity index in 260 females (95 with breast cancer, 95 with benign breast lesions, and 70 healthy controls) to verify its potential value in discriminating malignant from benign breast lesions. The criteria of the American Joint Committee on Cancer were used for staging of breast cancer patients. DNA integrity index was measured by real-time PCR. DNA integrity index was significantly higher in breast cancer than in benign breast patients and healthy subjects (P = <0.001). DNA integrity index is correlated with TNM stage. Given 100 % specificity, the highest sensitivity achieved in detecting cancer group was 85.3 % at 0.55 DNA integrity index cutoff. In conclusion, the plasma DNA integrity index may be a promising molecular diagnostic marker of malignancy in breast lesions.

  10. Calponin-h2: a potential serum marker for the early detection of human breast cancer?

    PubMed

    Debald, Manuel; Jin, Jian-Ping; Linke, Andrea; Walgenbach, Klaus-Jürgen; Rauch, Peter; Zellmer, Angela; Fimmers, Rolf; Kuhn, Walther; Hartmann, Gunther; Walgenbach-Brünagel, Gisela

    2014-11-01

    Early diagnosis is the key for the successful treatment of breast cancer. A serum marker for the early detection of breast cancer could significantly reduce breast cancer morbidity and mortality by bringing the time of diagnosis at an earlier and therefore still curable stage. So far, no biomarker for the early detection is available for the clinical routine. The aim of the present study was to evaluate the use of calponin-h2 as a blood-based biomarker for the early diagnosis of this disease. Using two monoclonal antibodies against calponin-h2, we developed a sandwich ELISA to analyze the serum levels of calponin-h2. In order to evaluate the diagnostic potential of this biomarker, patients with breast cancer (n = 76), benign diseases of the breast (n = 51) and healthy females (n = 24) were analyzed. Serum levels above 10 ng/ml were only observed in patients with breast cancer (n = 8; 10.5%). Further large-scale studies and preanalytic evaluations are necessary to clarify the definite role of calponin-h2 as a biomarker in breast cancer management.

  11. The Impact of AD Drug Treatments on Event-Related Potentials as Markers of Disease Conversion

    PubMed Central

    Chapman, Robert M.; Porsteinsson, Anton P.; Gardner, Margaret N.; Mapstone, Mark; McCrary, John W.; Sandoval, Tiffany C.; Guillily, Maria D.; Reilly, Lindsey A.; DeGrush, Elizabeth

    2013-01-01

    This paper investigates how commonly prescribed pharmacologic treatments for Alzheimer’s disease (AD) affect Event-Related Potential (ERP) biomarkers as tools for predicting AD conversion in individuals with Mild Cognitive Impairment (MCI). We gathered baseline ERP data from two MCI groups (those taking AD medications and those not) and later determined which subjects developed AD (Convert->AD) and which subjects remained cognitively stable (Stable). We utilized a previously developed and validated multivariate system of ERP components to measure medication effects among these four subgroups. Discriminant analysis produced classification scores for each individual as a measure of similarity to each clinical group (Convert->AD, Stable), and we found a large significant main Group effect but no main AD Medications effect and no Group by Medications interaction. This suggested AD medications have negligible influence on this set of ERP components as weighted markers of disease progression. These results provide practical information to those using ERP measures as a biomarker to identify and track AD in individuals in a clinical or research setting. PMID:23905997

  12. Platelet–lymphocyte ratios: a potential marker for pulmonary tuberculosis diagnosis in COPD patients

    PubMed Central

    Chen, Guozhong; Wu, Chunling; Luo, Zhiying; Teng, Yiming; Mao, Suping

    2016-01-01

    Background In recent decades, morbidity and mortality have been found to be significantly increased in patients with chronic obstructive pulmonary disease (COPD) complicated with pulmonary tuberculosis (PTB). Platelet–lymphocyte ratio (PLR) is an indicator for inflammatory diseases. This study aims to investigate whether PLR could act as a potential marker for patients with COPD complicated with PTB. Methods In this retrospective study, laboratory characteristics of 87 COPD patients complicated with PTB (determined by Mycobacterium tuberculosis positive culture from sputum or bronchial lavage fluid) and 83 COPD patients (as the control group, determined by M. tuberculosis culture negativity from sputum or bronchial lavage fluid) were investigated. Data obtained on the day of admission were analyzed. Results PLR >216.82 was identified as the optimal cutoff value for discriminating COPD patients with PTB (sensitivity 92.4%, specificity 84.5%, positive-predictive value 91.6%, negative-predictive value 86.2%, and area under the curve [AUC] was 0.87) from patients with COPD alone. The AUC of PLR was significantly greater than that of neutrophil–lymphocyte count ratio (AUC, 0.74; 95% confidence interval, 0.67–0.81; P<0.01). Conclusion PLR could be developed as a valuable maker for identifying tuberculosis infection in COPD patients. PMID:27843310

  13. FXYD5 is a Marker for Poor Prognosis and a Potential Driver for Metastasis in Ovarian Carcinomas

    PubMed Central

    Raman, Pichai; Purwin, Timothy; Pestell, Richard; Tozeren, Aydin

    2015-01-01

    Ovarian cancer (OC) is a leading cause of cancer mortality, but aside from a few well-studied mutations, very little is known about its underlying causes. As such, we performed survival analysis on ovarian copy number amplifications and gene expression datasets presented by The Cancer Genome Atlas in order to identify potential drivers and markers of aggressive OC. Additionally, two independent datasets from the Gene Expression Omnibus web platform were used to validate the identified markers. Based on our analysis, we identified FXYD5, a glycoprotein known to reduce cell adhesion, as a potential driver of metastasis and a significant predictor of mortality in OC. As a marker of poor outcome, the protein has effective antibodies against it for use in tissue arrays. FXYD5 bridges together a wide variety of cancers, including ovarian, breast cancer stage II, thyroid, colorectal, pancreatic, and head and neck cancers for metastasis studies. PMID:26494976

  14. Expression of T-plastin, FoxP3 and other tumor-associated markers by leukemic T-cells of cutaneous T-cell lymphoma.

    PubMed

    Capriotti, Elisabetta; Vonderheid, Eric C; Thoburn, Christopher J; Wasik, Mariusz A; Bahler, David W; Hess, Allan D

    2008-06-01

    Peripheral blood cells from 28 patients with leukemic cutaneous T-cell lymphoma including 25 patients with Sezary syndrome were evaluated for expression of regulatory T-cell-associated markers (FoxP3, CD25, CTLA-4, neurophilin-1), T-cell activation markers (CD28 and its ligands B7.1 and B7.2) and NK cell-associated markers (NKG2D and its ligands Mic-A and Mic-B) using real-time quantitative polymerase chain reaction. T-plastin served as a positive genetic marker, and its expression correlated to blood tumor burden. More than 90% of samples had transcripts for CD28 and Mic-B, but less than 30% of samples expressed FoxP3, CTLA-4 and CD25. Expression of Mic-B by neoplastic cells could provide another mechanism to inhibit anti-tumor immune responses. FoxP3 expression correlated with a poor prognosis. Although the underlying mechanisms accounting for this correlation remain unclear, the expression of the Foxp3 and CTLA-4 regulatory elements indicates that a subset of leukemic cases displays a regulatory T-cell phenotype.

  15. Expression of endoplasmic reticulum stress proteins is a candidate marker of brain metastasis in both ErbB-2+ and ErbB-2- primary breast tumors.

    PubMed

    Sanz-Pamplona, Rebeca; Aragüés, Ramón; Driouch, Keltouma; Martín, Berta; Oliva, Baldo; Gil, Miguel; Boluda, Susana; Fernández, Pedro L; Martínez, Antonio; Moreno, Víctor; Acebes, Juan J; Lidereau, Rosette; Reyal, Fabien; Van de Vijver, Marc J; Sierra, Angels

    2011-08-01

    The increasing incidence of breast cancer brain metastasis in patients with otherwise well-controlled systemic cancer is a key challenge in cancer research. It is necessary to understand the properties of brain-tropic tumor cells to identify patients at risk for brain metastasis. Here we attempt to identify functional phenotypes that might enhance brain metastasis. To obtain an accurate classification of brain metastasis proteins, we mapped organ-specific brain metastasis gene expression signatures onto an experimental protein-protein interaction network based on brain metastatic cells. Thirty-seven proteins were differentially expressed between brain metastases and non-brain metastases. Analysis of metastatic tissues, the use of bioinformatic approaches, and the characterization of protein expression in tumors with or without metastasis identified candidate markers. A multivariate analysis based on stepwise logistic regression revealed GRP94, FN14, and inhibin as the best combination to discriminate between brain and non-brain metastases (ROC AUC = 0.85, 95% CI = 0.73 to 0.96 for the combination of the three proteins). These markers substantially improve the discrimination of brain metastasis compared with ErbB-2 alone (AUC = 0.76, 95% CI = 0.60 to 0.93). Furthermore, GRP94 was a better negative marker (LR = 0.16) than ErbB-2 (LR = 0.42). We conclude that, in breast carcinomas, certain proteins associated with the endoplasmic reticulum stress phenotype are candidate markers of brain metastasis.

  16. Tumor-Activated Mesenchymal Stromal Cells Promote Osteosarcoma Stemness and Migratory Potential via IL-6 Secretion

    PubMed Central

    Cortini, Margherita; Massa, Annamaria; Avnet, Sofia; Bonuccelli, Gloria; Baldini, Nicola

    2016-01-01

    Osteosarcoma (OS) is an aggressive bone malignancy with a high relapse rate despite combined treatment with surgery and multiagent chemotherapy. As for other cancers, OS-associated microenvironment may contribute to tumor initiation, growth, and metastasis. We consider mesenchymal stromal cells (MSC) as a relevant cellular component of OS microenvironment, and have previously found that the interaction between MSC and tumor cells is bidirectional: tumor cells can modulate their peripheral environment that in turn becomes more favorable to tumor growth through metabolic reprogramming. Here, we determined the effects of MSC on OS stemness and migration, two major features associated with recurrence and chemoresistance. The presence of stromal cells enhanced the number of floating spheres enriched in cancer stem cells (CSC) of the OS cell population. Furthermore, the co-culturing with MSC stimulated the migratory capacity of OS via TGFβ1 and IL-6 secretion, and the neutralizing antibody anti-IL-6 impaired this effect. Thus, stromal cells in combination with OS spheres exploit a vicious cycle where the presence of CSC stimulates mesenchymal cytokine secretion, which in turn increases stemness, proliferation, migration, and metastatic potential of CSC, also through the increase of expression of adhesion molecules like ICAM-1. Altogether, our data corroborate the concept that a comprehensive knowledge of the interplay between tumor and stroma that also includes the stem-like fraction of tumor cells is needed to develop novel and effective anti-cancer therapies. PMID:27851822

  17. Primary pulmonary glomus tumor of uncertain malignant potential: A case report with literature review focusing on current concepts of malignancy grade estimation.

    PubMed

    Oide, Takashi; Yasufuku, Kazuhiro; Shibuya, Kiyoshi; Yoshino, Ichiro; Nakatani, Yukio; Hiroshima, Kenzo

    2016-01-01

    We report a 38-year-old woman with a left lung tumor presenting as obstructive pneumonia. Bronchoscopic examination revealed a polypoid tumor filling the left main bronchus. The tumor was partially resected by a snaring procedure for diagnostic purposes. Microscopic examination revealed a submucosal tumor located underneath normal bronchial epithelium. The tumor was composed of sheets of uniform oval to cuboidal cells encompassing numerous blood vessels. Immunohistochemically, the tumor cells exhibited smooth muscle markers, but were negative for neuroendocrine markers. The diagnosis of primary pulmonary glomus tumor was therefore made. Subsequent bronchoscopic intervention allowed us to pin-point the origin of the tumor: superior segmental B(6a/b). She underwent a left lower lobe superior segmental resection successfully. Glomus tumors are relatively rare soft tissue tumors, and those of bronchopulmonary origin are exceedingly rare clinical condition. Among primary lung tumors, the carcinoid tumor is a mimic of the glomus tumor, and differentiating these tumors is known to be difficult, especially using small biopsy samples. In the present case, a large tissue sample obtained by bronchoscopic snaring was quite useful for the correct preoperative diagnosis. Because of the disease rarity, malignancy grade estimation of visceral glomus tumors has not been clearly addressed. Recently, the histopathological diagnostic criteria for malignant glomus tumors was defined in the WHO classification of soft tissue and bone tumors 4th edition. Here we also reviewed the literature on primary bronchopulmonary glomus tumors with special attention to the current concept of malignancy grade estimation.

  18. CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis

    PubMed Central

    Tu, Ziwei; Chen, Qu; Zhang, Jie Ting; Jiang, Xiaohua; Xia, Yunfei; Chan, Hsiao Chang

    2016-01-01

    While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage (p = 0.026), distant metastasis (p < 0.001) and poor prognosis (p < 0.01). Multivariate analysis identified CFTR as an independent prognostic factor (p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC. PMID:27769067

  19. APRIL, a proliferation-inducing ligand, as a potential marker of lupus nephritis

    PubMed Central

    2012-01-01

    Introduction BLyS and APRIL are cytokines from the tumor necrosis factor family which play an important role in systemic lupus erythematosus (SLE). Previous works suggested an association between both molecules and SLE disease activity although their correlation with lupus nephritis is not known. We therefore assessed serum BLyS and APRIL in active lupus nephritis patients. Methods Serum samples from active lupus nephritis and at 6 months post-treatment were obtained. Serum levels of BLyS and APRIL (n = 47) as well as renal mRNA expression were measured. Serum levels of both molecules and clinical data (n = 27) were available at 6 months follow-up. All biopsy-proven lupus nephritis patients were treated with similar immunosuppressive drugs. Results Serum levels of APRIL were associated with proteinuria (Rs = 0.44, P value < 0.01) and degree of histological activity (Rs = 0.34; P value < 0.05) whereas BLyS levels were associated with complement levels (Rs = 0.46; P value < 0.01) and dosage of immunosuppressant. Interestingly, serum APRIL as well as its intrarenal mRNA levels were associated with resistance to treatment. From the receiver operating characteristic (ROC) analysis, high levels (> 4 ng/mL) of serum APRIL predicted treatment failure with a positive predictive value of 93 percent. Conclusion APRIL could be a potential biomarker for predicting difficult-to-treat cases of lupus nephritis. PMID:23171638

  20. CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis.

    PubMed

    Tu, Ziwei; Chen, Qu; Zhang, Jie Ting; Jiang, Xiaohua; Xia, Yunfei; Chan, Hsiao Chang

    2016-11-22

    While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage (p = 0.026), distant metastasis (p < 0.001) and poor prognosis (p < 0.01). Multivariate analysis identified CFTR as an independent prognostic factor (p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC.

  1. Heterogeneous proliferative potential of occult metastatic cells in bone marrow of patients with solid epithelial tumors

    PubMed Central

    Solakoglu, Oender; Maierhofer, Christine; Lahr, Georgia; Breit, Elisabeth; Scheunemann, Peter; Heumos, Isabella; Pichlmeier, Uwe; Schlimok, Günter; Oberneder, Ralph; Köllermann, Manfred W.; Köllermann, Jens; Speicher, Michael R.; Pantel, Klaus

    2002-01-01

    Bone marrow is a major homing site for circulating epithelial tumor cells. The present study was aimed to assess the proliferative capacity of occult metastatic cells in bone marrow of patients with operable solid tumors especially with regard to their clinical outcome. We obtained bone marrow aspirates from 153 patients with carcinomas of the prostate (n = 46), breast (n = 45), colon (n = 33), and kidney (n = 29). Most of the patients (87%) had primary disease with no clinical signs of overt metastases [tumor-node-metastasis (TNM)-stage UICC (Union Internationale Contre le Cancer) I-III]. After bone marrow was cultured for 21–102 days under special cell culture conditions, viable epithelial cells were detected by cytokeratin staining in 124 patients (81%). The cultured epithelial cells harbored Ki-ras2 mutations and numerical chromosomal aberrations. The highest median number of expanded tumor cells was observed in prostate cancer (2,619 per flask). There was a significant positive correlation between the number of expanded tumor cells and the UICC-stage of the patients (P = 0.03) or the presence of overt metastases (P = 0.04). Moreover, a strong expansion of tumor cells was correlated to an increased rate of cancer-related deaths (P = 0.007) and a reduced survival of the patients (P = 0.006). In conclusion, the majority of cancer patients have viable tumor cells in their bone marrow at primary tumor diagnosis, and the proliferative potential of these cells determines the clinical outcome. PMID:11854519

  2. Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents

    PubMed Central

    Wang, Limin; Zha, Zhihao; Qu, Wenchao; Qiao, Hongwen; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2012-01-01

    Introduction This paper reports the synthesis and labeling of 18F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine-serine-cysteine preferring (ASC) transporter system. Methods Three new 18F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labelling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[18F]fluoromethyl)-L-alanine (L[18F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma). Results New 18F alanine derivatives were prepared with 7–34% uncorrected radiochemical yields, excellent enantiomeric purity (>99%) and good radiochemical purity (>99%). In vitro uptake of the L-[18F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than those observed for other two alanine derivatives and [18F]FDG in first 1 h. Inhibition of cell uptake studies suggested that L-[18F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[18F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[18F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[18F]FMA in both 9L rat and transgenic mouse. Conclusion L-[18F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor

  3. Tumor

    MedlinePlus

    ... plants (aflatoxins) Excessive sunlight exposure Genetic problems Obesity Radiation exposure Viruses Types of tumors known to be caused by or linked with viruses are: Cervical cancer (human papillomavirus) Most anal cancers (human papillomavirus) Some throat ...

  4. Transition from colitis to cancer: high Wnt activity sustains the tumor-initiating potential of colon cancer stem cell precursors.

    PubMed

    Shenoy, Anitha K; Fisher, Robert C; Butterworth, Elizabeth A; Pi, Liya; Chang, Lung-Ji; Appelman, Henry D; Chang, Myron; Scott, Edward W; Huang, Emina H

    2012-10-01

    Ulcerative colitis (UC) increases the risk of colorectal cancer (CRC), but the mechanisms involved in colitis-to-cancer transition (CCT) are not well understood. CCT may involve a inflammation-dysplasia-carcinoma progression sequence compared with the better characterized adenoma-carcinoma progression sequence associated with sporadic CRC. One common thread may be activating mutations in components of the Wnt/β-catenin signaling pathway, which occur commonly as early events in sporadic CRC. To examine this hypothesis, we evaluated possible associations between Wnt/β-catenin signaling and CCT based on the cancer stem cell (CSC) model. Wnt/β-catenin immunostaining indicated that UC patients have a level of Wnt-pathway-active cells that is intermediate between normal colon and CRC. These UC cells exhibiting activation of the Wnt pathway constituted a major subpopulation (52% + 7.21) of the colonic epithelial cells positive for aldehyde dehydrogenase (ALDH), a putative marker of precursor colon CSC (pCCSC). We further fractionated this subpopulation of pCCSC using a Wnt pathway reporter assay. Over successive passages, pCCSCs with the highest Wnt activity exhibited higher clonogenic and tumorigenic potential than pCCSCs with the lowest Wnt activity, thereby establishing the key role of Wnt activity in driving CSC-like properties in these cells. Notably, 5/20 single cell injections of high-Wnt pCCSC resulted in tumor formation, suggesting a correlation with CCT. Attenuation of Wnt/β-catenin in high-Wnt pCCSC by shRNA-mediated downregulation or pharmacological inhibition significantly reduced tumor growth rates. Overall, the results of our study indicates (i) that early activation of Wnt/β-catenin signaling is critical for CCT and (ii) that high levels of Wnt/β-catenin signaling can further demarcate high-ALDH tumor-initiating cells in the nondysplastic epithelium of UC patients. As such, our findings offer plausible diagnostic markers and therapeutic target in the

  5. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    SciTech Connect

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  6. Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers.

    PubMed

    Alvarez, Ruth; Lee, Hye-Lim; Wang, Cun-Yu; Hong, Christine

    2015-12-18

    Mesenchymal stem cell (MSC)-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations: CD51/CD140α, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells (DMSCs) from heterogeneous periodontal ligament cells (PDLCs). Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51(+)/CD140α(+), 0.8% were CD271(+), and 2.4% were STRO-1(+)/CD146(+). Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271(+) DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.

  7. Chaperone proteins and brain tumors: Potential targets and possible therapeutics1

    PubMed Central

    Graner, Michael W.; Bigner, Darell D.

    2005-01-01

    Chaperone proteins are most notable for the proteo- and cyotoprotective capacities they afford during cellular stress. Under conditions of cellular normalcy, chaperones still play integral roles in the folding of nascent polypeptides into functional entities, in assisting in intracellular/intraorganellar transport, in assembly and maintenance of multi-subunit protein complexes, and in aiding and abetting the degradation of senescent proteins. Tumors frequently have relatively enhanced needs for chaperone number and activity because of the stresses of rapid proliferation, increased metabolism, and overall genetic instability. Thus, it may be possible to take advantage of this reliance that tumor cells have on chaperones by pharmacologic and biologic means. Certain chaperones are abundant in the brain, which implies important roles for them. While it is presumed that the requirements of brain tumors for chaperone proteins are similar to those of any other cell type, tumor or otherwise, very little inquiry has been directed at the possibility of using chaperone proteins as therapeutic targets or even as therapeutic agents against central nervous system malignancies. This review highlights some of the research on the functions of chaperone proteins, on what can be done to modify those functions, and on the physiological responses that tumors and organisms can have to chaperone-targeted or chaperone-based therapies. In particular, this review will also underscore areas of research where brain tumors have been part of the field, although in general those instances are few and far between. This relative dearth of research devoted to chaperone protein targets and therapeutics in brain tumors reveals much untrodden turf to explore for potential treatments of these dreadfully refractive diseases. PMID:16053701

  8. Gum arabic-coated magnetic nanoparticles for potential application in simultaneous magnetic targeting and tumor imaging.

    PubMed

    Zhang, Lei; Yu, Faquan; Cole, Adam J; Chertok, Beata; David, Allan E; Wang, Jingkang; Yang, Victor C

    2009-12-01

    Magnetic iron oxide nanoparticles (MNP) coated with gum arabic (GA), a biocompatible phytochemical glycoprotein widely used in the food industry, were successfully synthesized and characterized. GA-coated MNP (GA-MNP) displayed a narrow hydrodynamic particle size distribution averaging about 100 nm; a GA content of 15.6% by dry weight; a saturation magnetization of 93.1 emu/g Fe; and a superparamagnetic behavior essential for most magnetic-mediated applications. The GA coating offers two major benefits: it both enhances colloidal stability and provides reactive functional groups suitable for coupling of bioactive compounds. In vitro results showed that GA-MNP possessed a superior stability upon storage in aqueous media when compared to commercial MNP products currently used in magnetic resonance imaging (MRI). In addition, significant cellular uptake of GA-MNP was evaluated in 9L glioma cells by electron spin resonance (ESR) spectroscopy, fluorescence microscopy, and MRI analyses. Based on these findings, it was hypothesized that GA-MNP might be utilized as a MRI-visible drug carrier in achieving both magnetic tumor targeting and intracellular drug delivery. Indeed, preliminary in vivo investigations validate this clinical potential. MRI visually confirmed the accumulation of GA-MNP at the tumor site following intravenous administration to rats harboring 9L glioma tumors under the application of an external magnetic field. ESR spectroscopy quantitatively revealed a 12-fold increase in GA-MNP accumulation in excised tumors when compared to contralateral normal brain. Overall, the results presented show promise that GA-MNP could potentially be employed to achieve simultaneous tumor imaging and targeted intra-tumoral drug delivery.

  9. The sweet trap in tumors: aerobic glycolysis and potential targets for therapy

    PubMed Central

    Wang, Liantang; Chen, Shangwu

    2016-01-01

    Metabolic change is one of the hallmarks of tumor, which has recently attracted a great of attention. One of main metabolic characteristics of tumor cells is the high level of glycolysis even in the presence of oxygen, known as aerobic glycolysis or the Warburg effect. The energy production is much less in glycolysis pathway than that in tricarboxylic acid cycle. The molecular mechanism of a high glycolytic flux in tumor cells remains unclear. A large amount of intermediates derived from glycolytic pathway could meet the biosynthetic requirements of the proliferating cells. Hypoxia-induced HIF-1α, PI3K-Akt-mTOR signaling pathway, and many other factors, such as oncogene activation and tumor suppressor inactivation, drive cancer cells to favor glycolysis over mitochondrial oxidation. Several small molecules targeting glycolytic pathway exhibit promising anticancer activity both in vitro and in vivo. In this review, we will focus on the latest progress in the regulation of aerobic glycolysis and discuss the potential targets for the tumor therapy. PMID:26918353

  10. Infrared spectroscopic studies of cells and tissues: triple helix proteins as a potential biomarker for tumors.

    PubMed

    Stelling, Allison L; Toher, Deirdre; Uckermann, Ortrud; Tavkin, Jelena; Leipnitz, Elke; Schweizer, Julia; Cramm, Holger; Steiner, Gerald; Geiger, Kathrin D; Kirsch, Matthias

    2013-01-01

    In this work, the infrared (IR) spectra of living neural cells in suspension, native brain tissue, and native brain tumor tissue were investigated. Methods were developed to overcome the strong IR signal of liquid water so that the signal from the cellular biochemicals could be seen. Measurements could be performed during surgeries, within minutes after resection. Comparison between normal tissue, different cell lineages in suspension, and tumors allowed preliminary assignments of IR bands to be made. The most dramatic difference between tissues and cells was found to be in weaker IR absorbances usually assigned to the triple helix of collagens. Triple helix domains are common in larger structural proteins, and are typically found in the extracellular matrix (ECM) of tissues. An algorithm to correct offsets and calculate the band heights and positions of these bands was developed, so the variance between identical measurements could be assessed. The initial results indicate the triple helix signal is surprisingly consistent between different individuals, and is altered in tumor tissues. Taken together, these preliminary investigations indicate this triple helix signal may be a reliable biomarker for a tumor-like microenvironment. Thus, this signal has potential to aid in the intra-operational delineation of brain tumor borders.

  11. Nordihydroguaiaretic acid ameliorates cisplatin induced nephrotoxicity and potentiates its anti-tumor activity in DMBA induced breast cancer in female Sprague-Dawley rats.

    PubMed

    Mundhe, Nitin Arunrao; Kumar, Parveen; Ahmed, Sahabuddin; Jamdade, Vinayak; Mundhe, Sanjay; Lahkar, Mangala

    2015-09-01

    Cisplatin is a widely used antineoplastic drug, but its clinical usefulness is limited due to dose dependent nephrotoxicity. Nordihydroguaiaretic acid (NDGA) is a natural compound with broad pharmacological properties like antioxidant, anti-inflammatory and anticancer activity. The present study was undertaken to evaluate the possible beneficial effects of NDGA on cisplatin induced nephrotoxicity as well as its anticancer activity in rats bearing DMBA induced mammary tumors. The effect of NDGA on cisplatin induced nephrotoxicity was evaluated by checking serum nephrotoxicity markers, antioxidant enzymes and inflammatory markers level and kidney histopathology. NDGA induced amelioration of cisplatin nephrotoxicity was clearly visible from significant reductions in serum blood urea nitrogen (86.51 g/dl) and creatinine (5.30 g/dl) levels and significant improvement in body weight change (-10.34 g) and kidney weight (728 mg/kg). The protective effect of NDGA against cisplatin induced nephrotoxicity in the rats was further confirmed by significant restoration of antioxidant enzymes like SOD (86.28% inhibition), inflammatory markers like TNF-α (34.6 pg/ml) and histopathological examination. Moreover, our results showed that NDGA potentiated anti-breast cancer activity of cisplatin through an increment in the expression of antioxidant enzymes like SOD (85.35% inhibition) in breast cancer tissue. These results indicated that NDGA potentiated the anti-breast cancer activity of cisplatin, which was clearly evident from the tumor volume and % tumor inhibition in breast cancer rats. The current study demonstrated that NDGA may modify the therapeutic effect of cisplatin in DMBA induced breast cancer in female Sprague-Dawley rats.

  12. Testing the potential of a ribosomal 16S marker for DNA metabarcoding of insects

    PubMed Central

    Elbrecht, Vasco; Taberlet, Pierre; Dejean, Tony; Valentini, Alice; Usseglio-Polatera, Philippe; Beisel, Jean-Nicolas; Coissac, Eric; Boyer, Frederic

    2016-01-01

    Cytochrome c oxidase I (COI) is a powerful marker for DNA barcoding of animals, with good taxonomic resolution and a large reference database. However, when used for DNA metabarcoding, estimation of taxa abundances and species detection are limited due to primer bias caused by highly variable primer binding sites across the COI gene. Therefore, we explored the ability of the 16S ribosomal DNA gene as an alternative metabarcoding marker for species level assessments. Ten bulk samples, each containing equal amounts of tissue from 52 freshwater invertebrate taxa, were sequenced with the Illumina NextSeq 500 system. The 16S primers amplified three more insect species than the Folmer COI primers and amplified more equally, probably due to decreased primer bias. Estimation of biomass might be less biased with 16S than with COI, although variation in read abundances of two orders of magnitudes is still observed. According to these results, the marker choice depends on the scientific question. If the goal is to obtain a taxonomic identification at the species level, then COI is more appropriate due to established reference databases and known taxonomic resolution of this marker, knowing that a greater proportion of insects will be missed using COI Folmer primers. If the goal is to obtain a more comprehensive survey the 16S marker, which requires building a local reference database, or optimised degenerated COI primers could be more appropriate. PMID:27114891

  13. Comparison of the Hypoxia PET Tracer 18F-EF5 to Immunohistochemical Marker EF5 in 3 Different Human Tumor Xenograft Models

    PubMed Central

    Chitneni, Satish K.; Bida, Gerald T.; Zalutsky, Michael R.; Dewhirst, Mark W.

    2014-01-01

    The availability of 18F-labeled and unlabeled 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5) allows for a comparative assessment of tumor hypoxia by PET and immunohistochemistry; however, the combined use of these 2 approaches has not been fully assessed in vivo. The aim of this study was to evaluate 18F-EF5 tumor uptake versus EF5 binding and hypoxia as determined from immunohistochemistry at both macroscopic and microregional levels. Methods Three tumor models— PC3, HCT116, and H460—were evaluated. Tumor-bearing animals were coinjected with 18F-EF5 and EF5 (30 mg/kg), and PET imaging was performed at 2.5 h after injection. After PET imaging and 2 min after Hoechst 33342 injection, the tumors were excised and evaluated for 18F-EF5 distribution by autoradiography and EF5 binding by immunohistochemistry. Additionally, the effects of nonradioactive EF5 (30 mg/kg) on the hypoxia-imaging characteristics of 18F-EF5 were evaluated by comparing the PET data for H460 tumors with those from animals injected with 18F-EF5 alone. Results The uptake of 18F-EF5 in hypoxic tumor regions and the spatial relationship between 18F-EF5 uptake and EF5 binding varied among tumors. H460 tumors showed higher tumor-to-muscle contrast in PET imaging; however, the distribution and uptake of the tracer was less specific for hypoxia in H460 than in HCT116 and PC3 tumors. Correlation analyses revealed that the highest spatial correlation between 18F-EF5 uptake and EF5 binding was in PC3 tumors (r = 0.73 ± 0.02) followed by HCT116 (r = 0.60 ± 0.06) and H460 (r = 0.53 ± 0.10). Uptake and binding of 18F-EF5 and EF5 correlated negatively with Hoechst 33342 perfusion marker distribution in the 3 tumor models. Image contrast and heterogeneous uptake of 18F-EF5 in H460 tumors was significantly higher when the radiotracer was used alone versus in combination with unlabeled EF5 (tumor-to-muscle ratio of 2.51 ± 0.33 vs. 1.71 ± 0.17, P , 0.001). Conclusion The uptake

  14. Hypofractionated Irradiation Has Immune Stimulatory Potential and Induces a Timely Restricted Infiltration of Immune Cells in Colon Cancer Tumors

    PubMed Central

    Frey, Benjamin; Rückert, Michael; Weber, Julia; Mayr, Xaver; Derer, Anja; Lotter, Michael; Bert, Christoph; Rödel, Franz; Fietkau, Rainer; Gaipl, Udo S.

    2017-01-01

    In addition to locally controlling the tumor, hypofractionated radiotherapy (RT) particularly aims to activate immune cells in the RT-modified microenvironment. Therefore, we examined whether hypofractionated RT can activate dendritic cells (DCs), induce immune cell infiltration in tumors, and how the chronology of immune cell migration into tumors occurs to gain knowledge for future definition of radiation breaks and inclusion of immunotherapy. Colorectal cancer treatments offer only limited survival benefit, and immunobiological principles for additional therapies need to be explored with preclinical models. The impact of hypofractionated RT on CT26 colon cancer tumor cell death, migration of DCs toward supernatants (SN) of tumor cells, and activation of DCs by SN were analyzed. The subcutaneous tumor of a BALB/c-CT26 mouse model was locally irradiated with 2 × 5 Gy, the tumor volume was monitored, and the infiltration of immune cells in the tumor was determined by flow cytometry daily. Hypofractionated RT induced a mixture of apoptotic and necrotic CT26 cells, which is known to be in particular immunogenic. DCs that migrated toward SN of CT26 cells particularly upregulated the activation markers CD80 and CD86 when in contact with SN of irradiated tumor cells. After hypofractionated RT, the tumor outgrowth was significantly retarded and in the irradiated tumors an increased infiltration of macrophages (CD11bhigh/F4-80+) and DCs (MHC-II+), but only between day 5 and 10 after the first irradiation, takes place. While CD4+ T cells migrated into non-irradiated and irradiated tumors, CD8+ T cells were only found in tumors that had been irradiated and they were highly increased at day 8 after the first irradiation. Myeloid-derived suppressor cells and regulatory T cells show regular turnover in irradiated and non-irradiated tumors. Tumor cell-specific anti-IgM antibodies were enhanced in the serum of animals with irradiated tumors. We conclude that

  15. Hypofractionated Irradiation Has Immune Stimulatory Potential and Induces a Timely Restricted Infiltration of Immune Cells in Colon Cancer Tumors.

    PubMed

    Frey, Benjamin; Rückert, Michael; Weber, Julia; Mayr, Xaver; Derer, Anja; Lotter, Michael; Bert, Christoph; Rödel, Franz; Fietkau, Rainer; Gaipl, Udo S

    2017-01-01

    In addition to locally controlling the tumor, hypofractionated radiotherapy (RT) particularly aims to activate immune cells in the RT-modified microenvironment. Therefore, we examined whether hypofractionated RT can activate dendritic cells (DCs), induce immune cell infiltration in tumors, and how the chronology of immune cell migration into tumors occurs to gain knowledge for future definition of radiation breaks and inclusion of immunotherapy. Colorectal cancer treatments offer only limited survival benefit, and immunobiological principles for additional therapies need to be explored with preclinical models. The impact of hypofractionated RT on CT26 colon cancer tumor cell death, migration of DCs toward supernatants (SN) of tumor cells, and activation of DCs by SN were analyzed. The subcutaneous tumor of a BALB/c-CT26 mouse model was locally irradiated with 2 × 5 Gy, the tumor volume was monitored, and the infiltration of immune cells in the tumor was determined by flow cytometry daily. Hypofractionated RT induced a mixture of apoptotic and necrotic CT26 cells, which is known to be in particular immunogenic. DCs that migrated toward SN of CT26 cells particularly upregulated the activation markers CD80 and CD86 when in contact with SN of irradiated tumor cells. After hypofractionated RT, the tumor outgrowth was significantly retarded and in the irradiated tumors an increased infiltration of macrophages (CD11b(high)/F4-80(+)) and DCs (MHC-II(+)), but only between day 5 and 10 after the first irradiation, takes place. While CD4(+) T cells migrated into non-irradiated and irradiated tumors, CD8(+) T cells were only found in tumors that had been irradiated and they were highly increased at day 8 after the first irradiation. Myeloid-derived suppressor cells and regulatory T cells show regular turnover in irradiated and non-irradiated tumors. Tumor cell-specific anti-IgM antibodies were enhanced in the serum of animals with irradiated tumors. We conclude that

  16. Therapeutic Potential and Challenges of Natural Killer Cells in Treatment of Solid Tumors

    PubMed Central

    Gras Navarro, Andrea; Björklund, Andreas T.; Chekenya, Martha

    2015-01-01

    Natural killer (NK) cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing, requiring one-to-one target engagement and site-directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells, and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME) and augment adaptive immune responses by promoting differentiation, activation, and/or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes, and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach. PMID:25972872

  17. Potential of Start Codon Targeted (SCoT) markers for DNA fingerprinting of newly synthesized tritordeums and their respective parents.

    PubMed

    Cabo, Sandra; Ferreira, Luciana; Carvalho, Ana; Martins-Lopes, Paula; Martín, António; Lima-Brito, José Eduardo

    2014-08-01

    Hexaploid tritordeum (H(ch)H(ch)AABB; 2n = 42) results from the cross between Hordeum chilense (H(ch)H(ch); 2n = 14) and cultivated durum wheat (Triticum turgidum ssp. durum (AABB; 2n = 28). Morphologically, tritordeum resembles the wheat parent, showing promise for agriculture and wheat breeding. Start Codon Targeted (SCoT) polymorphism is a recently developed technique that generates gene-targeted markers. Thus, we considered it interesting to evaluate its potential for the DNA fingerprinting of newly synthesized hexaploid tritordeums and their respective parents. In this study, 60 SCoT primers were tested, and 18 and 19 of them revealed SCoT polymorphisms in the newly synthesized tritordeum lines HT27 and HT22, respectively, and their parents. An analysis of the presence/absence of bands among tritordeums and their parents revealed three types of polymorphic markers: (i) shared by tritordeums and one of their parents, (ii) exclusively amplified in tritordeums, and (iii) exclusively amplified in the parents. No polymorphism was detected among individuals of each parental species. Three SCoT markers were exclusively amplified in tritordeums of lines HT22 and HT27, being considered as polyploidization-induced rearrangements. About 70% of the SCoT markers of H. chilense origin were not transmitted to the allopolyploids of both lines, and most of the SCoTs scored in the newly synthesized allopolyploids originated from wheat, reinforcing the potential use of tritordeum as an alternative crop.

  18. Caveolin-1 expression is variably displayed in astroglial-derived tumors and absent in oligodendrogliomas: concrete premises for a new reliable diagnostic marker in gliomas.

    PubMed

    Cassoni, Paola; Senetta, Rebecca; Castellano, Isabella; Ortolan, Erika; Bosco, Martino; Magnani, Ivana; Ducati, Alessandro

    2007-05-01

    Caveolins are basic constituents of flask-shaped cell membrane microdomains (caveolae), which are involved in many cell functions, including signalling, trafficking, and cellular growth control. The distribution of caveolae within the normal brain and in brain tumors is controversial. In the present study, we describe the expression of caveolin-1 (cav-1) in 64 brain tumors of different grade, of either astroglial or oligodendroglial origin. All studied astrocitomas of any grade (from II to IV) were cav-1 positive, displaying staining patterns and intensity specifically associated to the different tumor grades. In all glioblastomas and gliosarcomas, cav-1 staining was extremely intense, typically localized at the cell membrane and recognized a variable percentage of cells, including the majority of spindle cells and palisade-oriented perinecrotic cells. In anaplastic astrocytomas, a less intense membrane staining or a cytoplasmic dotlike immunoreactivity were present, the latter being almost the exclusive pattern observed in diffuse astrocitomas grade II. In contrast to astroglial tumors, the striking totality of grade II oligodendrogliomas and the large majority of grade III were lacking cav-1 expression. Interestingly, a cav-1 distribution overlapping the pattern described in tissues was observed also in primary cell cultures of human glioblastomas and astrocytomas, and also in one established glioblastoma cell line (U251 MG), analyzed by means of confocal microscopy and flow cytometry. In conclusion, among astroglial tumors cav-1 expression varies in distribution, pattern, and intensity specifically according to tumor types and grades. The association between tumor progression and a more structured membranous pattern of cav-1 expression could suggest the hypothesis of a neoplastic shift towards a mesenchymal phenotype, whose behavioral and biologic significance worth further studies. Finally, the lack of cav-1 immunoreactivity in oligodendrogliomas suggests its

  19. Examination of ancestral informative markers and self-reported race with tumor characteristics of breast cancer among Black and White women.

    PubMed

    Reding, Kerryn W; Carlson, Christopher S; Kahsai, Orsalem; Chen, Christina C; McDavid, Andrew; Doody, David R; Chen, Chu; Ornelas, India; Lowe, Kimberly; Bernstein, Leslie; Weiss, Linda; McDonald, Jill A; Simon, Michael S; Strom, Brian; Marchbanks, Polly A; Burkman, Ronald; Spirtas, Robert; Liff, Jonathan M; Malone, Kathleen E

    2012-07-01

    African American (AA) women have a higher mortality from breast cancer (BC) compared to European American (EA) women. This may be due to the higher proportion of AA women with tumors that are diagnosed at more advanced stages and are characterized as being estrogen receptor negative (ER-)/progesterone receptor negative (PR-). Our study sought to determine whether self-reported race and percent African ancestry were associated with BC tumor characteristics. In a multi-center, population-based case-control study of BC, we determined percent African ancestry using ancestry informative markers (AIM) among women self-reporting race as AA or Black. BC tumor characteristics were associated with self-reported race (including a 30 % reduction in ER+/PR+ tumors [95 % confidence interval [CI]: 0.6-0.9] and a 1.5-fold increased risk of high grade [95 % CI: 1.2-1.9] for AA women compared to EA women). AIMs among AA women were not associated with BC tumor characteristics (AA women with ≥95 % versus <80 % African ancestry, odds ratio [OR] = 1.0 for ER+/PR+ [95 % CI: 0.6-1.8] and OR = 0.9 for high-grade tumors [95 % CI: 0.6-1.4]). Similar findings were observed for BC stage. While BC subtypes were associated with self-reported race, BC subtypes were not associated with percent African ancestry. These study results suggest that subtle differences in percent African ancestry are less important than the overall presence of African ancestry in relation to BC tumor characteristics.

  20. Copeptin - A potential endocrine surrogate marker of CCK-4-induced panic symptoms?

    PubMed

    Demiralay, Cüneyt; Agorastos, Agorastos; Yassouridis, Alexander; Jahn, Holger; Wiedemann, Klaus; Kellner, Michael

    2017-02-01

    Intravenous cholecystokinin-tetrapeptide (CCK-4) administration reliably and dose-dependently provokes panic anxiety in man, accompanied by adrenocorticotropic hormone (ACTH) and cortisol release. Preclinical findings suggest that behavioral and endocrine effects of CCK-4 are mediated via corticotropin-releasing hormone (CRH) release. Anxiogenic stimulation of the central CCK-receptors in man was shown to increase as well vasopressin (AVP), which acts synergistically with CRH as pituitary-adrenocortical axis stimulator during stress. Copeptin (CoP), the C-terminal part of pre-pro-AVP, is released in an equimolar ratio to AVP. It is more stable in the circulation and easier to determine than AVP and it was found to closely mirror the production of AVP. So far, CoP secretion has not been characterized during panic provocation. In 30 healthy male human subjects, we repeatedly measured CoP in plasma during a panic challenge and studied its correlation to Acute Panic Inventory (API) ratings and plasma ACTH and cortisol. CoP levels correlated positively with the increase in API ratings (r=0.41, p=0.03), while ACTH or cortisol did not (r=0.08, p=0.68 and r=0.12, p=0.53, respectively). CoP levels correlated also positively with ACTH (r=0.48, p=0.009) and cortisol (r=0.48, p=0.01) concentrations throughout the CCK-4 challenge. As expected, we found a positive correlation between plasma ACTH and cortisol levels (r=0.57, p=0.001). A vasopressinergic activation during CCK-4 induced panic was demonstrated, which was correlated positively to panic symptoms and pituitary-adrenocortical release. Our findings suggest a role of CoP as a potential surrogate marker of CCK-4 panic symptoms. Further studies are needed to replicate our results and to further clarify the role of CoP as a stress-sensitive hormone in different panic paradigms as well as in panic patients.

  1. Tumor escape mechanisms: Potential role of soluble HLA antigens and NK cells activating ligands

    PubMed Central

    Campoli, Michael; Ferrone, Soldano

    2009-01-01

    The crucial role played by HLA antigens and natural killer (NK) cell activating ligands in the interactions of malignant cells with components of the host's immune system has stimulated interest in the characterization of their expression by malignant cells. Convincing evidence generated by the immunohistochemical staining of surgically removed malignant lesions with monoclonal antibodies (mAb) recognizing HLA antigens and NK cell activating ligands indicates that the surface expression of these molecules is frequently altered on malignant cells. These changes appear to have clinical significance, since in some types of malignant disease they are associated with the histopathological characteristics of the lesions as well as with disease free interval and survival. These associations have been suggested to reflect the effect of HLA antigen and NK cell activating ligand abnormalities on the interactions of tumor cells with antigen-specific cytotoxic T lymphocytes (CTL) and with NK cells. Nevertheless, there are examples in which disease progresses in the face of appropriate HLA antigen and/or NK cell activating ligand as well as tumor antigen expression by malignant cells and of functional antigen-specific CTL in the investigated patient. In such scenarios, it is likely that the tumor microenvironment is unfavorable for CTL and NK cell activity and contributes to tumor immune escape. Many distinct escape mechanisms have been shown to protect malignant cells from immune recognition and destruction in the tumor microenvironment. In this paper, following the description of the structural and functional characteristics of soluble HLA antigens and NK cell activating ligands, we will review changes in their serum level in malignant disease and discuss their potential role in the escape mechanisms utilized by tumor cells to avoid recognition and destruction. PMID:18700879

  2. Circulating exosomes potentiate tumor malignant properties in a mouse model of chronic sleep fragmentation

    PubMed Central

    Khalyfa, Abdelnaby; Almendros, Isaac; Gileles-Hillel, Alex; Akbarpour, Mahzad; Trzepizur, Wojciech; Mokhlesi, Babak; Huang, Lei; Andrade, Jorge; Farré, Ramon; Gozal, David

    2016-01-01

    Background Chronic sleep fragmentation (SF) increases cancer aggressiveness in mice. Exosomes exhibit pleiotropic biological functions, including immune regulatory functions, antigen presentation, intracellular communication and inter-cellular transfer of RNA and proteins. We hypothesized that SF-induced alterations in biosynthesis and cargo of plasma exosomes may affect tumor cell properties. Results SF-derived exosomes increased tumor cell proliferation (~13%), migration (~2.3-fold) and extravasation (~10%) when compared to exosomes from SC-exposed mice. Similarly, Pre exosomes from OSA patients significantly enhanced proliferation and migration of human adenocarcinoma cells compared to Post. SF-exosomal cargo revealed 3 discrete differentially expressed miRNAs, and exploration of potential mRNA targets in TC1 tumor cells uncovered 132 differentially expressed genes that encode for multiple cancer-related pathways. Methods Plasma-derived exosomes from C57/B6 mice exposed to 6 wks of SF or sleep control (SC), and from adult human patients with obstructive sleep apnea (OSA) before (Pre) and after adherent treatment for 6 wks (Post) were co-cultured with mouse lung TC1 or human adenocarcinoma tumor cell lines, respectively. Proliferation, migration, invasion, endothelial barrier integrity and extravasation assays of tumor cells were performed. Plasma mouse exosomal miRNAs were profiled with arrays, and transcriptomic assessments of TC1 cells exposed to SF or SC exosomes were conducted to identify gene targets. Conclusions Chronic SF induces alterations in exosomal miRNA cargo that alter the biological properties of TC1 lung tumor cells to enhance their proliferative, migratory and extravasation properties, and similar findings occur in OSA patients, in whom SF is a constitutive component of their sleep disorder. Thus, exosomes could participate, at least in part, in the adverse cancer outcomes observed in OSA. PMID:27419627

  3. Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors.

    PubMed

    Delgado-Goñi, T; Martín-Sitjar, J; Simões, R V; Acosta, M; Lope-Piedrafita, S; Arús, C

    2013-02-01

    Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n=3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n=3) and MRSI (n=9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5-fold higher than in control mouse brain (p<0.05). A faster wash-out was detected in normal brain parenchyma with respect to GBM tissue: half-lives of 2.06 ± 0.58 and 4.57 ± 1.15 h, respectively. MRSI maps of time-course DMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T(1) contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact blood-brain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors 'invisible' to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response.

  4. Adenosine potentiates the therapeutic effects of neural stem cells expressing cytosine deaminase against metastatic brain tumors.

    PubMed

    Kang, Wonyoung; Seol, Ho Jun; Seong, Dong-Ho; Kim, Jandi; Kim, Yonghyun; Kim, Seung U; Nam, Do-Hyun; Joo, Kyeung Min

    2013-09-01

    Tumor-tropic properties of neural stem cells (NSCs) provide a novel approach with which to deliver targeting therapeutic genes to brain tumors. Previously, we developed a therapeutic strategy against metastatic brain tumors using a human NSC line (F3) expressing cytosine deaminase (F3.CD). F3.CD converts systemically administered 5-fluorocytosine (5-FC), a blood-brain barrier permeable nontoxic prodrug, into the anticancer agent 5-fluorouracil (5-FU). In this study, we potentiated a therapeutic strategy of treatment with nucleosides in order to chemically facilitate the endogenous conversion of 5-FU to its toxic metabolite 5-FU ribonucleoside (5-FUR). In vitro, 5-FUR showed superior cytotoxic activity against MDA-MB-435 cancer cells when compared to 5-FU. Although adenosine had little cytotoxic activity, the addition of adenosine significantly potentiated the in vitro cytotoxicity of 5-FU. When MDA-MB‑435 cells were co-cultured with F3.CD cells, F3.CD cells and 5-FC inhibited the growth of MDA-MB-435 cells more significantly in the presence of adenosine. Facilitated 5-FUR production by F3.CD was confirmed by an HPLC analysis of the conditioned media derived from F3.CD cells treated with 5-FC and adenosine. In vivo systemic adenosine treatment also significantly potentiated the therapeutic effects of F3.CD cells and 5-FC in an MDA-MB-435 metastatic brain tumor model. Simple adenosine addition improved the antitumor activity of the NSCs carrying the therapeutic gene. Our results demonstrated an increased therapeutic potential, and thereby, clinical applicability of NSC-based gene therapy.

  5. Study of serum tumor markers CEA, CA 15.3 and CA 27.29 as diagnostic parameters in patients with breast carcinoma.

    PubMed

    Rodríguez de Paterna, L; Arnaiz, F; Estenoz, J; Ortuño, B; Lanzós, E

    1995-01-01

    Serum levels of CEA, CA 15.3 and CA 27.29 were measured during the follow-up of 499 breast cancer patients. Studies included three different groups of women: 82 blood donors free of disease, 42 patients with non-malignant breast diseases and 499 breast cancer patients. After the determination of cut-off values, serum levels of tumor markers did not show significant elevations in benign breast diseases. On the basis of our results CA 15.3 (sensitivity = 57%; accuracy = 87%) was the most effective marker, CA 27.29 (sensitivity = 62%; accuracy = 83%) was the most sensitive and CEA (sensitivity = 45%; accuracy = 81%) was the least sensitive and effective marker. The combined use of markers was evaluated by step-wise logistic regression analysis. The regression coefficients showed that CA 15.3 (coeff. = 2.97) and CA 27.29 (coeff. = 1.46) were suitable for the detection of possible metastases during follow-up. Finally, we studied the relationship between pT, pN, pM and circulating levels of CA 15.3 and CA 27.29.

  6. Geriatric forensics - Part 2 “Prevalence of elder abuse and their potential forensic markers among medical and dental patients”

    PubMed Central

    Mattoo, Khurshid A.; Garg, Rishabh; Kumar, Shalabh

    2015-01-01

    Context: This study is a continuation of the earlier studies and has been extended to investigate the potential forensic markers of elder abuse. Aims: To determine the prevalence of elder abuse in various outpatient departments (OPDs). To study the associated parameters related to the abuser and the abused. To determine the existence of potential forensic markers of elder abuse. Settings and Design: The subjects were randomly selected from the medical and the dental OPDs of the university. Materials and Methods: Eight hundred and thirty two elderly subjects in the age range 40-60 years were interviewed using a questionnaire to determine the existence of elder abuse. The subjects were investigated and examined for weight, nutrition and hydration, vital signs, habits, existing visual and auditory capabilities, medications, disclosure of wills/deeds, signs of depression, and documented cleanliness. The mini-mental state examination, the Geriatric Depression Scale, the Clock drawing test, and the Brief Psychiatric Rating Scale were used to determine the potential forensic markers. Statistical Analysis Used: Mean values in percentage were determined by dividing the number of determined subjects by the total number of subjects for that parameter. Results: About 37% in medical and 41% in dental OPDs were found to have suffered from abuse, mostly in the age group 60-70 years. Females received more abuse and a combination of son and daughter-in-law constituted most abusers. Various potential markers of elder abuse and neglect investigated among the elder abuse victims included depression (89%), signs of improper feeding (83%), changes in personal hygiene (69%), need for medical/dental treatment (78%), medication misuse (67%), changes in wills/deeds (26%), decubiti (10%), bruises (17%), skin tears (27%), and confusion (23%). Conclusions: Elder abuse exists in one or more forms in both medical and dental OPDs among both males and females in all age groups. PMID:26816460

  7. Navigated marker placement for motion compensation in radiotherapy

    NASA Astrophysics Data System (ADS)

    Winterstein, A.; März, K.; Franz, A. M.; Hafezi, M.; Fard, N.; Sterzing, F.; Mehrabi, A.; Maier-Hein, L.

    2015-03-01

    Radiotherapy is frequently used to treat unoperated or partially resected tumors. Tumor movement, e.g. caused by respiration, is a major challenge in this context. Markers can be implanted around the tumor prior to radiation therapy for accurate tracking of tumor movement. However, accurate placement of these markers while keeping a secure margin around the target and while taking into account critical structures is a difficult task. Computer-assisted needle insertion has been an active field of research in the past decades. However, the challenge of navigated marker placement for motion compensated radiotherapy has not yet been addressed. This work presents a system to support marker implantation for radiotherapy under consideration of safety margins and optimal marker configuration. It is designed to allow placement of markers both percutaneously and during an open liver surgery. To this end, we adapted the previously proposed EchoTrack system which integrates ultrasound (US) imaging and electromagnetic (EM) tracking in a single mobile modality. The potential of our new marker insertion concept was evaluated in a phantom study by inserting sets of three markers around dedicated targets (n=22) simultaneously spacing the markers evenly around the target as well as placing the markers in a defined distance to the target. In all cases the markers were successfully placed in a configuration fulfilling the predefined criteria. This includes a minimum distance of 18.9 ± 2.4 mm between marker and tumor as well as a divergence of 2.1 ± 1.5 mm from the planned marker positions. We conclude that our system has high potential to facilitate the placement of markers in suitable configurations for surgeons without extensive experience in needle punctions as high quality configurations were obtained even by medical non-experts.

  8. DNA methylome profiling of maternal peripheral blood and placentas reveal potential fetal DNA markers for non-invasive prenatal testing.

    PubMed

    Xiang, Yuqian; Zhang, Junyu; Li, Qiaoli; Zhou, Xinyao; Wang, Teng; Xu, Mingqing; Xia, Shihui; Xing, Qinghe; Wang, Lei; He, Lin; Zhao, Xinzhi

    2014-09-01

    Utilizing epigenetic (DNA methylation) differences to differentiate between maternal peripheral blood (PBL) and fetal (placental) DNA has been a promising strategy for non-invasive prenatal testing (NIPT). However, the differentially methylated regions (DMRs) have yet to be fully ascertained. In the present study, we performed genome-wide comparative methylome analysis between maternal PBL and placental DNA from pregnancies of first trimester by methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) and Infinium HumanMethylation450 BeadChip assays. A total of 36 931 DMRs and 45 804 differentially methylated sites (DMSs) covering the whole genome, exclusive of the Y chromosome, were identified via MeDIP-Seq and Infinium 450k array, respectively, of which 3759 sites in 2188 regions were confirmed by both methods. Not only did we find the previously reported potential fetal DNA markers in our identified DMRs/DMSs but also we verified fully the identified DMRs/DMSs in the validation round by MassARRAY EpiTYPER. The screened potential fetal DNA markers may be used for NIPT on aneuploidies and other chromosomal diseases, such as cri du chat syndrome and velo-cardio-facial syndrome. In addition, these potential markers may have application in the early diagnosis of placental dysfunction, such as pre-eclampsia.

  9. Dialkyl bisphosphonate platinum(II) complex as a potential drug for metastatic bone tumor.

    PubMed

    Nakatake, Hidetoshi; Ekimoto, Hisao; Aso, Mariko; Ogawa, Atsushi; Yamaguchi, Asami; Suemune, Hiroshi

    2011-01-01

    Bisphosphonates have high affinity for hydroxyapatite (HA), which is abundantly present in bone. Also, platinum complexes are known that have a wide spectrum of antitumor activities. The conjugate of bisphosphonate and a platinum complex might have HA affinity and antitumor activity, and become a drug for metastatic bone tumor. In this study, the authors synthesized platinum complexes that had dialkyl bisphosphonic acid as a ligand, and evaluated the possibility of the synthesized complexes as a drug for metastatic bone tumor. The synthesized dialkyl bisphosphonate platinum(II) complex was characterized, and its stability in an aqueous solution was also confirmed. The synthesized platinum complex showed higher HA affinity than other platinum complexes such as cisplatin and carboplatin in an experiment of adsorption to HA. In vitro, the platinum complex showed tumor growth inhibitory effect stronger than or equal to cisplatin, which is the most commonly used antitumor agent. Moreover, the platinum complex showed a bone absorption inhibitory effect on the osteoclast. These results suggest potential of dialkyl bisphosphonate platinum(II) complexes as a drug for metastatic bone tumor.

  10. Multiple Breast Cancer Cell-Lines Derived from a Single Tumor Differ in Their Molecular Characteristics and Tumorigenic Potential

    PubMed Central

    Mosoyan, Goar; Nagi, Chandandeep; Marukian, Svetlana; Teixeira, Avelino; Simonian, Anait; Resnick-Silverman, Lois; DiFeo, Analisa; Johnston, Dean; Reynolds, Sandra R.; Roses, Daniel F.; Mosoian, Arevik

    2013-01-01

    Background Breast cancer cell lines are widely used tools to investigate breast cancer biology and to develop new therapies. Breast cancer tissue contains molecularly heterogeneous cell populations. Thus, it is important to understand which cell lines best represent the primary tumor and have similarly diverse phenotype. Here, we describe the development of five breast cancer cell lines from a single patient’s breast cancer tissue. We characterize the molecular profiles, tumorigenicity and metastatic ability in vivo of all five cell lines and compare their responsiveness to 4-hydroxytamoxifen (4-OHT) treatment. Methods Five breast cancer cell lines were derived from a single patient’s primary breast cancer tissue. Expression of different antigens including HER2, estrogen receptor (ER), CK8/18, CD44 and CD24 was determined by flow cytometry, western blotting and immunohistochemistry (IHC). In addition, a Fuorescent In Situ Hybridization (FISH) assay for HER2 gene amplification and p53 genotyping was performed on all cell lines. A xenograft model in nude mice was utilized to assess the tumorigenic and metastatic abilities of the breast cancer cells. Results We have isolated, cloned and established five new breast cancer cell lines with different tumorigenicity and metastatic abilities from a single primary breast cancer. Although all the cell lines expressed low levels of ER, their growth was estrogen-independent and all had high-levels of expression of mutated non-functional p53. The HER2 gene was rearranged in all cell lines. Low doses of 4-OHT induced proliferation of these breast cancer cell lines. Conclusions All five breast cancer cell lines have different antigenic expression profiles, tumorigenicity and organ specific metastatic abilities although they derive from a single tumor. None of the studied markers correlated with tumorigenic potential. These new cell lines could serve as a model for detailed genomic and proteomic analyses to identify mechanisms

  11. Gastrointestinal stromal tumors - quantitative detection of the Ki-67, TPX2, TOP2A, and hTERT telomerase subunit mRNA levels to determine proliferation activity and a potential for aggressive biological behavior.

    PubMed

    Kalfusova, A; Hilska, I; Krskova, L; Kalinova, M; Linke, Z; Kodet, R

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) have an unpredictable biological potential ranging from benign to malignant. Molecular markers involved in the mechanisms of proliferation and cellular senescence may provide additional information about biological behavior of the tumor. The aim of the present study was to investigate Ki-67, TPX2, TOP2A and hTERT mRNA expression levels in specimens from patients with GISTs to define relationships between proliferation activity and biological potential and progression of the disease. We measured Ki-67, TPX2, TOP2A and hTERT mRNA levels using quantitative real-time reverse transcription PCR (RQ RT PCR). The highest Ki-67, TPX2, TOP2A and hTERT mRNA expression levels were found in the highly proliferative BLs (18 specimens), in comparison with GISTs (137 specimens) and LMSs (9 specimens). Patients with GISTs and adequate information about mitotic activity, tumor size and anatomical site (84 specimens) were divided into two groups - GISTs with benign (29 patients) and with malignant (55 patients) potential. We observed association between higher Ki-67, TPX2 and hTERT mRNA levels and the GISTs with malignant potential. Univariate analysis (57 patients with available follow-up information) of survival (Kaplan Meier curves method) revealed a correlation between higher levels of TPX2, Ki-67 and hTERT markers and shorter event-free survival (EFS) or poorer overall survival (OS). The results demonstrate the importance of quantitative assessment of the proliferation activity in GISTs. Proliferation markers of Ki-67, TPX2, TOP2A and hTERT are suitable markers for detection the proliferation activity and telomerase activity of these tumors. Furthermore, the assessment of TPX2, Ki-67 and hTERT expression levels is appropriate for determination of malignant potential of GISTs.

  12. Comparison of BOLD cerebrovascular reactivity mapping and DSC MR perfusion imaging for prediction of neurovascular uncoupling potential in brain tumors.

    PubMed

    Pillai, Jay J; Zacà, Domenico

    2012-08-01

    The coupling mechanism between neuronal firing and cerebrovascular dilatation can be significantly compromised in cerebral diseases, making it difficult to identify eloquent cortical areas near or within resectable lesions by using Blood Oxygen Level Dependent (BOLD) fMRI. Several metabolic and vascular factors have been considered to account for this lesion-induced neurovascular uncoupling (NVU), but no imaging gold standard exists currently for the detection of NVU. However, it is critical in clinical fMRI studies to evaluate the risk of NVU because the presence of NVU may result in false negative activation that may result in inadvertent resection of eloquent cortex, resulting in permanent postoperative neurologic deficits. Although NVU results from a disruption of one or more components of a complex cellular and chemical neurovascular coupling cascade (NCC) MR imaging is only able to evaluate the final step in this NCC involving the ultimate cerebrovascular response. Since anything that impairs cerebrovascular reactivity (CVR) will necessarily result in NVU, regardless of its effect more proximally along the NCC, we can consider mapping of CVR as a surrogate marker of NVU potential. We hypothesized that BOLD breath-hold (BH) CVR mapping can serve as a better marker of NVU potential than T2* Dynamic Susceptibility Contrast gadolinium perfusion MR imaging, because the latter is known to only reflect NVU risk associated with high grade gliomas by determining elevated relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) related to tumor angiogenesis. However, since low and intermediate grade gliomas are not associated with such tumoral hyperperfusion, BOLD BH CVR mapping may be able to detect such NVU potential even in lower grade gliomas without angiogenesis, which is the hallmark of glioblastomas. However, it is also known that glioblastomas are associated with variable NVU, since angiogenesis may not always result in NVU. Perfusion

  13. Mirror-like slip surfaces in dolostone: natural and experimental constraints on a potential seismic marker

    NASA Astrophysics Data System (ADS)

    Fondriest, M.; Smith, S. A.; Di Toro, G.; Nielsen, S. B.

    2012-12-01

    The lack of clear geological markers of seismic faulting represents a major limitation in our current comprehension of earthquake physics. At present pseudotachylytes (i.e. friction-induced melts) are the only unambiguously identified indicator of ancient seismicity in exhumed fault zones, but pseudotachylytes are not found in many rock types, including carbonates. We report the occurrence of small-displacement, mirror-like slip surfaces from a fault zone cutting dolostones. A combination of field observations and rotary shear friction experiments suggests that such slip surfaces: 1) are formed only at seismic slip rates, and 2) could potentially be used to estimate power dissipation during individual slip events. The Foiana Line (FL) is a major NNE-SSW-trending sinistral transpressive fault in the Italian Southern Alps. The outcropping fault zone consists of a <300 m wide zone of heavily fractured ("pulverized") dolostones cut by a network of mirror-like slip surfaces. The slip surfaces have displacements ranging between 0.04 m and 0.5 m and their mirror-like appearance indicates that the wavelength of surface roughness is <1 μm. The slip surfaces have mainly dip-slip reverse kinematics and were exhumed from ~2 km depth. Resolved normal stress on the slip surfaces is estimated in the range 30-50 MPa. To understand how the mirror-like slip surfaces may have developed, slow- to high-velocity rotary-shear experiments using SHIVA (INGV, Rome) were performed on 3 mm thick layers of dolomite gouge (grain size <250 μm) collected from the FL. Tests were conducted using a purpose-built gouge sample holder at slip rates of 0.0001-1.13 m/s, normal stresses up to 26 MPa and displacements in the range 0.02-3.5 m. At seismic slip rates of 1.13 m/s the dolomite gouge shows a dramatic reduction of the friction coefficient (μ) from a peak value of ~0.7 to a steady-state value of ~0.25. The gouge starts to weaken above a threshold velocity in the range 0.19-0.49 m/s following a

  14. Identification of innovative potential quality markers in rocket and melon fresh-cut produce.

    PubMed

    Cavaiuolo, Marina; Cocetta, Giacomo; Bulgari, Roberta; Spinardi, Anna; Ferrante, Antonio

    2015-12-01

    Ready-to-eat fresh cut produce are exposed to pre- and postharvest abiotic stresses during the production chain. Our work aimed to identify stress responsive genes as new molecular markers of quality that can be widely applied to leaves and fruits and easily determined at any stage of the production chain. Stress responsive genes associated with quality losses were isolated in rocket and melon fresh-cut produce and their expression levels analyzed by quantitative real time PCR (qRT-PCR) at different time points after harvest at 20 °C and 4 °C. qRT-PCR results were supported by correlation analysis with physiological and biochemical determinations evaluated at the same conditions such as chlorophyll a fluorescence indices, total, reducing sugars, sucrose, ethylene, ascorbic acid, lipid peroxidation and reactive oxygen species. In both species the putative molecular markers increased their expression soon after harvest suggesting a possible use as novel and objective quality markers of fresh-cut produces.

  15. Evaluation of boronated EGF as a potential delivery agent for BNCT of brain tumors

    SciTech Connect

    Yang, Weilian; Barth, R.F.; Adams, D.M.

    1996-12-31

    The epidermal growth factor receptor (EGFR) gene is often amplified in human glioblastomas, but, reflecting the cellular heterogeneity of these tumors, the frequency of amplification is variable. Since the number of EGFR has been considered as a potential target for the specific delivery of diagnostic and therapeutic agents to brain tumors. Initially, the focus was on using anti-EGFR monoclonal antibodies or their fragments, but within the past few years there has been increasing interest in using EGF based bioconjugates as targeting agents. Recently, we have described a method for the boronation of EGF and have characterized the resulting bioconjugates in vitro. In the present study, we have investigated the potential usefulness of boronated EGF as a delivery agent for neutron capture therapy in rats bearing intracerebral implants of the C6 glioma, which has been transfected with the gene encoding EGFR. Our results indicate that following intratumoral injection, boronated EGF selectivity targeted the transfected EGFR positive C6 glioma, and that the amount of delivered to the tumor exceeded by 3-4 orders of magnitude that which could be delivered by intravenous injection.

  16. Histone demethylase GASC1 - a potential prognostic and predictive marker in invasive breast cancer

    PubMed Central

    2012-01-01

    Background The histone demethylase GASC1 (JMJD2C) is an epigenetic factor suspected of involvement in development of different cancers, including breast cancer. It is thought to be overexpressed in the more aggressive breast cancer types based on mRNA expression studies on cell lines and meta analysis of human breast cancer sets. This study aimed to evaluate the prognostic and predictive value of GASC1 for women with invasive breast cancer. Methods All the 355 cases were selected from a cohort enrolled in the Kuopio Breast Cancer Project between April 1990 and December 1995. The expression of GASC1 was studied by immunohistochemistry (IHC) on tissue microarrays. Additionally relative GASC1 mRNA expression was measured from available 57 cases. Results In our material, 56% of the cases were GASC1 negative and 44% positive in IHC staining. Women with GASC1 negative tumors had two years shorter breast cancer specific survival and time to relapse than the women with GASC1 positive tumors (p=0.017 and p=0.034 respectively). The majority of GASC1 negative tumors were ductal cases (72%) of higher histological grade (84% of grade II and III altogether). When we evaluated estrogen receptor negative and progesterone receptor negative cases separately, there was 2 times more GASC1 negative than GASC1 positive tumors in each group (chi2, p= 0.033 and 0.001 respectively). In the HER2 positive cases, there was 3 times more GASC1 negative cases than GASC1 positives (chi2, p= 0.029). Patients treated with radiotherapy (n=206) and hormonal treatment (n=62) had better breast cancer specific survival, when they were GASC1 positive (Cox regression: HR=0.49, p=0.007 and HR=0.33, p=0.015, respectively). The expression of GASC1 mRNA was in agreement with the protein analysis. Conclusions This study indicates that the GASC1 is both a prognostic and a predictive factor for women with invasive breast cancer. GASC1 negativity is associated with tumors of more aggressive histopathological

  17. Assessing Therapeutic Potential of Magnetic Mesoporous Nanoassemblies for Chemo-Resistant Tumors.

    PubMed

    Pradhan, Lina; Thakur, Bhushan; Srivastava, Rohit; Ray, Pritha; Bahadur, Dhirendra

    2016-01-01

    Smart drug delivery system with strategic drug distribution is the future state-of-the-art treatment for any malignancy. To investigate therapeutic potential of such nanoparticle mediated delivery system, we examined the efficacy of dual drug-loaded, pH and thermo liable lipid coated mesoporous iron oxide-based magnetic nanoassemblies (DOX:TXL-LMMNA) in mice bearing both drug sensitive (A2780(S)) and drug resistant (A2780-CisR) ovarian cancer tumor xenografts. In presence of an external AC magnetic field (ACMF), DOX:TXL-LMMNA particles disintegrate to release encapsulated drug due to hyperthermic temperatures (41-45 ºC). In vivo bio distribution study utilizing the optical and magnetic properties of DOX:TXL-LMMNA particles demonstrated minimum organ specific toxicity. Noninvasive bioluminescence imaging of mice bearing A2780(S) tumors and administered with DOX-TXL-LMMNA followed by the application of ACMF revealed 65% less luminescence signal and 80% mice showed complete tumor regression within eight days. A six months follow-up study revealed absence of relapse in 70% of the mice. Interestingly, the A2780-CisR tumors which did not respond to drug alone (DOX:TXL) showed 80% reduction in luminescence and tumor volume with DOX:TXL-LMMNA after thermo-chemotherapy within eight days. Cytotoxic effect of DOX:TXL-LMMNA particles was more pronounced in A2780-CisR cells than in their sensitive counterpart. Thus these novel stimuli sensitive nanoassemblies hold great promise for therapy resistant malignancies and future clinical applications.

  18. Assessing Therapeutic Potential of Magnetic Mesoporous Nanoassemblies for Chemo-Resistant Tumors

    PubMed Central

    Pradhan, Lina; Thakur, Bhushan; Srivastava, Rohit; Ray, Pritha; Bahadur, Dhirendra

    2016-01-01

    Smart drug delivery system with strategic drug distribution is the future state-of-the-art treatment for any malignancy. To investigate therapeutic potential of such nanoparticle mediated delivery system, we examined the efficacy of dual drug-loaded, pH and thermo liable lipid coated mesoporous iron oxide-based magnetic nanoassemblies (DOX:TXL-LMMNA) in mice bearing both drug sensitive (A2780S) and drug resistant (A2780-CisR) ovarian cancer tumor xenografts. In presence of an external AC magnetic field (ACMF), DOX:TXL-LMMNA particles disintegrate to release encapsulated drug due to hyperthermic temperatures (41-45 ºC). In vivo bio distribution study utilizing the optical and magnetic properties of DOX:TXL-LMMNA particles demonstrated minimum organ specific toxicity. Noninvasive bioluminescence imaging of mice bearing A2780S tumors and administered with DOX-TXL-LMMNA followed by the application of ACMF revealed 65% less luminescence signal and 80% mice showed complete tumor regression within eight days. A six months follow-up study revealed absence of relapse in 70% of the mice. Interestingly, the A2780-CisR tumors which did not respond to drug alone (DOX:TXL) showed 80% reduction in luminescence and tumor volume with DOX:TXL-LMMNA after thermo-chemotherapy within eight days. Cytotoxic effect of DOX:TXL-LMMNA particles was more pronounced in A2780-CisR cells than in their sensitive counterpart. Thus these novel stimuli sensitive nanoassemblies hold great promise for therapy resistant malignancies and future clinical applications. PMID:27446490

  19. Engineering of double recombinant vaccinia virus with enhanced oncolytic potential for solid tumor virotherapy

    PubMed Central

    Kochneva, Galina; Sivolobova, Galina; Tkacheva, Anastasiya; Grazhdantseva, Antonina; Troitskaya, Olga; Nushtaeva, Anna; Tkachenko, Anastasiya; Kuligina, Elena; Richter, Vladimir; Koval, Olga

    2016-01-01

    Vaccinia virus (VACV) oncolytic therapy has been successful in a number of tumor models. In this study our goal was to generate a double recombinant vaccinia virus (VV-GMCSF-Lact) with enhanced antitumor activity that expresses exogenous proteins: the antitumor protein lactaptin and human granulocyte-macrophage colony-stimulating factor (GM-CSF). Lactaptin has previously been demonstrated to act as a tumor suppressor in mouse hepatoma as well as MDA-MB-231 human adenocarcinoma cells grafted into SCID mice. VV-GMCSF-Lact was engineered from Lister strain (L-IVP) vaccinia virus and has deletions of the viral thymidine kinase and vaccinia growth factor genes. Cell culture experiments revealed that engineered VV-GMCSF-Lact induced the death of cultured cancer cells more efficiently than recombinant VACV coding only GM-CSF (VV-GMCSF-dGF). Normal human MCF-10A cells were resistant to both recombinants up to 10 PFU/cell. The selectivity index for breast cancer cells measured in pair cultures MCF-7/MCF-10A was 200 for recombinant VV-GMCSF-Lact coding lactaptin and 100 for VV-GMCSF-dGF. Using flow cytometry we demonstrated that both recombinants induced apoptosis in treated cells but that the rate in the cells with active caspase −3 and −7 was higher after treatment with VV-GMCSF-Lact than with VV-GMCSF-dGF. Tumor growth inhibition and survival outcomes after VV-GMCSF-Lact treatment were estimated using immunodeficient and immunocompetent mice models. We observed that VV-GMCSF-Lact efficiently delays the growth of sensitive and chemoresistant tumors. These results demonstrate that recombinant VACVs coding an apoptosis-inducing protein have good therapeutic potential against chemoresistant tumors. Our data will also stimulate further investigation of coding lactaptin double recombinant VACV in clinical settings. PMID:27708236

  20. Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

    NASA Astrophysics Data System (ADS)

    Etame, Arnold B.

    The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

  1. Peripheral papillary tumor of type-II pneumocytes: a rare neoplasm of undetermined malignant potential.

    PubMed

    Dessy, E; Braidotti, P; Del Curto, B; Falleni, M; Coggi, G; Santa Cruz, G; Carai, A; Versace, R; Pietra, G G

    2000-03-01

    Peripheral papillary adenomas of the lung are uncommon neoplasms (only ten cases have been described so far in the English literature) composed predominantly of type-II pneumocytes and generally considered benign. We describe here two additional cases of this lung tumor. In both cases histological examination revealed an encapsulated papillary neoplasm with invasion of the capsule and, in one case, invasion of the adjacent alveoli and visceral pleura too. The proliferative index (Ki67) was less than 2% and the epithelial cells were positive for cytokeratins, surfactant apoproteins (SP), and nuclear thyroid transcription factor-1 (TTF- 1). Ultrastructurally, the epithelial cells showed the characteristic surface microvilli and cytoplasmic lamellar inclusions of type-II cells. Review of the literature has revealed two other cases of peripheral papillary adenoma of type-II pneumocytes with infiltrative features. Thus, we propose replacing the term peripheral papillary adenoma with peripheral papillary tumor of undetermined malignant potential.

  2. Potentiated DNA Damage Response in Circulating Breast Tumor Cells Confers Resistance to Chemotherapy*

    PubMed Central

    Gong, Chang; Liu, Bodu; Yao, Yandan; Qu, Shaohua; Luo, Wei; Tan, Weige; Liu, Qiang; Yao, Herui; Zou, Lee; Su, Fengxi; Song, Erwei

    2015-01-01

    Circulating tumor cells (CTCs) are seeds for cancer metastasis and are predictive of poor prognosis in breast cancer patients. Whether CTCs and primary tumor cells (PTCs) respond to chemotherapy differently is not known. Here, we show that CTCs of breast cancer are more resistant to chemotherapy than PTCs because of potentiated DNA repair. Surprisingly, the chemoresistance of CTCs was recapitulated in PTCs when they were detached from the extracellular matrix. Detachment of PTCs increased the levels of reactive oxygen species and partially activated the DNA damage checkpoint, converting PTCs to a CTC-like state. Inhibition of checkpoint kinases Chk1 and Chk2 in CTCs reduces the basal checkpoint response and sensitizes CTCs to DNA damage in vitro and in mouse xenografts. Our results suggest that DNA damage checkpoint inhibitors may benefit the chemotherapy of breast cancer patients by suppressing the chemoresistance of CTCs and reducing the risk of cancer metastasis. PMID:25897074

  3. Potentiated DNA Damage Response in Circulating Breast Tumor Cells Confers Resistance to Chemotherapy.

    PubMed

    Gong, Chang; Liu, Bodu; Yao, Yandan; Qu, Shaohua; Luo, Wei; Tan, Weige; Liu, Qiang; Yao, Herui; Zou, Lee; Su, Fengxi; Song, Erwei

    2015-06-12

    Circulating tumor cells (CTCs) are seeds for cancer metastasis and are predictive of poor prognosis in breast cancer patients. Whether CTCs and primary tumor cells (PTCs) respond to chemotherapy differently is not known. Here, we show that CTCs of breast cancer are more resistant to chemotherapy than PTCs because of potentiated DNA repair. Surprisingly, the chemoresistance of CTCs was recapitulated in PTCs when they were detached from the extracellular matrix. Detachment of PTCs increased the levels of reactive oxygen species and partially activated the DNA damage checkpoint, converting PTCs to a CTC-like state. Inhibition of checkpoint kinases Chk1 and Chk2 in CTCs reduces the basal checkpoint response and sensitizes CTCs to DNA damage in vitro and in mouse xenografts. Our results suggest that DNA damage checkpoint inhibitors may benefit the chemotherapy of breast cancer patients by suppressing the chemoresistance of CTCs and reducing the risk of cancer metastasis.

  4. The potential role of natural tumor promoters in marine turtle fibropapillomatosis

    USGS Publications Warehouse

    Landsberg, J.H.; Balazs, G.H.; Steidinger, K.A.; Baden, D.G.; Work, T.M.; Russel, D.J.

    1999-01-01

    Fibropapillomatosis (FP) in green turtles Chelonia mydas is a debilitating, neoplastic disease that has reached worldwide epizootic levels. The etiology of FP is unknown but has been linked to oncogenic viruses. Toxic benthic dinoflagellates (Prorocentrum spp.) are not typically considered tumorigenic agents, yet they have a worldwide distribution and produce a tumor promoter, okadaic acid (OA). Prorocentrum spp. are epiphytic on macroalgae and seagrasses that are normal components of green turtle diets. Here we show that green turtles in the Hawaiian Islands consume Prorocentrum and that high-risk FP areas are associated with areas where P. lima and P. concavum are both highly prevalent and abundant. The presence of presumptive OA in the tissues of Hawaiian green turtles further suggests exposure and a potential role for this tumor promoter in the etiology of FP.

  5. Is a stable or decreasing prolactin level in a patient with prolactinoma a surrogate marker for lack of tumor growth?

    PubMed

    Alkabbani, Abdulrahman G; Mon, Sann Y; Hatipoglu, Betul; Kennedy, Laurence; Faiman, Charles; Weil, Robert J; Hamrahian, Amir H

    2014-04-01

    The optimal interval for follow-up imaging of patients with prolactinomas is unclear. We wish to determine the likelihood of tumor enlargement in patients with prolactinomas who have a stable or reduced prolactin (PRL) level over time, whether or not they are treated with a dopamine agonist (DA). We identified 80 patients with prolactinomas (34 men, 46 women) who had at least two paired sets of serum PRL levels and pituitary MRIs, 3 or more months apart. Patients with hyperprolactinemia due to drug or stalk effects were excluded. The median (range) age was 45 (25-77) years. Sixty-three patients (78.8%) were treated with DA. PRL levels (ng/mL) at the initial and latest sets were 114 (0.3-15,732) and 16 (0.3-1,204), respectively. In patients with identifiable tumors, the maximum tumor diameters (mm) at the initial and latest MRI studies were 12.5 (2-60) and 12.5 (2-39) respectively, with an interval of 2.9 (0.3-9.7) years. Sixty percent of patients (n = 48) had a macroadenoma. Forty-two (52.5%) patients had either disappearance of the tumor (n = 22) or reduction (n = 20) in tumor size. In the remainder, tumor size was stable in 35 but increased in 3 patients. One of these patients, observed off therapy had a concomitant rise in PRL level. The other 2 had evidence of pituitary hemorrhage with no PRL increase. Tumor growth in prolactinoma patients with a stable or decreasing PRL level, regardless of size, is a rare event. Repetitive pituitary imaging in these patients may not be warranted.

  6. An orthotopic xenograft model of intraneural NF1 MPNST suggests a potential association between steroid hormones and tumor cell proliferation.

    PubMed

    Perrin, George Q; Li, Hua; Fishbein, Lauren; Thomson, Susanne A; Hwang, Min S; Scarborough, Mark T; Yachnis, Anthony T; Wallace, Margaret R; Mareci, Thomas H; Muir, David

    2007-11-01

    Malignant peripheral nerve sheath tumors (MPNST) are the most aggressive cancers associated with neurofibromatosis type 1 (NF1). Here we report a practical and reproducible model of intraneural NF1 MPNST, by orthotopic xenograft of an immortal human NF1 tumor-derived Schwann cell line into the sciatic nerves of female scid mice. Intraneural injection of the cell line sNF96.2 consistently produced MPNST-like tumors that were highly cellular and showed extensive intraneural growth. These xenografts had a high proliferative index, were angiogenic, had significant mast cell infiltration and rapidly dominated the host nerve. The histopathology of engrafted intraneural tumors was consistent with that of human NF1 MPNST. Xenograft tumors were readily examined by magnetic resonance imaging, which also was used to assess tumor vascularity. In addition, the intraneural proliferation of sNF96.2 cell tumors was decreased in ovariectomized mice, while replacement of estrogen or progesterone restored tumor cell proliferation. This suggests a potential role for steroid hormones in supporting tumor cell growth of this MPNST cell line in vivo. The controlled orthotopic implantation of sNF96.2 cells provides for the precise initiation of intraneural MPNST-like tumors in a model system suitable for therapeutic interventions, including inhibitors of angiogenesis and further study of steroid hormone effects on tumor cell growth.

  7. Human anti-mouse antibodies: pitfalls in tumor marker measurement and strategies for enhanced assay robustness; including results with Elecsys CEA.

    PubMed

    Nussbaum, S; Roth, H J

    2000-01-01

    Therapies using monoclonal antibodies may have undesirable consequences for the diagnostic use of tumor markers. These effects can be minimised by employing chimeric antibodies as well as special interference eliminating reagents. Human Anti-Mouse Antibodies (HAMA) are produced as a result of the immune response of a patient to treatment with murine monoclonal antibodies. The interaction of HAMA with the murine monoclonal antibodies of a tumor marker assay can simulate (false) positive or negative results leading to misdiagnosis and to inadequate disease management of a patient. To avoid HAMA-interferences "Roche Diagnostics" established a three-component-system: The use of chimeric antibodies, the interference elimination, which is realised in the parameters most frequently used like CEA and TSH. By employing such a chimeric antibody, Elecsys CEA proved to be extremely robust against HAMA-interferences. With 20 clinical relevant samples from different Mab-approaches, no HAMA-interference was observed. By fragmentation of the antibodies, i.e., elimination of the constant region and using monovalent fab-fragments (antigen binding fragment) combined with the addition of special blocking reagents all not-chimerized, Elecsys assays showed comparable results to chimerisation. This could also be shown with 20 clinical relevant samples.

  8. Prognostic Impact of the Tumor Marker CA 15-3 in Patients With Breast Cancer and Bone Metastases Treated With Palliative Radiotherapy

    PubMed Central

    Nieder, Carsten; Dalhaug, Astrid; Haukland, Ellinor; Mannsaker, Bard; Pawinski, Adam

    2017-01-01

    Background The aim of the study was to explore the prognostic impact of different abnormal blood tests and the tumor marker CA 15-3 as well as established parameters such as disease extent and receptor status in patients with bone metastases from breast cancer who received palliative radiotherapy in addition to contemporary systemic treatment. Methods This was a retrospective uni- and multivariate analysis of 118 female patients treated in the time period from 2007 to 2014 (median follow-up 28 months). Results The median age was 61 years and the median time interval from the initial diagnosis of breast cancer was 57 months (median time interval from metastatic disease to radiotherapy was 7 months). Only 16% of patients had normal serum CA 15-3. HER2 receptor status correlated with CA 15-3. The median survival was 17.6 months (lowest CA 15-3 quartile), 14.7 months (intermediate), and 6.9 months (highest quartile) (P = 0.002). However, multivariate analysis showed that survival was influenced by extent of extra-skeletal metastases, pleural metastases/effusion, lung metastases, estrogen receptor status, serum C-reactive protein, and anemia with need for blood transfusion (all P < 0.05) rather than CA 15-3. Conclusions Survival was highly variable. The tumor marker CA 15-3 did not provide independent prognostic information. Nevertheless, the results of simple blood tests contributed to the multivariate prognostic model. PMID:28179964

  9. Individual and combined usefulness of lipid associated sialic acid, mucoid proteins and hexoses as tumor markers in breast carcinoma.

    PubMed

    Patel, P S; Baxi, B R; Adhvaryu, S G; Balar, D B

    1990-06-15

    Serum levels of lipid associated sialic acid (LASA), mucoid proteins (MP) and hexoses (galactose + mannose) were measured in 41 breast cancer patients, 14 patients with benign breast diseases and 36 healthy age matched female individuals. In breast carcinoma patients, we have observed significant increase in the levels of the three markers compared with the controls (P less than 0.001) and in MP and hexoses compared to the patients with benign breast diseases (P less than 0.001). LASA and hexoses levels were significantly higher in benign breast diseases with respect to controls (P less than 0.001 and P less than 0.01, respectively). We evaluated the sensitivity and specificity of the markers individually and in combination. MP were most sensitive (71.8%) and specific (71.4%). Both sensitivity and specificity were increased when combinations of the markers were studied. Combination of MP with LASA was most sensitive (97.4%) while the combination of MP and hexoses was most specific (92.9%). LASA was significantly elevated in infiltrating duct carcinoma compared to lobular carcinoma (P less than 0.001). MP and hexoses also showed higher mean value in infiltrating duct carcinoma than lobular carcinoma. The present study suggests that the combination of the markers investigated might be useful for diagnosis and classification of breast carcinoma.

  10. The Continuum of Serous Tumors of Low Malignant Potential and Low-Grade Serous Carcinomas of the Ovary

    PubMed Central

    Wong, Kwong-Kwok; Gershenson, David

    2007-01-01

    The role of serous tumors of low malignant potential (LMP) in the development of invasive epithelial cancer of the ovary is debatable. This review summarizes the current clinical, genetic, and genomic evidence for the existence of a continuum comprising both LMP serous tumors and low-grade serous ovarian carcinomas. PMID:18057521

  11. Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients

    NASA Astrophysics Data System (ADS)

    Tsai, Wen-Sy; Chen, Jinn-Shiun; Shao, Hung-Jen; Wu, Jen-Chia; Lai-Ming, Jr.; Lu, Si-Hong; Hung, Tsung-Fu; Chiu, Yen-Chi; You, Jeng-Fu; Hsieh, Pao-Shiu; Yeh, Chien-Yuh; Hung, Hsin-Yuan; Chiang, Sum-Fu; Lin, Geng-Ping; Tang, Reiping; Chang, Ying-Chih

    2016-04-01

    Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.

  12. Circulating Tumor Cell Count Correlates with Colorectal Neoplasm Progression and Is a Prognostic Marker for Distant Metastasis in Non-Metastatic Patients.

    PubMed

    Tsai, Wen-Sy; Chen, Jinn-Shiun; Shao, Hung-Jen; Wu, Jen-Chia; Lai, Jr-Ming; Lu, Si-Hong; Hung, Tsung-Fu; Chiu, Yen-Chi; You, Jeng-Fu; Hsieh, Pao-Shiu; Yeh, Chien-Yuh; Hung, Hsin-Yuan; Chiang, Sum-Fu; Lin, Geng-Ping; Tang, Reiping; Chang, Ying-Chih

    2016-04-14

    Enumeration of circulating tumor cells (CTCs) has been proven as a prognostic marker for metastatic colorectal cancer (m-CRC) patients. However, the currently available techniques for capturing and enumerating CTCs lack of required sensitivity to be applicable as a prognostic marker for non-metastatic patients as CTCs are even more rare. We have developed a microfluidic device utilizing antibody-conjugated non-fouling coating to eliminate nonspecific binding and to promote the multivalent binding of target cells. We then established the correlation of CTC counts and neoplasm progression through applying this platform to capture and enumerate CTCs in 2 mL of peripheral blood from healthy (n = 27), benign (n = 21), non-metastatic (n = 95), and m-CRC (n = 15) patients. The results showed that the CTC counts progressed from 0, 1, 5, to 36. Importantly, after 2-year follow-up on the non-metastatic CRC patients, we found that those who had ≥5 CTCs were 8 times more likely to develop distant metastasis within one year after curable surgery than those who had <5. In conclusion, by employing a sensitive device, CTC counts show good correlation with colorectal neoplasm, thus CTC may be as a simple, independent prognostic marker for the non-metastatic CRC patients who are at high risk of early recurrence.

  13. Statistical strategies to reveal potential vibrational markers for in vivo analysis by confocal Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Oliveira Mendes, Thiago de; Pinto, Liliane Pereira; Santos, Laurita dos; Tippavajhala, Vamshi Krishna; Téllez Soto, Claudio Alberto; Martin, Airton Abrahão

    2016-07-01

    The analysis of biological systems by spectroscopic techniques involves the evaluation of hundreds to thousands of variables. Hence, different statistical approaches are used to elucidate regions that discriminate classes of samples and to propose new vibrational markers for explaining various phenomena like disease monitoring, mechanisms of action of drugs, food, and so on. However, the technical statistics are not always widely discussed in applied sciences. In this context, this work presents a detailed discussion including the various steps necessary for proper statistical analysis. It includes univariate parametric and nonparametric tests, as well as multivariate unsupervised and supervised approaches. The main objective of this study is to promote proper understanding of the application of various statistical tools in these spectroscopic methods used for the analysis of biological samples. The discussion of these methods is performed on a set of in vivo confocal Raman spectra of human skin analysis that aims to identify skin aging markers. In the Appendix, a complete routine of data analysis is executed in a free software that can be used by the scientific community involved in these studies.

  14. Zeta potential change of Neuro-2a tumor cells after exposure to alumina nanoparticles

    NASA Astrophysics Data System (ADS)

    Kazantsev, Sergey O.; Fomenko, Alla N.; Korovin, Matvey S.

    2016-08-01

    In recent years, researches have paid much attention to the physical, chemical, biophysical and biochemical properties of a cell surface. It is known that most of the cells' surfaces are charged. This charge depends on the biochemical structure of the cell membranes. Therefore, measurement of a cell surface charge is a significant criterion that gives information about the cell surface. Evaluation of the cells zeta-potential is important to understand the interaction mechanisms of various drugs, antibiotics, as well as the interaction of nanoparticles with the cell surface. In this study, we use the dynamic light scattering method to detect the zeta-potential change of Neuro-2a tumor cells. It has been observed that zeta-potential shifted to negative values after exposure to metal oxide nanoparticles and inducing apoptosis.

  15. Denosumab, a Potential Alternative to the Surgical Treatment of Distal Radius Giant Cell Tumor of Bone: Case Report.

    PubMed

    Park, Min Jung; Ganjoo, Kristen N; Ladd, Amy L

    2015-08-01

    Juxta-articular giant cell tumors can pose major surgical challenges. Aggressive distal radius giant cell tumors often require complex reconstructive procedures that are associated with numerous complications. We present a case of a 25-year old man with a Campanacci grade 3 giant cell tumor of the distal radius that was successfully treated with denosumab without complex reconstructive procedures. At 3.5-year follow-up and 1-year drug free period, the patient remained asymptomatic without histologic evidence of recurrent tumor. With denosumab therapy, patients can potentially avoid surgery and achieve a successful outcome.

  16. Galectin-3 as a Potential Therapeutic Target in Tumors Arising from Malignant Endothelia1

    PubMed Central

    Johnson, Kim D; Glinskii, Olga V; Mossine, Valeri V; Turk, James R; Mawhinney, Thomas P; Anthony, Douglas C; Henry, Carolyn J; Huxley, Virginia H; Glinsky, Gennadi V; Pienta, Kenneth J; Raz, Avraham; Glinsky, Vladislav V

    2007-01-01

    Angiosarcoma (ASA) in humans and hemangiosarcoma (HSA) in dogs are deadly neoplastic diseases characterized by an aggressive growth of malignant cells with endothelial phenotype, widespread metastasis, and poor response to chemotherapy. Galectin-3 (Gal-3), a β-galactoside-binding lectin implicated in tumor progression and metastasis, endothelial cell biology and angiogenesis, and regulation of apoptosis and neoplastic cell response to cytotoxic drugs, has not been studied before in tumors arising from malignant endothelia. Here, we tested the hypothesis that Gal-3 could be widely expressed in human ASA and canine HSA and could play an important role in malignant endothelial cell biology. Immunohistochemical analysis demonstrated that 100% of the human ASA (10 of 10) and canine HSA (17 of 17) samples analyzed expressed Gal-3. Two carbohydrate-based Gal-3 inhibitors, modified citrus pectin (MCP) and lactulosyl-l-leucine (LL), caused a dose-dependent reduction of SVR murine ASA cell clonogenic survival through the inhibition of Gal-3 antiapoptotic function. Furthermore, both MCP and LL sensitized SVR cells to the cytotoxic drug doxorubicin to a degree sufficient to reduce the in vitro IC50 of doxorubicin by 10.7-fold and 3.6-fold, respectively. These results highlight the important role of Gal-3 in the biology of ASA and identify Gal-3 as a potential therapeutic target in tumors arising from malignant endothelial cells. PMID:17786185

  17. Identification and expression of troponin T, a new marker on the surface of cultured tumor endothelial cells by aptamer ligand

    PubMed Central

    Ara, Mst Naznin; Hyodo, Mamoru; Ohga, Noritaka; Akiyama, Kosuke; Hida, Kyoko; Hida, Yasuhiro; Shinohara, Nobuo; Harashima, Hideyoshi

    2014-01-01

    The identification of a specific biomarker involves the development of new clinical diagnostic tools, and an in-depth understanding of the disease at the molecular level. When new blood vessels form in tumor cells, endothelial cell production is induced, a process that plays a key role in disease progression and metastasis to distinct organs for solid tumor types. The present study reports on the identification of a new biomarker on primary cultured mouse tumor endothelial cells (mTECs) using our recently developed high-affinity DNA aptamer AraHH001 (Kd = 43 nmol/L) assisted proteomics approach. We applied a strategy involving aptamer-facilitated biomarker discovery. Biotin-tagged AraHH001 was incubated with lysates of mTECs and the aptamer-proteins were then conjugated with streptavidin magnetic beads. Finally, the bound proteins were separated by sodiumdodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with silver staining. We identified troponin T via matrix assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, the molecular target of aptamer AraHH001, and its presence was confirmed by measuring mRNA, protein levels, western blot, immunostaining, a gel shift assay of AraHH001 with troponin T. We first report here on the discovery of troponin T on mTECs, a promising and interesting diagnostic tool in the development of antiangiogenic therapy techniques the involves the targeting of the tumor vasculature. PMID:24810801

  18. Inflammatory and oncogenic roles of a tumor stem cell marker doublecortin-like kinase (DCLK1) in virus-induced chronic liver diseases

    PubMed Central

    Ali, Naushad; Chandrakesan, Parthasarathy; Nguyen, Charles B.; Husain, Sanam; Gillaspy, Allison F.; Huycke, Mark; Berry, William L.; May, Randal; Qu, Dongfeng; Weygant, Nathaniel; Sureban, Sripathi M.; Bronze, Michael S.; Dhanasekaran, Danny N.; Houchen, Courtney W.

    2015-01-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. We previously showed that a tumor/cancer stem cell (CSC) marker, doublecortin-like kinase (DCLK1) positively regulates hepatitis C virus (HCV) replication, and promotes tumor growth in colon and pancreas. Here, we employed transcriptome analysis, RNA interference, tumor xenografts, patient's liver tissues and hepatospheroids to investigate DCLK1-regulated inflammation and tumorigenesis in the liver. Our studies unveiled novel DCLK1-controlled feed-forward signaling cascades involving calprotectin subunit S100A9 and NFκB activation as a driver of inflammation. Validation of transcriptome data suggests that DCLK1 co-expression with HCV induces BRM/SMARCA2 of SW1/SNF1 chromatin remodeling complexes. Frequently observed lymphoid aggregates including hepatic epithelial and stromal cells of internodular septa extensively express DCLK1 and S100A9. The DCLK1 overexpression also correlates with increased levels of S100A9, c-Myc, and BRM levels in HCV/HBV-positive patients with cirrhosis and HCC. DCLK1 silencing inhibits S100A9 expression and hepatoma cell migration. Normal human hepatocytes (NHH)-derived spheroids exhibit CSC properties. These results provide new insights into the molecular mechanism of the hepatitis B/C-virus induced liver inflammation and tumorigenesis via DCLK1-controlled networks. Thus, DCLK1 appears to be a novel therapeutic target for the treatment of inflammatory diseases and HCC. PMID:25948779

  19. Inflammatory and oncogenic roles of a tumor stem cell marker doublecortin-like kinase (DCLK1) in virus-induced chronic liver diseases.

    PubMed

    Ali, Naushad; Chandrakesan, Parthasarathy; Nguyen, Charles B; Husain, Sanam; Gillaspy, Allison F; Huycke, Mark; Berry, William L; May, Randal; Qu, Dongfeng; Weygant, Nathaniel; Sureban, Sripathi M; Bronze, Michael S; Dhanasekaran, Danny N; Houchen, Courtney W

    2015-08-21

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. We previously showed that a tumor/cancer stem cell (CSC) marker, doublecortin-like kinase (DCLK1) positively regulates hepatitis C virus (HCV) replication, and promotes tumor growth in colon and pancreas. Here, we employed transcriptome analysis, RNA interference, tumor xenografts, patient's liver tissues and hepatospheroids to investigate DCLK1-regulated inflammation and tumorigenesis in the liver. Our studies unveiled novel DCLK1-controlled feed-forward signaling cascades involving calprotectin subunit S100A9 and NFκB activation as a driver of inflammation. Validation of transcriptome data suggests that DCLK1 co-expression with HCV induces BRM/SMARCA2 of SW1/SNF1 chromatin remodeling complexes. Frequently observed lymphoid aggregates including hepatic epithelial and stromal cells of internodular septa extensively express DCLK1 and S100A9. The DCLK1 overexpression also correlates with increased levels of S100A9, c-Myc, and BRM levels in HCV/HBV-positive patients with cirrhosis and HCC. DCLK1 silencing inhibits S100A9 expression and hepatoma cell migration. Normal human hepatocytes (NHH)-derived spheroids exhibit CSC properties. These results provide new insights into the molecular mechanism of the hepatitis B/C-virus induced liver inflammation and tumorigenesis via DCLK1-controlled networks. Thus, DCLK1 appears to be a novel therapeutic target for the treatment of inflammatory diseases and HCC.

  20. Boron neutron capture therapy of brain tumors: past history, current status, and future potential.

    PubMed

    Barth, R F; Soloway, A H; Brugger, R M

    1996-01-01

    Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield alpha particles and recoiling lithium-7 nuclei. High-grade astrocytomas, glioblastoma multiforme, and metastatic brain tumors constitute a major group of neoplasms for which there is no effective treatment. There is growing interest in using BNCT in combination with surgery to treat patients with primary, and possibly metastatic brain tumors. For BNCT to be successful, a large number of 10B atoms must be localized on or preferably within neoplastic cells, and a sufficient number of thermal neutrons must reach and be absorbed by the 10B atoms to sustain a lethal 10B(n, alpha)7 Li reaction. Two major questions will be addressed in this review. First, how can a large number of 10B atoms be delivered selectively to cancer cells? Second, how can a high fluence of neutrons be delivered to the tumor? Two boron compounds currently are being used clinically, sodium borocaptate (BSH) and boronophenylalanine (BPA), and a number of new delivery agents are under investigation, including boronated porphyrins, nucleosides, amino acids, polyamines, monoclonal and bispecific antibodies, liposomes, and epidermal growth factor. These will be discussed, and potential problems associated with their use as boron delivery agents will be considered. Nuclear reactors, currently, are the only source of neutrons for BNCT, and the fission process within the core produces a mixture of lower-energy thermal and epithermal neutrons, fast or high (> 10,000 eV) energy neutrons, and gamma rays. Although thermal neutron beams have been used clinically in Japan to treat patients with brain tumors and cutaneous melanomas, epithermal neutron beams should be more useful because of their superior tissue-penetrating properties. Beam sources and characteristics will be discussed in the context of current and future BNCT trials. Finally, the past and present

  1. Potentiation of Methoxymorpholinyl Doxorubicin Anti-Tumor Activity by P450 3A4 Gene Transfer#

    PubMed Central

    Lu, Hong; Chen, Chong-Sheng; Waxman, David J.

    2008-01-01

    Summary Preclinical and clinical studies of CYP gene-directed enzyme-prodrug therapy have focused on anticancer prodrugs activated by CYP2B enzymes, which have low endogenous expression in human liver; however, the gene therapeutic potential of CYP3A enzymes, which are highly expressed in human liver, remains unknown. This study investigated methoxymorpholinyl-doxorubicin (MMDX), a novel CYP3A-activated anticancer prodrug. Retroviral transfer of CYP3A4 increased 9L gliosarcoma cell chemosensitivity to MMDX 120-fold (IC50=0.2nM). In CHO cells, overexpression of P450 reductase in combination with CYP3A4 enhanced chemosensitivity to MMDX, and to ifosfamide, another CYP3A4 prodrug, 11–23-fold compared to CYP3A4 expression alone. CYP3A4 expression and MMDX chemosensitivity were increased in human lung (A549) and brain (U251) tumor cells infected with replication-defective adenovirus encoding CYP3A4. Co-infection with Onyx-017, a replication-conditional adenovirus that co-amplifies and co-replicates the Adeno-3A4 virus, led to large increases in CYP3A4 RNA but only modest increases in CYP3A4 protein and activity. MMDX induced remarkable growth delay of 9L/3A4 tumors, but not 9L tumors, in immunodeficient mice administered low-dose MMDX either i.v. or by direct intratumoral injection (60µg/kg, every 7-days ×3), with the intratumoral route being substantially less toxic to the mouse host. No antitumor activity was observed with i.p. MMDX treatment, suggesting a substantial hepatic first pass effect, and with activated MMDX metabolites formed in the liver having poor access to the tumor site. These studies demonstrate that human CYP3A4 has strong potential for MMDX prodrug activation therapy, and suggest that endogenous tumor cell expression of CYP3A4, and not hepatic CYP3A4 activity, is a key determinant of responsiveness to MMDX therapy in cancer patients in vivo. PMID:19011599

  2. Genome-wide association analysis of bacterial cold water disease resistance in rainbow trout reveals the potential of a hybrid approach between genomic selection and marker assisted selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic selection (GS) simultaneously incorporates dense SNP marker genotypes with phenotypic data from related animals to predict animal-specific genomic breeding value (GEBV), which circumvents the need to measure the disease phenotype in potential breeders. Marker assisted selection (MAS) involv...

  3. Expression Profiling of Ribosome Biogenesis Factors Reveals Nucleolin as a Novel Potential Marker to Predict Outcome in AML Patients.

    PubMed

    Marcel, Virginie; Catez, Frédéric; Berger, Caroline M; Perrial, Emeline; Plesa, Adriana; Thomas, Xavier; Mattei, Eve; Hayette, Sandrine; Saintigny, Pierre; Bouvet, Philippe; Diaz, Jean-Jacques; Dumontet, Charles

    2017-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis. Here, we investigated the usage of ribosome biogenesis factors as clinical markers in adult patients with AML. We showed that nucleoli, the nucleus compartments where ribosome production takes place, are modified in AML by analyzing a panel of AML and healthy donor cells using immunofluorescence staining. Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL) as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML.

  4. [Polymorphism of DNA nucleotide sequence as a source of enhancement of the discrimination potential of the STR-markers].

    PubMed

    Zemskova, E Yu; Timoshenko, T V; Leonov, S N; Ivanov, P L

    2016-01-01

    The objective of the present pilot investigation was to reveal and to study polymorphism of nucleotide sequence in the alleles of STR loci of human autosomal DNA with special reference to the role of this phenomenon as a source of the differences between homonymous allelic variants. The secondary objection was to evaluate the possibility of using the data thus obtained for the enhancement of the informative value of the forensic medical genotyping of STR loci by means of identification of single nucleotide polymorphisms (SNP) for the purpose of extending their allelic spectrum. The methodological basis of the study was constituted by the comprehensive amplified fragment length polymorphism (AFLP) analysis and amplified fragment sequence polymorphisms (AFSP) analysis of DNA with the use of the PLEX-ID^TM analytical mass-spectrometry platform (Abbot Molecular, USA). The study has demonstrated that polymorphism of DNA nucleotide sequence can be regarded as the possible source of enhancement of the discriminating potential of STR markers. It means that the analysis of polymorphism of DNA nucleotide sequence for genotyping AFLP-type markers of chromosomal DNA can considerably increase the effectiveness of their application as individualizing markers for the purpose of molecular genetic expertises.

  5. Expression Profiling of Ribosome Biogenesis Factors Reveals Nucleolin as a Novel Potential Marker to Predict Outcome in AML Patients

    PubMed Central

    Berger, Caroline M.; Perrial, Emeline; Plesa, Adriana; Thomas, Xavier; Mattei, Eve; Hayette, Sandrine; Saintigny, Pierre; Bouvet, Philippe; Diaz, Jean-Jacques; Dumontet, Charles

    2017-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease. Prognosis is mainly influenced by patient age at diagnosis and cytogenetic alterations, two of the main factors currently used in AML patient risk stratification. However, additional criteria are required to improve the current risk classification and better adapt patient care. In neoplastic cells, ribosome biogenesis is increased to sustain the high proliferation rate and ribosome composition is altered to modulate specific gene expression driving tumorigenesis. Here, we investigated the usage of ribosome biogenesis factors as clinical markers in adult patients with AML. We showed that nucleoli, the nucleus compartments where ribosome production takes place, are modified in AML by analyzing a panel of AML and healthy donor cells using immunofluorescence staining. Using four AML series, including the TCGA dataset, altogether representing a total of about 270 samples, we showed that not all factors involved in ribosome biogenesis have clinical values although ribosome biogenesis is increased in AML. Interestingly, we identified the regulator of ribosome production nucleolin (NCL) as over-expressed in AML blasts. Moreover, we found in two series that high NCL mRNA expression level was associated with a poor overall survival, particular in elderly patients. Multivariate analyses taking into account age and cytogenetic risk indicated that NCL expression in blast cells is an independent marker of reduced survival. Our study identifies NCL as a potential novel prognostic factor in AML. Altogether, our results suggest that the ribosome biogenesis pathway may be of interest as clinical markers in AML. PMID:28103300

  6. VDAC3 As a Potential Marker of Mitochondrial Status Is Involved in Cancer and Pathology

    PubMed Central

    Reina, Simona; Guarino, Francesca; Magrì, Andrea; De Pinto, Vito

    2016-01-01

    VDAC3 is the least known isoform of the mammalian voltage-dependent anion selective channels of the outer mitochondrial membrane. It has been recently shown that cysteine residues of VDAC3 are found over-oxidized. The VDAC3 cysteine over-oxidation was associated with the oxidizing environment and the abundance of reactive oxygen species (ROS) in the intermembrane space. In this work, we have examined the role of VDAC3 in general pathogenic mechanisms at the basis of mitochondrial dysfunction and involving the mitochondrial quality control. Many of the diseases reported here, including cancer and viral infections, are often associated with significant changes in the intracellular redox state. In this sense, VDAC3 bearing oxidative modifications could become marker of the oxidative load in the mitochondria and part of the ROS signaling pathway. PMID:28066720

  7. MTHFR Gene Mutations: A Potential Marker of Late-Onset Alzheimer's Disease?

    PubMed

    Román, Gustavo C

    2015-01-01

    Recent epigenome-wide association studies have confirmed the importance of epigenetic effects mediated by DNA methylation in late-onset Alzheimer's disease (LOAD). Metabolic folate pathways and methyl donor reactions facilitated by B-group vitamins may be critical in the pathogenesis of LOAD. Methylenetetrahydrofolate reductase (MTHFR) gene mutations were studied in consecutive Alzheimer's Disease & Memory Clinic patients up to December 2014. DNA analyses of MTHFR-C667T and - A1298C homozygous and heterozygous polymorphisms in 93 consecutive elderly patients revealed high prevalence of MTHFR mutations (92.5%). Findings require confirmation in a larger series, but MTHFR mutations may become a LOAD marker, opening novel possibilities for prevention and treatment.

  8. Expression of p63 and Bcl-2 in Malignant Thyroid Tumors and their Correlation with other Diagnostic Immunocytochemical Markers

    PubMed Central

    Jain, Shyama; Khurana, Nita; Kakar, Arun Kumar

    2016-01-01

    Introduction Bcl-2 is a marker recently studied in thyroid tumours and proposed to have prognostic significance. p63 is expressed in a proportion of papillary thyroid carcinoma cases and may have a role in tumour progression. Aim To study expression of Bcl2 and p63 in thyroid tumours and correlation of Bcl-2 with diagnostic markers including Thyroglobulin, Calcitonin and Carcinoembryonic antigen. Materials and Methods Cytology smears of 35 cases of thyroid cancer were studied over a period of 18 months. In 20 cases histopathology was available. Immunocytochemistry for Bcl-2 and p63 was done, and diagnostic markers were applied as and when required. Results p63 showed focal nuclear expression in 46.1% of papillary thyroid carcinoma cases, and was negative in all other tumours. Bcl-2 was positive in 88.9% of follicular carcinomas, 100% of papillary carcinomas and 83.3% of medullary carcinoma cases, and showed focal weak expression in 40% of Anaplastic Carcinoma (ATC) cases, thereby signifying down regulation (p-value = 0.001). There was significant down regulation of Thyroglobulin (Tg) in ATC vs well differentiated follicular derived tumours (p-value ≤ 0.016). Positive correlation was noted between expression of Bcl-2 and Calcitonin (0.93) and Bcl-2 and Carcinoembryonic Antigen (CEA) (0.89), and weak positive correlation (0.65) between Tg and Bcl-2. Conclusion Bcl-2 is downregulated in anaplastic carcinomas as compared to well differentiated thyroid tumours, and shows correlation with differentiation associated tumour antigens. Thus, loss of Bcl-2 was associated with loss of differentiation in thyroid tumours. Anaplastic carcinoma as such is associated with worse prognosis and loss of Bcl-2 may be partly responsible for the same. p63 is specific but less sensitive marker for PTC. Further studies are required to determine the role of Bcl-2 and p63 in thyroid tumours. PMID:27630849

  9. CD44v6-competent tumor exosomes promote motility, invasion and cancer-initiating cell marker expression in pancreatic and colorectal cancer cells

    PubMed Central

    Wang, Zhe; von Au, Anja; Schnölzer, Martina; Hackert, Thilo; Zöller, Margot

    2016-01-01

    Cancer-initiating cells (CIC) account for metastatic spread, which may rely mostly on CIC exosomes (TEX) that affect host cells and can transfer CIC features into Non-CIC. The CIC marker CD44 variant isoform v6 (CD44v6) being known for metastasis-promotion, we elaborated in cells its contribution to migration and invasion and in TEX the tranfer of migratory and invasive capacity to Non-CIC, using a CD44v6 knockdown (CD44v6kd) as Non-CIC model. A CD44v6kd in human pancreatic and colorectal cancer (PaCa, CoCa) lines led to loss of CIC characteristics including downregulation of additional CIC markers, particularly Tspan8. This aggravated the loss of CD44v6-promoted motility and invasion. Loss of motility relies on the distorted cooperation of CD44v6 and Tspan8 with associated integrins and loss of invasiveness on reduced protease expression. These deficits, transferred into TEX, severely altered the CD44v6kd-TEX composition. As a consequence, unlike the CIC-TEX, CD44v6kd TEX were not taken up by CD44v6kd cells and CIC. The uptake of CIC-TEX was accompanied by partial correction of CIC marker and protease expression in CD44v6kd cells, which regained migratory, invasive and metastatic competence. CIC-TEX also fostered angiogenesis and expansion of myeloid cells, likely due to a direct impact of CIC-TEX on the host, which could be supported by reprogrammed CD44v6kd cells. Taken together, the striking loss of tumor progression by a CD44v6kd relies on the capacity of CD44v6 to cooperate with associating integrins and proteases and its promotion of additional CIC marker expression. The defects by a CD44v6kd are efficiently corrected upon CIC-TEX uptake. PMID:27419629

  10. CD44v6-competent tumor exosomes promote motility, invasion and cancer-initiating cell marker expression in pancreatic and colorectal cancer cells.

    PubMed

    Wang, Zhe; von Au, Anja; Schnölzer, Martina; Hackert, Thilo; Zöller, Margot

    2016-08-23

    Cancer-initiating cells (CIC) account for metastatic spread, which may rely mostly on CIC exosomes (TEX) that affect host cells and can transfer CIC features into Non-CIC. The CIC marker CD44 variant isoform v6 (CD44v6) being known for metastasis-promotion, we elaborated in cells its contribution to migration and invasion and in TEX the tranfer of migratory and invasive capacity to Non-CIC, using a CD44v6 knockdown (CD44v6kd) as Non-CIC model.A CD44v6kd in human pancreatic and colorectal cancer (PaCa, CoCa) lines led to loss of CIC characteristics including downregulation of additional CIC markers, particularly Tspan8. This aggravated the loss of CD44v6-promoted motility and invasion. Loss of motility relies on the distorted cooperation of CD44v6 and Tspan8 with associated integrins and loss of invasiveness on reduced protease expression. These deficits, transferred into TEX, severely altered the CD44v6kd-TEX composition. As a consequence, unlike the CIC-TEX, CD44v6kd TEX were not taken up by CD44v6kd cells and CIC. The uptake of CIC-TEX was accompanied by partial correction of CIC marker and protease expression in CD44v6kd cells, which regained migratory, invasive and metastatic competence. CIC-TEX also fostered angiogenesis and expansion of myeloid cells, likely due to a direct impact of CIC-TEX on the host, which could be supported by reprogrammed CD44v6kd cells.Taken together, the striking loss of tumor progression by a CD44v6kd relies on the capacity of CD44v6 to cooperate with associating integrins and proteases and its promotion of additional CIC marker expression. The defects by a CD44v6kd are efficiently corrected upon CIC-TEX uptake.

  11. Assessment of four molecular markers as potential DNA barcodes for red algae Kappaphycus Doty and Eucheuma J. Agardh (Solieriaceae, Rhodophyta).

    PubMed

    Tan, Ji; Lim, Phaik-Eem; Phang, Siew-Moi; Hong, Dang Diem; Sunarpi, H; Hurtado, Anicia Q

    2012-01-01

    DNA barcoding has been a major advancement in the field of taxonomy, seeing much effort put into the barcoding of wide taxa of organisms, macro and microalgae included. The mitochondrial-encoded cox1 and plastid-encoded rbcL has been proposed as potential DNA barcodes for rhodophytes, but are yet to be tested on the commercially important carrageenophytes Kappaphycus and Eucheuma. This study gauges the effectiveness of four markers, namely the mitochondrial cox1, cox2, cox2-3 spacer and the plastid rbcL in DNA barcoding on selected Kappaphycus and Eucheuma from Southeast Asia. Marker assessments were performed using established distance and tree-based identification criteria from earlier studies. Barcoding patterns on a larger scale were simulated by empirically testing on the commonly used cox2-3 spacer. The phylogeny of these rhodophytes was also briefly described. In this study, the cox2 marker which satisfies the prerequisites of DNA barcodes was found to exhibit moderately high interspecific divergences with no intraspecific variations, thus a promising marker for the DNA barcoding of Kappaphycus and Eucheuma. However, the already extensively used cox2-3 spacer was deemed to be in overall more appropriate as a DNA barcode for these two genera. On a wider scale, cox1 and rbcL were still better DNA barcodes across the rhodophyte taxa when practicality and cost-efficiency were taken into account. The phylogeny of Kappaphycus and Eucheuma were generally similar to those earlier reported. Still, the application of DNA barcoding has demonstrated our relatively poor taxonomic comprehension of these seaweeds, thus suggesting more in-depth efforts in taxonomic restructuring as well as establishment.

  12. Assessment of Four Molecular Markers as Potential DNA Barcodes for Red Algae Kappaphycus Doty and Eucheuma J. Agardh (Solieriaceae, Rhodophyta)

    PubMed Central

    Tan, Ji; Lim, Phaik-Eem; Phang, Siew-Moi; Hong, Dang Diem; Sunarpi, H.; Hurtado, Anicia Q.

    2012-01-01

    DNA barcoding has been a major advancement in the field of taxonomy, seeing much effort put into the barcoding of wide taxa of organisms, macro and microalgae included. The mitochondrial-encoded cox1 and plastid-encoded rbcL has been proposed as potential DNA barcodes for rhodophytes, but are yet to be tested on the commercially important carrageenophytes Kappaphycus and Eucheuma. This study gauges the effectiveness of four markers, namely the mitochondrial cox1, cox2, cox2-3 spacer and the plastid rbcL in DNA barcoding on selected Kappaphycus and Eucheuma from Southeast Asia. Marker assessments were performed using established distance and tree-based identification criteria from earlier studies. Barcoding patterns on a larger scale were simulated by empirically testing on the commonly used cox2-3 spacer. The phylogeny of these rhodophytes was also briefly described. In this study, the cox2 marker which satisfies the prerequisites of DNA barcodes was found to exhibit moderately high interspecific divergences with no intraspecific variations, thus a promising marker for the DNA barcoding of Kappaphycus and Eucheuma. However, the already extensively used cox2-3 spacer was deemed to be in overall more appropriate as a DNA barcode for these two genera. On a wider scale, cox1 and rbcL were still better DNA barcodes across the rhodophyte taxa when practicality and cost-efficiency were taken into account. The phylogeny of Kappaphycus and Eucheuma were generally similar to those earlier reported. Still, the application of DNA barcoding has demonstrated our relatively poor taxonomic comprehension of these seaweeds, thus suggesting more in-depth efforts in taxonomic restructuring as well as establishment. PMID:23285223

  13. Label-free visualization of collagen in submucosa as a potential diagnostic marker for early detection of colorectal cancer

    NASA Astrophysics Data System (ADS)

    Qiu, Jingting; Yang, Yinghong; Jiang, Weizhong; Feng, Changyin; Chen, Zhifen; Guan, Guoxian; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Jianxin

    2014-09-01

    The collagen signature in colorectal submucosa is changed due to remodeling of the extracellular matrix during the malignant process and plays an important role in noninvasive early detection of human colorectal cancer. In this work, multiphoton microscopy (MPM) was used to monitor the changes of collagen in normal colorectal submucosa (NCS) and cancerous colorectal submucosa (CCS). What's more, the collagen content was quantitatively measured. It was found that in CCS the morphology of collagen becomes much looser and the collagen content is significantly reduced compared to NCS. These results suggest that MPM has the ability to provide collagen signature as a potential diagnostic marker for early detection of colorectal cancer.

  14. Evaluation of potential internal target volume of liver tumors using cine-MRI

    SciTech Connect

    Akino, Yuichi; Oh, Ryoong-Jin; Masai, Norihisa; Shiomi, Hiroya; Inoue, Toshihiko

    2014-11-01

    Purpose: Four-dimensional computed tomography (4DCT) is widely used for evaluating moving tumors, including lung and liver cancers. For patients with unstable respiration, however, the 4DCT may not visualize tumor motion properly. High-speed magnetic resonance imaging (MRI) sequences (cine-MRI) permit direct visualization of respiratory motion of liver tumors without considering radiation dose exposure to patients. Here, the authors demonstrated a technique for evaluating internal target volume (ITV) with consideration of respiratory variation using cine-MRI. Methods: The authors retrospectively evaluated six patients who received stereotactic body radiotherapy (SBRT) to hepatocellular carcinoma. Before acquiring planning CT, sagittal and coronal cine-MRI images were acquired for 30 s with a frame rate of 2 frames/s. The patient immobilization was conducted under the same condition as SBRT. Planning CT images were then acquired within 15 min from cine-MRI image acquisitions, followed by a 4DCT scan. To calculate tumor motion, the motion vectors between two continuous frames of cine-MRI images were calculated for each frame using the pyramidal Lucas–Kanade method. The target contour was delineated on one frame, and each vertex of the contour was shifted and copied onto the following frame using neighboring motion vectors. 3D trajectory data were generated with the centroid of the contours on sagittal and coronal images. To evaluate the accuracy of the tracking method, the motion of clearly visible blood vessel was analyzed with the motion tracking and manual detection techniques. The target volume delineated on the 50% (end-exhale) phase of 4DCT was translated with the trajectory data, and the distribution of the occupancy probability of target volume was calculated as potential ITV (ITV {sub Potential}). The concordance between ITV {sub Potential} and ITV estimated with 4DCT (ITV {sub 4DCT}) was evaluated using the Dice’s similarity coefficient (DSC). Results

  15. Down-regulation of microRNA-181b is a potential prognostic marker of non-small cell lung cancer.

    PubMed

    Yang, Junquan; Liu, Hongxia; Wang, Hongbin; Sun, Yuman

    2013-08-01

    The aim of this study was to investigate the clinical significance of microRNA-181b (miR-181b) expression in non-small cell lung cancer (NSCLC). MiR-181b expression in 126 pairs of surgically removed NSCLC tissues and their corresponding normal lung tissues was measured by real-time quantitative RT-PCR assay. Additionally, the correlation of miR-181b expression with clinicopathological factors or prognosis of patients was analyzed. At first, miR-181b expression was significantly down-regulated in NSCLC tissues as compared with their normal counterparts (P<0.001). Then, the low miR-181b expression was found to be closely correlated with larger tumor size (P=0.02), higher p-TNM stage (P=0.008) and positive lymph node metastasis (P=0.03) of NSCLC patients. After that, survival analysis found that the overall survival (P=0.001) and disease-free survival (P=0.008) of NSCLC patients with low miR-181b expression were both significantly poorer compared to those patients with high miR-181b expression. Finally, both univariate and multivariate analyses demonstrated that low miR-181b expression may be a poor prognostic marker of NSCLC patients. This is the first study to indicate that down-regulation of miR-181b may be correlated with aggressive disease progression and poor prognosis of NSCLC patients, suggesting that miR-181b might be involved in lung carcinogenesis and become a potential prognostic marker for NSCLC.

  16. MicroRNA-196a Is a Potential Marker of Progression during Barrett’s Metaplasia-Dysplasia-Invasive Adenocarcinoma Sequence in Esophagus

    PubMed Central

    Maru, Dipen M.; Singh, Rajesh R.; Hannah, Christina; Albarracin, Constance T.; Li, Yong X.; Abraham, Ronald; Romans, Angela M.; Yao, Hui; Luthra, Madan G.; Anandasabapathy, Sharmila; Swisher, Stephen G.; Hofstetter, Wayne L.; Rashid, Asif; Luthra, Rajyalakshmi

    2009-01-01

    Barrett’s esophagus (BE)/Barrett’s metaplasia (BM) is a recognized precursor of esophageal adenocarcinoma (EA) with an intermediary stage of dysplasia. The low yield and high cost of endoscopic screening of patients with BE underscores the need for novel biomarkers, such as microRNA (miRNA), which have emerged as important players in neoplastic progression for risk assessment of developing dysplasia/adenocarcinoma. Recently, we reported highly elevated levels of miRNA-196a (miR-196a) in EA and demonstrated its growth-promoting and anti-apoptotic functions. Here, we evaluated miR-196a as a marker of BE progression to low-grade dysplasia, high-grade dysplasia, and EA using microdissected paraffin-embedded tissues from 11 patients. Higher levels of miR-196a were observed in EA, BE, and dysplastic lesions compared with normal squamous mucosa, and in high-grade dysplasia compared with BE and low-grade dysplasia. Using frozen tumor tissues from 10 additional patients who had advanced EA, we evaluated the correlation of miR-196a with its in silico-predicted targets, keratin 5 (KRT5), small proline-rich protein 2C (SPRR2C), and S100 calcium-binding protein A9 (S100A9), which are down-regulated during BE progression. MiR-196a levels inversely correlated with the predicted target mRNA levels in EA. We confirmed that miR-196a specifically targets KRT5, SPRR2C, and S100A9 3′ UTRs using miR-196a-mimic and luciferase reporter-based assays. In conclusion, this study identified miR-196a as a potential marker of progression of BE and KRT5, SPRR2C, and S100A9 as its targets. PMID:19342367

  17. The ZNF217 Breast Cancer Oncogene Amplified at 20q13: A Potential Marker for Invasiveness

    DTIC Science & Technology

    2012-03-01

    downstream ZNF217 effector genes and cell signaling pathways driving the ZNF217-induced morphology ZNF217, invasive cancer, 20q13 amplification 16...Status  of  the  ZNF217  biomarker would  then  be  used  for  tumor  prognosis  and meaningful  stratification to determine patient  therapy  for...and localization.  Genes  Dev 2011; 25: 471‐84.  5. Xiang B, Muthuswamy SK. Using three‐dimensional acinar structures for molecular and cell biological

  18. ALDH1A Isozymes Are Markers of Human Melanoma Stem Cells and Potential Therapeutic Targets

    PubMed Central

    Luo, Yuchun; Dallaglio, Katiuscia; Chen, Ying; Robinson, William A; Robinson, Steven E; McCarter, Martin D; Wang, Jianbin; Gonzalez, Rene; Thompson, David C; Norris, David A; Roop, Dennis R; Vasiliou, Vasilis; Fujita, Mayumi

    2012-01-01

    Although the concept of cancer stem cells (CSCs) is well accepted for many tumors, the existence of such cells in human melanoma has been the subject of debate. In the present study, we demonstrate the existence of human melanoma cells that fulfill the criteria for CSCs (self-renewal and differentiation) by serially xenotransplanting cells into NOD/SCID mice. These cells possess high aldehyde dehydrogenase (ALDH) activity with ALDH1A1 and ALDH1A3 being the predominant ALDH isozymes. ALDH-positive melanoma cells are more tumorigenic than ALDH-negative cells in both NOD/SCID mice and NSG mice. Biological analyses of the ALDH-positive melanoma cells reveal the ALDH isozymes to be key molecules regulating the function of these cells. Silencing ALDH1A by siRNA or shRNA leads to cell cycle arrest, apoptosis and decreased cell viability in vitro and reduced tumorigenesis in vivo. ALDH-positive melanoma cells are more resistant to chemotherapeutic agents and silencing ALDH1A by siRNA sensitizes melanoma cells to drug-induced cell death. Furthermore, we, for the first time, examined the molecular signatures of ALDH-positive CSCs from patient-derived tumor specimens. The signatures of melanoma CSCs include retinoic acid (RA)-driven target genes with RA response elements and genes associated with stem cell function. These findings implicate that ALDH isozymes are not only biomarkers of CSCs but also attractive therapeutic targets for human melanoma. Further investigation of these isozymes and genes will enhance our understanding of the molecular mechanisms governing CSCs and reveal new molecular targets for therapeutic intervention of cancer. PMID:22887839

  19. Cell-Free RNA Content in Peripheral Blood as Potential Biomarkers for Detecting Circulating Tumor Cells in Non-Small Cell Lung Carcinoma

    PubMed Central

    Yu, Xin-Min; Wu, Yi-Chen; Liu, Xiang; Huang, Xian-Cong; Hou, Xiu-Xiu; Wang, Jiu-Li; Cheng, Xiang-Liu; Mao, Wei-Min; Ling, Zhi-Qiang

    2016-01-01

    Circulating tumor cells (CTCs) have been implicated in tumor progression and prognosis. Techniques detecting CTCs in the peripheral blood of patients with non-small cell lung carcinoma (NSCLC) may help to identify individuals likely to benefit from early systemic treatment. However, the detection of CTCs with a single marker is challenging, owing to low specificity and sensitivity and due to the heterogeneity and rareness of CTCs. Herein, the probability of cell-free RNA content in the peripheral blood as a potential biomarker for detecting CTCs in cancer patients was investigated. An immunomagnetic enrichment of real-time reverse-transcription PCR (RT-PCR) technology for analysis of CTCs in NSCLC patients was also developed. The mRNA levels of four candidate genes, cytokeratin 7 (CK7), E74-like factor 3 (ELF3), epidermal growth factor receptor (EGFR), and erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) that were significantly elevated in tumor tissues and peripheral blood mononuclear cells (PBMCs) were determined. The expression of CK7 and ELF3 in tumor tissues and EGFR in PBMCs was associated with lymph node metastasis (all p < 0.05). The expression of CK7 in PBMCs was correlated with age and EphB4 in PBMCs correlated with histopathological type, respectively (all p < 0.05). The expression of all four genes in tumor tissues and PBMCs was significantly correlated with the clinical stage (all p < 0.01). Survival analysis showed that the patients with enhanced expression of CK7, ELF3, EGFR, and EphB4 mRNA in PBMCs had poorer disease-free survival (DFS) and overall survival (OS) than those without (all p < 0.0001). The present study showed that this alteration of cell-free RNA content in peripheral blood might have clinical ramifications in the diagnosis and treatment of NSCLC patients. PMID:27827952

  20. The chloroplast DNA locus psbZ-trnfM as a potential barcode marker in Phoenix L. (Arecaceae).

    PubMed

    Ballardini, Marco; Mercuri, Antonio; Littardi, Claudio; Abbas, Summar; Couderc, Marie; Ludeña, Bertha; Pintaud, Jean-Christophe

    2013-12-30

    The genus Phoenix (Arecaceae) comprises 14 species distributed from Cape Verde Islands to SE Asia. It includes the economically important species Phoenix dactylifera. The paucity of differential morphological and anatomical useful characters, and interspecific hybridization, make identification of Phoenix species difficult. In this context, the development of reliable DNA markers for species and hybrid identification would be of great utility. Previous studies identified a 12 bp polymorphic chloroplast minisatellite in the trnG (GCC)-trnfM (CAU) spacer, and showed its potential for species identification in Phoenix. In this work, in order to develop an efficient DNA barcode marker for Phoenix, a longer cpDNA region (700 bp) comprising the mentioned minisatellite, and located between the psbZ and trnfM (CAU) genes, was sequenced. One hundred and thirty-six individuals, representing all Phoenix species except P. andamanensis,were analysed. The minisatellite showed 2-7 repetitions of the 12 bp motif, with 1-3 out of seven haplotypes per species. Phoenix reclinata and P. canariensis had species-specific haplotypes. Additional polymorphisms were found in the flanking regions of the minisatellite, including substitutions, indels and homopolymers. All this information allowed us to identify unambiguously eight out of the 13 species, and overall 80% of the individuals sampled. Phoenix rupicola and P. theophrasti had the same haplotype, and so had P. atlantica, P. dactylifera, and P. sylvestris (the "date palm complex" sensu Pintaud et al. 2013). For these species, additional molecular markers will be required for their unambiguous identification. The psbZ-trnfM (CAU) region therefore could be considered as a good basis for the establishment of a DNA barcoding system in Phoenix, and is potentially useful for the identification of the female parent in Phoenix hybrids.

  1. Personality traits as potential susceptibility markers: differential susceptibility to support among parents.

    PubMed

    Slagt, Meike; Dubas, Judith Semon; Denissen, Jaap J A; Deković, Maja; van Aken, Marcel A G

    2015-04-01

    In this study, we examined whether parents are differentially susceptible to support from their spouse and adolescent child depending on their personality traits, and whether differences in susceptibility to support among parents, in turn, are linked to the quality of support parents give to their children. Participants in this three-wave longitudinal study were 288 two-parent Dutch families with an adolescent child. Fathers were on average 43.9 years old (SD = 3.7 years), mothers were 41.7 years old (SD = 3.3 years), and adolescents (50% girls) were 14.5 years old (SD = 0.8 years). We found that the association between support from children toward their parents and subsequent support from parents toward their children was more pronounced for parents high on Openness, for better and for worse. Extraversion, Agreeableness, Conscientiousness, and Emotional Stability did not emerge as markers of differences in susceptibility. Also, parents did not differ in their susceptibility to support from their spouse, nor were differences in susceptibility found a year later when using data from a third wave. We found very modest support for differential susceptibility, only for Openness, and depending on the source of perceived support and on the timing of measurement.

  2. MicroRNA-155 is a potential molecular marker of natural killer/T-cell lymphoma

    PubMed Central

    Huang, Ruixia; Li, Lifeng; Wang, Xinhua; Li, Ling; Fu, Xiaorui; Sun, Zhenchang; Li, Zhaoming; Chen, Qingjiang; Zhang, Mingzhi

    2016-01-01

    Natural killer/T-cell lymphoma (NKTCL) is characterized by its highly aggressive nature and rapid progression. MicroRNAs (miRNAs) play key roles in the development of NKTCL. We utilized next-generation Solexa high-throughput sequencing to compare miRNA expression in the SNK-6 and YTS NKTCL cell lines with expression in normal NK cells. We found that 195 miRNAs were upregulated in the SNK-6 cells and 286 miRNAs were upregulated in the YTS cells. Based on those results, we selected six miRNAs, including miRNA-155, and confirmed their expression using real-time polymerase chain reaction. Expression of miRNA-155 was higher in SNK-6 and YKS cells than in normal NK cells. We next determined the levels of miRNA-155 in the serum of healthy individuals and NKTCL patients, and correlated its expression with clinical parameters and inflammatory factors detected using enzyme-linked immunoabsorbent assays. Levels of miRNA-155 were higher in NKTCL patients’ serum than in serum from healthy individuals. miRNA-155 expression was higher in patients with stable or progressive disease (SD+PD) than in those with partial or complete remission (PR+CR). While further studies are needed to clarify the underlying molecular mechanisms, it appears miRNA-155 may be a molecular marker of NKTCL. PMID:27462776

  3. Basal cytokeratin as a potential marker of low risk of invasion in ductal carcinoma in situ

    PubMed Central

    Aguiar, Fernando N.; Mendes, Henrique N.; Cirqueira, Cinthya S.; Bacchi, Carlos E.; Carvalho, Filomena M.

    2013-01-01

    OBJECTIVES: Biological markers that predict the development of invasive breast cancer are needed to improve personalized therapy for patients diagnosed with ductal carcinoma in situ. We investigated the role of basal cytokeratin 5/6 in the risk of invasion in breast ductal carcinoma in situ. METHODS: We constructed tissue microarrays using 236 ductal carcinoma in situ samples: 90 pure samples (group 1) and 146 samples associated with invasive carcinoma (group 2). Both groups had similar nuclear grades and were obtained from patients of similar ages. The groups were compared in terms of estrogen (ER) and progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) expression, cytokeratin 5/6 immunostaining, human epidermal growth factor receptor 1 (EGFR) membrane staining and molecular subtype, as indicated by their immunohistochemistry profiles. RESULTS: ER/PR-negative status was predictive of invasion, whereas HER2 superexpression and cytokeratin 5/6-positive status were negatively associated with invasion. Among the high-grade ductal carcinoma in situ cases, a triple-positive profile (positive for estrogen receptor, progesterone receptor, and HER2) and cytokeratin 5/6 expression by neoplastic cells were negatively associated with invasion. In the low-grade ductal carcinoma in situ subgroup, only cytokeratin 5/6 expression exhibited a negative association with the probability of invasion. CONCLUSION: The immunohistochemical expression of cytokeratin 5/6 by ductal carcinoma in situ epithelial cells may prov