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Sample records for blood tumour marker

  1. Fc receptor-bearing peripheral blood mononuclear cells in breast cancer patients: a possible marker of tumour burden and prognosis.

    PubMed Central

    Bray, J; McPherson, T A

    1981-01-01

    Indirect immunofluorescence was used to identify and quantitate peripheral blood mononuclear (PBM) cells possessing high avidity Fc receptors in 105 patients upon referral to the breast cancer clinic at the Cross Cancer Institute. The cell detected was shown to be a non-adherent PBM, probably belonging to the T or null cell population. The mean percentage +/- 2 standard deviations of PBM-positive cells in 75 patients with no disease or benign breast disease was 5.3 +/- ;6.7, and this was significantly (P less than 0.001) less than the percentage found for 31 patients with breast cancer. The percentage of PBM-positive cells correlated directly with tumour burden in patient with small (less than or equal to 5 cm) tumours without regional node or extranodal metastases (5/13 had greater than or equal to 12% positive PBM) and in those with small tumours plus regional node metastases, but without extranodal metastases (8/10 had greater than or equal to 12% positive PBM). This correlation was less, however, in patients with large tumours (greater than 5 cm), and in those with extranodal metastases (4/8 had greater than or equal to 12% positive PBM), and in patients tested postoperatively (1/13 had greater than or equal to 12% positive PBM) even though 6!13 had regional node metastases at the time of surgery. Thus, this relatively simple assay, which can be done on peripheral blood samples, may turn out to be useful in patients with breast cancer as a prognostic marker insofar as it may be an indirect indicator of tumour burden preoperatively. If so, it may lead to a more aggressive postoperative adjuvant therapy approach to the subpopulation of node-negative PBM-positive breast cancer patients than is currently used for node-negative patients. PMID:7035033

  2. Tumour Markers and Kidney Function: A Systematic Review

    PubMed Central

    Rivoli, Laura; Mazza, Giuseppe; Presta, Piera

    2014-01-01

    Tumour markers represent useful tools in diagnosis and clinical management of patients with cancer, because they are easy to use, minimally invasive, and easily measured in either blood or urine. Unfortunately, such an ideal marker, as yet, does not exist. Different pathological states may increase the level of a tumour marker in the absence of any neoplasia. Alternatively, low levels of tumour markers could be also found in the presence of neoplasias. We aimed at reviewing studies currently available in the literature examining the association between tumour markers and different renal impairment conditions. Each tumour marker was found to be differently influenced by these criteria; additionally we revealed in many cases a lack of available published data. PMID:24689048

  3. Tumour marker detection in oesophageal carcinoma.

    PubMed

    Mealy, K; Feely, J; Reid, I; McSweeney, J; Walsh, T; Hennessy, T P

    1996-10-01

    Levels of the tumour markers CEA, CA 19-9, CA 125 and SCC were measured in 58 patients presenting with oesophageal carcinoma and compared with levels in patients with benign oesophageal disease and levels in normal volunteers. CEA and CA 19-9 were significantly increased in the patients with oesophageal cancer, however, individual sensitivity for CEA, CA 19-9, CA 125 and SCC was only 28, 34, 10, and 32%, respectively. The combined sensitivity of all markers was 64% and specificity was 80%. There was no difference in combined tumour marker sensitivity between squamous or adenocarcinomas of the oesophagus. No consistent change in marker levels occurred with treatment, and tumour marker levels could not be significantly correlated with stage of disease or short-term survival. These results indicate that tumour marker sensitivity is too low for oesophageal cancer screening and has poor prognostic significance in those undergoing treatment.

  4. Glycosyltransferases as marker genes for the quantitative polymerase chain reaction-based detection of circulating tumour cells from blood samples of patients with breast cancer undergoing adjuvant therapy.

    PubMed

    Kölbl, Alexandra C; Hiller, Roman A; Ilmer, Mathias; Liesche, Friederike; Heublein, Sabine; Schröder, Lennard; Hutter, Stefan; Friese, Klaus; Jeschke, Udo; Andergassen, Ulrich

    2015-08-01

    Altered glycosylation is a predominant feature of tumour cells; it serves for cell adhesion and detachment, respectively, and facilitates the immune escape of these cells. Therefore changes in the expression of glycosyltransferase genes could help to identify circulating tumour cells (CTCs) in the blood samples of cancer patients using a quantitative polymerase chain reaction (PCR) approach. Blood samples of healthy donors were inoculated with certain numbers of established breast cancer cell line cells, thus creating a model system. These samples were analysed by quantitative PCR for the expression of six different glycosyltransferase genes. The three genes with the best results in the model system were consecutively applied to samples from adjuvant breast cancer patients and of healthy donors. FUT3 and GALNT6 showed the highest increase in relative expression, while GALNT6 and ST3GAL3 were the first to reach statistically significant different ∆CT-values comparing the sample with and without addition of tumour cells. These three genes were applied to patient samples, but did not show any significant results that may suggest the presence of CTCs in the blood. Although the relative expression of some of the glycosyltransferase genes exhibited reasonable results in the model system, their application to breast cancer patient samples will have to be further improved, e.g. by co-analysis of patient blood samples by gold-standard methods.

  5. Multiple RT-PCR markers for the detection of circulating tumour cells of metastatic canine mammary tumours.

    PubMed

    da Costa, A; Kohn, B; Gruber, A D; Klopfleisch, R

    2013-04-01

    In humans, detection of circulating tumour cells (CTCs) using nucleic acid-based methods such as reverse transcription polymerase chain reaction (RT-PCR) has proven to be of prognostic relevance. However, similar procedures are still lacking in veterinary oncology. To assess the correlation of CTC markers with the metastatic potential of canine mammary tumours, 120 peripheral blood samples from bitches with mammary carcinomas with (group 1) and without (group 2) histological evidence of vascular invasion and/or presence of lymph node metastases and mammary adenomas (group 3) were analyzed. Blood samples were collected in EDTA tubes and RNA was extracted within 48 h. Subsequently, the samples were tested by RT-PCR for a panel of seven CTC mRNA markers. CRYAB was the most sensitive single marker with a sensitivity of 35% and also the most specific marker with a specificity of 100% to detect group 1 blood samples. A multimarker assay combining four genes enhanced the sensitivity up to 77.5%, but decreased the specificity to 80%. CRYAB appeared to be highly specific but only moderately sensitive at detecting blood samples from dogs with metastatic tumours and detection significantly correlated with vascular invasion of primary mammary tumours. However, a multimarker assay of four genes significantly enhanced the sensitivity of the assay and is therefore preferable for CTC detection. PMID:23036177

  6. Activation of blood coagulation in cancer: implications for tumour progression.

    PubMed

    Lima, Luize G; Monteiro, Robson Q

    2013-09-04

    Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies.

  7. Activation of blood coagulation in cancer: implications for tumour progression

    PubMed Central

    Lima, Luize G.; Monteiro, Robson Q.

    2013-01-01

    Several studies have suggested a role for blood coagulation proteins in tumour progression. Herein, we discuss (1) the activation of the blood clotting cascade in the tumour microenvironment and its impact on primary tumour growth; (2) the intravascular activation of blood coagulation and its impact on tumour metastasis and cancer-associated thrombosis; and (3) antitumour therapies that target blood-coagulation-associated proteins. Expression levels of the clotting initiator protein TF (tissue factor) have been correlated with tumour cell aggressiveness. Simultaneous TF expression and PS (phosphatidylserine) exposure by tumour cells promote the extravascular activation of blood coagulation. The generation of blood coagulation enzymes in the tumour microenvironment may trigger the activation of PARs (protease-activated receptors). In particular, PAR1 and PAR2 have been associated with many aspects of tumour biology. The procoagulant activity of circulating tumour cells favours metastasis, whereas the release of TF-bearing MVs (microvesicles) into the circulation has been correlated with cancer-associated thrombosis. Given the role of coagulation proteins in tumour progression, it has been proposed that they could be targets for the development of new antitumour therapies. PMID:23889169

  8. Nanoparticle-blood interactions: the implications on solid tumour targeting.

    PubMed

    Lazarovits, James; Chen, Yih Yang; Sykes, Edward A; Chan, Warren C W

    2015-02-18

    Nanoparticles are suitable platforms for cancer targeting and diagnostic applications. Typically, less than 10% of all systemically administered nanoparticles accumulate in the tumour. Here we explore the interactions of blood components with nanoparticles and describe how these interactions influence solid tumour targeting. In the blood, serum proteins adsorb onto nanoparticles to form a protein corona in a manner dependent on nanoparticle physicochemical properties. These serum proteins can block nanoparticle tumour targeting ligands from binding to tumour cell receptors. Additionally, serum proteins can also encourage nanoparticle uptake by macrophages, which decreases nanoparticle availability in the blood and limits tumour accumulation. The formation of this protein corona will also increase the nanoparticle hydrodynamic size or induce aggregation, which makes nanoparticles too large to enter into the tumour through pores of the leaky vessels, and prevents their deep penetration into tumours for cell targeting. Recent studies have focused on developing new chemical strategies to reduce or eliminate serum protein adsorption, and rescue the targeting potential of nanoparticles to tumour cells. An in-depth and complete understanding of nanoparticle-blood interactions is key to designing nanoparticles with optimal physicochemical properties with high tumour accumulation. The purpose of this review article is to describe how the protein corona alters the targeting of nanoparticles to solid tumours and explains current solutions to solve this problem.

  9. Towards fluoroscopic respiratory gating for lung tumours without radiopaque markers

    NASA Astrophysics Data System (ADS)

    Berbeco, Ross I.; Mostafavi, Hassan; Sharp, Gregory C.; Jiang, Steve B.

    2005-10-01

    Due to the risk of pneumothorax, many clinicians are reluctant to implant radiopaque markers within patients' lungs for the purpose of radiographic or fluoroscopic tumour localization. We propose a method of gated therapy using fluoroscopic information without the implantation of radiopaque markers. The method presented here does not rely on any external motion signal either. Breathing phase information is found by analysing the fluoroscopic intensity fluctuations in the lung. As the lungs fill/empty, the radiological pathlength through them shortens/lengthens, giving brighter/darker fluoroscopic intensities. The phase information is combined with motion-enhanced template matching to turn the beam on when the tumour is in the desired location. A study based on patient data is presented to demonstrate the feasibility of this procedure. The resulting beam-on pattern is similar to that produced by an external gating system. The only discrepancies occur briefly and at the gate edges.

  10. Suppression of tumour growth by orally administered osteopontin is accompanied by alterations in tumour blood vessels

    PubMed Central

    Rittling, S R; Wejse, P L; Yagiz, K; Warot, G A; Hui, T

    2014-01-01

    Background: The integrin-binding protein osteopontin is strongly associated with tumour development, yet is an abundant dietary component as a constituent of human and bovine milk. Therefore, we tested the effect of orally administered osteopontin (o-OPN) on the development of subcutaneous tumours in mice. Methods: Bovine milk osteopontin was administered in drinking water to tumour-bearing immune-competent mice. Tumour growth, proliferation, necrosis, apoptosis and blood vessel size and number were measured. Expression of the α9 integrin was determined. Results: o-OPN suppressed tumour growth, increased the extent of necrosis, and induced formation of abnormally large blood vessels. Anti-OPN reactivity detected in the plasma of OPN-null mice fed OPN suggested that tumour-blocking peptides were absorbed during digestion, but the o-OPN effect was likely distinct from that of an RGD peptide. Expression of the α9 integrin was detected on both tumour cells and blood vessels. Potential active peptides from the α9 binding site of OPN were identified by mass spectrometry following in vitro digestion, and injection of these peptides suppressed tumour growth. Conclusions: These results suggest that peptides derived from o-OPN are absorbed and interfere with tumour growth and normal vessel development. o-OPN-derived peptides that target the α9 integrin are likely involved. PMID:24473400

  11. Treatment precision of image-guided liver SBRT using implanted fiducial markers depends on marker-tumour distance

    NASA Astrophysics Data System (ADS)

    Seppenwoolde, Y.; Wunderink, W.; Wunderink-van Veen, S. R.; Storchi, P.; Méndez Romero, A.; Heijmen, B. J. M.

    2011-09-01

    The purpose of this study is to assess the accuracy of day-to-day predictions of liver tumour position using implanted gold markers as surrogates and to compare the method with alternative set-up strategies, i.e. no correction, vertebrae and 3D diaphragm-based set-up. Twenty patients undergoing stereotactic body radiation therapy (SBRT) with abdominal compression for primary or metastatic liver cancer were analysed. We determined the day-to-day correlation between gold marker and tumour positions in contrast-enhanced CT scans acquired at treatment preparation and before each treatment session. The influence of marker-tumour distance on the accuracy of prediction was estimated by introducing a method extension of the set-up error paradigm. The distance between gold markers and the centre of the tumour varied between 5 and 96 mm. Marker-guidance was superior to guiding treatment using other surrogates, although both the random and systematic components of the prediction error SD depended on the tumour-marker distance. For a marker-tumour distance of 4 cm, we observed σ = 1.3 mm and Σ = 1.6 mm. The 3D position of the diaphragm dome was the second best predictor. In conclusion, the tumour position can be predicted accurately using implanted markers, but marker-guided set-up accuracy decreases with increasing distance between implanted markers and the tumour.

  12. Human endodermal sinus tumour in nude mice and its markers for diagnosis and management.

    PubMed Central

    Takeuchi, T; Nakayasu, M; Hirohashi, S; Kameya, T; Kaneko, M; Yokomori, K; Tsuchida, Y

    1979-01-01

    Two human endodermal sinus tumours (yolk sac tumours) were transplanted successfully into nude mice. The transplanted tumours maintained not only morphological characters, such as Schiller-Duval bodies, but also the ability to synthesise alpha-fetoprotein, lactic dehydrogenase 1, liver and bone type alkaline phosphatase, and some human serum proteins. Since these tumours produced lactic dehydrogenase 1 but not the other four isozymes of lactic dehydrogenase, this isozyme, like alpha-fetoprotein, seems to be a good marker for the diagnosis and management of cases of endodermal sinus tumour. One of the two tumours produced another fetal antigen or carcinoembryonic antigen in addition to alpha-fetoprotein. These two endodermal sinus tumours, with their various markers in nude mice, will be useful in studies on diagnostic markers. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:91627

  13. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

    PubMed Central

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-01-01

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

  14. Microfluidic impedance cytometry of tumour cells in blood.

    PubMed

    Spencer, Daniel; Hollis, Veronica; Morgan, Hywel

    2014-11-01

    The dielectric properties of tumour cells are known to differ from normal blood cells, and this difference can be exploited for label-free separation of cells. Conventional measurement techniques are slow and cannot identify rare circulating tumour cells (CTCs) in a realistic timeframe. We use high throughput single cell microfluidic impedance cytometry to measure the dielectric properties of the MCF7 tumour cell line (representative of CTCs), both as pure populations and mixed with whole blood. The data show that the MCF7 cells have a large membrane capacitance and size, enabling clear discrimination from all other leukocytes. Impedance analysis is used to follow changes in cell viability when cells are kept in suspension, a process which can be understood from modelling time-dependent changes in the dielectric properties (predominantly membrane conductivity) of the cells. Impedance cytometry is used to enumerate low numbers of MCF7 cells spiked into whole blood. Chemical lysis is commonly used to remove the abundant erythrocytes, and it is shown that this process does not alter the MCF7 cell count or change their dielectric properties. Combining impedance cytometry with magnetic bead based antibody enrichment enables MCF7 cells to be detected down to 100 MCF7 cells in 1 ml whole blood, a log 3.5 enrichment and a mean recovery of 92%. Microfluidic impedance cytometry could be easily integrated within complex cell separation systems for identification and enumeration of specific cell types, providing a fast in-line single cell characterisation method.

  15. The influence of hydralazine on the vasculature, blood perfusion and chemosensitivity of MAC tumours.

    PubMed

    Quinn, P K; Bibby, M C; Cox, J A; Crawford, S M

    1992-08-01

    We have studied the influence of the peripheral vasodilator hydralazine (HDZ) on the vasculature and blood perfusion of two members of a series of subcutaneous murine adenocarcinomata of the colon (MAC tumours), and the influence of HDZ on the efficacy and/or toxicity of TCNU and melphalan. The fluorescent DNA stain Hoechst 33342, showed that HDZ caused a shutdown of tumour vasculature, related in magnitude to both dose and tumour differentiation state; 10 mg kg-1 caused an 80% vascular shutdown of well differentiated MAC 26 tumours, but only a 50% shutdown of the poorly differentiated MAC 15A tumours. 2.5 mg kg-1 was ineffective. The blood perfusion marker 99mTc-HMPAO showed that the normal perfusion of MAC tumours was consistently markedly less than that of lung, liver or kidneys (4-5% of lung perfusion). HDZ (10 mg kg-1) decreased MAC 26 perfusion by 63%, and that of MAC 15A by 20%. Again, 2.5 mg kg-1) was ineffective. Use of in vivo to in vitro clonogenic assays showed that HDZ (10 mg kg-1) potentiated the efficacy of melphalan (1-10 mg kg-1 i.p.) by a factor of 2.1, and increased the efficacy of TCNU (1-10 mg kg-1 i.v., factor = 1.7) when given 10 or 15 min respectively after dosing. However, the addition of HDZ increased the acute bone marrow toxicity of melphalan, but not that of TCNU. The clinical relevance of these results is discussed.

  16. Cancers Screening in an Asymptomatic Population by Using Multiple Tumour Markers

    PubMed Central

    Wang, Hsin-Yao; Hsieh, Chia-Hsun; Wen, Chiao-Ni; Wen, Ying-Hao

    2016-01-01

    Background Analytic measurement of serum tumour markers is one of commonly used methods for cancer risk management in certain areas of the world (e.g. Taiwan). Recently, cancer screening based on multiple serum tumour markers has been frequently discussed. However, the risk–benefit outcomes appear to be unfavourable for patients because of the low sensitivity and specificity. In this study, cancer screening models based on multiple serum tumour markers were designed using machine learning methods, namely support vector machine (SVM), k-nearest neighbour (KNN), and logistic regression, to improve the screening performance for multiple cancers in a large asymptomatic population. Methods AFP, CEA, CA19-9, CYFRA21-1, and SCC were determined for 20 696 eligible individuals. PSA was measured in men and CA15-3 and CA125 in women. A variable selection process was applied to select robust variables from these serum tumour markers to design cancer detection models. The sensitivity, specificity, positive predictive value (PPV), negative predictive value, area under the curve, and Youden index of the models based on single tumour markers, combined test, and machine learning methods were compared. Moreover, relative risk reduction, absolute risk reduction (ARR), and absolute risk increase (ARI) were evaluated. Results To design cancer detection models using machine learning methods, CYFRA21-1 and SCC were selected for women, and all tumour markers were selected for men. SVM and KNN models significantly outperformed the single tumour markers and the combined test for men. All 3 studied machine learning methods outperformed single tumour markers and the combined test for women. For either men or women, the ARRs were between 0.003–0.008; the ARIs were between 0.119–0.306. Conclusion Machine learning methods outperformed the combined test in analysing multiple tumour markers for cancer detection. However, cancer screening based solely on the application of multiple tumour

  17. Immunohistochemistry of soft tissue tumours - review with emphasis on 10 markers.

    PubMed

    Miettinen, Markku

    2014-01-01

    Immunohistochemistry is an integral component in the proper analysis of soft tissue tumours, and a simple panel of six markers is useful in practical triage: CD34, desmin, epithelial membrane antigen (EMA), keratin cocktail AE1/AE3, S100 protein and alpha smooth muscle actin (SMA). These markers frequently assist in the differential diagnosis of fibroblastic, myoid, nerve sheath and perineurial cell tumours, synovial and epithelioid sarcoma and others. However, they all are multispecific, so that one has to be cognizant of their distribution in normal and neoplastic tissues. Four additional useful markers for specific tumour types are discussed here: CD31 and ERG for vascular endothelial tumours, and KIT and DOG1/Ano-1 for gastrointestinal stromal tumours (GISTs). However, hardly any marker is totally monospecific for any one type of tumour. Furthermore, variably lineage-specific markers do not usually distinguish between benign and malignant proliferations, so that this distinction has to be made on histological grounds. Immunohistochemical evaluation is most useful, efficient and cost-effective when used in the context of careful histological evaluation by an experienced pathologist, aware of all diagnostic entities and their histological spectra. Additional diagnostic steps that must be considered in difficult cases include clinicoradiological correlation and additional sampling of remaining wet tissue, if possible. PMID:24111893

  18. Third Gordon Hamilton-Fairley Memorial Lecture. Tumour markers--where do we go from here?

    PubMed Central

    Bagshawe, K. D.

    1983-01-01

    An overview of the application of markers for solid tumours is presented. Some of the potential problems with general cancer tests are considered as well as the ways in which the more specific markers have been applied. The limited specificities of markers defined so far remain a serious limitation but they have found useful clinical application. Their use in radioimmunolocalisation provides an interesting challenge to the physical methods of tumour localisation and the possibilities of drug targeting by antibodies are as exciting as the difficulties are formidable. It is, I suggest, a field that will continue to evolve and be productive. PMID:6192836

  19. Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery

    NASA Astrophysics Data System (ADS)

    Matsumoto, Yu; Nichols, Joseph W.; Toh, Kazuko; Nomoto, Takahiro; Cabral, Horacio; Miura, Yutaka; Christie, R. James; Yamada, Naoki; Ogura, Tadayoshi; Kano, Mitsunobu R.; Matsumura, Yasuhiro; Nishiyama, Nobuhiro; Yamasoba, Tatsuya; Bae, You Han; Kataoka, Kazunori

    2016-06-01

    Enhanced permeability in tumours is thought to result from malformed vascular walls with leaky cell-to-cell junctions. This assertion is backed by studies using electron microscopy and polymer casts that show incomplete pericyte coverage of tumour vessels and the presence of intercellular gaps. However, this gives the impression that tumour permeability is static amid a chaotic tumour environment. Using intravital confocal laser scanning microscopy we show that the permeability of tumour blood vessels includes a dynamic phenomenon characterized by vascular bursts followed by brief vigorous outward flow of fluid (named ‘eruptions’) into the tumour interstitial space. We propose that ‘dynamic vents’ form transient openings and closings at these leaky blood vessels. These stochastic eruptions may explain the enhanced extravasation of nanoparticles from the tumour blood vessels, and offer insights into the underlying distribution patterns of an administered drug.

  20. Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery.

    PubMed

    Matsumoto, Yu; Nichols, Joseph W; Toh, Kazuko; Nomoto, Takahiro; Cabral, Horacio; Miura, Yutaka; Christie, R James; Yamada, Naoki; Ogura, Tadayoshi; Kano, Mitsunobu R; Matsumura, Yasuhiro; Nishiyama, Nobuhiro; Yamasoba, Tatsuya; Bae, You Han; Kataoka, Kazunori

    2016-06-01

    Enhanced permeability in tumours is thought to result from malformed vascular walls with leaky cell-to-cell junctions. This assertion is backed by studies using electron microscopy and polymer casts that show incomplete pericyte coverage of tumour vessels and the presence of intercellular gaps. However, this gives the impression that tumour permeability is static amid a chaotic tumour environment. Using intravital confocal laser scanning microscopy we show that the permeability of tumour blood vessels includes a dynamic phenomenon characterized by vascular bursts followed by brief vigorous outward flow of fluid (named 'eruptions') into the tumour interstitial space. We propose that 'dynamic vents' form transient openings and closings at these leaky blood vessels. These stochastic eruptions may explain the enhanced extravasation of nanoparticles from the tumour blood vessels, and offer insights into the underlying distribution patterns of an administered drug. PMID:26878143

  1. Physiological noise in murine solid tumours using T2*-weighted gradient-echo imaging: a marker of tumour acute hypoxia?

    NASA Astrophysics Data System (ADS)

    Baudelet, Christine; Ansiaux, Réginald; Jordan, Bénédicte F.; Havaux, Xavier; Macq, Benoit; Gallez, Bernard

    2004-08-01

    with no contrast enhancement as the result of vessel functional impairment. Furthermore, transient fluctuations appeared to occur preferentially in neoangiogenic hyperpermeable vessels. The present study suggests that spontaneous T2*-weighted GRE fluctuations are very likely to be related to the spontaneous fluctuations in blood flow and oxygenation associated with the pathophysiology of acute hypoxia in tumours. The disadvantage of the T2*-weighted GRE MRI technique is the complexity of signal interpretation with regard to pO2 changes. Compared to established techniques such as intravital microscopy or histological assessments, the major advantage of the MRI technique lies in its capacity to provide simultaneously both temporal and detailed spatial information on spontaneous fluctuations throughout the tumour.

  2. The expression profile for the tumour suppressor gene PTEN and associated polymorphic markers

    PubMed Central

    Hamilton, J A; Stewart, L M D; Ajayi, L; Gray, I C; Gray, N E; Roberts, K G; Watson, G J; Kaisary, A V; Snary, D

    2000-01-01

    PTEN, a putative tumour suppressor gene associated with prostate and other cancers, is known to be located within the chromosomal region 10q23.3. Transcription of the PTEN gives rise to multiple mRNA species. Analyses by Northern blots, using cell lines which express PTEN together with cell lines which have lost the PTEN or carry a truncated version of the gene, has allowed us to demonstrate that the pseudogene is not transcribed. In addition, 3′ RACE studies confirmed that the multiple mRNA species arising from the gene probably result from the use of alternative polyadenylation sites. No evidence for tissue- or cell-specific patterns of transcription was found. Analysis by 5′ RACE placed the putative site for the start of transcription around 830 bp upstream of the start codon. A map of the location of the PTEN gene with a series of overlapping YAC, BAC and PACs has been constructed and the relative position of eight microsatellite markers sited. Two known and one novel marker have been positioned within the gene, the others are in flanking regions. The more accurate location of these markers should help in future studies of the extent of gene loss. Several polymorphisms were also identified, all were within introns. Four of the common polymorphisms appear to be linked. In blood, DNA from 200 individuals, including normal, BPH and prostate cancer patients, confirmed this link. Only two samples of 200 did not carry the linked haplotype, both were patients with advanced prostate cancer. It is possible that such rearrangements within PTEN could be evidence of predisposition to prostate cancer in this small number of cases. © 2000 Cancer Research Campaign PMID:10817502

  3. Reduced capacity of tumour blood vessels to produce endothelium-derived relaxing factor: significance for blood flow modification.

    PubMed Central

    Tozer, G. M.; Prise, V. E.; Bell, K. M.; Dennis, M. F.; Stratford, M. R.; Chaplin, D. J.

    1996-01-01

    The effect of nitric oxide-dependent vasodilators on vascular resistance of tumours and normal tissue was determined with the aim of modifying tumour blood flow for therapeutic benefit. Isolated preparations of the rat P22 tumour and normal rat hindlimb were perfused ex vivo. The effects on tissue vascular resistance of administration of sodium nitroprusside (SNP) and the diazeniumdiolate (or NONO-ate) NOC-7, vasodilators which act via direct release of nitric oxide (NO), were compared with the effects of acetylcholine (ACh), a vasodilator which acts primarily via receptor stimulation of endothelial cells to release NO in the form of endothelium-derived relaxing factor (EDRF). SNP and NOC-7 effectively dilated tumour blood vessels after preconstriction with phenylephrine (PE) or potassium chloride (KCl) as indicated by a decrease in vascular resistance. SNP also effectively dilated normal rat hindlimb vessels after PE/KCl constriction. Vasodilatation in the tumour preparations was accompanied by a significant rise in nitrite levels measured in the tumour effluent. ACh induced a significant vasodilation in the normal hindlimb but an anomalous vasoconstriction in the tumour. This result suggests that tumours, unlike normal tissues are incapable of releasing NO (EDRF) in response to ACh. Capacity for EDRF production may represent a difference between tumour and normal tissue blood vessels, which could be exploited for selective pharmacological manipulation of tumour blood flow. PMID:8980396

  4. A new tumour associated antigen of non-small cell lung cancer: tumour liberated proteins (TLP)--a possible new tumor marker.

    PubMed

    Garaci, E; Sinibaldi, P; Rasi, G

    1996-01-01

    TLP (Tumour Liberated Proteins) is a 214 kDa protein, isolated from lung cancer tissue and synthetic nonapeptide CSH-275 is a major epitope identified on a 100 kDa TLP fragment and used to create antibodies in rabbit (antiserum termed CSH-419). CSH-419 antiserum, labelled or conjugated as necessary, was used to detect TLP on sera from NSCLC patients by a new ELISA test set up as a 1 step sandwich format test. This ELISA was performed on sera from 534 individuals. TLP was detected in 53.1% of NSCLC patients, with a 0% response in patients with cancers other than NSCLC, 7.6% response in unknown blood donors, and 17.4% response in patients with chronic lung diseases correlated with an elevated risk for lung cancer. TLP was particularly present in early stages of disease: 75% in stage I, 56% in stage II and III and 45% in stage IV. The presence of TLP antigen in sera from NSCLC patients indicates that TLP could represent an useful tumour marker.

  5. Evaluation of blood loss during limb salvage surgery for pelvic tumours

    PubMed Central

    Tang, Xiaodong; Yang, Rongli; Tang, Shun; Ji, Tao

    2008-01-01

    As a large amount of blood loss is sometimes encountered in limb salvage procedures for pelvic tumours, it is essential to identify risk factors predicting the possibility of extensive haemorrhage. We retrospectively reviewed 137 patients who underwent pelvic tumour resections. Patients with an estimated blood loss greater than 3,000 ml were classified as having a large amount of blood loss. Sixty-one (44.53%) patients had blood loss greater than 3,000 ml. Tumours involving the acetabulum or sacrum, tumour volume greater than 400 cm3, aorta occlusion, resection method, reconstruction and operative time were all associated with a large amount of blood loss. Pelvic tumours involving the acetabulum or sacrum (odds ratio: 4.837), tumour volume greater than 400 cm3 (odds ratio: 3.005) and planned operation time of more than 200 min (odds ratio: 3.784) independently predicted a large amount of blood loss. Pelvic tumours with these characteristics were likely to have a large amount of blood loss during surgery. PMID:19089426

  6. Renal Tumours in Adults with Correlation between Fuhrman Grading and Proliferative Marker

    PubMed Central

    Mukhopadhyay, Sabuj Ghana; Mukherjee, Krishnendu; Kr. Manna, Asim

    2015-01-01

    Background: Definite data regarding the incidence and distribution of renal tumours in eastern India is not known. For better management, as it is essential to identify patients with poor prognosis, prognostic factors like stage, nuclear grade and their relationship to molecular markers are also unclear in this region. The purpose of our study was to assess the spectrum of adult renal tumours with respect to age and sex and to correlate Fuhrman nuclear grading with Ki-67 labeling index in a tertiary care hospital in eastern India. Methods: All adult patients with kidney tumour referred to our hospital who were preoperatively diagnosed and undergone surgical resection were included. Distribution of histological subtypes of kidney tumours according to age and sex were done by Hematoxylin and Eosin stain. Fuhrman grading, performed by ocular morphometry and derivation of Ki-67 labeling index (LI), were done in malignant cases only. Correlation of Fuhrman grading and KI-67 LI were done individually. Results: Among total 36 cases, 3 were benign and 33 were malignant. Among the malignant cases: Fifteen, twelve, four and two cases were of Fuhrman grade I, II, III, IV with mean Ki67 labeling index of 6.5, 18.2,44 and 76 respectively. Statistical correlation between mean Ki-67 LI and Fuhrman grading revealed significant correlation between Grade I and II, II and III and combined Grade I,II and III,IV tumours. Conclusion: Malignant Kidney tumours, especially, grade I RCC were commonest tumour. Fuhrman grading correlated well with Ki-67 labeling index. A 2-tier system for grading is proposed for better correlation with proliferation. PMID:26351498

  7. 1H MRS markers of tumour growth in intrasplenic tumours and liver metastasis induced by injection of HT-29 cells in nude mice spleen.

    PubMed

    Moreno, A; López, L A; Fabra, A; Arús, C

    1998-05-01

    We have characterized, by in vitro magnetic resonance spectroscopy (MRS), the metabolite pattern of perchloric acid (PCA) extracts of intrasplenic tumours and hepatic metastasis, produced by intra-spleen injection of the human colorectal carcinoma cell line HT-29 and its metastatic variant HT-29 MMM into nude mice. Our aim was to gain further understanding of colorectal tumour metabolism as a basis for future in vivo studies of human colon cancer by 1H MRS. Metabolite PCA extract analysis showed a good reproduction of the spectral pattern observed in human primary colon tumours, while they were very different from the spectral pattern of the host tissues (spleen and liver). The main differences between host and tumour tissues involved taurine, phosphocholine (PC), phosphoethanolamine (PE), creatine, glycogen and glucose. Creatine is the most promising marker to follow tumour growth because of its practical absence in the nude mice host tissues. Detection of variable levels of this compound and of taurine in hepatic foci in man, are suggested as possible diagnostic markers. No correlation could be found between spectral pattern differences and the different ability to metastasize of the two HT-29 cell lines used. Furthermore, indirect evidence for a functional link between taurine and myo-inositol in colon tumour cells is presented. In summary, our data suggest that the nude mice model may be a suitable system for the MRS study of the changes taking place in host tissues upon tumour progression.

  8. Serum tumour markers as a diagnostic and prognostic tool in Libyan breast cancer.

    PubMed

    Elfagieh, Mohamed; Abdalla, Fathi; Gliwan, Asma; Boder, Jamela; Nichols, Wafa; Buhmeida, Abdelbaset

    2012-12-01

    Results from studies on efficacy of carcinoembryonic antigen (CEA), carbohydrate antigen 15.3 (CA 15.3) and thymidine kinase (TK1) as diagnostic and prognostic tools for primary breast cancer (BC) have presented conflicting results, and usefulness of these markers for clinical use in BC remains unclear. The aim of this study is to evaluate potential of concentration of the sera CEA, CA15.3 and TK1 peptides' use as markers in the diagnosis and prognosis of breast lesions of Libyan patients. Serum tumour markers were studied in 20 healthy subjects, 30 patient with benign lesion diseases and 50 patients with histologically confirmed BC diagnosed at the National Cancer Institute (NCI), Misurata, Libya during the period 2005-2009. The concentrations of the BC patients' cutoff points used for diagnostic and prognostic sensitivity were 8.82 ng/ml, 35.57 U/ml and 32.57 U/mg/protein for CEA, CA15.3 and TK1, respectively. Increased CEA (>8.82 ng/ml), CA 15.3 (>35.57 U/ml) and TK1 (>32.57 U/mg/protein) concentrations were found in 62 %, 70 % and 78 % of the BC patients, respectively. For all three tumour markers, increased concentrations correlated increased tumour size and nodal involvement. Significantly higher serum TK1 levels were found in patients with advanced disease (p < 0.0001) and TK1 levels also correlated with disease-specific survival (DSS, p < 0.07). The combined data set of the three markers' data from three markers increased the diagnostic sensitivity to 90 %. The serum marker analysis for CEA, CA 15.3, and S-TK1 concentrations is shown to be a useful tool for identification of malignant cases in our BC population and for the prognostic evaluation of patients with primary BC. Increased concentrations of the markers were also observed to be higher in patients with advanced tumours and indicative of the development of distant metastasis.

  9. [Value of urinary markers in the diagnosis and follow-up of urothelial bladder tumours].

    PubMed

    Campos-Fernandes, Jean-Louis; Descotes, Françoise; André, Jean; Perrin, Paul; Devonec, Marian; Ruffion, Alain

    2007-02-01

    Urothelial bladder tumours require regular surveillance: cystoscopy associated with urine cytology are reference examinations. Several new markers currently under evaluation or already validated have recently been proposed to replace cytology and potentially reduce or even replace unnecessary cystoscopies. The biological fluid studied for all of these markers is the same as that of urine cytology, i.e. urine. The authors review the results of recent studies on these new urinary markers. The results of these markers demonstrate a better global sensitivity than urine cytology, but often a lower specificity. In the majority of cases, these tests are performed during patient follow-up (NMP22, BTA, CYFRA 21-l., etc.), but do not replace cystoscopy, due to a large number of false-positives. Other techniques, such as FISH, uCyt+ or microsatellites appear to be more promising, especially for the diagnosis of low-grade tumours. The best solution in practice may consist of a combination of several markers to further improve sensitivity and to decrease the false-positive rate responsible for unnecessary cystoscopies.

  10. Crosstalk between cancer cells and blood endothelial and lymphatic endothelial cells in tumour and organ microenvironment

    PubMed Central

    Lee, Esak; Pandey, Niranjan B.; Popel, Aleksander S.

    2015-01-01

    Tumour and organ microenvironments are crucial for cancer progression and metastasis. Crosstalk between multiple non-malignant cell types in the microenvironments and cancer cells promotes tumour growth and metastasis. Blood and lymphatic endothelial cells (BEC and LEC) are two of the components in the microenvironments. Tumour blood vessels (BV), comprising BEC, serve as conduits for blood supply into the tumour, and are important for tumour growth as well as haematogenous tumour dissemination. Lymphatic vessels (LV), comprising LEC, which are relatively leaky compared with BV, are essential for lymphogenous tumour dissemination. In addition to describing the conventional roles of the BV and LV, we also discuss newly emerging roles of these endothelial cells: their crosstalk with cancer cells via molecules secreted by the BEC and LEC (also called angiocrine and lymphangiocrine factors). This review suggests that BEC and LEC in various microenvironments can be orchestrators of tumour progression and proposes new mechanism-based strategies to discover new therapies to supplement conventional anti-angiogenic and anti-lymphangiogenic therapies. PMID:25634527

  11. The development of tumours under a ketogenic diet in association with the novel tumour marker TKTL1: A case series in general practice

    PubMed Central

    JANSEN, NATALIE; WALACH, HARALD

    2016-01-01

    Since the initial observations by Warburg in 1924, it has become clear in recent years that tumour cells require a high level of glucose to proliferate. Therefore, a ketogenic diet that provides the body with energy mainly through fat and proteins, but contains a reduced amount of carbohydrates, has become a dietary option for supporting tumour treatment and has exhibited promising results. In the present study, the first case series of such a treatment in general practice is presented, in which 78 patients with tumours were treated within a time window of 10 months. The patients were monitored regarding their levels of transketolase-like-1 (TKTL1), a novel tumour marker associated with aerobic glycolysis of tumour cells, and the patients' degree of adherence to a ketogenic diet. Tumour progression was documented according to oncologists' reports. Tumour status was correlated with TKTL1 expression (Kruskal-Wallis test, P<0.0001), indicating that more progressed and aggressive tumours may require a higher level of aerobic glycolysis. In palliative patients, a clear trend was observed in patients who adhered strictly to a ketogenic diet, with one patient experiencing a stagnation in tumour progression and others an improvement in their condition. The adoption of a ketogenic diet was also observed to affect the levels of TKTL1 in those patients. In conclusion, the results from the present case series in general practice suggest that it may be beneficial to advise tumour patients to adopt a ketogenic diet, and that those who adhere to it may have positive results from this type of diet. Thus, the use of a ketogenic diet as a complementary treatment to tumour therapy must be further studied in rigorously controlled trials. PMID:26870251

  12. Prognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib.

    PubMed

    Seifert, Heike; Fisher, Rosalie; Martin-Liberal, Juan; Edmonds, Kim; Hughes, Peta; Khabra, Komel; Gore, Martin; Larkin, James

    2016-04-01

    The BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti-CTLA4-antibody, ipilimumab, is a standard first-line and second-line treatment option in Europe, with a median time to response of 2-3 months, but some patients show rapid clinical deterioration before that. The aim of this analysis was to identify prognostic markers for survival after failure of vemurafenib treatment to identify patients who have a sufficient life expectancy to respond to new immunotherapy treatments. We retrospectively analysed 101 consecutive unselected patients treated with vemurafenib for metastatic melanoma at a single institution. The association between clinical parameters and death within 3 months after cessation of vemurafenib (n=69) was assessed by binary logistic and Cox regression. Of the patients, 45% died within 3 months of progression on vemurafenib. Elevated baseline serum lactate dehydrogenase, absence of normalization of serum lactate dehydrogenase on vemurafenib therapy, performance status of at least 2 at progression and time from primary tumour to metastatic disease less than 5 years were identified as poor prognostic markers. In an exploratory tumour growth kinetics analysis (n=16), we found that following cessation of vemurafenib, approximately a third each showed a stable, decelerated or accelerated rate of tumour growth. Patients with these poor prognostic markers are unlikely to have sufficient life expectancy to complete ipilimumab treatment after failure with vemurafenib. Consideration needs to be given to the elective use of immunotherapy before patients become resistant to vemurafenib. This requires prospective randomized evaluation. Our tumour growth kinetics analysis requires confirmation; however, it may suggest that intermittent vemurafenib treatment should be investigated in clinical trials.

  13. Prognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib.

    PubMed

    Seifert, Heike; Fisher, Rosalie; Martin-Liberal, Juan; Edmonds, Kim; Hughes, Peta; Khabra, Komel; Gore, Martin; Larkin, James

    2016-04-01

    The BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti-CTLA4-antibody, ipilimumab, is a standard first-line and second-line treatment option in Europe, with a median time to response of 2-3 months, but some patients show rapid clinical deterioration before that. The aim of this analysis was to identify prognostic markers for survival after failure of vemurafenib treatment to identify patients who have a sufficient life expectancy to respond to new immunotherapy treatments. We retrospectively analysed 101 consecutive unselected patients treated with vemurafenib for metastatic melanoma at a single institution. The association between clinical parameters and death within 3 months after cessation of vemurafenib (n=69) was assessed by binary logistic and Cox regression. Of the patients, 45% died within 3 months of progression on vemurafenib. Elevated baseline serum lactate dehydrogenase, absence of normalization of serum lactate dehydrogenase on vemurafenib therapy, performance status of at least 2 at progression and time from primary tumour to metastatic disease less than 5 years were identified as poor prognostic markers. In an exploratory tumour growth kinetics analysis (n=16), we found that following cessation of vemurafenib, approximately a third each showed a stable, decelerated or accelerated rate of tumour growth. Patients with these poor prognostic markers are unlikely to have sufficient life expectancy to complete ipilimumab treatment after failure with vemurafenib. Consideration needs to be given to the elective use of immunotherapy before patients become resistant to vemurafenib. This requires prospective randomized evaluation. Our tumour growth kinetics analysis requires confirmation; however, it may suggest that intermittent vemurafenib treatment should be investigated in clinical trials. PMID:26684061

  14. Lectins as markers for blood grouping.

    PubMed

    Khan, Fauzia; Khan, Rizwan H; Sherwani, Asma; Mohmood, Sameena; Azfer, Md A

    2002-12-01

    Lectins are unique proteins of varying biological importance. They are characterized by specific binding to carbohydrate residues, whether monosaccharides, disaccharides or polysaccharides. The sugar heads on the surface of the erythrocyte specify the different blood groups. Lectins, as an antigenic determinant of blood group, have come to be an important tool in the identification of different blood groups. A handful of lectins may be considered excellent reagents for anti-A, anti-B, anti-N etc, but the anti-A and anti-M are not yet regarded as commercially suitable antisera. Lectin from Vicia cracca has been proved to be a good anti-A, lectin from Dolichus biflorus can be used as anti-A1, and lectin from Griffonia simplicifolia as anti-B. Lectin from Vicia graminea is said to be a good typing reagent as Anti-N. On the other hand, the lectins involved in polyagglutination are absolutely essential as the reagent of choice and these cannot as yet be replaced by antibodies of any kind. Erythrocytes with exposed cryptantigens are significantly more sensitive to agglutination by certain lectins than by polyclonal antibodies. Peanut agglutinin (PNA), Polybrene, and Glycine max lectins are frequently used for the identification of different cryptantigens. The application of lectins as an anti-B reagent has proven to be as useful as human polyclonal or mouse monoclonal antibodies. Besides their specificity, lectins are excellent reagents because of their lower cost and indigenous production. The importance of various lectins used as markers for blood grouping is discussed.

  15. FDG PET and tumour markers in the diagnosis of recurrent and metastatic breast cancer.

    PubMed

    Siggelkow, Wulf; Rath, Werner; Buell, Udalrich; Zimny, Michael

    2004-06-01

    Breast cancer continues to be one of the most common cancers in North America and Western Europe. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG PET) represents a non-invasive functional imaging modality that is based on metabolic characteristics of malignant tumours. In breast cancer, FDG PET is more accurate than conventional methods for staging of distant metastases or local recurrences and enables early assessment of treatment response in patients undergoing primary chemotherapy. Recent data indicate a rationale for the use of FDG PET in cases of asymptomatically elevated tumour marker levels in the presence of uncertain results of conventional imaging. Despite the fact that PET cannot rule out microscopic disease, it does have particular value in providing, in a single examination, a reliable assessment of the true extent of the disease. This technique is complementary to morphological imaging for primary diagnosis, staging and re-staging. It may become the method of choice for the assessment of asymptomatic patients with elevated tumour marker levels. This method, however, cannot replace invasive procedures if microscopic disease is of clinical relevance. PMID:15146295

  16. ERBB3 is a marker of a ganglioneuroblastoma/ganglioneuroma-like expression profile in neuroblastic tumours

    PubMed Central

    2013-01-01

    demonstrates the importance of performing unsupervised clustering and subtype discovery of data sets prior to analyses to avoid a mixture of tumour subtypes, which may otherwise give distorted results and lead to incorrect conclusions. The current study identifies ERBB3 as a clear-cut marker of a GNB/GN-like expression profile, and we suggest a 7-gene expression signature (including ERBB3) as a complement to histopathology analysis of neuroblastic tumours. Further studies of ErbB3 and other ErbB family members and their role in neuroblastic differentiation and pathogenesis are warranted. PMID:23835063

  17. LRIG1 is a triple threat: ERBB negative regulator, intestinal stem cell marker and tumour suppressor.

    PubMed

    Wang, Y; Poulin, E J; Coffey, R J

    2013-05-14

    In baseball parlance, a triple threat is a person who can run, hit and throw with aplomb. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a cell surface protein that antagonises ERBB receptor signalling by downregulating receptor levels. Over 10 years ago, Hedman et al postulated that LRIG1 might be a tumour suppressor. Recently, Powell et al provided in vivo evidence substantiating that claim by demonstrating that Lrig1 loss in mice leads to spontaneously arising, highly penetrant intestinal adenomas. Interestingly, Lrig1 also marks stem cells in the gut, suggesting a potential role for Lrig1 in maintaining intestinal epithelial homeostasis. In this review, we will discuss the ability of LRIG1 to act as a triple threat: pan-ERBB negative regulator, intestinal stem cell marker and tumour suppressor. We will summarise studies of LRIG1 expression in human cancers and discuss possible related roles for LRIG2 and LRIG3.

  18. The role of tumour markers in predicting skeletal metastases in breast cancer patients with equivocal bone scintigraphy

    PubMed Central

    Nicolini, A; Ferrari, P; Sagripanti, A; Carpi, A

    1999-01-01

    Bone scintigraphy (BS) is commonly performed in the staging and postoperative monitoring of breast cancer. Nevertheless, due to low specificity it often demonstrates hot spots with equivocal interpretation, which may be misleading in the management of these patients. The aim of this study was to assess the value of a serum tumour marker panel in selecting among the patients with equivocal BS those with bone metastases. Between January 1986 and December 1995, 297 breast cancer patients were followed-up after mastectomy with serial determinations of a CEA-TPA-CA15.3 tumour marker panel, BS and liver echography. The tumour marker panel was used to select patients with equivocal BS for examination of suspicious bone areas by further imaging techniques. Up to December 1995, 158 (53%) patients showed an equivocal BS and 47 patients developed bone metastases. In the 158 patients with equivocal BS, prolonged clinical and imaging follow-up over 45 months (mean; range 12–120) was used to ascertain the presence or absence of bone metastases. In these 158 patients the negative predictive value and positive predictive value of the tumour marker panel to predict bone metastases was 97% and 75% respectively. This study shows that in breast cancer patients the CEA-TPA-CA15.3 tumour marker panel has a high value in selecting those patients with bone metastases, or at high risk of developing clinically-evident bone metastases, among the large number of subjects with equivocal BS. © 1999 Cancer Research Campaign PMID:10188888

  19. Divergent effects of flavone acetic acid on established versus developing tumour blood flow.

    PubMed Central

    Mahadevan, V.; Hart, I. R.

    1991-01-01

    Flavone Acetic Acid (FAA) exerts much of its effect by reducing tumour blood flow. Previous studies on FAA-induced changes in blood flow have used established tumours with a functional microvasculature. Using radioactive Xenon(133Xe) clearance to monitor local blood flow we show that the effects of FAA are dependent on the presence of this functional microvasculature with no evidence that FAA inhibits the actual development of tumour microcirculation. Thus, administration of multiple doses of FAA around the time of tumour cell injection failed to diminish t1/2 values of 133Xe (e.g. t1/2 16 min for FAA vs 14 min for saline controls at 10 days) or to affect tumour volumes (5.55 +/- 0.06 cm3 in FAA-treated animals vs 5.7 +/- 1.3 cm3 in controls at 25 days). In marked contrast a single dose of FAA (200 mg kg-1 body weight) 2 weeks after tumour cell injection dramatically extended t1/2 times (47 min for FAA vs 7 min for controls; P less than 0.001) and significantly reduced tumour burden. This effect is specific for tumour microvasculature and is not directed simply at new vessels since a similar treatment of animals with implanted-sponge-induced granulation tissue had no effect on t1/2 times (6.8 +/- 1.1 min for FAA at 200 mg kg-1 vs 7.2 +/- 1.0 min for saline-treated controls. PMID:1712621

  20. Glutamate dependent NMDA receptor 2D is a novel angiogenic tumour endothelial marker in colorectal cancer

    PubMed Central

    Ward, Stephen; Heath, Victoria L.; Ismail, Tariq; Bicknell, Roy

    2016-01-01

    Current vascular-targeted therapies in colorectal cancer (CRC) have shown limited benefit. The lack of novel, specific treatment in CRC has been hampered by a dearth of specific endothelial markers. Microarray comparison of endothelial gene expression in patient-matched CRC and normal colon identified a panel of putative colorectal tumour endothelial markers. Of these the glutamate dependent NMDA receptor GRIN2D emerged as the most interesting target. GRIN2D expression was shown to be specific to colorectal cancer vessels by RTqPCR and IHC analysis. Its expression was additionally shown be predictive of improved survival in CRC. Targeted knockdown studies in vitro demonstrated a role for GRIN2D in endothelial function and angiogenesis. This effect was also shown in vivo as vaccination against the extracellular region of GRIN2D resulted in reduced vascularisation in the subcutaneous sponge angiogenesis assay. The utility of immunologically targeting GRIN2D in CRC was demonstrated by the vaccination approach inhibiting murine CRC tumour growth and vascularisation. GRIN2D represents a promising target for the future treatment of CRC. PMID:26943033

  1. Serum carcinoembryonic antigen as a tumour marker in patients with endometrial cancer

    PubMed Central

    Hashiguchi, Y.; Kasai, M.; Fukuda, T.; Ichimura, T.; Yasui, T.; Sumi, T.

    2016-01-01

    Background No potential tumour markers have been validated for prognosis in endometrial cancer. However, carcinoembryonic antigen (cea) is one of the most widely used tumour markers in various types of cancer. Although cea expression in endometrial cancer has been investigated, its prognostic value remains controversial, and no studies have investigated serum cea levels in large case series. In the present study, we investigated diagnostic and prognostic applications of serum cea for endometrial cancer. Methods This prospective study was approved by our Institutional Review Board. Between January 2006 and December 2012, serum cea was measured prospectively in 215 patients with endometrial cancer and was subsequently measured during treatment and at scheduled follow-up examinations in patients with elevated baseline serum cea. Results During the study period, 215 patients (142 stage i, 19 stage ii, 32 stage iii, 22 stage iv) were treated for endometrial cancer. By the time of last follow-up, 52 had relapsed (24.2%), and the median follow-up duration was 45 months (range: 1–95 months). Elevated serum cea was identified in 25 patients (11.6%) and was associated with histologic type (p = 0.04), histologic grade (p = 0.03), and myometrial invasion depth (p = 0.01). Elevated serum cea was not related to clinical stage, lymph node metastasis, distant metastasis, age, menopausal status, or body mass index. Relapse of disease was related to elevated serum cea (p = 0.006). Conclusions Serum cea is a potential prognostic indicator for endometrial cancer. PMID:27803603

  2. Tumour marker CA15-3: possible uses in the routine management of breast cancer.

    PubMed

    Tomlinson, I P; Whyman, A; Barrett, J A; Kremer, J K

    1995-06-01

    Tumour markers are a potentially powerful means of obtaining information about cancers whilst causing minimal morbidity, inconvenience and cost. CA15-3 has been suggested as a marker of distant metastasis (M+ disease) in breast cancer. We have measured CA15-3 in 77 patients with carcinoma of the breast in order to determine whether routine assay of this tumour marker would be useful in the oncology unit of a district general hospital. A highly significant correlation existed between elevated CA15-3 levels (> or = 30 U/ml) and M+ disease. The CA15-3 assay was found to have a sensitivity of 70%, a specificity of 96% and a predictive value of 87%, in agreement with previous studies. There was evidence that CA15-3 levels frequently increased in advance of otherwise detectable distant metastases. 70 patients had a 99m Tc bone scan close to the date on which CA15-3 was measured. All patients with a positive bone scan and raised levels of CA15-3 were subsequently confirmed as having bony metastases; no patient with normal bone scan and normal CA15-3 developed M+ disease (to the date of follow-up). CA15-3 levels were raised in 83% of patients who developed non-bony distant metastases. In clinical practice it may be possible to exploit the high specificity of CA15-3, in order to provide additional information to that already determined by current investigations. For example, CA15-3 might be assayed alongside a bone scan to confirm positive or negative results. Another role might be as a screen for breast cancer metastases in departments with limited access to bone scans and other imaging facilities. CA15-3 might also be used in monitoring patients for the development of distant metastases during follow-up. It is, however, unlikely that CA15-3 can substitute directly for a bone scan or other imaging currently used routinely by a department. Clinical trials are now necessary to determine the effect of using tumour markers such as CA15-3 on patient morbidity and mortality.

  3. Tumour sublines with different metastatic capacity induce similar blood coagulation changes in the host.

    PubMed Central

    Delaini, F.; Giavazzi, R.; De Bellis Vitti, G.; Alessandri, G.; Mantovani, A.; Donati, M. B.

    1981-01-01

    This paper is aimed at investigating how metastatic tumour growth influenced the haemostatic system of the host. Blood platelet count, blood fibrinogen level, the activated partial thromboplastin time (APTT) and the prothrombin time (PT) were determined at various intervals during growth and metastasis of a murine fibrosarcoma (mFS6) or one of its sublines with different metastatic capacity. Progressive thrombocytopenia and increase in fibrinogen level were observed during development of the tumour in all the animal groups studied, irrespective of the metastatic potential of the various sublines. No significant changes were observed in the PT or APTT values. These data support the concept that primary rather than metastatic growth influences the haemostatic system of tumour-bearing animals. PMID:7459231

  4. Accuracy of early detection of colorectal tumours by stool methylation markers: A meta-analysis

    PubMed Central

    Zhang, Hu; Qi, Jian; Wu, Ya-Qiong; Zhang, Ping; Jiang, Jun; Wang, Qi-Xian; Zhu, You-Qing

    2014-01-01

    AIM: To evaluate the accuracy of methylation of genes in stool samples for diagnosing colorectal tumours. METHODS: Electronic databases including PubMed, Web of Science, Chinese Journals Full-Text Database and Wanfang Journals Full-Text Database were searched to find relevant original articles about methylated genes to be used in diagnosing colorectal tumours. A quality assessment of diagnostic accuracy studies tool (QADAS) was used to evaluate the quality of the included articles, and the Meta-disc 1.4 and SPSS 13.0 software programs were used for data analysis. RESULTS: Thirty-seven articles met the inclusion criteria, and 4484 patients were included. The sensitivity and specificity for the detection of colorectal cancer (CRC) were 73% (95%CI: 71%-75%) and 92% (95%CI: 90%-93%), respectively. For adenoma, the sensitivity and specificity were 51% (95%CI: 47%-54%) and 92% (95%CI: 90%-93%), respectively. Pooled diagnostic performance of SFRP2 methylation for CRC provided the following results: the sensitivity was 79% (95%CI: 75%-82%), the specificity was 93% (95%CI: 90%-96%), the diagnostic OR was 47.57 (95%CI: 20.08-112.72), the area under the curve was 0.9565. Additionally, the results of accuracy of SFRP2 methylation for detecting colorectal adenomas were as follows: sensitivity was 43% (95%CI: 38%-49%), specificity was 94% (95%CI: 91%-97%), the diagnostic OR was 11.06 (95%CI: 5.77-21.18), and the area under the curve was 0.9563. CONCLUSION: Stool-based DNA testing may be useful for noninvasively diagnosing colorectal tumours and SFRP2 methylation is a promising marker that has great potential in early CRC diagnosis. PMID:25320544

  5. Systemic Inflammatory Response and Elevated Tumour Markers Predict Worse Survival in Resectable Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Salmiheimo, Aino; Mustonen, Harri; Stenman, Ulf-Håkan; Puolakkainen, Pauli; Kemppainen, Esko; Seppänen, Hanna; Haglund, Caj

    2016-01-01

    Background Estimation of the prognosis of resectable pancreatic ductal adenocarcinoma (PDAC) currently relies on tumour-related factors such as resection margins and on lymph-node ratio (LNR) both inconveniently available only postoperatively. Our aim was to assess the accuracy of preoperative laboratory data in predicting PDAC prognosis. Methods Collection of laboratory and clinical data was retrospective from 265 consecutive patients undergoing surgery for PDAC at Helsinki University Hospital. Cancer-specific survival assessment utilized Kaplan-Meier analysis, and independent associations between factors were by the Cox regression model. Results During follow-up, 76% of the patients died of PDAC, with a median survival time of 19.6 months. In univariate analysis, CRP, albumin, CEA, and CA19-9 were significantly associated with postoperative cancer-specific survival. In multivariate analysis, taking into account age, gender, LNR, resection margins, tumour status, and adjuvant chemotherapy, the preoperative biomarkers independently associated with adverse prognosis were hypoalbuminemia (< 36 g/L, hazard ratio (HR) 1.56, 95% confidence interval (CI) 1.10–2.19, p = 0.011), elevated CRP (> 5 mg/L, HR 1.44, 95% CI 1.03–2.02, p = 0.036), CEA (> 5 μg/L, HR 1.60, 95% CI 1.07–2.53, p = 0.047), and CA19-9 (≥555 kU/L, HR 1.91, 95% CI 1.18–3.08, p = 0.008). Conclusion For patients with resectable PDAC, preoperative CRP, along with albumin and tumour markers, is useful for predicting prognosis. PMID:27632196

  6. Ovarian dysgerminoma with normal serum tumour markers presenting in a child with precocious puberty.

    PubMed

    Kamal, Naglaa M; Khan, Ubaidullah; Mirza, Shazia; Mazoun, Kais; Mirza, Farahat M; Jundi, Majd

    2015-01-01

    A 7-year-old female child was presented to the emergency room with acute abdominal pain and vaginal bleeding. Her assessment revealed a firm large lower abdominal mass with evidence of precocious puberty with bilaterally symmetrically enlarged breast (Tanner stage B4-P1-A1). Abdominal imaging showed a well-defined soft midline pelvi-abdominal single mass measuring 7.0×12.6×11.7 cms with no ascites. Serum tumour markers including lactate dehydrogenase (LDH), beta-subunit of human chorionic gonadotropin (B-hCG) and luteinizing hormone/follicular stimulating hormone (LH/FSH) were all normal. At operation, there was a huge abdominal tumour weighing 558 grams, localized to the right ovary sparing the left ovary, uterus, lymph nodes and other abdominal organs. Unilateral right salpingo-oophorectomy was performed. Histopathologic examination revealed ovarian dysgerminoma with intact capsule; FIGO Ia. Immunohistochemical stainings were positive for placental alkaline phosphatase (PALP), CD 117(c-kit) and calretinin focally but was negative for cancer antigen-125 (CA-125), B-hCG, S-100, carcinoembryonic antigen (CEA), and leukocyte common antigen (LCA). Being fitting in the low risk classification, the wait and see protocol was selected with strict follow-up with pediatric oncologist and pediatric surgeon. Along the duration of 2 years follow up, there was no more vaginal bleeding with dramatic reduction of the breast size and no recurrence. PMID:26458677

  7. Minimal residual disease in canine lymphoma: An objective marker to assess tumour cell burden in remission.

    PubMed

    Sato, Masahiko; Yamazaki, Jumpei; Goto-Koshino, Yuko; Setoguchi, Asuka; Takahashi, Masashi; Baba, Kenji; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime

    2016-09-01

    Lymphoma is the most common haematopoietic malignancy in dogs. Since a high proportion of dogs with lymphoma achieve remission soon after initiation of chemotherapy, an objective marker assessing treatment efficacy is required. Following clinical remission, the residual population of tumour cells can be referred to as the minimal residual disease (MRD). MRD traditionally has been detected by cytology and flow cytometry; however, if the burden of malignant cells is low, these methods might not be sufficiently sensitive to detect MRD. As an extension of the development of PCR for antigen receptor gene rearrangements (PARR) in dogs, there has been recent progress in the application of real-time quantitative PCR (RT-qPCR) to canine lymphoma. With the RT-qPCR system, a very high sensitivity (1 cell per 10,000 cells) has been achieved by preparing allele-specific oligonucleotide primers and probes designed from neoplastic clones of each dog. A series of MRD diagnostics studies employing the RT-qPCR system has revealed its usefulness as a prognostic indicator, an objective marker of treatment efficacy and a predictor of relapse for dogs with lymphoma receiving chemotherapy. Introduction of the MRD monitoring system will provide an innovative scientific tool in the development of superior treatments and monitoring strategies for canine lymphoma.

  8. Acarboxy prothrombin (PIVKA II) as a tumour marker for hepatocellular carcinoma and other liver diseases.

    PubMed

    Mohamedein, A; Yousif-Kadaru, A G; Ahmed, S A; Saida, H; Zaki, Z A; Eldin; Fedail, S S

    1995-09-01

    The clinical usefulness of plasma abnormal prothrombin, defined as protein induced by vitamin K absence or antagonist II: (PIVKA II) as a tumour marker for hepatocellular carcinoma (HCC) and other liver diseases has been evaluated. PIVKA II concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) with monoclonal antibody that reacts with PIVKA II but does not cross-react with normal prothrombin. Seventy four patients (74%) out of 100 with HCC had abnormal PIVKA II levels above 0.5 AU/ml (median = 3.4 AU/ml). The level was above 1.0 AU/ml in 66 (66%) of the patients. In contrast the level of PIVKA II was low in patients with bilharzial periportal fibrosis (median = 0.09 AU/ml), patients with liver cirrhosis (median = 0.13 AU/ml), patients with hepatitis (median = 0.025 AU/ml), and essentially undetectable in all the 34 controls. The diagnostic ability of serum alphafoetoprotein (AFP) was also evaluated in these patients. AFP alone can diagnose 51% of the HCC cases. Of the remaining patients with low or negative AFP levels (65%) can be diagnosed using PIVKA II. Abnormal prothrombin is a potential marker for the laboratory diagnosis of hepatocellular carcinoma.

  9. Improvement of the separation of tumour cells from peripheral blood cells using magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Schwalbe, M.; Pachmann, K.; Höffken, K.; Clement, J. H.

    2006-09-01

    Circulating tumour cells are a key challenge in tumour therapy. Numerous approaches are on the way to achieving the elimination of these potential sources of metastasis formation. Antibody-directed magnetic cell sorting is supposed to enrich tumour cells with high selectivity, but low efficiency. The short term application of carboxymethyl dextran (CMD) coated magnetit/maghemit nanoparticles allows the discrimination of tumour cells from leukocytes. In the present work we show that the interaction of CMD nanoparticles is cell-type specific and time dependent. The breast cancer cell line MCF-7 and the CML cell line K-562 are characterized by a rapid and high interaction rate, whereas leukocytes exhibit a decelerated behaviour. The addition of carboxymethyl dextran or glucose stimulated the magnetic labelling of leukocytes. The variation of the degree of substitution of dextran with carboxymethyl groups did not affect the labelling profile of leukocytes and MCF-7 cells. In order to verify the in vitro results, whole blood samples from 13 cancer patients were analysed ex vivo. Incubation of the purified leukocyte fraction with CMD nanoparticles in the presence of low amounts of plasma reduced the overall cell content in the positive fraction. In contrast, the absolute number of residual tumour cells in the positive fraction was 90% of the initial amount.

  10. Diagnostic Role of Tumour Markers CEA, CA15-3, CA19-9 and CA125 in Lung Cancer.

    PubMed

    Ghosh, Indranath; Bhattacharjee, Debojyoti; Das, Anjan Kumar; Chakrabarti, Goutam; Dasgupta, Anindya; Dey, Subir Kumar

    2013-01-01

    The aim of this study was to assess the diagnostic yield of the tumour markers carcinoembryonic antigen, carbohydrate antigen 15-3, carbohydrate antigen 19-9 and carbohydrate antigen 125, in serum and bronchoalveolar lavage fluid in a group of patients with bronchogenic carcinoma. Serum and bronchoalveolar lavage fluid samples were collected in a group of 90 patients with benign or malignant pulmonary diseases. After appropriate processing, tumour markers were determined by enzyme immunoassay. The diagnostic yields (sensitivity, specificity and predictive values) in each environment (serum and bronchoalveolar lavage fluid) were obtained by using "Receivers operating characteristic" curve. Determined individually, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 125, showed the greatest diagnostic accuracy in bronchoalveolar lavage fluid. Carbohydrate antigen 15-3 did so in serum. Carcinoembryonic antigen was the most relevant marker in bronchoalveolar lavage fluid. For the factors evaluated in this study, determination of carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 125 in bronchoalveolar lavage fluid were clinically more useful markers in comparison with serum, although the latter may also be helpful in certain situations. Although there is no specific tumour marker for lung cancer, the combination of several can be used to diagnose most patients with lung cancer and also to rule out false positive and negative cases.

  11. The proliferation marker Chromatin Assembly Factor-1 is of clinical value in predicting the biological behaviour of salivary gland tumours.

    PubMed

    Staibano, Stefania; Mascolo, Massimo; Rocco, Alba; Lo Muzio, Lorenzo; Ilardi, Gennaro; Siano, Maria; Pannone, Giuseppe; Vecchione, Maria Luisa; Nugnes, Loredana; Califano, Luigi; Zamparese, Rosanna; Bufo, Pantaleo; De Rosa, Gaetano

    2011-01-01

    Salivary gland tumours (SGT) constitute a diagnostically challenging group of neoplasms with frequently unpredictable clinical outcome. The proliferation rate facilitates the identification of aggressive SGT. The Chromatin Assembly Factor-1 (CAF-1) is a major epigenetic regulator of nuclear chromatin organization during DNA replication. It plays a critical function in human tumourigenesis and has been proposed as a new proliferation and prognostic marker for some malignancies. This study focused on the role of CAF-1/p60 protein as a marker of clinical value for SGT. The expression of CAF-1/p60 was evaluated by immunohistochemistry on a retrospective series of 362 surgically excised benign and malignant SGT with different histogenesis and, when available, on fine-needle pre-surgical cytological biopsies. The resulting data were compared with traditional prognostic parameters, including the expression of the routine proliferation marker ki67/MIB1. CAF-1/p60 was detectable in all SGT, with highest degree of expression in metastasizing malignant tumours. Moreover, the cases of benign tumours which progressed to carcinoma during the follow-up, showed significantly higher CAF-1/p60 expression than non-progressing benign SGT, both on histological sections and cytological smears of the primary tumour. Cox's multiple regression analysis selected CAF-1/p60 expression as the best independent predictor of cancer development for benign SGT (p<0.0001), and the best independent predictor of metastasis onset for malignant tumours (p<0.0004). Overexpression of CAF-1/p60, on histological and/or cytological samples, characterizes malignant SGT with aggressive behaviour, irrespective of their specific histotype, and allows the early diagnosis of progression toward malignancy of morphologically benign tumours.

  12. Metastases and the Normalization of Tumour Blood Vessels by ICRF 159: A New Type of Drug Action

    PubMed Central

    Le Serve, A. W.; Hellmann, K.

    1972-01-01

    Profound modification of the structure and arrangement of the blood vessels has been shown in tumours after treatment with ICRF 159. X-ray angiography, carbon black (Pelikan ink) labelling, and intravital staining with lissamine green were used to demonstrate the changes. Alteration of the morphology of the blood vessels at the edge of a tumour may affect the escape of malignant cells and the rate of blood flow (and thus the concentration of anticancer drugs) through the tumour. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5FIG. 6 PMID:4111169

  13. Tumour prothymosin alpha content, a potential prognostic marker for primary breast cancer

    PubMed Central

    Magdalena, C; Dominguez, F; Loidi, L; Puente, J L

    2000-01-01

    In a previous report we suggested that the estimation of prothymosin α (PTA) levels in primary breast tumours might be used to identify breast cancer patients at high risk for distant metastasis (Dominguez F et al (1993) Eur J Cancer29A: 893–897). Here the role of tumour PTA levels as predictor was investigated with respect to both disease-free survival (DFS) and survival. Tumours were obtained from a series of 210 consecutive female patients with ductal carcinoma who underwent surgery at the Hospital Xeral de Galicia (Santiago de Compostela, Spain). Characteristics including PTA tumour levels, number of positive axillary nodes, patient's age at surgery and tumour histological grade were significantly associated with DFS and survival, as determined by univariate analysis. Patients with tumours with low or moderate PTA levels demonstrated a statistically decreased rate of tumour recurrence and a statistically significant increased overall survival in comparison with those whose tumours had high PTA levels. Patient's relative risk of dying was 2.1 times greater for tumours with high PTA levels than for those tumours with low or moderate PTA levels. In conclusion, these data support the hypothesis that tumour high PTA levels is associated with a worse outcome. © 2000 Cancer Research Campaign PMID:10682670

  14. Genetic profiling of tumours using both circulating free DNA and circulating tumour cells isolated from the same preserved whole blood sample.

    PubMed

    Rothwell, Dominic G; Smith, Nigel; Morris, Daniel; Leong, Hui Sun; Li, Yaoyong; Hollebecque, Antoine; Ayub, Mahmood; Carter, Louise; Antonello, Jenny; Franklin, Lynsey; Miller, Crispin; Blackhall, Fiona; Dive, Caroline; Brady, Ged

    2016-04-01

    Molecular information obtained from cancer patients' blood is an emerging and powerful research tool with immense potential as a companion diagnostic for patient stratification and monitoring. Blood, which can be sampled routinely, provides a means of inferring the current genetic status of patients' tumours via analysis of circulating tumour cells (CTCs) or circulating tumour DNA (ctDNA). However, accurate assessment of both CTCs and ctDNA requires all blood cells to be maintained intact until samples are processed. This dictates for ctDNA analysis EDTA blood samples must be processed with 4 h of draw, severely limiting the use of ctDNA in multi-site trials. Here we describe a blood collection protocol that is amenable for analysis of both CTCs and ctDNA up to four days after blood collection. We demonstrate that yields of circulating free DNA (cfDNA) obtained from whole blood CellSave samples are equivalent to those obtained from conventional EDTA plasma processed within 4 h of blood draw. Targeted and genome-wide NGS revealed comparable DNA quality and resultant sequence information from cfDNA within CellSave and EDTA samples. We also demonstrate that CTCs and ctDNA can be isolated from the same patient blood sample, and give the same patterns of CNA enabling direct analysis of the genetic status of patients' tumours. In summary, our results demonstrate the utility of a simple approach that enabling robust molecular analysis of CTCs and cfDNA for genotype-directed therapies in multi-site clinical trials and represent a significant methodological improvement for clinical benefit. PMID:26639657

  15. Blood groups as genetic markers in glaucoma.

    PubMed

    Brooks, A M; Gillies, W E

    1988-04-01

    A series of 474 mixed cases of glaucoma was assessed to determine whether there were any genetic differences between different types of glaucoma. A careful distinction was made between chronic open angle glaucoma (COAG), acute and chronic angle closure glaucoma, ocular hypertension, low tension glaucoma, patients with large cup disc ratios, and various types of secondary glaucoma including pseudoexfoliation of the lens capsule, uveitic and traumatic glaucoma. Using ABO blood groups, Rhesus groups, ABH secretion or non-secretion, and phenylthiourea tasting we identified certain differences. The differences from normal were significant decrease in Rh-negative patients in chronic closed angle glaucoma (p less than 0.05), a decrease in ABH secretors in ocular hypertension (p less than 0.01), and fewer HB secretors in patients with COAG (p less than 0.02). There was a significant decrease in AH secretors and increase in HB secretors in both pseudoexfoliation with raised intraocular pressure compared with COAG (p less than 0.01) and in secondary glaucomas as a group compared with COAG (p less than 0.01). Tasters of phenylthiourea were more common in traumatic and uveitic glaucoma than in normal controls (p less than 0.05). These results suggest that secondary glaucoma develops in different subjects from COAG, while patients who develop a rise in intraocular pressure proceed to cupping and field loss if they have a certain genetic constitution. The groups of patients are too small for the differences to be of great prognostic value.

  16. Immunolocalization of the human basal epithelial marker monoclonal antibody 312C8-1 in normal tissue and mammary tumours of rodents.

    PubMed

    Tsubura, A; Inui, T; Senzaki, H; Morii, S; Dairkee, S H

    1989-01-01

    Using immunoperoxidase staining of monoclonal antibody 312C8-1 against 51,000 dalton human keratin polypeptide, immunolocalization was observed in frozen sections of normal tissue and mammary tumours of adult female mice and rats. In normal tissue, the epitope was recognized in myoepithelial cells of the mammary, sweat and salivary glands, and in basal and suprabasal cells of the epidermis. However, the antibody did not react with luminal epithelial cells of the above glands or with mesenchymal cells. In spontaneous mammary tumours of mice, marker-positive tumour cells were distributed only in the outer layer of adenocarcinoma Type A, while they were scattered in some foci of adenocarcinoma Type B, and encircled the epithelial foci of pregnancy dependent tumours (plaque). All layers of epidermoid structures in adenoacanthoma revealed positivity. In rat mammary tumours induced by local dusting with 7, 12-dimethylbenz(a)anthracene (DMBA) powder, the staining pattern of benign tumours was comparable to that of the normal mammary gland. But, in addition to basally situated cells, marker-positive tumour cells were found scattered in the foci of adenocarcinoma, and were not restricted to basal cells in squamous cell carcinoma. The marker was not found in sarcomatous tissue. This antibody can therefore also be applied to rodents, and the staining pattern can be used to identify the epithelial subclass specific marker in normal tissue and in mammary tumours.

  17. The induction of human peripheral blood lymphoid colonies by conditioned media from human tumour cell lines.

    PubMed Central

    Vesole, D H; Moore, G E

    1980-01-01

    Conditioned medium (CM) from 29 human tumour cell lines and 3 malignant pleural fluids were tested for their ability to stimulate lymphoid colony formation in semi-solid agar; 9 of 14 malignant melanomas, 3 of 6 colonic carcinomas, 2 of 5 ovarian carcinomas, 3 of 4 breast carcinomas and 1 of 3 pleural fluids from breast cancer patients contained colony-stimulating activity (CSA) for human peripheral blood lymphoid cells (PBL) in semi-solid agar. Conditioned media also stimulated PBL proliferation in liquid medium; these effects were dose dependent. With the exception of one pleural fluid, extensive dialysis of CM did not significantly increase colony formation; CM from two tumour cell lines demonstrated a significant decrease in the induction of colony formation after dialysis. PMID:6970165

  18. Benign epithelial ovarian tumours-cancer precursors or markers for ovarian cancer risk?

    PubMed

    Jordan, Susan; Green, Adèle; Webb, Penelope

    2006-06-01

    The natural history of the development of epithelial ovarian cancer remains obscure and no effective screening test exists. In several human malignancies progression from benign to invasive tumour occurs, but this sequence has not been established for epithelial ovarian cancer. We have reviewed epidemiological, histopathological and molecular studies of benign epithelial ovarian tumours to assess the evidence for and against such a progression in ovarian cancer. These data suggest that a diagnosis of a benign ovarian cyst or tumour is associated with an increased risk of ovarian cancer later in life. Current evidence also suggests that benign serous tumours can progress to low-grade serous cancer and that benign mucinous tumours can progress to mucinous cancer. The more common high-grade serous ovarian cancers are likely to arise de novo.

  19. Displacement-type amperometric immunosensing platform for sensitive determination of tumour markers.

    PubMed

    Zhang, Bing; Ding, Chuanmin

    2016-08-15

    The sensitive determination of carcino embryonie antigen (CEA)-a set of highly related glycoproteins involved in cell adhesion-is beneficial to the early diagnosis of colorectal cancer. In this study, a novel displacement-type amperometric immunosensing platform, based on the fact that glucose and Alizarin Red S (ARS) compete for phenylboronic acid bindng sites, was projected for sensitive detection of tumour marker (CEA, used as a model) on a PAMAM dendrimer-encapsulated nanogold (PAMAM-Au)-functionlized sensing interface. Firstly, 4(-)mercaptophenylboronic acid (S-PBA) was assembled onto the PAMAM-Au via the S-Au interaction, and then ARS was immobilized by S-PBA binding of cis-diol moieties, which was dropped on the surface of glassy carbon electrode as sensing platform to combine antibody. Meanwhile, amylase modified gold nanoparticles were employed as labels. Accompanying the sandwich immunoassay, the carried amylase could hydrolyze amylose into glucose, and the displacement-type format was triggered due to the stronger adhesion between glucose and PBA, which resulted in the change of electrochemical signals due to the decrease of ARS (as an electron mediator). Under optimal conditions, the SWV signals were related to the concentration of CEA, indicating a certain proportional relation in a range of 0.01~50ngmL(-1) with a detection limit (LOD) of 0.003ngmL(-1). Intra- and inter-assay coefficients of variation were below 10%, respectively. In addition, the methodology showed good accordance with a commercialized enzyme-linked immunosorbent assay (ELISA) method. PMID:27058441

  20. Genetic Kinship Investigation from Blood Groups to DNA Markers.

    PubMed

    Geserick, Gunther; Wirth, Ingo

    2012-06-01

    The forensic application of hereditary characteristics became possible after the discovery of human blood groups by Karl Landsteiner in 1901. The foundation for their use in kinship investigation was laid by Emil von Dungern and Ludwig Hirschfeld in 1910 by clarification of the inheritance of the ABO groups. Up to the middle of the 20th century further red cell membrane systems were discovered. From the 1920s Fritz Schiff and Georg Strassmann fought for the introduction of blood groups into forensic kinship investigation. A new era of hemogenetics was opened from 1955 as genetic polymorphisms were described in serum proteins. Starting in 1958 there followed the complex HLA system of white blood cells, which from 1963 was joined by polymophisms in erythrocyte enzymes. Therefore, from the 1980s, it was possible to clarify the majority of kinship cases with a combination of conventional markers. From 1990 to 2000 the conventional markers were gradually replaced by the more effective DNA markers. Simultaneously typing shifted from the phenotype level to the genotype level. The genomic structure of conventional genetic markers could also now be explained. As a reflection of scientific progress the legal situation also changed, particularly in the form of the official guidelines for kinship investigation.

  1. Genetic Kinship Investigation from Blood Groups to DNA Markers

    PubMed Central

    Geserick, Gunther; Wirth, Ingo

    2012-01-01

    The forensic application of hereditary characteristics became possible after the discovery of human blood groups by Karl Landsteiner in 1901. The foundation for their use in kinship investigation was laid by Emil von Dungern and Ludwig Hirschfeld in 1910 by clarification of the inheritance of the ABO groups. Up to the middle of the 20th century further red cell membrane systems were discovered. From the 1920s Fritz Schiff and Georg Strassmann fought for the introduction of blood groups into forensic kinship investigation. A new era of hemogenetics was opened from 1955 as genetic polymorphisms were described in serum proteins. Starting in 1958 there followed the complex HLA system of white blood cells, which from 1963 was joined by polymophisms in erythrocyte enzymes. Therefore, from the 1980s, it was possible to clarify the majority of kinship cases with a combination of conventional markers. From 1990 to 2000 the conventional markers were gradually replaced by the more effective DNA markers. Simultaneously typing shifted from the phenotype level to the genotype level. The genomic structure of conventional genetic markers could also now be explained. As a reflection of scientific progress the legal situation also changed, particularly in the form of the official guidelines for kinship investigation. PMID:22851931

  2. Radiochemotherapy-induced changes of tumour vascularity and blood supply estimated by dynamic contrast-enhanced CT and fractal analysis in malignant head and neck tumours

    PubMed Central

    Hietschold, V; Appold, S; von Kummer, R; Abolmaali, N

    2015-01-01

    Objective: To investigate radiochemotherapy (RChT)-induced changes of transfer coefficient (Ktrans) and relative tumour blood volume (rTBV) estimated by dynamic contrast-enhanced CT (DCE-CT) and fractal analysis in head and neck tumours (HNTs). Methods: DCE-CT was performed in 15 patients with inoperable HNTs before RChT, and after 2 and 5 weeks. The dynamics of Ktrans and rTBV as well as lacunarity, slope of log(lacunarity) vs log(box size), and fractal dimension were compared with tumour behaviour during RChT and in the 24-month follow-up. Results: In 11 patients, an increase of Ktrans and/or rTBV after 20 Gy followed by a decrease of both parameters after 50 Gy was noted. Except for one local recurrence, no tumour residue was found during the follow-up. In three patients with partial tumour reduction during RChT, a decrease of Ktrans accompanied by an increase in rTBV between 20 and 50 Gy was detected. In one patient with continuous elevation of both parameters, tumour progressed after RChT. Pre-treatment difference in intratumoral heterogeneity with its decline under RChT for the responders vs non-responders was observed. Conclusion: Initial growth of Ktrans and/or rTBV followed by further reduction of both parameters along with the decline of the slope of log(lacunarity) vs log(box size) was associated with positive radiochemotherapeutic response. Increase of Ktrans and/or rTBV under RChT indicated a poor outcome. Advances in knowledge: The modification of Ktrans and rTBV as measured by DCE-CT may be applied for the assessment of tumour sensitivity to chose RChT regimen and, consequently, to reveal clinical impact allowing individualization of RChT strategy in patients with HNT. PMID:25412001

  3. Pediatric Blood Pressure and Adult Preclinical Markers of Cardiovascular Disease

    PubMed Central

    Magnussen, Costan G.; Smith, Kylie J.

    2016-01-01

    A high blood pressure level in adults is considered the single most important modifiable risk factor for global disease burden, especially those of cardiovascular (CV) origin such as stroke and ischemic heart disease. Because blood pressure levels have been shown to persist from childhood to adulthood, elevations in pediatric levels have been hypothesized to lead to increased CV burden in adulthood and, as such, might provide a window in the life course where primordial and primary prevention could be focused. In the absence of substantive data directly linking childhood blood pressure levels to overt adult CV disease, this review outlines the available literature that examines the association between pediatric blood pressure and adult preclinical markers of CV disease. PMID:27168729

  4. Quercetin mediated reduction of angiogenic markers and chaperones in DLA-induced solid tumours.

    PubMed

    Anand, Kushi; Asthana, Pallavi; Kumar, Anup; Ambasta, Rashmi K; Kumar, Pravir

    2011-01-01

    Diet-derived flavonoids, in particular quercetin, may play advantageous roles by preventing or/and inhibiting oncogenesis. Evidence suggests that quercetin can elicit various properties depending on the cell type. The aim of this study was to evaluate its effects on Dalton's lymphoma ascites (DLA) induced solid tumours and to identify the target(s) of action. We addressed this question by inducing subcutaneous solid tumours in Swiss albino mice and investigated whether the quercetin affects essential biological processes that are responsible for tumour growth, morphology, angiogenesis and apoptosis. We also studied influence on several heat shock proteins (HSPs). Our findings demonstrate that intra-tumour administration of quercetin results in decreased volume/weight. Furthermore, we demonstrate that quercetin promotes apoptosis of cancer cells by down-regulating the levels of Hsp90 and Hsp70. Depletion of these two chaperones by quercetin might result in triggering of caspase-3 in treated tumours. Moreover, it also down-regulated the expression of major key angiogenic or pro-angiogenic factors, like HIF-1α and VEGF In addition, H and E staining together with immunofluorescence of fixed tumour tissue provided evidence in support of increased cell death in quercetin-treated mice. PMID:22393949

  5. Expression of blood group antigens in urinary tract tumours: prospective fluorescence study using cryostat sections of fresh frozen tissues.

    PubMed Central

    Thorpe, S J; Abel, P; Henderson, D; Jones, N; Feizi, T

    1986-01-01

    Cryostat sections of fresh frozen tissues were used in a prospective study of blood group H and A antigen fluorescence in 73 transitional cell carcinomas of the bladder. The aim was to evaluate antigen expression without subjecting the tumour tissues to organic solvents that extract blood group active glycolipids. Deletion of the genetically predicted antigen was twice as common in tumours of pT1 or greater stage than those of pTa stage and also twice as common in poorly differentiated than in moderately well differentiated tumours. The considerable heterogeneity and overlap, however, in patterns of reactivity in tumours of various histopathological stages and grades and the effect of secretor status on antigenicity meant that there was no obvious antigenic feature that correlated precisely with invasive stage or differentiation grade. It remains to be determined whether the antigen positive and antigen negative tumours represent different disease entities with differing clinical courses. Our results indicate, however, that studies of the blood group antigens in urinary tract tumours are more likely to be of value in research into biochemical disorders in the neoplastic process than in routine clinical assessment as a guide to treatment. Images Fig 1 Fig 2 Fig 3 PMID:3540013

  6. 31P-nuclear magnetic resonance spectroscopy in vivo of six human melanoma xenograft lines: tumour bioenergetic status and blood supply.

    PubMed Central

    Lyng, H.; Olsen, D. R.; Southon, T. E.; Rofstad, E. K.

    1993-01-01

    Six human melanoma xenograft lines grown s.c. in BALB/c-nu/nu mice were subjected to 31P-nuclear magnetic resonance (31P-NMR) spectroscopy in vivo. The following resonances were detected: phosphomonoesters (PME), inorganic phosphate (Pi), phosphodiesters (PDE), phosphocreatine (PCr) and nucleoside triphosphate gamma, alpha and beta (NTP gamma, alpha and beta). The main purpose of the work was to search for possible relationships between 31P-NMR resonance ratios and tumour pH on the one hand and blood supply per viable tumour cell on the other. The latter parameter was measured by using the 86Rb uptake method. Tumour bioenergetic status [the (PCr + NTP beta)/Pi resonance ratio], tumour pH and blood supply per viable tumour cell decreased with increasing tumour volume for five of the six xenograft lines. The decrease in tumour bioenergetic status was due to a decrease in the (PCr + NTP beta)/total resonance ratio as well as an increase in the Pi/total resonance ratio. The decrease in the (PCr + NTP beta)/total resonance ratio was mainly a consequence of a decrease in the PCr/total resonance ratio for two lines and mainly a consequence of a decrease in the NTP beta/total resonance ratio for three lines. The magnitude of the decrease in the (PCr + NTP beta)/total resonance ratio and the magnitude of the decrease in tumour pH were correlated to the magnitude of the decrease in blood supply per viable tumour cell. Tumour pH decreased with decreasing tumour bioenergetic status, and the magnitude of this decrease was larger for the tumour lines showing a high than for those showing a low blood supply per viable tumour cell. No correlations across the tumour lines were found between tumour pH and tumour bioenergetic status or any other resonance ratio on the one hand and blood supply per viable tumour cell on the other. The differences in the 31P-NMR spectrum between the tumour lines were probably caused by differences in the intrinsic biochemical properties of the tumour

  7. Exosomes serve as tumour markers for personalized diagnostics owing to their important role in cancer metastasis

    PubMed Central

    An, Taixue; Qin, Sihua; Xu, Yong; Tang, Yueting; Huang, Yiyao; Situ, Bo; Inal, Jameel M.; Zheng, Lei

    2015-01-01

    Exosomes, membrane vesicles of 40–100 nm in diameter, are derived from endosomes in various cells. The bioactive molecules specifically packed into exosomes can be horizontally transferred into recipient cells changing their biological properties, by which tumour cells continuously modify their surrounding microenvironment and distant target cells favouring cancer metastasis. It has been suspected for a long time that exosomes participate in the whole process of tumour metastasis. Although there is much unknown and many controversies in the role of cancer exosome, the major contribution of tumour-associated exosomes to different steps of cancer metastasis are demonstrated in this review. Mainly because these exosomes are easily accessible and capable of representing their parental cells, exosomes draw much attention as a promising biomarker for tumour screening, diagnosis and prognosis. Currently, researchers have found numerous biomarkers in exosomes with great potential to be utilized in personalized medicine. In this article, we summarize the roles of biomarkers, which are validated by clinical samples. Even though many conundrums remain, such as exosome extraction, large multicentre validation of biomarkers and data interpretation, exosomes are certain to be used in clinical practice in the near future as the field rapidly expands. PMID:26095380

  8. Maternal blood metal levels and fetal markers of metabolic function

    SciTech Connect

    Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E.; Ettinger, Adrienne S.; Shapiro, Gabriel D.; Fisher, Mandy; Taback, Shayne; Bouchard, Maryse F.; Monnier, Patricia; Dallaire, Renee; Fraser, William D.

    2015-01-15

    Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between metals and

  9. Is mean blood saturation a useful marker of tissue oxygenation?

    PubMed

    Thorn, Clare E; Matcher, Stephen J; Meglinski, Igor V; Shore, Angela C

    2009-05-01

    Increasingly we are monitoring the distribution of oxygen through the microcirculation using optical techniques such as optical reflectance spectroscopy (ORS) and near-infrared spectroscopy. Mean blood oxygen saturation (S(mb)O(2)) and tissue oxygenation index measured by these two techniques, respectively, evoke a concept of the measurement of oxygen delivery to tissue. This study aims to establish whether S(mb)O(2) is an appropriate indicator of tissue oxygenation. Spontaneous fluctuations in S(mb)O(2) observed as changes in concentration of oxyhemoglobin ([HbO(2)]) and deoxyhemoglobin ([Hb]) were measured by ORS in the skin microcirculation of 30 healthy subjects (15 men, age 21-42 yr). Fourier analysis identified two distinctly different spontaneous falls in S(mb)O(2). The first type of swing, thought to be induced by fluctuations in arterial blood volume, resulted from the effects of respiration, endothelial, sympathetic, and myogenic activity. There was no apparent change in [Hb]. In contrast, a second type of swing resulted from a fall in [HbO(2)] accompanied by a rise in [Hb] and was only induced by endothelial and sympathetic activity. Thus the same fall in S(mb)O(2) can be induced by two distinct responses. A "type I" swing does not suggest an inadequacy in oxygen delivery whereas a "type II" swing may indicate a change in oxygen delivery from blood to tissue. S(mb)O(2) alone cannot therefore be accepted as a definitive marker of tissue oxygenation.

  10. Regan isoenzyme of alkaline phosphatase as a tumour marker for renal cell carcinoma.

    PubMed

    Bukowczan, J; Pattman, S; Jenkinson, F; Quinton, R

    2014-09-01

    Alkaline phosphatase is an enzyme present in all tissues of the human body. Several isoforms of this enzyme have been described with different catalytic nature, stability and antigenic structure. Rises in the activity of alkaline phosphatase are recognised in various states including bone diseases, liver disease, pregnancy, hyperthyroidism and malignant processes. The Regan isoenzyme, a rare variant of placental alkaline phosphatase, has been identified circulating in association with various tumours. The reported case describes a rising Regan isoform of alkaline phosphatase concentrations that led to a new diagnosis of occult renal cell carcinoma and persistently elevated activity postoperatively signposting persistent or recurrent disease.

  11. Phosphatidylethanol in blood as a marker of ethanol consumption in healthy volunteers: comparison with other markers.

    PubMed

    Varga, A; Hansson, P; Lundqvist, C; Alling, C

    1998-11-01

    Phosphatidylethanol is a "pathological" phospholipid, formed via the action of phospholipase D only in the presence of ethanol. The present study was made to elucidate how different levels and patterns of alcohol intake affect blood levels of phosphatidylethanol in comparison with other markers of abuse. We used a new HPLC-evaporative light-scattering detection technique for phosphatidylethanol quantitation. This method had a total coefficient of variation of <20% at the detection limit of 0.2 nmol, equaling 0.8 micromol/liter of whole blood. Two groups were studied. (a) Five healthy volunteers were given 32 to 47 g of ethanol in a single dose, to give blood ethanol levels of approximately 25 mmol/liter after 30 to 60 min. Phosphatidylethanol, carbohydrate-deficient transferrin (CDT), and blood ethanol were measured before and after the intake. (b) Twelve student volunteers were studied during a 3 week period of prolonged alcohol consumption (total estimated intake: 1334 +/- 488 g, mean +/- SD) and phosphatidylethanol, serum-CDT, gamma-glutamyltransferase, and blood ethanol were measured at the start of the period (day 1) and twice at the end of the period (days 18 and 21). In group (a), no phosphatidylethanol was detected at any time after ethanol dosage/intake. In group (b), no blood phosphatidylethanol or blood ethanol could be demonstrated at the start, and serum-CDT was below the discrimination limit (1.3%) in all persons. No phosphatidylethanol was detected in those four persons with the lowest intake (742 +/- 150 g). However, the remaining eight persons had detectable levels of phosphatidylethanol (1.0 to 2.1 micromol/liter), and these had a higher total intake (1630 +/- 389 g). There was a statistically significant (p = 0.02) increase in serum CDT for 3 weeks. However, only 3 of 12 persons increased above the discrimination limit. The present results indicate that a substantial alcohol intake is needed to elevate blood phosphatidylethanol. In comparison

  12. INSL5 is a novel marker for human enteroendocrine cells of the large intestine and neuroendocrine tumours.

    PubMed

    Thanasupawat, Thatchawan; Hammje, Katrin; Adham, Ibrahim; Ghia, Jean-Eric; Del Bigio, Marc R; Krcek, Jerry; Hoang-Vu, Cuong; Klonisch, Thomas; Hombach-Klonisch, Sabine

    2013-01-01

    We report for the first time the distribution of human INSL5 and its cognate leucine rich G-protein coupled receptor RXFP4 in the large intestine and in neuroendocrine/carcinoid tissues. Immunoreactive INSL5 was uniquely expressed by enteroendocrine cells (EECs) located within the colonic mucosa, whereas colonocytes were immunopositive for RXFP4. INSL5+ and RXFP4+ cells were also detected in human neuroendocrine/carcinoid tissues. We employed a recently described Insl5 knockout mouse model and 2 mouse models of induced colitis to address the relevance of Insl5 in EEC development and in acute inflammation of the colon. We identified INSL5 as a specific marker for synaptophysin+ EECs in the mucosa of the normal human and mouse colon. Insl5 was not essential for the development of mouse synaptophysin+ EECs. The mouse models of chemically induced colitis (dextran sulfate sodium and dinitrobenzene-sulfonic acid) failed to show changes in the numbers of Insl5+ EECs at inflammatory sites during the acute phase of colitis. In conclusion, we showed that INSL5 is a novel marker of colorectal EECs and provide first evidence for the presence of a potentially autocrine/paracrine INSL5-RXFP4 signaling system in the normal human and mouse colon and in rare human neuroendocrine tumours.

  13. Decrease in drug accumulation and in tumour aggressiveness marker expression in a fenretinide-induced resistant ovarianumour cell line

    PubMed Central

    Appierto, V; Cavadini, E; Pergolizzi, R; Cleris, L; Lotan, R; Canevari, S; Formelli, F

    2001-01-01

    We investigated whether the efficacy of fenretinide (HPR) against ovarian tumours may be limited by induction of resistance. The human ovarian carcinoma cell line A2780, which is sensitive to a pharmacologically achievable HPR concentration (IC 50= 1 μM), became 10-fold more resistant after exposure to increasing HPR concentrations. The cells (A2780/HPR) did not show cross-resistance to the synthetic retinoid 6-[3-adamantyl-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and were not sensitive, similarly to the parent line, to all- trans -retinoic acid, 13- cis -retinoic acid or N-(4-methoxyphenyl)retinamide. A2780/HPR cells showed, compared to parental cells, a 3-fold reduction in colony-forming ability in agar. The development of HPR resistance was associated with a marked increase in retinoic acid receptor β (RARβ) mRNA and protein levels, which decreased, together with drug resistance, after drug removal. The expression of cell surface molecules associated with tumour progression including HER-2, laminin receptor and β1 integrin was markedly reduced. The increase in the levels of reactive oxygen species is not involved in HPR-resistance because it was similar in parental and resistant cells. Conversely differences in pharmacokinetics may account for resistance because, in A2780/HPR cells, intracellular peak drug levels were 2 times lower than in A2780 cells and an as yet unidentified polar metabolite was present. These data suggest that acquired resistance to HPR is associated with changes in marker expression, suggestive of a more differentiated status and may be explained, at least in part, by reduced drug accumulation and increased metabolism. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11384104

  14. Clinical evaluation of serum tumour marker CA 242 in non-small cell lung cancer.

    PubMed Central

    Pujol, J. L.; Cooper, E. H.; Lehmann, M.; Purves, D. A.; Dan-Aouta, M.; Midander, J.; Godard, P.; Michel, F. B.

    1993-01-01

    CA 242, a novel tumour carbohydrate antigen present in serum (upper limit of normal values: 20.0 U ml-1), has been measured in a group of 102 pathologically confirmed non-small cell lung cancer patients. The aim of the present prospective study was to identify any relationship between pre-treatment serum CA 242 level and different features of lung cancer including prognosis. Serum CA 242 was measured using the delayed europium lanthanide fluoroimmunometric assay. Sensitivity and specificity were 28.5% and 95.6% respectively. Its level was significantly lower in squamous cell carcinoma in comparison with non-squamous histologies (adenocarcinoma and large cell carcinoma). The CA 242 level was higher in metastatic disease (median: 15.3 U ml-1) in comparison with non-metastatic (median: 7.9 U ml-1; Mann Whitney U test; P < 0.003), and increased significantly from stage I to stage IV. In 50 patients who underwent chemotherapy, the serum CA 242 level was higher in non-responder patients when compared with responders (median: 16.8 U ml-1 and 9.5 U ml-1 respectively; Mann Whitney; P < 0.02). Univariate analysis of the entire population showed serum CA 242 levels were not related to survival. However, patients with unresectable non-small cell lung cancer and elevated CA 242 level proved to have a significantly shorter survival than those with a CA 242 < 20 U ml-1. In Cox's model analysis, stage of the disease and performance status were the only significant determinants of survival. We conclude that a high level of serum CA 242 (1) is significantly related to the stage of disease, (2) predictive of no response to chemotherapy but seems to add weak prognostic information to stage of disease and performance status, the main prognostic determinants of non-small cell lung cancer. PMID:8390291

  15. Rapid dual-tracer PTSM+ATSM PET imaging of tumour blood flow and hypoxia: a simulation study.

    PubMed

    Rust, T C; Kadrmas, D J

    2006-01-01

    Blood flow and hypoxia are interrelated aspects of physiology that affect cancer treatment and response. Cu-PTSM and Cu-ATSM are related PET tracers for blood flow and hypoxia, and the ability to rapidly image both tracers in a single scan would bring several advantages over conventional single-tracer techniques. Using dynamic imaging with staggered injections, overlapping signals for multiple PET tracers may be recovered utilizing information from kinetics and radioactive decay. In this work, rapid dual-tracer PTSM+ATSM PET was simulated and tested as a function of injection delay, order and relative dose for several copper isotopes, and the results were compared relative to separate single-tracer data. Time-activity curves representing a broad range of tumour blood flow and hypoxia levels were simulated, and parallel dual-tracer compartment modelling was used to recover the signals for each tracer. The main results were tested further using a torso phantom simulation of PET tumour imaging. Using scans as short as 30 minutes, the dual-tracer method provided measures of blood flow and hypoxia similar to single-tracer imaging. The best performance was obtained by injecting PTSM first and using a somewhat higher dose for ATSM. Comparable results for different copper isotopes suggest that tracer kinetics with staggered injections play a more important role than radioactive decay in the signal separation process. Rapid PTSM+ATSM PET has excellent potential for characterizing both tumour blood flow and hypoxia in a single, fast scan, provided that technological hurdles related to algorithm development and routine use can be overcome.

  16. Pt NPs and DNAzyme functionalized polymer nanospheres as triple signal amplification strategy for highly sensitive electrochemical immunosensor of tumour marker.

    PubMed

    Chang, Honghong; Zhang, Haochun; Lv, Jia; Zhang, Bing; Wei, Wenlong; Guo, Jingang

    2016-12-15

    Highly sensitive determination of tumour markers is the key for early diagnosis of cancer. Herein, triple signal amplification strategy resulting from polymer nanospheres, Pt NPs, and DNAzyme was proposed in the developed electrochemical immunosensor. First, electroactive polymer nanospheres were synthesized by infinite coordination polymerization of ferrocenedicarboxylic acid, which could generate strong electrochemical signals due to plentiful ferrocene molecules. Further, the polymer nanospheres were functionalized by Pt NPs and DNAzyme (hemin/G-quadruplex) with the ability of catalyzing H2O2, which contributes to enhance the electrochemical signals. The prepared conjugations were characterized by transmission electron microscope (TEM) and energy dispersive X-ray spectroscopy (EDX). And the process of preparation was monitored by zeta potential. Based on the sandwich-type immunoassay, the electrochemical immunosensor was constructed employing the conjugations as signal tags. Under optimal conditions, the DPV peak increased with the increasing of alpha fetal protein (AFP) concentration, and the linear range was from 0.1pgmL(-1) to 100ngmL(-1) with low detection limit of 0.086pgmL(-1). Meanwhile, the designed immunosensor exhibited excellent selectivity and anti-interference property, good reproducibility and stability. More importantly, there were no significant differences in analyzing real clinical samples between designed immunosensor and commercial ELISA.

  17. Blood Contamination in Saliva: Impact on the Measurement of Salivary Oxidative Stress Markers.

    PubMed

    Kamodyová, Natália; Baňasová, Lenka; Janšáková, Katarína; Koborová, Ivana; Tóthová, Ľubomíra; Stanko, Peter; Celec, Peter

    2015-01-01

    Salivary oxidative stress markers represent a promising tool for monitoring of oral diseases. Saliva can often be contaminated by blood, especially in patients with periodontitis. The aim of our study was to examine the impact of blood contamination on the measurement of salivary oxidative stress markers. Saliva samples were collected from 10 healthy volunteers and were artificially contaminated with blood (final concentration 0.001-10%). Next, saliva was collected from 12 gingivitis and 10 control patients before and after dental hygiene treatment. Markers of oxidative stress were measured in all collected saliva samples. Advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), and antioxidant status were changed in 1% blood-contaminated saliva. Salivary AOPP were increased in control and patients after dental treatment (by 45.7% and 34.1%, p < 0.01). Salivary AGEs were decreased in patients after microinjury (by 69.3%, p < 0.001). Salivary antioxidant status markers were decreased in both control and patients after dental treatment (p < 0.05 and p < 0.01). One % blood contamination biased concentrations of salivary oxidative stress markers. Saliva samples with 1% blood contamination are visibly discolored and can be excluded from analyses without any specific biochemic detection of blood constituents. Salivary markers of oxidative stress were significantly altered in blood-contaminated saliva in control and patients with gingivitis after dental hygiene treatment.

  18. Seroprevalence of infectious markers & their trends in blood donors in a hospital based blood bank in north india

    PubMed Central

    Makroo, R.N.; Hegde, Vikas; Chowdhry, Mohit; Bhatia, Aakanksha; Rosamma, N.L.

    2015-01-01

    Background & objectives: Hepatitis B virus (HBV), human immunodeficiency virus (HIV), hepatitis C virus (HCV) and syphilis infections pose a great threat to blood safety. This study was undertaken to investigate the seroprevalence of serologic markers for transfusion transmitted infections (TTIs) among blood donors at a hospital based blood centre in north India over a period of nine years. Methods: The results of serologic markers for TTIs (HBsAg, anti-HCV, anti-HIV and syphilis) of all blood donations (both voluntary and replacement) at our hospital from January 2005 to December 2013 were screened. Additional analysis was conducted to examine the prevalence trends associated with each of the positive marker. Results: The data of 180,477 donors [173,019 (95.86%) males and 7,458 (4.13%) females] were analyzed. Replacement donations [174,939 (96.93%)] represented the majority whereas, only 5,538 (3.06%) donations were from the voluntary donors. The risk of blood being reactive was three times higher in male donors when compared with the female donors. The risk of blood being reactive for one or more infectious markers was 2.1 times higher in replacement donors when compared with the voluntary donors. Seropositivity of HIV, HBsAg, HBcAb, syphilis showed a significant decreasing trend (P<0.05) while there was an increasing trend in HCV infection which was insignificant. Interpretation & conclusions: This study reflects that the risk of TTIs has been decreased over time with respect to HIV, HBV and syphilis, but the trends for HCV remains almost the same in blood donors. Blood transfusion remains a risk factor for the spread of blood-borne infections. Therefore, improvements are needed to strengthen both safety and availability of blood. PMID:26458348

  19. Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients

    PubMed Central

    Panse, J; Friedrichs, K; Marx, A; Hildebrandt, Y; Luetkens, T; Bartels, K; Horn, C; Stahl, T; Cao, Y; Milde-Langosch, K; Niendorf, A; Kröger, N; Wenzel, S; Leuwer, R; Bokemeyer, C; Hegewisch-Becker, S; Atanackovic, D

    2008-01-01

    The abilities of chemokines in orchestrating cellular migration are utilised by different (patho-)biological networks including malignancies. However, except for CXCR4/CXCL12, little is known about the relation between tumour-related chemokine expression and the development and progression of solid tumours like breast cancer. In this study, microarray analyses revealed the overexpression of chemokine CXCL13 in breast cancer specimens. This finding was confirmed by real-time polymerase chain reaction in a larger set of samples (n=34) and cell lines, and was validated on the protein level performing Western blot, ELISA, and immunohistochemistry. Levels of CXCR5, the receptor for CXCL13, were low in malignant and healthy breast tissues, and surface expression was not detected in vitro. However, we observed a strong (P=0.0004) correlation between the expressions of CXCL13 and CXCR5 in breast cancer tissues, indicating a biologically relevant role of CXCR5 in vivo. Finally, we detected significantly elevated serum concentrations of CXCL13 in patients with metastatic disease (n=54) as compared with controls (n=44) and disease-free patients (n=48). In conclusion, CXCL13 is overexpressed within breast cancer tissues, and increased serum levels of this cytokine can be found in breast cancer patients with metastatic disease pointing to a role of CXCL13 in the progression of breast cancer, suggesting that CXCL13 might serve as a useful therapeutic target and/or diagnostic marker in this malignancy. PMID:18781150

  20. Selection of microsatellite markers for bladder cancer diagnosis without the need for corresponding blood.

    PubMed

    van Tilborg, Angela A G; Kompier, Lucie C; Lurkin, Irene; Poort, Ricardo; El Bouazzaoui, Samira; van der Keur, Kirstin; Zuiverloon, Tahlita; Dyrskjot, Lars; Orntoft, Torben F; Roobol, Monique J; Zwarthoff, Ellen C

    2012-01-01

    Microsatellite markers are used for loss-of-heterozygosity, allelic imbalance and clonality analyses in cancers. Usually, tumor DNA is compared to corresponding normal DNA. However, normal DNA is not always available and can display aberrant allele ratios due to copy number variations in the genome. Moreover, stutter peaks may complicate the analysis. To use microsatellite markers for diagnosis of recurrent bladder cancer, we aimed to select markers without stutter peaks and a constant ratio between alleles, thereby avoiding the need for a control DNA sample. We investigated 49 microsatellite markers with tri- and tetranucleotide repeats in regions commonly lost in bladder cancer. Based on analysis of 50 blood DNAs the 12 best performing markers were selected with few stutter peaks and a constant ratio between peaks heights. Per marker upper and lower cut off values for allele ratios were determined. LOH of the markers was observed in 59/104 tumor DNAs. We then determined the sensitivity of the marker panel for detection of recurrent bladder cancer by assaying 102 urine samples of these patients. Sensitivity was 63% when patients were stratified for LOH in their primary tumors. We demonstrate that up-front selection of microsatellite markers obliterates the need for a corresponding blood sample. For diagnosis of bladder cancer recurrences in urine this significantly reduces costs. Moreover, this approach facilitates retrospective analysis of archival tumor samples for allelic imbalance.

  1. High incidence of SV40-like sequences detection in tumour and peripheral blood cells of Japanese osteosarcoma patients

    PubMed Central

    Yamamoto, H; Nakayama, T; Murakami, H; Hosaka, T; Nakamata, T; Tsuboyama, T; Oka, M; Nakamura, T; Toguchida, J

    2000-01-01

    Recent studies have revealed the evidence for the significance of SV40 genome in human malignancies. In this paper, the presence of SV40-like sequences was investigated in 54 Japanese osteosarcomas in which mutations of the retinoblastoma (Rb), p53, MDM2, and CDK4 genes had been already analysed. Using polymerase chain reaction and Southern hybridization, SV40-like sequences were detected in 25 cases (46.3%). In most cases, only a part of SV40 genome was detected, and the regulatory region containing enhancer sequences was most frequently found (21/54, 38.9%). There was no apparent relationship between the presence of SV40-like sequences and tumour suppressor genes mutations in each tumour. The SV40-like sequences were also detected in peripheral blood cells of substantial proportion of the patients (43.3%), whereas the incidence was much lower (4.7%) in normal healthy controls. This difference is statistically highly significant (P< 0.0001), suggesting that the presence of SV40-like sequences, even if only a part, may play some roles to predispose individuals to osteosarcoma. © 2000 Cancer Research Campaign PMID:10817503

  2. Walker 256 tumour cells increase substance P immunoreactivity locally and modify the properties of the blood-brain barrier during extravasation and brain invasion.

    PubMed

    Lewis, Kate M; Harford-Wright, Elizabeth; Vink, Robert; Nimmo, Alan J; Ghabriel, Mounir N

    2013-01-01

    It is not yet known how tumour cells traverse the blood-brain barrier (BBB) to form brain metastases. Substance P (SP) release is a key component of neurogenic inflammation which has been recently shown to increase the permeability of the BBB following CNS insults, making it a possible candidate as a mediator of tumour cell extravasation into the brain. This study investigated the properties of the BBB in the early stages of tumour cell invasion into the brain, and the possible involvement of SP. Male Wistar rats were injected with Walker 256 breast carcinoma cells via the internal carotid artery and euthanised at 1, 3, 6 and 9 days post tumour inoculation. Culture medium-injected animals served as controls at 1 and 9 days. Evidence of tumour cell extravasation across the BBB was first observed at 3 days post-inoculation, which corresponded with significantly increased albumin (p < 0.05) and SP immunoreactivity (p < 0.01) and significantly reduced endothelial barrier antigen labelling of microvessels when compared to culture medium control animals (p < 0.001). By day 9 after tumour cell inoculation, 100 % of animals developed large intracranial neoplasms that had significantly increased albumin in the peri-tumoral area (p < 0.001). The increased SP immunoreactivity and altered BBB properties at 3 days post-inoculation that coincided with early tumour invasion may be indicative of a mechanism for tumour cell extravasation into the brain. Thus, extravasation of tumour cells into the brain to form cerebral metastases may be a SP-mediated process.

  3. OP04QUANTITATIVE MEASUREMENT OF BLOOD FLOW IN PAEDIATRIC BRAIN TUMOURS - A COMPARATIVE STUDY OF DYNAMIC SUSCEPTIBILITY CONTRAST AND MULTI-TIMEPOINT ARTERIAL SPIN LABEL IMAGING

    PubMed Central

    Abernethy, L.J.; Vidyasagar, R.; Pizer, B.L.; Mallucci, C.L.; Avula, S.; Parkes, L.M.

    2014-01-01

    INTRODUCTION: Arterial spin labeling (ASL) is a MR technique that allows for noninvasive quantification of cerebral blood flow (CBF). This technique, predominately used in research, has seen significant technical developments in the last few years that have led to more clinical applications. Currently, the main MR method used to provide perfusion measures in brain tumours is dynamic susceptibility contrast (DSC). DSC traces the signal changes caused by the transit of a bolus of gadolinium contrast agent. ASL has the advantage of not requiring bolus injection of contrast. We have performed a comparative study of DSC and multi-timepoint ASL in paediatric brain tumours (PBT). METHOD: Data from a total of 19 PBT patients (mean age: 9 ± 5 years; 10 females, 9 males) were included in the analyses for this study. Data used were from first presentation scans performed before any surgical intervention. Comparisons of the quantitative measures of CBF and blood arrival time between the two techniques were carried out to test the feasibility of ASL to provide useful quantification measures of CBF in PBT. RESULTS: DSC measurements of tumour blood flow showed a significant decrease in flow in comparison with normal brain, but this is not seen with ASL. There was a strong correlation between ASL and DSC measures of blood flow in normal brain (r = 0.65, p = 0.009), but not in tumour blood flow (r = 0.33, p = 0.2). CONCLUSION: This study demonstrates the feasibility and potential utility of ASL as a non-invasive technique for measuring blood flow in PBT. However, there is a discrepancy between ASL and DSC measures, that may be due to leakage of gadolinium contrast, reflecting the abnormal characteristics of tumour blood vessels in PBT.

  4. Changes in blood biochemical markers before, during, and after a 2-day ultramarathon.

    PubMed

    Arakawa, Kazuyuki; Hosono, Akihiro; Shibata, Kiyoshi; Ghadimi, Reza; Fuku, Mizuho; Goto, Chiho; Imaeda, Nahomi; Tokudome, Yuko; Hoshino, Hideki; Marumoto, Mitsuhiro; Kobayashi, Masaaki; Suzuki, Sadao; Tokudome, Shinkan

    2016-01-01

    We studied changes in blood markers of 18 nonprofessional, middle-aged runners of a 2-day, 130 km ultramarathon. Blood was sampled at baseline, after the goals on the first and second day, and at three time points (1, 3, and 5/6 days) after the race. Blood indices showed three patterns. First pattern indices showed essentially no changes after the two goals and after the race, including red blood cell indices, gamma-glutamyl transferase, and tumor necrosis factor-α. Second pattern markers, including the majority of indices, were elevated during the race (and also after the race for some parameters) and then returned to baseline afterward, including hemolysis/red blood cell destruction markers (indirect bilirubin) and an iron reservoir index (ferritin), muscle damage parameters (uric acid, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase), renal function markers (creatinine and blood urea nitrogen), liver injury index (alanine aminotransferase), lipid metabolism indices (free fatty acid), reactive oxygen species and inflammation parameters (white blood cells, interleukin-6, and C-reactive protein), and energy production and catecholamines (adrenaline, noradrenaline, and dopamine). Third pattern index of a lipid metabolism marker - triglyceride - decreased during the race periods and started returning to baseline from then onward. Some hormonal markers such as insulin, leptin, and adiponectin showed unique patterns. These findings appeared informative for nonprofessional athletes to know about an optimal physical activity level, duration, and total exercise for elevating physical performance and monitoring physical/mental conditioning as well as for prevention of overtraining and physical injuries. PMID:27186145

  5. Changes in blood biochemical markers before, during, and after a 2-day ultramarathon

    PubMed Central

    Arakawa, Kazuyuki; Hosono, Akihiro; Shibata, Kiyoshi; Ghadimi, Reza; Fuku, Mizuho; Goto, Chiho; Imaeda, Nahomi; Tokudome, Yuko; Hoshino, Hideki; Marumoto, Mitsuhiro; Kobayashi, Masaaki; Suzuki, Sadao; Tokudome, Shinkan

    2016-01-01

    We studied changes in blood markers of 18 nonprofessional, middle-aged runners of a 2-day, 130 km ultramarathon. Blood was sampled at baseline, after the goals on the first and second day, and at three time points (1, 3, and 5/6 days) after the race. Blood indices showed three patterns. First pattern indices showed essentially no changes after the two goals and after the race, including red blood cell indices, gamma-glutamyl transferase, and tumor necrosis factor-α. Second pattern markers, including the majority of indices, were elevated during the race (and also after the race for some parameters) and then returned to baseline afterward, including hemolysis/red blood cell destruction markers (indirect bilirubin) and an iron reservoir index (ferritin), muscle damage parameters (uric acid, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase), renal function markers (creatinine and blood urea nitrogen), liver injury index (alanine aminotransferase), lipid metabolism indices (free fatty acid), reactive oxygen species and inflammation parameters (white blood cells, interleukin-6, and C-reactive protein), and energy production and catecholamines (adrenaline, noradrenaline, and dopamine). Third pattern index of a lipid metabolism marker – triglyceride – decreased during the race periods and started returning to baseline from then onward. Some hormonal markers such as insulin, leptin, and adiponectin showed unique patterns. These findings appeared informative for nonprofessional athletes to know about an optimal physical activity level, duration, and total exercise for elevating physical performance and monitoring physical/mental conditioning as well as for prevention of overtraining and physical injuries. PMID:27186145

  6. Genetic markers in the blood of multiple sclerosis patients.

    PubMed

    Marković, S; Bozicević, D; Simić, D; Brzović, Z

    1991-01-01

    Poligenetically determined predisposition to multiple sclerosis (MS) defines the way of immunological reaction to environmental factors and leads to clinically manifest disease. Although the connection between MS and some loci of the HLA system has been established, the hereditary predisposition to MS remains to be elucidated. We determined the phenotypes of monogenic hereditary characteristics linked to the surface of red blood cells that were obtained from 45 MS patients and 458 healthy subjects. The antigens on the erythrocytic surface of the ABO, Rh, MN, Ss, Kell, Kidd, Duffy, P and Lewis system were analyzed. Our results demonstrate that the MS patients differ from the normal subjects with regard to the Rh, ABO and Lewis erythrocytic antigens. The Rh positive factor was present in 95.55% of the MS patients compared to 84.29% of the controls, whereas the Rh negative factor was found in only 4.45% of the MS patients and 15.71% of the healthy subjects. The blood group O was demonstrated in 22.22% of the MS patients compared to 40.42% of the healthy persons. The MS patients had the blood group A in 15.11% of the cases as opposed to 43.99% of the subjects in the control groups. The blood group B was found in 22.22% of the MS patients compared to 11.10% of the controls. The distribution of the Lewis system in the MS patients was also demonstrated to be different from that in the general population. The MS patients were found to have less frequently the Le a+b- phenotype (11.12%) and more frequently Le a- b- (13.33%) compared to the healthy subjects who had the Le a+b- phenotype in 12.00% of the cases and Le a- b- in 5.00%.

  7. Blood-derived DNA methylation markers of cancer risk.

    PubMed

    Marsit, Carmen; Christensen, Brock

    2013-01-01

    The importance of somatic epigenetic alterations in tissues targeted for carcinogenesis is now well recognized and considered a key molecular step in the development of a tumor. Particularly, alteration of gene-specific and genomic DNA methylation has been extensively characterized in tumors, and has become an attractive biomarker of risk due to its specificity and stability in human samples. It also is clear that tumors do not develop as isolated phenomenon in their target tissue, but instead result from altered processes affecting not only the surrounding cells and tissues, but other organ systems, including the immune system. Thus, alterations to DNA methylation profiles detectable in peripheral blood may be useful not only in understanding the carcinogenic process and response to environmental insults, but can also provide critical insights in a systems biological view of tumorigenesis. Research to date has generally focused on how environmental exposures alter genomic DNA methylation content in peripheral blood. More recent work has begun to translate these findings to clinically useful endpoints, by defining the relationship between DNA methylation alterations and cancer risk. This chapter highlights the existing research linking the environment, blood-derived DNA methylation alterations, and cancer risk, and points out how these epigenetic alterations may be contributing fundamentally to carcinogenesis.

  8. Tumour shrinkage measured with first treatment evaluation under VEGF-targeted therapy as prognostic marker in metastatic renal cell carcinoma (mRCC)

    PubMed Central

    Seidel, C; Busch, J; Weikert, S; Steffens, S; Bokemeyer, C; Grünwald, V

    2013-01-01

    Background: The aim of our analysis is to further characterise the prognostic relevance of early tumour shrinkage (TS) during VEGF-targeted therapy in mRCC, in order to explore whether this could define a group of patients with long-term survivorship. Methods: A hundred patients were stratified into five subgroups according to their change of tumour size with first treatment evaluation: −100% to −60% −59% to −30% and −29% to 0% TS or gain of tumour size from 1% to 19% and ⩾20% or occurrence of new lesions (i.e., progressive disease). Results: The median PFS and OS were 10.4 months and 28.2 months, respectively. The median OS stratified according to the subgroups as described above was 77.4, 33.5, 26.9, 30.0 and 14.3 months, respectively. Multivariate analysis revealed early TS as a prognostic marker (P=0.021; HR 1.624). Conclusion: The extent of TS defines a small proportion of patients with an excellent prognosis. Larger studies are warranted to define the relationship of long-term survivorship and extent of TS with targeted therapies. PMID:24169357

  9. Blood Lipids, Infection, and Inflammatory Markers in the Tsimane of Bolivia

    PubMed Central

    Vasunilashorn, Sarinnapha; Crimmins, Eileen M.; Kim, Jung KI; Winking, Jeff; Gurven, Michael; Kaplan, Hillard; Finch, Caleb E.

    2012-01-01

    Objectives Little is known about blood cholesterol (blood-C) levels under conditions of infection and limited diet. This study examines blood-C and markers of infection and inflammation in the Tsimane of the Bolivian Amazon, indigenous forager farmers living in conditions that model preindustrial European populations by their short life expectancy, high load of infections and inflammation, and limited diets. Methods We use multivariate models to determine the relationships between lipid levels and markers of infection and inflammation. Adult Tsimane (N = 418, age 20–84) were characterized for blood lipids, cells, and inflammatory markers in relation to individual loads of parasites and village region. Results Most of the Tsimane (60%) carried at least one parasite species, averaging 1.3 species per person. Serum high-density lipoprotein cholesterol (HDL-C), total cholesterol (total-C), and low-density lipoprotein cholesterol (LDL-C) were below the U.S. norms and varied inversely with markers of infection and inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), immunoglobulin (Ig) E and eosinophil count. Although no relationship of parasite load to blood-C was found, there was an association between anemia and parasite prevalence. Conclusions We conclude that the highly infected environment of the Tsimane is related to low levels of blood total-C, HDL-C, and LDL-C. This may suggest a potential reason why arterial disease is largely absent in the Tsimane. PMID:20721985

  10. The effect of ketanserin upon postoperative blood pressure, cerebral blood flow and oxygen metabolism in patients subjected to craniotomy for cerebral tumours.

    PubMed

    Felding, M; Cold, G E; Jacobsen, C J; Stjernholm, P; Voss, K

    1995-07-01

    Hypertension and cerebral hyperperfusion are often seen in the immediate postoperative period after craniotomy for supratentorial tumours. This study was performed to evaluate the effect of ketanserin, given at the end of the peroperative period, upon cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) before extubation. Mean arterial blood pressure (MABP), cerebral arterio-venous oxygen content difference (AVDO2), PaO2, and PaCO2 were repeatedly measured during the operation, and 180 minutes after extubation. Ten patients were included in this study. The results were compared to those from a recent study in which ten patients served as control. All patients were anaesthetized with thiopentone, fentanyl, nitrous oxide 67%, halothane 0.5% anesthesia. Ten patients were given ketanserin 10-20 mg (mean 18.5 mg) before extubation. There was no significant difference in CBF- and CMRO2 values between the two groups. During the period between closure of the dura and 5 minutes after extubation, an increase in MABP was observed in the control group (P < 0.05) but not in the ketanserin group. During the same period, a decrease in AVDO2 was observed in both groups (P < 0.05) and during the next 10 minutes an increase was observed. However, no difference in AVDO2 values between the two groups was found. These findings suggest that peroperative treatment with ketanserin reduces postoperative hypertension without influencing the cerebral blood flow or metabolism. PMID:7572004

  11. TP53 Mutational Status Is a Potential Marker for Risk Stratification in Wilms Tumour with Diffuse Anaplasia

    PubMed Central

    Chagtai, Tasnim; Popov, Sergey D.; Sebire, Neil J.; Vujanic, Gordan; Perlman, Elizabeth; Anderson, James R.; Grundy, Paul; Dome, Jeffrey S.; Pritchard-Jones, Kathy

    2014-01-01

    Purpose The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whether TP53 mutational status confers additional prognostic information. Patients and Methods We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. Results From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26–16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36–31.7) compared to tumours lacking TP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. Conclusion This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker. PMID:25313908

  12. Flavylium chromophores as species markers for dragon's blood resins from Dracaena and Daemonorops trees.

    PubMed

    Sousa, Micaela M; Melo, Maria J; Parola, A Jorge; Seixas de Melo, J Sérgio; Catarino, Fernando; Pina, Fernando; Cook, Frances E M; Simmonds, Monique S J; Lopes, João A

    2008-10-31

    A simple and rapid liquid chromatographic method with diode-array UV-vis spectrophotometric detection has been developed for the authentication of dragon's blood resins from Dracaena and Daemonorops trees. Using this method it was discovered that the flavylium chromophores, which contribute to the red colour of these resins, differ among the species and could be used as markers to differentiate among species. A study of parameters, such as time of extraction, proportion of MeOH and pH, was undertaken to optimise the extraction of the flavyliums. This method was then used to make extracts from samples of dragon's blood resin obtained from material of known provenance. From the samples analysed 7,6-dihydroxy-5-methoxyflavylium (dracorhodin), 7,4'-dihydroxy-5-methoxyflavylium (dracoflavylium) and 7,4'-dihydroxyflavylium were selected as species markers for Daemonorops spp., Dracaena draco and Dracaena cinnabari, respectively. The chromatograms from these samples were used to build an HPLC-DAD database. The ability to discriminate among species of dragon's blood using the single marker compounds was compared with a principal components analysis of the chromatograms in the HPLC-DAD database. The results from the HPLC-DAD method based on the presence of these flavylium markers was unequivocal. The HPLC-DAD method was subsequently applied to 37 samples of dragon blood resins from the historical samples in the Economic Botany Collection, Royal Botanic Gardens, Kew. The method identified anomalies in how samples in this collection had been labelled. It is clear that the method can be used to evaluate the provenance of samples used in different areas of cultural heritage. It also could be used to monitor the trade of endangered species of dragon's blood and the species being used in complex formulations of traditional Chinese medicine.

  13. Flavylium chromophores as species markers for dragon's blood resins from Dracaena and Daemonorops trees.

    PubMed

    Sousa, Micaela M; Melo, Maria J; Parola, A Jorge; Seixas de Melo, J Sérgio; Catarino, Fernando; Pina, Fernando; Cook, Frances E M; Simmonds, Monique S J; Lopes, João A

    2008-10-31

    A simple and rapid liquid chromatographic method with diode-array UV-vis spectrophotometric detection has been developed for the authentication of dragon's blood resins from Dracaena and Daemonorops trees. Using this method it was discovered that the flavylium chromophores, which contribute to the red colour of these resins, differ among the species and could be used as markers to differentiate among species. A study of parameters, such as time of extraction, proportion of MeOH and pH, was undertaken to optimise the extraction of the flavyliums. This method was then used to make extracts from samples of dragon's blood resin obtained from material of known provenance. From the samples analysed 7,6-dihydroxy-5-methoxyflavylium (dracorhodin), 7,4'-dihydroxy-5-methoxyflavylium (dracoflavylium) and 7,4'-dihydroxyflavylium were selected as species markers for Daemonorops spp., Dracaena draco and Dracaena cinnabari, respectively. The chromatograms from these samples were used to build an HPLC-DAD database. The ability to discriminate among species of dragon's blood using the single marker compounds was compared with a principal components analysis of the chromatograms in the HPLC-DAD database. The results from the HPLC-DAD method based on the presence of these flavylium markers was unequivocal. The HPLC-DAD method was subsequently applied to 37 samples of dragon blood resins from the historical samples in the Economic Botany Collection, Royal Botanic Gardens, Kew. The method identified anomalies in how samples in this collection had been labelled. It is clear that the method can be used to evaluate the provenance of samples used in different areas of cultural heritage. It also could be used to monitor the trade of endangered species of dragon's blood and the species being used in complex formulations of traditional Chinese medicine. PMID:18817913

  14. Raman spectroscopy of stored red blood cells: evaluating clinically-relevant biochemical markers in donated blood

    NASA Astrophysics Data System (ADS)

    Atkins, Chad G.; Buckley, Kevin; Chen, Deborah; Schulze, H. G.; Devine, Dana V.; Blades, Michael W.; Turner, Robin F. B.

    2015-07-01

    Modern transfusion medicine relies on the safe, secure, and cost-effective delivery of donated red blood cells (RBCs). Once isolated, RBCs are suspended in a defined additive solution and stored in plastic blood bags in which, over time, they undergo chemical, physiological, and morphological changes that may have a deleterious impact on some patients. Regulations limit the storage period to 42 days and the cells do not routinely undergo analytical testing before use. In this study, we use Raman spectroscopy to interrogate stored RBCs and we identify metabolic and cell-breakdown products, such as haemoglobin and membrane fragments, that build-up in the blood bags as the cells age. Our work points the way to the development of an instrument which could quickly and easily assess the biochemical nature of stored RBC units before they are transfused.

  15. The prognostic value of the tumour marker Cyfra 21-1 in carcinoma of head and neck and its role in early detection of recurrent disease

    PubMed Central

    Doweck, I; Barak, M; Uri, N; Greenberg, E

    2000-01-01

    This study examines a new tumour marker, Cyfra 21-1, as a prognostic marker in predicting the survival of H&N cancer patients, and its correlation with clinical outcome during prolonged follow up of these patients. The study included 67 patients with primary detection of carcinoma of H&N. The survival of these patients was evaluated in correlation with the disease stage and Cyfra 21-1 levels at initial diagnosis. 38 patients were followed clinically and with serial assays for at least 12 months, or until recurrence was diagnosed. Cyfra 21-1 levels were determined periodically, using an Elisa kit. Patients with Cyfra 21-1 < 1.5 ng ml–1had a higher survival rate compared to patients with Cyfra 21-1 ≥ 1.5 ng ml–1(63% vs. 20%, respectively). The risk ratio of Ln(Cyfra 21-1) is 1.62 (P = 0.028). In a Cox regression model that included the disease stage and Ln(Cyfra 21-1), Ln(Cyfra 21-1) was preferred as the main parameter for predicting patients survival. In 83% of the 12 patients with recurrent or residual disease, Cyfra 21-1 was elevated before or during clinical detection of the recurrence. Cyfra 21-1 was found to be a prognostic marker for carcinoma of H&N, unrelated to the stage of the disease. Elevated levels of Cyfra 21-1 without clinical evidence of disease can be attributed to the marker's mean lead-time as compared to the clinical appearance of the disease. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11104568

  16. A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours.

    PubMed

    Torres, Luz-María; Rivera-Espinosa, Liliana; Chávez-Pacheco, Juan L; Navas, Carlos F; Demetrio, Joel A; Alemón-Medina, Radamés; Trujillo, Francisca; Pérez, Martín; Zapata, Martha M; Cárdenas, Rocío; Salinas, Citlaltepetl; Aquino, Arnoldo; Velázquez-Cruz, Rafael; Castillejos, Manuel-de-Jesús

    2015-01-01

    Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100-10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7-19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4-Q75 29.0) and 3.8 μmol/L (Q25 1.5-Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients.

  17. A New Method to Quantify Ifosfamide Blood Levels Using Dried Blood Spots and UPLC-MS/MS in Paediatric Patients with Embryonic Solid Tumours

    PubMed Central

    Chávez-Pacheco, Juan L.; Navas, Carlos F.; Demetrio, Joel A.; Alemón-Medina, Radamés; Trujillo, Francisca; Pérez, Martín; Zapata, Martha M.; Cárdenas, Rocío; Salinas, Citlaltepetl; Aquino, Arnoldo; Velázquez-Cruz, Rafael; Castillejos, Manuel-de-Jesús

    2015-01-01

    Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100–10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7–19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4–Q75 29.0) and 3.8 μmol/L (Q25 1.5–Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients. PMID:26600181

  18. OP40POST-OPERATIVE T2 HYPERINTENSITY IN PERI RESECTION MARGIN FOLLOWING AWAKE MACROSCOPIC INTRAGYRAL TOTAL RESECTION OF LOW GRADE GLIOMA IS NOT A RELIABLE MARKER OF RESIDUAL TUMOUR

    PubMed Central

    Khor, Huai Hao; Bryne, Paul; Basu, Surajit

    2014-01-01

    INTRODUCTION: Awake craniotomy for resection of tumours from eloquent brain area is an established technique. We describe six year outcome data of awake surgery for radiological low grade glial series tumours resected using natural subpial and vascular intergyral planes. We describe immediate post-operative radiological findings and its correlation with long term outcome. METHOD: This is a retrospective analysis of clinical and radiological records of awake craniotomies undertaken between 2007-2014. Patients were identified from operative department records and radiological data were retrieved from hospital's electronic image archive. A correlative analysis was done between immediate post-operative T2 changes and long term tumour progression. RESULTS: 38 patients underwent awake craniotomy with average age of 41.1 yrs(range 21-79). 6 patients have died (average survival 2.69 years, range 1-84 months) due to tumour progression. 5 of these had initial diagnosis of grade 3 tumour or above; 1 patient had malignant melanoma. 32 (85%) patients have survived the survey period(2.38 years, range 1-72 months). On MRI most patients had post-operative T2 hyperintensity around the resection margins. The T2 hyperintensity persisted in 6 patient. This was correlated with either a peri-operative decision to sub-totally resect, or subsequent tumour progression. In other 32 patients the T2 changes either reduced or remained static. Histology of these patients showed 4 grade 2, 22 grade 3, and 6 grade 4 tumours. CONCLUSION: T2 changes in peri-resection brain parenchyma following a macroscopic complete resection of low grade tumours using awake techniques is not a reliable marker of tumour residual or recurrence. 85% of such changes resolved.

  19. New markers for old stains: stable mRNA markers for blood and saliva identification from up to 16-year-old stains.

    PubMed

    Zubakov, Dmitry; Kokshoorn, Mieke; Kloosterman, Ate; Kayser, Manfred

    2009-01-01

    In forensic science, the unequivocal identification of the cellular origin of crime scene samples used for DNA profiling can provide crucial information for crime scene reconstruction. We have previously shown that various mRNA markers from genes with expression patterns specific for blood and saliva can be established from whole-genome expression analysis of time-wise degraded samples and were stable enough to specifically identify blood and saliva stains up to 180 days of age. Here, we showed that nine blood-specific and five saliva-specific mRNA markers can be amplified successfully and reliably in much older blood (13-16 years) and saliva (2-6 years) stains, respectively, suggesting their suitability for tissue identification in forensic case work. Moreover, our findings imply that forensic RNA testing can be reliable and robust if degraded samples are considered in the marker ascertainment procedure, with promising expectations beyond tissue identification purposes. PMID:18594850

  20. Comparative analysis of Napsin A, alpha-methylacyl-coenzyme A racemase (AMACR, P504S), and hepatocyte nuclear factor 1 beta as diagnostic markers of ovarian clear cell carcinoma: an immunohistochemical study of 279 ovarian tumours.

    PubMed

    Fadare, Oluwole; Zhao, Chengquan; Khabele, Dineo; Parkash, Vinita; Quick, Charles M; Gwin, Katja; Desouki, Mohamed M

    2015-02-01

    Napsin A and α-methylacyl-coenzyme A racemase (AMACR, P504S) have recently been described as being frequently expressed in clear cell carcinomas (CCC) of the gynecological tract. The present study was conducted to assess the test performance of these newer markers relative to the more traditional marker, hepatocyte nuclear factor 1β (HNF1β), in a large and histotypically diverse dataset. A total of 279 ovarian tumours in tissue microarrays were immunohistochemically assessed for the expression of Napsin A, AMACR and HNF1β. HNF1β, Napsin A and AMACR were expressed in 92%, 82% and 63% of 65 CCC, 7%, 1% and 1% of 101 serous carcinomas, 37%, 5.3% and 0% of 19 endometrioid carcinomas, 60%, 0% and 0% of 45 mucinous tumours, 100%, 0% and 0% of seven yolk sac tumours, and 0%, 16.7% and 16.7% of six steroid cell tumours NOS, respectively. All other tumours, including 18 adult-type granulosa cell tumours, eight dysgerminomas and nine other miscellaneous tumour types were negative for all three markers. Using a benchmark of ≥1% of tumour cells for positivity and CCC as the diagnostic end-point, the sensitivity, specificity, negative predictive value and positive predictive value of Napsin A expression were 0.82, 0.99, 0.94, and 0.98, respectively (odds ratio 439, p < 0.0001). Respective parameters were 0.92, 0.79, 0.97, and 0.58 (odds ratio 44, p < 0.0001) for HNF1β and 0.63, 0.99, 0.89, and 0.5 (odds ratio 112, p < 0.0001) for AMACR. The combination of any two positive markers, irrespective of the staining pattern of the third, significantly predicted the CCC histotype in every analytic scenario. In summary, HNF1β is highly sensitive but is suboptimally specific in isolation, whereas AMACR is highly specific but is suboptimally sensitive. Napsin A is specific but of intermediate sensitivity. Napsin A, AMACR and HNF1β are all viable markers of CCC that can be deployed as components of larger panels when CCC is a diagnostic consideration.

  1. Comparative analysis of Napsin A, alpha-methylacyl-coenzyme A racemase (AMACR, P504S), and hepatocyte nuclear factor 1 beta as diagnostic markers of ovarian clear cell carcinoma: an immunohistochemical study of 279 ovarian tumours.

    PubMed

    Fadare, Oluwole; Zhao, Chengquan; Khabele, Dineo; Parkash, Vinita; Quick, Charles M; Gwin, Katja; Desouki, Mohamed M

    2015-02-01

    Napsin A and α-methylacyl-coenzyme A racemase (AMACR, P504S) have recently been described as being frequently expressed in clear cell carcinomas (CCC) of the gynecological tract. The present study was conducted to assess the test performance of these newer markers relative to the more traditional marker, hepatocyte nuclear factor 1β (HNF1β), in a large and histotypically diverse dataset. A total of 279 ovarian tumours in tissue microarrays were immunohistochemically assessed for the expression of Napsin A, AMACR and HNF1β. HNF1β, Napsin A and AMACR were expressed in 92%, 82% and 63% of 65 CCC, 7%, 1% and 1% of 101 serous carcinomas, 37%, 5.3% and 0% of 19 endometrioid carcinomas, 60%, 0% and 0% of 45 mucinous tumours, 100%, 0% and 0% of seven yolk sac tumours, and 0%, 16.7% and 16.7% of six steroid cell tumours NOS, respectively. All other tumours, including 18 adult-type granulosa cell tumours, eight dysgerminomas and nine other miscellaneous tumour types were negative for all three markers. Using a benchmark of ≥1% of tumour cells for positivity and CCC as the diagnostic end-point, the sensitivity, specificity, negative predictive value and positive predictive value of Napsin A expression were 0.82, 0.99, 0.94, and 0.98, respectively (odds ratio 439, p < 0.0001). Respective parameters were 0.92, 0.79, 0.97, and 0.58 (odds ratio 44, p < 0.0001) for HNF1β and 0.63, 0.99, 0.89, and 0.5 (odds ratio 112, p < 0.0001) for AMACR. The combination of any two positive markers, irrespective of the staining pattern of the third, significantly predicted the CCC histotype in every analytic scenario. In summary, HNF1β is highly sensitive but is suboptimally specific in isolation, whereas AMACR is highly specific but is suboptimally sensitive. Napsin A is specific but of intermediate sensitivity. Napsin A, AMACR and HNF1β are all viable markers of CCC that can be deployed as components of larger panels when CCC is a diagnostic consideration. PMID:25551297

  2. Blood acylpeptide hydrolase activity is a sensitive marker for exposure to some organophosphate toxicants.

    PubMed

    Quistad, Gary B; Klintenberg, Rebecka; Casida, John E

    2005-08-01

    Acylpeptide hydrolase (APH) unblocks N-acetyl peptides. It is a major serine hydrolase in rat blood, brain, and liver detected by derivatization with (3)H-diisopropyl fluorophosphate (DFP) or a biotinylated fluorophosphonate. Although APH does not appear to be a primary target of acute poisoning by organophosphorus (OP) compounds, the inhibitor specificity of this secondary target is largely unknown. This study fills the gap and emphasizes blood APH as a potential marker of OP exposure. The most potent in vitro inhibitors for human erythrocyte and mouse brain APH are DFP (IC(50) 11-17 nM), chlorpyrifos oxon (IC(50) 21-71 nM), dichlorvos (IC(50) 230-560 nM), naled (IC(50) 370-870 nM), and their analogs with modified alkyl substituents. (3)H-diisopropyl fluorophosphate is a potent inhibitor of mouse blood and brain APH in vivo (ED(50) 0.09-0.2 mg/kg and 0.02-0.03 mg/l for ip and vapor exposure, respectively). Mouse blood and brain APH and blood butyrylcholinesterase (BChE) are of similar sensitivity to DFP in vitro and in vivo (ip and vapor exposure), but APH inhibition is much more persistent in vivo (still >80% inhibition after 4 days). The inhibitory potency of OP pesticides in vivo in mice varies from APH selective (dichlorvos, naled, and trichlorfon), to APH and BChE selective (profenofos and tribufos), to ChE selective or nonselective (many commercial insecticides). Sarin administered ip at a lethal dose to guinea pigs inhibits blood acetylcholinesterase and BChE completely but erythrocyte APH only partially. Blood APH activity is therefore a sensitive marker for exposure to some but not all OP pesticides and chemical warfare agents. PMID:15888665

  3. Blood ammonia and lactate as markers of muscle metabolites during leg press exercise.

    PubMed

    Gorostiaga, Esteban M; Navarro-Amézqueta, Ion; Calbet, Jose A L; Sánchez-Medina, Luis; Cusso, Roser; Guerrero, Mario; Granados, Cristina; González-Izal, Miriam; Ibáñez, Javier; Izquierdo, Mikel

    2014-10-01

    To examine whether blood lactate and ammonia concentrations can be used to estimate the functional state of the muscle contractile machinery with regard to muscle lactate and adenosine triphosphate (ATP) levels during leg press exercise. Thirteen men (age, 34 ± 5 years; 1 repetition maximum leg press strength 199 ± 33 kg) performed either 5 sets of 10 repetitions to failure (5×10RF), or 10 sets of 5 repetitions not to failure (10×5RNF) with the same initial load (10RM) and interset rests (2 minutes) on 2 separate sessions in random order. Capillary blood samples were obtained before and during exercise and recovery. Six subjects underwent vastus lateralis muscle biopsies at rest, before the first set and after the final exercise set. The 5×10RF resulted in a significant and marked decrease in power output (37%), muscle ATP content (24%), and high levels of muscle lactate (25.0 ± 8.1 mmol·kg wet weight), blood lactate (10.3 ± 2.6 mmol·L), and blood ammonia (91.6 ± 40.5 μmol·L). During 10×5RNF no or minimal changes were observed. Significant correlations were found between: (a) blood ammonia and muscle ATP (r = -0.75), (b) changes in peak power output and blood ammonia (r = -0.87) and blood lactate (r = -0.84), and (c) blood and muscle lactate (r = 0.90). Blood lactate and ammonia concentrations can be used as extracellular markers for muscle lactate and ATP contents, respectively. The decline in mechanical power output can be used to indirectly estimate blood ammonia and lactate during leg press exercise.

  4. Stability of cytokines, chemokines and soluble activation markers in unprocessed blood stored under different conditions

    PubMed Central

    Aziz, Najib; Detels, Roger; Quint, Joshua J.; Li, Qian; Gjertson, David; Butch, Anthony W.

    2016-01-01

    Background Biomarkers such as cytokines, chemokines, and soluble activation markers can be unstable when processing of blood is delayed. The stability of various biomarkers in serum and plasma was investigated when unprocessed blood samples were stored for up to 24 h at room and refrigerator temperature. Methods Blood was collected from 16 healthy volunteers. Unprocessed serum, EDTA and heparinized blood was stored at room (20–25 °C) and refrigerator temperature (4–8 °C) for 0.5, 2, 4, 6, 8, and 24 h after collection before centrifugation and separation of serum and plasma. Samples were batch tested for various biomarkers using commercially available immunoassays. Statistically significant changes were determined using the generalized estimating equation. Results IFN-γ, sIL-2Rα, sTNF-RII and β2-microglobulin were stable in unprocessed serum, EDTA and heparinized blood samples stored at either room or refrigerator temperature for up to 24 h. IL-6, TNF-α, MIP-1β and RANTES were unstable in heparinized blood at room temperature; TNF-α, and MIP-1β were unstable in unprocessed serum at room temperature; IL-12 was unstable in unprocessed serum at refrigerator temperature; and neopterin was unstable in unprocessed EDTA blood at room temperature. IL-1ra was stable only in unprocessed serum at room temperature. Conclusion All the biomarkers studied, with the exception of IL-1ra, were stable in unprocessed EDTA blood stored at refrigerator temperature for 24 h. This indicates that blood for these biomarkers should be collected in EDTA and if delays in processing are anticipated the unseparated blood should be stored at refrigerator temperature until processing. PMID:27208752

  5. Blood Transcriptomic Markers in Patients with Late-Onset Major Depressive Disorder.

    PubMed

    Miyata, Shigeo; Kurachi, Masashi; Okano, Yoshiko; Sakurai, Noriko; Kobayashi, Ayumi; Harada, Kenichiro; Yamagata, Hirotaka; Matsuo, Koji; Takahashi, Keisuke; Narita, Kosuke; Fukuda, Masato; Ishizaki, Yasuki; Mikuni, Masahiko

    2016-01-01

    We investigated transcriptomic markers of late-onset major depressive disorder (LOD; onset age of first depressive episode ≥ 50 years) from the genes expressed in blood cells and identified state-dependent transcriptomic markers in these patients. We assessed the genes expressed in blood cells by microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD. To select potential candidates from those probes, we assessed the genes expressed in the blood of an animal model of depression, ovariectomized female mice exposed to chronic ultra-mild stress, by microarray and cross-matched the differentially expressed genes between the patients and the model mice. We identified 14 differentially expressed genes that were similarly changed in both patients and the model mice. By assessing statistical significance using real-time quantitative PCR (RT-qPCR), the following 4 genes were selected as candidates: cell death-inducing DFFA-like effector c (CIDEC), ribonuclease 1 (RNASE1), solute carrier family 36 member-1 (SLC36A1), and serine/threonine/tyrosine interacting-like 1 (STYXL1). The discriminating ability of these 4 candidate genes was evaluated in an independent cohort that was validated. Among them, CIDEC showed the greatest discriminant validity (sensitivity 91.3% and specificity 87.5%). Thus, these 4 biomarkers should be helpful for properly diagnosing LOD.

  6. Blood Transcriptomic Markers in Patients with Late-Onset Major Depressive Disorder.

    PubMed

    Miyata, Shigeo; Kurachi, Masashi; Okano, Yoshiko; Sakurai, Noriko; Kobayashi, Ayumi; Harada, Kenichiro; Yamagata, Hirotaka; Matsuo, Koji; Takahashi, Keisuke; Narita, Kosuke; Fukuda, Masato; Ishizaki, Yasuki; Mikuni, Masahiko

    2016-01-01

    We investigated transcriptomic markers of late-onset major depressive disorder (LOD; onset age of first depressive episode ≥ 50 years) from the genes expressed in blood cells and identified state-dependent transcriptomic markers in these patients. We assessed the genes expressed in blood cells by microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD. To select potential candidates from those probes, we assessed the genes expressed in the blood of an animal model of depression, ovariectomized female mice exposed to chronic ultra-mild stress, by microarray and cross-matched the differentially expressed genes between the patients and the model mice. We identified 14 differentially expressed genes that were similarly changed in both patients and the model mice. By assessing statistical significance using real-time quantitative PCR (RT-qPCR), the following 4 genes were selected as candidates: cell death-inducing DFFA-like effector c (CIDEC), ribonuclease 1 (RNASE1), solute carrier family 36 member-1 (SLC36A1), and serine/threonine/tyrosine interacting-like 1 (STYXL1). The discriminating ability of these 4 candidate genes was evaluated in an independent cohort that was validated. Among them, CIDEC showed the greatest discriminant validity (sensitivity 91.3% and specificity 87.5%). Thus, these 4 biomarkers should be helpful for properly diagnosing LOD. PMID:26926397

  7. Blood Transcriptomic Markers in Patients with Late-Onset Major Depressive Disorder

    PubMed Central

    Miyata, Shigeo; Kurachi, Masashi; Okano, Yoshiko; Sakurai, Noriko; Kobayashi, Ayumi; Harada, Kenichiro; Yamagata, Hirotaka; Matsuo, Koji; Takahashi, Keisuke; Narita, Kosuke; Fukuda, Masato; Ishizaki, Yasuki; Mikuni, Masahiko

    2016-01-01

    We investigated transcriptomic markers of late-onset major depressive disorder (LOD; onset age of first depressive episode ≥ 50 years) from the genes expressed in blood cells and identified state-dependent transcriptomic markers in these patients. We assessed the genes expressed in blood cells by microarray and found that the expression levels of 3,066 probes were state-dependently changed in the blood cells of patients with LOD. To select potential candidates from those probes, we assessed the genes expressed in the blood of an animal model of depression, ovariectomized female mice exposed to chronic ultra-mild stress, by microarray and cross-matched the differentially expressed genes between the patients and the model mice. We identified 14 differentially expressed genes that were similarly changed in both patients and the model mice. By assessing statistical significance using real-time quantitative PCR (RT-qPCR), the following 4 genes were selected as candidates: cell death-inducing DFFA-like effector c (CIDEC), ribonuclease 1 (RNASE1), solute carrier family 36 member-1 (SLC36A1), and serine/threonine/tyrosine interacting-like 1 (STYXL1). The discriminating ability of these 4 candidate genes was evaluated in an independent cohort that was validated. Among them, CIDEC showed the greatest discriminant validity (sensitivity 91.3% and specificity 87.5%). Thus, these 4 biomarkers should be helpful for properly diagnosing LOD. PMID:26926397

  8. 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…

  9. Improved age determination of blood and teeth samples using a selected set of DNA methylation markers

    PubMed Central

    Kamalandua, Aubeline

    2015-01-01

    Age estimation from DNA methylation markers has seen an exponential growth of interest, not in the least from forensic scientists. The current published assays, however, can still be improved by lowering the number of markers in the assay and by providing more accurate models to predict chronological age. From the published literature we selected 4 age-associated genes (ASPA, PDE4C, ELOVL2, and EDARADD) and determined CpG methylation levels from 206 blood samples of both deceased and living individuals (age range: 0–91 years). This data was subsequently used to compare prediction accuracy with both linear and non-linear regression models. A quadratic regression model in which the methylation levels of ELOVL2 were squared showed the highest accuracy with a Mean Absolute Deviation (MAD) between chronological age and predicted age of 3.75 years and an adjusted R2 of 0.95. No difference in accuracy was observed for samples obtained either from living and deceased individuals or between the 2 genders. In addition, 29 teeth from different individuals (age range: 19–70 years) were analyzed using the same set of markers resulting in a MAD of 4.86 years and an adjusted R2 of 0.74. Cross validation of the results obtained from blood samples demonstrated the robustness and reproducibility of the assay. In conclusion, the set of 4 CpG DNA methylation markers is capable of producing highly accurate age predictions for blood samples from deceased and living individuals PMID:26280308

  10. Blood transcriptomic markers for major depression: from animal models to clinical settings.

    PubMed

    Redei, Eva E; Mehta, Neha S

    2015-05-01

    Depression is a heterogeneous disorder and, similar to other spectrum disorders, its manifestation varies by age of onset, severity, comorbidity, treatment responsiveness, and other factors. A laboratory blood test based on specific biomarkers for major depressive disorder (MDD) and its subgroups could increase diagnostic accuracy and expedite the initiation of treatment. We identified candidate blood biomarkers by examining genome-wide expression differences in the blood of animal models representing both the genetic and environmental/stress etiologies of depression. Human orthologs of the resulting transcript panel were tested in pilot studies. Transcript abundance of 11 blood markers differentiated adolescent subjects with early-onset MDD from adolescents with no disorder (ND). A set of partly overlapping transcripts distinguished adolescent patients who had comorbid anxiety disorders from those with only MDD. In adults, blood levels of nine transcripts discerned subjects with MDD from ND controls. Even though cognitive behavioral therapy (CBT) resulted in remission of some patients, the levels of three transcripts consistently signaled prior MDD status. A coexpression network of transcripts seems to predict responsiveness to CBT. Thus, our approach can be developed into clinically valid diagnostic panels of blood transcripts for different manifestations of MDD, potentially reducing diagnostic heterogeneity and advancing individualized treatment strategies.

  11. Soluble tumour necrosis factor (TNF)-receptor levels in serum as markers of anti-viral host reactivity

    PubMed Central

    Bartholdy, C; Nansen, A; Marker, O; Thomsen, A R

    1999-01-01

    The role of soluble receptors for TNF-α (sTNF-Rs) as markers of virus-induced host responses was studied by the use of murine model infections. A marked elevation in serum levels of sTNF-R75, but not sTNF-R55, was found 1 day after infection with vesicular stomatitis virus (VSV). In mice infected with lymphocytic choriomeningitis virus (LCMV), an early increase was also revealed, but peak levels of sTNF-R75 were observed later temporally related to maximal T cell-mediated anti-viral activity. Analysing different well characterized knockout mice, it was found that elevated release of sTNF-R75 into serum early after VSV infection was independent of T cells, whereas interferon (IFN)-α/β seemed to be a major mediator. In contrast, increased release of sTNF-R75 into serum 8 days post-LCMV infection was mediated via T cells but independently of both CD40 ligand and IFN-γ. A simple correlation between release of sTNF-Rs in vivo and macrophage activation in vitro was not present. These findings indicate that sTNF-R75 is indeed a sensitive marker of both innate and specific cell-mediated host reactivity during viral infection, but it is not correlated to a single immunological parameter. PMID:10337022

  12. Inflammatory Markers in Blood and Exhaled Air after Short-Term Exposure to Cooking Fumes

    PubMed Central

    Svedahl, Sindre Rabben

    2013-01-01

    Objectives: Cooking fumes contain aldehydes, alkanoic acids, polycyclic aromatic hydrocarbons, and heterocyclic compounds. The inhalation of cooking fumes entails a risk of deleterious health effects. The aim of this study was to see if the inhalation of cooking fumes alters the expression of inflammatory reactions in the bronchial mucosa and its subsequent systemic inflammatory response in blood biomarkers. Methods: Twenty-four healthy volunteers stayed in a model kitchen on two different occasions for 2 or 4h. On the first occasion, there was only exposure to normal air, and on the second, there was exposure to controlled levels of cooking fumes. On each occasion, samples of blood, exhaled air, and exhaled breath condensate (EBC) were taken three times in 24h and inflammatory markers were measured from all samples. Results: There was an increase in the concentration of the d-dimer in blood from 0.27 to 0.28mg ml–1 on the morning after exposure to cooking fumes compared with the levels the morning before (P-value = 0.004). There was also a trend of an increase in interleukin (IL)-6 in blood, ethane in exhaled air, and IL-1β in EBC after exposure to cooking fumes. In a sub-analysis of 12 subjects, there was also an increase in the levels of ethane—from 2.83 parts per billion (ppb) on the morning before exposure to cooking fumes to 3.53 ppb on the morning after exposure (P = 0.013)—and IL-1β—from 1.04 on the morning before exposure to cooking fumes to 1.39 pg ml–1 immediately after (P = 0.024). Conclusion: In our experimental setting, we were able to unveil only small changes in the levels of inflammatory markers in exhaled air and in blood after short-term exposure to moderate concentrations of cooking fumes. PMID:23179989

  13. Blood metabolite markers of neocortical amyloid-β burden: discovery and enrichment using candidate proteins

    PubMed Central

    Voyle, N; Kim, M; Proitsi, P; Ashton, N J; Baird, A L; Bazenet, C; Hye, A; Westwood, S; Chung, R; Ward, M; Rabinovici, G D; Lovestone, S; Breen, G; Legido-Quigley, C; Dobson, R J B; Kiddle, S J

    2016-01-01

    We believe this is the first study to investigate associations between blood metabolites and neocortical amyloid burden (NAB) in the search for a blood-based biomarker for Alzheimer's disease (AD). Further, we present the first multi-modal analysis of blood markers in this field. We used blood plasma samples from 91 subjects enrolled in the University of California, San Francisco Alzheimer's Disease Research Centre. Non-targeted metabolomic analysis was used to look for associations with NAB using both single and multiple metabolic feature models. Five metabolic features identified subjects with high NAB, with 72% accuracy. We were able to putatively identify four metabolites from this panel and improve the model further by adding fibrinogen gamma chain protein measures (accuracy=79%). One of the five metabolic features was studied in the Alzheimer's Disease Neuroimaging Initiative cohort, but results were inconclusive. If replicated in larger, independent studies, these metabolic features and proteins could form the basis of a blood test with potential for enrichment of amyloid pathology in anti-amyloid trials. PMID:26812040

  14. Blood-Borne Markers of Fatigue in Competitive Athletes – Results from Simulated Training Camps

    PubMed Central

    Hecksteden, Anne; Skorski, Sabrina; Schwindling, Sascha; Hammes, Daniel; Pfeiffer, Mark; Kellmann, Michael; Ferrauti, Alexander; Meyer, Tim

    2016-01-01

    Assessing current fatigue of athletes to fine-tune training prescriptions is a critical task in competitive sports. Blood-borne surrogate markers are widely used despite the scarcity of validation trials with representative subjects and interventions. Moreover, differences between training modes and disciplines (e.g. due to differences in eccentric force production or calorie turnover) have rarely been studied within a consistent design. Therefore, we investigated blood-borne fatigue markers during and after discipline-specific simulated training camps. A comprehensive panel of blood-born indicators was measured in 73 competitive athletes (28 cyclists, 22 team sports, 23 strength) at 3 time-points: after a run-in resting phase (d 1), after a 6-day induction of fatigue (d 8) and following a subsequent 2-day recovery period (d 11). Venous blood samples were collected between 8 and 10 a.m. Courses of blood-borne indicators are considered as fatigue dependent if a significant deviation from baseline is present at day 8 (Δfatigue) which significantly regresses towards baseline until day 11 (Δrecovery). With cycling, a fatigue dependent course was observed for creatine kinase (CK; Δfatigue 54±84 U/l; Δrecovery -60±83 U/l), urea (Δfatigue 11±9 mg/dl; Δrecovery -10±10 mg/dl), free testosterone (Δfatigue -1.3±2.1 pg/ml; Δrecovery 0.8±1.5 pg/ml) and insulin linke growth factor 1 (IGF-1; Δfatigue -56±28 ng/ml; Δrecovery 53±29 ng/ml). For urea and IGF-1 95% confidence intervals for days 1 and 11 did not overlap with day 8. With strength and high-intensity interval training, respectively, fatigue-dependent courses and separated 95% confidence intervals were present for CK (strength: Δfatigue 582±649 U/l; Δrecovery -618±419 U/l; HIIT: Δfatigue 863±952 U/l; Δrecovery -741±842 U/l) only. These results indicate that, within a comprehensive panel of blood-borne markers, changes in fatigue are most accurately reflected by urea and IGF-1 for cycling and by CK

  15. Blood-Borne Markers of Fatigue in Competitive Athletes - Results from Simulated Training Camps.

    PubMed

    Hecksteden, Anne; Skorski, Sabrina; Schwindling, Sascha; Hammes, Daniel; Pfeiffer, Mark; Kellmann, Michael; Ferrauti, Alexander; Meyer, Tim

    2016-01-01

    Assessing current fatigue of athletes to fine-tune training prescriptions is a critical task in competitive sports. Blood-borne surrogate markers are widely used despite the scarcity of validation trials with representative subjects and interventions. Moreover, differences between training modes and disciplines (e.g. due to differences in eccentric force production or calorie turnover) have rarely been studied within a consistent design. Therefore, we investigated blood-borne fatigue markers during and after discipline-specific simulated training camps. A comprehensive panel of blood-born indicators was measured in 73 competitive athletes (28 cyclists, 22 team sports, 23 strength) at 3 time-points: after a run-in resting phase (d 1), after a 6-day induction of fatigue (d 8) and following a subsequent 2-day recovery period (d 11). Venous blood samples were collected between 8 and 10 a.m. Courses of blood-borne indicators are considered as fatigue dependent if a significant deviation from baseline is present at day 8 (Δfatigue) which significantly regresses towards baseline until day 11 (Δrecovery). With cycling, a fatigue dependent course was observed for creatine kinase (CK; Δfatigue 54±84 U/l; Δrecovery -60±83 U/l), urea (Δfatigue 11±9 mg/dl; Δrecovery -10±10 mg/dl), free testosterone (Δfatigue -1.3±2.1 pg/ml; Δrecovery 0.8±1.5 pg/ml) and insulin linke growth factor 1 (IGF-1; Δfatigue -56±28 ng/ml; Δrecovery 53±29 ng/ml). For urea and IGF-1 95% confidence intervals for days 1 and 11 did not overlap with day 8. With strength and high-intensity interval training, respectively, fatigue-dependent courses and separated 95% confidence intervals were present for CK (strength: Δfatigue 582±649 U/l; Δrecovery -618±419 U/l; HIIT: Δfatigue 863±952 U/l; Δrecovery -741±842 U/l) only. These results indicate that, within a comprehensive panel of blood-borne markers, changes in fatigue are most accurately reflected by urea and IGF-1 for cycling and by CK

  16. Circulating tumour cells: insights into tumour heterogeneity.

    PubMed

    Hayes, D F; Paoletti, C

    2013-08-01

    Tumour heterogeneity is a major barrier to cure breast cancer. It can exist between patients with different intrinsic subtypes of breast cancer or within an individual patient with breast cancer. In the latter case, heterogeneity has been observed between different metastatic sites, between metastatic sites and the original primary tumour, and even within a single tumour at either a metastatic or a primary site. Tumour heterogeneity is a function of two separate, although linked, processes. First, genetic instability is a hallmark of malignancy, and results in 'fixed' genetic changes that are almost certainly carried forward through progression of the cancer over time, with increasingly complex additional genetic changes in new metastases as they arise. The second type of heterogeneity is due to differential but 'plastic' expression of various genes important in the biology and response to various therapies. Together, these processes result in highly variable cancers with differential response, and resistance, to both targeted (e.g. endocrine or anti-human epithelial growth receptor type 2 (HER2) agents) and nontargeted therapies (e.g. chemotherapy). Ideally, tumour heterogeneity would be monitored over time, especially in relation to therapeutic strategies. However, biopsies of metastases require invasive and costly procedures, and biopsies of multiple metastases, or serially over time, are impractical. Circulating tumour cells (CTCs) represent a potential surrogate for tissue-based cancer and therefore might provide the opportunity to monitor serial changes in tumour biology. Recent advances have enabled accurate and reliable quantification and molecular characterization of CTCs with regard to a number of important biomarkers including oestrogen receptor alpha and HER2. Preliminary data have demonstrated that expression of these markers between CTCs in individual patients with metastatic breast cancer reflects the heterogeneity of the underlying tumours. Future

  17. Comparative usefulness of inflammatory markers to indicate bacterial infection-analyzed according to blood culture results and related clinical factors.

    PubMed

    Nishikawa, Hirokazu; Shirano, Michinori; Kasamatsu, Yu; Morimura, Ayumi; Iida, Ko; Kishi, Tomomi; Goto, Tetsushi; Okamoto, Saki; Ehara, Eiji

    2016-01-01

    To assess relationships of inflammatory markers and 2 related clinical factors with blood culture results, we retrospectively investigated inpatients' blood culture and blood chemistry findings that were recorded from January to December 2014 using electronic medical records and analyzed the data of 852 subjects (426 culture-positive and 426 culture-negative). Results suggested that the risk of positive blood culture statistically increased as inflammatory marker levels and the number of related factors increased. Concerning the effectiveness of inflammatory markers, when the outcome definition was also changed for C-reactive protein (CRP), the odds ratio had a similar value, whereas when the outcome definition of blood culture positivity was used for procalcitonin (PCT), the greatest effectiveness of that was detected. Therefore, the current results suggest that PCT is more useful than CRP as an auxiliary indication of bacterial infection.

  18. Peripheral blood eosinophils: a surrogate marker for airway eosinophilia in stable COPD

    PubMed Central

    Negewo, Netsanet A; McDonald, Vanessa M; Baines, Katherine J; Wark, Peter AB; Simpson, Jodie L; Jones, Paul W; Gibson, Peter G

    2016-01-01

    Introduction Sputum eosinophilia occurs in approximately one-third of stable chronic obstructive pulmonary disease (COPD) patients and can predict exacerbation risk and response to corticosteroid treatments. Sputum induction, however, requires expertise, may not always be successful, and does not provide point-of-care results. Easily applicable diagnostic markers that can predict sputum eosinophilia in stable COPD patients have the potential to progress COPD management. This study investigated the correlation and predictive relationship between peripheral blood and sputum eosinophils. It also examined the repeatability of blood eosinophil counts. Methods Stable COPD patients (n=141) were classified as eosinophilic or noneosinophilic based on their sputum cell counts (≥3%), and a cross-sectional analysis was conducted comparing their demographics, clinical characteristics, and blood cell counts. Receiver operating characteristic curve analysis was used to assess the predictive ability of blood eosinophils for sputum eosinophilia. Intraclass correlation coefficient was used to examine the repeatability of blood eosinophil counts. Results Blood eosinophil counts were significantly higher in patients with sputum eosinophilia (n=45) compared to those without (0.3×109/L vs 0.15×109/L; P<0.0001). Blood eosinophils correlated with both the percentage (ρ=0.535; P<0.0001) and number of sputum eosinophils (ρ=0.473; P<0.0001). Absolute blood eosinophil count was predictive of sputum eosinophilia (area under the curve =0.76, 95% confidence interval [CI] =0.67–0.84; P<0.0001). At a threshold of ≥0.3×109/L (specificity =76%, sensitivity =60%, and positive likelihood ratio =2.5), peripheral blood eosinophil counts enabled identification of the presence or absence of sputum eosinophilia in 71% of the cases. A threshold of ≥0.4×109/L had similar classifying ability but better specificity (91.7%) and higher positive likelihood ratio (3.7). In contrast, ≥0.2×109/L

  19. [Hepatitis B and delta: the prevalence of seroepidemiological markers in volunteer blood donors and their families].

    PubMed

    Alvarez-Muñoz, M T; Bustamante-Calvillo, M E; Guiscafré-Gallardo, J P; Muñoz, O

    1991-01-01

    41 volunteer blood donors and his relatives were studied in order to know about the prevalence of hepatitis B and D virus infections in selected groups. Frequency of HBsAg+ carriers was 0.34 per cent in the Centro Nacional de la Transfusión Sanguínea and 0.15 per cent in the Banco Central de Sangre, IMSS. Most of the HBsAg+ blood donors were 21 to 40 years old (87.8%); 21.9 per cent had IgM antibodies against HBc and just 2.4 per cent were HBeAg positive. Forty one (26.9%) of 152 relatives had one or more of the HBV markers, 3.9 per cent were HBsAg carriers and 1.3 per cent were HBeAg positive. In the infected relatives group 36.6 per cent were ancestory or brothers and just 14.6 per cent of wives were infected. None of the HBsAg+ blood donors or his relatives had antibodies against delta agent. These results support the fact that the frequency of asymptomatic carriers of HBsAg in the volunteer blood donors group is similar to he frequency in the general population and identifies the group of relatives as those with the highest risk to acquire HBV infection.

  20. Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion.

    PubMed

    Cai, Yan; Wu, Jie; Li, Zhiyong; Long, Quan

    2016-01-01

    We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth.

  1. Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion

    PubMed Central

    Cai, Yan; Wu, Jie; Li, Zhiyong; Long, Quan

    2016-01-01

    We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth. PMID:26934465

  2. Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion.

    PubMed

    Cai, Yan; Wu, Jie; Li, Zhiyong; Long, Quan

    2016-01-01

    We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth. PMID:26934465

  3. Galectin-3: a possible complementary marker to the PSA blood test

    PubMed Central

    Nangia-Makker, Pratima; Kho, Dhonghyo; Bajaj, Madhuri; Smith, Daryn; Heilbrun, Lance; Raz, Avraham; Heath, Elisabeth

    2013-01-01

    The prostate-specific antigen (PSA) test has served as a blood marker of prostate cancer (PCa), and for monitoring recurrence/metastasis in patients after therapeutic intervention. However, the applicability/reliability of the PSA test was recently questioned as it is not without challenges, in particular in men who have PCa without an elevated PSA (false negative), or in men who are disease-free with elevated levels of PSA (false positive). Galectin-3 is a tumor-associated protein; present in the seminal fluid and is a substrate for the PSA enzyme e.g., a chymotrypsin-like serine protease. We hypothesized that the cleavage status and level of galectin-3 in the prostate tissue and sera are associated with PCa. Thus, we compared galectin-3 levels obtained from sera of non-cancer urology patients to those of metastatic PCa patients. The data were confirmed by analyzing PCa tissue arrays. Here, we report that galectin-3 levels in the sera of patients with metastatic PCa were uniformly higher as compared to the non-cancer patient controls. The data suggest that galectin-3 serum level may be a useful serum complementary marker to the PSA blood test to be used for initial and follow-up PSA complimentary diagnostic/prognostic tool for recurrence in PCa patients. PMID:23625538

  4. [Transcripts of satellite DNA in blood plasma: probable markers of tumor growth].

    PubMed

    Kondratova, V N; Botezatu, I V; Shelepov, V P; Likhtenshtein, A V

    2014-01-01

    A recent study of human normal and tumor tissues revealed a high transcriptional activity of pericentromeric satellite DNA repeats (they produce half of all transcripts in tumor cells that is many times higher than in normal ones). It was found also that the two subtypes of satellite DNA (HSATII and GSATII) are transcribed reciprocally, i.e. there is a sharp prevalence of HSATII transcription in tumors, while GSATII transcription prevails in the corresponding normal tissues. As different RNAs are present in blood plasma, and some of them serve as effectivetumor markers, we attempted for the first time to evaluate satellite HSATII and GSATII RNAs in the blood plasma of healthy donors and cancer patients. The RT-PCR protocol designed for this purpose allowed us to detect transcripts of both HSATII and GSATII repeats. As it has been shown, HSATII transcripts are more abundant than GSATII ones in plasma of healthy donors and vice versa in plasma of cancer patients; these ratios being diametrically opposed to those that exist within the cells. Some suggestions concerning origins of circulating satellite RNAs and their probable role as tumor markers are discussed.

  5. Levels of DNA Methylation Vary at CpG Sites across the BRCA1 Promoter, and Differ According to Triple Negative and "BRCA-Like" Status, in Both Blood and Tumour DNA.

    PubMed

    Daniels, Sarah L; Burghel, George J; Chambers, Philip; Al-Baba, Shadi; Connley, Daniel D; Brock, Ian W; Cramp, Helen E; Dotsenko, Olena; Wilks, Octavia; Wyld, Lynda; Cross, Simon S; Cox, Angela

    2016-01-01

    Triple negative breast cancer is typically an aggressive and difficult to treat subtype. It is often associated with loss of function of the BRCA1 gene, either through mutation, loss of heterozygosity or methylation. This study aimed to measure methylation of the BRCA1 gene promoter at individual CpG sites in blood, tumour and normal breast tissue, to assess whether levels were correlated between different tissues, and with triple negative receptor status, histopathological scoring for BRCA-like features and BRCA1 protein expression. Blood DNA methylation levels were significantly correlated with tumour methylation at 9 of 11 CpG sites examined (p<0.0007). The levels of tumour DNA methylation were significantly higher in triple negative tumours, and in tumours with high BRCA-like histopathological scores (10 of 11 CpG sites; p<0.01 and p<0.007 respectively). Similar results were observed in blood DNA (6 of 11 CpG sites; p<0.03 and 7 of 11 CpG sites; p<0.02 respectively). This study provides insight into the pattern of CpG methylation across the BRCA1 promoter, and supports previous studies suggesting that tumours with BRCA1 promoter methylation have similar features to those with BRCA1 mutations, and therefore may be suitable for the same targeted therapies. PMID:27463681

  6. Levels of DNA Methylation Vary at CpG Sites across the BRCA1 Promoter, and Differ According to Triple Negative and “BRCA-Like” Status, in Both Blood and Tumour DNA

    PubMed Central

    Burghel, George J.; Chambers, Philip; Al-Baba, Shadi; Connley, Daniel D.; Brock, Ian W.; Cramp, Helen E.; Dotsenko, Olena; Wilks, Octavia; Wyld, Lynda; Cross, Simon S.; Cox, Angela

    2016-01-01

    Triple negative breast cancer is typically an aggressive and difficult to treat subtype. It is often associated with loss of function of the BRCA1 gene, either through mutation, loss of heterozygosity or methylation. This study aimed to measure methylation of the BRCA1 gene promoter at individual CpG sites in blood, tumour and normal breast tissue, to assess whether levels were correlated between different tissues, and with triple negative receptor status, histopathological scoring for BRCA-like features and BRCA1 protein expression. Blood DNA methylation levels were significantly correlated with tumour methylation at 9 of 11 CpG sites examined (p<0.0007). The levels of tumour DNA methylation were significantly higher in triple negative tumours, and in tumours with high BRCA-like histopathological scores (10 of 11 CpG sites; p<0.01 and p<0.007 respectively). Similar results were observed in blood DNA (6 of 11 CpG sites; p<0.03 and 7 of 11 CpG sites; p<0.02 respectively). This study provides insight into the pattern of CpG methylation across the BRCA1 promoter, and supports previous studies suggesting that tumours with BRCA1 promoter methylation have similar features to those with BRCA1 mutations, and therefore may be suitable for the same targeted therapies. PMID:27463681

  7. Corrections of arterial input function for dynamic H215O PET to assess perfusion of pelvic tumours: arterial blood sampling versus image extraction

    NASA Astrophysics Data System (ADS)

    Lüdemann, L.; Sreenivasa, G.; Michel, R.; Rosner, C.; Plotkin, M.; Felix, R.; Wust, P.; Amthauer, H.

    2006-06-01

    Assessment of perfusion with 15O-labelled water (H215O) requires measurement of the arterial input function (AIF). The arterial time activity curve (TAC) measured using the peripheral sampling scheme requires corrections for delay and dispersion. In this study, parametrizations with and without arterial spillover correction for fitting of the tissue curve are evaluated. Additionally, a completely noninvasive method for generation of the AIF from a dynamic positron emission tomography (PET) acquisition is applied to assess perfusion of pelvic tumours. This method uses a volume of interest (VOI) to extract the TAC from the femoral artery. The VOI TAC is corrected for spillover using a separate tissue TAC and for recovery by determining the recovery coefficient on a coregistered CT data set. The techniques were applied in five patients with pelvic tumours who underwent a total of 11 examinations. Delay and dispersion correction of the blood TAC without arterial spillover correction yielded in seven examinations solutions inconsistent with physiology. Correction of arterial spillover increased the fitting accuracy and yielded consistent results in all patients. Generation of an AIF from PET image data was investigated as an alternative to arterial blood sampling and was shown to have an intrinsic potential to determine the AIF noninvasively and reproducibly. The AIF extracted from a VOI in a dynamic PET scan was similar in shape to the blood AIF but yielded significantly higher tissue perfusion values (mean of 104.0 ± 52.0%) and lower partition coefficients (-31.6 ± 24.2%). The perfusion values and partition coefficients determined with the VOI technique have to be corrected in order to compare the results with those of studies using a blood AIF.

  8. Dynamic markers based on blood perfusion fluctuations for selecting skin melanocytic lesions for biopsy

    NASA Astrophysics Data System (ADS)

    Lancaster, Gemma; Stefanovska, Aneta; Pesce, Margherita; Marco Vezzoni, Gian; Loggini, Barbara; Pingitore, Raffaele; Ghiara, Fabrizio; Barachini, Paolo; Cervadoro, Gregorio; Romanelli, Marco; Rossi, Marco

    2015-08-01

    Skin malignant melanoma is a highly angiogenic cancer, necessitating early diagnosis for positive prognosis. The current diagnostic standard of biopsy and histological examination inevitably leads to many unnecessary invasive excisions. Here, we propose a non-invasive method of identification of melanoma based on blood flow dynamics. We consider a wide frequency range from 0.005-2 Hz associated with both local vascular regulation and effects of cardiac pulsation. Combining uniquely the power of oscillations associated with individual physiological processes we obtain a marker which distinguishes between melanoma and atypical nevi with sensitivity of 100% and specificity of 90.9%. The method reveals valuable functional information about the melanoma microenvironment. It also provides the means for simple, accurate, in vivo distinction between malignant melanoma and atypical nevi, and may lead to a substantial reduction in the number of biopsies currently undertaken.

  9. Dynamic markers based on blood perfusion fluctuations for selecting skin melanocytic lesions for biopsy.

    PubMed

    Lancaster, Gemma; Stefanovska, Aneta; Pesce, Margherita; Marco Vezzoni, Gian; Loggini, Barbara; Pingitore, Raffaele; Ghiara, Fabrizio; Barachini, Paolo; Cervadoro, Gregorio; Romanelli, Marco; Rossi, Marco

    2015-08-11

    Skin malignant melanoma is a highly angiogenic cancer, necessitating early diagnosis for positive prognosis. The current diagnostic standard of biopsy and histological examination inevitably leads to many unnecessary invasive excisions. Here, we propose a non-invasive method of identification of melanoma based on blood flow dynamics. We consider a wide frequency range from 0.005-2 Hz associated with both local vascular regulation and effects of cardiac pulsation. Combining uniquely the power of oscillations associated with individual physiological processes we obtain a marker which distinguishes between melanoma and atypical nevi with sensitivity of 100% and specificity of 90.9%. The method reveals valuable functional information about the melanoma microenvironment. It also provides the means for simple, accurate, in vivo distinction between malignant melanoma and atypical nevi, and may lead to a substantial reduction in the number of biopsies currently undertaken.

  10. Intestinal Microbiota Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

    PubMed Central

    Broin, Pilib Ó; Vaitheesvaran, Bhavapriya; Saha, Subhrajit; Hartil, Kirsten; Chen, Emily I.; Goldman, Devorah; Fleming, William Harv; Kurland, Irwin J.; Guha, Chandan; Golden, Aaron

    2014-01-01

    Purpose Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials Groups of C57BL/6 mice (n=12 per group) were exposed to 0 Gy, 2 Gy, 4 Gy, 8 Gy, and 10.4 Gy of whole-body γ-radiation. At 24 hours post treatment all animals were euthanized and both plasma and liver biopsies obtained - the latter being used to deconvolve a distinct hepatic radiation injury response within plasma. A semi-quantitative untargeted metabolites/lipid profiling using both GC/MS and LC/MS/MS platforms was performed and identified 354 biochemicals. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence to indicate that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusion Plasma profiling of specific metabolites related to the pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites in particular represent an attractive marker for radiation injury within blood plasma. PMID:25636760

  11. Reassessment of Blood Gene Expression Markers for the Prognosis of Relapsing-Remitting Multiple Sclerosis

    PubMed Central

    Hecker, Michael; Paap, Brigitte Katrin; Goertsches, Robert Hermann; Kandulski, Ole; Fatum, Christian; Koczan, Dirk; Hartung, Hans-Peter; Thiesen, Hans-Juergen; Zettl, Uwe Klaus

    2011-01-01

    Despite considerable advances in the treatment of multiple sclerosis, current drugs are only partially effective. Most patients show reduced disease activity with therapy, but still experience relapses, increasing disability, and new brain lesions. Since there are no reliable clinical or biological markers of disease progression, long-term prognosis is difficult to predict for individual patients. We identified 18 studies that suggested genes expressed in blood as predictive biomarkers. We validated the prognostic value of those genes with three different microarray data sets comprising 148 patients in total. Using these data, we tested whether the genes were significantly differentially expressed between patients with good and poor courses of the disease. Poor progression was defined by relapses and/or increase of disability during a two-year follow-up, independent of the administered therapy. Of 110 genes that have been proposed as predictive biomarkers, most could not be confirmed in our analysis. However, the G protein-coupled membrane receptor GPR3 was expressed at significantly lower levels in patients with poor disease progression in all data sets. GPR3 has therefore a high potential to be a biomarker for predicting future disease activity. In addition, we examined the IL17 cytokines and receptors in more detail and propose IL17RC as a new, promising, transcript-based biomarker candidate. Further studies are needed to better understand the roles of these receptors in multiple sclerosis and its treatment and to clarify the utility of GPR3 and IL17RC expression levels in the blood as markers of long-term prognosis. PMID:22216338

  12. Blood antioxidant enzymes as markers of exposure or effect in coal miners.

    PubMed Central

    Perrin-Nadif, R; Auburtin, G; Dusch, M; Porcher, J M; Mur, J M

    1996-01-01

    OBJECTIVE--To investigate if blood Cu++/Zn++ superoxide dismutase, glutathione peroxidase, catalase, and total plasma antioxidant activities could be markers of biological activity resulting from exposure to respirable coal mine dust in active miners, and of pneumoconiosis in retired miners. METHODS--Blood samples were randomly obtained from active surface workers (n = 30) and underground miners (n = 34), and from retired miners without (n = 21), and with (n = 33) pneumoconiosis. Antioxidant enzyme activities and total plasma antioxidants were measured in erythrocytes and plasma. Non-parametric tests were completed by analyses of covariance to compare antioxidants between groups, taking into account potential confounding factors (age, smoking history (pack-years)). RESULTS--Erythrocyte Cu++/Zn++ superoxide dismutase activity was significantly higher in the group of underground miners than the group of surface workers. The differences in total plasma antioxidants and plasma glutathione peroxidase activity between both groups were related to age. Glutathione peroxidase activity increased in the plasma of retired miners with pneumoconiosis, compared with retired miners without pneumoconiosis. No differences were found either in erythrocyte antioxidant enzyme activities or in total plasma antioxidants between the groups of retired miners without and with pneumoconiosis. CONCLUSIONS--In this study, erythrocyte Cu++/Zn++ superoxide dismutase activity may be considered as a marker of effect of respirable coal mine dust in exposed workers. This result is in agreement with the hypothesis that reactive oxygen species are involved in cell injury induced by coal mine dust, and may be predictive of the degree of inflammation and pneumoconiosis induced by coal mine dust. The increase in glutathione peroxidase activity in the plasma of retired miners with pneumoconiosis may be the result of a response to the increasing hydrogen peroxide (H2O2) production due to the disease

  13. Intestinal Microbiota-Derived Metabolomic Blood Plasma Markers for Prior Radiation Injury

    SciTech Connect

    Ó Broin, Pilib; Vaitheesvaran, Bhavapriya; Saha, Subhrajit; Hartil, Kirsten; Chen, Emily I.; Goldman, Devorah; Fleming, William Harv; Kurland, Irwin J.; Guha, Chandan; Golden, Aaron

    2015-02-01

    Purpose: Assessing whole-body radiation injury and absorbed dose is essential for remediation efforts following accidental or deliberate exposure in medical, industrial, military, or terrorist incidents. We hypothesize that variations in specific metabolite concentrations extracted from blood plasma would correlate with whole-body radiation injury and dose. Methods and Materials: Groups of C57BL/6 mice (n=12 per group) were exposed to 0, 2, 4, 8, and 10.4 Gy of whole-body gamma radiation. At 24 hours after treatment, all animals were euthanized, and both plasma and liver biopsy samples were obtained, the latter being used to identify a distinct hepatic radiation injury response within plasma. A semiquantitative, untargeted metabolite/lipid profile was developed using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry, which identified 354 biochemical compounds. A second set of C57BL/6 mice (n=6 per group) were used to assess a subset of identified plasma markers beyond 24 hours. Results: We identified a cohort of 37 biochemical compounds in plasma that yielded the optimal separation of the irradiated sample groups, with the most correlated metabolites associated with pyrimidine (positively correlated) and tryptophan (negatively correlated) metabolism. The latter were predominantly associated with indole compounds, and there was evidence that these were also correlated between liver and plasma. No evidence of saturation as a function of dose was observed, as has been noted for studies involving metabolite analysis of urine. Conclusions: Plasma profiling of specific metabolites related to pyrimidine and tryptophan pathways can be used to differentiate whole-body radiation injury and dose response. As the tryptophan-associated indole compounds have their origin in the intestinal microbiome and subsequently the liver, these metabolites particularly represent an attractive marker for radiation injury within blood plasma.

  14. Differentially expressed genes in human peripheral blood as potential markers for statin response.

    PubMed

    Won, Hong-Hee; Kim, Suk Ran; Bang, Oh Young; Lee, Sang-Chol; Huh, Wooseong; Ko, Jae-Wook; Kim, Hyung-Gun; McLeod, Howard L; O'Connell, Thomas M; Kim, Jong-Won; Lee, Soo-Youn

    2012-02-01

    There is a considerable inter-individual variation in response to statin therapy and one third of patients do not meet their treatment goals. We aimed to identify differentially expressed genes that might be involved in the effects of statin treatment and to suggest potential markers to guide statin therapy. Forty-six healthy Korean subjects received atorvastatin; their whole-genome expression profiles in peripheral blood were analyzed before and after atorvastatin administration in relation with changes in lipid profiles. The expression patterns of the differentially expressed genes were also compared with the data of familial hypercholesterolemia (FH) patients and controls. Pairwise comparison analyses revealed differentially expressed genes involved in diverse biological processes and molecular functions related with immune responses. Atorvastain mainly affected antigen binding, immune or inflammatory response including interleukin pathways. Similar expression patterns of the genes were observed in patients with FH and controls. The Charcol-Leyden crystal (CLC), CCR2, CX3CR1, LRRN3, FOS, LDLR, HLA-DRB1, ERMN, and TCN1 genes were significantly associated with cholesterol levels or statin response. Interestingly, the CLC gene, which was significantly altered by atorvastatin administration and differentially expressed between FH patients and controls, showed much bigger change in high-responsive group than in low-responsive group. We identified differentially expressed genes that might be involved in mechanisms underlying the known pleiotropic effects of atorvastatin, baseline cholesterol levels, and drug response. Our findings suggest CLC as a new candidate marker for statin response, and further validation is needed.

  15. Comparison of direct and indirect alcohol markers with PEth in blood and urine in alcohol dependent inpatients during detoxication.

    PubMed

    Winkler, M; Skopp, G; Alt, A; Miltner, E; Jochum, Th; Daenhardt, C; Sporkert, F; Gnann, H; Weinmann, W; Thierauf, A

    2013-07-01

    The importance of direct and indirect alcohol markers to evaluate alcohol consumption in clinical and forensic settings is increasingly recognized. While some markers are used to prove abstinence from ethanol, other markers are suitable for detection of alcohol misuse. Phosphatidyl ethanol (PEth) is ranked among the latter. There is only little information about the correlation between PEth and other currently used markers (ethyl glucuronide, ethyl sulfate, carbohydrate deficient transferrin, gamma-glutamyl transpeptidase, and methanol) and about their decline during detoxification. To get more information, 18 alcohol-dependent patients in withdrawal therapy were monitored for these parameters in blood and urine for up to 19 days. There was no correlation between the different markers. PEth showed a rapid decrease at the beginning of the intervention, a slow decline after the first few days, and could still be detected after 19 days of abstinence from ethanol. PMID:23274938

  16. T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement.

    PubMed

    Olavarria, E; Child, F; Woolford, A; Whittaker, S J; Davis, J G; McDonald, C; Chilcott, S; Spittle, M; Grieve, R J; Stewart, S; Apperley, J F; Russell-Jones, R

    2001-09-01

    Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T-cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable rearrangements of the T-cell receptor (TCR) gamma-gene demonstrated by polymerase chain reaction (PCR)/single-stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high-dose etoposide (1.6 g/m2) and granulocyte colony-stimulating factor (G-CSF). The apheresis products underwent rigorous T-cell depletion with immunomagnetic methods. Double CD34-positive and CD4/CD8-negative selection achieved a median reduction of 3.89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2-14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T-cell depleted graft. A T-cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse-free survival, most patients achieved good disease control at the time of relapse.

  17. Tumour endothelial cells in high metastatic tumours promote metastasis via epigenetic dysregulation of biglycan

    PubMed Central

    Maishi, Nako; Ohba, Yusuke; Akiyama, Kosuke; Ohga, Noritaka; Hamada, Jun-ichi; Nagao-Kitamoto, Hiroko; Alam, Mohammad Towfik; Yamamoto, Kazuyuki; Kawamoto, Taisuke; Inoue, Nobuo; Taketomi, Akinobu; Shindoh, Masanobu; Hida, Yasuhiro; Hida, Kyoko

    2016-01-01

    Tumour blood vessels are gateways for distant metastasis. Recent studies have revealed that tumour endothelial cells (TECs) demonstrate distinct phenotypes from their normal counterparts. We have demonstrated that features of TECs are different depending on tumour malignancy, suggesting that TECs communicate with surrounding tumour cells. However, the contribution of TECs to metastasis has not been elucidated. Here, we show that TECs actively promote tumour metastasis through a bidirectional interaction between tumour cells and TECs. Co-implantation of TECs isolated from highly metastatic tumours accelerated lung metastases of low metastatic tumours. Biglycan, a small leucine-rich repeat proteoglycan secreted from TECs, activated tumour cell migration via nuclear factor-κB and extracellular signal–regulated kinase 1/2. Biglycan expression was upregulated by DNA demethylation in TECs. Collectively, our results demonstrate that TECs are altered in their microenvironment and, in turn, instigate tumour cells to metastasize, which is a novel mechanism for tumour metastasis. PMID:27295191

  18. Molecular markers and mechanisms of stroke: RNA studies of blood in animals and humans

    PubMed Central

    Sharp, Frank R; Jickling, Glen C; Stamova, Boryana; Tian, Yingfang; Zhan, Xinhua; Liu, DaZhi; Kuczynski, Beth; Cox, Christopher D; Ander, Bradley P

    2011-01-01

    Whole genome expression microarrays can be used to study gene expression in blood, which comes in part from leukocytes, immature platelets, and red blood cells. Since these cells are important in the pathogenesis of stroke, RNA provides an index of these cellular responses to stroke. Our studies in rats have shown specific gene expression changes 24 hours after ischemic stroke, hemorrhage, status epilepticus, hypoxia, hypoglycemia, global ischemia, and following brief focal ischemia that simulated transient ischemic attacks in humans. Human studies show gene expression changes following ischemic stroke. These gene profiles predict a second cohort with >90% sensitivity and specificity. Gene profiles for ischemic stroke caused by large-vessel atherosclerosis and cardioembolism have been described that predict a second cohort with >85% sensitivity and specificity. Atherosclerotic genes were associated with clotting, platelets, and monocytes, and cardioembolic genes were associated with inflammation, infection, and neutrophils. These gene profiles predicted the cause of stroke in 58% of cryptogenic patients. These studies will provide diagnostic, prognostic, and therapeutic markers, and will advance our understanding of stroke in humans. New techniques to measure all coding and noncoding RNAs along with alternatively spliced transcripts will markedly advance molecular studies of human stroke. PMID:21505474

  19. New evidence for the origin of intracranial germ cell tumours from primordial germ cells: expression of pluripotency and cell differentiation markers.

    PubMed

    Hoei-Hansen, C E; Sehested, A; Juhler, M; Lau, Y-F C; Skakkebaek, N E; Laursen, H; Rajpert-de Meyts, E

    2006-05-01

    Primary intracranial germ cell tumours are rare neoplasms that occur in children and adolescents. This study examined both the biology and the origin of these tumours, as it has been hypothesized that they originate from a totipotent primordial germ cell. We applied recent knowledge from gonadal germ cell tumours and analysed expression of a wide panel of stem cell-related proteins (C-KIT, OCT-3/4 (POU5F1), AP-2gamma (TFAP2C), and NANOG) and developmentally regulated germ cell-specific proteins (including MAGE-A4, NY-ESO-1, and TSPY). Expression at the protein level was analysed in 21 children and young adults with intracranial germinomas and non-germinomas, contributing to a careful description of these unusual tumours and adding to the understanding of pathogenesis. Stem cell related proteins were highly expressed in intracranial germ cell tumours, and many similarities were detected with their gonadal equivalents, including a close similarity with primordial germ cells. A notable difference was the sex-specific expression of TSPY, a gene previously implicated in the origin of gonadoblastoma. TSPY was only detected in germ cell tumours in the central nervous system (CNS) from males, suggesting that it is not required for the initiation of malignant germ cell transformation. The expression of genes associated with embryonic stem cell pluripotency in CNS germ cell tumours strongly suggests that these tumours are derived from cells that retain, at least partially, an embryonic stem cell-like phenotype, which is a hallmark of primordial germ cells. PMID:16456896

  20. Mildly elevated blood pressure is a marker for better health status in Polish centenarians.

    PubMed

    Szewieczek, Jan; Dulawa, Jan; Francuz, Tomasz; Legierska, Katarzyna; Hornik, Beata; Włodarczyk-Sporek, Iwona; Janusz-Jenczeń, Magdalena; Batko-Szwaczka, Agnieszka

    2015-02-01

    The number of centenarians is projected to rise rapidly. However, knowledge of evidence-based health care in this group is still poor. Hypertension is the most common condition that leads to multiple organ complications, disability, and premature death. No guidelines for the management of high blood pressure (BP) in centenarians are available. We have performed a cross-sectional study to characterize clinical and functional state of Polish centenarians, with a special focus on BP. The study comprised 86 consecutive 100.9 ± 1.2 years old (mean ± SD) subjects (70 women and 16 men). The assessment included structured interview, physical examination, geriatric functional assessment, resting electrocardiography, and blood and urine sampling. The subjects were followed-up on the phone. Subjects who survived 180 days (83 %) as compared to non-survivors had higher systolic BP (SBP), diastolic BP (DPB), mean arterial pressure (MAP), pulse pressure (PP), higher mini-mental state examination, Barthel Index of Activities of Daily Living and Lawton Instrumental Activities of Daily Living Scale scores, higher serum albumin and calcium levels, and total iron-binding capacity, while lower serum creatinine, cystatin C, folate, and C-reactive protein levels. SBP ≥140 mm Hg, DBP ≥90 mm Hg, MAP ≥100 mm Hg, and PP ≥40 mm Hg were associated with higher 180-day survival probability. Results suggest that mildly elevated blood pressure is a marker for better health status in Polish centenarians.

  1. Tumor Endothelial Marker 8 Amplifies Canonical Wnt Signaling in Blood Vessels

    PubMed Central

    Verma, Kiran; Gu, Jingsheng; Werner, Erica

    2011-01-01

    Tumor Endothelial Marker 8/Anthrax Toxin Receptor 1 (TEM8/ANTXR1) expression is induced in the vascular compartment of multiple tumors and therefore, is a candidate molecule to target tumor therapies. This cell surface molecule mediates anthrax toxin internalization, however, its physiological function in blood vessels remains largely unknown. We identified the chicken chorioallantoic membrane (CAM) as a model system to study the endogenous function of TEM8 in blood vessels as we found that TEM8 expression was induced transiently between day 10 and 12 of embryonic development, when the vascular tree is undergoing final development and growth. We used the cell-binding component of anthrax toxin, Protective Antigen (PA), to engage endogenous TEM8 receptors and evaluate the effects of PA-TEM8 complexes on vascular development. PA applied at the time of highest TEM8 expression reduced vascular density and disrupted hierarchical branching as revealed by quantitative morphometric analysis of the vascular tree after 48h. PA-dependent reduced branching phenotype was partially mimicked by Wnt3a application and ameliorated by the Wnt antagonist, Dikkopf-1. These results implicate TEM8 expression in endothelial cells in regulating the canonical Wnt signaling pathway at this day of CAM development. Consistent with this model, PA increased beta catenin levels acutely in CAM blood vessels in vivo and in TEM8 transfected primary human endothelial cells in vitro. TEM8 expression in Hek293 cells, which neither express endogenous PA-binding receptors nor Wnt ligands, stabilized beta catenin levels and amplified beta catenin-dependent transcriptional activity induced by Wnt3a. This agonistic function is supported by findings in the CAM, where the increase in TEM8 expression from day 10 to day 12 and PA application correlated with Axin 2 induction, a universal reporter gene for canonical Wnt signaling. We postulate that the developmentally controlled expression of TEM8 modulates

  2. Mildly elevated blood pressure is a marker for better health status in Polish centenarians.

    PubMed

    Szewieczek, Jan; Dulawa, Jan; Francuz, Tomasz; Legierska, Katarzyna; Hornik, Beata; Włodarczyk-Sporek, Iwona; Janusz-Jenczeń, Magdalena; Batko-Szwaczka, Agnieszka

    2015-02-01

    The number of centenarians is projected to rise rapidly. However, knowledge of evidence-based health care in this group is still poor. Hypertension is the most common condition that leads to multiple organ complications, disability, and premature death. No guidelines for the management of high blood pressure (BP) in centenarians are available. We have performed a cross-sectional study to characterize clinical and functional state of Polish centenarians, with a special focus on BP. The study comprised 86 consecutive 100.9 ± 1.2 years old (mean ± SD) subjects (70 women and 16 men). The assessment included structured interview, physical examination, geriatric functional assessment, resting electrocardiography, and blood and urine sampling. The subjects were followed-up on the phone. Subjects who survived 180 days (83 %) as compared to non-survivors had higher systolic BP (SBP), diastolic BP (DPB), mean arterial pressure (MAP), pulse pressure (PP), higher mini-mental state examination, Barthel Index of Activities of Daily Living and Lawton Instrumental Activities of Daily Living Scale scores, higher serum albumin and calcium levels, and total iron-binding capacity, while lower serum creatinine, cystatin C, folate, and C-reactive protein levels. SBP ≥140 mm Hg, DBP ≥90 mm Hg, MAP ≥100 mm Hg, and PP ≥40 mm Hg were associated with higher 180-day survival probability. Results suggest that mildly elevated blood pressure is a marker for better health status in Polish centenarians. PMID:25637333

  3. Acute effects of whey protein isolate on blood pressure, vascular function and inflammatory markers in overweight postmenopausal women.

    PubMed

    Pal, Sebely; Ellis, Vanessa

    2011-05-01

    Previous evidence indicates that chronic consumption of dairy whey proteins has beneficial effects on CVD risk factors. The present study investigated the postprandial effects of whey protein isolate on blood pressure, vascular function and inflammatory markers in overweight and obese postmenopausal women. This was a randomised, three-way cross-over design study where twenty overweight and obese postmenopausal women consumed a breakfast meal in conjunction with one of three supplements: 45 g whey protein isolate, 45 g sodium caseinate or 45 g of a glucose control. Fasting and postprandial blood samples, blood pressure and pulse wave analysis readings were taken for up to 6 h. After consumption of the meal, both systolic and diastolic blood pressure, and augmentation index (AI) decreased initially for all interventions and gradually returned to baseline levels by 6 h. However, there were no significant differences in AI, systolic or diastolic blood pressure within or between the glucose control, casein or whey groups. There were also no significant group effects on plasma inflammatory markers (IL-6, TNF-α and C-reactive protein). The health effects previously seen with chronic whey protein ingestion were not seen in the acute 6 h postprandial period in relation to blood pressure, vascular function or inflammatory markers when compared with casein and a glucose control. This suggests that such effects are better observed from the long-term consumption of whey proteins.

  4. Short-term Effects of Air Temperature on Blood Markers of Coagulation and Inflammation in Potentially Susceptible Individuals

    EPA Science Inventory

    Objectives: Changes in air temperature are associated with an increase in cardiovascular events, but the role of pro-coagulant and pro-inflammatory blood markers is still poorly understood. We investigated the association between air temperature and fibrinogen, plasminogen act...

  5. Pitfalls in colour photography of choroidal tumours

    PubMed Central

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  6. Pitfalls in colour photography of choroidal tumours.

    PubMed

    Schalenbourg, A; Zografos, L

    2013-02-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.

  7. The LWb blood group as a marker of prehistoric Baltic migrations and admixture.

    PubMed

    Sistonen, P; Virtaranta-Knowles, K; Denisova, R; Kucinskas, V; Ambrasiene, D; Beckman, L

    1999-06-01

    Archaeological findings and historical records indicate frequent migrations and exchange of genetic material between populations in the Baltic Sea area. However, there have so far been very few attempts to trace migrations in this area using genetic markers. We have studied the Baltic populations with respect to exceptional variations in the frequencies of the Landsteiner-Wiener (LW) blood group. The frequency of the uncommon LWb gene was high in the Balts, around 6% among Latvians and Lithuanians, very low among the other western Europeans (0-0.1%) and apparently absent in Asiatic and African populations. From the Baltic region of peak frequency there was a regular decline of LWb incidence (a descending cline) in the neighboring populations: 4.0% in the Estonians, 2.9% in the Finns, 2. 2% in the Vologda Russians, and 2.0% in the Poles. Thus the distribution of LWb suggests considerable and extensive Baltic admixture, especially in the north and northeast direction. In Southern Sweden with an LWb frequency of 0.3%, the Baltic influence appeared slight, while in the population of the Swedish island Gotland in the middle of the Baltic Sea there was a significantly increased LWb frequency of 1.0% compared with that of Western European countries. The distinction of codominantly inherited LW antigenic forms, LWa and LWb (previously Nea), is known to be due to a single base substitution. Based on our population data, it is plausible that the expansion of this point mutation occurred only once during human history. Furthermore, our data indicate that the expansion of the LWb mutation occurred in Balts and that LWb can be considered a 'Baltic tribal marker', its presence in other populations being an indicator of the degree of Baltic genetic influence. PMID:10364680

  8. Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients

    PubMed Central

    YAMAMOTO, NOBUYUKI; KOZAKI, AIKO; HARTOMO, TRI BUDI; YANAI, TOMOKO; HASEGAWA, DAIICHIRO; KAWASAKI, KEIICHIRO; KOSAKA, YOSHIYUKI; MATSUO, MASAFUMI; HIRASE, SATOSHI; MORI, TAKESHI; HAYAKAWA, AKIRA; IIJIMA, KAZUMOTO; NISHIO, HISAHIDE; NISHIMURA, NORIYUKI

    2015-01-01

    Neuroblastoma is an aggressive solid tumor that leads to tumor relapse in more than half of high-risk patients. Minimal residual disease (MRD) is primarily responsible for tumor relapses and may be detected in peripheral blood (PB) and bone marrow (BM) samples. To evaluate the disease status and treatment response, a number of MRD detection protocols based on either common or distinct markers for PB and BM samples have been reported. However, the correlation between the expression of MRD markers in PB and BM samples remains elusive in the clinical samples. In the present study, the expression of 11 previously validated MRD markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) was determined in 23 pairs of PB and BM samples collected from seven high-risk neuroblastoma patients at the same time point, and the sample was scored as MRD-positive if one of the MRD markers exceeded the normal range. Although the number of MRD-positive samples was not significantly different between PB and BM samples, the two most sensitive markers for PB samples (CRMP1 and KIF1A) were different from those for BM samples (PHOX2B and DBH). There was no statistically significant correlation between the expression of MRD markers in the PB and BM samples. These results suggest that MRD markers were differentially expressed in PB and BM samples from high-risk neuroblastoma patients. PMID:26722317

  9. New blood markers detection technology: A leap in the diagnosis of gastric cancer.

    PubMed

    Beeharry, Maneesh K; Liu, Wen-Tao; Yan, Min; Zhu, Zheng-Gang

    2016-01-21

    Gastric cancer (GC) is still one of the malignant tumors with high morbidity and mortality in the world, with a 5-year survival rate of less than 30%. GC is often either asymptomatic or causes only nonspecific symptoms in its early stages, whereas when the symptoms manifest, the cancer has usually reached an advanced stage, which is one of the main causes of its relatively poor prognosis. Hence, the main focus of GC research has been on discovering new tools and technology to predict, screen and diagnose GC at an early stage which would prompt early treatment. With the tremendous advances in the OMICS technology, serum proteomics has been in the limelight of cancer research over the last few decades and has steered the development of several methods helping to understand the mechanisms underlying gastric carcinogenesis, resulting in the identification of a large number of molecular targets such as circulating tumor cells (CTCs), cell free DNA (cfDNA) and cell tumor DNA (ctDNA) and their sub-molecular components such as miRNA, that show great promise as GC biomarkers. In this review, we are underlying the recent breakthroughs about new blood markers technology for GC while scrutinizing the potential clinical use of CTCs, cfDNA, ctDNA and the role of the methylation of their sub-molecular components in the pathogenesis, diagnosis and management of GC.

  10. New blood markers detection technology: A leap in the diagnosis of gastric cancer.

    PubMed

    Beeharry, Maneesh K; Liu, Wen-Tao; Yan, Min; Zhu, Zheng-Gang

    2016-01-21

    Gastric cancer (GC) is still one of the malignant tumors with high morbidity and mortality in the world, with a 5-year survival rate of less than 30%. GC is often either asymptomatic or causes only nonspecific symptoms in its early stages, whereas when the symptoms manifest, the cancer has usually reached an advanced stage, which is one of the main causes of its relatively poor prognosis. Hence, the main focus of GC research has been on discovering new tools and technology to predict, screen and diagnose GC at an early stage which would prompt early treatment. With the tremendous advances in the OMICS technology, serum proteomics has been in the limelight of cancer research over the last few decades and has steered the development of several methods helping to understand the mechanisms underlying gastric carcinogenesis, resulting in the identification of a large number of molecular targets such as circulating tumor cells (CTCs), cell free DNA (cfDNA) and cell tumor DNA (ctDNA) and their sub-molecular components such as miRNA, that show great promise as GC biomarkers. In this review, we are underlying the recent breakthroughs about new blood markers technology for GC while scrutinizing the potential clinical use of CTCs, cfDNA, ctDNA and the role of the methylation of their sub-molecular components in the pathogenesis, diagnosis and management of GC. PMID:26811658

  11. Relationships between oxidative stress markers and red blood cell characteristics in renal azotemic dogs.

    PubMed

    Buranakarl, C; Trisiriroj, M; Pondeenana, S; Tungjitpeanpong, T; Jarutakanon, P; Penchome, R

    2009-04-01

    Oxidative stress parameters and erythrocyte characteristics were studied in 15 normal healthy dogs and 33 renal azotaemic dogs from Small Animal Hospital, Faculty of Veterinary Science, Chulalongkorn University. Dogs with renal azotaemia had reduced mean corpuscular volume (MCV) (P<0.01), packed cell volume (PCV) (P<0.001) and increased mean corpuscular hemoglobin concentration (MCHC) (P<0.001). The relationship was found between degree of azotaemia and MCV, PCV and MCHC. Dogs with severe renal azotaemia had higher intraerythrocytic sodium contents (RBC-Na) (P<0.05). The red blood cell catalase activity and glutathione and plasma malondialdehyde were unaltered while urinary malondialdehyde-creatinine ratio (U-MDA/Cr) increased significantly (P<0.001). The U-MDA/Cr was correlated significantly with plasma creatinine concentration (P<0.05), urinary protein-creatinine ratio (P<0.05) and fractional excretion of sodium (P<0.001). The results suggest some changes in RBC characteristics and urine oxidative stress marker in renal azotaemic dogs. Moreover, the U-MDA/Cr is a sensitive biochemical parameter which increased along with degree of renal dysfunction.

  12. Assessment of red blood cell distribution width as a prognostic marker in chronic lymphocytic leukemia

    PubMed Central

    Podhorecka, Monika; Halicka, Dorota; Szymczyk, Agnieszka; Macheta, Arkadiusz; Chocholska, Sylwia; Hus, Marek; Darzynkiewicz, Zbigniew

    2016-01-01

    Red blood cell distribution width (RDW) is a quantitative measure of the variability in size of circulating erythrocytes. It was recently reported that RDW is a prognostic factor for infection diseases, cardiovascular and pulmonary diseases, as well as some neoplasms. Moreover, RDW is remarkably strong predictor of longevity, including all causes of death, for adults aged 45 years and older. To explain this occurrence it was proposed that persistent IGFs/mTOR signaling is one of the factors that play a role in affecting the RDW and mortality. The above observations induced us to analyze the prognostic role of RDW in chronic lymphocytic leukemia (CLL) being the most frequent type of adult leukemia in Western countries. The obtained results have shown that RDW may be considered as a potential CLL prognostic marker. Elevated RDW level at the moment of diagnosis was associated with advanced disease and presence of other poor prognostic factors. It is also connected with overall survival indicating shorter time in patients with elevated RDW. It is possible that the presently observed correlation between mortality and RDW of the CLL patients is affected by their metabolic (IGF-1/mTOR driven)- rather than chronological- aging. The patients with high level of RDW are expected to have an increased persistent level of IGF-1/mTOR signaling. Within the framework of personalized therapy, these CLL patients therefore would be expected to be more sensitive to the treatment with mTOR inhibitors. PMID:27147570

  13. Neonatal tumours.

    PubMed

    Moore, S W

    2013-12-01

    Neonatal or perinatal tumours frequently relate to prenatal or developmental events and have a short exposure window which provides an opportunity to study tumours in a selective sensitive period of development. As a result, they display a number of host-specific features which include occasional spontaneous maturational changes with cells still responding to developmental influences. Neonatal tumours (NNT) are studied for a number of important reasons. Firstly, many of the benign tumours arising from soft tissue appear to result from disturbances in growth and development and some are associated with other congenital anomalies. Study of these aspects may open the door for investigation of genetic and epigenetic changes in genes controlling foetal development as well as environmental and drug effects during pregnancy. Secondly, the clinical behaviour of NNT differs from that of similar tumours occurring later in childhood. In addition, certain apparently malignant NNT can 'change course' in infancy leading to the maturation of apparently highly malignant tumours. Thirdly, NNT underline the genetic associations of most tumours but appear to differ in the effects of proto-oncogenes and other oncogenic factors. In this context, there are also connections between the foetal and neonatal period and some "adult" cancers. Fourthly, they appear to arise in a period in which minimal environmental interference has occurred, thus providing a unique potential window of opportunity to study the pathogenesis of tumour behaviour. This study will seek to review what is currently known in each of these areas of study as they apply to NNT. Further study of the provocative differences in tumour behaviour in neonates provides insights into the natural history of cancer in humans and promotes novel cancer therapies.

  14. Blood DNA methylation markers in prospectively identified hepatocellular carcinoma cases and controls from Taiwan

    PubMed Central

    Wu, Hui-Chen; Shen, Jing; Yang, Hwai-I; Tsai, Wei-Yann; Chen, Chien-Jen; Santella, Regina M

    2016-01-01

    AIM: To determine if gene-specific DNA methylation in prospectively collected blood samples is associated with later development of hepatocellular carcinoma (HCC). METHODS: Comparing genome-wide DNA methylation profiles using Illumina Human methylation 450K arrays, we previously identified a list of loci that were differentially methylated between tumor and adjacent nontumor tissues. To examine if dysregulation of DNA methylation patterns observed in tumor tissues can be detected in white blood cell (WBC) DNA, we conducted a prospective case-control study nested within a community-based cancer screening cohort in Taiwan with 16 years of follow up. We measured methylation levels in ninety-six loci that were aberrant in DNA methylation in HCC tumor tissues compared to adjacent tissues. Baseline WBC DNA from 159 HCC cases and 312 matched controls were bisulfite treated and assayed by Illumina BeadArray. We used the χ2 test for categorical variables and student’s t-test for continuous variables to assess the difference in selected characteristics between cases and controls. To estimate associations with HCC risk, we used conditional logistic regression models stratified on the matching factors to calculate odds ratios (OR) and 95%CI. RESULTS: We found that high methylation level in cg10272601 in WNK2 was associated with increased risk of HCC, with an OR of 1.91 (95%CI: 1.27-2.86). High methylation levels in both cg12680131 in TPO and cg22511877 in MYT1L, however, were associated with decreased risk. The ORs (95%CI) were 0.59 (0.39-0.87) and 0.50 (0.33-0.77), respectively, for those with methylation levels of cg12680131 and cg22511877 above the median compared with those with levels below the median. These associations were still statistically significant in multivariable conditional logistic regression models after adjusting for hepatitis B virus infection and alcohol consumption. CONCLUSION: These findings support the measurement of methylation markers in WBC DNA

  15. Running Pace Decrease during a Marathon Is Positively Related to Blood Markers of Muscle Damage

    PubMed Central

    Del Coso, Juan; Fernández, David; Abián-Vicen, Javier; Salinero, Juan José; González-Millán, Cristina; Areces, Francisco; Ruiz, Diana; Gallo, César; Calleja-González, Julio; Pérez-González, Benito

    2013-01-01

    Background Completing a marathon is one of the most challenging sports activities, yet the source of running fatigue during this event is not completely understood. The aim of this investigation was to determine the cause(s) of running fatigue during a marathon in warm weather. Methodology/Principal Findings We recruited 40 amateur runners (34 men and 6 women) for the study. Before the race, body core temperature, body mass, leg muscle power output during a countermovement jump, and blood samples were obtained. During the marathon (27 °C; 27% relative humidity) running fatigue was measured as the pace reduction from the first 5-km to the end of the race. Within 3 min after the marathon, the same pre-exercise variables were obtained. Results Marathoners reduced their running pace from 3.5 ± 0.4 m/s after 5-km to 2.9 ± 0.6 m/s at the end of the race (P<0.05), although the running fatigue experienced by the marathoners was uneven. Marathoners with greater running fatigue (> 15% pace reduction) had elevated post-race myoglobin (1318 ± 1411 v 623 ± 391 µg L−1; P<0.05), lactate dehydrogenase (687 ± 151 v 583 ± 117 U L−1; P<0.05), and creatine kinase (564 ± 469 v 363 ± 158 U L−1; P = 0.07) in comparison with marathoners that preserved their running pace reasonably well throughout the race. However, they did not differ in their body mass change (−3.1 ± 1.0 v −3.0 ± 1.0%; P = 0.60) or post-race body temperature (38.7 ± 0.7 v 38.9 ± 0.9 °C; P = 0.35). Conclusions/Significance Running pace decline during a marathon was positively related with muscle breakdown blood markers. To elucidate if muscle damage during a marathon is related to mechanistic or metabolic factors requires further investigation. PMID:23460881

  16. Air pollution and blood lipid markers levels: Estimating short and long-term effects on elderly hypertension inpatients complicated with or without type 2 diabetes.

    PubMed

    Xiao, Sanhua; Liu, Ranran; Wei, Youxiu; Feng, Lin; Lv, Xuemin; Tang, Fei

    2016-08-01

    With the development of society and the economy, many Chinese cities are shrouded in pollution haze for much of the year. Scientific studies have identified various adverse effects of air pollutants on human beings. However, the relationships between air pollution and blood lipid levels are still unclear. The objective of this study is to explore the short and long-term effects of air pollution on eight blood lipid markers among elderly hypertension inpatients complicated with or without type 2 diabetes (T2D). Blood lipid markers which met the pre-established inclusion criteria were exported from the medical record system. Air pollution data were acquired from the official environmental protection website. Associations between the air quality index and the blood lipid indexes were analyzed by one-way ANOVA and further Bonferroni correction. In an exposure time of 7 days or longer, blood lipid markers were somewhat affected by poor air quality. However, the results could not predict whether atherosclerosis would be promoted or inhibited by poorer air condition. Changes of blood lipid markers of hypertension inpatients with or without T2D were not completely the same, but no blood lipid markers had an opposite trend between the two populations. The air quality index was associated with changes to blood lipid markers to some extent in a population of hypertension inpatients with or without T2D. Further studies are needed to investigate the potential mechanism by which air pollutants induce blood lipids changes.

  17. Air pollution and blood lipid markers levels: Estimating short and long-term effects on elderly hypertension inpatients complicated with or without type 2 diabetes.

    PubMed

    Xiao, Sanhua; Liu, Ranran; Wei, Youxiu; Feng, Lin; Lv, Xuemin; Tang, Fei

    2016-08-01

    With the development of society and the economy, many Chinese cities are shrouded in pollution haze for much of the year. Scientific studies have identified various adverse effects of air pollutants on human beings. However, the relationships between air pollution and blood lipid levels are still unclear. The objective of this study is to explore the short and long-term effects of air pollution on eight blood lipid markers among elderly hypertension inpatients complicated with or without type 2 diabetes (T2D). Blood lipid markers which met the pre-established inclusion criteria were exported from the medical record system. Air pollution data were acquired from the official environmental protection website. Associations between the air quality index and the blood lipid indexes were analyzed by one-way ANOVA and further Bonferroni correction. In an exposure time of 7 days or longer, blood lipid markers were somewhat affected by poor air quality. However, the results could not predict whether atherosclerosis would be promoted or inhibited by poorer air condition. Changes of blood lipid markers of hypertension inpatients with or without T2D were not completely the same, but no blood lipid markers had an opposite trend between the two populations. The air quality index was associated with changes to blood lipid markers to some extent in a population of hypertension inpatients with or without T2D. Further studies are needed to investigate the potential mechanism by which air pollutants induce blood lipids changes. PMID:27180144

  18. Can We Reduce Negative Blood Cultures With Clinical Scores and Blood Markers? Results From an Observational Cohort Study

    PubMed Central

    Laukemann, Svenja; Kasper, Nina; Kulkarni, Prasad; Steiner, Deborah; Rast, Anna Christina; Kutz, Alexander; Felder, Susan; Haubitz, Sebastian; Faessler, Lukas; Huber, Andreas; Fux, Christoph A.; Mueller, Beat; Schuetz, Philipp

    2015-01-01

    Abstract Only a small proportion of blood cultures routinely performed in emergency department (ED) patients is positive. Multiple clinical scores and biomarkers have previously been examined for their ability to predict bacteremia. Conclusive clinical validation of these scores and biomarkers is essential. This observational cohort study included patients with suspected infection who had blood culture sampling at ED admission. We assessed 5 clinical scores and admission concentrations of procalcitonin (PCT), C-reactive protein (CRP), lymphocyte and white blood cell counts, the neutrophil-lymphocyte count ratio (NLCR), and the red blood cell distribution width (RDW). Two independent physicians assessed true blood culture positivity. We used logistic regression models with area under the curve (AUC) analysis. Of 1083 patients, 104 (9.6%) had positive blood cultures. Of the clinical scores, the Shapiro score performed best (AUC 0.729). The best biomarkers were PCT (AUC 0.803) and NLCR (AUC 0.700). Combining the Shapiro score with PCT levels significantly increased the AUC to 0.827. Limiting blood cultures only to patients with either a Shapiro score of ≥4 or PCT > 0.1 μg/L would reduce negative sampling by 20.2% while still identifying 100% of positive cultures. Similarly, a Shapiro score ≥3 or PCT >0.25 μg/L would reduce cultures by 41.7% and still identify 96.1% of positive blood cultures. Combination of the Shapiro score with admission levels of PCT can help reduce unnecessary blood cultures with minimal false negative rates. The study was registered on January 9, 2013 at the ‘ClinicalTrials.gov’ registration web site (NCT01768494). PMID:26656373

  19. Concentration and Methylation of Cell-Free DNA from Blood Plasma as Diagnostic Markers of Renal Cancer

    PubMed Central

    Tsyba, Liudmyla; Onyshchenko, Kateryna; Kashparova, Olena; Nikolaienko, Oleksii; Panasenko, Grigory; Vozianov, Sergii; Romanenko, Alina; Rynditch, Alla

    2016-01-01

    The critical point for successful treatment of cancer is diagnosis at early stages of tumor development. Cancer cell-specific methylated DNA has been found in the blood of cancer patients, indicating that cell-free DNA (cfDNA) circulating in the blood is a convenient tumor-associated DNA marker. Therefore methylated cfDNA can be used as a minimally invasive diagnostic marker. We analysed the concentration of plasma cfDNA and methylation of six tumor suppressor genes in samples of 27 patients with renal cancer and 15 healthy donors as controls. The cfDNA concentrations in samples from cancer patients and healthy donors was measured using two different methods, the SYBR Green I fluorescence test and quantitative real-time PCR. Both methods revealed a statistically significant increase of cfDNA concentrations in cancer patients. Hypermethylation on cfDNA was detected for the LRRC3B (74.1%), APC (51.9%), FHIT (55.6%), and RASSF1 (62.9%) genes in patients with renal cancer. Promoter methylation of VHL and ITGA9 genes was not found on cfDNA. Our results confirmed that the cfDNA level and methylation of CpG islands of RASSF1A, FHIT, and APC genes in blood plasma can be used as noninvasive diagnostic markers of cancer. PMID:27725787

  20. Modelling circulating tumour cells for personalised survival prediction in metastatic breast cancer.

    PubMed

    Ascolani, Gianluca; Occhipinti, Annalisa; Liò, Pietro

    2015-05-01

    Ductal carcinoma is one of the most common cancers among women, and the main cause of death is the formation of metastases. The development of metastases is caused by cancer cells that migrate from the primary tumour site (the mammary duct) through the blood vessels and extravasating they initiate metastasis. Here, we propose a multi-compartment model which mimics the dynamics of tumoural cells in the mammary duct, in the circulatory system and in the bone. Through a branching process model, we describe the relation between the survival times and the four markers mainly involved in metastatic breast cancer (EPCAM, CD47, CD44 and MET). In particular, the model takes into account the gene expression profile of circulating tumour cells to predict personalised survival probability. We also include the administration of drugs as bisphosphonates, which reduce the formation of circulating tumour cells and their survival in the blood vessels, in order to analyse the dynamic changes induced by the therapy. We analyse the effects of circulating tumour cells on the progression of the disease providing a quantitative measure of the cell driver mutations needed for invading the bone tissue. Our model allows to design intervention scenarios that alter the patient-specific survival probability by modifying the populations of circulating tumour cells and it could be extended to other cancer metastasis dynamics.

  1. Modelling Circulating Tumour Cells for Personalised Survival Prediction in Metastatic Breast Cancer

    PubMed Central

    2015-01-01

    Ductal carcinoma is one of the most common cancers among women, and the main cause of death is the formation of metastases. The development of metastases is caused by cancer cells that migrate from the primary tumour site (the mammary duct) through the blood vessels and extravasating they initiate metastasis. Here, we propose a multi-compartment model which mimics the dynamics of tumoural cells in the mammary duct, in the circulatory system and in the bone. Through a branching process model, we describe the relation between the survival times and the four markers mainly involved in metastatic breast cancer (EPCAM, CD47, CD44 and MET). In particular, the model takes into account the gene expression profile of circulating tumour cells to predict personalised survival probability. We also include the administration of drugs as bisphosphonates, which reduce the formation of circulating tumour cells and their survival in the blood vessels, in order to analyse the dynamic changes induced by the therapy. We analyse the effects of circulating tumour cells on the progression of the disease providing a quantitative measure of the cell driver mutations needed for invading the bone tissue. Our model allows to design intervention scenarios that alter the patient-specific survival probability by modifying the populations of circulating tumour cells and it could be extended to other cancer metastasis dynamics. PMID:25978366

  2. Effect of age and Blood Pressure on Surrogate Markers of Atherosclerosis in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Kulkarni, Namrata Bindurao; Ganu, Meghana Ulhas; Godbole, Sanjay Ganesh

    2014-01-01

    Background: Increased arterial stiffness may be an important path- way linking diabetes mellitus to increased cardiovascular risk. Aim: The study was conducted to assess the surrogate markers of arterial stiffness in patients with Type 2 diabetes mellitus (T2DM), and compare with age-matched hypertensive and healthy controls. Also the effect of age and blood pressure on these markers was evaluated. Settings and Design: This cross-sectional study was carried out at a tertiary care hospital in West India. Methods: After a detailed medical history and anthropometric evaluation, all the participants were subjected to measurements of Arterial Stiffness Index (ASI), Pulse Wave Velocity (PWV), and Augmentation Index (AIx) using a non-invasive oscillometric method. The four study groups consisted of patients with T2DM (>5 years) along with hypertension, newly diagnosed patients with T2DM (<2years) without hypertension, hypertensive controls, and healthy controls. Results: PWV, ASI, AIx were elevated in patients with T2DM compared to healthy controls (p<0.05). Patients with T2DM above 60 years had higher carotid-femoral PWV, ASI and AIx than those below 60 years (p<0.05). ASI and AIx were significantly increased in patients with T2DM with hypertension having systolic BP > 140 mmHg compared to those with systolic BP < 140 mmHg. A very strong correlation between PWV and AIx in patients with T2DM and hypertensive controls was observed. Conclusion: This study reveals that markers of arterial stiffness (PWV, ASI, AIx) were increased significantly in patients with T2DM compared to healthy controls. Age and systolic blood pressure had significant influence on these markers. Thus, oscillometric markers have potential utility in identifying subclinical atherosclerosis in patients with T2DM. PMID:25120969

  3. REACTIVE OXYGEN SPECIES IN WHOLE BLOOD, BLOOD PLASMA AND BREAST MILK: VALIDATION OF A POTENTIAL MARKER OF EXPOSURE AND EFFECT

    EPA Science Inventory

    Reactive oxygen species (ROS) are recognized to contribute to the pathobiology of many diseases. We have applied a simple chemiluminescent (CL) probe to detect ROS in various biological fluids (plasma, whole blood, urine and breast milk) in an environmental arsenic drinking wate...

  4. In vivo magnetic enrichment and multiplex photoacoustic detection of circulating tumour cells.

    PubMed

    Galanzha, Ekaterina I; Shashkov, Evgeny V; Kelly, Thomas; Kim, Jin-Woo; Yang, Lily; Zharov, Vladimir P

    2009-12-01

    The spread of cancer cells between organs, a process known as metastasis, is the cause of most cancer deaths. Detecting circulating tumour cells -- a common marker for the development of metastasis -- is difficult because ex vivo methods are not sensitive enough owing to limited blood sample volume and in vivo diagnosis is time-consuming as large volumes of blood must be analysed. Here, we show a way to magnetically capture circulating tumour cells in the bloodstream of mice followed by rapid photoacoustic detection. Magnetic nanoparticles, which were functionalized to target a receptor commonly found in breast cancer cells, bound and captured circulating tumour cells under a magnet. To improve detection sensitivity and specificity, gold-plated carbon nanotubes conjugated with folic acid were used as a second contrast agent for photoacoustic imaging. By integrating in vivo multiplex targeting, magnetic enrichment, signal amplification and multicolour recognition, our approach allows circulating tumour cells to be concentrated from a large volume of blood in the vessels of tumour-bearing mice, and this could have potential for the early diagnosis of cancer and the prevention of metastasis in humans.

  5. MED12 exon 2 mutation as a highly sensitive and specific marker in distinguishing phyllodes tumours from other spindle neoplasms of the breast.

    PubMed

    Lien, Huang-Chun; Huang, Chiun-Sheng; Yang, Ya-Wen; Jeng, Yung-Ming

    2016-05-01

    Spindle neoplasms of the breast (SNB) primarily include metaplastic breast carcinoma (MBC), phyllodes tumour (PT), fibromatosis and primary nonspecific sarcoma (PNS). Mutations in MED12 exon 2 have been reported in PTs. Because spindle tumour components are shared by SNB, we assessed the diagnostic use of MED12 exon 2 mutation in SNB. We investigated MED12 exon 2 mutations in a total of 91 samples of SNB, including 49 PT cases that have been previously analysed. Mutations were identified using direct sequencing. MED12 exon 2 mutation was absent in all cases of MBC, fibromatosis and PNS, in contrast to the 71.4% positivity in PTs. MED12 mutations were identified in four of six previously diagnosed monophasic sarcomatous MCB cases, however, these four cases were revised as malignant PT based on additional bcl-2 staining, albeit very focal. Consistence in the MED12 mutational status between a paired core biopsy and a surgical specimen was observed in all 20 tested PT cases. In conclusion, we demonstrated the restriction of MED12 exon 2 mutation to PTs (73.6%, 39/53) and its absence in other SNB. MED12 exon 2 mutational analysis can be included in the differential diagnosis between PT and other SNB, especially with limited specimen where diagnostic clues are not evident.

  6. THE STABILITY OF MARKERS IN DRIED-BLOOD SPOTS FOR RECOMMENDED NEWBORN SCREENING DISORDERS IN THE UNITED STATES

    PubMed Central

    Adam, BW; Hall, EM; Sternberg, M; Lim, TH; Flores, SR; O’Brien, S; Simms, D; Li, LX; De Jesus, VR; Hannon, WH

    2015-01-01

    Objective We aimed to measure separately the contributions of heat and humidity to changes in levels of 34 markers of inborn disorders in dried-blood-spot (DBS) samples. Design and Methods Paired sets of DBSs were stored at 37°C for predetermined intervals in low-humidity and high-humidity environments. Marker levels of all samples in each complete sample set were measured in a single analytic run. Results During the 30±5 day study, galactose-1-phosphate uridyltransferase and biotinidase lost almost 65% of initial activities in low-humidity storage; most of the degradation in 27 other markers was attributable to adverse effects of high humidity storage; seven markers in DBSs stored at high humidity lost more than 90% of initial levels by the end of the study and four of the seven lost more than 50% of initial levels within the first week of storage. Conclusions Minimizing both humidity and temperature in the DBS transportation and storage environments is essential to maintaining sample integrity. PMID:21963384

  7. Ontogeny of four blood-brain barrier markers: an immunocytochemical comparison of pial and cerebral cortical microvessels.

    PubMed Central

    Cassella, J P; Lawrenson, J G; Allt, G; Firth, J A

    1996-01-01

    Pial and cortical microvessels possess many blood-brain barrier (BBB) properties in common, including impermeability to electron dense tracers, high transendothelial electrical resistance and specialised endothelial cell ultrastructural features. To compare pial and cortical microvessels further, a developmental, immunocytochemical study was undertaken of 4 BBB markers in the rat: OX-47, EBA, GLUT-1 and s-laminin. The appearance of the markers was monitored from embryonic d 16, to postnatal and adult stages. Each of the 4 markers appeared simultaneously in both pial and cortical vessels. GLUT-1 and OX-47 were present in endothelial cells of the BBB from E 16 to the adult. EBA and s-laminin appeared from postnatal d 7 through to the adult. Pial microvessels lack the ensheathment of astrocytes which may be involved in the induction and/or maintenance of BBB markers in the cortex. It is possible that astrocyte-derived factors diffusing from the brain surface are responsible for induction of BBB properties in the pial microvessels. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 PMID:8886962

  8. The chronic effects of whey proteins on blood pressure, vascular function, and inflammatory markers in overweight individuals.

    PubMed

    Pal, Sebely; Ellis, Vanessa

    2010-07-01

    Limited evidence suggests that dairy whey protein may be the major dairy component that is responsible for health benefits currently associated with increased dairy consumption. Whey proteins may reduce blood pressure and improve cardiovascular health. This study evaluated the effects of whey protein supplementation on blood pressure, vascular function and inflammatory markers compared to casein and glucose (control) supplementation in overweight/obese individuals. The subjects were randomized to either whey protein, casein or glucose supplementation for 12 weeks according to a parallel design. In all, 70 men and women with a mean (+/-s.e.m.) BMI (kg/m(2)) of 31.3 +/- 0.8 completed the study. Systolic blood pressure (SBP) decreased significantly at week 6 compared to baseline in the whey and casein groups, (P = 0.028 and P = 0.020, respectively) and at week 12 (P = 0.020, and P = 0.017, respectively). Diastolic blood pressure (DBP) decreased significantly compared to baseline in the whey and casein groups (P = 0.038 and P = 0.042, respectively) at week 12. DBP decreased significantly in the whey and casein groups (P = 0.025, P = 0.038, respectively) at week 12 compared to the control group. Augmentation index (AI) was significantly lower from baseline at 12 weeks (P = 0.021) in the whey group. AI decreased significantly in the whey group at 12 weeks compared to control (P = 0.006) and casein (P = 0.006). There were no significant changes in inflammatory markers within or between groups. This study demonstrated that supplementation with whey protein improves blood pressure and vascular function in overweight and obese individuals.

  9. Prevalence and heterogeneity of circulating tumour cells in metastatic cutaneous melanoma.

    PubMed

    Khoja, Leila; Shenjere, Patrick; Hodgson, Clare; Hodgetts, Jackie; Clack, Glen; Hughes, Andrew; Lorigan, Paul; Dive, Caroline

    2014-02-01

    We previously demonstrated that circulating tumour cells (CTCs) are detectable by the MelCAM and high molecular weight melanoma-associated antigen (HMW-MAA)-dependent CellSearch platform. However, CTCs which do not express these capture and detection markers are not detectable by CellSearch. Consequently, we explored the use of isolation by size of epithelial tumour cells (ISET), a marker independent, filtration-based device to determine the prevalence and heterogeneity of CTCs in metastatic cutaneous melanoma patients. Ninety patients were prospectively recruited and blood samples taken before treatment. Patients' blood was filtered using the ISET platform. CTCs were enumerated using dual immunohistochemistry with positive selection by S100 expression and exclusion of leucocytes and endothelial cells expressing CD45 or CD144, respectively. A panel of markers (Melan-A, MITF, MelCAM, high molecular melanoma-associated antigen, CD271 and MAGEC) was also examined. Fifty-one patients (57%) had CTCs (range 1-44 CTCs/4 ml blood) and 12 patients also had circulating tumour microemboli. Seven patients had S100- CTCs, 11 patients' CTCs were S100+ and 33 patients had S100+ and S100- CTCs. Substantial intrapatient and interpatient heterogeneity was observed for all other melanoma-associated markers. CTCs in metastatic cutaneous melanoma are detectable using the flexible marker-independent ISET platform. CTCs display significant marker expression heterogeneity implying that marker-dependent platforms would not detect all CTCs and multimarker assays are now required to reveal the biological significance of this CTC heterogeneity.

  10. Prevalence and heterogeneity of circulating tumour cells in metastatic cutaneous melanoma.

    PubMed

    Khoja, Leila; Shenjere, Patrick; Hodgson, Clare; Hodgetts, Jackie; Clack, Glen; Hughes, Andrew; Lorigan, Paul; Dive, Caroline

    2014-02-01

    We previously demonstrated that circulating tumour cells (CTCs) are detectable by the MelCAM and high molecular weight melanoma-associated antigen (HMW-MAA)-dependent CellSearch platform. However, CTCs which do not express these capture and detection markers are not detectable by CellSearch. Consequently, we explored the use of isolation by size of epithelial tumour cells (ISET), a marker independent, filtration-based device to determine the prevalence and heterogeneity of CTCs in metastatic cutaneous melanoma patients. Ninety patients were prospectively recruited and blood samples taken before treatment. Patients' blood was filtered using the ISET platform. CTCs were enumerated using dual immunohistochemistry with positive selection by S100 expression and exclusion of leucocytes and endothelial cells expressing CD45 or CD144, respectively. A panel of markers (Melan-A, MITF, MelCAM, high molecular melanoma-associated antigen, CD271 and MAGEC) was also examined. Fifty-one patients (57%) had CTCs (range 1-44 CTCs/4 ml blood) and 12 patients also had circulating tumour microemboli. Seven patients had S100- CTCs, 11 patients' CTCs were S100+ and 33 patients had S100+ and S100- CTCs. Substantial intrapatient and interpatient heterogeneity was observed for all other melanoma-associated markers. CTCs in metastatic cutaneous melanoma are detectable using the flexible marker-independent ISET platform. CTCs display significant marker expression heterogeneity implying that marker-dependent platforms would not detect all CTCs and multimarker assays are now required to reveal the biological significance of this CTC heterogeneity. PMID:24201293

  11. Peripheral blood and neuropsychological markers for the onset of action of antidepressant drugs in patients with Major Depressive Disorder

    PubMed Central

    2011-01-01

    Background In Major Depressive Disorder (MDD), treatment outcomes with currently available strategies are often disappointing. Therefore, it is sensible to develop new strategies to increase remission rates in acutely depressed patients. Many studies reported that true drug response can be observed within 14 days (early improvement) of antidepressant treatment. The identical time course of symptom amelioration after early improvement in patients treated with antidepressants of all classes or with placebo strongly suggests a common biological mechanism, which is not specific for a particular antidepressant medication. However, the biology underlying early improvement and final treatment response is not understood and there is no established biological marker as yet, which can predict treatment response for the individual patient before initiation or during the course of antidepressant treatment. Peripheral blood markers and executive functions are particularly promising candidates as markers for the onset of action and thus the prediction of final treatment outcome in MDD. Methods/Design The present paper presents the rationales, objectives and methods of a multi-centre study applying close-meshed repetitive measurements of peripheral blood and neuropsychological parameters in patients with MDD and healthy controls during a study period of eight weeks for the identification of biomarkers for the onset of antidepressants' action in patients with MDD. Peripheral blood parameters and depression severity are assessed in weekly intervals from baseline to week 8, executive performance in bi-weekly intervals. Patients are participating in a randomized controlled multi-level clinical trial, healthy controls are matched according to mean age, sex and general intelligence. Discussion This investigation will help to identify a biomarker or a set of biomarkers with decision-making quality in the treatment of MDD in order to increase the currently disappointing remission rates

  12. Isolated, disseminated and circulating tumour cells in prostate cancer.

    PubMed

    Schilling, David; Todenhöfer, Tilman; Hennenlotter, Jörg; Schwentner, Christian; Fehm, Tanja; Stenzl, Arnulf

    2012-08-01

    The loss of single cells from a tumour cell cluster marks an early event in the metastatic process of cancer progression. Although the metastatic cascade in prostate cancer is yet to be fully understood, monitoring circulating tumour cells (CTCs) and quantifying the load of tumour cell dissemination is currently being implemented into routine clinical practice for diagnosing minimal residual disease (MRD), estimating prognosis and monitoring treatment success. Current methods for enrichment of CTCs or disseminated tumour cells (DTCs) and detection of MRD rely on the expression of specific marker genes or proteins that might be altered during the process of tumour cell dissemination, therefore disrupting tumour cell detection. The tumour origin and malignant potential for metastasis of marker-positive cells is not yet clear. Some studies have demonstrated the potential of CTCs or DTCs as prognostic or predictive markers, leading to the increasing implementation of CTC measurement as an end point in clinical trials.

  13. Intra-tumoural microvessel density in human solid tumours

    PubMed Central

    Hasan, J; Byers, R; Jayson, G C

    2002-01-01

    Over the last decade assessment of angiogenesis has emerged as a potentially useful biological prognostic and predictive factor in human solid tumours. With the development of highly specific endothelial markers that can be assessed in histological archival specimens, several quantitative studies have been performed in various solid tumours. The majority of published studies have shown a positive correlation between intra-tumoural microvessel density, a measure of tumour angiogenesis, and prognosis in solid tumours. A minority of studies have not demonstrated an association and this may be attributed to significant differences in the methodologies employed for sample selection, immunostaining techniques, vessel counting and statistical analysis, although a number of biological differences may account for the discrepancy. In this review we evaluate the quantification of angiogenesis by immunohistochemistry, the relationship between tumour vascularity and metastasis, and the clinicopathological studies correlating intra-tumoral microvessel density with prognosis and response to anti-cancer therapy. In view of the extensive nature of this retrospective body of data, comparative studies are needed to identify the optimum technique and endothelial antigens (activated or pan-endothelial antigens) but subsequently prospective studies that allocate treatment on the basis of microvessel density are required. British Journal of Cancer (2002) 86, 1566–1577. DOI: 10.1038/sj/bjc/6600315 www.bjcancer.com © 2002 Cancer Research UK PMID:12085206

  14. Ultrasound-based Measurement of Molecular Marker Concentration in Large Blood Vessels: A Feasibility Study

    PubMed Central

    Wang, Shiying; Mauldin, F. William; Klibanov, Alexander L.; Hossack, John A.

    2014-01-01

    Ultrasound molecular imaging has demonstrated efficacy in pre-clinical studies for cancer and cardiovascular inflammation. However, these techniques often require lengthy protocols due to waiting periods or additional control microbubble injections. Moreover, they are not capable of quantifying molecular marker concentration in human tissue environments that exhibit variable attenuation and propagation path lengths. Our group recently investigated a modulated Acoustic Radiation Force (ARF)-based imaging sequence, which was demonstrated to detect targeted adhesion independent of control measurements. In the present study, this sequence was tested against various experimental parameters to determine feasibility for quantitative measurements of molecular marker concentration. Results demonstrated that measurements obtained from the sequence (residual-to-saturation ratio, Rresid) were independent of acoustic pressure and attenuation (p> 0.13, n = 10)when acoustic pressures were sufficiently low. The Rresid parameter exhibited a linear relationship with measured molecular marker concentration (R2> 0.94). Consequently, feasibility was demonstrated in vitro, for quantification of molecular marker concentration in large vessels using a modulated ARF-based sequence. Moreover, these measurements were independent of absolute acoustic reflection amplitude and used short imaging protocols(3 min) without control measurements. PMID:25308943

  15. Ultrasound-based measurement of molecular marker concentration in large blood vessels: a feasibility study.

    PubMed

    Wang, Shiying; Mauldin, F William; Klibanov, Alexander L; Hossack, John A

    2015-01-01

    Ultrasound molecular imaging has demonstrated efficacy in pre-clinical studies for cancer and cardiovascular inflammation. However, these techniques often require lengthy protocols because of waiting periods or additional control microbubble injections. Moreover, they are not capable of quantifying molecular marker concentration in human tissue environments that exhibit variable attenuation and propagation path lengths. Our group recently investigated a modulated acoustic radiation force-based imaging sequence, which was found to detect targeted adhesion independent of control measurements. In the present study, this sequence was tested against various experimental parameters to determine its feasibility for quantitative measurements of molecular marker concentration. Results indicated that measurements obtained from the sequence (residual-to-saturation ratio, Rresid) were independent of acoustic pressure and attenuation (p > 0.13, n = 10) when acoustic pressures were sufficiently low. The Rresid parameter exhibited a linear relationship with measured molecular marker concentration (R(2) > 0.94). Consequently, feasibility was illustrated in vitro, for quantification of molecular marker concentration in large vessels using a modulated acoustic radiation force-based sequence. Moreover, these measurements were independent of absolute acoustic reflection amplitude and used short imaging protocols (3 min) without control measurements.

  16. Expression of Early Activation Marker CD69 on Peripheral Blood Lymphocytes from Pregnant Women after First Trimester Alloimmunization.

    PubMed

    Krechetova, L V; Vtorushina, V V; Nikolaeva, M A; Golubeva, E L; Van'ko, L V; Saribegova, V A; Tetruashvili, N K

    2016-08-01

    We studied the expression of an early activation marker CD69 in peripheral blood lymphocytes of pregnant women with a history of recurrent pregnancy loss after immunization with paternal lymphocytes. Spontaneous and phytohemagglutinin-stimulated expression of CD69 on the surface of T cells and NK cells isolated from the peripheral blood was analyzed. On gestation week 5-6, the number of T cells expressing CD69 spontaneously and after stimulation was significantly higher in women with miscarriage than in woman with prolonged pregnancy. However, the number of cells with CD56(+) phenotype expressing CD69 did not differ in these groups. No differences were found in the number of cells of all subpopulations expressing CD69 after stimulation on gestation week 12 in woman with full-term current pregnancy and in woman with physiological pregnancy. PMID:27591871

  17. Solitary fibrous tumour: a diagnostic dilemma.

    PubMed

    Ghosh, Sharmila; Shet, Tanuja M; Chinoy, R F; Kane, S V

    2007-07-01

    Solitary fibrous tumour (SFT) is a rare spindle cell neoplasm arising at pleural and extrapleural sites. Five cases of SFT diagnosed at our institution over a five year period were reviewed. Haematoxylin and eosin stained histological sections, immuno-histochemical markers including CD34 and electron microscopy were the different methods used to study these tumours. Three histological features were consistently observed in all the tumours: the tumours were composed of short spindle cells separated by dense collagen bands and arranged in alternate hypocellular and hypercellular areas. CD34 positivity was seen in all the cases. SFT's have been reported to behave in an unpredictable fashion and hence prolonged follow up is essential. Histology, CD34 positivity and electron microscopy are useful tools in diagnosing SFT. While the pleural tumours can be diagnosed based on histology, this must be substantiated by ancillary techniques in case of extrapleural tumours.

  18. Cyclic volatile methylsiloxanes in human blood as markers for ruptured silicone gel-filled breast implants.

    PubMed

    Rosendahl, Pia; Hippler, Joerg; Schmitz, Oliver J; Hoffmann, Oliver; Rusch, Peter

    2016-05-01

    The replacement of medical-grade silicone with industrial-grade silicone material in some silicone gel-filled breast implants (SBI) manufactured by Poly Implant Prothèse and Rofil Medical Nederland B.V., reported in 2010, which resulted in a higher rupture tendency of these SBI, demonstrates the need for non-invasive, sensitive monitoring and screening methods. Therefore a sensitive method based on large volume injection-gas chromatography coupled to mass spectrometry (LVI-GC/MS) was developed to determine octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), and dodecamethylcyclo-hexasiloxane (D6) in blood samples from women with intact (n = 13) and ruptured SBI (n = 11). With dichloromethane extraction, sample cooling during preparation, and analysis extraction efficiencies up to 100 % and limits of detection of 0.03-0.05 ng D4-D6/g blood were achieved. Blood samples from women with SBI were investigated. In contrast to women with intact SBI, in blood from women with ruptured SBI higher D4 and D6 concentrations up to 0.57 ng D4/g blood and 0.16 ng D6/g blood were detected. With concentrations above 0.18 D4 ng/blood and 0.10 ng D6/g blood as significant criteria for ruptured SBI, this developed analytical preoperative diagnostic method shows a significant increase of the recognition rate. Finally a higher precision (error rate 17%) than the commonly used clinical diagnostic method, mamma sonography (error rate 46%), was achieved. PMID:26968566

  19. Ambient particulate air pollution, heart rate variability, and blood markers of inflammation in a panel of elderly subjects.

    PubMed Central

    Pope, C Arden; Hansen, Matthew L; Long, Russell W; Nielsen, Karen R; Eatough, Norman L; Wilson, William E; Eatough, Delbert J

    2004-01-01

    Epidemiologic studies report associations between particulate air pollution and cardiopulmonary morbidity and mortality. Although the underlying pathophysiologic mechanisms remain unclear, it has been hypothesized that altered autonomic function and pulmonary/systemic inflammation may play a role. In this study we explored the effects of air pollution on autonomic function measured by changes in heart rate variability (HRV) and blood markers of inflammation in a panel of 88 elderly subjects from three communities along the Wasatch Front in Utah. Subjects participated in multiple sessions of 24-hr ambulatory electrocardiographic monitoring and blood tests. Regression analysis was used to evaluate associations between fine particulate matter [aerodynamic diameter less than or equal to 2.5 microm (PM2.5)] and HRV, C-reactive protein (CRP), blood cell counts, and whole blood viscosity. A 100- microg/m3 increase in PM2.5 was associated with approximately a 35 (SE = 8)-msec decline in standard deviation of all normal R-R intervals (SDNN, a measure of overall HRV); a 42 (SE = 11)-msec decline in square root of the mean of the squared differences between adjacent normal R-R intervals (r-MSSD, an estimate of short-term components of HRV); and a 0.81 (SE = 0.17)-mg/dL increase in CRP. The PM2.5-HRV associations were reasonably consistent and statistically robust, but the CRP association dropped to 0.19 (SE = 0.10) after excluding the most influential subject. PM2.5 was not significantly associated with white or red blood cell counts, platelets, or whole-blood viscosity. Most short-term variability in temporal deviations of HRV and CRP was not explained by PM2.5; however, the small statistically significant associations that were observed suggest that exposure to PM2.5 may be one of multiple factors that influence HRV and CRP. PMID:14998750

  20. In vivo detection of small tumour lesions by multi-pinhole SPECT applying a 99mTc-labelled nanobody targeting the Epidermal Growth Factor Receptor

    PubMed Central

    Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

    2016-01-01

    The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody 99mTc-D10 for visualizing small tumour lesions with volumes below 100 mm3 by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody 99mTc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm3 ± 21.2 and 26.6 mm3 ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of 99mTc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody 99mTc-D10. PMID:26912069

  1. 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. PMID:24996894

  2. Blood biochemical markers of bone turnover: pre-analytical and technical aspects of sample collection and handling.

    PubMed

    Lombardi, Giovanni; Lanteri, Patrizia; Colombini, Alessandra; Banfi, Giuseppe

    2012-02-03

    Casual or systematic errors occurring in pre-analytical, analytical or post-analytical phases influence laboratory test results. The areas where pre-analytical phase errors most often arise are: timing of specimen collection; selection of specimen type; and time and temperature of storage/transport. Bone turnover markers are clinically useful in evaluating bone metabolism. Although unquestionably valuable tools, little is known about the pre-analytical precautions for their correct use and there is no consensus on kind of sample, or storage time and temperature before analysis. Moreover, biological variability, because of uncontrollable and controllable factors, will affect pre-analytical variability. Serum should be preferred to simplify blood drawing; therefore, only one tube should be used for the analysis of all bone markers. Short-term storage at 4°C may be advisable to preserve stability, immediate storage at -70°C is recommended for longer periods, while avoiding repeated freeze-thawing cycles. Sampling should be performed in the morning in fasting subjects who have abstained from physical exercise for 24 h. This review aimed to give a knowledge update on pre-analytical phase precautions in performing bone turnover marker measurement.

  3. 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.

  4. 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

  5. Daily kiwifruit consumption did not improve blood pressure and markers of cardiovascular function in men with hypercholesterolemia.

    PubMed

    Gammon, Cheryl S; Kruger, Rozanne; Brown, Stephen J; Conlon, Cathryn A; von Hurst, Pamela R; Stonehouse, Welma

    2014-03-01

    Increasing fruit and vegetable consumption is a key lifestyle modification in the prevention and treatment of hypertension. Kiwifruit has previously been shown to have favorable effects on blood pressure (BP), likely through inhibiting angiotensin I-converting enzyme activity. We hypothesized that the replacement of 2 fruit servings in a healthy diet with 2 green kiwifruit a day would significantly improve BP and other markers of cardiovascular function, including heart rate, stroke volume, cardiac output, and total peripheral resistance, in a group of hypercholesterolemic men. Using a controlled cross-over study design, 85 subjects completed a 4-week healthy diet run-in period before randomization to one of two 4-week intervention sequences in which they either consumed 2 green kiwifruit a day plus a healthy diet (intervention) or consumed a healthy diet alone (control). Blood pressure and other measures of cardiovascular function (using a Finometer MIDI [Finapres Medical Systems B.V, Amsterdam, The Netherlands] and standard oscillometric device) and anthropometric measurements were taken before and at the end of the treatment periods. A physical activity questionnaire was completed during the last visit. Subjects were found to be predominantly normotensive (43.5%) or prehypertensive (50.6%) and quite physically active (>30 minutes of moderate to vigorous physical activity/day in >80% subjects). No significant differences were seen for BP or any of the other markers, including heart rate, stroke volume, cardiac output, and total peripheral resistance. In conclusion, in this hypercholesterolemic, nonhypertensive group, no beneficial effects on BP or other markers of cardiovascular function were seen when consuming 2 kiwifruit a day against the background of a healthy diet.

  6. Estimation of nonpaternity in the Mexican population of Nuevo Leon: a validation study with blood group markers.

    PubMed

    Cerda-Flores, R M; Barton, S A; Marty-Gonzalez, L F; Rivas, F; Chakraborty, R

    1999-07-01

    A method for estimating the general rate of nonpaternity in a population was validated using phenotype data on seven blood groups (A1A2BO, MNSs, Rh, Duffy, Lutheran, Kidd, and P) on 396 mother, child, and legal father trios from Nuevo León, Mexico. In all, 32 legal fathers were excluded as the possible father based on genetic exclusions at one or more loci (combined average exclusion probability of 0.694 for specific mother-child phenotype pairs). The maximum likelihood estimate of the general nonpaternity rate in the population was 0.118 +/- 0.020. The nonpaternity rates in Nuevo León were also seen to be inversely related with the socioeconomic status of the families, i.e., the highest in the low and the lowest in the high socioeconomic class. We further argue that with the moderately low (69.4%) power of exclusion for these seven blood group systems, the traditional critical values of paternity index (PI > or = 19) were not good indicators of true paternity, since a considerable fraction (307/364) of nonexcluded legal fathers had a paternity index below 19 based on the seven markers. Implications of these results in the context of genetic-epidemiological studies as well as for detection of true fathers for child-support adjudications are discussed, implying the need to employ a battery of genetic markers (possibly DNA-based tests) that yield a higher power of exclusion. We conclude that even though DNA markers are more informative, the probabilistic approach developed here would still be needed to estimate the true rate of nonpaternity in a population or to evaluate the precision of detecting true fathers. PMID:10407460

  7. PCR-based detection of salivary bacteria as a marker of expirated blood.

    PubMed

    Power, Daniel A; Cordiner, Stephen J; Kieser, Jules A; Tompkins, Geoffrey R; Horswell, Jacqui

    2010-06-01

    Distinguishing between bloodstains caused by a spatter pattern or by expirated blood may be crucial to a forensic investigation. Expirated blood is likely to be contaminated with saliva but current techniques have limited sensitivity, especially with small bloodstains. We report that a PCR assay, designed to detect salivary bacteria, can amplify streptococcal DNA from saliva stains applied to fabrics for at least 62 days after seeding. Bacterial DNA was detected when 0.01 microl of saliva was present in the stain and the amplification was not affected by contamination with blood. These findings indicate that PCR amplification of salivary microbial DNA may have application in the identification of expirated bloodstains in forensic case-work.

  8. Gastric calcifying fibrous tumour

    PubMed Central

    Attila, Tan; Chen, Dean; Gardiner, Geoffrey W; Ptak, Theadore W; Marcon, Norman E

    2006-01-01

    Intramucosal gastric tumours are most commonly found to be gastrointestinal stromal tumours or leiomyomas (smooth muscle tumours); however, a variety of other uncommon mesenchymal tumours can occur in the stomach wall. A rare benign calcifying fibrous tumour is reported and the endoscopic appearance, ultrasound findings and morphology are documented. A review of the literature found only two similar cases. PMID:16858502

  9. Blood genetic marker studies of a sheep-goat hybrid and its back-cross offspring.

    PubMed

    Tucker, E M; Denis, B; Kilgour, L

    1989-01-01

    Blood samples from a female sheep-goat hybrid and its back-cross male offspring were tested for electrophoretic variants of plasma albumin, transferrin and esterase, and of red cell carbonic anhydrase, nucleoside phosphorylase, NADH-diaphorase, 'X'-protein, superoxide dismutase, malic enzyme and haemoglobin. Red cells were also tested for blood group antigens. Both animals showed variants that could not be attributed to either sheep or goat alone, thus confirming previous chromosomal data that the female was a genuine sheep-goat hybrid. PMID:2757269

  10. DHA concentration of red blood cells is inversely associated with markers of lipid peroxidation in men taking DHA supplement

    PubMed Central

    Shichiri, Mototada; Adkins, Yuriko; Ishida, Noriko; Umeno, Aya; Shigeri, Yasushi; Yoshida, Yasukazu; Fedor, Dawn M.; Mackey, Bruce E.; Kelley, Darshan S.

    2014-01-01

    An increase in the proportion of fatty acids with higher numbers of double bonds is believed to increase lipid peroxidation, which augments the risk for many chronic diseases. (n-3) Polyunsaturated fatty acids provide various health benefits, but there is a concern that they might increase lipid peroxidation. We examined the effects of docosahexaenoic acid [22:6 (n-3)] supplementation on lipid peroxidation markers in plasma and red blood cells (RBC) and their associations with red blood cell and plasma fatty acids. Hypertriglyceridemic men (n = 17 per group) aged 39–66 years participated in a double-blind, randomized, placebo-controlled, parallel study. They received no supplements for the first 8 days and then received 7.5 g/day docosahexaenoic acid oil (3 g/day docosahexaenoic acid) or olive oil (placebo) for 90 days. Fasting blood samples were collected 0, 45, and 91 days after supplementation. Docosahexaenoic acid supplementation did not change plasma or RBC concentrations of lipid peroxidation markers (total hydroxyoctadecadienoic acid, total hydroxyeicosatetraenoic acid, total 8-isoprostaglandin F2α, 7α-hydroxycholesterol, 7β-hydroxycholesterol) when pre- and post-supplement values were compared. However, the post-supplement docosahexaenoic acid (DHA) concentration was inversely associated with RBC concentrations of ZE-HODE, EE-HODE, t-HODE, and total 8-isoprostaglandin F2α, (p<0.05). RBC concentration of hydroxycholesterol was also inversely associated with DHA but it did not attain significance (p = 0.07). Our results suggest that increased concentration of DHA in RBC lipids reduced lipid peroxidation. This may be another health benefit of DHA in addition to its many other health promoting effects. PMID:25411526

  11. The use of ABO blood groups as markers for mosquito biting studies.

    PubMed

    Bryan, J H; Smalley, M E

    1978-01-01

    Discrepancies between malaria inoculation rates measured entomologically and parasitologically may be explained, at least in part, if infants and children receive less mosquito bites per night than do adults. We found that this problem could be studied by choosing women and children of different ABO blood groups. In preliminary laboratory studies it was found that the blood group of a mosquito's blood meal could be determined in parous and nulliparous mosquitoes for at least 24 hours, and, nullipares up to 34 hours, after feeding. An antiserum against the O group was necessary to distinguish non A or B red cells from those of animal origin. Cross reactions did occur, presumably as a result of the digestion by mosquitoes of the red cell surfaces, but in every case the strongest and earliest developing agglutination was that of the host. Field studies were made using women and children sleeping under mosquito nets, the holes in which made the nets a trapping device. The women, on average, received over seven times more bites per night than did the children. The migration of blood-fed mosquitoes from one net to another was negligible.

  12. Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins.

    PubMed

    Ballard, Kevin D; Quann, Erin E; Kupchak, Brian R; Volk, Brittanie M; Kawiecki, Diana M; Fernandez, Maria Luz; Seip, Richard L; Maresh, Carl M; Kraemer, William J; Volek, Jeff S

    2013-11-01

    Statins positively impact plasma low-density lipoprotein cholesterol, inflammation and vascular endothelial function (VEF). Carbohydrate restricted diets (CRD) improve atherogenic dyslipidemia, and similar to statins, have been shown to favorably affect markers of inflammation and VEF. No studies have examined whether a CRD provides additional benefit beyond that achieved by habitual statin use. We hypothesized that a CRD (<50 g carbohydrate/d) for 6 weeks would improve lipid profiles and insulin sensitivity, reduce blood pressure, decrease cellular adhesion and inflammatory biomarkers, and augment VEF (flow-mediated dilation and forearm blood flow) in statin users. Participants (n = 21; 59.3 ± 9.3 y, 29.5 ± 3.0 kg/m(2)) decreased total caloric intake by approximately 415 kcal at 6 weeks (P < .001). Daily nutrient intakes at baseline (46/36/17% carb/fat/pro) and averaged across the intervention (11/58/28% carb/fat/pro) demonstrated dietary compliance, with carbohydrate intake at baseline nearly 5-fold greater than during the intervention (P < .001). Compared to baseline, both systolic and diastolic blood pressure decreased after 3 and 6 weeks (P < .01). Peak forearm blood flow, but not flow-mediated dilation, increased at week 6 compared to baseline and week 3 (P ≤ .03). Serum triglyceride, insulin, soluble E-Selectin and intracellular adhesion molecule-1 decreased (P < .01) from baseline at week 3, and this effect was maintained at week 6. In conclusion, these findings demonstrate that individuals undergoing statin therapy experience additional improvements in metabolic and vascular health from a 6 weeks CRD as evidenced by increased insulin sensitivity and resistance vessel endothelial function, and decreased blood pressure, triglycerides, and adhesion molecules. PMID:24176230

  13. Epigenome-wide methylation in DNA from peripheral blood as a marker of risk for breast cancer.

    PubMed

    Severi, Gianluca; Southey, Melissa C; English, Dallas R; Jung, Chol-hee; Lonie, Andrew; McLean, Catriona; Tsimiklis, Helen; Hopper, John L; Giles, Graham G; Baglietto, Laura

    2014-12-01

    Aberrant DNA methylation is a key feature of breast carcinoma. We aimed to test the association between breast cancer risk and epigenome-wide methylation in DNA from peripheral blood. Nested case-control study within the prospective Melbourne Collaborative Cohort Study. DNA was extracted from before-diagnosis blood samples (420 incident cases and matched controls). Methylation was measured with the Illumina Infinium Human Methylation 450 BeadChip array. Odds ratio (OR) for epigenome-wide methylation, quantified as the mean beta values across the CpGs, in relation to breast cancer risk were estimated using conditional logistic regression. Overall, the OR for breast cancer was 0.42 (95% CI 0.20-0.90) for the top versus bottom quartile of epigenome-wide DNA methylation and the OR for a one standard deviation increment was 0.69 (95% CI 0.50-0.95; test for linear trend, p = 0.02). Epigenome-wide DNA methylation of CpGs within functional promoters was associated with an increased risk, whereas epigenome-wide DNA methylation of genomic regions outside promoters was associated with decreased risk (test for heterogeneity, p = 0.0002). The increased risk associated with epigenome-wide DNA methylation in functional promoters did not vary by time between blood collection and diagnosis, whereas the inverse association with epigenome-wide DNA methylation outside functional promoters was strongest when the interval from blood collection to diagnosis was less than 5 years and weakest for the longest interval. Epigenome-wide methylation in DNA extracted from peripheral blood collected before diagnosis may have potential utility as markers of breast cancer risk and for early detection.

  14. Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins.

    PubMed

    Ballard, Kevin D; Quann, Erin E; Kupchak, Brian R; Volk, Brittanie M; Kawiecki, Diana M; Fernandez, Maria Luz; Seip, Richard L; Maresh, Carl M; Kraemer, William J; Volek, Jeff S

    2013-11-01

    Statins positively impact plasma low-density lipoprotein cholesterol, inflammation and vascular endothelial function (VEF). Carbohydrate restricted diets (CRD) improve atherogenic dyslipidemia, and similar to statins, have been shown to favorably affect markers of inflammation and VEF. No studies have examined whether a CRD provides additional benefit beyond that achieved by habitual statin use. We hypothesized that a CRD (<50 g carbohydrate/d) for 6 weeks would improve lipid profiles and insulin sensitivity, reduce blood pressure, decrease cellular adhesion and inflammatory biomarkers, and augment VEF (flow-mediated dilation and forearm blood flow) in statin users. Participants (n = 21; 59.3 ± 9.3 y, 29.5 ± 3.0 kg/m(2)) decreased total caloric intake by approximately 415 kcal at 6 weeks (P < .001). Daily nutrient intakes at baseline (46/36/17% carb/fat/pro) and averaged across the intervention (11/58/28% carb/fat/pro) demonstrated dietary compliance, with carbohydrate intake at baseline nearly 5-fold greater than during the intervention (P < .001). Compared to baseline, both systolic and diastolic blood pressure decreased after 3 and 6 weeks (P < .01). Peak forearm blood flow, but not flow-mediated dilation, increased at week 6 compared to baseline and week 3 (P ≤ .03). Serum triglyceride, insulin, soluble E-Selectin and intracellular adhesion molecule-1 decreased (P < .01) from baseline at week 3, and this effect was maintained at week 6. In conclusion, these findings demonstrate that individuals undergoing statin therapy experience additional improvements in metabolic and vascular health from a 6 weeks CRD as evidenced by increased insulin sensitivity and resistance vessel endothelial function, and decreased blood pressure, triglycerides, and adhesion molecules.

  15. Selective targeting of tumour neovasculature by a radiohalogenated human antibody fragment specific for the ED-B domain of fibronectin.

    PubMed

    Demartis, S; Tarli, L; Borsi, L; Zardi, L; Neri, D

    2001-04-01

    Angiogenesis is a characteristic feature of many aggressive tumours and other disorders. Antibodies capable of binding to new blood vessels, but not to mature vessels, could be used as selective targeting agents for immunoscintigraphic and radioimmunotherapeutic applications. Here we show that scFv(L19), a recombinant human antibody fragment with sub-nanomolar affinity for the ED-B domain of fibronectin, a marker of angiogenesis, can be stably labelled with iodine-125 and astatine-211 with full retention of immunoreactivity, using a trimethyl-stannyl benzoate bifunctional derivative. Biodistribution studies in mice bearing two different types of tumour grafted subcutaneously, followed by ex vivo micro-autoradiographic analysis, revealed that scFv(L19) rapidly localises around tumour blood vessels, but not around normal vessels. Four hours after intravenous injection of the stably radioiodinated scFv(L19), tumour to blood ratios were 6:1 in mice bearing the F9 murine teratocarcinoma and 9:1 in mice bearing an FE8 rat sarcoma. As expected, all other organs (including kidney) contained significantly less radioactivity than the tumour. Since the ED-B domain of fibronectin has an identical sequence in mouse and man, scFv(L19) is a pan-species antibody and the results presented here suggest clinical utility of radiolabelled scFv(L19) for the scintigraphic detection of angiogenesis in vivo. Furthermore, it should now be possible to investigate scFv(L19) for the selective delivery of 211At to the tumour neovasculature, causing the selective death of tumour endothelial cells and tumour collapse. PMID:11357506

  16. Diagnostic Performance of DNA Hypermethylation Markers in Peripheral Blood for the Detection of Colorectal Cancer: A Meta-Analysis and Systematic Review

    PubMed Central

    Li, Bingsheng; Gan, Aihua; Chen, Xiaolong; Wang, Xinying; He, Weifeng; Zhang, Xiaohui; Huang, Renxiang; Zhou, Shuzhu; Song, Xiaoxiao; Xu, Angao

    2016-01-01

    DNA hypermethylation in blood is becoming an attractive candidate marker for colorectal cancer (CRC) detection. To assess the diagnostic accuracy of blood hypermethylation markers for CRC in different clinical settings, we conducted a meta-analysis of published reports. Of 485 publications obtained in the initial literature search, 39 studies were included in the meta-analysis. Hypermethylation markers in peripheral blood showed a high degree of accuracy for the detection of CRC. The summary sensitivity was 0.62 [95% confidence interval (CI), 0.56–0.67] and specificity was 0.91 (95% CI, 0.89–0.93). Subgroup analysis showed significantly greater sensitivity for the methylated Septin 9 gene (SEPT9) subgroup (0.75; 95% CI, 0.67–0.81) than for the non-methylated SEPT9 subgroup (0.58; 95% CI, 0.52–0.64). Sensitivity and specificity were not affected significantly by target gene number, CRC staging, study region, or methylation analysis method. These findings show that hypermethylation markers in blood are highly sensitive and specific for CRC detection, with methylated SEPT9 being particularly robust. The diagnostic performance of hypermethylation markers, which have varied across different studies, can be improved by marker optimization. Future research should examine variation in diagnostic accuracy according to non-neoplastic factors. PMID:27158984

  17. FDG uptake, a surrogate of tumour hypoxia?

    PubMed Central

    Van de Wiele, Christophe

    2008-01-01

    Introduction Tumour hyperglycolysis is driven by activation of hypoxia-inducible factor-1 (HIF-1) through tumour hypoxia. Accordingly, the degree of 2-fluro-2-deoxy-d-glucose (FDG) uptake by tumours might indirectly reflect the level of hypoxia, obviating the need for more specific radiopharmaceuticals for hypoxia imaging. Discussion In this paper, available data on the relationship between hypoxia and FDG uptake by tumour tissue in vitro and in vivo are reviewed. In pre-clinical in vitro studies, acute hypoxia was consistently shown to increase FDG uptake by normal and tumour cells within a couple of hours after onset with mobilisation or modification of glucose transporters optimising glucose uptake, followed by a delayed response with increased rates of transcription of GLUT mRNA. In pre-clinical imaging studies on chronic hypoxia that compared FDG uptake by tumours grown in rat or mice to uptake by FMISO, the pattern of normoxic and hypoxic regions within the human tumour xenografts, as imaged by FMISO, largely correlated with glucose metabolism although minor locoregional differences could not be excluded. In the clinical setting, data are limited and discordant. Conclusion Further evaluation of FDG uptake by various tumour types in relation to intrinsic and bioreductive markers of hypoxia and response to radiotherapy or hypoxia-dependent drugs is needed to fully assess its application as a marker of hypoxia in the clinical setting. PMID:18509637

  18. Incidence of viral markers and evaluation of the estimated risk in the Swiss blood donor population from 1996 to 2003.

    PubMed

    Niederhauser, C; Schneider, P; Fopp, M; Ruefer, A; Lévy, G

    2005-02-01

    Among the well known transfusion-associated risks, the transmission of pathogenic viruses is regarded as one of the most serious. Over the past two decades, a series of overlapping safety procedures have been successively implemented to minimise this risk. It is now generally considered that the risk of transmitting viral infections via blood products is very low in developed countries. The present study analyses the incidence of the key infectious diseases HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) between 1996 and 2003 from 99% of voluntary repeat blood donors visiting the blood transfusion service of the Swiss Red Cross. Furthermore the estimated risk of these viral markers was calculated. From 1996 to 2003 the incidence rate for HCV decreased continuously, whereas no significant decrease in the incidence rate of HIV and HBV was observed. From 2001 to 2003, the last calculated period, the residual risk was estimated to be 1 in 1,900,000 for HIV, 1 in 2,200,0000 for HCV and 1 in 115,000 for HBV, respectively. This agrees with international studies, which have been shown that the estimated residual risk for HBV between 1996 and 2003 is higher than that of HCV and HIV.

  19. Benign tumours of the bone: A review☆

    PubMed Central

    Hakim, David N.; Pelly, Theo; Kulendran, Myutan; Caris, Jochem A.

    2015-01-01

    Benign tumours of the bone are not cancerous and would not metastasise to other regions of the body. However, they can occur in any part of the skeleton, and can still be dangerous as they may grow and compress healthy bone tissue. There are several types of benign tumours that can be classified by the type of matrix that the tumour cells produce; such as bone, cartilage, fibrous tissue, fat or blood vessel. Overall, 8 different types can be distinguished: osteochondroma, osteoma, osteoid osteoma, osteoblastoma, giant cell tumour, aneurysmal bone cyst, fibrous dysplasia and enchondroma. The incidence of benign bone tumours varies depending on the type. However, they most commonly arise in people less than 30 years old, often triggered by the hormones that stimulate normal growth. The most common type is osteochondroma. This review discusses the different types of common benign tumours of the bone based on information accumulated from published literature. PMID:26579486

  20. Retention of indocyanine green as a potential marker for optical detection of blood brain barrier disruption

    NASA Astrophysics Data System (ADS)

    Ergin, A.; Joshi, S.; Wang, M.; Bigio, I. J.

    2011-03-01

    Preliminary studies have shown that there is great variability in the degree of disruption of blood-brain barrier (BBBD) after the intraarterial injection of mannitol in rabbit models. The disruption of blood-brain barrier (BBB) is affected by a number of factors, and the variations could have a profound impact on regional delivery of chemotherapeutics. Optically measured brain tissue concentrations of indocyanine green (ICG) and Evan's blue (EB) enable the quantification of BBBD after intraarterial administration of mannitol. Using the optical pharmacokinetics technique, a variation of diffuse reflectance spectroscopy, we are able to track in vivo brain tissue concentrations of ICG and EB in rabbits, before and after barrier disruption. This study shows the feasibility of optical monitoring of BBBD, a method that can help improve intraarterial delivery of chemotherapeutic drugs.

  1. A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker

    PubMed Central

    Khoja, L; Backen, A; Sloane, R; Menasce, L; Ryder, D; Krebs, M; Board, R; Clack, G; Hughes, A; Blackhall, F; Valle, J W; Dive, C

    2012-01-01

    Background: Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet needs. We compared prospectively the utility of two platforms for CTC enumeration and characterisation in pancreatic cancer patients in a pilot exploratory study. Patients and methods: Blood samples were obtained prospectively from 54 consenting patients and analysed by CellSearch and isolation by size of epithelial tumour cells (ISET). CellSearch exploits immunomagnetic capture of CTCs-expressing epithelial markers, whereas ISET is a marker independent, blood filtration device. Circulating tumour cell expression of epithelial and mesenchymal markers was assessed to explore any discrepancy in CTC number between the two platforms. Results: ISET detected CTCs in more patients than CellSearch (93% vs 40%) and in higher numbers (median CTCs/7.5 ml, 9 (range 0–240) vs 0 (range 0–144)). Heterogeneity observed for epithelial cell adhesion molecule, pan-cytokeratin (CK), E-Cadherin, Vimentin and CK 7 expression in CTCs may account for discrepancy in CTC number between platforms. Conclusion: ISET detects more CTCs than CellSearch and offers flexible CTC characterisation with potential to investigate CTC biology and develop biomarkers for pancreatic cancer patient management. PMID:22187035

  2. Blood DNA methylation markers in potentially identified Chinese patients with hepatocellular carcinoma.

    PubMed

    Liu, Zongying; Yan, Haixiu; Zhang, Jinshu

    2016-07-01

    To determine whether blood DNA methylation is associated with hepatocellular carcinoma (HCC) for Chinese patients, we used genome-wide DNA methylation detection to access the blood samples of Chinese patients by Illumina Human methylation 450K arrays. Sixty potentially gene locis which had different methylated levels significantly among tumor and adjacent normal tissues would be tested in this study. A previous study was conducted in China communities and followed with 7 years. The DNA from white blood cells (WBC) from 192 patients with HCC and 215 matched controls were assayed in this study. The χ2 test was used to measure data to categorize variables and t -test was used to evaluate the different characteristics among groups. Besides, odds ratios (OR) and 95%CI was calculated for matching factors by conditional logistic regression models. We found that high methylation in WNK2 was related to increased risk of HCC, and high methylation in TPO were related to decreased risk of HCC. In our multivariable conditional logistic regression models, these results all exist. Those findings support the methylated changes of WNK2 and TPO may become a new detection index for HCC patients in clinical laboratory. However, the results should be replicated in additional prospective studies with lager samples. PMID:27592479

  3. Imaging of testicular tumours.

    PubMed

    Owens, E J; Kabala, J; Goddard, P

    2004-01-01

    This article reviews the diagnosis, pathology and imaging of testicular tumours, predominantly germ cell tumours. It will discuss the imaging techniques used in their diagnosis, staging and surveillance.

  4. Blood

    MedlinePlus

    ... solid part of your blood contains red blood cells, white blood cells, and platelets. Red blood cells (RBC) deliver oxygen from your lungs to your tissues and organs. White blood cells (WBC) fight infection and are part of your ...

  5. Measuring Markers of Liver Function Using a Micro-Patterned Paper Device Designed for Blood from a Fingerstick

    PubMed Central

    Vella, Sarah J.; Beattie, Patrick; Cademartiri, Rebecca; Laromaine, Anna; Martinez, Andres W.; Phillips, Scott T.; Mirica, Katherine A.

    2012-01-01

    This paper describes a paper-based microfluidic device that measures two enzymatic markers of liver function (alkaline phosphatase ALP, and aspartate aminotransferase AST) and total serum protein. A device consists of four components: i) a top plastic sheet, ii) a filter membrane, iii) a patterned paper chip containing the reagents necessary for analysis, and iv) a bottom plastic sheet. The device performs both the sample preparation (separating blood plasma from erythrocytes) and the assays; it also enables both qualitative and quantitative analysis of data. The data obtained from the paper-microfluidic devices show standard deviations in calibration runs and “spiked” standards that are acceptable for routine clinical use. This device illustrates a type of test useable for a range of assays in resource-poor settings. PMID:22390675

  6. Early markers of blood coagulation and fibrinolysis activation in Argentine hemorrhagic fever.

    PubMed

    Heller, M V; Marta, R F; Sturk, A; Maiztegui, J I; Hack, C E; Cate, J W; Molinas, F C

    1995-03-01

    Junin virus, an arenaviridae, is the etiological agent of Argentine hemorrhagic fever. In addition to thrombocytopenia, patients present several alterations in both the blood coagulation and the fibrinolytic system, but diffuse intravascular coagulation could not be demonstrated. To investigate further the activation status of the two systems, levels of thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2, protein C, total and free protein S, C4bBP, antithrombin III, t-PA, PAI-1 and D-dimer were measured. Fourteen patients with a confirmed diagnosis of Argentine hemorrhagic fever were included in the study, 2 were severe, 3 moderate and 9 mild clinical cases, but hemorrhages were slight throughout. Blood samples were collected for 6 consecutive days on admission and on remission. At admission TAT and F1 + 2 levels were increased in 13/14 patients, reaching 0.33 nM (0.06-0.87) and 2.16 nM (0.96-6.5), respectively. PC was low in 4 cases, fPS in 6 and tPS in 2, whereas C4bBP and ATIII values were within normal range. t-PA and D-dimer levels were high in 11/14 patients, reaching 20 ng/ml (2.7-106) and 1660 ng/ml (877-3780) respectively, while PAI-1 was considerably increased in the 2 severe cases and normal in the remainder. These results suggest low level though persistent process of blood coagulation and fibrinolysis activation in this viral hemorrhagic disease. We believe these abnormalities may lead to the well described bleeding manifestations in these patients.

  7. Continuous positive airway pressure therapy reduces oxidative stress markers and blood pressure in sleep apnea-hypopnea syndrome patients.

    PubMed

    Murri, Mora; García-Delgado, Regina; Alcázar-Ramírez, José; Fernández de Rota, Luis; Fernández-Ramos, Ana; Cardona, Fernando; Tinahones, Francisco J

    2011-12-01

    Sleep apnea-hypopnea syndrome (SAHS) is characterized by recurrent episodes of hypoxia/reoxygenation, which seems to promote oxidative stress. SAHS patients experience increases in hypertension, obesity and insulin resistance (IR). The purpose was to evaluate in SAHS patients the effects of 1 month of treatment with continuous positive airway pressure (CPAP) on oxidative stress and the association between oxidative stress and insulin resistance and blood pressure (BP). Twenty-six SAHS patients requiring CPAP were enrolled. Measurements were recorded before and 1 month after treatment. Cellular oxidative stress parameters were notably decreased after CPAP. Intracellular glutathione and mitochondrial membrane potential increased significantly. Also, total antioxidant capacity and most of the plasma antioxidant activities increased significantly. Significant decreases were seen in BP. Negative correlations were observed between SAHS severity and markers of protection against oxidative stress. BP correlated with oxidative stress markers. In conclusion, we observed an obvious improvement in oxidative stress and found that it was accompanied by an evident decrease in BP with no modification in IR. Consequently, we believe that the decrease in oxidative stress after 1 month of CPAP treatment in these patients is not contributing much to IR genesis, though it could be related to the hypertension etiology.

  8. Stable RNA markers for identification of blood and saliva stains revealed from whole genome expression analysis of time-wise degraded samples.

    PubMed

    Zubakov, Dmitry; Hanekamp, Eline; Kokshoorn, Mieke; van Ijcken, Wilfred; Kayser, Manfred

    2008-03-01

    Human body fluids such as blood and saliva represent the most common source of biological material found at a crime scene. Reliable tissue identification in forensic science can reveal significant insights into crime scene reconstruction and can thus contribute toward solving crimes. Limitations of existing presumptive tests for body fluid identification in forensics, which are usually based on chemoluminescence or protein analysis, are expected to be overcome by RNA-based methods, provided that stable RNA markers with tissue-specific expression patterns are available. To generate sets of stable RNA markers for reliable identification of blood and saliva stains we (1) performed whole-genome gene expression analyses on a series of time-wise degraded blood and saliva stain samples using the Affymetrix U133 plus2 GeneChip, (2) consulted expression databases to obtain additional information on tissue specificity, and (3) confirmed expression patterns of the most promising candidate genes by quantitative real-time polymerase chain reaction including additional forensically relevant tissues such as semen and vaginal secretion. Overall, we identified nine stable mRNA markers for blood and five stable mRNA markers for saliva detection showing tissue-specific expression signals in stains aged up to 180 days of age, expectedly older. Although, all of the markers were able to differentiate blood/saliva from semen samples, none of them could differentiate vaginal secretion because of the complex nature of vaginal secretion and the biological similarity of buccal and vaginal mucosa. We propose the use of these 14 stable mRNA markers for identification of blood and saliva stains in future forensic practice. PMID:17579879

  9. Evaluation of a Microarray-Based Assay for Rapid Identification of Gram-Positive Organisms and Resistance Markers in Positive Blood Cultures

    PubMed Central

    Tibbetts, Robert J.; Agotesku, Adam; Fey, Margaret; Hensley, Rhonda; Meier, Frederick A.

    2013-01-01

    Rapid identification of pathogens directly from positive blood cultures can play a major role in reducing patient mortality rates. We evaluated the performance of the Verigene Gram-Positive Blood Culture (BC-GP) assay (Nanosphere Inc., Northbrook, IL) for detection of commonly isolated Gram-positive organisms as well as associated resistance markers from positive blood cultures. Positive blood cultures (VersaTREK; Trek Diagnostic Systems, Independence, OH) from 203 patients with Gram-positive organism infections were analyzed using the BC-GP assay within 12 h for the detection of 12 different organisms, including staphylococci, streptococci, and enterococci, as well as for the presence of 3 resistance markers (mecA, vanA, and vanB). Results were compared to those of routine laboratory methods for identification and susceptibility testing. For identification of organisms and detection of resistance markers in 178 monomicrobial positive blood cultures, the BC-GP assay showed 94% and 97% concordance, respectively, with routine methods. After 25 polymicrobial cultures were included, the results showed 92% and 96% agreement for identification and resistance markers, respectively, for a total of 203 positive cultures. In 6/25 polymicrobial cultures, at least 1 isolate was not detected. Concordance levels for detection of major pathogens such Staphylococcus aureus (n = 45) and enterococci (n = 19) were 98% and 95%, respectively. Agreement levels for detection of resistance markers such as mecA and vanA/B were 92% and 100%, respectively. The BC-GP assay is capable of providing rapid identification of Gram-positive cocci as well as detection of resistance markers directly from positive blood cultures at least 24 to 48 h earlier than conventional methods. PMID:23363838

  10. Stable RNA markers for identification of blood and saliva stains revealed from whole genome expression analysis of time-wise degraded samples.

    PubMed

    Zubakov, Dmitry; Hanekamp, Eline; Kokshoorn, Mieke; van Ijcken, Wilfred; Kayser, Manfred

    2008-03-01

    Human body fluids such as blood and saliva represent the most common source of biological material found at a crime scene. Reliable tissue identification in forensic science can reveal significant insights into crime scene reconstruction and can thus contribute toward solving crimes. Limitations of existing presumptive tests for body fluid identification in forensics, which are usually based on chemoluminescence or protein analysis, are expected to be overcome by RNA-based methods, provided that stable RNA markers with tissue-specific expression patterns are available. To generate sets of stable RNA markers for reliable identification of blood and saliva stains we (1) performed whole-genome gene expression analyses on a series of time-wise degraded blood and saliva stain samples using the Affymetrix U133 plus2 GeneChip, (2) consulted expression databases to obtain additional information on tissue specificity, and (3) confirmed expression patterns of the most promising candidate genes by quantitative real-time polymerase chain reaction including additional forensically relevant tissues such as semen and vaginal secretion. Overall, we identified nine stable mRNA markers for blood and five stable mRNA markers for saliva detection showing tissue-specific expression signals in stains aged up to 180 days of age, expectedly older. Although, all of the markers were able to differentiate blood/saliva from semen samples, none of them could differentiate vaginal secretion because of the complex nature of vaginal secretion and the biological similarity of buccal and vaginal mucosa. We propose the use of these 14 stable mRNA markers for identification of blood and saliva stains in future forensic practice.

  11. Medical devices; immunology and microbiology devices; classification of multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures. Final order.

    PubMed

    2015-05-27

    The Food and Drug Administration (FDA) is classifying multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures into class II (special controls). The special controls that will apply to this device are identified in this order and will be part of the codified language for the multiplex nucleic acid assay for identification of microorganisms and resistance markers from positive blood cultures. The Agency is classifying the device into class II (special controls) in order to provide a reasonable assurance of safety and effectiveness of the device.

  12. The Effect of Protandim® Supplementation on Athletic Performance and Oxidative Blood Markers in Runners

    PubMed Central

    Ueberschlag, Seteena L.; Seay, James R.; Roberts, Alexandra H.; DeSpirito, Pamela C.; Stith, Jeremy M.; Folz, Rodney J.; Carter, Kathleen A.; Weiss, Edward P.

    2016-01-01

    The purpose of this study determined if oral supplementation of Protandim® (a nutraceutical) for 90 days improved 5-km running performance and reduced serum thiobarbituric acid-reacting substances (TBARS) at rest, an indicator of oxidative stress. Secondary objectives were to measure whole blood superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GPX), at rest and 10 minutes after completion of the race before and after supplementation as well as quality of life. In a double-blind, randomized, placebo controlled trial, 38 runners [mean (SD) = 34 (7) yrs; BMI = 22 (2) kg/m2] received either 90 days of Protandim® [1 pill a day, n = 19)] or placebo (n = 19). Randomization was done in blocks of two controlling for sex and 5-km baseline performance. A 5-km race was performed at baseline and after 90 days of supplementation, with blood samples taken before and 10-min after each race. Fasting blood samples were acquired at baseline, after 30, 60, and 90 days of supplementation. TBARS, SOD, GPX, and GSH were assayed in an out-of-state accredited lab. Running performance was not altered by Protandim® or placebo [20.3 (2.1) minutes, with an -8 (33) seconds change in 5-km time regardless of group]. There was no change in TBARS, SOD, or GPX (at rest) after three months of Protandim® supplementation compared to placebo. However, in a subgroup ≥ 35 years of age, there was a 2-fold higher increase in SOD in those taking Protandim® for three months compared to those on placebo (p = 0.038). The mean post-race change in TBARS (compared to pre-race) increased by about 20% in half of the subjects, but was not altered between groups, even after three months of supplementation. Quality of life was also not different between the two conditions. In conclusion, Protandim® did not (1) alter 5-km running time, (2) lower TBARS at rest (3) raise antioxidant enzyme concentrations compared to placebo (with exception of SOD in those ≥ 35 years old) or, (4) affect

  13. Highway proximity associations with blood markers of inflammation: Evidence for a role for IL-1β

    PubMed Central

    Lane, Kevin J.; Stewart, Andrea; Tai, Albert K; Woodin, Mark

    2015-01-01

    Cardiovascular disease is associated with proximity to major roadways and highways. We analyzed blood samples from 20 near highway and 20 urban background residents for cytokines and other biomarkers. Near highway participants had significantly lower SES and significantly higher occupational vehicle exhaust exposure and higher LDL levels (p = 0.046). Controlling for exposure to vehicle exhaust on-the-job, IL-6 was borderline significantly higher (p = 0.07) in near highway participants. In logistic regression analyses IL-1β was elevated near highway (OR = 3.27; p = 0.09). It is interesting that we found elevations in IL-1β, a key cytokine linked to inflammation from particulate matter. More research is needed with larger sample sizes to assess the possible role of IL-1β. PMID:23356649

  14. Utilization of molecular markers for the conservation of blood cockles, Anadara granosa (Arcidae).

    PubMed

    Chee, S Y; Azizah, M N S; Devakie, M N

    2011-01-01

    We examined genetic variation in blood cockles in an effort to obtain information useful for the sustainability, management, and the stability of this species as a major commodity in the fisheries sector. Ten populations of cockles were sampled from the north to the south of the west coast of peninsular Malaysia. The cockles were collected in collaboration with the Fisheries Research Institute, Penang. The population genetic analysis of the cockles were studied via RAPD-PCR and mtDNA sequencing. Three hundred individuals were analyzed with RAPD-PCR experiments. High gene diversity over all loci was observed (Shannon index = 0.549 ± 0.056 and Nei's gene diversity = 0.4852 ± 0.0430 among 35 loci). The second method, mtDNA sequencing, was employed to complement the information obtained from RAPD-PCR. The gene selected for mtDNA sequencing was cytochrome c oxidase I (COI). One hundred and fifty individuals were sequenced, yielding a partial gene of 585 bp. Statistical analysis showed homogeneity in general but did reveal some degree of variability between the populations in Johor and the rest of the populations. The Mantel test showed a positive but nonsignificant correlation between geographic and genetic distances (r = 0.2710, P = 0.622), as in the RAPD analysis. We propose that the homogeneity between distant populations is caused by two factors: 1) the translocation of the spats; 2) larvae are carried by current movement from the north of the peninsula to the south. The different genetic composition found in Johor could be due to pollution, mutagenic substances or physical factors such as the depth of the water column. This population genetic study is the first for this species in peninsular Malaysia. The data from this study have important implications for fishery management, conservation of blood cockles and translocation policies for aquaculture and stock enhancement programs. PMID:21732289

  15. Are the increases in local tumour necrosis factor and lipid peroxidation observed in pre-starved mice infected with Salmonella typhimurium markers of increased liver damage?

    PubMed

    Rishi, Praveen; Kaur, Harsimran; Tirkey, Naveen; Chopra, Kanwaljit; Bharrhan, Sushma; Chanana, Vishal; Koul, Ashwani

    2006-06-01

    Pathogenic microorganisms are known to sense and process signals within their hosts, including those resulting from starvation. Therefore, an attempt was made to evaluate the extent and the possible underlying mechanism of Salmonella typhimurium-induced hepatic damage using pre-starved laboratory mice. The following parameters were analysed, comparing control, fed infected, starved, and starved infected mice: the bacterial load in the liver, fluctuations in liver-derived enzymes alanine-aminotransferase and aspartate-aminotransferase, histopathological changes, lipid peroxidation as well as estimation of reduced glutathione, superoxide dismutase and catalase, along with the TNF content in livers. The number of bacterial cells recovered from starved infected livers at 3 days post-S. typhimurium inoculation was comparable to the number recovered from fed infected livers at 5 days post-Salmonella inoculation, indicating an early increase in the development of the bacteria in starved mice. A marked elevation in liver-derived enzymes in mouse serum and significant histopathological changes are markers of liver damage of higher amplitude in starved infected mice. Analysis of the liver indicated a significant increase in lipid peroxidation in starved infected mice compared to their control counterparts, a process coupled with increased TNF level. Although the reduced glutathione levels showed a marked increase in the starved infected mice, there was a significant decrease in superoxide dismutase and catalase activities in this group.

  16. Tenascin-W is a specific marker of glioma-associated blood vessels and stimulates angiogenesis in vitro.

    PubMed

    Martina, Enrico; Degen, Martin; Rüegg, Curzio; Merlo, Adrian; Lino, Maddalena M; Chiquet-Ehrismann, Ruth; Brellier, Florence

    2010-03-01

    The microenvironment hosting a tumor actively participates in regulating tumor cell proliferation, migration, and invasion. Among the extracellular matrix proteins enriched in the stroma of carcinomas are the tenascin family members tenascin-C and tenascin-W. Whereas tenascin-C overexpression in gliomas is known to correlate with poor prognosis, the status of tenascin-W in brain tumors has not been investigated so far. In the present study, we analyzed protein levels of tenascin-W in 38 human gliomas and found expression of tenascin-W in 80% of the tumor samples, whereas no tenascin-W could be detected in control, nontumoral brain tissues. Double immunohistochemical staining of tenascin-W and von Willebrand factor revealed that tenascin-W is localized around blood vessels, exclusively in tumor samples. In vitro, the presence of tenascin-W increased the proportion of elongated human umbilical vein endothelial cells (HUVECs) and augmented the mean speed of cell migration. Furthermore, tenascin-W triggered sprouting of HUVEC spheroids to a similar extent as the proangiogenic factor tenascin-C. In conclusion, our study identifies tenascin-W as a candidate biomarker for brain tumor angiogenesis that could be used as a molecular target for therapy irrespective of the glioma subtype.-Martina, E., Degen, M., Rüegg, C., Merlo, A., Lino, M. M., Chiquet-Ehrismann, R., Brellier, F. Tenascin-W is a specific marker of glioma-associated blood vessels and stimulates angiogenesis in vitro.

  17. IFI27 Is a Useful Genetic Marker for Diagnosis of Immunoglobulin A Nephropathy and Membranous Nephropathy Using Peripheral Blood

    PubMed Central

    Muso, Eri; Yamamoto, Ryohei; Shinzawa, Maki; Iwasaki, Yukako; Iwatani, Hirotsugu; Nakanishi, Takeshi; Isaka, Yoshitaka; Nojima, Hiroshi

    2016-01-01

    Diagnosis of chronic glomerulonephritis (CGN) depends primarily on renal biopsy, which is expensive and requires hospitalization, creating a demand for noninvasive diagnostic method for this disease. We used DNA microarray analysis to search for genes whose expression levels in peripheral blood mononuclear cells (PBMCs) could distinguish between patients with CGN and healthy volunteers (HVs). We selected immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) as typical forms of CGN. The mRNA level of the gene encoding interferon (IFN)-alpha-inducible protein 27, IFI27, which is preferentially expressed in podocytes of glomeruli, was lower in PBMCs of IgAN and MN patients than in those of HVs. This result was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Moreover, qRT-PCR analysis revealed that the IFI27 mRNA level was reduced in PBMCs of patients with other types of chronic glomerulonephritis. IFI27 immunohistochemical staining of biopsied specimens also confirmed reduced expression of IFI27 protein in IgAN and MN patients. Based on these results, we propose that IFI27 could serve as a noninvasive diagnostic marker for CGNs using peripheral blood. PMID:27100186

  18. IFI27 Is a Useful Genetic Marker for Diagnosis of Immunoglobulin A Nephropathy and Membranous Nephropathy Using Peripheral Blood.

    PubMed

    Nagasawa, Yasuyuki; Okuzaki, Daisuke; Muso, Eri; Yamamoto, Ryohei; Shinzawa, Maki; Iwasaki, Yukako; Iwatani, Hirotsugu; Nakanishi, Takeshi; Isaka, Yoshitaka; Nojima, Hiroshi

    2016-01-01

    Diagnosis of chronic glomerulonephritis (CGN) depends primarily on renal biopsy, which is expensive and requires hospitalization, creating a demand for noninvasive diagnostic method for this disease. We used DNA microarray analysis to search for genes whose expression levels in peripheral blood mononuclear cells (PBMCs) could distinguish between patients with CGN and healthy volunteers (HVs). We selected immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) as typical forms of CGN. The mRNA level of the gene encoding interferon (IFN)-alpha-inducible protein 27, IFI27, which is preferentially expressed in podocytes of glomeruli, was lower in PBMCs of IgAN and MN patients than in those of HVs. This result was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Moreover, qRT-PCR analysis revealed that the IFI27 mRNA level was reduced in PBMCs of patients with other types of chronic glomerulonephritis. IFI27 immunohistochemical staining of biopsied specimens also confirmed reduced expression of IFI27 protein in IgAN and MN patients. Based on these results, we propose that IFI27 could serve as a noninvasive diagnostic marker for CGNs using peripheral blood. PMID:27100186

  19. Effects of acute cigarette smoking on total blood count and markers of oxidative stress in active and passive smokers

    PubMed Central

    Lymperaki, E; Makedou, K; Iliadis, S; Vagdatli, E

    2015-01-01

    Background: Free radicals, as a product of cigarette smoke, are considered to have deleterious effects causing oxidative stress. Acute active smoking seems to be followed by transient leukocytosis and delayed increase in neutrophil activation. The aim of the present study was to investigate the oxidative status of smokers and passive non-smokers, as well as the impact that acute cigarette smoking has on hematological parameters. Methods: Thirty-two healthy volunteers, 16 active smokers (Group A) aged 20-23 years and 16 age-matched, non-smokers (Group B), 18 women and 14 men in total, participated voluntarily in the study. All subjects did not have any food, drink, or cigarette smoking for eight hours before the study. Each time, two active smokers and two non-smokers were exposed simultaneously for half an hour to the smoke of two cigarettes smoked consecutively by the smokers. Blood was drawn before and after the exposure to cigarette smoke. Whole blood was analyzed immediately for total blood count parameters and serum was stored in -70◦C until serum levels of malondialdehyde (MDA) and vitamin E (VitE), and total antioxidant capacity (TAC) were determined. Results: No statistical significant difference was observed in the values of white blood cells and their subpopulations between the two groups and within the same group before and after exposure to cigarette smoke. In the group of smokers, granulocyte/lymphocyte ratio increased significantly, MDA levels showed significant elevation and protective VitE serum levels decreased significantly, whereas TAC was reduced, but not significantly, after the exposure. In the group of passive, non-smokers the results of the blood count parameters, MDA and VitE were similar to Group A, and there was a significant decrease in TAC, as well. Between the two groups, only hematocrit values and MDA levels differed significantly before the exposure to smoke, and no other significant difference was detected before or after the

  20. Sertoliform cystadenoma: a rare benign tumour of the rete testis

    PubMed Central

    2013-01-01

    Abstract Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335 PMID:23406299

  1. Comparison Between Immunological Markers in Cord Blood of Preterm and Term Babies in Hospital USM

    PubMed Central

    Ashari, Noor Suryani Mohd; Hussin, Che Maraina Che; Musa, Mustaffa; Rostenberghe, Han Vans

    2008-01-01

    A cross sectional pilot study using convenient sampling method was conducted to evaluate various immunological parameters in preterm babies and term babies. Cord blood from 36 preterm and 36 term babies was taken and the following parameters were determined: Immunoglobulin G, A and M, Complement 3 and 4 and NBT. The results showed that NBT was significantly reduced in preterm babies compared to term babies (7.5% versus 12.0%; p= 0.001). The complement levels, C3 (0.5114 versus 0.7192 g/l; p<0.001) and C4 (0.07 versus 0.14g/l; p<0.001) were significantly lower in preterm babies than in the term babies. The mean IgG level in preterm babies was significantly lower than in term babies (9.5583 versus 14.2806 g/l, p<0.001). IgM (0.1 versus 0.2g/l; p<0.001) and IgA (0.210 versus 0.225g/l; p=0.036l) levels were significantly lower in the preterm than in term babies. In conclusion, we found that NBT reduction, IgG, IgA, IgM, C3 and C4 levels were significantly lower in the preterm compared to term babies. PMID:22589619

  2. Blood pressure and sodium: Association with MRI markers in cerebral small vessel disease.

    PubMed

    Heye, Anna K; Thrippleton, Michael J; Chappell, Francesca M; Hernández, Maria del C Valdés; Armitage, Paul A; Makin, Stephen D; Maniega, Susana Muñoz; Sakka, Eleni; Flatman, Peter W; Dennis, Martin S; Wardlaw, Joanna M

    2016-01-01

    Dietary salt intake and hypertension are associated with increased risk of cardiovascular disease including stroke. We aimed to explore the influence of these factors, together with plasma sodium concentration, in cerebral small vessel disease (SVD). In all, 264 patients with nondisabling cortical or lacunar stroke were recruited. Patients were questioned about their salt intake and plasma sodium concentration was measured; brain tissue volume and white-matter hyperintensity (WMH) load were measured using structural magnetic resonance imaging (MRI) while diffusion tensor MRI and dynamic contrast-enhanced MRI were acquired to assess underlying tissue integrity. An index of added salt intake (P = 0.021), pulse pressure (P = 0.036), and diagnosis of hypertension (P = 0.0093) were positively associated with increased WMH, while plasma sodium concentration was associated with brain volume (P = 0.019) but not with WMH volume. These results are consistent with previous findings that raised blood pressure is associated with WMH burden and raise the possibility of an independent role for dietary salt in the development of cerebral SVD.

  3. Frequency and significance of antibodies against hepatitis B core (anti-HBc) antigen as the only serological marker for hepatitis B infection in Lebanese blood donors.

    PubMed Central

    Ramia, S.; Ramlawi, F.; Kanaan, M.; Klayme, S.; Naman, R.

    2005-01-01

    During a 2-year period, blood samples from 2505 Lebanese blood donors were chosen at random, at various periods of time at one blood donation centre (Hotel Dieu de France, Beirut, Lebanon) and were screened for markers of HBV infection (HBsAg, anti-HBc and anti-HBs). The study showed HBsAg positivity of 0.6% and an overall exposure rate to HBV of 10.0%. Out of the 2505 blood donors screened, 56 (22%) were found to be 'anti-HBc alone' positive which is almost four times the HBsAg positivity. The 56 'anti-HBc alone' samples were retested by another ELISA kit commercially available and 54 samples were 'anti-HBc alone' positive by both assays. The 54 samples had no serological markers as evidence of infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV). Only seven (13%) out of the 54 samples were HBV DNA positive by PCR and all were HBV genotype D. All seven HBV DNA-positive samples had HBV DNA levels below 400 copies/ml. Although any circulating HBV DNA among our 'anti-HBc alone' blood donors was below the detection limit of our Amplicor Monitor assay, some of these samples had circulating virus. A national study, where a larger number of blood donors from different blood donation centres across the country will perhaps determine whether screening for anti-HBc in addition to HBsAg detection is needed in Lebanese blood donors. PMID:16050516

  4. Peripheral blood immunological parameters for use as markers of pre-invasive to invasive colorectal cancer.

    PubMed

    Berghella, Anna Maria; Contasta, Ida; Pellegrini, Patrizia; Del Beato, Tiziana; Adorno, Domenico

    2002-02-01

    In cancer, the extent to which the disease has spread is probably the most important factor in determining patient prognosis. Hence practical and non-invasive methods are needed to identify disease stage. In a previous paper we showed how diagnostic and prognostic indices for disease progression could be defined by evaluating parameters in peripheral blood. The aim of this study was to identify further serum parameters that could be used. Serum levels of interferon (IFN) gamma, interleukin (IL)4, IL8, IL7, IL1 beta, tumor necrosis factor (TNF) alpha, granulocyte macrophage-colony stimulating factor (GM-CSF), soluble (s) IL2 receptor (R) and sIL6R were studied but only levels of IL4, sIL2R, IL8 and IL7 were found to be significant and would therefore be of use in defining diagnostic and prognostic indices for disease progression. In further detail, our results indicate that when serum levels of sIL2R < 522 U/ml, IL4 < 159 pg/ml and IL8 > 339 pg/ml there is a 95% probability that the disease is in stage I or II where there is no infiltration of lymph nodes; when serum levels of sIL2R > or = 522 Ug/ml, 159 pg/ml < or = IL4 < or = 319 pg/ml, and IL7 < 54 pg/ml, there is a 95% probability that the disease is in stage III and the tumor has invaded the lymph nodes; when the serum levels of IL4 > or = 431 pg/ml and IL7 > or = 54 pg/ml, there is a 95% probability that the disease is in stage IV and there is metastasis.

  5. Association of preoperative levels of selected blood inflammatory markers with prognosis in gliomas

    PubMed Central

    Auezova, Raushan; Ryskeldiev, Nurzhan; Doskaliyev, Aidos; Kuanyshev, Yerbol; Zhetpisbaev, Berik; Aldiyarova, Nurgul; Ivanova, Natalia; Akshulakov, Serik; Auezova, Lizette

    2016-01-01

    Background Red cell distribution width (RDW), neutrophil–lymphocyte ratio (NLR), and platelet count (PLT) routinely tested as part of the complete blood count are indicative of systemic inflammation. The prognostic significance of NLR and PLT in cancer was demonstrated in many studies while the role of RDW has been hardly investigated. The present study aimed to assess the association of RDW, NLR, and PLT with survival and tumor grade in glioma patients. Methods Clinical data from 178 patients with primary gliomas treated in a single institution were retrospectively analyzed. Receiver operating characteristic curves for cutoff value determination, Kaplan–Meier survival analysis, various bivariate tests, and univariate and multivariate Cox regression analyses were performed. Results Patients with high RDW (≥13.95) and NLR (≥4) levels had worse overall survival (OS) (Wilcoxon test, P<0.026 and P<0.003, respectively) while the effect of thrombocytosis (≥400×109/L) on prognosis was not significant. Besides, a strong association between RDW and NLR was found (Spearman’s rho =0.230, P<0.02; χ2=8.887, P<0.03; Mann–Whitney U-test, P<0.017). Moreover, RDW and NLR were significantly associated with tumor grade. In univariate Cox analysis, elevated NLR (hazard ratio, HR 1.385; confidence interval, CI 1.020–1.881, P<0.037), older age (HR 0.452, CI 0.329–0.621, P<0), and higher tumor grade (HR 1.624, CI 1.187–2.223, P<0.002) were associated with poor outcomes. In the multivariate analysis, tumor grade, age, and Karnofsky performance score were identified as being independently prognostic for OS. Conclusion Preoperative NLR and RDW values can help to evaluate disease progression and outcomes in patients with gliomas, thereby contributing to patient follow-up optimization. PMID:27785058

  6. Collaboration of cancer-associated fibroblasts and tumour-associated macrophages for neuroblastoma development.

    PubMed

    Hashimoto, Okito; Yoshida, Makiko; Koma, Yu-Ichiro; Yanai, Tomoko; Hasegawa, Daiichiro; Kosaka, Yoshiyuki; Nishimura, Noriyuki; Yokozaki, Hiroshi

    2016-10-01

    Neuroblastoma is the most common extracranial solid tumour in children and is histologically classified by its Schwannian stromal cells. Although having fewer Schwannian stromal cells is generally associated with more aggressive phenotypes, the exact roles of other stromal cells (mainly macrophages and fibroblasts) are unclear. Here, we examined 41 cases of neuroblastoma using immunohistochemistry for the tumour-associated macrophage (TAM) markers CD68, CD163, and CD204, and a cancer-associated fibroblast (CAF) marker, alpha smooth muscle actin (αSMA). Each case was assigned to low/high groups on the basis of the number of TAMs or three groups on the basis of the αSMA-staining area for CAFs. Both the number of TAMs and the area of CAFs were significantly correlated with clinical stage, MYCN amplification, bone marrow metastasis, histological classification, histological type, and risk classification. Furthermore, TAM settled in the vicinity of the CAF area, suggesting their close interaction within the tumour microenvironment. We next determined the effects of conditioned medium of a neuroblastoma cell line (NBCM) on bone marrow-derived mesenchymal stem cells (BM-MSCs) and peripheral blood mononuclear cell (PBMC)-derived macrophages in vitro. The TAM markers CD163 and CD204 were significantly up-regulated in PBMC-derived macrophages treated with NBCM. The expression of αSMA by BM-MSCs was increased in NBCM-treated cells. Co-culturing with CAF-like BM-MSCs did not enhance the invasive ability but supported the proliferation of tumour cells, whereas tumour cells co-cultured with TAM-like macrophages had the opposite effect. Intriguingly, TAM-like macrophages enhanced not only the invasive abilities of tumour cells and BM-MSCs but also the proliferation of BM-MSCs. CXCL2 secreted from TAM-like macrophages plays an important role in tumour invasiveness. Taken together, these results indicate that PBMC-derived macrophages and BM-MSCs are recruited to a tumour site

  7. Collaboration of cancer-associated fibroblasts and tumour-associated macrophages for neuroblastoma development.

    PubMed

    Hashimoto, Okito; Yoshida, Makiko; Koma, Yu-Ichiro; Yanai, Tomoko; Hasegawa, Daiichiro; Kosaka, Yoshiyuki; Nishimura, Noriyuki; Yokozaki, Hiroshi

    2016-10-01

    Neuroblastoma is the most common extracranial solid tumour in children and is histologically classified by its Schwannian stromal cells. Although having fewer Schwannian stromal cells is generally associated with more aggressive phenotypes, the exact roles of other stromal cells (mainly macrophages and fibroblasts) are unclear. Here, we examined 41 cases of neuroblastoma using immunohistochemistry for the tumour-associated macrophage (TAM) markers CD68, CD163, and CD204, and a cancer-associated fibroblast (CAF) marker, alpha smooth muscle actin (αSMA). Each case was assigned to low/high groups on the basis of the number of TAMs or three groups on the basis of the αSMA-staining area for CAFs. Both the number of TAMs and the area of CAFs were significantly correlated with clinical stage, MYCN amplification, bone marrow metastasis, histological classification, histological type, and risk classification. Furthermore, TAM settled in the vicinity of the CAF area, suggesting their close interaction within the tumour microenvironment. We next determined the effects of conditioned medium of a neuroblastoma cell line (NBCM) on bone marrow-derived mesenchymal stem cells (BM-MSCs) and peripheral blood mononuclear cell (PBMC)-derived macrophages in vitro. The TAM markers CD163 and CD204 were significantly up-regulated in PBMC-derived macrophages treated with NBCM. The expression of αSMA by BM-MSCs was increased in NBCM-treated cells. Co-culturing with CAF-like BM-MSCs did not enhance the invasive ability but supported the proliferation of tumour cells, whereas tumour cells co-cultured with TAM-like macrophages had the opposite effect. Intriguingly, TAM-like macrophages enhanced not only the invasive abilities of tumour cells and BM-MSCs but also the proliferation of BM-MSCs. CXCL2 secreted from TAM-like macrophages plays an important role in tumour invasiveness. Taken together, these results indicate that PBMC-derived macrophages and BM-MSCs are recruited to a tumour site

  8. Intraoperative intravital microscopy permits the study of human tumour vessels

    PubMed Central

    Fisher, Daniel T.; Muhitch, Jason B.; Kim, Minhyung; Doyen, Kurt C.; Bogner, Paul N.; Evans, Sharon S.; Skitzki, Joseph J.

    2016-01-01

    Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment. PMID:26883450

  9. Intraoperative intravital microscopy permits the study of human tumour vessels.

    PubMed

    Fisher, Daniel T; Muhitch, Jason B; Kim, Minhyung; Doyen, Kurt C; Bogner, Paul N; Evans, Sharon S; Skitzki, Joseph J

    2016-02-17

    Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment.

  10. A CD138-independent strategy to detect minimal residual disease and circulating tumour cells in multiple myeloma.

    PubMed

    Muz, Barbara; de la Puente, Pilar; Azab, Feda; Luderer, Micah John; King, Justin; Vij, Ravi; Azab, Abdel Kareem

    2016-04-01

    CD138 (also termed SDC1) has been the gold-standard surface marker to detect multiple myeloma (MM) cells for decades; however, drug-resistant residual and circulating MM cells were shown to have lower expression of this marker. In this study, we have shown that residual MM cells following bortezomib treatment are hypoxic. This combination of drug exposure and hypoxia down-regulates their CD138 expression, thereby making this marker unsuitable for detecting residual or other hypoxic MM cells, such as circulating tumour cells, in MM. Hence, we developed an alternative biomarker set which detects myeloma cells independent of their hypoxic and CD138 expression status in vitro, in vivo and in primary MM patients. The new markers were able to identify a clonal CD138-negative population as minimal residual disease in the bone marrow and peripheral blood of MM patients. Further investigation to characterize the role of this population as a prognostic marker in MM is warranted.

  11. Tumour biology: Senescence in premalignant tumours

    NASA Astrophysics Data System (ADS)

    Collado, Manuel; Gil, Jesús; Efeyan, Alejo; Guerra, Carmen; Schuhmacher, Alberto J.; Barradas, Marta; Benguría, Alberto; Zaballos, Angel; Flores, Juana M.; Barbacid, Mariano; Beach, David; Serrano, Manuel

    2005-08-01

    Oncogene-induced senescence is a cellular response that may be crucial for protection against cancer development, but its investigation has so far been restricted to cultured cells that have been manipulated to overexpress an oncogene. Here we analyse tumours initiated by an endogenous oncogene, ras, and show that senescent cells exist in premalignant tumours but not in malignant ones. Senescence is therefore a defining feature of premalignant tumours that could prove valuable in the diagnosis and prognosis of cancer.

  12. Clinical impact of circulating microRNAs as blood-based marker in childhood acute lymphoblastic leukemia.

    PubMed

    Swellam, Menha; El-Khazragy, Nashwa

    2016-08-01

    Aberrant microRNA (miRNA) expression participates in childhood acute lymphoblastic leukemia (ALL). This study aimed to investigate the expression of miRNA-100, miRNA-196a, and miRNA-146a among childhood ALL and study their correlation with other hematological parameters and different phenotypes. Peripheral blood mononuclear cells (PMNCs) were obtained from 85 childhood ALL and 25 healthy children for the detection of miRNA expression using quantitative real-time PCR. Significant higher median levels were reported for ALL compared to control children. The diagnostic efficacy for miRNA-146a was superior as both sensitivity and specificity were absolute. A significant correlation was observed between higher expression of miRNA-100 and lower platelet and lymphocyte counts; high expression of miRNA-146a showed significant correlation with low total leukocyte count (TLC) and lymphocyte counts. Significant relation was reported between studied miRNAs and different phenotyping. miRNA-100, miRNA-196a, and miRNA-146a have significant role in childhood ALL leukemogenesis, and they may be useful as biological diagnostic molecular markers. PMID:26857279

  13. MicroRNAs as markers for neurally committed CD133+/CD34+ stem cells derived from human umbilical cord blood.

    PubMed

    Hafizi, Maryam; Atashi, Amir; Bakhshandeh, Behnaz; Kabiri, Mahboubeh; Nadri, Samad; Hosseini, Reza Haji; Soleimani, Masoud

    2013-04-01

    Neural differentiation of the CD133+/CD34+ subpopulation of human umbilical cord blood stem cells was investigated, and neuro-miR (mir-9 and mir-124) expression was examined. An efficient induction protocol for neural differentiation of hematopoietic stem cells together with the exclusion of retinoic acid in this process was also studied. Transcription of some neural markers such as microtubule-associated protein-2, beta-tubulin III, and neuron-specific enolase was evaluated by real-time PCR, immunocytochemistry, and western blotting. Increased expression of neural indicators in the treated cells confirmed the appropriate neural differentiation, which supported the high efficiency of our defined neuronal induction protocol. Verified high expression of neuro-miRNAs along with neuronal specific proteins not only strengthens the regulatory role of miRNAs in determining stem cell fate but also introduces these miRNAs as novel indicators of neural differentiation. These data highlight the prominent therapeutic potential of hematopoietic stem cells for use in cell therapy of neurodegenerative diseases.

  14. Giant Mediastinal Germ Cell Tumour: An Enigma of Surgical Consideration

    PubMed Central

    Ali, Nurayub Mohd; Azizan, Nornazirah; Zakaria, Andee Dzulkarnaen; Rahman, Mohd Ramzisham Abdul

    2016-01-01

    We present a case of 16-year-old male, who was referred from private centre for dyspnoea, fatigue, and orthopnea. The chest radiograph revealed complete opacification of left chest which was confirmed by computed tomography as a large left mediastinal mass measuring 14 × 15 × 18 cm. The diagnostic needle core biopsy revealed mixed germ cell tumour with possible combination of embryonal carcinoma, yolk sac, and teratoma. After 4 cycles of neoadjuvant BEP regime, there was initial response of tumour markers but not tumour bulk. Instead of classic median sternotomy or clamshell incision, posterolateral approach with piecemeal manner was chosen. Histology confirmed mixed germ cell tumour with residual teratomatous component without yolk sac or embryonal carcinoma component. Weighing 3.5 kg, it is one of the largest mediastinal germ cell tumours ever reported. We describe this rare and gigantic intrathoracic tumour and discuss the spectrum of surgical approach and treatment of this exceptional tumour. PMID:27807495

  15. Ovarian tumours in pregnancy: a literature review.

    PubMed

    Aggarwal, Pakhee; Kehoe, Sean

    2011-04-01

    Ovarian tumours in pregnancy are a diagnostic and management challenge that is increasingly being faced by the clinician. While most masses are benign and resolve spontaneously, there are others that persist and indicate the need for surgical management. Ultrasound not only detects asymptomatic masses but also helps to guide their management based on presence or absence of features suspicious of malignancy. The role of tumour markers in pregnancy is limited due to their non-specific nature. Most masses treated in pregnancy are benign (most commonly dermoids), and most malignancies are either of low malignant potential or germ cell tumours, usually early stage disease. Surgical management is indicated for symptomatic masses or those with increasing size or complexity indicating possible malignancy. Both laparoscopy and laparotomy have similar results with regard to obstetric outcome. Conservative management is preferred in the remainder. MRI may help in better characterization of doubtful masses. National tumour registries can help to establish guidelines.

  16. Paediatric extracranial germ-cell tumours.

    PubMed

    Shaikh, Furqan; Murray, Matthew J; Amatruda, James F; Coleman, Nicholas; Nicholson, James C; Hale, Juliet P; Pashankar, Farzana; Stoneham, Sara J; Poynter, Jenny N; Olson, Thomas A; Billmire, Deborah F; Stark, Daniel; Rodriguez-Galindo, Carlos; Frazier, A Lindsay

    2016-04-01

    Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across a wide age range and vary in site, histology, and clinical behaviour. Patients with germ-cell tumours are managed by a diverse array of specialists. Thus, staging, risk stratification, and treatment approaches for germ-cell tumours have evolved disparately along several trajectories. Paediatric germ-cell tumours differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate, evidence-based care. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis, or platinum-resistant disease. Survivors have significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into improved patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxic effects, rational reduction of therapy for low-risk patients and novel approaches for poor-risk patients, and improved international collaboration across paediatric and adult cooperative research groups. PMID:27300675

  17. White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults

    PubMed Central

    Beydoun, M A; Beydoun, H A; Dore, G A; Canas, J-A; Fanelli-Kuczmarski, M T; Evans, M K; Zonderman, A B

    2016-01-01

    Total white blood cell count (TWBCC) and percentage (%) composition of lymphocytes (PL) or neutrophils (PN) are linked to mid- and late-life depression, though sex-specific temporal relationships between those inflammatory markers and depressive symptoms remain unclear. The association between inflammation and depressive symptoms in longitudinal data on ethnically and socioeconomically diverse urban adults was examined with two hypotheses. In hypothesis 1, we examined the relationship between TWBCC, PL and PN with change in level of depressive symptoms from baseline to follow-up, stratifying by sex. In hypothesis 2, we examined reverse causality, by testing the relationship of depressive symptoms with change in TWBCC, PL and PN. Multiple linear mixed-effects regression models were performed to examine both the hypotheses. The sample sizes of participants (n) and repeated observations (n') were: Hypothesis 1 (n=2009; n'=3501); Hypothesis 2 (n=2081; n'=3560). Among key findings (Hypothesis 1), in women, higher TWBCC was linked to a faster increase in depressive symptom total score (γ1112±s.e.: +0.81±0.28, P=0.003), with a slower increase over time in the positive affect subdomain coupled with faster increases in depressed affect and somatic complaints. Among women, baseline score on somatic complaints was positively associated with low PN (γ01a=+1.61±0.48, P<0.001) and high PL (γ01a=+1.16±0.45, P=0.011), whereas baseline score on positive affect was inversely related to higher PL (γ01a=−0.69±0.28, P=0.017). Results among men indicated that there was a positive cross-sectional relationship between low TWBCC and depressive symptoms, depressed affect and an inverse cross-sectional relationship with positive affect. However, over time, a low TWBCC in men was linked to a higher score on positive affect. There was no evidence of a bi-directional relationship between WBC parameters and depressive symptoms (Hypothesis 2). In sum, TWBCC and related markers were

  18. White blood cell inflammatory markers are associated with depressive symptoms in a longitudinal study of urban adults.

    PubMed

    Beydoun, M A; Beydoun, H A; Dore, G A; Canas, J-A; Fanelli-Kuczmarski, M T; Evans, M K; Zonderman, A B

    2016-01-01

    Total white blood cell count (TWBCC) and percentage (%) composition of lymphocytes (PL) or neutrophils (PN) are linked to mid- and late-life depression, though sex-specific temporal relationships between those inflammatory markers and depressive symptoms remain unclear. The association between inflammation and depressive symptoms in longitudinal data on ethnically and socioeconomically diverse urban adults was examined with two hypotheses. In hypothesis 1, we examined the relationship between TWBCC, PL and PN with change in level of depressive symptoms from baseline to follow-up, stratifying by sex. In hypothesis 2, we examined reverse causality, by testing the relationship of depressive symptoms with change in TWBCC, PL and PN. Multiple linear mixed-effects regression models were performed to examine both the hypotheses. The sample sizes of participants (n) and repeated observations (n') were: Hypothesis 1 (n=2009; n'=3501); Hypothesis 2 (n=2081; n'=3560). Among key findings (Hypothesis 1), in women, higher TWBCC was linked to a faster increase in depressive symptom total score (γ1112±s.e.: +0.81±0.28, P=0.003), with a slower increase over time in the positive affect subdomain coupled with faster increases in depressed affect and somatic complaints. Among women, baseline score on somatic complaints was positively associated with low PN (γ01a=+1.61±0.48, P<0.001) and high PL (γ01a=+1.16±0.45, P=0.011), whereas baseline score on positive affect was inversely related to higher PL (γ01a=-0.69±0.28, P=0.017). Results among men indicated that there was a positive cross-sectional relationship between low TWBCC and depressive symptoms, depressed affect and an inverse cross-sectional relationship with positive affect. However, over time, a low TWBCC in men was linked to a higher score on positive affect. There was no evidence of a bi-directional relationship between WBC parameters and depressive symptoms (Hypothesis 2). In sum, TWBCC and related markers were

  19. Stress kinases, endoplasmic reticulum stress, and Alzheimer’s disease related markers in peripheral blood mononuclear cells from subjects with increased body weight

    PubMed Central

    Lei, Ting; Yu, Lugang; Qin, Liqiang; Xu, Baohui; Zhou, Lingmei; Cheng, Jinbo; Zhou, Hui; Pang, Xing; Wan, Zhongxiao

    2016-01-01

    We aimed to characterize endoplasmic reticulum stress, inflammation, and Alzheimer’s disease (AD) related markers in peripheral blood mononuclear cells (PBMCs) from males with varied BMI; and to explore whether high glucose and fatty acids (FFAs) might be critical factors for inducing metabolic alterations in PBMCs under obese condition. Approximately 45 middle-aged men were enrolled with varied BMI. At the protein expression level, compared to the lean, the phosphorylation of AMPK, and p-Akt at serine 473 were significantly reduced from the overweight (OW) and/or obese (OB); while the protein expression of p-JNK, cleaved caspase 3, CHOP and p-eIF2α were elevated from the OW and/or OB. At the mRNA expression level, ER stress markers (i.e. GRP78, CHOP and XBP-1), inflammatory markers (i.e.TLR2, TLR4 and CCR2) and AD markers (i.e. APP, PS1 and PS2) were significantly higher in PBMCs from OB compared to lean. In cultured PBMCs, high glucose and FFAs induced GRP78, CHOP and XBP-1 mRNA, and high glucose also induced APP, PS1 and PS2 mRNA. In conclusion, altered markers including AMPK, ER stress and AD related makers under obese condition could be easily obtained from PBMCs. These markers might provide new mechanistic links between obesity and other metabolic complications including AD. PMID:27481183

  20. A rapid, reliable, and inexpensive method for detection of di- and trinucleotide repeat markers and disease loci from dried blood spots

    SciTech Connect

    Holden, J.A. |; Chalifoux, M.; Wing, M.

    1996-08-09

    We used a rapid and inexpensive method for studying the FMR1 CGG-repeat from dried blood spots, prepared from heel pricks, finger pricks, or an aliquot of blood from a venipuncture. The procedure includes a single tube for preparation of template DNA for PCR and minimal handling, avoiding opportunities for mislabelling specimens and loss of template. We extended the protocol to numerous di- and trinucleotide repeat markers and disease loci, including FRAXE, FRAXF, DXS548, DRPLA, and ZFY. The use of a highly reliable and very inexpensive method which employs blood spots as a source for target DNA means that newborn Guthrie cards can be used to establish allele frequencies for linkage disequilibrium studies, that large populations can be screened for genetic disorders, and that mapping studies can proceed rapidly even when only small amounts of blood are available from key family members. 16 refs., 5 figs.

  1. Markers of hepatitis C and B virus infections among blood donors in Ho Chi Minh City and Hanoi, Vietnam.

    PubMed

    Song, P; Duc, D D; Hien, B; Nakata, S; Chosa, T; Watanabe, J; Tsuda, F; Murata, K; Okamoto, H

    1994-07-01

    Blood donors in two cities in Vietnam were tested for markers of hepatitis C virus (HCV) and hepatitis B virus infections. Antibody to HCV was detected by passive hemagglutination with antigens of the second generation in 101 (20.6%) of 491 donors in Ho Chi Minh City; it was detected less frequently (P < 0.001) in donors in hanoi (4 [0.8%] of 499). HCV RNA was tested for in donors with antibody by PCR with nested primers from the 5'-noncoding region and detected in 79 donors in Ho Chi Minh City and 4 donors in Hanoi. HCV RNA was genotyped by PCR with type-specific primers from the core gene. Of 83 HCV carriers from Vietnam, 24 (29%) were infected with HCV of genotype I/1a 19 (23%) were infected with II/1b, 4 (5%) were infected with III/2a, and 2 (2%) were infected with mixed genotypes (I/1a and II/1b); HCV genotypes in the remaining 34 (41%) donors, including all 4 donors in Hanoi, were not classifiable into I/1a, II/2a, IV/2b, or V/3a. Of the 10 isolates with unclassifiable genotypes, 2 showed substantial sequence divergence within the 5'-noncoding region from reported isolates with known genotypes (I/1a to 6a). An analysis of part of the core gene sequence indicated that six of the remaining isolates most likely represented new HCV genotypes. Hepatitis B surface antigen and the corresponding antibody, respectively, were detected in 15 (3.1%) and 234 (47.7%) donors in Ho Chi Minh City as well as 15 (3.0%) and 248 (49.7%) donors in Hanoi. These results indicate an extensive spread of HCV among Ho Chi Minh City donors and HCV of novel genotypes in vietnam.

  2. The active metabolite of prasugrel inhibits ADP-stimulated thrombo-inflammatory markers of platelet activation: Influence of other blood cells, calcium, and aspirin.

    PubMed

    Frelinger, Andrew L; Jakubowski, Joseph A; Li, Youfu; Barnard, Marc R; Fox, Marsha L; Linden, Matthew D; Sugidachi, Atsuhiro; Winters, Kenneth J; Furman, Mark I; Michelson, Alan D

    2007-07-01

    The novel thienopyridine prodrug prasugrel, a platelet P2Y(12) ADP receptor antagonist, requires in vivo metabolism for activity. Although pharmacological data have been collected on the effects of prasugrel on platelet aggregation, there are few data on the direct effects of the prasugrel's active metabolite, R-138727, on other aspects of platelet function. Here we examined the effects of R-138727 on thrombo-inflammatory markers of platelet activation, and the possible modulatory effects of other blood cells, calcium, and aspirin. Blood (PPACK or citrate anticoagulated) from healthy donors pre- and post-aspirin was incubated with R-138727 and the response to ADP assessed in whole blood or platelet-rich plasma (PRP) by aggregometry and flow cytometric analysis of leukocyte-platelet aggregates, platelet surface P-selectin, and GPIIb-IIIa activation. Low-micromolar concentrations of R-138727 resulted in a rapid and consistent inhibition of these ADP-stimulated thrombo-inflammatory markers. These rapid kinetics required physiological calcium levels, but were largely unaffected by aspirin. Lower IC(50) values in whole blood relative to PRP suggested that other blood cells affect ADP-induced platelet activation and hence the net inhibition by R-138727. R-138727 did not inhibit P2Y(12)-mediated ADP-induced shape change, even at concentrations that completely inhibited platelet aggregation, confirming the specificity of R-138727 for P2Y(12). In conclusion, R-138727, the active metabolite of prasugrel, results in rapid, potent, consistent, and selective inhibition of P2Y(12)-mediated up-regulation of thrombo-inflammatory markers of platelet activation. This inhibition is enhanced in the presence other blood cells and calcium, but not aspirin. PMID:17598013

  3. White blood cell counts and neutrophil to lymphocyte ratio in the diagnosis of testicular cancer: a simple secondary serum tumor marker

    PubMed Central

    Yuksel, Ozgur Haki; Verit, Ayhan; Sahin, Aytac; Urkmez, Ahmet; Uruc, Fatih

    2016-01-01

    ABSTRACT Purpose The aim of the study was to investigate white blood cell counts and neutrophil to lymphocyte ratio (NLR) as markers of systemic inflammation in the diagnosis of localized testicular cancer as a malignancy with initially low volume. Materials and Methods Thirty-six patients with localized testicular cancer with a mean age of 34.22±14.89 years and 36 healthy controls with a mean age of 26.67±2.89 years were enrolled in the study. White blood cell counts and NLR were calculated from complete blood cell counts. Results White blood cell counts and NLR were statistically significantly higher in patients with testicular cancer compared with the control group (p<0.0001 for all). Conclusions Both white blood cell counts and NLR can be used as a simple test in the diagnosis of testicular cancer besides the well-known accurate serum tumor markers as AFP (alpha fetoprotein), hCG (human chorionic gonadotropin) and LDH (lactate dehydrogenase). PMID:27136467

  4. Pathway Markers for Pro-resolving Lipid Mediators in Maternal and Umbilical Cord Blood: A Secondary Analysis of the Mothers, Omega-3, and Mental Health Study

    PubMed Central

    Mozurkewich, Ellen L.; Greenwood, Matthew; Clinton, Chelsea; Berman, Deborah; Romero, Vivian; Djuric, Zora; Qualls, Clifford; Gronert, Karsten

    2016-01-01

    The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are precursors to immune regulatory and specialized pro-resolving mediators (SPM) of inflammation termed resolvins, maresins, and protectins. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5-lipoxygenase (LOX) and 15-LOX metabolic pathway precursors and downstream metabolites. We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and Mental Health study to determine whether SPM and SPM precursors are augmented by dietary EPA- and DHA-rich fish oil supplementation compared to soy oil placebo. We also aimed to study whether SPM and their precursors differ in early and late pregnancy or between maternal and umbilical cord blood. We found that compared to placebo supplementation, EPA- and DHA-rich fish oil supplementation increased SPM precursor 17-hydroxy docosahexaenoic acid (17-HDHA) concentrations in maternal and umbilical cord blood (P = 0.02). We found that the D-series resolvin pathway marker 17-HDHA increased significantly between enrollment and late pregnancy (P = 0.049). Levels of both 14-HDHA, a maresin pathway marker, and 17-HDHA were significantly greater in umbilical cord blood than in maternal blood (P < 0.001, both). PMID:27656142

  5. Pathway Markers for Pro-resolving Lipid Mediators in Maternal and Umbilical Cord Blood: A Secondary Analysis of the Mothers, Omega-3, and Mental Health Study

    PubMed Central

    Mozurkewich, Ellen L.; Greenwood, Matthew; Clinton, Chelsea; Berman, Deborah; Romero, Vivian; Djuric, Zora; Qualls, Clifford; Gronert, Karsten

    2016-01-01

    The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are precursors to immune regulatory and specialized pro-resolving mediators (SPM) of inflammation termed resolvins, maresins, and protectins. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5-lipoxygenase (LOX) and 15-LOX metabolic pathway precursors and downstream metabolites. We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and Mental Health study to determine whether SPM and SPM precursors are augmented by dietary EPA- and DHA-rich fish oil supplementation compared to soy oil placebo. We also aimed to study whether SPM and their precursors differ in early and late pregnancy or between maternal and umbilical cord blood. We found that compared to placebo supplementation, EPA- and DHA-rich fish oil supplementation increased SPM precursor 17-hydroxy docosahexaenoic acid (17-HDHA) concentrations in maternal and umbilical cord blood (P = 0.02). We found that the D-series resolvin pathway marker 17-HDHA increased significantly between enrollment and late pregnancy (P = 0.049). Levels of both 14-HDHA, a maresin pathway marker, and 17-HDHA were significantly greater in umbilical cord blood than in maternal blood (P < 0.001, both).

  6. Pathway Markers for Pro-resolving Lipid Mediators in Maternal and Umbilical Cord Blood: A Secondary Analysis of the Mothers, Omega-3, and Mental Health Study.

    PubMed

    Mozurkewich, Ellen L; Greenwood, Matthew; Clinton, Chelsea; Berman, Deborah; Romero, Vivian; Djuric, Zora; Qualls, Clifford; Gronert, Karsten

    2016-01-01

    The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are precursors to immune regulatory and specialized pro-resolving mediators (SPM) of inflammation termed resolvins, maresins, and protectins. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5-lipoxygenase (LOX) and 15-LOX metabolic pathway precursors and downstream metabolites. We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and Mental Health study to determine whether SPM and SPM precursors are augmented by dietary EPA- and DHA-rich fish oil supplementation compared to soy oil placebo. We also aimed to study whether SPM and their precursors differ in early and late pregnancy or between maternal and umbilical cord blood. We found that compared to placebo supplementation, EPA- and DHA-rich fish oil supplementation increased SPM precursor 17-hydroxy docosahexaenoic acid (17-HDHA) concentrations in maternal and umbilical cord blood (P = 0.02). We found that the D-series resolvin pathway marker 17-HDHA increased significantly between enrollment and late pregnancy (P = 0.049). Levels of both 14-HDHA, a maresin pathway marker, and 17-HDHA were significantly greater in umbilical cord blood than in maternal blood (P < 0.001, both). PMID:27656142

  7. Pathway Markers for Pro-resolving Lipid Mediators in Maternal and Umbilical Cord Blood: A Secondary Analysis of the Mothers, Omega-3, and Mental Health Study.

    PubMed

    Mozurkewich, Ellen L; Greenwood, Matthew; Clinton, Chelsea; Berman, Deborah; Romero, Vivian; Djuric, Zora; Qualls, Clifford; Gronert, Karsten

    2016-01-01

    The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are precursors to immune regulatory and specialized pro-resolving mediators (SPM) of inflammation termed resolvins, maresins, and protectins. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5-lipoxygenase (LOX) and 15-LOX metabolic pathway precursors and downstream metabolites. We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and Mental Health study to determine whether SPM and SPM precursors are augmented by dietary EPA- and DHA-rich fish oil supplementation compared to soy oil placebo. We also aimed to study whether SPM and their precursors differ in early and late pregnancy or between maternal and umbilical cord blood. We found that compared to placebo supplementation, EPA- and DHA-rich fish oil supplementation increased SPM precursor 17-hydroxy docosahexaenoic acid (17-HDHA) concentrations in maternal and umbilical cord blood (P = 0.02). We found that the D-series resolvin pathway marker 17-HDHA increased significantly between enrollment and late pregnancy (P = 0.049). Levels of both 14-HDHA, a maresin pathway marker, and 17-HDHA were significantly greater in umbilical cord blood than in maternal blood (P < 0.001, both).

  8. [Markers of viral hepatitis B and D and levels of alanine aminotransferase in military blood donors: a profile of 30,000 blood donations in 1989].

    PubMed

    Boulesteix, G; Bourin, P; Fabre, G; Blanchard de Vaucouleurs, A; Molinié, C; Denee, J M; Buisson, Y; Schill, H; Joussemet, M

    1990-01-01

    Serologic data for B and D viral hepatitis are studied on 30,000 military blood donors. Because of legal norms of blood products for transfusion 761 donations (2.53% have been destroyed). Exclusion criteria for viral B hepatitis and ALT are independent. In this study the prevalency of HBV infections is significantly lower than for other blood centers: probably in account of the young age of military blood donors.

  9. Discrimination between two different grades of human glioma based on blood vessel infrared spectral imaging.

    PubMed

    Wehbe, Katia; Forfar, Isabelle; Eimer, Sandrine; Cinque, Gianfelice

    2015-09-01

    Gliomas are brain tumours classified into four grades with increasing malignancy from I to IV. The development and the progression of malignant glioma largely depend on the tumour vascularization. Due to their tissue heterogeneity, glioma cases can be difficult to classify into a specific grade using the gold standard of histological observation, hence the need to base classification on a quantitative and reliable analytical method for accurately grading the disease. Previous works focused specifically on vascularization study by Fourier transform infrared (FTIR) spectroscopy, proving this method to be a way forward to detect biochemical changes in the tumour tissue not detectable by visual techniques. In this project, we employed FTIR imaging using a focal plane array (FPA) detector and globar source to analyse large areas of glioma tumour tissue sections via molecular fingerprinting in view of helping to define markers of the tumour grade. Unsupervised multivariate analysis (hierarchical cluster analysis and principal component analysis) of blood vessel spectral data, retrieved from the FPA images, revealed the fine structure of the borderline between two areas identified by a pathologist as grades III and IV. Spectroscopic indicators are found capable of discriminating different areas in the tumour tissue and are proposed as biomolecular markers for potential future use of grading gliomas. Graphical Abstract Infrared imaging of glioma blood vessels provides a means to revise the pathologists' line of demarcation separating grade III (GIII) from grade IV (GIV) parts. PMID:26168973

  10. Bronchial mucous gland tumours.

    PubMed

    Spencer, H

    1979-07-27

    Tumours arising in the bronchial mucous glands closely resemble tumours arising in the mixed salivary glands. Bronchial mucous gland tumours account for less than 0.5 per cent of all lung tumours. Twenty six tumours are reviewed and they have been divided into five types, (a) adenoidcystic carcinomas, (b) muco-epidermoid tumors, (c) mixed (pleomorphic) tumors, (d) cystadenomas and (f) oxyphilic adenoma. The clinical features, and postoperative course of the patients are reviewed. Adenocystic carcinomas, arising in the bronchus frequently involve the neighbouring trachea and spread mainly by direct infiltration. Most muco-epidermoid bronchial tumours were confined to young persons, and the only malignant muco-epidermoid tumour occurred in an elderly person. The prognosis in young persons is good provided the tumours are completely excised. The two mixed bronchial tumours resembled their salivary counterparts and one subsequently behaved as a carcinoma and metastasised. Bronchial cystadenomas all proved to be benign tumours but in two cases were associated with surface papillary proliferation. The only example of an oxyphil cell adenoma was discovered at post mortem examination. The histogenesis of the tumours is considered.

  11. Markers for blood-brain barrier integrity: how appropriate is Evans blue in the twenty-first century and what are the alternatives?

    PubMed Central

    Saunders, Norman R.; Dziegielewska, Katarzyna M.; Møllgård, Kjeld; Habgood, Mark D.

    2015-01-01

    In recent years there has been a resurgence of interest in brain barriers and various roles their intrinsic mechanisms may play in neurological disorders. Such studies require suitable models and markers to demonstrate integrity and functional changes at the interfaces between blood, brain, and cerebrospinal fluid. Studies of brain barrier mechanisms and measurements of plasma volume using dyes have a long-standing history, dating back to the late nineteenth-century. Their use in blood-brain barrier studies continues in spite of their known serious limitations in in vivo applications. These were well known when first introduced, but seem to have been forgotten since. Understanding these limitations is important because Evans blue is still the most commonly used marker of brain barrier integrity and those using it seem oblivious to problems arising from its in vivo application. The introduction of HRP in the mid twentieth-century was an important advance because its reaction product can be visualized at the electron microscopical level, but it also has limitations. Advantages and disadvantages of these markers will be discussed together with a critical evaluation of alternative approaches. There is no single marker suitable for all purposes. A combination of different sized, visualizable dextrans and radiolabeled molecules currently seems to be the most appropriate approach for qualitative and quantitative assessment of barrier integrity. PMID:26578854

  12. 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.

  13. Neuroendoscopic management of pineal region tumours.

    PubMed

    Ferrer, E; Santamarta, D; Garcia-Fructuoso, G; Caral, L; Rumià, J

    1997-01-01

    The management of pineal tumours remains controversial. During 1994 we treated four consecutive adults (16-44 yrs) harbouring a pineal tumour with a neuroendoscopic procedure. All of them presented with hydrocephalus. Pre-operative workup included cranial computerized tomography (CT), craniospinal magnetic resonance imaging (MRI) and serum levels of biological tumour markers. The endoscopic procedure consisted of a third ventriculostomy followed by biopsy with a flexible, steerable neuroendoscope. Histological diagnosis was achieved in three patients who no longer required a shunt device. Recorded complications were: bleeding during ventriculostomy that prevented us from obtaining a good sample for biopsy, short-term memory loss that cleared over a two-week period, and transient increase of pre-operative hemiparesis. Complications and morbidity are emphasized so as to be avoided with further technical experience. Neuroendoscopy affords a minimally invasive way of reaching three objectives by one-step surgery in the management of pineal region lesions: 1) CSF sample for analysis of tumour markers. 2) Treatment of hydrocephalus by third ventriculostomy. 3) Several biopsy specimens can be obtained identifying tumours which will require further open surgery or adjuvant radiation and/or chemotherapy. PMID:9059706

  14. Tumour progression and metastasis.

    PubMed

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour's survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible.

  15. Consensus on biomarkers for neuroendocrine tumour disease

    PubMed Central

    Oberg, Kjell; Modlin, Irvin M; De Herder, Wouter; Pavel, Marianne; Klimstra, David; Frilling, Andrea; Metz, David C; Heaney, Anthony; Kwekkeboom, Dik; Strosberg, Jonathan; Meyer, Timothy; Moss, Steven F; Washington, Kay; Wolin, Edward; Liu, Eric; Goldenring, James

    2016-01-01

    Management of neuroendocrine neoplasia represents a clinical challenge because of its late presentation, lack of treatment options, and limitations in present imaging modalities and biomarkers to guide management. Monoanalyte biomarkers have poor sensitivity, specificity, and predictive ability. A National Cancer Institute summit, held in 2007, on neuroendocrine tumours noted biomarker limitations to be a crucial unmet need in the management of neuroendocrine tumours. A multinational consensus meeting of multidisciplinary experts in neuroendocrine tumours assessed the use of current biomarkers and defined the perquisites for novel biomarkers via the Delphi method. Consensus (at >75%) was achieved for 88 (82%) of 107 assessment questions. The panel concluded that circulating multianalyte biomarkers provide the highest sensitivity and specificity necessary for minimum disease detection and that this type of biomarker had sufficient information to predict treatment effectiveness and prognosis. The panel also concluded that no monoanalyte biomarker of neuroendocrine tumours has yet fulfilled these criteria and there is insufficient information to support the clinical use of miRNA or circulating tumour cells as useful prognostic markers for this disease. The panel considered that trials measuring multianalytes (eg, neuroendocrine gene transcripts) should also identify how such information can optimise the management of patients with neuroendocrine tumours. PMID:26370353

  16. Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach

    PubMed Central

    Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N.

    2016-01-01

    It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination. PMID:26861829

  17. Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach.

    PubMed

    Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N

    2016-01-01

    It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination. PMID:26861829

  18. Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach

    NASA Astrophysics Data System (ADS)

    Lolas, Georgios; Bianchi, Arianna; Syrigos, Konstantinos N.

    2016-02-01

    It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination.

  19. Predictive and prognostic value of metabolic tumour volume and total lesion glycolysis in solid tumours.

    PubMed

    Van de Wiele, Christophe; Kruse, Vibeke; Smeets, Peter; Sathekge, Mike; Maes, Alex

    2013-01-01

    Data available in patients suffering from squamous cell carcinoma of the head and neck, lung carcinoma, oesophageal carcinoma and gynaecological malignancies suggest that metabolic tumour volume and to a lesser extent total lesion glycolysis have the potential to become valuable in the imaging of human solid tumours as prognostic biomarkers for short- to intermediate-term survival outcomes, adding value to clinical staging, for assessment of response to treatment with neoadjuvant and concurrent chemotherapy, and for treatment optimization; for example, based on early treatment response assessment using changes in metabolic tumour volume over time, it might be possible to select patients who require a more aggressive treatment to improve their outcome. Prospective studies enrolling consecutive patients, adopting standardized protocols for FDG PET acquisition and processing, adjusting for potential confounders in the analysis (tumour size and origin) and determining the optimal methodology for determination of these novel markers are mandatory.

  20. Tumour progression and metastasis

    PubMed Central

    Arvelo, Francisco; Sojo, Felipe; Cotte, Carlos

    2016-01-01

    The two biological mechanisms that determine types of malignancy are infiltration and metastasis, for which tumour microenvironment plays a key role in developing and establishing the morphology, growth and invasiveness of a malignancy. The microenvironment is formed by complex tissue containing the extracellular matrix, tumour and non-tumour cells, a signalling network of cytokines, chemokines, growth factors, and proteases that control autocrine and paracrine communication among individual cells, facilitating tumour progression. During the development of the primary tumour, the tumour stroma and continuous genetic changes within the cells makes it possible for them to migrate, having to count on a pre-metastatic niche receptor that allows the tumour’s survival and distant growth. These niches are induced by factors produced by the primary tumour; if it is eradicated, the active niches become responsible for activating the latent disseminated cells. Due to the importance of these mechanisms, the strategies that develop tumour cells during tumour progression and the way in which the microenvironment influences the formation of metastasis are reviewed. It also suggests that the metastatic niche can be an ideal target for new treatments that make controlling metastasis possible. PMID:26913068

  1. Melanoma miRNA trafficking controls tumour primary niche formation.

    PubMed

    Dror, Shani; Sander, Laureen; Schwartz, Hila; Sheinboim, Danna; Barzilai, Aviv; Dishon, Yuval; Apcher, Sebastien; Golan, Tamar; Greenberger, Shoshana; Barshack, Iris; Malcov, Hagar; Zilberberg, Alona; Levin, Lotan; Nessling, Michelle; Friedmann, Yael; Igras, Vivien; Barzilay, Ohad; Vaknine, Hananya; Brenner, Ronen; Zinger, Assaf; Schroeder, Avi; Gonen, Pinchas; Khaled, Mehdi; Erez, Neta; Hoheisel, Jörg D; Levy, Carmit

    2016-09-01

    Melanoma originates in the epidermis and becomes metastatic after invasion into the dermis. Prior interactions between melanoma cells and dermis are poorly studied. Here, we show that melanoma cells directly affect the formation of the dermal tumour niche by microRNA trafficking before invasion. Melanocytes, cells of melanoma origin, are specialized in releasing pigment vesicles, termed melanosomes. In melanoma in situ, we found melanosome markers in distal fibroblasts before melanoma invasion. The melanosomes carry microRNAs into primary fibroblasts triggering changes, including increased proliferation, migration and pro-inflammatory gene expression, all known features of cancer-associated fibroblasts (CAFs). Specifically, melanosomal microRNA-211 directly targets IGF2R and leads to MAPK signalling activation, which reciprocally encourages melanoma growth. Melanosome release inhibitor prevented CAF formation. Since the first interaction of melanoma cells with blood vessels occurs in the dermis, our data suggest an opportunity to block melanoma invasion by preventing the formation of the dermal tumour niche. PMID:27548915

  2. Neuron-specific enolase: reference values in cord blood.

    PubMed

    Kintzel, K; Sonntag, J; Strauss, E; Obladen, M

    1998-04-01

    With foetal sonography prenatal detection of tumours has become more frequent. To evaluate and treat these infants it is necessary to identify the tumour postnatally. Elevated neuron-specific enolase is a biochemical marker of neuroblastoma. Since conditions during birth may influence neuron-specific enolase concentration in foetal serum, specific reference values in cord blood are required. Cord blood samples were taken from 192 healthy term newborns and concentration of neuron-specific enolase was measured by enzyme immunoassay (EIA). Median neuron-specific enolase concentration in the reference group was 8.0 micrograms/l and the 5th-95th percentiles were 4.8-19.4 micrograms/l. No differences between male and female newborns were detected (p = 0.13). Measurement of neuron-specific enolase in cord blood, in comparison with our reference values, offers an early postnatal possibility of confirming the diagnosis of neuroblastoma.

  3. Decomposition of spontaneous fluctuations in tumour oxygenation using BOLD MRI and independent component analysis

    PubMed Central

    Gonçalves, Miguel R; Johnson, S Peter; Ramasawmy, Rajiv; Pedley, R Barbara; Lythgoe, Mark F; Walker-Samuel, Simon

    2015-01-01

    Background: Solid tumours can undergo cycles of hypoxia, followed by reoxygenation, which can have significant implications for the success of anticancer therapies. A need therefore exists to develop methods to aid its detection and to further characterise its biological basis. We present here a novel method for decomposing systemic and tumour-specific contributions to fluctuations in tumour deoxyhaemoglobin concentration, based on magnetic resonance imaging measurements. Methods: Fluctuations in deoxyhaemoglobin concentration in two tumour xenograft models of colorectal carcinoma were decomposed into distinct contributions using independent component analysis. These components were then correlated with systemic pulse oximetry measurements to assess the influence of systemic variations in blood oxygenation in tumours, compared with those that arise within the tumour itself (tumour-specific). Immunohistochemical staining was used to assess the physiological basis of each source of fluctuation. Results: Systemic fluctuations in blood oxygenation were found to contribute to cycling hypoxia in tumours, but tumour-specific fluctuations were also evident. Moreover, the size of the tumours was found to influence the degree of systemic, but not tumour-specific, oscillations. The degree of vessel maturation was related to the amplitude of tumour-specific, but not systemic, oscillations. Conclusions: Our results provide further insights into the complexity of spontaneous fluctuations in tumour oxygenation and its relationship with tumour pathophysiology. These observations could be used to develop improved drug delivery strategies. PMID:26484634

  4. Circulating tumour cells and circulating nucleic acids as a measure of tumour dissemination in non-metastatic colorectal cancer surgery.

    PubMed

    Lim, S H; Spring, K J; de Souza, P; MacKenzie, S; Bokey, L

    2015-03-01

    There is accumulating evidence for circulating tumour cells (CTCs) and circulating tumour nucleic acids (ctNAs) as prognostic and predictive biomarkers in colorectal cancer. Their role in the perioperative setting is evolving. These blood-borne biomarkers can potentially demonstrate tumour dissemination at time of colorectal cancer surgery and estimate the completeness of a surgical resection. CTCs and circulating ctNA levels at time of surgery, and persistent levels post-surgery, may correlate with poorer patient outcomes. These biomarkers can be utilised to refine surgical techniques to minimise tumour dissemination and determine the need for adjuvant therapy.

  5. Identification of novel molecular markers for detection of gastric cancer cells in the peripheral blood circulation using genome-wide microarray analysis.

    PubMed

    Matsumura, Nobuyuki; Zembutsu, Hitoshi; Yamaguchi, Koji; Sasaki, Kazuaki; Tsuruma, Tetsuhiro; Nishidate, Toshihiko; Denno, Ryuichi; Hirata, Koichi

    2011-07-01

    Although metastasis or relapse is a leading cause of death for patients with gastric cancer, the hematogenous spread of cancer cells remains undetected at the time of initial therapy. The development of novel diagnostic molecular marker(s) to detect circulating gastric cancer cells is an issue of great clinical importance. We obtained peripheral blood samples from 10 patients with gastric cancer who underwent laparotomy and 4 healthy volunteers. Microarray analysis consisting of 30,000 genes or ESTs was carried out using eight gastric cancer tissues and normal gastric mucosae. We selected 53 genes up-regulated in gastric cancer compared to normal gastric mucosae from our microarray data set, and, among these, identified five candidate marker genes (TSPAN8, EPCAM, MMP12, MMP7 and REG3A) which were not expressed in peripheral blood mononuclear cells (PBMCs) from 4 healthy volunteers. We further carried out semi-quantitative nested reverse transcription-polymerase chain reaction (RT-PCR) for HRH1, EGFR, CK20 and CEA in addition to the five newly identified genes using PBMCs of patients with gastric cancer, and found that expression of one or more genes out of the nine was detected in 80% of the patients with gastric cancer. Moreover, the numbers of genes expressed in PBMCs were ≤2 and ≥2 in all vascular invasion-negative cases and in 5 of 6 positive cases, respectively, showing significant differences between the two groups (P=0.041). Nested RT-PCR analysis for the set of nine marker genes using PBMCs may provide the potential for detection of circulating gastric cancer cells prior to metastasis formation in other organs.

  6. Solitary fibrous tumour of the chest wall.

    PubMed

    Mohtarrudin, N; Nor Hanipah, Z; Mohd Dusa, N

    2016-04-01

    Extrapleural solitary fibrous tumours (SFTs) are rare tumours characterized by patternless spindle cells with haemangiopericytoma-like vascular spaces. Previously the tumours have been classified as haemangiopericytoma, an entity that is now considered obsolete. We report a case of extrapleural SFT arising in the soft tissue of the chest wall. The patient was a 31-year-old Malay lady presenting with a mobile swelling of the right chest wall for more than five years. During excision the tumour was noted to be well-circumscribed and yellowish in colour, giving an impression of lipoma. Microscopically, the tumour had patternless architecture, characterized by hypocellular and hypercellular areas. It was composed of uniform, spindle-shaped cells displaying oval nuclei, inconspicuous nucleoli, pale cytoplasm and indistinct cell borders. The mitotic count was 2 per 10 HPF. Branching, medium-sized thin-walled blood vessels in a haemangiopericytomatous growth pattern, some with hyalinised wall were identified. The neoplastic cells were immunoreactive to CD99 and CD34 and were non-immunoreactive to Desmin, Smooth Muscle Actin, S100 protein and EMA. We elucidate the challenges in diagnosing this tumour in this unusual location.

  7. Solitary fibrous tumour of the chest wall.

    PubMed

    Mohtarrudin, N; Nor Hanipah, Z; Mohd Dusa, N

    2016-04-01

    Extrapleural solitary fibrous tumours (SFTs) are rare tumours characterized by patternless spindle cells with haemangiopericytoma-like vascular spaces. Previously the tumours have been classified as haemangiopericytoma, an entity that is now considered obsolete. We report a case of extrapleural SFT arising in the soft tissue of the chest wall. The patient was a 31-year-old Malay lady presenting with a mobile swelling of the right chest wall for more than five years. During excision the tumour was noted to be well-circumscribed and yellowish in colour, giving an impression of lipoma. Microscopically, the tumour had patternless architecture, characterized by hypocellular and hypercellular areas. It was composed of uniform, spindle-shaped cells displaying oval nuclei, inconspicuous nucleoli, pale cytoplasm and indistinct cell borders. The mitotic count was 2 per 10 HPF. Branching, medium-sized thin-walled blood vessels in a haemangiopericytomatous growth pattern, some with hyalinised wall were identified. The neoplastic cells were immunoreactive to CD99 and CD34 and were non-immunoreactive to Desmin, Smooth Muscle Actin, S100 protein and EMA. We elucidate the challenges in diagnosing this tumour in this unusual location. PMID:27126667

  8. Value of A103 (melan-A) immunostaining in the differential diagnosis of ovarian sex cord stromal tumours

    PubMed Central

    Stewart, C; Nandini, C; Richmond, J

    2000-01-01

    Aims—To assess A103 (melan-A) immunoreactivity in a range of ovarian sex cord stromal tumours and to evaluate it for the differential diagnosis of other neoplasms. Methods—Paraffin embedded tissue sections from 45 sex cord stromal tumours and 44 potential histological mimics were examined immunohistochemically using the antibody A103. The sex cord stromal group included 21 adult granulosa cell tumours (AGCT), two juvenile granulosa cell tumours (JGCT), eight tumours showing Sertoli cell or Sertoli-Leydig cell differentiation, two unclassified tumours, two gonadoblastomas, one sex cord tumour with annular tubules, two steroid cell tumours, five thecomas/fibrothecomas, and two sclerosing stromal tumours. The histological mimics include 14 primary ovarian carcinomas, 13 metastatic carcinomas, four carcinoid tumours, four lymphomas, three endometrioid stromal sarcomas, two ovarian tumours of probable Wolffian origin, and one case each of small cell carcinoma, desmoplastic small round cell tumour, melanoma, and primitive neuroectodermal tumour. Results—A103 immunoreactivity was identified in 25 sex cord stromal tumours including 10 AGCT, two JGCT, six Sertoli/Sertoli-Leydig cell tumours, two steroid cell tumours, three thecomas/fibrothecomas, and two sclerosing stromal tumours. Of the potential histological mimics, staining was present only in the two ovarian tumours of probable Wolffian origin and the melanoma. Immunoreactive stromal cells were noted in a minority of cases. Normal hilus cells and rete ovarii epithelium also expressed A103. Conclusions—A103 is a moderately sensitive and specific marker of sex cord stromal differentiation within the range of tumours examined in this study and as such is a valuable adjunct to other immunocytochemical markers in the assessment of diagnostically problematic ovarian tumours. The staining of normal and neoplastic Wolffian elements merits further investigation. Key Words: ovarian tumours • A103

  9. Physical exercise, fitness and dietary pattern and their relationship with circadian blood pressure pattern, augmentation index and endothelial dysfunction biological markers: EVIDENT study protocol

    PubMed Central

    2010-01-01

    Background Healthy lifestyles may help to delay arterial aging. The purpose of this study is to analyze the relationship of physical activity and dietary pattern to the circadian pattern of blood pressure, central and peripheral blood pressure, pulse wave velocity, carotid intima-media thickness and biological markers of endothelial dysfunction in active and sedentary individuals without arteriosclerotic disease. Methods/Design Design: A cross-sectional multicenter study with six research groups. Subjects: From subjects of the PEPAF project cohort, in which 1,163 who were sedentary became active, 1,942 were sedentary and 2,346 were active. By stratified random sampling, 1,500 subjects will be included, 250 in each group. Primary measurements: We will evaluate height, weight, abdominal circumference, clinical and ambulatory blood pressure with the Radial Pulse Wave Acquisition Device (BPro), central blood pressure and augmentation index with Pulse Wave Application Software (A-Pulse) and SphymgoCor System Px (Pulse Wave Analysis), pulse wave velocity (PWV) with SphymgoCor System Px (Pulse Wave Velocity), nutritional pattern with a food intake frequency questionnaire, physical activity with the 7-day PAR questionnaire and accelerometer (Actigraph GT3X), physical fitness with the cycle ergometer (PWC-170), carotid intima-media thickness by ultrasound (Micromax), and endothelial dysfunction biological markers (endoglin and osteoprotegerin). Discussion Determining that sustained physical activity and the change from sedentary to active as well as a healthy diet improve circadian pattern, arterial elasticity and carotid intima-media thickness may help to propose lifestyle intervention programs. These interventions could improve the cardiovascular risk profile in some parameters not routinely assessed with traditional risk scales. From the results of this study, interventional approaches could be obtained to delay vascular aging that combine physical exercise and diet

  10. Improving tumour heterogeneity MRI assessment with histograms

    PubMed Central

    Just, N

    2014-01-01

    By definition, tumours are heterogeneous. They are defined by marked differences in cells, microenvironmental factors (oxygenation levels, pH, VEGF, VPF and TGF-α) metabolism, vasculature, structure and function that in turn translate into heterogeneous drug delivery and therapeutic outcome. Ways to estimate quantitatively tumour heterogeneity can improve drug discovery, treatment planning and therapeutic responses. It is therefore of paramount importance to have reliable and reproducible biomarkers of cancerous lesions' heterogeneity. During the past decade, the number of studies using histogram approaches increased drastically with various magnetic resonance imaging (MRI) techniques (DCE-MRI, DWI, SWI etc.) although information on tumour heterogeneity remains poorly exploited. This fact can be attributed to a poor knowledge of the available metrics and of their specific meaning as well as to the lack of literature references to standardised histogram methods with which surrogate markers of heterogeneity can be compared. This review highlights the current knowledge and critical advances needed to investigate and quantify tumour heterogeneity. The key role of imaging techniques and in particular the key role of MRI for an accurate investigation of tumour heterogeneity is reviewed with a particular emphasis on histogram approaches and derived methods. PMID:25268373

  11. Risk factors associated with hepatitis B or C markers or elevated alanine aminotransferase level among blood donors on a tropical island: the Guadeloupe experience.

    PubMed

    Fest, T; Viel, J F; Agis, F; Coffe, C; Dupond, J L; Hervé, P

    1992-10-01

    Donated blood is currently screened for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc), antibody to hepatitis C virus (anti-HCV), and alanine aminotransferase (ALT) levels to prevent posttransfusion hepatitis. A prospective study of 2368 blood donors was carried out in Guadeloupe (French West Indies) with a view to determining the risk factors associated with serologic abnormalities. Blood donors included in the study had to complete a questionnaire. Statistical analysis was performed on the data thus obtained: 571 donations (24%) were positive for at least one of the four analyzed markers. The results were that 3.2 percent were positive for HBsAg, 22 percent for anti-HBc, and 0.8 percent for anti-HCV, and 1.4 percent had ALT > or = 45 IU per L. A good correlation was found between anti-HCV and elevated ALT. Transfusion history and two socioeconomic categories (working class, military personnel) were found to be risk factors. Other risk factors were lifelong residence in Guadeloupe (with risk increasing with the number of years), birthplace and current residence in the southern part of the island, and the existence of gastrointestinal discomfort unrelated to viral hepatitis (odds ratio = 2.98). The results of this study illustrate the difficulty of implementing a preventive policy against posttransfusion hepatitis in a tropical area. The unique epidemiologic situation of Guadeloupe as regards hepatitis B virus has led to more restrictive criteria for the acceptance of blood donors. PMID:1412685

  12. Twenty-four-Hour Ambulatory Blood Pressure Monitor Heart Rate: A Potential Marker for Gestational Hypertension in at-Risk Women

    PubMed Central

    Booker, Corenthian J.; Dodson, William C.; Kunselman, Allen R.; Repke, John T.; Legro, Richard S.

    2013-01-01

    We prospectively correlated the 24-hour ambulatory blood pressure measurements (ABPM) to conventional sphygmomanometer blood pressure measurements (CSM) in women at risk for gestational hypertensive disorders (GHTNDs) and identified predictive factors from ABPM for GHTND. We analyzed 73 women with ≥1 risk factor for developing a GHTND. Using both the CSM and ABPM, the systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), and heart rate (HR) were measured for 24 hours during three periods (14 to 24 weeks; 24 to 32 weeks; and 33 weeks to delivery). Correlation between the CSM and ABPM lessened as pregnancy progressed. Seventeen (25%) of women developed a GHTND. MAP variability increased in the GHTND group versus those without a GHTND. The odds of developing a GHTND increased 1.5 times for every 1 beat per minute increase in the ABPM 24-hour HR at visit 1 and reversed by visit 3. In women at risk for a GHTND, CSM and ABPM correlate less well as pregnancy advances. HR changes in at-risk women may be a marker for the development of a GHTND and may reflect increased sympathetic activity and/or decreased baroreceptor sensitivity. PMID:22147639

  13. The Early Expression of HLA-DR and CD64 Myeloid Markers Is Specifically Compartmentalized in the Blood and Lungs of Patients with Septic Shock

    PubMed Central

    Mikaszewska-Sokolewicz, Małgorzata; Hoser, Grażyna; Zielińska-Borkowska, Urszula

    2016-01-01

    Identification of reliable biomarkers is key to guide targeted therapies in septic patients. Expression monitoring of monocyte HLA-DR and neutrophil CD64 could fulfill the above need. However, it is unknown whether their expression on circulating cells reflects the status of tissue resident cells. We compared expressions of HLA-DR and CD64 markers in the circulation and airways of septic shock patients and evaluated their outcome prognostic value. The expression of CD64 on neutrophils and HLA-DR on monocytes was analyzed in the peripheral blood and mini-bronchoalveolar lavage fluid cells by flow cytometry. Twenty-seven patients with septic shock were enrolled into the study. The fluorescence intensity of HLA-DR on circulating monocytes was 3.5-fold lower than on the pulmonary monocytes (p = 0.01). The expression of CD64 on circulating and airway neutrophils was similar (p = 0.47). Only the expression of CD64 on circulating neutrophils was higher in nonsurvivors versus survivors (2.8-fold; p = 0.031). Pulmonary monocytes display a higher level of HLA-DR activation compared to peripheral blood monocytes but the expression of neutrophil CD64 is similar on lung and circulating cells. Death in septic patients was effectively predicted by neutrophil CD64 but not monocytic HLA-DR. Prognostic value of cellular activation markers in septic shock appears to strongly depend on their level of compartmentalization. PMID:27413252

  14. The use of a spaceflight-compatible device to perform WBC surface marker staining and whole-blood mitogenic activation for cytokine detection by flow cytometry

    NASA Technical Reports Server (NTRS)

    Crucian, B. E.; Sams, C. F.

    1999-01-01

    Significant changes have recently been described regarding circulating peripheral immune cells immediately following spaceflight. Existing methods for immunophenotype staining of peripheral blood in terrestrial labs do not meet the constraints for flight on the Space Shuttle. We have recently described the development and use of the Whole Blood Staining Device (WBSD), a simple device for staining flow cytometry specimens during spaceflight. When preparing samples with the WBSD, all liquids are safely contained as the cells are moved through staining, lysis and fixation steps. Here we briefly review the use of the WBSD, and then describe another versatile adaptation, a modification to perform intracellular staining of cytokines for detection by flow cytometry. Alterations in cytokine production have been reported both in ground-based simulated microgravity culture and in astronaut samples returning from spaceflight. Data regarding microgravity effects on cytokine production for specific subpopulations of cells is lacking. Flow cytometric cytokine analysis offers the unique ability to perform simultaneous surface marker analysis and positively identity cytokine producing subsets of cells. The utilization of the WBSD provides the ability to perform rapid and routine mitogenic activation during spaceflight coupled with the ability to perform simultaneous surface marker analysis. The only external requirements for this procedure are an in-flight 37-degree incubator and the capacity for 4-degree storage.

  15. A module of human peripheral blood mononuclear cell transcriptional network containing primitive and differentiation markers is related to specific cardiovascular health variables.

    PubMed

    Moldovan, Leni; Anghelina, Mirela; Kantor, Taylor; Jones, Desiree; Ramadan, Enass; Xiang, Yang; Huang, Kun; Kolipaka, Arunark; Malarkey, William; Ghasemzadeh, Nima; Mohler, Peter J; Quyyumi, Arshed; Moldovan, Nicanor I

    2014-01-01

    Peripheral blood mononuclear cells (PBMCs), including rare circulating stem and progenitor cells (CSPCs), have important yet poorly understood roles in the maintenance and repair of blood vessels and perfused organs. Our hypothesis was that the identities and functions of CSPCs in cardiovascular health could be ascertained by analyzing the patterns of their co-expressed markers in unselected PBMC samples. Because gene microarrays had failed to detect many stem cell-associated genes, we performed quantitative real-time PCR to measure the expression of 45 primitive and tissue differentiation markers in PBMCs from healthy and hypertensive human subjects. We compared these expression levels to the subjects' demographic and cardiovascular risk factors, including vascular stiffness. The tested marker genes were expressed in all of samples and organized in hierarchical transcriptional network modules, constructed by a bottom-up approach. An index of gene expression in one of these modules (metagene), defined as the average standardized relative copy numbers of 15 pluripotency and cardiovascular differentiation markers, was negatively correlated (all p<0.03) with age (R2 = -0.23), vascular stiffness (R2 = -0.24), and central aortic pressure (R2 = -0.19) and positively correlated with body mass index (R2 = 0.72, in women). The co-expression of three neovascular markers was validated at the single-cell level using mRNA in situ hybridization and immunocytochemistry. The overall gene expression in this cardiovascular module was reduced by 72±22% in the patients compared with controls. However, the compactness of both modules was increased in the patients' samples, which was reflected in reduced dispersion of their nodes' degrees of connectivity, suggesting a more primitive character of the patients' CSPCs. In conclusion, our results show that the relationship between CSPCs and vascular function is encoded in modules of the PBMCs transcriptional network

  16. Uveal tumour resection

    PubMed Central

    Char, D.; Miller, T.; Crawford, J

    2001-01-01

    AIM—To review the ocular retention rates, visual results, and metastases in uveal tumours managed with eye wall resection techniques.
METHODS—This was a retrospective analysis of consecutive local uveal tumour resections performed by a single surgeon. All enucleation specimens were reviewed by one author. Both parametric and non-parametric analysis of data were performed.
RESULTS—138 eyes were scheduled for eye wall resection surgery. The mean age was 52 years (range 11-86 years). Tumours involved predominantly the iris in 14 cases, iris-ciliary body in 57, ciliary body alone in 18 patients, and in 49 cases the choroid was involved (ciliochoroidal, iris-ciliary body-choroid, or choroid). 125 eyes harboured melanomas; posterior tumours were more likely to have epithelioid cells (p<0.05). The mean follow up was 6 years. The mean clock hours in iris and iris-ciliary body tumours was 3.5. In tumours that involved the choroid the mean largest diameter was 12.9 mm and the mean thickness 8.5 mm. 105 of 138 (76%) eyes were retained. Histological assessment of surgical margins did not correlate evidence of tumour in enucleated eyes or metastatic disease. Surgical margins of more anterior tumours were more likely to be clear on histological evaluation (p<0.05). Approximately 53% of retained eyes had a final visual acuity of ⩾20/40; visual results were significantly better in more anteriorly located tumours (p<0.05). All retained iris tumour cases had ⩾20/40 final visual acuity. In tumours that involved the choroid nine of 31 retained eyes kept that level of visual acuity. Eight patients developed metastases; all metastatic events developed in patients with tumours that involved the choroid, and seven of eight were mixed cell melanomas.
CONCLUSIONS—76% of eyes were retained and 53% of these had a final visual acuity of ⩾20/40. Only 7% of uveal melanoma patients developed metastatic disease with a mean follow up of 6 years. Survival did not

  17. Lysyl oxidase-like-2 promotes tumour angiogenesis and is a potential therapeutic target in angiogenic tumours.

    PubMed

    Zaffryar-Eilot, Shelly; Marshall, Derek; Voloshin, Tali; Bar-Zion, Avinoam; Spangler, Rhyannon; Kessler, Ofra; Ghermazien, Haben; Brekhman, Vera; Suss-Toby, Edith; Adam, Dan; Shaked, Yuval; Smith, Victoria; Neufeld, Gera

    2013-10-01

    Lysyl oxidase-like 2 (LOXL2), a secreted enzyme that catalyzes the cross-linking of collagen, plays an essential role in developmental angiogenesis. We found that administration of the LOXL2-neutralizing antibody AB0023 inhibited bFGF-induced angiogenesis in Matrigel plug assays and suppressed recruitment of angiogenesis promoting bone marrow cells. Small hairpin RNA-mediated inhibition of LOXL2 expression or inhibition of LOXL2 using AB0023 reduced the migration and network-forming ability of endothelial cells, suggesting that the inhibition of angiogenesis results from a direct effect on endothelial cells. To examine the effects of AB0023 on tumour angiogenesis, AB0023 was administered to mice bearing tumours derived from SKOV-3 ovarian carcinoma or Lewis lung carcinoma (LLC) cells. AB0023 treatment significantly reduced the microvascular density in these tumours but did not inhibit tumour growth. However, treatment of mice bearing SKOV-3-derived tumours with AB0023 also promoted increased coverage of tumour vessels with pericytes and reduced tumour hypoxia, providing evidence that anti-LOXL2 therapy results in the normalization of tumour blood vessels. In agreement with these data, treatment of mice bearing LLC-derived tumours with AB0023 improved the perfusion of the tumour-associated vessels as determined by ultrasonography. Improved perfusion and normalization of tumour vessels after treatment with anti-angiogenic agents were previously found to improve the delivery of chemotherapeutic agents into tumours and to result in an enhancement of chemotherapeutic efficiency. Indeed, treatment with AB0023 significantly enhanced the anti-tumourigenic effects of taxol. Our results suggest that inhibition of LOXL2 may prove beneficial for the treatment of angiogenic tumours.

  18. Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases.

    PubMed

    Bacioglu, Mehtap; Maia, Luis F; Preische, Oliver; Schelle, Juliane; Apel, Anja; Kaeser, Stephan A; Schweighauser, Manuel; Eninger, Timo; Lambert, Marius; Pilotto, Andrea; Shimshek, Derya R; Neumann, Ulf; Kahle, Philipp J; Staufenbiel, Matthias; Neumann, Manuela; Maetzler, Walter; Kuhle, Jens; Jucker, Mathias

    2016-07-01

    A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases. PMID:27292537

  19. Noise-induced hearing loss: A possible marker for high blood pressure in older noise-exposed populations

    SciTech Connect

    Talbott, E.O.; Findlay, R.C.; Kuller, L.H.; Lenkner, L.A.; Matthews, K.A.; Day, R.D.; Ishii, E.K. )

    1990-08-01

    The present study assessed the relationships among occupational noise exposure, noise-induced hearing loss, and high blood pressure. The study population consisted of 245 retired metal assembly workers from Pittsburgh aged 56 to 68 with chronic noise exposure of 30 or more years at greater than or equal to 89 dBA. Results of the audiometric testing indicated 52% of the younger workers (ages 56 to 63) have severe noise-induced hearing loss (greater than or equal to 65 dBA loss at 3, 4, or 6 kHz) and 67% of older workers (ages 64 to 68). Body mass index and alcohol intake were significantly related to systolic and diastolic blood pressure. Among older men, there was a marginally significant increased prevalence of high blood pressure (greater than or equal to 90 mm diastolic or taking blood pressure medicine) among those with severe noise-induced hearing loss (P = .05). Moreover, another measure of hearing loss at high frequencies, speech discrimination score in noise (measured in the better ear), referred to as the W-22 MAX score, was also found to be related to the prevalence of high blood pressure in the older (64 to 68) age group (P less than .05). Multiple regression analysis revealed W-22 MAX and severe noise-induced hearing loss were independent predictors of hypertension in the older, but not in the younger group of retired workers.

  20. Neurofilament Light Chain in Blood and CSF as Marker of Disease Progression in Mouse Models and in Neurodegenerative Diseases.

    PubMed

    Bacioglu, Mehtap; Maia, Luis F; Preische, Oliver; Schelle, Juliane; Apel, Anja; Kaeser, Stephan A; Schweighauser, Manuel; Eninger, Timo; Lambert, Marius; Pilotto, Andrea; Shimshek, Derya R; Neumann, Ulf; Kahle, Philipp J; Staufenbiel, Matthias; Neumann, Manuela; Maetzler, Walter; Kuhle, Jens; Jucker, Mathias

    2016-07-01

    A majority of current disease-modifying therapeutic approaches for age-related neurodegenerative diseases target their characteristic proteopathic lesions (α-synuclein, Tau, Aβ). To monitor such treatments, fluid biomarkers reflecting the underlying disease process are crucial. We found robust increases of neurofilament light chain (NfL) in CSF and blood in murine models of α-synucleinopathies, tauopathy, and β-amyloidosis. Blood and CSF NfL levels were strongly correlated, and NfL increases coincided with the onset and progression of the corresponding proteopathic lesions in brain. Experimental induction of α-synuclein lesions increased CSF and blood NfL levels, while blocking Aβ lesions attenuated the NfL increase. Consistently, we also found NfL increases in CSF and blood of human α-synucleinopathies, tauopathies, and Alzheimer's disease. Our results suggest that CSF and particularly blood NfL can serve as a reliable and easily accessible biomarker to monitor disease progression and treatment response in mouse models and potentially in human proteopathic neurodegenerative diseases.

  1. Clinicopathological features and proliferation markers in tongue squamous cell carcinomas.

    PubMed

    Gueiros, L A; Coletta, R D; Kowalski, L P; Lopes, M A

    2011-05-01

    The aim of this study was to evaluate the clinicopathological features and immunohistochemical expression of proliferation markers in oral tongue squamous cell carcinomas (OTSCC). Sixty-three patients without previous treatment or distant metastases were selected. Clinical information was retrieved from medical charts, histopathological analysis was performed and expression of proliferation markers (Ki-67, Mcm-2 and geminin) was evaluated. Most patients were men (81%) (male:female ratio 4.25:1). The age range was 31-92 years (mean 57.6 ± 11.81 years). A high Anneroth score was associated with tumour size (p=0.05), tumoural embolization of the blood vessels (p=0.003), nodal metastasis (p=0.05), nodal capsule rupture (p=0.016) and distant metastasis (p=0.002). Elevated Bryne scores were significantly associated with nodal capsule rupture (p=0.02), distant metastasis (p=0.002), shorter overall survival (OS) (p=0.03) and disease-free survival (DFS) (p=0.05) compared with patients with lower score. Elevated Ki-67+ cells (p=0.05) and Mcm-2+ cells (p=0.008) were associated with nodal metastasis and tumours with a high geminin score demonstrated a significant tendency for neural invasion (p=0.05). Anneroth and Bryne score in association with biomarkers of proliferation can be useful for evaluating the biological behaviour of OTSCC. PMID:21277167

  2. Effect of Cucurbita ficifolia and Probiotic Yogurt Consumption on Blood Glucose, Lipid Profile, and Inflammatory Marker in Type 2 Diabetes

    PubMed Central

    Bayat, Azade; Azizi-Soleiman, Fatemeh; Heidari-Beni, Motahar; Feizi, Awat; Iraj, Bijan; Ghiasvand, Reza; Askari, Gholamreza

    2016-01-01

    Background: Control of blood sugar, hypertension, and dyslipidemia are key factors in diabetes management. Cucurbita ficifolia (pumpkin) is a vegetable which has been used traditionally as a remedy for diabetes in Iran. In addition, consumption of probiotics may have beneficial effects on people with Type 2 diabetes. The aim of this study was an investigation of the effects of C. ficifolia and probiotic yogurt consumption alone or at the same time on blood glucose and serum lipids in diabetic patients. Methods: Eighty eligible participants randomly were assigned to four groups: 1 - green C. ficifolia (100 g); 2 - probiotic yogurt (150 g); 3 - C. ficifolia plus probiotic yogurt (100 g C. ficifolia plus 150 g yogurt); and 4 -control (dietary advice) for 8 weeks. Blood pressure, glycemic response, lipid profile, and high-sensitive C-reactive protein (hsCRP) were measured before and after the intervention. Results: Total cholesterol (TC) decreased significantly in yogurt and yogurt plus C. ficifolia groups (within groups P = 0.010, and P < 0.001, respectively). C. ficifolia plus yogurt consumption resulted in a decrease in triglyceride (TG) and an increase in high-density lipoprotein cholesterol (HDL-C) (within groups P < 0.001 and P = 0.001, respectively). All interventions led to a significant decrease in blood sugar, hemoglobin A1c (HbA1c), hsCRP, and low-density lipoprotein cholesterol (LDL-C) level within groups. Blood pressure decreased significantly in Cucurbita group and yogurt group (within groups P < 0.001, and P = 0.001 for systolic blood pressure [SBP] and P < 0.001, and P = 0.004 for diastolic blood pressure [DBP], respectively). All variables changed between groups significantly except LDL-C level. Conclusions: Variables including TG, HDL-C, TC, fasting blood sugar, HbA1c, SBP, DBP, and hsCRP changed beneficially between groups. It seems that consumption of C. ficifolia and probiotic yogurt may help treatment of diabetic patients. PMID:26955460

  3. Unusual presentation of a scrotal tumour

    PubMed Central

    Sarkar, Debashis; Parr, Nijel J

    2014-01-01

    A 59-year-old man had a wide excision of the right-sided scrotal cancer in the neck of the scrotum. On dissection it became apparent that the tumour had developed a blood supply from the right spermatic cord. Histology revealed G2T2 squamous cell carcinoma. A biopsy from an abnormal skin area from the opposite groin reported chronic folliculitis. He underwent an ultrasound scanning of the groin and fine-needle aspiration, which did not show any suspicious features. Follow-up CT of the abdomen and pelvis after 6 weeks did not show any evidence of intra-abdominal lymphadenopathy. Another CT has been arranged within the next 3 months to confirm that the spread of the tumour does not follow the pattern of a testicular tumour. PMID:24879734

  4. Unusual presentation of a scrotal tumour.

    PubMed

    Sarkar, Debashis; Parr, Nijel J

    2014-05-30

    A 59-year-old man had a wide excision of the right-sided scrotal cancer in the neck of the scrotum. On dissection it became apparent that the tumour had developed a blood supply from the right spermatic cord. Histology revealed G2T2 squamous cell carcinoma. A biopsy from an abnormal skin area from the opposite groin reported chronic folliculitis. He underwent an ultrasound scanning of the groin and fine-needle aspiration, which did not show any suspicious features. Follow-up CT of the abdomen and pelvis after 6 weeks did not show any evidence of intra-abdominal lymphadenopathy. Another CT has been arranged within the next 3 months to confirm that the spread of the tumour does not follow the pattern of a testicular tumour.

  5. Mouse Models of Brain Metastasis for Unravelling Tumour Progression.

    PubMed

    Soto, Manuel Sarmiento; Sibson, Nicola R

    2016-01-01

    Secondary tumours in the brain account for 40 % of triple negative breast cancer patients, and the percentage may be higher at the time of autopsy. The use of in vivo models allow us to recapitulate the molecular mechanisms potentially used by circulating breast tumour cells to proliferate within the brain.Metastasis is a multistep process that depends on the success of several stages including cell evasion from the primary tumour, distribution and survival within the blood stream and cerebral microvasculature, penetration of the blood-brain barrier and proliferation within the brain microenvironment. Cellular adhesion molecules are key proteins involved in all of the steps in the metastatic process. Our group has developed two different in vivo models to encompass both seeding and colonisation stages of the metastatic process: (1) haematogenous dissemination of tumour cells by direct injection into the left ventricle of the heart, and (2) direct implantation of the tumour cells into the mouse brain.This chapter describes, in detail, the practical implementation of the intracerebral model, which can be used to analyse tumour proliferation within a specific area of the central nervous system and tumour-host cell interactions. We also describe the use of immunohistochemistry techniques to identify, at the molecular scale, tumour-host cell interactions, which may open new windows for brain metastasis therapy.

  6. 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. PMID:26021306

  7. Detection of IP-10 protein marker in undiluted blood serum via an electrochemical E-DNA scaffold sensor

    PubMed Central

    Bonham, Andrew J.; Paden, Nicole G.; Ricci, Francesco

    2014-01-01

    We describe an electrochemical analog of fluorescence polarization that supports the quantitative measurement of a specific protein, the chemokine IP-10, directly in undiluted blood serum. The sensor is label-free, wash-free, and electronic, suggesting it could support point-of-care detection of diagnostic proteins in largely unprocessed clinical samples. PMID:23905162

  8. Metastatic colonization potential of primary tumour cells in mice.

    PubMed Central

    Tarin, D.; Price, J. E.

    1979-01-01

    A model has been developed for studying the capability of cells from primary murine mammary tumours to establish colonies in distant organs. The model involves the i.v. inoculation of disaggregated tumour cells into autologous and syngeneic recipients. The results show that the metastatic colonization potential of cells from a given tumour is consistent within the animals of an inoculated batch. Also, the findings are uniform in the autologous host and the syngeneic recipients. Tumours vary in their colonization potential and can be classified in 2 main groups designated high and low. These findings indicate that: (i) cells from 37% of mammary tumours can heavily colonize the lungs when inoculated i.v., even though the incidence of metastatic spread of these tumours in the undisturbed animal is almost zero. Thus, the relative infrequency of spontaneous metastasis from murine mammary tumours is not due to inability of the tumour cells to survive and colonize once free in the blood stream; and (ii) the colonization potential of the tumours is an intrinsic property of the tumour cells rather than of the host, whose prior acquaintance with the cells does not seem to confer resistance to colonization. The model presents opportunities for identification of possible differences between tumours of high and low colonization potential, and is being used to study cellular properties which favour colonization of distant organs by comparison of observations in vitro with the behaviour of cells from the same tumour in vivo. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:444412

  9. The expression of pluripotency genes and neuronal markers after neurodifferentiation in fibroblasts co-cultured with human umbilical cord blood mononuclear cells.

    PubMed

    Marinowic, D R; Domingues, M F; Machado, D C; DaCosta, J C

    2015-01-01

    Human umbilical cord blood is an attractive source of stem cells; however, it has a heterogeneous cell population with few mesenchymal stem cells. Cell reprogramming induced by different methodologies can confer pluripotency to differentiated adult cells. The objective of this study was to evaluate the reprogramming of fibroblasts and their subsequent neural differentiation after co-culture with umbilical cord blood mononuclear cells. Cells were obtained from four human umbilical cords. The mononuclear cells were cultured for 7 d and subsequently co-cultured with mouse fibroblast NIH-3T3 cells for 6 d. The pluripotency of the cells was evaluated by RT-PCR using primers specific for pluripotency marker genes. The pluripotency was also confirmed by adipogenic and osteogenic differentiation. Neural differentiation of the reprogrammed cells was evaluated by immunofluorescence. All co-cultured cells showed adipogenic and osteogenic differentiation capacity. After co-cultivation, cells expressed the pluripotency gene KLF4. Statistically significant differences in cell area, diameter, optical density, and fractal dimension were observed by confocal microscopy in the neurally differentiated cells. Contact in the form of co-cultivation of fibroblasts with umbilical cord blood mononuclear fraction for 6 d promoted the reprogramming of these cells, allowing the later induction of neural differentiation. PMID:25134818

  10. Prevalence and trends of markers of hepatitis B virus, hepatitis C virus and human Immunodeficiency virus in Argentine blood donors

    PubMed Central

    2014-01-01

    Background Transfusion-transmitted infections are a major problem associated with blood transfusion. The aim of this study was to determine prevalence and trends of HBV, HCV and HIV in blood donors in Argentina. Methods A retrospective study was carried out in blood donors of 27 transfusion centers covering the whole country over a period of eight years (2004-2011). Serologic screening assays for HBsAg, anti-HBc, anti-HCV, and anti-HIV were performed in all centers and nucleic acid amplification testing (NAT) was performed in 2 out of the 27 centers. Results The 2,595,852 samples tested nationwide from 2004 to 2011 showed that the prevalence of HBsAg decreased from 0.336% to 0.198% (p < 0.0001), that of anti-HBc from 2.391% to 2.007% (p < 0.0001), that of anti-HCV from 0.721% to 0.460%, (p < 0.0001) and that of anti-HIV from 0.208% to 0.200 (p = 0.075). The prevalence of HBV, HCV and HIV was unevenly distributed among the different regions of the country. Two out of 74,838 screening- negative samples were positive in NAT assays (1 HIV-RNA and 1 HCV-RNA); moreover, HBV-DNA, HCV-RNA and HIV-RNA were detected in 60.29, 24.54 and 66.67% of screening-positive samples of the corresponding assays. As regards donors age, positive HBV-DNA and HCV-RNA donors were significantly older than healthy donors (46.6, 50.5 and 39.5 y respectively, p < 0.001). Conclusions Argentina has a low prevalence of HBsAg, anti-HCV and anti-HIV in blood donors, with a decreasing trend for HBsAg, anti-HBc and anti-HCV but not for anti-HIV over the last 8 years. The uneven distribution of transfusion-transmitted infections prevalence among the different regions of the country highlights the need to implement regional awareness campaigns and prevention. The discrepancy between samples testing positive for screening assays and negative for NAT assays highlights the problem of blood donors who test repeatedly reactive in screening assays but are not confirmed as positive upon further testing. The

  11. Verification of genes differentially expressed in neuroblastoma tumours: a study of potential tumour suppressor genes

    PubMed Central

    Thorell, Kaisa; Bergman, Annika; Carén, Helena; Nilsson, Staffan; Kogner, Per; Martinsson, Tommy; Abel, Frida

    2009-01-01

    Background One of the most striking features of the childhood malignancy neuroblastoma (NB) is its clinical heterogeneity. Although there is a great need for better clinical and biological markers to distinguish between tumours with different severity and to improve treatment, no clear-cut prognostic factors have been found. Also, no major NB tumour suppressor genes have been identified. Methods In this study we performed expression analysis by quantitative real-time PCR (QPCR) on primary NB tumours divided into two groups, of favourable and unfavourable outcome respectively. Candidate genes were selected on basis of lower expression in unfavourable tumour types compared to favourables in our microarray expression analysis. Selected genes were studied in two steps: (1) using TaqMan Low Density Arrays (TLDA) targeting 89 genes on a set of 12 NB tumour samples, and (2) 12 genes were selected from the TLDA analysis for verification using individual TaqMan assays in a new set of 13 NB tumour samples. Results By TLDA analysis, 81 out of 87 genes were found to be significantly differentially expressed between groups, of which 14 have previously been reported as having an altered gene expression in NB. In the second verification round, seven out of 12 transcripts showed significantly lower expression in unfavourable NB tumours, ATBF1, CACNA2D3, CNTNAP2, FUSIP1, GNB1, SLC35E2, and TFAP2B. The gene that showed the highest fold change in the TLDA analysis, POU4F2, was investigated for epigenetic changes (CpG methylation) and mutations in order to explore the cause of the differential expression. Moreover, the fragile site gene CNTNAP2 that showed the largest fold change in verification group 2 was investigated for structural aberrations by copy number analysis. However, the analyses of POU4F2 and CNTNAP2 showed no genetic alterations that could explain a lower expression in unfavourable NB tumours. Conclusion Through two steps of verification, seven transcripts were found to

  12. Role of blood tumor markers in predicting metastasis and local recurrence after curative resection of colon cancer

    PubMed Central

    Peng, Yifan; Zhai, Zhiwei; Li, Zhongmin; Wang, Lin; Gu, Jin

    2015-01-01

    Aim: To investigate the prognostic value of carcinoembryonic antigen (CEA), CA199, CA724 and CA242 in peripheral blood and local draining venous blood in colon cancer patients after curative resection. Methods: 92 colon cancer patients who received curative resection were retrospectively analyzed. The CEA, CA199, CA724 and CA242 were detected in peripheral blood and local draining venous blood. Results: Metastasis or local recurrence was found in 29 (29/92, 31.5%) patients during follow-up period. 92 patients were divided into two groups: metastasis/local recurrence group (n = 29) and non-metastasis/local recurrence group (n = 63). Peripheral venous CEA, CA199, CA724 and CA242 (p-CEA, p-CA199, p-CA724 and p-CA242) were comparable between two groups (P > 0.05). The median draining venous CEA (d-CEA) in metastases/local recurrence group (23.7 ± 6.9 ng/ml) was significantly higher than that in non-metastases/local recurrence group (18.1 ± 6.3 ng/ml; P < 0.05), but marked differences were not observed in draining venous CA199, CA724 and CA242 (d-CA199, d-CA724 and d-CA242) between two groups (P > 0.05). The optimal cut-off value of d-CEA was 2.76 ng/ml, with the sensitivity and specificity of 90% and 40% in the prediction of metastasis or local recurrence, respectively. d-CEA correlated with tumor differentiation, T stage, TNM stage, metastasis and local recurrence. Subgroup analysis showed that, of 41 patients with stage II colon cancer, the optimal cut-off value of d-CEA was 8.78 ng/mL, and the sensitivity and specificity were 87.5% and 69.7% in the prediction of metastasis or local recurrence, respectively. Conclusion: d-CEA may be a prognostic factor for stage II colon cancer patients. PMID:25785084

  13. In vivo oxymetric analysis of mild hypercapnia upon cerebral oxygen, temperature and blood flow: markers of mood as proposed by concomitant bupropion challenge and electrochemical analysis?

    PubMed

    Crespi, Francesco

    2013-10-01

    Scientific interest has increased the influence of temperature in neurodegenerative and psychiatric disorders, and according to the monoamine hypothesis, depression is a neurochemical disorder arising from hypofunctioning of brain monoamine systems. Here, in vivo flow-oxymetry is applied to verify relationships between cerebral oxygen tension (pO2), blood flow (CBF), that are markers of brain metabolism, and temperature (T), while in vivo voltammetry is concomitantly applied in the medial prefrontal cortex of anaesthetized rats to monitor monoamine levels such as dopamine (DA) and serotonin. An induced mild hypercapnia via increasing exogenous carbon dioxide (CO2) concentration resulted in increased pO2, CBF and T in discrete brain areas. Concomitant in situ voltammetric analysis of extracellular levels of serotonin and DA has revealed significant changes in the latter, only. Parallel treatment with antidepressant bupropion has confirmed its described central thermogenic properties and its positive influence on dopaminergic activity. CBF was also enhanced by such antidepressant. Altogether these data support direct relationships between markers of brain metabolism such as pO2, CBF, T and brain monoamine[s], indicating the coupled in vivo methodology: oxymetry-voltammetry as a rapid in vivo tool for analyses of such indicators in psychiatric disorders.

  14. Tumours of the thymus

    PubMed Central

    Sellors, T. Holmes; Thackray, A. C.; Thomson, A. D.

    1967-01-01

    Eighty-eight cases of thymoma are discussed with the object of trying to co-ordinate the histological and clinical features. The pathological specimens were in all cases obtained at operation. The pathology classification introduced by Thomson and Thackray in 1957 has been found to correspond adequately with the clinical pattern. The most common groups of tumours are basically epithelial and can be separated into five or six subdivisions, each of which has a separate pattern of behaviour. Lymphoid and teratomatous tumours also occur, but there were only two examples in this series. Clinically, separation of patients who suffered from myasthenia (38) and those who did not (50) affords the first main grouping. The majority of patients who had myasthenia gravis had tumours classified as epidermoid (19) and lymphoepithelial (14), the former with a more malignant appearance and behaviour than the latter. Removal of the tumour with or without radiation gave considerable and sometimes complete relief from myasthenic symptoms. Non-myasthenic thymoma (50) was usually discovered as a result of pressure signs or in the course of routine radiography. Spindle or oval celled tumours followed a benign pattern whereas undifferentiated thymoma was in every sense malignant, as also were teratomatous growths. Granulomatous or Hodgkin-like thymomas were of special interest and had an unpredictable course, some patients surviving many years after what was regarded as inadequate treatment. The place of radiotherapy as a pre- or post-operative agent complementary to surgery is discussed. Images PMID:6033387

  15. Salivary gland tumours.

    PubMed

    Speight, P M; Barrett, A W

    2002-09-01

    Salivary gland tumours are a relatively rare and morphologically diverse group of lesions. Although most clinicians and pathologists will have encountered the more common benign neoplasms, few have experience of the full range of salivary cancers, which are best managed in specialist centres. This review considers some current areas of difficulty and controversy in the diagnosis and management of these neoplasms. The classification of these lesions is complex, encompassing nearly 40 different entities, but precise classification and terminology is essential for an accurate diagnosis and for the allocation of tumours to prognostic groups. For many salivary tumours diagnosis is straightforward but the wide range of morphological diversity between and within tumour types means that a diagnosis may not be possible on small incisional biopsies and careful consideration of the clinical and pathological features together is essential. Although tumour grading is important and helpful, it is not an independent prognostic indicator and must be considered in the context of stage. Large malignancies tend to have a poor prognosis regardless of grade and even high-grade neoplasms may do well when they are small. A helpful guide to management of salivary cancers is the '4 cm rule'.

  16. Training Status as a Marker of the Relationship between Nitric Oxide, Oxidative Stress, and Blood Pressure in Older Adult Women

    PubMed Central

    Mourão Jacomini, André; Celso Dutra de Souza, Hugo; da Silva Dias, Danielle; de Oliveira Brito, Janaina; Cezar Pinheiro, Lucas; Bernardino da Silva, Anderson; Fernanda da Silva, Roberta; Alexandre Trapé, Atila; De Angelis, Kátia; Tanus-Santos, José Eduardo; Lia do Amaral, Sandra; Saranz Zago, Anderson

    2016-01-01

    The purpose of this study was to evaluate the influence of functional fitness and oxidative capacity on the nitric oxide concentration associated with hemodynamic control in older adult women. The sample consisted of 134 women (65.73 ± 6.14 years old). All subjects underwent a physical examination to assess body mass index, waist-hip ratio, body fat measurement by dual energy X-ray absorptiometry, and blood pressure (BP). Training status (TS) was evaluated by indirect determination of maximal oxygen uptake by a treadmill test using Balke protocol modified for older adults. Functional fitness was also evaluated through a “Functional Fitness Battery Test” to determine the general fitness functional index (GFFI). All participants were separated according to the functional fitness (TS1, very weak and weak; TS2, regular; TS3, good and very good). Plasma blood samples were used to evaluate prooxidant and antioxidant activity and nitrite and nitrate concentrations. The general results of this study showed that good levels of TS were related to lower levels of lipoperoxidation and protein damage, higher levels of antioxidant, and higher concentration of nitrite and nitrate. This combination may be responsible for the lower levels of BP in subjects with better TS. PMID:26697141

  17. Increased Migratory and Activation Cell Markers of Peripheral Blood Lymphocytes in an Experimental Model of Nephrotic Syndrome

    PubMed Central

    Pereira, Wagner de Fátima; Brito-Melo, Gustavo Eustáquio Alvim; Carneiro, Cláudia Martins; Melo, Dirceu de Sousa; Costa, Karine Beatriz; Guimarães, Fábio Lourenço Tadeu; Rocha-Vieira, Etel; Vieira, Érica Leandro Marciano; Simões e Silva, Ana Cristina

    2015-01-01

    The present study aimed to evaluate the expression of CD80 and CD18 in subpopulations of peripheral blood leukocytes and oxidative kidney damage in rats with nephrotic syndrome (NS) induced by doxorubicin (Dox) in comparison to control animals at different time points. Male adult Wistar rats were submitted to 24-hour urine and blood collection for biochemical and immunological analysis at 7, 14, 21, and 28 days after Dox injection. After euthanasia, the kidneys were removed for histological analysis and the evaluation of oxidative stress. The phenotypic characterization of leukocytes was performed using flow cytometry. Dox-injected animals exhibited increased CD18 expression in cytotoxic T lymphocytes, NK cells, and monocytes and high CD80 expression in monocytes. Kidney oxidative damage was positively correlated with CD80 expression in monocytes and serum levels of creatinine. These results suggest that phagocytic and cytotoxic cells are preferentially recruited to the tissue injury site, which may contribute to kidney dysfunction in this animal model of NS. The blockade of integrin and costimulatory molecules may provide new therapeutic opportunities for NS. PMID:26063968

  18. Mathematical modeling of liver metastases tumour growth and control with radiotherapy

    NASA Astrophysics Data System (ADS)

    Campbell, Adrienne; Sivakumaran, Thiru; Davidson, Melanie; Lock, Michael; Wong, Eugene

    2008-12-01

    Generating an optimized radiation treatment plan requires understanding the factors affecting tumour control. Mathematical models of tumour dynamics may help in future studies of factors predicting tumour sensitivity to radiotherapy. In this study, a time-dependent differential model, incorporating biological cancer markers, is presented to describe pre-treatment tumour growth, response to radiation, and recurrence. The model uses Gompertzian-Exponential growth to model pre-treatment tumour growth. The effect of radiotherapy is handled by a realistic cell-kill term that includes a volume-dependent change in tumour sensitivity. Post-treatment, a Gompertzian, accelerated, delayed repopulation is employed. As proof of concept, we examined the fit of the model's prediction using various liver enzyme levels as markers of metastatic liver tumour growth in a liver cancer patient. A tumour clonogen population model was formulated. Each enzyme was coupled to the same tumour population, and served as surrogates of the tumour. This dynamical model was solved numerically and compared to the measured enzyme levels. By minimizing the mean-squared error of the model enzyme predictions, we determined the following tumour model parameters: growth rate prior to treatment was 0.52% per day; the fractional radiation cell kill for the prescribed dose (60 Gy in 15 fractions) was 42% per day, and the tumour repopulation rate was 2.9% per day. These preliminary results provided the basis to test the model in a larger series of patients, to apply biological markers for improving the efficacy of radiotherapy by determining the underlying tumour dynamics.

  19. Pretreatment whole blood Epstein-Barr virus-DNA is a significant prognostic marker in patients with Hodgkin lymphoma.

    PubMed

    Park, Ji Hyun; Yoon, Dok Hyun; Kim, Shin; Park, Jung Sun; Park, Chan-Sik; Sung, Heungsup; Lee, Sang-Wook; Huh, Jooryung; Suh, Cheolwon

    2016-04-01

    Epstein-Barr virus (EBV) in the peripheral blood has become a significant predictor of clinical outcomes in EBV-associated Hodgkin lymphoma (HL). However, due to its relative rarity, prevalence and prognostic role of circulating EBV-DNA has not been well established in Asian patients. Seventy patients with newly diagnosed HL were prospectively registered between October 2007 and January 2013, and underwent pretreatment whole blood (WB) EBV-DNA quantitation using real-time polymerase chain reaction (RT-PCR). WB EBV-DNA in baseline and serial RT-PCR within 1 year were investigated. Clinicopathologic parameters of the patients according to pretreatment WB EBV-DNA were also explored. Twelve patients (17.1 %) demonstrated WB EBV-DNA(+), which was significantly associated to older age, advanced stages, frequent involvements of extranodal sites, low serum albumin and hemoglobin levels, and high international prognostic scores ≥2. Three-year event-free survival (EFS) and overall survival (OS) were significantly inferior in patients with pretreatment WB EBV-DNA(+) (53.5 vs 67.0 and 65.6 vs 90.2 %) (p < 0.032 and <0.01). Negatively conversed EBV-DNA within 1 year after chemotherapy also significantly affected favorable EFS (p < 0.01). Taken together, pretreatment WB EBV-DNA(+) may be a significant predictor of inferior EFS and OS over EBV-encoded RNA in situ hybridization (EBER-ISH)(+) in Korean patients with HL. Serial EBV-DNA monitoring following chemotherapy also seems helpful to predict survival outcomes. PMID:26883027

  20. Reproducing the Hemoglobin Saturation Profile, a Marker of the Blood Oxygenation Level Dependent (BOLD) fMRI Effect, at the Microscopic Level.

    PubMed

    Hadjistassou, Constantinos; Moyle, Keri; Ventikos, Yiannis

    2016-01-01

    The advent of functional MRI in the mid-1990s has catalyzed progress pertaining to scientific discoveries in neuroscience. With the prospect of elucidating the physiological aspect of the Blood Oxygenation Level Dependent (BOLD) effect we present a computational capillary-tissue system capable of mapping venous hemoglobin saturation- a marker of the BOLD hemodynamic response. Free and facilitated diffusion and convection for hemoglobin and oxygen are considered in the radial and axial directions. Hemoglobin reaction kinetics are governed by the oxyhemoglobin dissociation curve. Brain activation, mimicked by dynamic transitions in cerebral blood velocity (CBv) and oxidative metabolism (CMRO2), is simulated by normalized changes in m = (ΔCBv/CBv)/(ΔCMRO2/CMRO2) of values 2, 3 and 4. Venous hemoglobin saturation profiles and peak oxygenation results, for m = 2, based upon a 50% and a 25% increase in CBv and CMRO2, respectively, lie within physiological limits exhibiting excellent correlation with the BOLD signal, for short-duration stimuli. Our analysis suggests basal CBv and CMRO2 values of 0.6 mm/s and 200 μmol/100g/min. Coupled CBv and CMRO2 responses, for m = 3 and m = 4, overestimate peak hemoglobin saturation, confirming the system's responsiveness to changes in hematocrit, CBv and CMRO2. Finally, factoring in neurovascular effects, we show that no initial dip will be observed unless there is a time delay in the onset of increased CBv relative to CMRO2. PMID:26939128

  1. Reproducing the Hemoglobin Saturation Profile, a Marker of the Blood Oxygenation Level Dependent (BOLD) fMRI Effect, at the Microscopic Level

    PubMed Central

    Hadjistassou, Constantinos; Moyle, Keri; Ventikos, Yiannis

    2016-01-01

    The advent of functional MRI in the mid-1990s has catalyzed progress pertaining to scientific discoveries in neuroscience. With the prospect of elucidating the physiological aspect of the Blood Oxygenation Level Dependent (BOLD) effect we present a computational capillary-tissue system capable of mapping venous hemoglobin saturation— a marker of the BOLD hemodynamic response. Free and facilitated diffusion and convection for hemoglobin and oxygen are considered in the radial and axial directions. Hemoglobin reaction kinetics are governed by the oxyhemoglobin dissociation curve. Brain activation, mimicked by dynamic transitions in cerebral blood velocity (CBv) and oxidative metabolism (CMRO2), is simulated by normalized changes in m = (ΔCBv/CBv)/(ΔCMRO2/CMRO2) of values 2, 3 and 4. Venous hemoglobin saturation profiles and peak oxygenation results, for m = 2, based upon a 50% and a 25% increase in CBv and CMRO2, respectively, lie within physiological limits exhibiting excellent correlation with the BOLD signal, for short-duration stimuli. Our analysis suggests basal CBv and CMRO2 values of 0.6 mm/s and 200 μmol/100g/min. Coupled CBv and CMRO2 responses, for m = 3 and m = 4, overestimate peak hemoglobin saturation, confirming the system’s responsiveness to changes in hematocrit, CBv and CMRO2. Finally, factoring in neurovascular effects, we show that no initial dip will be observed unless there is a time delay in the onset of increased CBv relative to CMRO2. PMID:26939128

  2. Thrombin-Mediated Platelet Activation of Lysed Whole Blood and Platelet-Rich Plasma: A Comparison Between Platelet Activation Markers and Ultrastructural Alterations.

    PubMed

    Augustine, Tanya N; van der Spuy, Wendy J; Kaberry, Lindsay L; Shayi, Millicent

    2016-06-01

    Platelet ultrastructural alterations representing spurious activation have been identified in pathological conditions. A limitation of platelet studies is that sample preparation may lead to artifactual activation processes which may confound results, impacting the use of scanning electron microscopy as a supplemental diagnostic tool. We used scanning electron microscopy and flow cytometry to analyze platelet activation in platelet-rich plasma (PRP) and whole blood (WB) samples. PRP generated using a single high g force centrifugation, and WB samples treated with a red blood cell lysis buffer, were exposed to increasing concentrations of the agonist thrombin. Platelets in lysed WB samples responded to thrombin by elevating the activation marker CD62p definitively, with corresponding ultrastructural changes indicating activation. Conversely, CD62p expression in PRP preparations remained static. Ultrastructural analysis revealed fully activated platelets even under low concentration thrombin stimulation, with considerable fibrin deposition. It is proposed that the method for PRP production induced premature platelet activation, preventable by using an inhibitor of platelet aggregation and fibrin polymerization. Nevertheless, our results show a definitive correspondence between flow cytometry and scanning electron microscopy in platelet activation studies, highlighting the potential of the latter technique as a supplemental diagnostic tool. PMID:27329313

  3. The Effect of Long-Term Exercise on the Production of Osteoclastogenic and Antiosteoclastogenic Cytokines by Peripheral Blood Mononuclear Cells and on Serum Markers of Bone Metabolism

    PubMed Central

    Dykes, Rhesa; Chi, David S.

    2016-01-01

    Although it is recognized that the mechanical stresses associated with physical activity augment bone mineral density and improve bone quality, our understanding of how exercise modulates bone homeostasis at the molecular level is lacking. In a before and after trial involving 43 healthy adults, we measured the effect of six months of supervised exercise training on the spontaneous and phytohemagglutinin-induced production of osteoclastogenic cytokines (interleukin-1α, tumor necrosis factor-α), antiosteoclastogenic cytokines (transforming growth factor-β1 and interleukins 4 and 10), pleiotropic cytokines with variable effects on osteoclastogenesis (interferon-γ, interleukin-6), and T cell growth and differentiation factors (interleukins 2 and 12) by peripheral blood mononuclear cells. We also measured lymphocyte phenotypes and serum markers of bone formation (osteocalcin), bone resorption (C-terminal telopeptides of Type I collagen), and bone homeostasis (25 (OH) vitamin D, estradiol, testosterone, parathyroid hormone, and insulin-like growth factor 1). A combination of aerobic, resistance, and flexibility exercises done on average of 2.5 hours a week attenuated the production of osteoclastogenic cytokines and enhanced the production of antiosteoclastogenic cytokines. These changes were accompanied by a 16% reduction in collagen degradation products and a 9.8% increase in osteocalcin levels. We conclude that long-term moderate intensity exercise exerts a favorable effect on bone resorption by changing the balance between blood mononuclear cells producing osteoclastogenic cytokines and those producing antiosteoclastogenic cytokines. This trial is registered with Clinical Trials.gov Identifier: NCT02765945.

  4. Effects of adaptive support ventilation and synchronized intermittent mandatory ventilation on peripheral circulation and blood gas markers of COPD patients with respiratory failure.

    PubMed

    Han, Ling; Wang, Yingxiao; Gan, Yonghua; Xu, Lijun

    2014-09-01

    The objective of the study was to investigate the effects of adaptive support ventilation (ASV) and synchronized intermittent mandatory ventilation (SIMV) on peripheral circulation of chronic obstructive pulmonary disease (COPD) patients with respiratory failure. 86 COPD patients with respiratory failure were recruited in this study. Self-control method was used to compare the effect of ASV and SIMV on the parameters of ventilation machine, heart rate, blood pressure, central venous pressure (CVP), and blood gas markers. When the patients in ASV and SIMV groups were compared, respiratory rate, tidal volume, and peak airway pressure (PIP) showed significant difference. When minute ventilation (MV) was compared, no significant difference was shown. When peripheral circulation parameters were compared, peripheral circulation heart rate, SBP, DBP, and CVP showed significant difference. Compared with SIMV group, PaO2, pH, and SaO2 values were remarkably increased (P < 0.01) while no significant difference was found for partial pressure of carbon dioxide (pCO2) when two groups were compared. In conclusion, when mechanical ventilation was used in COPD patients with respiratory failure, ASV can significantly improve clinical outcomes.

  5. The Effect of Long-Term Exercise on the Production of Osteoclastogenic and Antiosteoclastogenic Cytokines by Peripheral Blood Mononuclear Cells and on Serum Markers of Bone Metabolism

    PubMed Central

    Dykes, Rhesa; Chi, David S.

    2016-01-01

    Although it is recognized that the mechanical stresses associated with physical activity augment bone mineral density and improve bone quality, our understanding of how exercise modulates bone homeostasis at the molecular level is lacking. In a before and after trial involving 43 healthy adults, we measured the effect of six months of supervised exercise training on the spontaneous and phytohemagglutinin-induced production of osteoclastogenic cytokines (interleukin-1α, tumor necrosis factor-α), antiosteoclastogenic cytokines (transforming growth factor-β1 and interleukins 4 and 10), pleiotropic cytokines with variable effects on osteoclastogenesis (interferon-γ, interleukin-6), and T cell growth and differentiation factors (interleukins 2 and 12) by peripheral blood mononuclear cells. We also measured lymphocyte phenotypes and serum markers of bone formation (osteocalcin), bone resorption (C-terminal telopeptides of Type I collagen), and bone homeostasis (25 (OH) vitamin D, estradiol, testosterone, parathyroid hormone, and insulin-like growth factor 1). A combination of aerobic, resistance, and flexibility exercises done on average of 2.5 hours a week attenuated the production of osteoclastogenic cytokines and enhanced the production of antiosteoclastogenic cytokines. These changes were accompanied by a 16% reduction in collagen degradation products and a 9.8% increase in osteocalcin levels. We conclude that long-term moderate intensity exercise exerts a favorable effect on bone resorption by changing the balance between blood mononuclear cells producing osteoclastogenic cytokines and those producing antiosteoclastogenic cytokines. This trial is registered with Clinical Trials.gov Identifier: NCT02765945. PMID:27642534

  6. The Effect of Long-Term Exercise on the Production of Osteoclastogenic and Antiosteoclastogenic Cytokines by Peripheral Blood Mononuclear Cells and on Serum Markers of Bone Metabolism.

    PubMed

    Smith, J Kelly; Dykes, Rhesa; Chi, David S

    2016-01-01

    Although it is recognized that the mechanical stresses associated with physical activity augment bone mineral density and improve bone quality, our understanding of how exercise modulates bone homeostasis at the molecular level is lacking. In a before and after trial involving 43 healthy adults, we measured the effect of six months of supervised exercise training on the spontaneous and phytohemagglutinin-induced production of osteoclastogenic cytokines (interleukin-1α, tumor necrosis factor-α), antiosteoclastogenic cytokines (transforming growth factor-β1 and interleukins 4 and 10), pleiotropic cytokines with variable effects on osteoclastogenesis (interferon-γ, interleukin-6), and T cell growth and differentiation factors (interleukins 2 and 12) by peripheral blood mononuclear cells. We also measured lymphocyte phenotypes and serum markers of bone formation (osteocalcin), bone resorption (C-terminal telopeptides of Type I collagen), and bone homeostasis (25 (OH) vitamin D, estradiol, testosterone, parathyroid hormone, and insulin-like growth factor 1). A combination of aerobic, resistance, and flexibility exercises done on average of 2.5 hours a week attenuated the production of osteoclastogenic cytokines and enhanced the production of antiosteoclastogenic cytokines. These changes were accompanied by a 16% reduction in collagen degradation products and a 9.8% increase in osteocalcin levels. We conclude that long-term moderate intensity exercise exerts a favorable effect on bone resorption by changing the balance between blood mononuclear cells producing osteoclastogenic cytokines and those producing antiosteoclastogenic cytokines. This trial is registered with Clinical Trials.gov Identifier: NCT02765945. PMID:27642534

  7. Immunology of naturally transmissible tumours

    PubMed Central

    Siddle, Hannah V; Kaufman, Jim

    2015-01-01

    Naturally transmissible tumours can emerge when a tumour cell gains the ability to pass as an infectious allograft between individuals. The ability of these tumours to colonize a new host and to cross histocompatibility barriers contradicts our understanding of the vertebrate immune response to allografts. Two naturally occurring contagious cancers are currently active in the animal kingdom, canine transmissible venereal tumour (CTVT), which spreads among dogs, and devil facial tumour disease (DFTD), among Tasmanian devils. CTVT are generally not fatal as a tumour-specific host immune response controls or clears the tumours after transmission and a period of growth. In contrast, the growth of DFTD tumours is not controlled by the Tasmanian devil's immune system and the disease causes close to 100% mortality, severely impacting the devil population. To avoid the immune response of the host both DFTD and CTVT use a variety of immune escape strategies that have similarities to many single organism tumours, including MHC loss and the expression of immunosuppressive cytokines. However, both tumours appear to have a complex interaction with the immune system of their respective host, which has evolved over the relatively long life of these tumours. The Tasmanian devil is struggling to survive with the burden of this disease and it is only with an understanding of how DFTD passes between individuals that a vaccine might be developed. Further, an understanding of how these tumours achieve natural transmissibility should provide insights into general mechanisms of immune escape that emerge during tumour evolution. PMID:25187312

  8. The effects of a 6-month resistance training and dried plum consumption intervention on strength, body composition, blood markers of bone turnover, and inflammation in breast cancer survivors.

    PubMed

    Simonavice, Emily; Liu, Pei-Yang; Ilich, Jasminka Z; Kim, Jeong-Su; Arjmandi, Bahram; Panton, Lynn B

    2014-06-01

    The purpose of this study was to examine the effects of resistance training (RT) and dried plum (DP) consumption on strength, body composition, blood markers of bone, and inflammation in breast cancer survivors (BCS). Twenty-three BCS (RT, n = 12; RT+DP, n = 11), aged 64 ± 7 years, were evaluated at baseline and after 6 months of intervention on the following: muscular strength (chest press and leg extension) via 1-repetition maximums (1RMs); body composition, specifically bone mineral density (BMD) by dual energy X-ray absorptiometry; biochemical markers of bone turnover (bone-specific alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP-5b)); and inflammation (C-reactive protein (CRP)). Target RT prescription was 2 days/week of 10 exercises, including 2 sets of 8-12 repetitions at ∼60%-80% of 1RM. RT+DP also consumed 90 g of DP daily. There were no baseline differences between groups or any group-by-time interactions for any of the variables. BCS increased upper (p < 0.05) (RT: 64 ± 14 to 80 ± 17 kg; RT+DP: 72 ± 23 to 91 ± 20 kg) and lower (p < 0.05) (RT: 69 ± 20 to 87 ± 28 kg; RT+DP: 78 ± 19 to 100 ± 21 kg) body strength. Body composition and BMD improvements were not observed. TRAP-5b decreased in the RT group (p < 0.05) (4.55 ± 1.57 to 4.04 ± 1.63 U/L) and the RT+DP group (p = 0.07) (5.10 ± 2.75 to 4.27 ± 2.03 U/L). Changes in BAP and CRP were not observed. RT was effective for improving biochemical markers of bone turnover and muscular strength in BCS. A longer and higher intensity intervention may be needed to reveal the true effects of RT and DP on body composition and biochemical markers of inflammation.

  9. In Vivo Tumour Mapping Using Electrocorticography Alterations During Awake Brain Surgery: A Pilot Study.

    PubMed

    Boussen, Salah; Velly, Lionel; Benar, Christian; Metellus, Philippe; Bruder, Nicolas; Trébuchon, Agnès

    2016-09-01

    During awake brain surgery for tumour resection, in situ EEG recording (ECoG) is used to identify eloquent areas surrounding the tumour. We used the ECoG setup to record the electrical activity of cortical and subcortical tumours and then performed frequency and connectivity analyses in order to identify ECoG impairments and map tumours. We selected 16 patients with cortical (8) and subcortical (8) tumours undergoing awake brain surgery. For each patient, we computed the spectral content of tumoural and healthy areas in each frequency band. We computed connectivity of each electrode using connectivity markers (linear and non-linear correlations, phase-locking and coherence). We performed comparisons between healthy and tumour electrodes. The ECoG alterations were used to implement automated classification of the electrodes using clustering or neural network algorithms. ECoG alterations were used to image cortical tumours.Cortical tumours were found to profoundly alter all frequency contents (normalized and absolute power), with an increase in the δ activity and a decreases for the other bands (P < 0.05). Cortical tumour electrodes showed high level of connectivity compared to surrounding electrodes (all markers, P < 0.05). For subcortical tumours, a relative decrease in the γ1 band and in the alpha band in absolute amplitude (P < 0.05) were the only abnormalities. The neural network algorithm classification had a good performance: 93.6 % of the electrodes were classified adequately on a test subject. We found significant spectral and connectivity ECoG changes for cortical tumours, which allowed tumour recognition. Artificial neural algorithm pattern recognition seems promising for electrode classification in awake tumour surgery. PMID:27324381

  10. In Vivo Tumour Mapping Using Electrocorticography Alterations During Awake Brain Surgery: A Pilot Study.

    PubMed

    Boussen, Salah; Velly, Lionel; Benar, Christian; Metellus, Philippe; Bruder, Nicolas; Trébuchon, Agnès

    2016-09-01

    During awake brain surgery for tumour resection, in situ EEG recording (ECoG) is used to identify eloquent areas surrounding the tumour. We used the ECoG setup to record the electrical activity of cortical and subcortical tumours and then performed frequency and connectivity analyses in order to identify ECoG impairments and map tumours. We selected 16 patients with cortical (8) and subcortical (8) tumours undergoing awake brain surgery. For each patient, we computed the spectral content of tumoural and healthy areas in each frequency band. We computed connectivity of each electrode using connectivity markers (linear and non-linear correlations, phase-locking and coherence). We performed comparisons between healthy and tumour electrodes. The ECoG alterations were used to implement automated classification of the electrodes using clustering or neural network algorithms. ECoG alterations were used to image cortical tumours.Cortical tumours were found to profoundly alter all frequency contents (normalized and absolute power), with an increase in the δ activity and a decreases for the other bands (P < 0.05). Cortical tumour electrodes showed high level of connectivity compared to surrounding electrodes (all markers, P < 0.05). For subcortical tumours, a relative decrease in the γ1 band and in the alpha band in absolute amplitude (P < 0.05) were the only abnormalities. The neural network algorithm classification had a good performance: 93.6 % of the electrodes were classified adequately on a test subject. We found significant spectral and connectivity ECoG changes for cortical tumours, which allowed tumour recognition. Artificial neural algorithm pattern recognition seems promising for electrode classification in awake tumour surgery.

  11. Parallel evolution of tumour subclones mimics diversity between tumours.

    PubMed

    Martinez, Pierre; Birkbak, Nicolai Juul; Gerlinger, Marco; McGranahan, Nicholas; Burrell, Rebecca A; Rowan, Andrew J; Joshi, Tejal; Fisher, Rosalie; Larkin, James; Szallasi, Zoltan; Swanton, Charles

    2013-08-01

    Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale of heterogeneity within a tumour (intratumour heterogeneity) relative to genetic differences between tumours (intertumour heterogeneity) is unknown. To address this, we obtained 48 biopsies from eight stage III and IV clear cell renal cell carcinomas (ccRCCs) and used DNA copy-number analyses to compare biopsies from the same tumour with 440 single tumour biopsies from the Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering of TCGA and multi-region ccRCC samples revealed segregation of samples from the same tumour into unrelated clusters; 25% of multi-region samples appeared more similar to unrelated samples than to any other sample originating from the same tumour. We found that the majority of recurrent DNA copy number driver aberrations in single biopsies were not present ubiquitously in late-stage ccRCCs and were likely to represent subclonal events acquired during tumour progression. Such heterogeneous subclonal genetic alterations within individual tumours may impair the identification of robust ccRCC molecular subtypes classified by distinct copy number alterations and clinical outcomes. The co-existence of distinct subclonal copy number events in different regions of individual tumours reflects the diversification of individual ccRCCs through multiple evolutionary routes and may contribute to tumour sampling bias and impact upon tumour progression and clinical outcome.

  12. Parallel evolution of tumour subclones mimics diversity between tumours.

    PubMed

    Martinez, Pierre; Birkbak, Nicolai Juul; Gerlinger, Marco; McGranahan, Nicholas; Burrell, Rebecca A; Rowan, Andrew J; Joshi, Tejal; Fisher, Rosalie; Larkin, James; Szallasi, Zoltan; Swanton, Charles

    2013-08-01

    Intratumour heterogeneity (ITH) may foster tumour adaptation and compromise the efficacy of personalized medicine approaches. The scale of heterogeneity within a tumour (intratumour heterogeneity) relative to genetic differences between tumours (intertumour heterogeneity) is unknown. To address this, we obtained 48 biopsies from eight stage III and IV clear cell renal cell carcinomas (ccRCCs) and used DNA copy-number analyses to compare biopsies from the same tumour with 440 single tumour biopsies from the Cancer Genome Atlas (TCGA). Unsupervised hierarchical clustering of TCGA and multi-region ccRCC samples revealed segregation of samples from the same tumour into unrelated clusters; 25% of multi-region samples appeared more similar to unrelated samples than to any other sample originating from the same tumour. We found that the majority of recurrent DNA copy number driver aberrations in single biopsies were not present ubiquitously in late-stage ccRCCs and were likely to represent subclonal events acquired during tumour progression. Such heterogeneous subclonal genetic alterations within individual tumours may impair the identification of robust ccRCC molecular subtypes classified by distinct copy number alterations and clinical outcomes. The co-existence of distinct subclonal copy number events in different regions of individual tumours reflects the diversification of individual ccRCCs through multiple evolutionary routes and may contribute to tumour sampling bias and impact upon tumour progression and clinical outcome. PMID:23716380

  13. An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models

    PubMed Central

    2011-01-01

    Background Many factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression. Methods Primary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively. Results Significant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells. Conclusions Our results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression. PMID:21521500

  14. Primary retroperitoneal tumours and cysts.

    PubMed

    Bors, G; Polyák, L; Frang, D

    1986-01-01

    The authors give a summarizing report on retroperitoneal tumours and cysts. They review the origin and classification of tumours and cysts, their diagnostic and differential diagnostic possibilities as well as the therapeutic measures. Finally, their own 3 cases are reported.

  15. Loss of heterozygosity on chromosome 16 in sporadic Wilms' tumour.

    PubMed Central

    Grundy, R. G.; Pritchard, J.; Scambler, P.; Cowell, J. K.

    1998-01-01

    To establish whether loss of heterozygosity (LOH) for chromosome 16q in Wilms' tumours confers an adverse prognosis, DNA from 40 Wilms' tumour/normal pairs were analysed using highly polymorphic microsatellite markers along the length of 16q. Fifteen per cent of tumours showed LOH for 16q. Although the common region of allele loss spanned the 16q24-qter region, a second distinct region of LOH was identified in 16q21. Five out of six tumours showing LOH were either (1) high stage or (2) low stage with unfavourable histology. In addition, there was a higher mortality rate in patients showing LOH for 16q than those that did not. These data strongly support the suggestion that LOH for 16q is associated with an adverse prognosis. Images Figure 1 PMID:9820177

  16. Impact of chronic periodontitis on quality-of-life and on the level of blood metabolic markers

    PubMed Central

    Mourão, Leila Cristina; Cataldo, Dionisia de Matos; Moutinho, Helena; Canabarro, Antonio

    2015-01-01

    Context: Despite the recognition that systemic factors can alter the risk to the chronic periodontitis (CP), only recently has evidence begun to emerge, still under investigation, that infections of the oral cavity are related with low quality-of-life (QoL) and are able to influence the occurrence and severity of certain conditions and systemic diseases. Aims: The aim of this study was to evaluate the impact of CP on the QoL and on the metabolic systemic condition of CP patients. Settings and Designs: Cross–sectional, case-controlled, age- and gender-matched study. Subjects and Methods: Quality-of-life assessment (Functional Assessment of Chronic Illness Therapy-Fatigue), periodontal examinations and blood tests were obtained from 20 CP patients and 20 age- and gender-matched healthy controls (HC). Statistical Analysis Used: parametric paired t-test for numerical data (metabolic parameters) and nonparametric paired Wilcoxon signed rank test to compare the QoL ordinal data of both groups. Statistical significance was determined at the 0.05 level. Results: Healthy controls had fewer negative impacts in all QoL areas studied. CP patients showed higher levels of low-density lipoprotein cholesterol, glucose, and uric acid compared with the HC. Conclusions: Chronic periodontitis negatively affected the overall well-being and systemic condition of a group of Brazilian individuals. PMID:26015664

  17. Tumour Cell Heterogeneity

    PubMed Central

    Gay, Laura; Baker, Ann-Marie; Graham, Trevor A.

    2016-01-01

    The population of cells that make up a cancer are manifestly heterogeneous at the genetic, epigenetic, and phenotypic levels. In this mini-review, we summarise the extent of intra-tumour heterogeneity (ITH) across human malignancies, review the mechanisms that are responsible for generating and maintaining ITH, and discuss the ramifications and opportunities that ITH presents for cancer prognostication and treatment. PMID:26973786

  18. Elastosis in malignant tumours.

    PubMed

    Isaacson, C; Greeff, H; Murray, J F; Posen, J; Schmaman, A

    1985-07-01

    Elastosis is common in infiltrating ductal and lobular carcinomas of the breast, occurring in approximately 90% of cases. It is also well described in some benign lesions of the breast and tumours of the salivary gland. Reports of venous elastosis in association with large-bowel carcinomas are rare. We describe elastosis in single cases of prostatic, gastric, bronchiolar-alveolar and cervical carcinoma.

  19. Tumour associated antigens in diagnosis of serous effusions.

    PubMed Central

    Mezger, J; Permanetter, W; Gerbes, A L; Wilmanns, W; Lamerz, R

    1988-01-01

    The use of tumour associated antigens in the diagnosis of serous effusions was studied in 76 patients with benign and 200 patients with malignant disease. Tissue polypeptide antigen (TPA), alpha fetoprotein, and CA 125 were found to be of little value. At cut off points of 3 ng/ml, 10 U/ml, and 30 U/ml, respectively, carcinoembryonic antigen (CEA), biliary glycoprotein I (BGP I), and CA 19-9 discriminated between benign and malignant serous effusions with a sensitivity of between 24% and 67%. The immunocytochemical staining for these markers resulted in malignant cells being detected in 18% to 33% of cases. Various combinations of conventional cytological examination, effusion fluid tumour marker determination, and immunocytochemical analysis identified malignant cells in serous effusions in up to 72% of cases; conventional cytology alone detected tumour cells in only 30%. Images Fig 1 Fig 2 Fig 3 Fig 4 PMID:2454957

  20. Prothrombin activation fragment 1 + 2 as a marker of coagulation activation in cord blood collection for banking.

    PubMed

    Juutistenaho, S; Vahtera, E; Aranko, K; Kekomäki, R

    2010-08-01

    There have been efforts to increase the quality of cord blood (CB) collections aimed at banking and transplantation. Yet, the effect of CB collection techniques on haemostatic activation is scarcely studied, despite the unique nature of the neonatal haemostatic system. The aim of this study was to explore coagulation system and platelet (PLT) activation during CB collection at a national CB bank. At three time points over a 9-year period (in 1998, 2000 and 2006), CB collections were assessed to evaluate the collection process during bank setup and changes in procedures. Thrombin generation and PLT activation were assessed with prothrombin activation fragment 1 + 2 (F1 + 2) and PLT factor 4 (PF4), respectively. The median F1 + 2 level was 2.8 nmol L(-1) in 1998 (n = 11), 0.7 nmol L(-1) in 2000 (n = 10) and 0.7 nmol L(-1) in 2006 (n = 6), the decrease being statistically significant (1998 vs 2000, P < 0.001; 1998 vs 2006, P = 0.01). The median PF4 level was 117 IU mL(-1) in 1998 and 104 IU mL(-1) in 2000. PF4 was not measured in 2006. The level of F1 + 2 correlated with that of PF4 (n = 21; Spearman's Rho = 0.59, P = 0.006). Haemostatic activation, assessed as a part of CB bank process control, decreased from the first to the subsequent sample series. F1 + 2 may be a candidate for quality control in CB banking; however, further studies are needed to optimise the analyses and to assess the effect of haemostatic activation on CB quality. PMID:20345383

  1. Detection of tumor cell-specific mRNA in the peripheral blood of patients with breast cancer—evaluation of several markers with real-time reverse transcription-PCR.

    PubMed

    Andergassen, Ulrich; Hofmann, Simone; Kölbl, Alexandra C; Schindlbeck, Christian; Neugebauer, Julia; Hutter, Stefan; Engelstädter, Verena; Ilmer, Matthias; Friese, Klaus; Jeschke, Udo

    2013-01-08

    It is widely known that cells from epithelial tumors, e.g., breast cancer, detach from their primary tissue and enter blood circulation. We show that the presence of circulating tumor cells (CTCs) in samples of patients with primary and metastatic breast cancer can be detected with an array of selected tumor-marker-genes by reverse transcription real-time PCR. The focus of the presented work is on detecting differences in gene expression between healthy individuals and adjuvant and metastatic breast cancer patients, not an accurate quantification of these differences. Therefore, total RNA was isolated from blood samples of healthy donors and patients with primary or metastatic breast cancer after enrichment of mononuclear cells by density gradient centrifugation. After reverse transcription real-time PCR was carried out with a set of marker genes (BCSP, CK8, Her2, MGL, CK18, CK19). B2M and GAPDH were used as reference genes. Blood samples from patients with metastatic disease revealed increased cytokine gene levels in comparison to normal blood samples. Detection of a single gene was not sufficient to detect CTCs by reverse transcription real-time PCR. Markers used here were selected based on a recent study detecting cancer cells on different protein levels. The combination of such a marker array leads to higher and more specific discovery rates, predominantly in metastatic patients. Identification of CTCs by PCR methods may lead to better diagnosis and prognosis and could help to choose an adequate therapy.

  2. Disseminated and circulating tumour cells and their role in breast cancer.

    PubMed

    Čabiňaková, M; Tesařová, P

    2012-01-01

    Metastatic spread of the primary tumour is responsible for the vast majority of cancer-related deaths. Detection of disseminated tumour cells in the bone marrow and circulating tumour cells in the peripheral blood is correlated with early metastatic relapse in breast cancer. Positive detection of disseminated tumour cells was associated with poor overall survival of patients. Current research has been focused on integrating minimal residual disease as a prognostic and predictive tool in the management of breast cancer. Detection of disseminated tumour cells/circulating tumour cells is not yet standardized in clinical practice because of using different enrichment and detection methods. Therefore, standardization of the used methods is necessary in the future. Previous achieved findings must be verified in larger prospective multicentre studies. Further characterization of disseminated tumour cells/circulating tumour cells will be essential for developing and monitoring the efficacy of new therapeutic concepts. The aim of this review was to provide a short survey of the metastatic cascade and cancer stem cell theory, and data on the molecular and functional characterization of disseminated tumour cells/circulating tumour cells. Finally, we discuss the potential clinical impact of disseminated tumour cells/circulating tumour cells and results of several recent studies.

  3. Quantification of longitudinal tissue pO2 gradients in window chamber tumours: impact on tumour hypoxia

    PubMed Central

    Dewhirst, M W; Ong, E T; Braun, R D; Smith, B; Klitzman, B; Evans, S M; Wilson, D

    1999-01-01

    We previously reported that the arteriolar input in window chamber tumours is limited in number and is constrained to enter the tumour from one surface, and that the pO2 of tumour arterioles is lower than in comparable arterioles of normal tissues. On average, the vascular pO2 in vessels of the upper surface of these tumours is lower than the pO2 of vessels on the fascial side, suggesting that there may be steep vascular longitudinal gradients (defined as the decline in vascular pO2 along the afferent path of blood flow) that contribute to vascular hypoxia on the upper surface of the tumours. However, we have not previously measured tissue pO2 on both surfaces of these chambers in the same tumour. In this report, we investigated the hypothesis that the anatomical constraint of arteriolar supply from one side of the tumour results in longitudinal gradients in pO2 sufficient in magnitude to create vascular hypoxia in tumours grown in dorsal flap window chambers. Fischer-344 rats had dorsal flap window chambers implanted in the skin fold with simultaneous transplantation of the R3230AC tumour. Tumours were studied at 9–11 days after transplantation, at a diameter of 3–4 mm; the tissue thickness was 200 μm. For magnetic resonance microscopic imaging, gadolinium DTPA bovine serum albumin (BSA-DTPA-Gd) complex was injected i.v., followed by fixation in 10% formalin and removal from the animal. The sample was imaged at 9.4 T, yielding voxel sizes of 40 μm. Intravital microscopy was used to visualize the position and number of arterioles entering window chamber tumour preparations. Phosphorescence life time imaging (PLI) was used to measure vascular pO2. Blue and green light excitations of the upper and lower surfaces of window chambers were made (penetration depth of light ~50 vs >200 μm respectively). Arteriolar input into window chamber tumours was limited to 1 or 2 vessels, and appeared to be constrained to the fascial surface upon which the tumour grows. PLI of

  4. Surrogate markers for cerebral blood flow correlate with [¹⁸F]-fallypride binding potential at dopamine D(2/3) receptors in human striatum.

    PubMed

    Cumming, Paul; Xiong, Guoming; la Fougère, Christian; Rominger, Axel; Bartenstein, Peter; Buchholz, Hans-Georg; Piel, Markus; Rösch, Frank; Gründer, Gerhard; Vernaleken, Ingo

    2013-04-01

    Positron emission tomography (PET) with the high affinity dopamine D(2/3) receptor ligand [¹⁸F]-fallypride affords estimates of the binding potential (BP(ND) ) in extra-striatal regions of low receptor abundance, but the sufficient recording time for accurate measurements in striatum has been called into question. We have earlier argued that transient equilibrium measurements are obtained in striatum with [¹⁸F]-fallypride PET recordings of 3 h duration, which may be the practical limit for clinical investigations without interrupted scanning. However, the high extraction fraction of [¹⁸F]-fallypride predicts flow-dependence of tracer delivery to brain, which may be a source of variance of the apparent BP(ND) in regions of high binding. To test this prediction, we conducted a retrospective analysis of [¹⁸F]-fallypride PET data from a group of 50 healthy volunteers (age 18-58 years [mean ± SD: 32.6 ± 10.6), who had participated in clinical studies without arterial input measurements. We used the initial 120-s integral (AUC) of the venous confluence (VC) as a surrogate marker for cerebral blood flow (CBF) and tested for correlations between regional estimates of BP(ND) calculated by the simplified reference tissue model (SRTM) and the individual VC-AUC. The magnitude of BP(ND) in a high binding region (putamen), but not in a low binding region (thalamus) correlated positively with VC-AUC, suggesting that approximately 9% of the variance in the [¹⁸F]-fallypride BP(ND) in putamen can be attributed to individual differences in this surrogate marker for CBF, a contribution equal in magnitude to the effects of age on BP(ND) in putamen of the present healthy control group. PMID:23239525

  5. MINDEC-An Enhanced Negative Depletion Strategy for Circulating Tumour Cell Enrichment

    PubMed Central

    Lapin, Morten; Tjensvoll, Kjersti; Oltedal, Satu; Buhl, Tove; Gilje, Bjørnar; Smaaland, Rune; Nordgård, Oddmund

    2016-01-01

    Most current methods of circulating tumour cell (CTC) enrichment target the epithelial protein EpCAM, which is commonly expressed in adenocarcinoma cells. However, such methods will not recover the fraction of CTCs that have a non-epithelial phenotype due to epithelial–mesenchymal transition. For phenotype-independent CTC enrichment, we developed a new enhanced negative depletion strategy—termed MINDEC—that is based on multi-marker (CD45, CD16, CD19, CD163, and CD235a/GYPA) depletion of blood cells rather than targeted enrichment of CTCs. Here we validated the performance of MINDEC using epithelial and mesenchymal cancer cell lines, demonstrating a mean recovery of 82 ± 10%, high depletion (437 ± 350 residual white blood cells (WBCs)/mL peripheral blood), linearity between spiked and recovered cells (correlation coefficient: r = 0.995), and a low detection limit (≥1 cell recovered in all four replicates spiked with 3 cells). For clinical validation of this method, we enumerated CTCs in peripheral blood samples from patients with metastatic pancreatic cancer, detecting CTCs in 15 of 21 blood samples (71%) from 9 patients. The promising performance of the MINDEC enrichment strategy in our study encourages validation in larger clinical trials. PMID:27432216

  6. Metallothionein expression and nuclear size in benign, borderline, and malignant serous ovarian tumours.

    PubMed

    Tan, Y; Sinniah, R; Bay, B H; Singh, G

    1999-09-01

    Metallothioneins (MTs) are low-molecular-weight proteins involved in metalloregulatory functions such as cell proliferation, growth, and differentiation. In recent years, MT expression has been linked with carcinogenesis, resistance to cancer therapy, and tumour progression. However, the significance of MT expression in ovarian cancers is at present inadequately documented. In this study, MT immunohistochemistry was performed in 12 benign, 14 borderline, and eight malignant serous tumours of the ovary. The intensity of the immunostaining was evaluated by image analysis. There was a significantly higher number of MT-immunopositive cells in the multilayered epithelial cells of borderline serous tumours (atypical proliferative serous tumours) than in the single layered epithelial cells within the same tumour, and in the single cell layer of benign serous tumours. There was no difference in the expression of MTs in the single layered tumour cells of benign and borderline serous tumours. Significantly higher numbers of MT-immunopositive cells were observed in both the single and the multilayered epithelial cells of serous carcinomas, the highest number being observed in the multiple layers of serous carcinomas. The positively stained malignant tumour cells in both single and multiple layers were larger than the negatively stained cells in benign, borderline, and malignant serous ovarian tumours. There was moderate to intense staining. These findings indicate that there is increased expression of MTs in the progression of malignancy, which could be used as a marker in grading the three groups of ovarian serous tumours and for determining prognosis.

  7. CYBA (p22phox) variants associate with blood pressure and oxidative stress markers in hypertension: a replication study in populations of diverse altitudes.

    PubMed

    Kumar, Rahul; Kohli, Samantha; Ali, Zahara; Duhan, Kanika; Ram, Rekhbala; Gupta, Mohit; Tyagi, Sanjay; Mohammad, Ghulam; Pasha, Ma Qadar

    2015-07-01

    CYBA (p22(phox)) is an integral constituent of the NADPH oxidases and is consequently a main component of oxidative stress, which is strongly associated with hypertension. This study investigates the contribution of CYBA polymorphisms toward the complex etiology of hypertension in two ethnically different populations, one located at a high altitude and the other at a low altitude. The significance of CYBA single nucleotide polymorphisms and their correlation with clinical and biochemical phenotypes were investigated in age- and ethnicity-matched unrelated permanent high-altitude residents (>3500 m) comprising 245 controls and 241 patients. The results were replicated in a second population comprising 935 controls and 545 patients who lived at a low altitude (<200 m). The analysis of covariance revealed that CYBA risk alleles and their haplotypes, rs8854A/rs9932581G/rs4873C and rs8854G/rs9932581G/rs4873C, were positively correlated with clinical parameters, for example, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP), and biochemical parameters, for example, 8-isoPGF2α level, and inversely correlated with catalase activity in patients compared with controls (P⩽0.01, each). Conversely, the protective alleles and their haplotype, rs8854G/rs9932581A/rs4873T, were inversely correlated with SBP, DBP, MAP and 8-isoPGF2α level, and positively correlated with catalase activity (P⩽0.001, each). Furthermore, correlation analysis between the clinical and biochemical parameters revealed a positive correlation of SBP, DBP and MAP with 8-isoPGF2α levels and a negative correlation with catalase activity in both populations (P<0.0001, each). CYBA (p22(phox)) variants influence the markers of oxidative stress and are associated with hypertension.

  8. Progression of radiographic changes in the temporomandibular joints of patients with rheumatoid arthritis in relation to inflammatory markers and mediators in the blood.

    PubMed

    Voog, Ulle; Alstergren, Per; Eliasson, Sören; Leibur, Edvitar; Kallikorm, Riina; Kopp, Sigvard

    2004-02-01

    The aim of this study was to investigate longitudinal radiographic changes in the temporomandibular joint (TMJ) with clinical involvement of rheumatoid arthritis (RA) and its relation to the blood level of inflammatory mediators and markers. Sixteen patients were investigated by computed tomography on two occasions 25-46 months apart. The radiographs were assessed independently for changes in presence of erosions, sclerosis, flattening, osteophytes, and subchondral pseudocysts. The serum (S) or plasma (P) concentrations of C-reactive protein (CRP), thrombocyte particle concentration, scrotonin (S-5-HT and P-5-HT), tumor necrosis factor alpha, interleukin-1 receptor antagonist, tumor necrosis factor soluble receptor type II, interleukin-1 soluble receptor type II (P-IL-1sRII) and interleukin 6 as well as the erythrocyte sedimentation rate (ESR) were measured. The radiographic status showed no consistent or significant change during the observation period, but the individual variation was considerable. The radiographic signs of erosion and sclerosis varied most. Regression of erosions was associated with high S-5-HT and P-IL-1sRII, while progression of erosions was associated with high P-5-HT. Regression of sclerosis was associated with an increase in P-5-HT and high ESR. Progression of flattening was associated with high CRP. In conclusion, this study indicates that the progression of radiographic changes that occurs in the TMJ of patients with well-controlled RA during a period of 25-46 months seems to be related to the blood levels of CRP, 5-HT, and IL-1sRII. However, only minor progression can be expected to occur, and with considerable individual variation. PMID:15124777

  9. Promotion of Growth of Tumour Cells in Acutely Inflamed Tissues

    PubMed Central

    van den Brenk, H. A. S.; Stone, M.; Kelly, H.; Orton, C.; Sharpington, C.

    1974-01-01

    Acute inflammatory reactions were induced in rats by the intravenous injection of cellulose sulphate (CS) or an extract of normal rat lung homogenate (LH), or by intraperitoneal injections of Compound 48/80. These treatments greatly increased survival and clonogenic growth in the lungs of rats of intravenously injected allogeneic W-256 and Y-P388 tumour cells. Increase in the dose of intravenously injected CS caused a logarithmic increase in colony forming efficiency (CFE) of tumour cells in the lungs. CFE was not stimulated by the intravenous injection of rats with pharmacological mediators of inflammation (histamine, 5-hydroxytryptamine, bradykinin and prostaglandins PGE1 and PGF2α) which are released from tissues by agents which induce inflammation. Stimulation of CFE by CS occurred in adrenalectomized rats but was inhibited by treatment of rats with an anti-inflammatory steroid, dexamethasone. CFE was stimulated by CS in tumour immunized rats; the inflammatory state did not prevent the expression of immunity but “rescued” a proportion (approximately 20%) of the injected tumour cells from immunodestruction in the lungs. A higher proportion of tumours grew in the paws of rats when a small number of W-256 cells were injected interdigitally into the acute inflammatory swellings produced by the local injection of paws with LH or CS. CS is a “synthetic heparin” which causes marked prolongation of blood clotting time and also increases fibrinolytic activity of the blood. Anticoagulant treatment of rats with heparin did not affect CFE. Thus, there was no direct correlation between blood clotting time and CFE of blood borne tumour cells in the rat. The mechanisms which may be responsible for the nonspecific growth promoting effects of inflammatory reactions induced by various types of tissue injury on tumour induction and growth are discussed. ImagesFig. 2 PMID:4451630

  10. Laryngeal solitary fibrous tumour.

    PubMed

    Stomeo, Francesco; Padovani, Davide; Bozzo, Corrado; Pastore, Antonio

    2007-09-01

    Solitary fibrous tumours (SFT) are rare neoplasms, with an uncommon laryngeal involvement. Only five cases of laryngeal localization have been described in literature. The following is a case of a 75-year-old man with a supraglottic neoplasm of the larynx; after the biopsy immunohistochemical study demonstrated a strong positivity for vimentin, CD34 and Bcl-2. The neoplasm was consequently classified as a SFT. CO(2) laser surgery of the supraglottic larynx, with a wide excision of the neoplasm, was performed. Twenty-four months on, the patient is alive, well and free of disease. Surgical resection is the treatment of choice for laryngeal SFT, but tumour-free resection margins must be achieved to prevent the possibility of local recurrence. Endoscopic resection by means of the CO(2) laser must be accurately planned with MRI or CT imaging to confirm of this kind of surgery.

  11. Clinical challenges in the molecular characterization of circulating tumour cells in breast cancer.

    PubMed

    Lianidou, E S; Mavroudis, D; Georgoulias, V

    2013-06-25

    Blood testing for circulating tumour cells (CTC) has emerged as one of the hottest fields in cancer research. CTC detection and enumeration can serve as a 'liquid biopsy' and an early marker of response to systemic therapy, whereas their molecular characterisation has a strong potential to be translated to individualised targeted treatments and spare breast cancer (BC) patients unnecessary and ineffective therapies. Different analytical systems for CTC detection and isolation have been developed and new areas of research are directed towards developing novel assays for CTC molecular characterisation. Molecular characterisation of single CTC holds considerable promise for predictive biomarker assessment and to explore CTC heterogeneity. The application of extremely powerful next-generation sequencing technologies in the area of CTC molecular characterisation in combination with reliable single CTC isolation opens new frontiers for the management of patients in the near future. This review is mainly focused on the clinical potential of the molecular characterisation of CTC in BC.

  12. In vitro opioid induced proliferation of peripheral blood immune cells correlates with in vivo cold pressor pain tolerance in humans: a biological marker of pain tolerance.

    PubMed

    Hutchinson, Mark R; La Vincente, Sophie F; Somogyi, Andrew A

    2004-08-01

    There is substantial evidence for bidirectional communication between the immune system and the central nervous system, as the cells and signalling molecules of the immune system influence many central nervous system functions, for instance nociception. Opioids, such as morphine, produce analgesia and numerous other central and peripheral effects including sedation and euphoria, while their effects on the immune system are wide-ranging. There is considerable interindividual variability in basal nociception and response to opioids, however, the physiological and biological mechanisms underlying this are unclear. Therefore, we investigated the relationship between the immune system and basal nociceptive thresholds, using the proliferative response of isolated peripheral blood mononuclear cells and cold pressor pain tolerance. Here we show that the percent increase in proliferation of peripheral immune cells from 13 healthy subjects incubated with morphine ex vivo is highly correlated with the subjects' tolerance to noxious cold stimuli (Pearson r = 0.92, P < 0.0001). These pilot data provide evidence of a novel objective biological marker of pain tolerance in humans, which also links the immune and opioid systems with basal pain tolerance.

  13. Molecular analysis of circulating tumour cells-biology and biomarkers.

    PubMed

    Krebs, Matthew G; Metcalf, Robert L; Carter, Louise; Brady, Ged; Blackhall, Fiona H; Dive, Caroline

    2014-03-01

    Growing evidence for intratumour heterogeneity informs us that single-site biopsies fall short of revealing the complete genomic landscape of a tumour. With an expanding repertoire of targeted agents entering the clinic, screening tumours for genomic aberrations is increasingly important, as is interrogating the tumours for resistance mechanisms upon disease progression. Multiple biopsies separated spatially and temporally are impractical, uncomfortable for the patient and not without risk. Here, we describe how circulating tumour cells (CTCs), captured from a minimally invasive blood test-and readily amenable to serial sampling-have the potential to inform intratumour heterogeneity and tumour evolution, although it remains to be determined how useful this will be in the clinic. Technologies for detecting and isolating CTCs include the validated CellSearch(®) system, but other technologies are gaining prominence. We also discuss how recent CTC discoveries map to mechanisms of haematological spread, previously described in preclinical models, including evidence for epithelial-mesenchymal transition, collective cell migration and cells with tumour-initiating capacity within the circulation. Advances in single-cell molecular analysis are enhancing our ability to explore mechanisms of metastasis, and the combination of CTC and cell-free DNA assays are anticipated to provide invaluable blood-borne biomarkers for real-time patient monitoring and treatment stratification.

  14. Electrochemotherapy of Tumours

    PubMed Central

    Sersa, Gregor; Miklavcic, Damijan

    2008-01-01

    Electrochemotherapy is a combined use of certain chemotherapeutic drugs and electric pulses applied to the treated tumour nodule. Local application of electric pulses to the tumour increases drug delivery into cells, specifically at the site of electric pulse application. Drug uptake by delivery of electric pulses is increased for only those chemotherapeutic drugs whose transport through the plasma membrane is impeded. Among many drugs that have been tested so far, bleomycin and cisplatin found their way from preclinical testing to clinical use. Clinical data collected within a number of clinical studies indicate that approximately 80% of the treated cutaneous and subcutaneous tumour nodules of different malignancies are in an objective response, from these, approximately 70% in complete response after a single application of electrochemotherapy. Usually only one treatment is needed, however, electrochemotherapy can be repeated several times every few weeks with equal effectiveness each time. The treatment results in an effective eradication of the treated nodules, with a good cosmetic effect without tissue scarring. PMID:19229171

  15. Tumour-associated macrophages are associated with vascular endothelial growth factor expression in canine mammary tumours.

    PubMed

    Raposo, T P; Pires, I; Carvalho, M I; Prada, J; Argyle, D J; Queiroga, F L

    2015-12-01

    Tumour-associated macrophages (TAMs) have been implicated in carcinogenesis including an important role in angiogenesis. In this study, we describe the relationship between TAMs and angiogenesis in canine mammary tumours (CMT). Formalin-fixed paraffin-embedded CMT samples [(n = 128: malignant (n = 97) and benign (n = 31)] were submitted to immunohistochemical staining to detect MAC387, vascular endothelial growth factor VEGF and CD31 expression. A statistical analysis was carried out to assess possible associations with clinicopathological variables and biological markers of tumour angiogenesis. TAMs, detected by MAC387 expression, were significantly associated with malignant CMT (P < 0.001) and VEGF positive tumours (P = 0.002) and also associated with VEGF expression within malignant CMT (P = 0.043). Associations with clinicopathological variables were found between TAMs and the presence of infiltrative growth (P = 0.031), low tubule formation (P = 0.040) and lymph node metastasis (P = 0.016). The results support the hypothesis that TAMs influence angiogenesis in CMT suggesting TAMs may represent a therapeutic target in this disease. PMID:24119241

  16. Establishing tumour tracking accuracy in free-breathing respiratory gated SBRT of lung cancer

    NASA Astrophysics Data System (ADS)

    Wen, Chuan-Dong; Wong, C.; Ackerly, T.; Ruben, J.; Millar, J.

    2014-03-01

    Free-breathing respiratory gated SBRT of surgically inoperable lung cancer has been clinically commissioned. This study was to establish the tumour tracking accuracy under clinical conditions based on an implanted fiducial marker. A VisicoilTM marker embedded in tissue-equivalent material mounted in a phantom (ET Gating PhantomTM Brainlab) driven by a patient's breathing data was treated with the ExacTracTM system. This one-dimensional moving marker represented a tumour motion in superior-inferior (S-I) direction measured through 4DCT study of the same patient. Both GafchromicTM films and the stereoscopic kV images were used for tracking the position of the marker. For tumour motion at magnitudes of 10, 20 and 29 mm and treated with corresponding gate widths of 50%, 33% and 20% of free breathing amplitude, the implanted marker was able to be tracked with a deviation <=1.53 mm to its planned position.

  17. Clinical features of gastroenteropancreatic tumours

    PubMed Central

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

    2015-01-01

    Gastroenteropancreatic (GEP) endocrine tumours (carcinoids and pancreatic islet cell tumours) are composed of multipotent neuroendocrine cells that exhibit a unique ability to produce, store, and secrete biologically active substances and cause distinct clinical syndromes. The classification of GEP tumours as functioning or non-functioning is based on the presence of symptoms that accompany these syndromes secondary to the secretion of hormones, neuropeptides and/or neurotransmitters (functioning tumours). Non-functioning tumours are considered to be neoplasms of neuroendocrine differentiation that are not associated with obvious symptoms attributed to the hypersecretion of metabolically active substances. However, a number of these tumours are either capable of producing low levels of such substances, which can be detected by immunohistochemistry but are insufficient to cause symptoms related to a clinical syndrome, or alternatively, they may secrete substances that are either metabolically inactive or inappropriately processed. In some cases, GEP tumours are not associated with the production of any hormone or neurotransmitter. Both functioning and non-functioning tumours can also produce symptoms due to mass effects compressing vital surrounding structures. Gastroenteropancreatic tumours are usually classified further according to the anatomic site of origin: foregut (including respiratory tract, thymus, stomach, duodenum, and pancreas), midgut (including small intestine, appendix, and right colon), and hindgut (including transverse colon, sigmoid, and rectum). Within these subgroups the biological and clinical characteristics of the tumours vary considerably, but this classification is still in use because a significant number of previous studies, mainly observational, have used it extensively. PMID:26516377

  18. Particular aspects in the cytogenetics and molecular biology of salivary gland tumours - current review of reports.

    PubMed

    Ochal-Choińska, Aleksandra J; Osuch-Wójcikiewicz, Ewa

    2016-01-01

    Salivary gland tumours are a group of lesions whose heterogeneity of biological and pathological features is widely reflected in the molecular aspect. This is demonstrated by an increasing number of studies in the field of genetics of these tumours. The aim of this study was to collect the most significant scientific reports on the cytogenetic and molecular data concerning these tumours, which might facilitate the identification of potential biomarkers and therapeutic targets. The analysis covered 71 papers included in the PubMed database. We focused on the most common tumours, such as pleomorphic adenoma, Warthin tumour, mucoepidermoid carcinoma, and others. The aim of this study is to present current knowledge about widely explored genotypic alterations (such as PLAG1 gene in pleomorphic adenoma or MECT1 gene in mucoepidermoid carcinoma), and also about rare markers, like Mena or SOX10 protein, which might also be associated with tumourigenesis and carcinogenesis of these tumours. PMID:27688723

  19. Validation of an algorithm able to differentiate small-cell lung cancer (SCLC) from non-small-cell lung cancer (NSCLC) patients by means of a tumour marker panel: analysis of the errors.

    PubMed Central

    Paone, G.; De Angelis, G.; Portalone, L.; Greco, S.; Giosué, S.; Taglienti, A.; Bisetti, A.; Ameglio, F.

    1997-01-01

    By means of a mathematical score previously generated by discriminant analysis on 90 lung cancer patients, a new and larger group of 261 subjects [209 with non-small-cell lung cancer (NSCLC) and 52 with small-cell lung cancer (SCLC)] was analysed to confirm the ability of the method to distinguish between these two types of cancers. The score, which included the serum neuron-specific enolase (NSE) and CYFRA-21.1 levels, permitted correct classification of 93% of the patients. When the misclassifications were analysed in detail, the most frequent errors were associated with limited disease SCLC with low NSE levels and with advanced NSCLC with high NSE levels. This demonstrates the importance of the marker in correctly categorizing patients. PMID:9020496

  20. Is immediate postoperative CA15.3 assay a predictive marker of early postoperative recurrence of carcinoma breast?

    PubMed

    Sarkar, Diptendra Kumar; Panda, Nilanjan; Biswas, Subikas; Saha, M L; Majumder, A

    2012-03-01

    Breast cancer is still an enigma. Systemic metastasis is an important prognostic factor. Tumour marker can predict occult systemic metastasis. To evaluate the immediate postoperative CA15.3 as predictor of early recurrence, a study was carried out in 48 patients of carcinoma breast in whom immediate postoperative marker level was done. In follow-up, recurrence was noted and relation with tumour size and stage done. Null hypothesis and 't' test were used for analysis. Relation of tumour size with marker is weak but strong relation exists between tumour stage with marker and recurrence with marker. CA15.3 predicts tumour load, can also predict occult residual/occult metastatic disease better than other prognostic markers which only predict tumour behaviour.

  1. Brain tumour stem cells: possibilities of new therapeutic strategies.

    PubMed

    Piccirillo, Sara G M; Vescovi, Angelo L

    2007-08-01

    Cancers are composed of heterogeneous cell populations, including highly proliferative immature precursors and differentiated cells, which may belong to different lineages. Recent advances in stem cell research have demonstrated the existence of tumour-initiating, cancer stem cells (CSCs) in non-solid and solid tumours. These cells are defined as CSCs because they show functional properties that resemble those of their normal counterpart to a significant extent. This concept applies to CSCs from brain tumours and, particularly, to glioblastoma stem-like cells, which self-renew under clonal conditions and differentiate into neuron- and glia-like cells, and into aberrant cells, with mixed neuronal/astroglia phenotypes. Notably, across serial transplantation into immunodeficient mice, glioblastoma stem-like cells are able to form secondary tumours which are a phenocopy of the human disease. A significant effort is underway to identify both CSC-specific markers and the molecular mechanism that underpin the tumorigenic potential of these cells, for this will have a critical impact on the understanding of the origin of malignant brain tumour and the discovery of new and more specific therapeutic approaches. Lately, the authors have shown that some of the bone morphogenetic proteins can reduce the tumorigenic ability of CSCs in GBMs. This suggests that mechanisms regulating the physiology of normal brain stem cells may be still in place in their cancerous siblings and that this may lead to the development of cures that selectively target the population CSCs found in the patients' tumour mass.

  2. Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis.

    PubMed

    Strilic, Boris; Yang, Lida; Albarrán-Juárez, Julián; Wachsmuth, Laurens; Han, Kang; Müller, Ulrike C; Pasparakis, Manolis; Offermanns, Stefan

    2016-08-11

    Metastasis is the leading cause of cancer-related death in humans. It is a complex multistep process during which individual tumour cells spread primarily through the circulatory system to colonize distant organs. Once in the circulation, tumour cells remain vulnerable, and their metastatic potential largely depends on a rapid and efficient way to escape from the blood stream by passing the endothelial barrier. Evidence has been provided that tumour cell extravasation resembles leukocyte transendothelial migration. However, it remains unclear how tumour cells interact with endothelial cells during extravasation and how these processes are regulated on a molecular level. Here we show that human and murine tumour cells induce programmed necrosis (necroptosis) of endothelial cells, which promotes tumour cell extravasation and metastasis. Treatment of mice with the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-inhibitor necrostatin-1 or endothelial-cell-specific deletion of RIPK3 reduced tumour-cell-induced endothelial necroptosis, tumour cell extravasation and metastasis. In contrast, pharmacological caspase inhibition or endothelial-cell-specific loss of caspase-8 promoted these processes. We furthermore show in vitro and in vivo that tumour-cell-induced endothelial necroptosis leading to extravasation and metastasis requires amyloid precursor protein expressed by tumour cells and its receptor, death receptor 6 (DR6), on endothelial cells as the primary mediators of these effects. Our data identify a new mechanism underlying tumour cell extravasation and metastasis, and suggest endothelial DR6-mediated necroptotic signalling pathways as targets for anti-metastatic therapies. PMID:27487218

  3. Development of luciferase tagged brain tumour models in mice for chemotherapy intervention studies.

    PubMed

    Kemper, E M; Leenders, W; Küsters, B; Lyons, S; Buckle, T; Heerschap, A; Boogerd, W; Beijnen, J H; van Tellingen, O

    2006-12-01

    The blood-brain barrier (BBB) is considered one of the major causes for the low efficacy of cytotoxic compounds against primary brain tumours. The aim of this study was to develop intracranial tumour models in mice featuring intact or locally disrupted BBB properties, which can be used in testing chemotherapy against brain tumours. These tumours were established by intracranial injection of suspensions of different tumour cell lines. All cell lines had been transfected with luciferase to allow non-invasive imaging of tumour development using a super-cooled CCD-camera. Following their implantation, tumours developed which displayed the infiltrative, invasive or expansive growth patterns that are also found in primary brain cancer or brain metastases. Contrast-enhanced magnetic resonance imaging showed that the Mel57, K1735Br2 and RG-2 lesions grow without disruption of the BBB, whereas the BBB was leaky in the U87MG and VEGF-A-transfected Mel57 lesions. This was confirmed by immunohistochemistry. Bioluminescence measurements allowed the visualisation of tumour burden already within 4 days after injection of the tumour cells. The applicability of our models for performing efficacy studies was demonstrated in an experiment using temozolomide as study drug. In conclusion, we have developed experimental brain tumour models with partly disrupted, or completely intact BBB properties. In vivo imaging by luciferase allows convenient follow-up of tumour growth and these models will be useful for chemotherapeutic intervention studies.

  4. Maspin as a Tumour Suppressor in Salivary Gland Tumour

    PubMed Central

    Ashok, Nipun; Sheirawan, Mohammad Kinan; Altamimi, Mohammed Alsakran; Alenzi, Faris; Azzeghaiby, Saleh Nasser; Baroudi, Kusai; Nassani, Mohammad Zakaria

    2014-01-01

    Maspin is a protein that belongs to serin protease inhibitor (serpin) superfamily. The purpose of this study was to review the literature concerning the expression of maspin in salivary gland tumours. A literature search was done using MEDLINE, accessed via the National Library of Medicine PubMed interface. Statistical analysis was not done because only seven studies were available in literature, the collected data were different and the results could not be compared. Expression of maspin was down regulated in more aggressive salivary gland tumours. Maspin may function as a tumour suppressor in salivary gland tumours. PMID:25654053

  5. [Laboratory markers of melanoma progression].

    PubMed

    Bánfalvi, Teodóra; Edesné, Mariann B; Gergye, Mária; Udvarhelyi, Nóra; Orosz, Zsolt; Gilde, Katalin; Kremmer, Tibor; Ottó, Szabolcs; Tímár, József

    2003-01-01

    Extracellular tumour markers may have potential role in the follow-up of patients with malignant melanoma, in therapy monitoring and in prediction of prognosis. In our article circulating tumour markers in melanoma (melanoma inhibitory activity, lipid bound sialic acid, neuron specific enolase, TA90 immune complex, S-100B protein, 5-S-cysteinyldopa, tyrosinase, cytokines, metalloproteinases, LDH) were reviewed. Among laboratory melanoma markers the S-100B protein is the most investigated. S-100B protein has high specificity, appropriate sensitivity and proved to be significant prognostic factor independent from stages. High serum values are associated with shorter survival. However, before S-100B monitoring immunohistochemistry for the detection of S-100B is required. In the case of malignant melanomas with low expression serum S-100B monitoring may not be sensitive enough to follow disease progression. Although the serum concentration of 5-S-cysteinyldopa did not prove to be independent prognostic factor in our previous studies comprising the highest patient number in the literature, the marker was suggested for therapy monitoring. The survival analysis indicated that the elevated 5-S-cysteinyldopa level predicts shorter survival. In spite of the calculated low correlation between the two markers, parallel elevation of S-100B protein and 5-S-cysteinyldopa indicated shorter survival. On the basis of the literature LDH is the most appropriate tumour marker in stage IV to predict prognosis, but its sensitivity and specificity could not achieve that of S-100B protein. S-100B and LDH proved to be similarly reliable in respect to the clinical outcome. Determination of serum concentration of MIA and tyrosinase are also reliable markers in malignant melanoma. The other investigated markers are not well known yet or do not provide useful information to the clinicians. PMID:12704461

  6. Comparison of noninvasive pulse transit time estimates as markers of blood pressure using invasive pulse transit time measurements as a reference.

    PubMed

    Gao, Mingwu; Olivier, N Bari; Mukkamala, Ramakrishna

    2016-05-01

    Pulse transit time (PTT) measured as the time delay between invasive proximal and distal blood pressure (BP) or flow waveforms (invasive PTT [I-PTT]) tightly correlates with BP PTT estimated as the time delay between noninvasive proximal and distal arterial waveforms could therefore permit cuff-less BP monitoring. A popular noninvasive PTT estimate for this application is the time delay between ECG and photoplethysmography (PPG) waveforms (pulse arrival time [PAT]). Another estimate is the time delay between proximal and distal PPG waveforms (PPG-PTT). PAT and PPG-PTT were assessed as markers of BP over a wide physiologic range using I-PTT as a reference. Waveforms for determining I-PTT, PAT, and PPG-PTT through central arteries were measured from swine during baseline conditions and infusions of various hemodynamic drugs. Diastolic, mean, and systolic BP varied widely in each subject (group average (mean ± SE) standard deviation between 25 ± 2 and 36 ± 2 mmHg). I-PTT correlated well with all BP levels (group average R(2) values between 0.86 ± 0.03 and 0.91 ± 0.03). PPG-PTT also correlated well with all BP levels (group average R(2) values between 0.81 ± 0.03 and 0.85 ± 0.02), and its R(2) values were not significantly different from those of I-PTT PAT correlated best with systolic BP (group average R(2) value of 0.70 ± 0.04), but its R(2) values for all BP levels were significantly lower than those of I-PTT (P < 0.005) and PPG-PTT (P < 0.02). The pre-ejection period component of PAT was responsible for its inferior correlation with BP In sum, PPG-PTT was not different from I-PTT and superior to the popular PAT as a marker of BP.

  7. Lymphopenia and Elevated Blood C-Reactive Protein Levels at Four Days Postoperatively Are Useful Markers for Early Detection of Surgical Site Infection Following Posterior Lumbar Instrumentation Surgery

    PubMed Central

    Shigematsu, Hideki; Koizumi, Munehisa; Nakajima, Hiroshi; Okuda, Akinori; Morimoto, Yasuhiko; Masuda, Keisuke; Tanaka, Yasuhito

    2016-01-01

    Study Design Case-control study. Purpose To identify the characteristics of candidate indexes for early detection of surgical site infection (SSI). Overview of Literature SSI is a serious complication of spinal instrumentation surgery. Early diagnosis and treatment are crucial for the welfare of the patient postoperation. Methods We retrospectively reviewed laboratory data of patients who underwent posterior lumbar instrumentation surgery for degenerative spine disease. The sensitivity and specificity of six laboratory markers for early detection of SSI were calculated: greater elevation of the white blood cell count at day 7 than at day 4 postoperatively, greater elevation of the C-reactive protein (CRP) level at day 7 than at day 4 postoperatively, a CRP level of >10 mg/dL at 4 days postoperatively, neutrophil percentage of >75% at 4 days postoperatively, a lymphocyte percentage of <10% at 4 days postoperatively, and a lymphocyte count of <1,000/µL at 4 days postoperatively. Statistical analysis was via Fisher's exact test and a p-value of <0.05 was considered significant. Results In total, 85 patients were enrolled. Of these, five patients developed deep SSI. The sensitivity and specificity of each index were as follows: index 1, 20.0% and 77.5%; index 2, 20.0% and 83.8%; index 3, 40.0% and 97.5%; index 4, 40.0% and 86.3%; index 5, 0% and 96.3%; and index 6, 80.0% and 80.0%. A significant difference was noted for indexes 3 and 6. Conclusions A CRP level of >10 mg/dL at 4 days postoperatively would be useful for definitive diagnosis of SSI, and a lymphocyte count of <1,000/µL at 4 days postoperatively would be a useful screening test for SSI. Although laboratory markers for early detection of SSI have been frequently reported, we believe that it is important to understand the characteristics of each index for a precise diagnosis. PMID:27114760

  8. Comparison of noninvasive pulse transit time estimates as markers of blood pressure using invasive pulse transit time measurements as a reference.

    PubMed

    Gao, Mingwu; Olivier, N Bari; Mukkamala, Ramakrishna

    2016-05-01

    Pulse transit time (PTT) measured as the time delay between invasive proximal and distal blood pressure (BP) or flow waveforms (invasive PTT [I-PTT]) tightly correlates with BP PTT estimated as the time delay between noninvasive proximal and distal arterial waveforms could therefore permit cuff-less BP monitoring. A popular noninvasive PTT estimate for this application is the time delay between ECG and photoplethysmography (PPG) waveforms (pulse arrival time [PAT]). Another estimate is the time delay between proximal and distal PPG waveforms (PPG-PTT). PAT and PPG-PTT were assessed as markers of BP over a wide physiologic range using I-PTT as a reference. Waveforms for determining I-PTT, PAT, and PPG-PTT through central arteries were measured from swine during baseline conditions and infusions of various hemodynamic drugs. Diastolic, mean, and systolic BP varied widely in each subject (group average (mean ± SE) standard deviation between 25 ± 2 and 36 ± 2 mmHg). I-PTT correlated well with all BP levels (group average R(2) values between 0.86 ± 0.03 and 0.91 ± 0.03). PPG-PTT also correlated well with all BP levels (group average R(2) values between 0.81 ± 0.03 and 0.85 ± 0.02), and its R(2) values were not significantly different from those of I-PTT PAT correlated best with systolic BP (group average R(2) value of 0.70 ± 0.04), but its R(2) values for all BP levels were significantly lower than those of I-PTT (P < 0.005) and PPG-PTT (P < 0.02). The pre-ejection period component of PAT was responsible for its inferior correlation with BP In sum, PPG-PTT was not different from I-PTT and superior to the popular PAT as a marker of BP. PMID:27233300

  9. Analysis of tumour cell composition in tumours composed of paired mixtures of mammary tumour cell lines.

    PubMed Central

    Miller, B. E.; Miller, F. R.; Wilburn, D. J.; Heppner, G. H.

    1987-01-01

    In order to quantitate the effects of tumour subpopulation interactions, we have devised a method to determine the subpopulation composition of tumours by using paired tumour cell lines able to grow in different selective media. Line 4T07 forms colonies in thioguanine but not in HAT and line 168 forms colonies in HAT but not in thioguanine. An independent technique of determining tumour cell content was used to validate this method: line 168 and 4T07 cells are distinguishable by flow cytometry after staining with propidium iodide for DNA content. Mixtures of cell suspensions prepared from each unmixed tumour, as well as from tumours arising from mixtures of these lines, were analysed by both the colony formation assay and by the DNA content assay. The colony formation assay yielded values in good agreement with the DNA content assay, but was considerably more sensitive in that it was able to quantitate minority subpopulations that constituted less than 10% of the tumour. Both methods revealed that in tumours arising from mixtures, the tumour cells were almost entirely line 4T07, even when the inoculum had contained a high proportion of 168 cells. Since line 168 cells are very tumorigenic per se, these results suggest that line 4T07 cells are capable of interfering with 168 proliferation in mixed tumours, either directly or through a host-mediated mechanism. PMID:3426919

  10. Circulating tumour cells in metastatic head and neck cancers.

    PubMed

    Kulasinghe, Arutha; Perry, Chris; Jovanovic, Lidija; Nelson, Colleen; Punyadeera, Chamindie

    2015-06-01

    Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer with 650,000 new cases p/a worldwide. HNSCC causes high morbidity with a 5-year survival rate of less than 60%, which has not improved due to the lack of early detection (Bozec et al. Eur Arch Otorhinolaryngol. 2013;270: 2745-9). Metastatic disease remains one of the leading causes of death in HNSCC patients. This review article provides a comprehensive overview of literature over the past 5 years on the detection of circulating tumour cells (CTCs) in HNSCC; CTC biology and future perspectives. CTCs are a hallmark of invasive cancer cells and key to metastasis. CTCs can be used as surrogate markers of overall survival and progression-free survival. CTCs are currently used as prognostic factors for breast, prostate and colorectal cancers using the CellSearch® system. CTCs have been detected in HNSCC, however, these numbers depend on the technique applied, time of blood collection and the clinical stage of the patient. The impact of CTCs in HNSCC is not well understood, and thus, not in routine clinical practice. Validated detection technologies that are able to capture CTCs undergoing epithelial-mesenchymal transition are needed. This will aid in the capture of heterogeneous CTCs, which can be compiled as new targets for the current food and drug administration-cleared CellSearch® system. Recent studies on CTCs in HNSCC with the CellSearch® have shown variable data. Therefore, there is an immediate need for large clinical trials encompassing a suite of biomarkers capturing CTCs in HNSCC, before CTCs can be used as prognostic markers in HNSCC patient management.

  11. Current issues in the utility of 19F nuclear magnetic resonance methodologies for the assessment of tumour hypoxia.

    PubMed Central

    Robinson, Simon P; Griffiths, John R

    2004-01-01

    It is now well established that uncontrolled proliferation of tumour cells together with the chaotic and poorly regulated blood supply of solid tumours result in tissue hypoxia, and that hypoxic regions of tumours are resistant to radiotherapy and chemotherapy. The development and application of non-invasive methods to rapidly determine the degree and extent of tumour hypoxia in an individual tumour would clearly enhance cancer treatment strategies. This review describes the current status of two (19)F nuclear magnetic resonance (NMR) methodologies that have been exploited to investigate tumour hypoxia, namely: (i) (19)F NMR oximetry following administration of perfluorocarbons, from which tumour p(O)(2) measurements can be made; and (ii) (19)F NMR measurements of the tumour retention of fluorinated 2-nitroimidazoles. PMID:15306411

  12. Melatonin Immunoreactivity in Malignant Small Intestinal Neuroendocrine Tumours

    PubMed Central

    Söderquist, Fanny; Janson, Eva Tiensuu; Rasmusson, Annica J.; Ali, Abir; Stridsberg, Mats; Cunningham, Janet L.

    2016-01-01

    Background/Aims Small intestinal neuroendocrine tumours (SI-NETs) are derived from enterochromaffin cells. After demonstrating melatonin in enterochromaffin cells, we hypothesized that SI-NETs may express and secrete melatonin, which may have an impact on clinical factors and treatment response. Methods Tumour tissue from 26 patients with SI-NETs, representing paired sections of primary tumour and metastasis, were immunohistochemically stained for melatonin and its receptors, MT1 and MT2. Plasma melatonin and immunoreactivity (IR) for melatonin, MT1 and MT2 in tumour cells were compared to other tumour markers and clinical parameters. Melatonin was measured at two time points in fasting morning plasma from 43 patients with SI-NETs. Results Melatonin IR was found in all SI-NETS. Melatonin IR intensity in primary tumours correlated inversely to proliferation index (p = 0.022) and patients reported less diarrhoea when melatonin IR was high (p = 0.012). MT1 IR was low or absent in tumours. MT2 expression was medium to high in primary tumours and generally reduced in metastases (p = 0.007). Plasma-melatonin ranged from 4.5 to 220.0 pg/L. Higher levels were associated with nausea at both time points (p = 0.027 and p = 0.006) and flush at the second sampling. In cases with disease stabilization or remission (n = 34), circulating melatonin levels were reduced in the second sample (p = 0.038). Conclusion Immunoreactive melatonin is present in SI-NETs. Circulating levels of melatonin in patients with SI-NETs are reduced after treatment. Our results are congruent with recent understanding of melatonin’s endocrine and paracrine functions and SI-NETs may provide a model for further studies of melatonin function. PMID:27736994

  13. LET-painting increases tumour control probability in hypoxic tumours.

    PubMed

    Bassler, Niels; Toftegaard, Jakob; Lühr, Armin; Sørensen, Brita Singers; Scifoni, Emanuele; Krämer, Michael; Jäkel, Oliver; Mortensen, Lise Saksø; Overgaard, Jens; Petersen, Jørgen B

    2014-01-01

    LET-painting was suggested as a method to overcome tumour hypoxia. In vitro experiments have demonstrated a well-established relationship between the oxygen enhancement ratio (OER) and linear energy transfer (LET), where OER approaches unity for high-LET values. However, high-LET radiation also increases the risk for side effects in normal tissue. LET-painting attempts to restrict high-LET radiation to compartments that are found to be hypoxic, while applying lower LET radiation to normoxic tissues. Methods. Carbon-12 and oxygen-16 ion treatment plans with four fields and with homogeneous dose in the target volume, are applied on an oropharyngeal cancer case with an identified hypoxic entity within the tumour. The target dose is optimised to achieve a tumour control probability (TCP) of 95% when assuming a fully normoxic tissue. Using the same primary particle energy fluence needed for this plan, TCP is recalculated for three cases assuming hypoxia: first, redistributing LET to match the hypoxic structure (LET-painting). Second, plans are recalculated for varying hypoxic tumour volume in order to investigate the threshold volume where TCP can be established. Finally, a slight dose boost (5-20%) is additionally allowed in the hypoxic subvolume to assess its impact on TCP. Results. LET-painting with carbon-12 ions can only achieve tumour control for hypoxic subvolumes smaller than 0.5 cm(3). Using oxygen-16 ions, tumour control can be achieved for tumours with hypoxic subvolumes of up to 1 or 2 cm(3). Tumour control can be achieved for tumours with even larger hypoxic subvolumes, if a slight dose boost is allowed in combination with LET-painting. Conclusion. Our findings clearly indicate that a substantial increase in tumour control can be achieved when applying the LET-painting concept using oxygen-16 ions on hypoxic tumours, ideally with a slight dose boost.

  14. VEGF targets the tumour cell.

    PubMed

    Goel, Hira Lal; Mercurio, Arthur M

    2013-12-01

    The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches.

  15. Brain Tumours Simulating Psychiatric Disease

    PubMed Central

    Hobbs, G. E.

    1963-01-01

    Brain tumours may present with symptoms indistinguishable from psychiatric disease. The impression of most psychiatrists is that individuals suffering from brain tumour rarely appear among their patients. A priori reasoning based on evidence from neurological, neurosurgical and pathological sources suggests the contrary. The present study is a frequency analysis of cases of previously undiagnosed brain tumours admitted to either an open psychoneurotic ward or a mental hospital over a period of 15 years. The results support the impression held by psychiatrists that brain tumours are uncommon among psychiatric patients. PMID:13954870

  16. Evaluation and correlation of risk recurrence in early breast cancer assessed by Oncotype DX(®), clinicopathological markers and tumor cell dissemination in the blood and bone marrow.

    PubMed

    Aktas, Bahriye; Bankfalvi, Agnes; Heubner, Martin; Kimmig, Rainer; Kasimir-Bauer, Sabine

    2013-11-01

    The Oncotype DX(®) assay is a validated genomic test that predicts the likelihood of breast cancer recurrence, patient survival within ten years of diagnosis and the benefit of chemotherapy in early-stage, node-negative, estrogen receptor-positive breast cancer. Further markers of recurrence include disseminated tumor cells (DTCs) in the bone marrow (BM) and circulating tumor cells (CTCs) in the blood, particularly stemness-like tumor cells (slCTCs). In this study, Oncotype DX, DTCs, CTCs and slCTCs were used to evaluate the risk of recurrence in 68 patients with human epidermal growth factor receptor 2-negative, early-stage breast cancer. Formalin-fixed, paraffin-embedded tissue sections were analyzed for the expression of 16 cancer genes and 5 reference genes by Oncotype DX, yielding a recurrence score (RS). G2 tumors were evaluated for urokinase-type plasminogen activator (uPA)/plasminogen activator inhibitor type 1 (PAI1) and Ki-67. Two BM aspirates were analyzed by immunocytochemistry for DTCs using the pan-cytokeratin antibody A45-B/B3. CTCs and slCTCs in the blood were detected using the AdnaTest BreastCancer, AdnaTest EMT and the AdnaTest TumorStemCell. Oncotype DX was performed in 68 cases, yielding a low RS in 30/68 patients (44%), an intermediate RS in 29/68 patients (43%) and a high RS in 9/68 patients (13%). DTCs were detected in 19/68 patients (28%), CTCs in 13/68 patients (19%) and slCTCs in 26/68 (38%) patients. Moreover, 8/68 patients (12%) with G2 tumors were positive for uPA, 6/68 (9%) for PAI1 and 21/68 (31%) for Ki-67. Ki-67, progesterone receptor (PR) and G3 tumors were significantly correlated with RS (P<0.001; P=0.006; and P=0,002, respectively), whereas no correlation was identified between DTCs, CTCs, slCTCs and RS. Ki-67 may support therapeutic decisions in cases where Oncotype DX is not feasible. Larger patient cohorts are required to estimate the additional detection of DTCs and CTCs for the determination of risk recurrence.

  17. Malignant testicular tumours

    PubMed Central

    Vecchio, Pierre Del; Tawil, Elie; Béland, Gilles

    1974-01-01

    A series of 71 patients with malignant testicular tumours treated primarily by orchiectomy and irradiation is reviewed with respect to pathological and clinical features and modes of treatment. The three-year crude survival rate in 36 patients with seminoma was 86% and in 24 patients with carcinoma it was 41.7%. There were no survivors among patients with choriocarcinoma. Our results are comparable with those of other series. A prospective study is proposed of the value of irradiation and subsequent limited lymph node dissection following orchiectomy in cases of carcinoma of the testis. PMID:4855670

  18. Cerebral Blood Flow Alterations as Assessed by 3D ASL in Cognitive Impairment in Patients with Subcortical Vascular Cognitive Impairment: A Marker for Disease Severity

    PubMed Central

    Sun, Yawen; Cao, Wenwei; Ding, Weina; Wang, Yao; Han, Xu; Zhou, Yan; Xu, Qun; Zhang, Yong; Xu, Jianrong

    2016-01-01

    Abnormal reductions in cortical cerebral blood flow (CBF) have been identified in subcortical vascular cognitive impairment (SVCI). However, little is known about the pattern of CBF reduction in relation with the degree of cognitive impairment. CBF measured with three-dimensional (3D) Arterial Spin Labeling (ASL) perfusion magnetic resonance imaging (MRI) helps detect functional changes in subjects with SVCI. We aimed to compare CBF maps in subcortical ischemic vascular disease (SIVD) subjects with and without cognitive impairment and to detect the relationship of the regions of CBF reduction in the brain with the degree of cognitive impairment according to the z-score. A total of 53 subjects with SVCI and 23 matched SIVD subjects without cognitive impairment (controls), underwent a whole-brain 3D ASL MRI in the resting state. Regional CBF (rCBF) was compared voxel wise by using an analysis of variance design in a statistical parametric mapping program, with patient age and sex as covariates. Correlations were calculated between the rCBF value in the whole brain and the z-score in the 53 subjects with SVCI. Compared with the control subjects, SVCI group demonstrated diffuse decreased CBF in the brain. Significant positive correlations were determined in the rCBF values in the left hippocampus, left superior temporal pole gyrus, right superior frontal orbital lobe, right medial frontal orbital lobe, right middle temporal lobe, left thalamus and right insula with the z-scores in SVCI group. The noninvasively quantified resting CBF demonstrated altered CBF distributions in the SVCI brain. The deficit brain perfusions in the temporal and frontal lobe, hippocampus, thalamus and insula was related to the degree of cognitive impairment. Its relationship to cognition indicates the clinical relevance of this functional marker. Thus, our results provide further evidence for the mechanisms underlying the cognitive deficit in patients with SVCI.

  19. Cerebral Blood Flow Alterations as Assessed by 3D ASL in Cognitive Impairment in Patients with Subcortical Vascular Cognitive Impairment: A Marker for Disease Severity.

    PubMed

    Sun, Yawen; Cao, Wenwei; Ding, Weina; Wang, Yao; Han, Xu; Zhou, Yan; Xu, Qun; Zhang, Yong; Xu, Jianrong

    2016-01-01

    Abnormal reductions in cortical cerebral blood flow (CBF) have been identified in subcortical vascular cognitive impairment (SVCI). However, little is known about the pattern of CBF reduction in relation with the degree of cognitive impairment. CBF measured with three-dimensional (3D) Arterial Spin Labeling (ASL) perfusion magnetic resonance imaging (MRI) helps detect functional changes in subjects with SVCI. We aimed to compare CBF maps in subcortical ischemic vascular disease (SIVD) subjects with and without cognitive impairment and to detect the relationship of the regions of CBF reduction in the brain with the degree of cognitive impairment according to the z-score. A total of 53 subjects with SVCI and 23 matched SIVD subjects without cognitive impairment (controls), underwent a whole-brain 3D ASL MRI in the resting state. Regional CBF (rCBF) was compared voxel wise by using an analysis of variance design in a statistical parametric mapping program, with patient age and sex as covariates. Correlations were calculated between the rCBF value in the whole brain and the z-score in the 53 subjects with SVCI. Compared with the control subjects, SVCI group demonstrated diffuse decreased CBF in the brain. Significant positive correlations were determined in the rCBF values in the left hippocampus, left superior temporal pole gyrus, right superior frontal orbital lobe, right medial frontal orbital lobe, right middle temporal lobe, left thalamus and right insula with the z-scores in SVCI group. The noninvasively quantified resting CBF demonstrated altered CBF distributions in the SVCI brain. The deficit brain perfusions in the temporal and frontal lobe, hippocampus, thalamus and insula was related to the degree of cognitive impairment. Its relationship to cognition indicates the clinical relevance of this functional marker. Thus, our results provide further evidence for the mechanisms underlying the cognitive deficit in patients with SVCI. PMID:27630562

  20. Cerebral Blood Flow Alterations as Assessed by 3D ASL in Cognitive Impairment in Patients with Subcortical Vascular Cognitive Impairment: A Marker for Disease Severity

    PubMed Central

    Sun, Yawen; Cao, Wenwei; Ding, Weina; Wang, Yao; Han, Xu; Zhou, Yan; Xu, Qun; Zhang, Yong; Xu, Jianrong

    2016-01-01

    Abnormal reductions in cortical cerebral blood flow (CBF) have been identified in subcortical vascular cognitive impairment (SVCI). However, little is known about the pattern of CBF reduction in relation with the degree of cognitive impairment. CBF measured with three-dimensional (3D) Arterial Spin Labeling (ASL) perfusion magnetic resonance imaging (MRI) helps detect functional changes in subjects with SVCI. We aimed to compare CBF maps in subcortical ischemic vascular disease (SIVD) subjects with and without cognitive impairment and to detect the relationship of the regions of CBF reduction in the brain with the degree of cognitive impairment according to the z-score. A total of 53 subjects with SVCI and 23 matched SIVD subjects without cognitive impairment (controls), underwent a whole-brain 3D ASL MRI in the resting state. Regional CBF (rCBF) was compared voxel wise by using an analysis of variance design in a statistical parametric mapping program, with patient age and sex as covariates. Correlations were calculated between the rCBF value in the whole brain and the z-score in the 53 subjects with SVCI. Compared with the control subjects, SVCI group demonstrated diffuse decreased CBF in the brain. Significant positive correlations were determined in the rCBF values in the left hippocampus, left superior temporal pole gyrus, right superior frontal orbital lobe, right medial frontal orbital lobe, right middle temporal lobe, left thalamus and right insula with the z-scores in SVCI group. The noninvasively quantified resting CBF demonstrated altered CBF distributions in the SVCI brain. The deficit brain perfusions in the temporal and frontal lobe, hippocampus, thalamus and insula was related to the degree of cognitive impairment. Its relationship to cognition indicates the clinical relevance of this functional marker. Thus, our results provide further evidence for the mechanisms underlying the cognitive deficit in patients with SVCI. PMID:27630562

  1. Cerebral Blood Flow Alterations as Assessed by 3D ASL in Cognitive Impairment in Patients with Subcortical Vascular Cognitive Impairment: A Marker for Disease Severity.

    PubMed

    Sun, Yawen; Cao, Wenwei; Ding, Weina; Wang, Yao; Han, Xu; Zhou, Yan; Xu, Qun; Zhang, Yong; Xu, Jianrong

    2016-01-01

    Abnormal reductions in cortical cerebral blood flow (CBF) have been identified in subcortical vascular cognitive impairment (SVCI). However, little is known about the pattern of CBF reduction in relation with the degree of cognitive impairment. CBF measured with three-dimensional (3D) Arterial Spin Labeling (ASL) perfusion magnetic resonance imaging (MRI) helps detect functional changes in subjects with SVCI. We aimed to compare CBF maps in subcortical ischemic vascular disease (SIVD) subjects with and without cognitive impairment and to detect the relationship of the regions of CBF reduction in the brain with the degree of cognitive impairment according to the z-score. A total of 53 subjects with SVCI and 23 matched SIVD subjects without cognitive impairment (controls), underwent a whole-brain 3D ASL MRI in the resting state. Regional CBF (rCBF) was compared voxel wise by using an analysis of variance design in a statistical parametric mapping program, with patient age and sex as covariates. Correlations were calculated between the rCBF value in the whole brain and the z-score in the 53 subjects with SVCI. Compared with the control subjects, SVCI group demonstrated diffuse decreased CBF in the brain. Significant positive correlations were determined in the rCBF values in the left hippocampus, left superior temporal pole gyrus, right superior frontal orbital lobe, right medial frontal orbital lobe, right middle temporal lobe, left thalamus and right insula with the z-scores in SVCI group. The noninvasively quantified resting CBF demonstrated altered CBF distributions in the SVCI brain. The deficit brain perfusions in the temporal and frontal lobe, hippocampus, thalamus and insula was related to the degree of cognitive impairment. Its relationship to cognition indicates the clinical relevance of this functional marker. Thus, our results provide further evidence for the mechanisms underlying the cognitive deficit in patients with SVCI.

  2. Altered of apoptotic markers of both extrinsic and intrinsic pathways induced by hepatitis C virus infection in peripheral blood mononuclear cells

    PubMed Central

    2012-01-01

    Background Chronic hepatitis C (CHC) has emerged as a leading cause of cirrhosis in the U.S. and across the world. To understand the role of apoptotic pathways in hepatitis C virus (HCV) infection, we studied the mRNA and protein expression patterns of apoptosis-related genes in peripheral blood mononuclear cells (PBMC) obtained from patients with HCV infection. Methods The present study included 50 subjects which plasma samples were positive for HCV, but negative for human immunodeficiency virus (HIV) or hepatitis B virus (HBV). These cases were divided into four groups according to METAVIR, a score-based analysis which helps to interpret a liver biopsy according to the degree of inflammation and fibrosis. mRNA expression of the studied genes were analyzed by reverse transcription of quantitative polymerase chain reaction (RT-qPCR) and protein levels, analyzed by ELISA, was also conducted. HCV genotyping was also determined. Results HCV infection increased mRNA expression and protein synthesis of caspase 8 in group 1 by 3 fold and 4 fold, respectively (p < 0.05). In group 4 HCV infection increased mRNA expression and protein synthesis of caspase 9 by 2 fold and 1,5 fold, respectively (p < 0.05). Also, caspase 3 mRNA expression and protein synthesis had level augumented by HCV infection in group 1 by 4 fold and 5 fold, respectively, and in group 4 by 6 fold and 7 fold, respectively (p < 0.05). Conclusions HCV induces alteration at both genomic and protein levels of apoptosis markers involved with extrinsic and intrinsic pathways. PMID:23256595

  3. Effects of Potassium Magnesium Citrate Supplementation on 24-Hour Ambulatory Blood Pressure and Oxidative Stress Marker in Prehypertensive and Hypertensive Subjects.

    PubMed

    Vongpatanasin, Wanpen; Peri-Okonny, Poghni; Velasco, Alejandro; Arbique, Debbie; Wang, Zhongyun; Ravikumar, Priya; Adams-Huet, Beverly; Moe, Orson W; Pak, Charles Y C

    2016-09-15

    Diet rich in fruits, vegetables, and dairy products, known as the Dietary Approaches to Stop Hypertension (DASH) diet, is known to reduce blood pressure (BP) in hypertensive patients. More recently, the DASH diet was shown to reduce oxidative stress in hypertensive and nonhypertensive humans. However, the main nutritional components responsible for these beneficial effects of the DASH diet remain unknown. Because the DASH diet is rich in potassium (K), magnesium (Mg), and alkali, we performed a randomized, double-blinded, placebo-controlled study to compare effects of potassium magnesium citrate (KMgCit), potassium chloride (KCl), and potassium citrate (KCit) to allow dissociation of the three components of K, Mg, and citrate on 24-hour ambulatory BP and urinary 8-isoprostane in hypertensive and prehypertensive subjects, using a randomized crossover design. We found that KCl supplementation for 4 weeks induced a significant reduction in nighttime SBP compared with placebo (116 ± 12 vs 121 ± 15 mm Hg, respectively, p <0.01 vs placebo), whereas KMgCit and KCit had no significant effect in the same subjects (118 ± 11 and 119 ± 13 mm Hg, respectively, p >0.1 vs placebo). In contrast, urinary 8-isoprostane was significantly reduced with KMgCit powder compared with placebo (13.5 ± 5.7 vs 21.1 ± 10.5 ng/mgCr, respectively, p <0.001), whereas KCl and KCit had no effect (21.4 ± 9.1 and 18.3 ± 8.4, respectively, p >0.1 vs placebo). In conclusion, our study demonstrated differential effects of KCl and KMgCit supplementation on BP and the oxidative stress marker in prehypertensive and hypertensive subjects. Clinical significance of the antioxidative effect of KMgCit remains to be determined in future studies. PMID:27448942

  4. Peripheral blood mononuclear cells as a source to detect markers of homeostatic alterations caused by the intake of diets with an unbalanced macronutrient composition.

    PubMed

    Díaz-Rúa, Rubén; Keijer, Jaap; Caimari, Antoni; van Schothorst, Evert M; Palou, Andreu; Oliver, Paula

    2015-04-01

    Peripheral blood mononuclear cells (PBMCs) are accessible in humans, and their gene expression pattern was shown to reflect overall physiological response of the body to a specific stimulus, such as diet. We aimed to study the impact of sustained intake (4months) of diets with an unbalanced macronutrient proportion (rich in fat or protein) administered isocalorically to a balanced control diet, as physiological stressors on PBMC whole-genome gene expression in rats, to better understand the effects of these diets on metabolism and health and to identify biomarkers of nutritional imbalance. Dietary macronutrient composition (mainly increased protein content) altered PBMC gene expression, with genes involved in immune response being the most affected. Intake of a high-fat (HF) diet decreased the expression of genes related to antigen recognition/presentation, whereas the high-protein (HP) diet increased the expression of these genes and of genes involved in cytokine signaling and immune system maturation/activation. Key energy homeostasis genes (mainly related to lipid metabolism) were also affected, reflecting an adaptive response to the diets. Moreover, HF diet feeding impaired expression of genes involved in redox balance regulation. Finally, we identified a common gene expression signature of 7 genes whose expression changed in the same direction in response to the intake of both diets. These genes, individually or together, constitute a potential risk marker of diet macronutrient imbalance. In conclusion, we newly show that gene expression analysis in PBMCs allows for detection of diet-induced physiological deviations that distinguish from a diet with a proper and equilibrated macronutrient composition.

  5. An unusual case of a well-differentiated neuroendocrine tumour of the ileum with peritoneal carcinomatosis: a case report.

    PubMed

    Celotti, Andrea; Pulcini, Giuseppe; Schieppati, Mattia; Ministrini, Silvia; Berruti, Alfredo; Ronconi, Maurizio

    2015-01-01

    Neuroendocrine tumours (NETs) are a family of neoplasms that come from neuroendocrine cells and express neural markers, such as synaptophysin or chromogranin A.The current classifications of these tumours are presented by the WHO 2000 classification, based on histological parameters, and the WHO 2010 classification, based on the proliferative index, that divides the NETs into a neuroendocrine tumour of a low grade, neuroendocrine tumour of a intermediate grade and neuroendocrine carcinoma (NEC) of a high grade.We are reporting a very rare case of a G1 low-grade neuroendocrine tumour (NET) of the ileum with a peritoneal carcinomatosis.This case is challenging because the tumour expresses low proliferative index as G1 tumours, but it has an aggressive clinical behaviour such as node metastasis and peritoneal carcinomatosis.The peritoneal carcinomatosis is not actually considered by the current classifications of NETs, so it is difficult to predict the prognosis of this patient.

  6. HMGA2 expression distinguishes between different types of postpubertal testicular germ cell tumour.

    PubMed

    Kloth, Lars; Gottlieb, Andrea; Helmke, Burkhard; Wosniok, Werner; Löning, Thomas; Burchardt, Käte; Belge, Gazanfer; Günther, Kathrin; Bullerdiek, Jörn

    2015-10-01

    The group of postpubertal testicular germ cell tumours encompasses lesions with highly diverse differentiation - seminomas, embryonal carcinomas, yolk sac tumours, teratomas and choriocarcinomas. Heterogeneous differentiation is often present within individual tumours and the correct identification of the components is of clinical relevance. HMGA2 re-expression has been reported in many tumours, including testicular germ cell tumours. This is the first study investigating HMGA2 expression in a representative group of testicular germ cell tumours with the highly sensitive method of quantitative real-time PCR as well as with immunohistochemistry. The expression of HMGA2 and HPRT was measured using quantitative real-time PCR in 59 postpubertal testicular germ cell tumours. Thirty specimens contained only one type of tumour and 29 were mixed neoplasms. With the exception of choriocarcinomas, at least two pure specimens from each subgroup of testicular germ cell tumour were included. In order to validate the quantitative real-time PCR data and gather information about the localisation of the protein, additional immunohistochemical analysis with an antibody specific for HMGA2 was performed in 23 cases. Expression of HMGA2 in testicular germ cell tumours depended on the histological differentiation. Seminomas and embryonal carcinomas showed no or very little expression, whereas yolk sac tumours strongly expressed HMGA2 at the transcriptome as well as the protein level. In teratomas, the expression varied and in choriocarcinomas the expression was moderate. In part, these results contradict data from previous studies but HMGA2 seems to represent a novel marker to assist pathological subtyping of testicular germ cell tumours. The results indicate a critical role in yolk sac tumours and some forms of teratoma. PMID:27499908

  7. Oral supplementation with 25(OH)D3 versus vitamin D3: effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To test the effect of 25(OH)D3 (HyD) compared to vitamin D3 on serum 25-hydroxyvitamin D levels (25(OH)D), lower extremity function, blood pressure, and markers of innate immunity. Twenty healthy postmenopausal women with an average 25(OH)D level of 13.23.9 ng/mL (meanSD) and a mean age of 61.57.2 y...

  8. Origin of CD57+ T cells which increase at tumour sites in patients with colorectal cancer.

    PubMed Central

    Okada, T; Iiai, T; Kawachi, Y; Moroda, T; Takii, Y; Hatakeyama, K; Abo, T

    1995-01-01

    Human T cells carrying natural killer (NK) markers, CD57 or CD56 antigens, appear to be distinguishable from other T cell subsets in terms of their granular lymphocyte morphology and their numerical increase in patients with AIDS and in recipients of bone marrow transplantation. At the beginning of this study, we observed that CD57+ T cells as well as CD56+ T cells were abundant at tumour sites in many patients with colorectal cancer. Since all these findings for CD57+ T cells are quite similar to those of extrathymic T cells seen in mice, we investigated how CD57+ T cells are distributed to various immune organs in humans. They were found to be present mainly in the bone marrow and liver, but to be completely absent in the thymus. Similar to the case of extrathymic T cells in mice, they were observed to consist of double-negative CD4-8- subsets as well as single-positive subsets (preponderance of CD8+ cells), and to contain a considerable proportion of gamma delta T cells. These features are striking when compared with those of CD57- T cells, which are characterized by an abundance of CD4+ subsets and alpha beta T cells. Not only at tumour sites but also in the peripheral blood, some patients with colorectal cancer displayed elevated levels of CD57+ cells. These results suggest that CD57+ T cells may be of extrathymic origin, possibly originating in the bone marrow and liver, and may be associated with tumour immunity, similar to another extrathymic population of CD56+ T cells in humans. PMID:7554383

  9. Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres

    NASA Astrophysics Data System (ADS)

    Jain, Anjana; Betancur, Martha; Patel, Gaurangkumar D.; Valmikinathan, Chandra M.; Mukhatyar, Vivek J.; Vakharia, Ajit; Pai, S. Balakrishna; Brahma, Barunashish; MacDonald, Tobey J.; Bellamkonda, Ravi V.

    2014-03-01

    Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants.

  10. Adapting radiotherapy to hypoxic tumours

    NASA Astrophysics Data System (ADS)

    Malinen, Eirik; Søvik, Åste; Hristov, Dimitre; Bruland, Øyvind S.; Rune Olsen, Dag

    2006-10-01

    In the current work, the concepts of biologically adapted radiotherapy of hypoxic tumours in a framework encompassing functional tumour imaging, tumour control predictions, inverse treatment planning and intensity modulated radiotherapy (IMRT) were presented. Dynamic contrast enhanced magnetic resonance imaging (DCEMRI) of a spontaneous sarcoma in the nasal region of a dog was employed. The tracer concentration in the tumour was assumed related to the oxygen tension and compared to Eppendorf histograph measurements. Based on the pO2-related images derived from the MR analysis, the tumour was divided into four compartments by a segmentation procedure. DICOM structure sets for IMRT planning could be derived thereof. In order to display the possible advantages of non-uniform tumour doses, dose redistribution among the four tumour compartments was introduced. The dose redistribution was constrained by keeping the average dose to the tumour equal to a conventional target dose. The compartmental doses yielding optimum tumour control probability (TCP) were used as input in an inverse planning system, where the planning basis was the pO2-related tumour images from the MR analysis. Uniform (conventional) and non-uniform IMRT plans were scored both physically and biologically. The consequences of random and systematic errors in the compartmental images were evaluated. The normalized frequency distributions of the tracer concentration and the pO2 Eppendorf measurements were not significantly different. 28% of the tumour had, according to the MR analysis, pO2 values of less than 5 mm Hg. The optimum TCP following a non-uniform dose prescription was about four times higher than that following a uniform dose prescription. The non-uniform IMRT dose distribution resulting from the inverse planning gave a three times higher TCP than that of the uniform distribution. The TCP and the dose-based plan quality depended on IMRT parameters defined in the inverse planning procedure (fields

  11. Dural invasion by pituitary tumours.

    PubMed

    Shaffi, O M; Wrightson, P

    1975-04-23

    In 12 cases of pituitary tumour the dura mater of the sella turcica or diaphragma sellae in contact with the tumour was examined histologically. In nine cases tumour cells were found lying deep in the substance of the dura. Dura from the sella of seven subjects without pituitary disease, obtianed at autopsy, showed no inclusions of pituitary tissue. Four of the cases studied were known before death to suffer from an invasive pituitary adenoma. Of eight surviving cases operated upon in the last two years, five showed dural invasion by tumour. The present report suggests that the condition may be more frequent than expected and that with more study it may provide an index of prognosis. It also defines a requirement for the surgeon aiming to prevent recurrence of tumour after operation or to achieve a complete endocrine ablation.

  12. Methods for detection of circulating tumour cells and their clinical value in cancer patients.

    PubMed

    Mikulová, V; Kološtová, K; Zima, T

    2011-01-01

    Currently available analytical methods enable identification, detection and characterization of circulating tumour cells in the peripheral blood and disseminated tumour cells in the bone marrow of breast cancer patients. About 0.01 % of the circulating tumour cells observed in the blood are able to form metastases. Therefore, they could be used for estimation of the risk for metastatic relapse, as a diagnostic tool for patient stratification, early determination of the therapy failure, or potential risk of resistance to the given therapeutic intervention. New therapeutic molecular targets could be identified for management of cancer patients using circulating tumour cell detection. The following review summarizes introduced methods of circulating tumour cell detection and their possible application in clinics.

  13. Heavy ion tumour therapy

    NASA Astrophysics Data System (ADS)

    Scholz, M.

    2000-03-01

    Ion beams represent a promising radiotherapy modality for the treatment of deep seated tumours. Compared to conventional photon beams, in particular beams of heavier ions like e.g. carbon show several advantages which are related to their different physical and radiobiological properties: The dose increases with penetration depth and shows a sharp distal fall off at the end of the particle range, i.e., the depth dose profile is inverted compared to photon beams. They exhibit an increased biological effectiveness in particular at the end of their range and thus in the target volume. The spatial distribution of stopping particles can be monitored by means of PET-techniques making use of the small amount of radioactive projectile fragments. Ion beams were first used for medical applications in 1954 in Berkeley. Since then, several treatment facilities for tumour therapy have been established worldwide, and approximately 25 000 patients have been treated with protons and 3000 patients with heavier ions successfully. As an example, the specific advantages of the heavy ion therapy facility at GSI Darmstadt established in cooperation with the Radiological Clinics and DKFZ Heidelberg and FZ Rossendorf will be described. In contrast to most existing facilities, it is based on an active beam delivery system, using magnetic deflection of a pencil beam (raster scan) and accelerator energy variation to adjust the penetration depth. Thus, an optimal conformation of the dose to the target volume is achieved. PET-measurements allow for a quasi on-line monitoring of the 3D distribution of stopping particles and in particular of the position of the distal edge of the dose distribution. Furthermore, in the treatment planning procedure the radiobiological properties of ion beams are taken into account in great detail. In December 1997, patient treatments started at GSI, and up to now 42 patients were treated with carbon ions alone or in a mixed carbon/photon beam regime.

  14. Marker development

    SciTech Connect

    Adams, M.R.

    1987-05-01

    This report is to discuss the marker development for radioactive waste disposal sites. The markers must be designed to last 10,000 years, and place no undue burdens on the future generations. Barriers cannot be constructed that preclude human intrusion. Design specifications for surface markers will be discussed, also marker pictograms will also be covered.

  15. bcl-2 expression in pleural and extrapleural solitary fibrous tumours.

    PubMed

    Chilosi, M; Facchettti, F; Dei Tos, A P; Lestani, M; Morassi, M L; Martignoni, G; Sorio, C; Benedetti, A; Morelli, L; Doglioni, C; Barberis, M; Menestrina, F; Viale, G

    1997-04-01

    This study evaluated the immunoreactivity for bcl-2, a molecule involved in the control of programmed cell death, in cases of pleural (14) and extrapleural (2) solitary fibrous tumour (SFT), malignant mesotheliomas of different histological types, and a variety of extrapleural CD34-positive and CD34-negative spindle-cell tumours. In all SFTs, strong and diffuse immunostaining was demonstrated with anti-bel-2 antibody, sharply contrasting with the complete lack of staining observed in all mesotheliomas. The specificity of immunodetection of bcl-2 in SFT was confirmed by immunoblot analysis, showing a band consistent with the bcl-2 protein. At extrapleural locations, strong bcl-2 immunoreactivity was observed in Schwannoma (2/3 cases), synovial sarcoma (4/4 cases), and all cases of CD34-positive gastrointestinal stromal tumour (GIST; 10/10 cases). Most sarcomas were bcl-2-negative. Lack of bcl-2 expression was demonstrated in tumours which can pose problems in the differential diagnosis of SFT and can exhibit haemangiopericytoma-like features, including haemangiopericytoma (3 cases), dermatofibrosarcoma protuberans (16 cases), and deep-seated fibrous histiocytoma (3 cases). The constitutive expression of bcl-2 in SFT widens the spectrum of available markers for these tumours, providing a useful adjunct to their differential diagnosis in difficult cases at pleural and extrapleural sites, and contributing to the understanding of their histogenesis and molecular pathogenesis.

  16. Circulating tumour cells as tumour biomarkers in melanoma: detection methods and clinical relevance.

    PubMed

    Khoja, L; Lorigan, P; Dive, C; Keilholz, U; Fusi, A

    2015-01-01

    Circulating tumour cells (CTCs) are cells of solid tumour origin detectable in the peripheral blood. Their occurrence is considered a prerequisite step for establishing distant metastases. Metastatic melanoma was the first malignancy in which CTCs were detected and numerous studies have been published on CTC detection in melanoma at various stages of disease. In spite of this, there is no general consensus as to the clinical utility of CTCs in melanoma, largely due to conflicting results from heterogeneous studies and discrepancies in methods of detection between studies. In this review, we examine the possible clinical significance of CTCs in cutaneous, mucosal and ocular melanoma, focusing on detection methods and prognostic value of CTC detection.

  17. Circulating tumour cells as tumour biomarkers in melanoma: detection methods and clinical relevance.

    PubMed

    Khoja, L; Lorigan, P; Dive, C; Keilholz, U; Fusi, A

    2015-01-01

    Circulating tumour cells (CTCs) are cells of solid tumour origin detectable in the peripheral blood. Their occurrence is considered a prerequisite step for establishing distant metastases. Metastatic melanoma was the first malignancy in which CTCs were detected and numerous studies have been published on CTC detection in melanoma at various stages of disease. In spite of this, there is no general consensus as to the clinical utility of CTCs in melanoma, largely due to conflicting results from heterogeneous studies and discrepancies in methods of detection between studies. In this review, we examine the possible clinical significance of CTCs in cutaneous, mucosal and ocular melanoma, focusing on detection methods and prognostic value of CTC detection. PMID:24907634

  18. Benign cardiac tumours, malignant arrhythmias

    PubMed Central

    Myers, Kimberley A; Wong, Kenny K; Tipple, Marion; Sanatani, Shubhayan

    2010-01-01

    Four cases of pediatric cardiac tumours (PCTs) associated with ventricular arrhythmias are reported. Sudden cardiac death attributable to the tumour occurred in two children. A third child received an implantable cardioverter defibrillator and the fourth had persistent ventricular arrhythmia despite medical therapy. Most PCTs are considered benign; however, the development of malignant arrhythmias may complicate the management of these tumours in some patients. The literature regarding the arrhythmogenic potential of PCTs and the use of implantable cardioverter defibrillators in these patients is reviewed. The series highlights the deficiency of prognostic information for this cohort. PMID:20151061

  19. Malignant tumours of the duodenum.

    PubMed

    Ryska, M; Hrabal, P

    2015-12-01

    No comprehensive knowledge of duodenal tumours exists in the current literature; individual types of malignant tumours may be described within malignancies of the small bowel, sets of case reports, or individual cases. Ampullary carcinomas are the exception and they are detailed in the current WHO histological classification of tumours of digestive system. Neither national nor international literature sources provide a comprehensive review of their therapy. The situation is similar when searching for surgical procedures. Resection procedures on the duodenum should thus be performed in specialized centres with sufficient experience with hepato-pancreato-biliary surgery. PMID:26767899

  20. Systemic anti-tumour effects of local thermally sensitive liposome therapy

    PubMed Central

    Viglianti, Benjamin L.; Dewhirst, Mark W.; Boruta, R.J.; Park, Ji-Young; Landon, Chelsea; Fontanella, Andrew N.; Guo, Jing; Manzoor, Ashley; Hofmann, Christina L.; Palmer, Gregory M.

    2015-01-01

    Purpose There were two primary objectives of this study: (1) to determine whether treatment of a tumour site with systemically administered thermally sensitive liposomes and local hyperthermia (HT) for triggered release would have dual anti-tumour effect on the primary heated tumour as well as an unheated secondary tumour in a distant site, and (2) to determine the ability of non-invasive optical spectroscopy to predict treatment outcome. The optical end points studied included drug levels, metabolic markers flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide phosphate (NAD(P)H), and physiological markers (total haemoglobin (Hb) and Hb oxygen saturation) before and after treatment. Materials and methods Mice were inoculated with SKOV3 human ovarian carcinoma in both hind legs. One tumour was selected for local hyperthermia and subsequent systemic treatment. There were four treatment groups: control, DOXIL® (non-thermally sensitive liposomes containing doxorubicin), and two different thermally sensitive liposome formulations containing doxorubicin. Optical spectroscopy was performed prior to therapy, immediately after treatment, and 6, 12, and 24 h post therapy. Results Tumour growth delay was seen with DOXIL and the thermally sensitive liposomes in the tumours that were heated, similar to previous studies. Tumour growth delay was also seen in the opposing tumour in the thermally sensitive liposome-treated groups. Optical spectroscopy demonstrated correlation between growth delay, doxorubicin (DOX) levels, and changes of NAD(P)H from baseline levels. Hb and Hb saturation were not correlated with growth delay. Discussion The study demonstrated that thermally sensitive liposomes affect the primary heated tumour as well as systemic efficacy. Non-invasive optical spectroscopy methods were shown to be useful in predicting efficacy at early time points post-treatment. PMID:25164143

  1. Markers of angiogenesis and epidermal growth factor receptor signalling in patients with pancreatic and gastroesophageal junction cancer.

    PubMed

    Rohrberg, Kristoffer Staal; Skov, Birgit Guldhammer; Lassen, Ulrik; Christensen, Ib Jarle; Høyer-Hansen, Gunilla; Buysschaert, Ian; Pappot, Helle

    2010-01-01

    The epidermal growth factor receptor (EGFR) and angiogenesis are well established targets in anti-cancer therapy. Several targeted anti-cancer therapies are in clinical trials in pancreatic and gastroesophageal (GEJ) cancer. However, many patients do not respond to these targeted therapies and there is therefore an increasing need for biomarkers for selection of patients to these therapies. We investigated the expression of EGFR, vascular endothelial growth factor A (VEGF-A), and VEGF receptor 2 (VEGFR-2) in tumour tissue by immunohistochemistry, and soluble EGFR (sEGFR), soluble VEGFR-2 (sVEGFR-2), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), plasminogen activator inhibitor 1 (PAI-1), and different forms of the urokinase plasminogen activator receptor (uPAR): uPAR (I), uPAR (I-III), and uPAR (I-III)+(II-III) in plasma by quantitative immunoassays in 14 patients with pancreatic and GEJ cancer. We found expression in tumour tissue and the plasma levels to be similar to those found in patients with other tumour types. No correlation was found between the blood levels of soluble receptors and the corresponding tumour tissue levels. We conclude that these markers are present in pancreatic and GEJ cancer patients, and could be investigated further as predictive biomarkers in such patients treated with EGFR or angiogenesis targeted therapies.

  2. Immunohistochemical expression of E-cadherin and β-catenin in feline mammary tumours.

    PubMed

    Zappulli, V; De Cecco, S; Trez, D; Caliari, D; Aresu, L; Castagnaro, M

    2012-01-01

    E-cadherin and β-catenin have been studied in carcinogenesis and tumour progression and reduced membrane expression of these molecules in canine mammary tumours has been associated with a poor prognosis. The present study investigated immunohistochemically the expression of E-cadherin and β-catenin in 53 mammary tumours and 48 hyperplastic or dysplastic lesions from 57 queens. E-cadherin and β-catenin expression was membranous in all samples and there was a significant decrease in expression in malignant tumours and metastases. Cytoplasmic expression of both markers was inversely correlated to the membrane localization. β-catenin nuclear labelling was detected in one lymph node metastasis (60% positive cells) and in the basal/myoepithelial cells of 6/7 ductal tumours. No correlation with survival was found for either marker. These results confirm the role of these proteins in maintaining tissue architecture and in inhibiting cell invasiveness and potentially indicate the oncogenic potential of the Wnt/β-catenin transduction pathway in feline mammary tumours. In addition, specific independent expression of β-catenin in the nuclei of basal/myoepithelial cells might suggest that this molecule is involved in regulation of the mammary stem/pluripotent cell component. Further studies should include more cases of benign mammary neoplasia and further investigate β-catenin nuclear expression in ductal tumours. PMID:22520821

  3. Rewiring macrophages for anti-tumour immunity.

    PubMed

    Lee, Yunqin; Biswas, Subhra K

    2016-06-28

    Tumour-associated macrophages facilitate cancer progression, but whether they can be reprogrammed to elicit an anti-tumour response remains unclear. Deletion of the microRNA-processing enzyme Dicer is now shown to rewire macrophages to an anti-tumour mode, leading to an enhanced response to immunotherapy and inhibition of tumour progression. PMID:27350442

  4. CD34-negative solitary fibrous tumour resistant to imatinib.

    PubMed

    Watanabe, Koichiro; Otsu, Satoshi; Morinaga, Ryotaro; Shirao, Kuniaki

    2013-01-01

    A 75-year-old man presented to our hospital with multifocal thickening of the left pleura and left pleural effusion. Histology of the pleura showed uniform and bipolar spindle cells with moderate mitosis in a collagenised stroma. It further showed abundant blood vessels in a haemangiopericytoma-like pattern. These findings were strongly suggestive of malignant solitary fibrous tumour (SFT). The tumour showed negative staining for CD34. The loss of CD34 expression could imply histologically high-grade tumour, as reported previously. Imatinib, a multityrosine kinase inhibitor with targets, including platelet-derived growth factor receptor (PDGFR)-α and PDGFR-β, has antitumour activity in some patients with SFT. Unfortunately, imatinib treatment failed to control disease progression in the present case that expressed PDGFR-β, but not PDGFR-α. This report described a case of CD34-negative SFT resistant to imatinib.

  5. Effect of heterogeneous microvasculature distribution on drug delivery to solid tumour

    NASA Astrophysics Data System (ADS)

    Zhan, Wenbo; Gedroyc, Wladyslaw; Xu, Xiao Yun

    2014-11-01

    Most of the computational models of drug transport in vascular tumours assume a uniform distribution of blood vessels through which anti-cancer drugs are delivered. However, it is well known that solid tumours are characterized by dilated microvasculature with non-uniform diameters and irregular branching patterns. In this study, the effect of heterogeneous vasculature on drug transport and uptake is investigated by means of mathematical modelling of the key physical and biochemical processes in drug delivery. An anatomically realistic tumour model accounting for heterogeneous distribution of blood vessels is reconstructed based on magnetic resonance images of a liver tumour. Numerical simulations are performed for different drug delivery modes, including direct continuous infusion and thermosensitive liposome-mediated delivery, and the anti-cancer effectiveness is evaluated through changes in tumour cell density based on predicted intracellular concentrations. Comparisons are made between regions of different vascular density, and between the two drug delivery modes. Our numerical results show that both extra- and intra-cellular concentrations in the liver tumour are non-uniform owing to the heterogeneous distribution of tumour vasculature. Drugs accumulate faster in well-vascularized regions, where they are also cleared out more quickly, resulting in less effective tumour cell killing in these regions. Compared with direct continuous infusion, the influence of heterogeneous vasculature on anti-cancer effectiveness is more pronounced for thermosensitive liposome-mediated delivery.

  6. Leydig cell tumours in childhood.

    PubMed

    Mengel, W; Knorr, D

    1983-01-01

    Two cases of Leydig cell tumours in childhood are presented. In one case, delayed diagnosis and operation led to pubertas praecox vera whereas in the other case normal growth and development occurred after early diagnosis and operation. PMID:6878724

  7. A rare benign ovarian tumour.

    PubMed

    Palmeiro, Marta Morna; Cunha, Teresa Margarida; Loureiro, Ana Luisa; Esteves, Gonçalo

    2016-01-01

    Sclerosing stromal tumour (SST) of the ovary is an extremely rare and benign ovarian neoplasm, accounting for 6% of the sex cord stromal ovarian tumours subtype. Usually, it is found during the second and third decades of life. Patients commonly present with pelvic pain, a palpable pelvic mass or menstrual irregularity. We report a case of a 20-year-old woman reporting of mild pelvic pain, with normal laboratory data. On imaging examinations, a large right adnexal tumour was found, with features suggesting an ovarian sex cord tumour. The patient underwent right salpingo-oophorectomy, diagnosing a SST of the ovary. This paper also reviews the literature, and emphasises the typical pathological and imaging characteristics of these rare benign ovarian lesions, and their impact, in a conservative surgery. PMID:26933186

  8. Multicellular Streaming in Solid Tumours

    NASA Astrophysics Data System (ADS)

    Kas, Josef

    As early as 400 BCE, the Roman medical encyclopaedist Celsus recognized that solid tumours are stiffer than surrounding tissue. However, cancer cell lines are softer, and softer cells facilitate invasion. This paradox raises several questions: Does softness emerge from adaptation to mechanical and chemical cues in the external microenvironment, or are soft cells already present inside a primary solid tumour? If the latter, how can a more rigid tissue contain more soft cells? Here we show that in primary tumour samples from patients with mammary and cervix carcinomas, cells do exhibit a broad distribution of rigidities, with a higher fraction of softer and more contractile cells compared to normal tissue. Mechanical modelling based on patient data reveals that, surprisingly, tumours with a significant fraction of very soft cells can still remain rigid. Moreover, in tissues with the observed distributions of cell stiffnesses, softer cells spontaneously self-organize into lines or streams, possibly facilitating cancer metastasis.

  9. Tumour of the juxtaoral organ.

    PubMed

    Bénateau, H; Rigau, V; Comoz, F; Benchemam, Y; Galateau, F; Compère, J F

    2003-02-01

    The juxtaoral organ is a normal and constant structure of the oral cavity. It consists of benign epithelial nests. We describe an intraoral tumour of the juxtaoral organ in a child. The tumour was not diagnosed after clinical and radiological examinations because it is extremely rare. A histological examination revealed a tumour of the juxtaoral organ, presumed to be neuroid hamartoma. This is only the second time that a tumour of the juxtaoral organ has been described in a child. We also describe the location, the embryology, the histology and the function of this organ. This is important because this structure can be confused with carcinomas of the oral cavity when examining frozen sections.

  10. Tumour necrosis factor in synovial exudates.

    PubMed Central

    Di Giovine, F S; Nuki, G; Duff, G W

    1988-01-01

    The actions of tumour necrosis factor (TNF) include resorption of bone and cartilage, suggesting a potential role in the pathogenesis of arthritis. TNF activity was looked for in synovial fluids from 137 patients with different rheumatic diseases. Unfractionated samples were tested in the L929 bioassay. Significant TNF activity that was neutralised by monoclonal antibody to TNF alpha occurred in 13 (30%) of 44 samples. Raised TNF levels were not associated with any particular disease type or routine laboratory markers of inflammation but were related to disease duration in osteoarthritis. The finding of biologically active TNF in symptomatic joints of arthritic patients supports the idea that it may contribute to the pathogenesis of joint damage in chronic rheumatic diseases. PMID:3263088

  11. Pro-tumour activity of interleukin-22 in HPAFII human pancreatic cancer cells

    PubMed Central

    Curd, L M; Favors, S E; Gregg, R K

    2012-01-01

    Interleukin (IL)-22 is a cytokine involved in inflammatory and wound healing processes that is secreted primarily by T helper type 17 (Th17) cells. IL-22 receptor (IL-22R) expression is limited to epithelial cells of the digestive organs, respiratory tract and skin. Most tumours originating in these sites over-express IL-22R. Interestingly, there is an increase in Th17 frequency within the peripheral blood and tumour microenvironment of advanced cancer patients. Subsequently, IL-17 has been shown to display both pro-tumour and anti-tumour functions. Because many tumours lack expression of the IL-17 receptor, the effects of IL-17 on tumour growth are generated by cells that surround the tumour cells. Like IL-17, high levels of IL-22 have been detected in tumour tissues and the peripheral blood of cancer patients; however, the direct effect of IL-22 on tumour cells has remained largely unknown. In this report, we show that IL-22 stimulated production of vascular endothelial growth factor (VEGF) and the anti-apoptotic factor Bcl-XL in IL-22R-positive HPAFII human pancreatic cancer cells. Additionally, IL-22 augmented HPAFII cell production of immunosuppressive cytokines. We show further that IL-22 activation of HPAFII cells diminished T cell production of interferon (IFN)-γ through the action of IL-10. Strikingly, we show for the first time that IL-22 can fully protect cancer cells from natural killer (NK) cell-mediated cytotoxicity by stimulating tumour production of IL-10 and transforming growth factor (TGF)-β1. Our data support the idea that IL-22 may act to promote the pathogenesis of cancers rather than function in anti-tumour immunity. PMID:22471280

  12. Pituitary tumours: acromegaly.

    PubMed

    Chanson, Philippe; Salenave, Sylvie; Kamenicky, Peter; Cazabat, Laure; Young, Jacques

    2009-10-01

    Excessive production of the growth hormone (GH) is responsible for acromegaly. It is related to a pituitary GH-secreting adenoma in most cases. Prevalence is estimated 40-130 per million inhabitants. It is characterised by slowly progressive acquired somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The rheumatologic, cardiovascular, respiratory and metabolic consequences determine its prognosis. The diagnosis is confirmed by an increased serum GH concentration, unsuppressible by an oral glucose load and by detection of increased levels of insulin-like growth factor-I (IGF-I). Treatment is aimed at correcting (or preventing) tumour compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. When surgery, the usual first-line treatment, fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogues and/or radiotherapy can be used. The GH-receptor antagonist (pegvisomant) is helpful in patients who are resistant to somatostatin analogues. Thanks to this multistep therapeutic strategy, adequate hormonal disease control is achieved in most cases, allowing a normal life expectancy. PMID:19945023

  13. Insulin-tumour interrelationship in EL4 lymphoma or thymoma-bearing mice. I. Alloxan-diabetic or non-diabetic mice.

    PubMed Central

    Yam, D.; Zilberstein, A.; Fink, A.; Nir, I.

    1990-01-01

    A study has been carried out in which a comparison was made between EL4 lymphoma (assumed to be an insulin-producing secreting tumour) and thymoma (an insulin-dependent tumour). Tumour development and incidence, 3H-thymidine incorporation and insulin content in tumours, the host's food intake, blood insulin, glucose and cholesterol were determined in non-diabetic and alloxan-diabetic mice. Whereas no significant differences were observed between the diabetic and non-diabetic EL4 tumour-bearing mice, the diabetic, thymoma tumour-bearing mice showed reduced tumour growth and lower tumour incidence as compared with their non-diabetic counterparts. Insulin administration to diabetic tumour bearing mice, enhanced 3H-thymidine incorporation in the thymoma tumour cells only, and the insulin content of the EL4 tumours was found to be higher than that of the thymoma tumours. Rapid diabetes remission was observed in the diabetic, EL4 tumour-bearing mice as compared with the thymoma tumour-bearing mice. PMID:2186773

  14. Imaging of skull base tumours.

    PubMed

    Thust, Stefanie Catherine; Yousry, Tarek

    2016-01-01

    The skull base is a highly complex and difficult to access anatomical region, which constitutes a relatively common site for neoplasms. Imaging plays a central role in establishing the differential diagnosis, to determine the anatomic tumour spread and for operative planning. All skull base imaging should be performed using thin-section multiplanar imaging, whereby CT and MRI can be considered complimentary. An interdisciplinary team approach is central to improve the outcome of these challenging tumours.

  15. Graded Associations of Blood Lead and Urinary Cadmium Concentrations with Oxidative-Stress–Related Markers in the U.S. Population: Results from the Third National Health and Nutrition Examination Survey

    PubMed Central

    Lee, Duk-Hee; Lim, Ji-Sun; Song, Kyungeun; Boo, Yongchool; Jacobs, David R.

    2006-01-01

    Although oxidative stress has been proposed as a mechanism of lead and cadmium toxicity mostly based on in vitro experiments or animal studies, it is uncertain whether this mechanism is relevant in the pathogenesis of lead- or cadmium-related diseases in the general population with low environmental exposure to lead and cadmium. We examined associations of blood lead and urinary cadmium levels with oxidative stress markers of serum γ-glutamyltransferase (GGT), vitamin C, carotenoids, and vitamin E among 10,098 adult participants in the third U.S. National Health and Nutrition Examination Survey. After adjusting for race, sex, and age (plus serum total cholesterol in the case of serum carotenoids and vitamin E), blood lead and urinary cadmium levels both showed graded associations, positive with serum GGT and inverse with serum vitamin C, carotenoids, and vitamin E (p for trend < 0.01, respectively). These associations were consistently observed among most subgroups: non-Hispanic white, non-Hispanic black, men, women, all age groups, non-drinkers, drinkers, nonsmokers, ex-smokers, current smokers, and body mass index (< 25, 25–29.9, and ≥30). The strong association of blood lead and urinary cadmium levels with oxidative stress markers in this population suggests that oxidative stress should be considered in the pathogenesis of lead- and cadmium-related diseases even among people with low environmental exposure to lead and cadmium. PMID:16507456

  16. A randomized, double-blind, placebo-controlled trial of the effect of dried purple carrot on body mass, lipids, blood pressure, body composition, and inflammatory markers in overweight and obese adults: the QUENCH trial.

    PubMed

    Wright, Olivia R L; Netzel, Gabriele A; Sakzewski, Amy R

    2013-06-01

    Obesity is a significant health issue worldwide and is associated with chronic, low-grade inflammation predisposing the individual to cardiovascular disease and impaired blood glucose homeostasis. Anthocyanins and phenolic acids from purple carrots are effective at reversing inflammation and metabolic alterations in animal models, potentially through inhibition of inflammatory pathways. The effects of dried purple carrot on body mass, body composition, blood pressure, lipids, inflammatory markers, liver function tests, and appetite were investigated in 16 males (aged 53.1 ± 7.6 years and with a mean BMI of 32.8 ± 4.6 kg/m(2)) with normal lipid and inflammatory markers. There was no evidence that 118.5 mg/day of anthocyanins and 259.2 mg/day of phenolic acids for 4 weeks resulted in statistically significant changes in body mass, body composition, appetite, dietary intake, low density lipoprotein, total cholesterol, blood pressure, or C-reactive protein in these obese participants at the dose and length of intervention used in this trial. High density lipoprotein cholesterol was lower in the intervention group (p < 0.05). Aspartate amino transferase and alanine amino transferase did not change, indicating that the intervention was safe. More studies are required to establish the bioavailability and pharmacokinetic effects of purple carrot anthocyanins and phenolic acids prior to further trials of efficacy with respect to treating inflammation and metabolic alterations.

  17. MRI characteristics of midbrain tumours.

    PubMed

    Sun, B; Wang, C C; Wang, J

    1999-03-01

    We diagnosed 60 cases of midbrain tumours by MRI between 1993 to 1997. There were 39 males and 21 females, aged 2-64 years, mean 25.6 years. We found 38 patients with true intramedullary mid-brain tumours, 11 predominantly in the tectum, 20 in the tegmentum and 7 with a downward extension to the pons; there were 7 within the cerebral aqueduct. There were 22 patients with infiltrating midbrain tumours extending from adjacent structures, 11 cases each from the thalamus and pineal region. All patients received surgical treatment. Gross total resection was achieved in 42 cases, subtotal (> 75 %) resection in 18. Pathological diagnoses included 16 low-grade and 15 high-grade astrocytomas; 5 oligodendroastrocytomas; 2 ependymomas; 11 glioblastomas; and 11 pineal parenchymal or germ-cell tumours. Midbrain tumours are a heterogeneous group of neoplasms, with wide variation in clinical and MRI features, related to the site and type of tumour. MRI not only allows precise analysis of their growth pattern, but also can lead to a correct preoperative diagnosis in the majority of cases.

  18. An integrated on-chip platform for negative enrichment of tumour cells.

    PubMed

    Bhuvanendran Nair Gourikutty, Sajay; Chang, Chia-Pin; Poenar, Daniel Puiu

    2016-08-15

    The study of cancer cells in blood, popularly called circulating tumour cells (CTCs), has exceptional prospects for cancer risk assessment and analysis. Separation and enrichment of CTCs by size-based methods suffer from a well-known recovery/purity trade-off while methods targeting certain specific surface proteins can lead to risk of losing CTCs due to Epithelial to Mesenchymal Transition (EMT) and thus adversely affect the separation efficiency. A negative selection approach is thus preferred for tumour cell isolation as it does not depend on biomarker expression or defines their physical property as the separation criteria. In this work, we developed a microfluidic chip to isolate CTCs from whole blood samples without targeting any tumour specific antigen. This chip employs a two-stage cell separation: firstly, magnetophoresis depletes the white blood cells (WBCs) from a whole blood sample and is then followed by a micro-slit membrane that enables depleting the red blood cells (RBCs) and retaining only the tumour cells. By creating strong magnetic field gradients along with customized antibody complexes to target WBCs, we are able to remove >99.9% of WBCs from 1:1 diluted blood at a sample processing rate of 500μL/min. This approach achieves an average of >80% recovery of spiked tumour cells from 2mL of whole blood in a total assay processing time of 50min without multiple processing steps. PMID:27344255

  19. An integrated on-chip platform for negative enrichment of tumour cells.

    PubMed

    Bhuvanendran Nair Gourikutty, Sajay; Chang, Chia-Pin; Poenar, Daniel Puiu

    2016-08-15

    The study of cancer cells in blood, popularly called circulating tumour cells (CTCs), has exceptional prospects for cancer risk assessment and analysis. Separation and enrichment of CTCs by size-based methods suffer from a well-known recovery/purity trade-off while methods targeting certain specific surface proteins can lead to risk of losing CTCs due to Epithelial to Mesenchymal Transition (EMT) and thus adversely affect the separation efficiency. A negative selection approach is thus preferred for tumour cell isolation as it does not depend on biomarker expression or defines their physical property as the separation criteria. In this work, we developed a microfluidic chip to isolate CTCs from whole blood samples without targeting any tumour specific antigen. This chip employs a two-stage cell separation: firstly, magnetophoresis depletes the white blood cells (WBCs) from a whole blood sample and is then followed by a micro-slit membrane that enables depleting the red blood cells (RBCs) and retaining only the tumour cells. By creating strong magnetic field gradients along with customized antibody complexes to target WBCs, we are able to remove >99.9% of WBCs from 1:1 diluted blood at a sample processing rate of 500μL/min. This approach achieves an average of >80% recovery of spiked tumour cells from 2mL of whole blood in a total assay processing time of 50min without multiple processing steps.

  20. Bone Markers

    MedlinePlus

    ... Alkaline Phosphatase; Osteocalcin; P1NP; Procollagen Type 1 N-Terminal Propeptide Formal name: Biochemical Markers of Bone Remodeling ... tests for evaluating bone turnover: C-telopeptide (C-terminal telopeptide of type 1 collagen (CTx)) – a marker ...

  1. Deciphering PDT-induced inflammatory responses using real-time FDG-PET in a mouse tumour model.

    PubMed

    Cauchon, Nicole; Hasséssian, Haroutioun M; Turcotte, Eric; Lecomte, Roger; van Lier, Johan E

    2014-10-01

    Dynamic positron emission tomography (PET), combined with constant infusion of 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG), enables real-time monitoring of transient metabolic changes in vivo, which can serve to understand the underlying physiology. Here we investigated characteristic changes in the tumour FDG-uptake profiles in relation to acute localized inflammatory responses induced by photodynamic therapy (PDT). Dynamic PET imaging with constant FDG infusion was used with EMT-6 tumour bearing mice. FDG time-activity uptake curves were measured simultaneously, in treated and reference tumours, for 3 hours, before, during and after PDT light treatment. Inflammation was studied when evoked, either by PDT using a trisulfonated porphyrazine photosensitizer, or lipopolysaccharide (LPS), and inhibited using indomethacin. The distinct transient patterns, characterized by drops and subsequent recovery of tumour FDG uptake rates, were also analysed using immunohistochemical markers for apoptosis, necrosis, and inflammation. Typical profiles for tumour FDG-uptake, consisted of a drop during PDT, followed by a gradual recovery period. Tumours treated with LPS, but not with light, showed a continuous increase in FDG-uptake during the 3 h experimental period. Treatment with indomethacin, inhibited the rise in FDG-uptake observed with either LPS or PDT. Tumour FDG-uptake profiles correlated with necrosis markers during PDT, and inflammatory response markers post-PDT, but not with an apoptosis marker at any time during or after PDT. Dynamic FDG-PET imaging combined with indomethacin reveals that, the drop in the tumour FDG-uptake rate during the PDT illumination phase reflects vascular collapse and necrosis, while the increased tumour FDG-uptake rate immediately post-illumination involves an acute localized inflammatory response. Dynamic FDG infusion and PET imaging, combined with the use of selective inhibitors, provides unique insight for deciphering the complex underlying

  2. Particular aspects in the cytogenetics and molecular biology of salivary gland tumours – current review of reports

    PubMed Central

    Osuch-Wójcikiewicz, Ewa

    2016-01-01

    Salivary gland tumours are a group of lesions whose heterogeneity of biological and pathological features is widely reflected in the molecular aspect. This is demonstrated by an increasing number of studies in the field of genetics of these tumours. The aim of this study was to collect the most significant scientific reports on the cytogenetic and molecular data concerning these tumours, which might facilitate the identification of potential biomarkers and therapeutic targets. The analysis covered 71 papers included in the PubMed database. We focused on the most common tumours, such as pleomorphic adenoma, Warthin tumour, mucoepidermoid carcinoma, and others. The aim of this study is to present current knowledge about widely explored genotypic alterations (such as PLAG1 gene in pleomorphic adenoma or MECT1 gene in mucoepidermoid carcinoma), and also about rare markers, like Mena or SOX10 protein, which might also be associated with tumourigenesis and carcinogenesis of these tumours. PMID:27688723

  3. Particular aspects in the cytogenetics and molecular biology of salivary gland tumours – current review of reports

    PubMed Central

    Osuch-Wójcikiewicz, Ewa

    2016-01-01

    Salivary gland tumours are a group of lesions whose heterogeneity of biological and pathological features is widely reflected in the molecular aspect. This is demonstrated by an increasing number of studies in the field of genetics of these tumours. The aim of this study was to collect the most significant scientific reports on the cytogenetic and molecular data concerning these tumours, which might facilitate the identification of potential biomarkers and therapeutic targets. The analysis covered 71 papers included in the PubMed database. We focused on the most common tumours, such as pleomorphic adenoma, Warthin tumour, mucoepidermoid carcinoma, and others. The aim of this study is to present current knowledge about widely explored genotypic alterations (such as PLAG1 gene in pleomorphic adenoma or MECT1 gene in mucoepidermoid carcinoma), and also about rare markers, like Mena or SOX10 protein, which might also be associated with tumourigenesis and carcinogenesis of these tumours.

  4. Loss of heterozygosity at chromosome 1p in different solid human tumours: association with survival

    PubMed Central

    Ragnarsson, G; Eiriksdottir, G; Johannsdottir, J Th; Jonasson, J G; Egilsson, V; Ingvarsson, S

    1999-01-01

    The distal half of chromosome 1p was analysed with 15 polymorphic microsatellite markers in 683 human solid tumours at different locations. Loss of heterozygosity (LOH) was observed at least at one site in 369 cases or 54% of the tumours. LOHs detected ranged from 30–64%, depending on tumour location. The major results regarding LOH at different tumour locations were as follows: stomach, 20/38 (53%); colon and rectum, 60/109 (55%); lung, 38/63 (60%); breast, 145/238 (61%); endometrium, 18/25 (72%); ovary, 17/31 (55%); testis, 11/30 (37%); kidney, 22/73 (30%); thyroid, 4/14 (29%); and sarcomas, 9/14 (64%). High percentages of LOH were seen in the 1p36.3, 1p36.1, 1p35–p34.3, 1p32 and 1p31 regions, suggesting the presence of tumour-suppressor genes. All these regions on chromosome 1p show high LOH in more than one tumour type. However, distinct patterns of LOH were detected at different tumour locations. There was a significant separation of survival curves, with and without LOH at chromosome 1p, in the breast cancer patients. Multivariate analysis showed that LOH at 1p in breast tumours is a better indicator for prognosis than the other variables tested in our model, including nodal metastasis. © 1999 Cancer Research Campaign PMID:10188892

  5. Pharmacological inhibition of caspase-8 limits lung tumour outgrowth

    PubMed Central

    Terlizzi, Michela; Di Crescenzo, Vincenzo Giuseppe; Perillo, Giuseppe; Galderisi, Antonio; Pinto, Aldo; Sorrentino, Rosalinda

    2015-01-01

    Background and Purpose Lung cancer is one of the leading causes of cancer death worldwide. Despite advances in therapy, conventional therapy is still the main treatment and has a high risk of chemotherapy resistance. Caspase-8 is involved in cell death and is a recognized marker for poor patient prognosis. Experimental Approach To elucidate the role of caspase-8 in lung carcinoma, we used human samples of non-small cell lung cancer (NSCLC) and a mouse model of carcinogen-induced lung cancer. Key Results Healthy and cancerous NSCLC samples had similar levels of the active form of caspase-8. Similarly, lung tumour-bearing mice had high levels of the active form of caspase-8. Pharmacological inhibition of caspase-8 by z-IETD-FMK robustly reduced tumour outgrowth and this was closely associated with a reduction in the release of pro-inflammatory cytokines, IL-6, TNF-α, IL-18, IL-1α, IL-33, but not IL-1β. Furthermore, inhibition of caspase-8 reduced the recruitment of innate suppressive cells, such as myeloid-derived suppressor cells, but not of regulatory T cells to lungs of tumour-bearing mice. However, despite the well-known role of caspase-8 in cell death, the apoptotic cascade (caspase-3, caspase-9 and Bcl-2 dependent) was not active in lungs of z-IETD-treated tumour-bearing mice, but instead higher levels of the short segment of c-FLIP (c-FLIPs) were detected. Similarly, human healthy lung samples had higher levels of c-FLIPs than cancerous samples. Conclusions and Implications Our data suggest that caspase-8 is an important orchestrator of cancer-associated inflammation and the presence of short segment of c-FLIP determines whether caspase-8 induces tumour proliferation or tumour arrest/regression in the lung. PMID:25917370

  6. Vascular marker expression during the development of various types of gynaecological malignancy.

    PubMed

    Urban, Peter; Rabajdova, Miroslava Bilecova; Varga, Jan; Kruzliak, Peter; Fialkovicova, Viera; Durovcova, Eva; Marekova, Maria

    2014-11-01

    Clinical diagnosis of gynaecological malignancies is usually successful in the advanced stages of the tumour, and this has a major impact on the success of therapy. Therefore, in the last few years, cancer research has tried to identify and characterise new biochemical and molecular markers needed as predictive indicators for the diagnosis of cancer. Our aim has been to search the molecular changes in gene expression of death receptor 6, glycoprotein M6B (Gpm6B) and genes associated with tumours of the female genital system. After isolation of messenger RNA (mRNA), transcription of mRNA into the cDNA was performed. The quantification of gene expression changes was detected using the reverse transcription polymerase chain reaction (RT-PCR) method. Analysis at the protein level was performed using the Western blot method. In both methods, we used actin as a housekeeping gene for normalisation. Numerical quantification of changes in expression and in the level of the specific proteins was evaluated using the Data Syngene program. Significant changes in the levels of protein and mRNA expression were detected, mainly in the death receptor 6 (Dr6) gene of patients suffering from cancer of the corpus and cervix uteri and ovarian cancer, which also corresponded with the level of protein Dr6. At the level of transcription, a significant increase in the expression levels of mRNA for the Gpm6B gene was detected, which led to an increase in corresponding protein in the peripheral blood of patients with gynaecological tumours against the healthy control group. This article could help to find an adequate marker for clinical application that will enable more sensitive detection of the early stages of gynaecological malignancies from the peripheral blood of patients.

  7. Therapy-induced tumour secretomes promote resistance and tumour progression

    PubMed Central

    Obenauf, Anna C.; Zou, Yilong; Ji, Andrew L.; Vanharanta, Sakari; Shu, Weiping; Shi, Hubing; Kong, Xiangju; Bosenberg, Marcus C.; Wiesner, Thomas; Rosen, Neal; Lo, Roger S.; Massagué, Joan

    2015-01-01

    Drug resistance invariably limits the clinical efficacy of targeted therapy with kinase inhibitors against cancer1,2. Here we show that targeted therapy with BRAF, ALK, or EGFR kinase inhibitors induces a complex network of secreted signals in drug-stressed melanoma and lung adenocarcinoma cells. This therapy-induced secretome (TIS) stimulates the outgrowth, dissemination, and metastasis of drug-resistant cancer cell clones and supports the survival of drug-sensitive cancer cells, contributing to incomplete tumour regression. The vemurafenib reactive secretome in melanoma is driven by down-regulation of the transcription factor FRA1. In situ transcriptome analysis of drug-resistant melanoma cells responding to the regressing tumour microenvironment revealed hyperactivation of multiple signalling pathways, most prominently the AKT pathway. Dual inhibition of RAF and PI3K/AKT/mTOR pathways blunted the outgrowth of the drug-resistant cell population in BRAF mutant melanoma tumours, suggesting this combination therapy as a strategy against tumour relapse. Thus, therapeutic inhibition of oncogenic drivers induces vast secretome changes in drug-sensitive cancer cells, paradoxically establishing a tumour microenvironment that supports the expansion of drug-resistant clones, but is susceptible to combination therapy. PMID:25807485

  8. Intralymphatic mRNA vaccine induces CD8 T-cell responses that inhibit the growth of mucosally located tumours

    PubMed Central

    Bialkowski, Lukasz; van Weijnen, Alexia; Van der Jeught, Kevin; Renmans, Dries; Daszkiewicz, Lidia; Heirman, Carlo; Stangé, Geert; Breckpot, Karine; Aerts, Joeri L.; Thielemans, Kris

    2016-01-01

    The lack of appropriate mouse models is likely one of the reasons of a limited translational success rate of therapeutic vaccines against cervical cancer, as rapidly growing ectopic tumours are commonly used for preclinical studies. In this work, we demonstrate that the tumour microenvironment of TC-1 tumours differs significantly depending on the anatomical location of tumour lesions (i.e. subcutaneously, in the lungs and in the genital tract). Our data demonstrate that E7-TriMix mRNA vaccine-induced CD8+ T lymphocytes migrate into the tumour nest and control tumour growth, although they do not express mucosa-associated markers such as CD103 or CD49a. We additionally show that despite the presence of the antigen-specific T cells in the tumour lesions, the therapeutic outcomes in the genital tract model remain limited. Here, we report that such a hostile tumour microenvironment can be reversed by cisplatin treatment, leading to a complete regression of clinically relevant tumours when combined with mRNA immunization. We thereby demonstrate the necessity of utilizing clinically relevant models for preclinical evaluation of anticancer therapies and the importance of a simultaneous combination of anticancer immune response induction with targeting of tumour environment. PMID:26931556

  9. Detecting alcohol abuse: traditional blood alcohol markers compared to ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) measurement in hair.

    PubMed

    Hastedt, Martin; Büchner, Mara; Rothe, Michael; Gapert, René; Herre, Sieglinde; Krumbiegel, Franziska; Tsokos, Michael; Kienast, Thorsten; Heinz, Andreas; Hartwig, Sven

    2013-12-01

    Alcohol abuse is a common problem in society; however, the technical capabilities of evaluating individual alcohol consumption using objective biomarkers are rather limited at present. In recent years research has focused on alcohol markers using hair analysis but data on performance and reliable cut-off values are still lacking. In this study 169 candidates were tested to compare traditional biomarkers, such as carbohydrate-deficient-transferrin (CDT), gamma glutamyl transferase (GGT), aspartate amino transferase, alanine amino transferase and the mean corpuscular volume of the erythrocytes, with alcohol markers detectable in hair such as ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs). This study revealed that EtG, GGT and CDT showed the best results, demonstrating areas under the curve calculated from receiver operating characteristics of 0.941, 0.943 and 0.899 respectively. The lowest false-negative and false-positive rates were obtained by using a combined interpretation system for hair EtG and FAEEs. All markers demonstrated only low to moderate correlations. Optimum cut-off values for differentiation between social and chronic excessive drinking calculated for hair EtG and FAEEs were 28 pg/mg and 0.675 ng/mg, respectively. The critical values published in the "Consensus on Alcohol Markers 2012" by the Society of Hair Testing were confirmed.

  10. Dietary zinc deficiency affects blood linoleic acid: dihomo-gamma-linolenic acid (LA:DGLA) ratio; a reactive physiological marker of zinc status in vivo (Gallus gallus)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary Zinc (Zn) deficiency affects approximately 30% of the world’s population. Zinc is a vital micronutrient and is important for the body’s ability to function. To date, accurate biological markers of the Zn subject’s status are still needed. The aim of this study was to evaluate the chicken mod...

  11. Multiple tumours in survival estimates.

    PubMed

    Rosso, Stefano; De Angelis, Roberta; Ciccolallo, Laura; Carrani, Eugenio; Soerjomataram, Isabelle; Grande, Enrico; Zigon, Giulia; Brenner, Hermann

    2009-04-01

    In international comparisons of cancer registry based survival it is common practice to restrict the analysis to first primary tumours and exclude multiple cancers. The probability of correctly detecting subsequent cancers depends on the registry's running time, which results in different proportions of excluded patients and may lead to biased comparisons. We evaluated the impact on the age-standardised relative survival estimates of also including multiple primary tumours. Data from 2,919,023 malignant cancers from 69 European cancer registries participating in the EUROCARE-4 collaborative study were used. A total of 183,683 multiple primary tumours were found, with an overall proportion of 6.3% over all the considered cancers, ranging from 0.4% (Naples, Italy) to 12.9% (Iceland). The proportion of multiple tumours varied greatly by type of tumour, being higher for those with high incidence and long survival (breast, prostate and colon-rectum). Five-year relative survival was lower when including patients with multiple cancers. For all cancers combined the average difference was -0.4 percentage points in women and -0.7 percentage points in men, and was greater for older registries. Inclusion of multiple tumours led to lower survival in 44 out of 45 cancer sites analysed, with the greatest differences found for larynx (-1.9%), oropharynx (-1.5%), and penis (-1.3%). Including multiple primary tumours in survival estimates for international comparison is advisable because it reduces the bias due to different observation periods, age, registration quality and completeness of registration. The general effect of inclusion is to reduce survival estimates by a variable amount depending on the proportion of multiple primaries and cancer site.

  12. Assessment of candidate immunohistochemical prognostic markers of meningioma recurrence.

    PubMed

    Csonka, T; Murnyák, B; Szepesi, R; Bencze, J; Bognár, L; Klekner, A; Hortobágyi, T

    2016-01-01

    Although tumour recurrence is an important and not infrequent event in meningiomas, predictive immunohistochemical markers have not been identified yet. The aim of this study was to address this clinically relevant problem by systematic retrospective analysis of surgically completely resected meningiomas with and without recurrence, including tumour samples from patients who underwent repeat surgeries. Three established immunohistochemical markers of routine pathological meningioma work-up have been assessed: the proliferative marker Ki-67 (clone Mib1), the tumour suppressor gene p53 and progesterone receptor (PR). All these proteins correlate with the tumour WHO grade, however the predictive value regarding recurrence and progression in tumour grade is unknown. One hundred and fourteen surgical specimens of 70 meningioma patients (16 male and 54 female) in a 16 years' interval have been studied. All tumours had apparently complete surgical removal. On Mib1, PR and p53 immunostained sections, the percentage of labelled tumour cells, the staining intensity and the multiplied values of these parameters (the histoscore) was calculated. Results were statistically correlated with tumour WHO grade, (sub)type, recurrence and progression in WHO grade at subsequent biopsies. Our results confirmed previous findings that the WHO grade is directly proportional to Mib1 and p53 and is inversely proportional to the PR immunostain. We have demonstrated that Mib1 and p53 have a significant correlation with and predictive value of relapse/recurrence irrespective of the histological subtype of the same WHO grade. As a quantitative marker, Mib1 has the best correlation with a percentage of labelled cells, whereas p53 with intensity and histoscore. In conclusion, the immunohistochemical panel of PR, p53, Mib1 in parallel with applying standard diagnostic criteria based on H and E stained sections is sufficient and reliable to predict meningioma recurrence in surgically completely

  13. Platelet-cytokine Complex Suppresses Tumour Growth by Exploiting Intratumoural Thrombin-dependent Platelet Aggregation

    PubMed Central

    Li, Yu-Tung; Nishikawa, Tomoyuki; Kaneda, Yasufumi

    2016-01-01

    Tumours constitute unique microenvironments where various blood cells and factors are exposed as a result of leaky vasculature. In the present study, we report that thrombin enrichment in B16F10 melanoma led to platelet aggregation, and this property was exploited to administer an anticancer cytokine, interferon-gamma induced protein 10 (IP10), through the formation of a platelet-IP10 complex. When intravenously infused, the complex reached platelet microaggregates in the tumour. The responses induced by the complex were solely immune-mediated, and tumour cytotoxicity was not observed. The complex suppressed the growth of mouse melanoma in vivo, while both platelets and the complex suppressed the accumulation of FoxP3+ regulatory T cells in the tumour. These results demonstrated that thrombin-dependent platelet aggregation in B16F10 tumours defines platelets as a vector to deliver anticancer cytokines and provide specific treatment benefits. PMID:27117228

  14. A potent oral P-selectin blocking agent improves microcirculatory blood flow and a marker of endothelial cell injury in patients with sickle cell disease.

    PubMed

    Kutlar, Abdullah; Ataga, Kenneth I; McMahon, Lillian; Howard, Joanna; Galacteros, Frederic; Hagar, Ward; Vichinsky, Elliott; Cheung, Anthony T W; Matsui, Neil; Embury, Stephen H

    2012-05-01

    Abnormal blood flow accounts for most of the clinical morbidity of sickle cell disease (SCD) [1,2]. Most notably, occlusion of flow in the microvasculature causes the acute pain crises [3] that are the commonest cause for patients with SCD to seek medical attention [4] and major determinants of their quality of life [5]. Based on evidence that endothelial P-selectin is central to the abnormal blood flow in SCD we provide results from four of our studies that are germane to microvascular blood flow in SCD. A proof-of-principle study established that doses of heparin lower than what are used for anticoagulation but sufficient to block P-selectin improved microvascular blood flow inpatients with SCD. An in vitro study showed that Pentosan Polysulfate Sodium (PPS) had greater P-selectin blocking activity than heparin. A Phase I clinical study demonstrated that a single oral dose of PPS increased microvascular blood flow in patients with SCD. A Phase II clinical study that was not completed documented that daily oral doses of PPS administered for 8 weeks lowered plasma levels of sVCAM-1 and tended to improve microvascular blood flow in patients with SCD. These data support the concept that P-selectin on the microvascular endothelium is critical to both acute vascular occlusion and chronically impaired microvascular blood flow in SCD. They also demonstrate that oral PPS is beneficial to microvascular sickle cell blood flow and has potential as an efficacious agent for long-term prophylactic therapy of SCD.

  15. Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment.

    PubMed

    Obonai, Toshifumi; Fuchigami, Hirobumi; Furuya, Fumiaki; Kozuka, Naoyuki; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2016-01-01

    The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma.

  16. Tenascin in salivary gland tumours.

    PubMed

    Soini, Y; Pääkkö, P; Virtanen, I; Lehto, V P

    1992-01-01

    The distribution of tenascin immunoreactivity was analysed in salivary gland tissue and in various benign and malignant tumours of the salivary gland. In the non-neoplastic tissue, tenascin was seen in the areas of basement membranes of the ductal epithelium. No immunoreactivity could be observed in the serous or mucous glands. In pleomorphic adenomas, tenascin immunoreactivity could be seen in the stromal compartment. It was more pronounced in the dense stromal areas and chondroid elements than in the myxoid area. In Warthin's tumours, strong tenascin immunoreactivity could be observed in the basement membrane zone of the epithelial component. In the lymphatic component, faint reticular staining could be seen. In adenoid cystic carcinomas, acinic cell tumours and mucoepidermoid carcinomas, tenascin showed a linear stromal distribution. No intracytoplasmic immunoreactivity could be seen in any of the cases. The widespread tenascin positivity in salivary gland tumours suggests that tenascin may play a role in the induction and progression of salivary gland tumours, presumably by interfering with the normal parenchymal-mesenchymal interaction.

  17. Objective assessment of blood and lymphatic vessel invasion and association with macrophage infiltration in cutaneous melanoma.

    PubMed

    Storr, Sarah J; Safuan, Sabreena; Mitra, Angana; Elliott, Faye; Walker, Christopher; Vasko, Mark J; Ho, Bernard; Cook, Martin; Mohammed, Rabab A A; Patel, Poulam M; Ellis, Ian O; Newton-Bishop, Julia A; Martin, Stewart G

    2012-04-01

    The aims of this study were to investigate the role of vascular invasion (blood and lymphatic), vessel density and the presence of tumour-associated macrophages as prognostic markers in 202 cutaneous melanoma patients. Sections of primary melanoma were stained with lymphatic-specific antibody D2-40 to assess lymphatic vessel invasion and density in intratumoural and peritumoural areas; an antibody against endothelial marker CD34 was used to determine blood vessel invasion and density, and an antibody against CD68 was used to determine macrophage counts. Immunohistochemically determined vascular invasion (combined blood and lymphatic) was compared with that determined using haematoxylin and eosin (H&E) staining. The use of immunohistochemistry increased detection of vascular invasion from 8-30% of patients, and histological exam of H&E-stained tissue was associated with a false positive rate of 64%. Lymphatic vessel invasion occurred at a much higher frequency than blood vessel invasion (27 and 4% of patients, respectively). Although immunohistochemically detected vessel invasion was significantly associated with histological markers of adverse prognosis, such as increased Breslow thickness, ulceration and mitotic rate (all P<0.001), no associations with relapse-free or overall survival were observed. High macrophage counts were significantly associated with markers of aggressive disease, such as Breslow thickness, ulceration and mitotic rate (P<0.001, P<0.001, P=0.005, respectively), and lymphatic vessel invasion and high microvessel density (P=0.002 and P=0.003, respectively). These results suggest that vascular invasion is more accurately detected using immunohistochemistry and occurs predominantly via lymphatic vessels. The association of vessel characteristics with histological characteristics of the primary melanoma provides evidence for their biological importance in melanoma, but that they were not associated with clinical outcome attests to the value of

  18. Tuberculosis simulating brain tumour.

    PubMed

    Chaudhry, U R; Farooq, M; Rauf, F; Bhatti, S K

    2011-06-30

    The purpose of the study is to highlight the varied presentation of tuberculosis (TB) simulating a brain tumour. Headache and seizures are becoming frequent presenting complaints without any history of tuberculosis. The study comprises 1200 patients of both sexes with ages ranging from ten to sixty years. CT scan and MRI brain control with and without contrast medium were the investigations performed in these cases. In some patients Electroencephalography (EEG), cerebral angiography (DSA) and spectroscopy were also performed. The final diagnosis of tuberculosis was made on the basis of craniotomy, stereotactic and burr hole biopsies with histopathology in most of the cases. Forty per cent of the patients were followed up for eight months. They were put on anti-tuberculosis treatment with symptomatic and anti-epileptic drugs. The incidence was 544 and 757 per 100,000 in Africa and Indo Pakistan respectively. The male to female ratio was 1:1. Tuberculosis, especially with CNS involvement, is not only common in immunosuppressed patients in our setting, but TB has been and remains an important public health problem. TB may involve the CNS either as meningitis or as parenchymal granulomas or abscesses. Patients with brain TB usually present with fever, multiple cranial nerve involvement and occasional behavioural changes. CSF findings remain non specific in most cases. The most common sites are the cerebral hemisphere and basal ganglion in adults and the cerebellum in children. Tuberculosis has unique findings on brain CT and MRI. Cortical and subcortical locations are typical whereas the brain stem is a less common site. Tuberculosis lesions are usually solitary but multiple in 10% to 35% of cases. In spite of all these facts some cases of brain TB still need aggressive neurointervention to reach the final diagnosis of brain TB. Tuberculosis in the CNS may manifest in many different ways. So one should always include tuberculosis in the differential diagnosis in the

  19. Evidence that platelet and tumour heparanases are similar enzymes.

    PubMed Central

    Freeman, C; Browne, A M; Parish, C R

    1999-01-01

    In order to enter tissues, blood-borne metastatic tumour cells and leucocytes need to extravasate through the vascular basal lamina (BL), a process which involves a battery of degradative enzymes. A key degradative enzyme is the endoglycosidase heparanase, which cleaves heparan sulphate (HS), an important structural component of the vascular BL. Previously, tumour-derived heparanase activity (which has been shown to be related to the metastatic potential of murine and human melanoma cell lines) was reported to cleave HS and be inhibited by heparin, as distinct from human platelet heparanase, which cleaved both substrates [Nakajima, Irimura and Nicolson (1988) J. Cell Biochem. 36, 157-167]. We recently reported the purification of human platelet heparanase and showed that the enzyme is a 50-kDa endoglucuronidase [Freeman and Parish (1998) Biochem. J. 330, 1341-1350]. We now report the purification and characterization of heparanase activity from highly metastatic rat 13762 MAT mammary adenocarcinoma and human HCT 116 colonic carcinoma cells and from rat liver using essentially the same procedure that was reported for purification of the human platelet enzyme. The rat 13762 MAT tumour enzyme, which has a native M(r) of 45 kDa when analysed by gel-filtration chromatography and by SDS/PAGE, was observed to be an endoglucuronidase that degraded heparin and HS to fragments of the same sizes as the human platelet enzyme does. N-deglycosylation of both the human platelet and rat 13762 MAT tumour enzymes gave, in each case, a 41-kDa band by SDS/PAGE analysis, demonstrating that the observed difference in M(r) between the platelet and tumour enzymes may have been due largely to differences in the relative amounts of N-glycosylation. Two peptides were isolated following Endoproteinase Lys-C digestion of both the human platelet and rat 13762 MAT tumour heparanases and were shown to be highly similar. Both the rat liver and human colonic carcinoma heparanases also degraded both

  20. HPV vaccine stimulates cytotoxic activity of killer dendritic cells and natural killer cells against HPV-positive tumour cells

    PubMed Central

    Van den Bergh, Johan M J; Guerti, Khadija; Willemen, Yannick; Lion, Eva; Cools, Nathalie; Goossens, Herman; Vorsters, Alex; Van Tendeloo, Viggo F I; Anguille, Sébastien; Van Damme, Pierre; Smits, Evelien L J M

    2014-01-01

    Cervarix™ is approved as a preventive vaccine against infection with the human papillomavirus (HPV) strains 16 and 18, which are causally related to the development of cervical cancer. We are the first to investigate in vitro the effects of this HPV vaccine on interleukin (IL)-15 dendritic cells (DC) as proxy of a naturally occurring subset of blood DC, and natural killer (NK) cells, two innate immune cell types that play an important role in antitumour immunity. Our results show that exposure of IL-15 DC to the HPV vaccine results in increased expression of phenotypic maturation markers, pro-inflammatory cytokine production and cytotoxic activity against HPV-positive tumour cells. These effects are mediated by the vaccine adjuvant, partly through Toll-like receptor 4 activation. Next, we demonstrate that vaccine-exposed IL-15 DC in turn induce phenotypic activation of NK cells, resulting in a synergistic cytotoxic action against HPV-infected tumour cells. Our study thus identifies a novel mode of action of the HPV vaccine in boosting innate immunity, including killing of HPV-infected cells by DC and NK cells. PMID:24979331

  1. Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study

    PubMed Central

    Wahl, Simone; Elliott, Hannah R; Rota, Federica; Scott, William R; Zhang, Weihua; Tan, Sian-Tsung; Campanella, Gianluca; Chadeau-Hyam, Marc; Yengo, Loic; Richmond, Rebecca C; Adamowicz-Brice, Martyna; Afzal, Uzma; Bozaoglu, Kiymet; Mok, Zuan Yu; Ng, Hong Kiat; Pattou, François; Prokisch, Holger; Rozario, Michelle Ann; Tarantini, Letizia; Abbott, James; Ala-Korpela, Mika; Albetti, Benedetta; Ammerpohl, Ole; Bertazzi, Pier Alberto; Blancher, Christine; Caiazzo, Robert; Danesh, John; Gaunt, Tom R; de Lusignan, Simon; Gieger, Christian; Illig, Thomas; Jha, Sujeet; Jones, Simon; Jowett, Jeremy; Kangas, Antti J; Kasturiratne, Anuradhani; Kato, Norihiro; Kotea, Navaratnam; Kowlessur, Sudhir; Pitkäniemi, Janne; Punjabi, Prakash; Saleheen, Danish; Schafmayer, Clemens; Soininen, Pasi; Tai, E-Shyong; Thorand, Barbara; Tuomilehto, Jaakko; Wickremasinghe, Ananda Rajitha; Kyrtopoulos, Soterios A; Aitman, Timothy J; Herder, Christian; Hampe, Jochen; Cauchi, Stéphane; Relton, Caroline L; Froguel, Philippe; Soong, Richie; Vineis, Paolo

    2016-01-01

    Summary Background Indian Asians, who make up a quarter of the world’s population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes. Methods We did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p<1 × 10−7. We compared methylation levels between Indian Asian and European controls without type 2 diabetes at baseline to estimate the potential contribution of DNA methylation to increased risk of future type 2 diabetes incidence among Indian Asians. Findings 1608 (11·9%) of 13 535 Indian Asians and 306 (4·3%) of 7066 Europeans developed type 2 diabetes over a mean of 8·5 years (SD 1·8) of follow-up. The age-adjusted and sex-adjusted incidence of type 2 diabetes was 3·1 times (95% CI 2·8–3·6; p<0·0001) higher among Indian Asians than among Europeans, and remained 2·5 times (2·1–2·9; p<0·0001) higher after adjustment for adiposity, physical activity, family history of type 2 diabetes, and baseline glycaemic measures. The mean absolute difference in methylation level between

  2. Eosinophils in the blood of hematopoietic stem cell transplanted patients are activated and have different molecular marker profiles in acute and chronic graft-versus-host disease

    PubMed Central

    Cromvik, Julia; Johnsson, Marianne; Vaht, Krista; Johansson, Jan-Erik; Wennerås, Christine

    2014-01-01

    While increased numbers of eosinophils may be detected in patients with graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation, it is not known if eosinophils play a role in GVHD. The aims of this study were to determine: whether eosinophils are activated during GVHD; whether the patterns of activation are similar in acute and chronic GVHD; and the ways in which systemic corticosteroids affect eosinophils. Transplanted patients (n = 35) were investigated for eosinophil numbers and the expression levels of 16 eosinophilic cell surface markers using flow cytometry; all the eosinophil data were analyzed by the multivariate method OPLS-DA. Different patterns of molecule expression were observed on the eosinophils from patients with acute, chronic, and no GVHD, respectively. The molecules that provided the best discrimination between acute and chronic GVHD were: the activation marker CD9; adhesion molecules CD11c and CD18; chemokine receptor CCR3; and prostaglandin receptor CRTH2. Patients with acute or chronic GVHD who received systemic corticosteroid treatment showed down-regulation of the cell surface markers on their eosinophils, whereas corticosteroid treatment had no effect on the eosinophil phenotype in the patients without GVHD. In summary, eosinophils are activated in GVHD, display different activation profiles in acute and chronic GVHD, and are highly responsive to systemic corticosteroids. PMID:25400930

  3. Tailored nanoparticles for tumour therapy.

    PubMed

    Jiang, Pei-Shin; Drake, Philip; Cho, Hui-Ju; Kao, Chao-Hung; Lee, Kun-Feng; Kuo, Chien-Hung; Lin, Xi-Zhang; Lin, Yuh-Jiuan

    2012-06-01

    Gd doped iron-oxide nanoparticles were developed for use in tumour therapy via magnetic fluid hyperthermia (MFH). The effect of the Gd3+ dopant on the particle size and magnetic properties was investigated. The final particle composition varied from Gd0.01Fe2.99O4 to Gd0.04Fe2.96O4 as determined by Inductively coupled plasma atomic emission spectroscopy (ICP-AES). TEM image analysis showed the average magnetic core diameters to be 12 nm and 33 nm for the lowest and highest Gd levels respectively. The specific power adsorption rate (SAR) determined with a field strength of 246 Oe and 52 kHz had a maximum of 38Wg(-1) [Fe] for the Gd0.03Fe2.97O4 sample. This value is about 4 times higher than the reported SAR values for Fe3O4. The potential for in vivo tumour therapy was investigated using a mouse model. The mouse models treated with Gd0.02Fe2.98O4 displayed much slower tumour growth after the first treatment cycle, the tumour had increased its mass by 25% after 7 days post treatment compared to a 79% mass increase over the same period for those models treated with standard iron-oxide or saline solution. After a second treatment cycle the mouse treated with Gd0.02Fe2.98O4 showed complete tumour regression with no tumour found for at least 5 days post treatment. PMID:22905580

  4. Hyperthermia-enhanced effectiveness of mitoxantrone in an experimental rat tumour.

    PubMed

    Schopman, E M; Van Bree, C; Bakker, P J; Kipp, J B; Barendsen, G W

    1996-01-01

    The influence of local hyperthermia (HT) on Mitoxantrone (MITOX) effectiveness was studied in an experimental rat tumour. R-1 rhabdomyosarcomas were treated with MITOX (5 mg/kg ip), HT (43 degrees C for 1 h) or combinations applied at various time intervals up to 24 h. Tumour growth delay and tumour cell clonogenicity were assessed in correlation with the pharmacokinetics in blood plasma and with MITOX-concentrations in tumour tissue. Combined treatments were more effective than expected on the basis of simple addition of effects of single treatments. With increasing time intervals between treatments up to 8 h, an increase in effectiveness was observed. Unfortunately, treatment with an 8-h interval resulted in a high mortality: 80% of the rats died with 5-10 days after treatment. Treatment with a 3-h interval between MITOX and HT was the most effective combination resulting in the highest therapeutic ratio. Even local tumour controls (14/18 rats) were observed. These enhanced effects were associated with a higher MITOX-concentration in the fraction of intact cells recovered from tumours. However, no differences were observed in MITOX-concentration in total tumour tissue nor in plasma concentrations. In conclusion, timing between MITOX and HT is important for drug availability, for interaction of the two modalities to increase damage in tumour cells and for limiting the toxicity to normal tissues. PMID:8926392

  5. Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours.

    PubMed

    Braekeveldt, Noémie; Wigerup, Caroline; Gisselsson, David; Mohlin, Sofie; Merselius, My; Beckman, Siv; Jonson, Tord; Börjesson, Anna; Backman, Torbjörn; Tadeo, Irene; Berbegall, Ana P; Ora, Ingrid; Navarro, Samuel; Noguera, Rosa; Påhlman, Sven; Bexell, Daniel

    2015-03-01

    Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers neural cell adhesion molecule, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma.

  6. Biological Monitoring of Blood Naphthalene Levels as a Marker of Occupational Exposure to PAHs among Auto-Mechanics and Spray Painters in Rawalpindi

    PubMed Central

    2011-01-01

    Background Routine exposure to chemical contaminants in workplace is a cause for concern over potential health risks to workers. In Pakistan, reports on occupational exposure and related health risks are almost non-existent, which reflects the scarce availability of survey data and criteria for determining whether an unsafe exposure has occurred. The current study was designed to evaluate blood naphthalene (NAPH) levels as an indicator of exposure to polycyclic aromatic hydrocarbons (PAHs) among automobile workshop mechanics (MCs) and car-spray painters (PNs). We further determined the relationship between blood NAPH levels and personal behavioural, job related parameters and various environmental factors that may further be associated with elevated risks of occupational exposures to PAHs. Methods Sixty blood samples (n = 20 for each group i.e. MC, PN and control group) were collected to compare their blood NAPH levels among exposed (MCs and PNs) and un-exposed (control) groups. Samples were analyzed using high pressure liquid chromatography (HPLC). Data regarding demographic aspects of the subjects and their socioeconomic features were collected using a questionnaire. Subjects were also asked to report environmental hygiene conditions of their occupational environment. Results We identified automobile work areas as potential sites for PAHs exposure, which was reflected by higher blood NAPH levels among MCs. Blood NAPH levels ranged from 53.7 to 1980.6 μgL-1 and 54.1 to 892.9 μgL-1 among MCs and PNs respectively. Comparison within each group showed that smoking enhanced exposure risks several fold and both active and passive smoking were among personal parameters that were significantly correlated with log-transformed blood NAPH levels. For exposed groups, work hours and work experience were job related parameters that showed strong associations with the increase in blood NAPH levels. Poor workplace hygiene and ventilation were recognized as most significant

  7. Staining Against Phospho-H2AX (γ-H2AX) as a Marker for DNA Damage and Genomic Instability in Cancer Tissues and Cells.

    PubMed

    Nagelkerke, Anika; Span, Paul N

    2016-01-01

    Phospho-H2AX or γ-H2AX- is a marker of DNA double-stranded breaks and can therefore be used to monitor DNA repair after, for example, irradiation. In addition, positive staining for phospho-H2AX may indicate genomic instability and telomere dysfunction in tumour cells and tissues. Here, we provide a protocol to perform immunostaining for phospho-H2AX on cells, cryosections and formalin-fixed, paraffin-embedded tissues. Crucial steps in the protocol and troubleshooting suggestions are indicated. We also provide suggestions on how to combine staining against γ-H2AX with stainings against components of the tumour microenvironment, such as hypoxia and blood vessels. PMID:27325258

  8. Molecular genetic analysis of flow-sorted ovarian tumour cells: improved detection of loss of heterozygosity.

    PubMed Central

    Abeln, E. C.; Corver, W. E.; Kuipers-Dijkshoorn, N. J.; Fleuren, G. J.; Cornelisse, C. J.

    1994-01-01

    Detection of loss of heterozygosity (LOH) is usually performed on homogenised tumour specimens. In this type of analysis samples with a low percentage of tumour cells have to be excluded and possible intra-tumour heterogeneity is obscured. In this study we report the application of polymerase chain reaction (PCR)-driven LOH detection with in total 22 microsatellite markers for chromosome 1q, 3p, 3q, 4p, 6p, 6q, 11p, 11q, 17p, 17q, 18p, 18q, Xp and Xq on flow-sorted cells from fresh and paraffin-embedded ovarian tumour tissue. Titration experiments showed that LOH can be detected with as few as 100 cell equivalents of DNA. Clear examples of LOH could be detected in the sorted aneuploid fractions from one unilateral and two bilateral ovarian tumours from three patients. In two samples the sorted fraction was less than 10% of the total sample. The bilateral tumours from the same patient showed loss of identical alleles for one marker (case OV64) and two markers (case OV69), indicative of their monoclonal origin. Multiparameter flow cytometry using two different ovarian tumour markers (MOv18 and BMA180), an anti-cytokeratin monoclonal antibody (MAb) (M9), an anti-vimentin MAb (V9) and a MAb against the panepithelial antigen 17-1A on the fresh ascites cells of the fourth ovarian cancer patient was used to investigate possible intra-tumour heterogeneity. We showed the presence of at least three phenotypically different populations, of which the diploid, keratin-positive, vimentin-negative population showed a similar LOH pattern as the aneuploid population (DNA index = 1.7), indicative of its neoplastic origin. The same LOH pattern was shown in an omentum metastasis from this patient also having the same aneuploid DNA index of 1.7. The sharing of the same LOH pattern by the diploid and aneuploid tumour cell populations suggests that the observed allele loss events occurred before the development of aneuploidy. PCR on flow-sorted cells is thus an important tool to study

  9. Phyllodes tumour in pregnancy: a case report

    PubMed Central

    Way, Jeffrey C.; Culham, Beverley A.

    1998-01-01

    Phyllodes tumour (cystosarcoma phyllodes) is a rare breast tumour that grows rapidly and to a relatively large size, especially during pregnancy. These tumours may be classified as benign, borderline or malignant. They have a high incidence of local recurrence but little tendency to metastasize to distant organs. The question of whether the tumour is hormone dependent remains unresolved. This report describes the case of a patient who had a phyllodes tumour that first became apparent in her 31st week of pregnancy. After enucleation and subsequent wide excision she remained tumour free through a second pregnancy. Although the follow-up period is short, it appears that subsequent pregnancy is not necessarily associated with recurrent or new disease for patients who have had their initial tumour completely excised. The goal for the management of these tumours is complete surgical excision. PMID:9793511

  10. The treatment of sublingual gland tumours.

    PubMed

    Sun, G; Yang, X; Tang, E; Wen, J; Lu, M; Hu, Q

    2010-09-01

    This study assessed the clinical and histological features and therapeutic efficacy of 25 cases of sublingual gland tumours from 1998 to 2008. There were 17 female patients and 8 male, the ratio of females to males was 2.1:1. The mean age was 48.6 years. 4 cases were benign tumours (16%). 21 cases were malignant sublingual gland tumours (84%) and of these, 18 were adenoid cystic carcinoma (86%). Adenoid cystic carcinoma was mainly of the histological type, and the other histological classifications included mucoepidermoid carcinoma, pleomorphic adenoma, myoepithelioma, oncocytoma and polymorphous low-grade adenocarcinoma. Sublingual gland tumours are rare and most are malignant. For malignant sublingual gland tumours, early diagnosis and aggressive surgical treatment, especially for tumours with nerve involvement, is the key to improving prognosis. Free radial forearm flap or pectoralis major myocutaneous flap are appropriate methods for mouth floor reconstruction. For benign sublingual gland tumours, the resection of tumour and sublingual gland is the preferred treatment.

  11. Performance of the Verigene Gram-Positive Blood Culture Assay for Direct Detection of Gram-Positive Organisms and Resistance Markers in a Pediatric Hospital

    PubMed Central

    Mestas, Javier; Polanco, Claudia M.; Felsenstein, Susanna

    2014-01-01

    The performance characteristics of the Verigene Gram-positive blood culture (BC-GP) assay were evaluated in pediatric patients. Concordance of the BC-GP assay was 95.8%, with significant decreases in turnaround time for identification and resistance detection. BC-GP is highly accurate and can be integrated into the routine workflow of the microbiology laboratory. PMID:24131696

  12. Solitary fibrous tumour of the oral cavity: clinicopathological and immunohistochemical characterization of three cases.

    PubMed

    Lukinmaa, P L; Hietanen, J; Warfvinge, G; Sane, J; Tuominen, S; Henriksson, V; Larsson, A

    2000-04-01

    Solitary fibrous tumour (SFT) is an uncommon mesenchymal neoplasm rarely located in the oral cavity. To characterize further oral SFT, we describe three new cases. Each tumour originated in the buccal mucosa of a middle-aged/elderly patient. Histological examination showed well-circumscribed tumours with densely cellular areas alternating with hypocellular areas in a variedly collagenous, vascular stroma. Mast cells were abundant. The spindle-shaped, neoplastic cells immunostained strongly for CD34 antigen and vimentin and weakly for bcl-2, but not for epithelial cell markers, alpha-smooth muscle actin, or neurofilament or S-100 proteins. Compatible with the virtual absence of mitoses and of marked nuclear atypia, the overall frequency of proliferating cells expressing Ki-67 was low. The expression of CD34 was useful in the differential diagnosis. The consistent location in the cheek and expansion of one tumour after local trauma does not preclude a traumatic element in the development of oral SFT.

  13. Induction of immune cell infiltration into murine SCCVII tumour by photofrin-based photodynamic therapy.

    PubMed Central

    Krosl, G.; Korbelik, M.; Dougherty, G. J.

    1995-01-01

    Cellular populations in the squamous cell carcinoma SCCVII, growing in C3H/HeN mice given Photofrin, were examined at various time intervals during the photodynamic light treatment and up to 8 h later. Cell populations present within excised tumours were identified by monoclonal antibodies directed against cell type-specific membrane markers using a combination of the indirect immunoperoxidase and Wright staining or by flow cytometry. Photofrin-based photodynamic therapy (PDT) induced dramatic changes in the level of different cellular populations contained in the treated tumour. The most pronounced was a rapid increase in the content of neutrophils, which increased 200-fold within 5 min after the initiation of light treatment. This was followed immediately by an increase in the levels of mast cells, while another type of myeloid cells, most likely monocytes, invaded the tumour between 0 and 2 h after PDT. The examination of cytolysis of in vitro cultured SCCVII tumour cells mediated by macrophages harvested from the SCCVII tumour revealed a pronounced increase in the tumoricidal activity of tumour-associated macrophages isolated at 2 h post PDT. It seems, therefore, that the PDT-induced acute inflammatory infiltration of myeloid cells into the treated tumour is associated with functional activation of immune cells. PMID:7880738

  14. Anti-VEGF antibody therapy does not promote metastasis in genetically engineered mouse tumour models.

    PubMed

    Singh, Mallika; Couto, Suzana S; Forrest, William F; Lima, Anthony; Cheng, Jason H; Molina, Rafael; Long, Jason E; Hamilton, Patricia; McNutt, Angela; Kasman, Ian; Nannini, Michelle A; Reslan, Hani Bou; Cao, Tim C; Ho, Calvin C K; Barck, Kai H; Carano, Richard A D; Foreman, Oded; Eastham-Anderson, Jeffrey; Jubb, Adrian M; Ferrara, Napoleone; Johnson, Leisa

    2012-08-01

    Resistance to anti-angiogenic therapy can occur via several potential mechanisms. Unexpectedly, recent studies showed that short-term inhibition of either VEGF or VEGFR enhanced tumour invasiveness and metastatic spread in preclinical models. In an effort to evaluate the translational relevance of these findings, we examined the consequences of long-term anti-VEGF monoclonal antibody therapy in several well-validated genetically engineered mouse tumour models of either neuroendocrine or epithelial origin. Anti-VEGF therapy decreased tumour burden and increased overall survival, either as a single agent or in combination with chemotherapy, in all four models examined. Importantly, neither short- nor long-term exposure to anti-VEGF therapy altered the incidence of metastasis in any of these autochthonous models, consistent with retrospective analyses of clinical trials. In contrast, we observed that sunitinib treatment recapitulated previously reported effects on tumour invasiveness and metastasis in a pancreatic neuroendocrine tumour (PNET) model. Consistent with these results, sunitinib treatment resulted in an up-regulation of the hypoxia marker GLUT1 in PNETs, whereas anti-VEGF did not. These results indicate that anti-VEGF mediates anti-tumour effects and therapeutic benefits without a paradoxical increase in metastasis. Moreover, these data underscore the concept that drugs targeting VEGF ligands and receptors may affect tumour metastasis in a context-dependent manner and are mechanistically distinct from one another.

  15. The relationship of blood- and urine-boron to boron exposure in borax-workers and usefulness of urine-boron as an exposure marker.

    PubMed Central

    Culver, B D; Shen, P T; Taylor, T H; Lee-Feldstein, A; Anton-Culver, H; Strong, P L

    1994-01-01

    Daily dietary-boron intake and on-the-job inspired boron were compared with blood- and urine-boron concentrations in workers engaged in packaging and shipping borax. Fourteen workers handling borax at jobs of low, medium, and high dust exposures were sampled throughout full shifts for 5 consecutive days each. Airborne borax concentrations ranged from means of 3.3 mg/m3 to 18 mg/m3, measured gravimetrically. End-of-shift mean blood-boron concentrations ranged from 0.11 to 0.26 microgram/g; end-of-shift mean urine concentrations ranged from 3.16 to 10.72 micrograms/mg creatinine. Creatinine measures were used to adjust for differences in urine-specific gravity such that 1 ml of urine contains approximately 1 mg creatinine. There was no progressive increase in end-of-shift blood- or urine-boron concentrations across the days of the week. Urine testing done at the end of the work shift gave a somewhat better estimate of borate exposure than did blood testing, was sampled more easily, and was analytically less difficult to perform. Personal air samplers of two types were used: one, the 37-mm closed-face, two-piece cassette to estimate total dust and the other, the Institute of Occupational Medicine (IOM) sampler to estimate inspirable particulate mass. Under the conditions of this study, the IOM air sampler more nearly estimated human exposure as measured by blood- and urine-boron levels than did the sampler that measured total dust.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7889874

  16. The relationship of blood- and urine-boron to boron exposure in borax-workers and usefulness of urine-boron as an exposure marker.

    PubMed

    Culver, B D; Shen, P T; Taylor, T H; Lee-Feldstein, A; Anton-Culver, H; Strong, P L

    1994-11-01

    Daily dietary-boron intake and on-the-job inspired boron were compared with blood- and urine-boron concentrations in workers engaged in packaging and shipping borax. Fourteen workers handling borax at jobs of low, medium, and high dust exposures were sampled throughout full shifts for 5 consecutive days each. Airborne borax concentrations ranged from means of 3.3 mg/m3 to 18 mg/m3, measured gravimetrically. End-of-shift mean blood-boron concentrations ranged from 0.11 to 0.26 microgram/g; end-of-shift mean urine concentrations ranged from 3.16 to 10.72 micrograms/mg creatinine. Creatinine measures were used to adjust for differences in urine-specific gravity such that 1 ml of urine contains approximately 1 mg creatinine. There was no progressive increase in end-of-shift blood- or urine-boron concentrations across the days of the week. Urine testing done at the end of the work shift gave a somewhat better estimate of borate exposure than did blood testing, was sampled more easily, and was analytically less difficult to perform. Personal air samplers of two types were used: one, the 37-mm closed-face, two-piece cassette to estimate total dust and the other, the Institute of Occupational Medicine (IOM) sampler to estimate inspirable particulate mass. Under the conditions of this study, the IOM air sampler more nearly estimated human exposure as measured by blood- and urine-boron levels than did the sampler that measured total dust.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Multiple cilia suppress tumour formation.

    PubMed

    Eberhart, Charles

    2016-04-01

    Primary cilia are cellular structures that have important functions in development and disease. The suppression of multiciliate differentiation of choroid plexus precursors, and maintenance of a single primary cilium by Notch1, is now shown to be involved in choroid plexus tumour formation. PMID:27027488

  18. Mixed tumour of the vagina.

    PubMed

    Fukunaga, M; Endo, Y; Ishikawa, E; Ushigome, S

    1996-05-01

    A 33-year-old Japanese woman presented with a polypoid 2.5 x 2.5 x 1.9 cm mass located in the posterior wall of the lower vagina. Microscopically, the tumour was composed of benign epithelial and stromal-type elements. Predominant epithelial elements were mucinous glands with squamous metaplasia and islands of mature squamous epithelium. The stromal-type cells showed reticular or short fascicular patterns with a transition to the epithelial elements. There was no dual epithelial-myoepithelial combination in the glands as seen in so-called mixed tumours (pleomorphic adenomas) of the salivary gland. Immunohistochemically, the epithelial elements were strongly positive for cytokeratin, PKK1 and epithelial membrane antigen, while the stromal-type cells co-expressed PKK1 and vimentin. Staining for S-100 protein, muscle actin, alpha-smooth muscle actin, desmin, and CD34 was uniformly negative in the tumour cells. The DNA pattern was diploid. The patient is alive and well without recurrence for 50 months after excision. These results indicate that an epithelial cell proliferation, probably of the remnant vestibular gland, plays a major role in the development of mixed tumours of the vagina.

  19. Tumour vasculature--a potential therapeutic target.

    PubMed Central

    Baillie, C. T.; Winslet, M. C.; Bradley, N. J.

    1995-01-01

    The tumour vasculature is vital for the establishment, growth and metastasis of solid tumours. Its physiological properties limit the effectiveness of conventional anti-cancer strategies. Therapeutic approaches directed at the tumour vasculature are reviewed, suggesting the potential of anti-angiogenesis and the targeting of vascular proliferation antigens as cancer treatments. PMID:7543770

  20. [Blood Content of Markers of Inflammation and Cytokines in Patients With Alcoholic Cardiomyopathy and Ischemic Heart Disease at Various Stages of Heart Failure].

    PubMed

    Panchenko, L F; Moiseev, V S; Pirozhkov, S V; Terebilina, N N; Naumova, T A; Baronets, V Iu; Goncharov, A S

    2015-01-01

    We conducted a comparative study of content proinflammatory cytokines, biomarkers of inflammatory process, biochemical indicators of congestive heart failure (CHF) and hemodynamic parameters in patients with alcoholic cardiomyopathy (ACMP) and ischemic heart disease (IHD) with various NYHA classes. We examined 62 men with ACMP (n = 45) and IHD (n = 17) and NYHA class III-IV CHF. Patients of both groups had lowered ejection fraction (EF), dilated cardiac chambers, and increased left ventricular (LV) myocardial mass index (MMI). Relative LV wall thickness was within normal limits but in the ACMP group it was significantly lower than in IHD group what corresponded to the eccentric type of myocardial hypertrophy. Higher NYHA class was associated with lower EF and larger end diastolic and end systolic LV dimensions. In ACMP it was also associated with larger dimension of the right ventricle while in IHD--with substantially larger (by 30%) dimension of atria. Substantial amount of endotoxin found in blood plasma of patients with IHD corresponded to the conception of increased intestinal permeability of in CHF. Alcohol abuse was an aggravating factor of endotoxin transmission and its concentration in patients with ACMP was 3 times higher than in patients with IHD. Patients with ACMP had substantially elevated blood concentrations of interleukins (IL) 6, 8, 12, tumor necrosis factor α (TNF-α), and its soluble receptor s-TNF-R; they also had twofold elevation of C-reactive protein concentration. ACMP was associated with manifold rise of blood content of brain natriuretic peptide (BNP). Patients with IHD also had elevated blood concentrations of IL 6, 8 and 12 but their values were 1.5-2 times lower than ACMP group. Blood content of TNF-α and s-TNF-R in IHD group was within normal limits. Higher NYHA class in ACMP patients was associated with higher concentrations of IL 6 and 8, TNF-a, and BNP. In both groups of patients contents of IL-12, s-TNF-R, TGF-1β and factors of

  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. Solitary fibrous tumour of the adrenal gland associated with pregnancy.

    PubMed

    Bongiovanni, M; Viberti, L; Giraudo, G; Morino, M; Papotti, M

    2000-10-01

    Solitary fibrous tumour (SFT), first described as a pleural lesion, has been reported in several extrathoracic sites over the past 10 years. We describe a SFT of the left adrenal gland incidentally discovered in a 23-year-old, 22-week pregnant woman and characterised by a rapid growth during the third trimester of pregnancy. Elevated serum and urinary levels of cortisol and elevated blood levels of delta 4 androstendione and 17-OH progesterone were observed. After spontaneous delivery, the patient underwent laparoscopic resectioning of the mass and of the left adrenal gland from which the tumour was apparently originating. The kidney was not involved, and no other abdominal tumours were found. Histological and immunohistochemical features were typical of SFT of pleura and other locations. Only one case of adrenal SFT is on record, and the adrenal gland is to be added to the long list of extrathoracic locations of SFT. The association with pregnancy was a previously unrecognised event in SFT. The focal expression of progesterone receptors in the tumour cells may be related to pregnancy. This observation prompted an analysis of steroid hormone receptors in SFT of classical sites (pleura). Two of five cases had focal progesterone receptors too, a finding which deserves further investigations in a much larger series of SFTs.

  3. A Novel Dried Blood Spot-LCMS Method for the Quantification of Methotrexate Polyglutamates as a Potential Marker for Methotrexate Use in Children

    PubMed Central

    Hawwa, Ahmed F.; AlBawab, AbdelQader; Rooney, Madeleine; Wedderburn, Lucy R.; Beresford, Michael W.; McElnay, James C.

    2014-01-01

    Objective Development and validation of a selective and sensitive LCMS method for the determination of methotrexate polyglutamates in dried blood spots (DBS). Methods DBS samples [spiked or patient samples] were prepared by applying blood to Guthrie cards which was then dried at room temperature. The method utilised 6-mm disks punched from the DBS samples (equivalent to approximately 12 µl of whole blood). The simple treatment procedure was based on protein precipitation using perchloric acid followed by solid phase extraction using MAX cartridges. The extracted sample was chromatographed using a reversed phase system involving an Atlantis T3-C18 column (3 µm, 2.1×150 mm) preceded by Atlantis guard column of matching chemistry. Analytes were subjected to LCMS analysis using positive electrospray ionization. Key Results The method was linear over the range 5–400 nmol/L. The limits of detection and quantification were 1.6 and 5 nmol/L for individual polyglutamates and 1.5 and 4.5 nmol/L for total polyglutamates, respectively. The method has been applied successfully to the determination of DBS finger-prick samples from 47 paediatric patients and results confirmed with concentrations measured in matched RBC samples using conventional HPLC-UV technique. Conclusions and Clinical Relevance The methodology has a potential for application in a range of clinical studies (e.g. pharmacokinetic evaluations or medication adherence assessment) since it is minimally invasive and easy to perform, potentially allowing parents to take blood samples at home. The feasibility of using DBS sampling can be of major value for future clinical trials or clinical care in paediatric rheumatology. PMID:24587116

  4. A comparison of the effects of unfractionated heparin, dalteparin and danaparoid on vascular endothelial growth factor-induced tumour angiogenesis and heparanase activity.

    PubMed

    Takahashi, Hidenori; Ebihara, Satoru; Okazaki, Tatsuma; Asada, Masanori; Sasaki, Hidetada; Yamaya, Mutsuo

    2005-10-01

    Disseminated intravascular coagulation (DIC) is the most common complication of solid tumours. In this study, the effectiveness of three polysaccharide anticoagulants (PSAs), at therapeutic doses, at inhibiting solid tumour growth was investigated. Mice with tumour xenografts were subcutaneously injected with either unfractionated heparin (UFH; 200 units kg(-1) day(-1)), dalteparin (75 units kg(-1) day(-1)) or danaparoid (50 units kg(-1) day(-1)). At these concentrations, these PSAs are equieffective at inhibiting blood coagulation activated factor X. In mice with Lewis lung carcinoma (LLC) tumours dalteparin and, to a lesser extent, UFH inhibited both tumour growth and angiogenesis, whereas danaparoid did not. In contrast, in mice with KLN205 tumours, all the PSAs inhibited tumour growth and angiogenesis. All the PSAs significantly inhibited proliferation, migration of endothelial cells and vessel formation in matrigel plugs containing vascular endothelial growth factor (VEGF) and there were no significant differences between these effects of the PSAs. The PSAs had no effect on endothelial cell tubular formation in vitro. Although all the PSAs inhibited VEGF production in KLN205 tumours in vivo and cells in vitro, in LLC tumours and cells only UFH and dalteparin inhibited VEGF production, whereas danaparoid did not. In both LLC and KLN205 tumours in vivo, heparanase activity was inhibited by UFH and dalteparin, but not by danaparoid. Hence, UFH and dalteparin may be more effective than danaparoid at inhibiting cancer progression in DIC patients with solid tumours, due at least in part to their ability to suppress VEGF and heparanase in tumours.

  5. Computerised counting of tumour infiltrating lymphocytes in 90 breast cancer specimens.

    PubMed

    Marsigliante, S; Biscozzo, L; Marra, A; Nicolardi, G; Leo, G; Lobreglio, G B; Storelli, C

    1999-05-01

    Tumour infiltrating lymphocytes (TILs) implicated in immunologic cytotoxicity were evaluated by immunohistochemistry and digitally counted in serial sections from 90 breast cancers in order to assess their number, the relationships between them and to tumour histology. CD3+, CD4+, CD8+, CD20+, CD25+ and CD56+ lymphocytes were found in 58 (64.4%), 52 (57.7%), 50 (55.5%), 22 (24.4%), 11 (12.2%) and 21 (23.3%) tumours, respectively. There was no difference in the number of TILs between pure infiltrating ductal (NOS) and non-ductal carcinomas, and no relationship between TILs and histological grades was found. CD3+ TILs directly correlated to age, while lymph node negative patients had tumours infiltrated by fewer CD4+ TILs with respect to lymph node positive patients. In 25/90 patients, randomly chosen, the status of peripheral blood lymphocytes was evaluated but no differences with respect to the status found in healthy blood donors was obtained; nonetheless while in some patients CD8+ TILs outnumbered CD4+ TILs in situ, the CD4/CD8 ratio was normal in their peripheral blood. The results show a considerable diversity of TILs among breast tumours, their lack of relationship with the status of the peripheral blood cells, and their potential important relationship with age (CD3+) and lymph node status (CD4+). PMID:10408906

  6. DNA methylation profiling of phyllodes and fibroadenoma tumours of the breast.

    PubMed

    Huang, Katie T; Dobrovic, Alexander; Yan, Max; Karim, Rooshdiya Z; Lee, C Soon; Lakhani, Sunil R; Fox, Stephen B

    2010-11-01

    Phyllodes tumours and cellular fibroadenomas are both fibroepithelial tumours of the breast. Phyllodes tumours, unlike fibroadenomas, have the ability to recur and metastasise. Although these lesions can be distinguished by their stromal cellularity, mitotic index, presence or absence of stromal overgrowth and cellular atypia, there is overlap and not infrequently a definitive diagnosis cannot be made, particularly on biopsy. We sought to evaluate whether DNA promoter methylation profiling using selected genes known to be methylated in cancer would allow us to learn more about the biology of these tumours, and whether it could identify methylation markers that could differentiate phyllodes tumours from fibroadenomas and/or distinguish phyllodes tumours of different grades. Methylation-sensitive high resolution melting (MS-HRM) was used to screen promoter DNA methylation changes in 86 phyllodes tumours (15 benign, 28 borderline, 43 malignant) and 26 fibroadenomas. A panel of 11 genes (RASSF1A, TWIST1, APC, WIF1, MGMT, MAL, RARβ, CDKN2A, CDH1, TP73 and MLH1) was tested. Methylation status was correlated with histology and with clinicopathological parameters. Five of the gene promoters showed some methylation in a proportion of phyllodes tumours; RASSF1A, 45.3%; TWIST1, 10.7%; APC, 4.1%; WIF1, 2.9% and MGMT, 1.3%. Only two genes showed any methylation in fibroadenomas usually at background levels; RASSF1A, 53.8% and MGMT, 8.3%. No CDKN2A methylation was observed in either tumour type, contrary to previous reports. Overall, the methylation patterns differed little from that which might be seen in normal cells. However, significant levels of methylation of RASSF1A (24.4%) and TWIST1 (7.1%) was observed in some phyllodes tumours. Elevated RASSF1A and/or TWIST1 methylation was significantly associated with phyllodes tumours compared with fibroadenomas (P = 0.02), TWIST1 methylation correlated with increasing malignancy in phyllodes tumours (P < 0.001). In conclusion

  7. Dietary Echium Oil Increases Long-Chain n–3 PUFAs, Including Docosapentaenoic Acid, in Blood Fractions and Alters Biochemical Markers for Cardiovascular Disease Independently of Age, Sex, and Metabolic Syndrome12

    PubMed Central

    Kuhnt, Katrin; Fuhrmann, Claudia; Köhler, Melanie; Kiehntopf, Michael; Jahreis, Gerhard

    2014-01-01

    Dietary supplementation with echium oil (EO) containing stearidonic acid (SDA) is a plant-based strategy to improve long-chain (LC) n–3 (ω-3) polyunsaturated fatty acid (PUFA) status in humans. We investigated the effect of EO on LC n–3 PUFA accumulation in blood and biochemical markers with respect to age, sex, and metabolic syndrome. This double-blind, parallel-arm, randomized controlled study started with a 2-wk run-in period, during which participants (n = 80) were administered 17 g/d run-in oil. Normal-weight individuals from 2 age groups (20–35 and 49–69 y) were allotted to EO or fish oil (FO; control) groups. During the 8-wk intervention, participants were administered either 17 g/d EO (2 g SDA; n = 59) or FO [1.9 g eicosapentaenoic acid (EPA); n = 19]. Overweight individuals with metabolic syndrome (n = 19) were recruited for EO treatment only. During the 10-wk study, the participants followed a dietary n–3 PUFA restriction, e.g., no fish. After the 8-wk EO treatment, increases in the LC n–3 metabolites EPA (168% and 79%) and docosapentaenoic acid [DPA (68% and 39%)] were observed, whereas docosahexaenoic acid (DHA) decreased (−5% and −23%) in plasma and peripheral blood mononuclear cells, respectively. Compared with FO, the efficacy of EO to increase EPA and DPA in blood was significantly lower (∼25% and ∼50%, respectively). A higher body mass index (BMI) was associated with lower relative and net increases in EPA and DPA. Compared with baseline, EO significantly reduced serum cholesterol, LDL cholesterol, oxidized LDL, and triglyceride (TG), but also HDL cholesterol, regardless of age and BMI. In the FO group, only TG decreased. Overall, daily intake of 15–20 g EO increased EPA and DPA in blood but had no influence on DHA. EO lowered cardiovascular risk markers, e.g., serum TG, which is particularly relevant for individuals with metabolic syndrome. Natural EO could be a noteworthy source of n–3 PUFA in human nutrition. This trial

  8. Grave Markers.

    ERIC Educational Resources Information Center

    DeMuro, Ted

    1985-01-01

    Junior high school students studied the cultural uses, symbolic meanings, and general physical forms of tombs and tombstones and then used basic slab building techniques to construct large clay grave markers. (RM)

  9. Clinical significance of detecting lymphatic and blood vessel invasion in stage II colon cancer using markers D2-40 and CD34 in combination.

    PubMed

    Lai, Jin-Huo; Zhou, Yong-Jian; Bin, Du; Qiangchen; Wang, Shao-Yuan

    2014-01-01

    This research was conducted to compare differences in colon cancer lymphatic vessel invasion (LVI) with D2-40 antibody labeling and regular HE staining, blood vessel invasion (BVI) with CD34 antibody labeling and HE staining and to assess the possibility of using D2-40-LVI/CD34-BVI in combination for predicting stage II colon cancer prognosis and guiding adjuvant chemotherapy.Anti-D2-40 and anti-CD34 antibodies were applied to tissue samples of 220 cases of stage II colon cancer to label lymphatic vessels and small blood vessels, respectively. LVI and BVI were assessed and multivariate COX regression analysis was performed for associations with colon cancer prognosis. Regular HE staining proved unable to differentiate lymphatic vessels from blood vessels, while D2-40 selectively labeled lymphatic endothelial cell cytosol and CD34 was widely expressed in large and small blood vessels of tumors as well as normal tissues. Compared to regular HE staining, D2-40-labeling for LVI and CD34-labeling for BVI significantly increased positive rate (22.3% vs 10.0% for LVI, and 19.1% vs 9.1% for BVI). Multivariate analysis indicated that TNM stage, pathology tissue type, post-surgery adjuvant chemotherapy, D2-40-LVI, and CD34-BVI were independent factors affecting whole group colon cancer prognosis, while HE staining-BVI, HE staining-LVI were not significantly related. When CD34-BVI/D2-40-LVI were used in combination for detection, the risk of death for patients with two or one positive results was 5.003 times that in the LVI(-)andBVI(-) group (95% CI 2.365 - 9.679). D2-40 antibody LVI labeling and CD34 antibody BVI labeling have higher specificity and accuracy than regular HE staining and can be used as molecular biological indicators for prognosis prediction and guidance of adjuvant chemotherapy for stage II colon cancer.

  10. The analysis of diagnostic markers of genetic disorders in human blood and urine using tandem mass spectrometry with liquid secondary ion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Millington, David S.; Kodo, Naoki; Terada, Naoto; Roe, Diane; Chace, Donald H.

    1991-12-01

    A method has been developed for the rapid diagnosis of metabolic diseases based on the analysis of characteristic metabolites in body fluids by fast atom bombardment or liquid secondary ion tandem mass spectrometry (FAB-MS--MS or LSIMS--MS). Acylcarnitine profiles were obtained from 100 [mu]l urine. 200 [mu]l plasma or 25 [mu]l whole blood spotted onto filter paper by simple solvent extraction, esterification and analysis using a precursor ion scan function on a triple quadrupole mass spectrometer. Specificity and sensitivity were improved by adding a small percentage of sodium octyl sulfate to the liquid matrix, which forms ion pairs with acylcarnitine esters. Acylglycines in urine were specifically detected as a group using a different precursor ion scan function. By forming methyl esters, metabolic profiles of both acylcarnitines and acylglycines were achieved in the same sample loading by application of alternating scan functions. Quantitative analysis of selected metabolites was achieved by use of stable isotope-labeled internal standards. Amino acid profiles were obtained from 100 [mu]l plasma and 25 [mu]l whole blood spots using butyl esters and a neutral loss scan function. The quantitative analysis of phenylalanine and tyrosine was achieved in these samples using stable isotope dilution. This capability will facilitate the diagnosis of phenylketonuria and other amino acidemias. These new methods have the requirements of speed, accuracy and capability for automation necessary for large-scale neonatal screening of inborn errors of matabolism.

  11. Chromosome Damage and Cell Proliferation Rates in In Vitro Irradiated Whole Blood as Markers of Late Radiation Toxicity After Radiation Therapy to the Prostate

    SciTech Connect

    Beaton, Lindsay A.; Ferrarotto, Catherine; Marro, Leonora; Samiee, Sara; Malone, Shawn; Grimes, Scott; Malone, Kyle; Wilkins, Ruth C.

    2013-04-01

    Purpose: In vitro irradiated blood samples from prostate cancer patients showing late normal tissue damage were examined for lymphocyte response by measuring chromosomal aberrations and proliferation rate. Methods and Materials: Patients were selected from a randomized trial evaluating the optimal timing of dose-escalated radiation and short-course androgen deprivation therapy. Of 438 patients, 3% experienced grade 3 late radiation proctitis and were considered to be radiosensitive. Blood samples were taken from 10 of these patients along with 20 matched samples from patients with grade 0 proctitis. The samples were irradiated at 6 Gy and, along with control samples, were analyzed for dicentric chromosomes and excess fragments per cell. Cells in first and second metaphase were also enumerated to determine the lymphocyte proliferation rate. Results: At 6 Gy, there were statistically significant differences between the radiosensitive and control cohorts for 3 endpoints: the mean number of dicentric chromosomes per cell (3.26 ± 0.31, 2.91 ± 0.32; P=.0258), the mean number of excess fragments per cell (2.27 ± 0.23, 1.43 ± 0.37; P<.0001), and the proportion of cells in second metaphase (0.27 ± 0.10, 0.46 ± 0.09; P=.0007). Conclusions: These results may be a valuable indicator for identifying radiosensitive patients and for tailoring radiation therapy.

  12. LC-MS/MS method development and validation for quantitative analyses of 2-aminothiazoline-4-carboxylic acid--a new cyanide exposure marker in post mortem blood.

    PubMed

    Giebułtowicz, Joanna; Rużycka, Monika; Fudalej, Marcin; Krajewski, Paweł; Wroczyński, Piotr

    2016-04-01

    2-aminothiazoline-4-carboxylic acid (ATCA) is a hydrogen cyanide metabolite that has been found to be a reliable biomarker of cyanide poisoning, because of its long-term stability in biological material. There are several methods of ATCA determination; however, they are restricted to extraction on mixed mode cation exchange sorbents. To date, there has been no reliable method of ATCA determination in whole blood, the most frequently used material in forensic analysis. This novel method for ATCA determination in post mortem specimen includes protein precipitation, and derivatization of interfering compounds and their later extraction with ethyl acetate. ATCA was quantitatively analyzed via high performance liquid chromatography-tandem mass spectrometry with positive electrospray ionization detection using a hydrophilic interaction liquid chromatography column. The method satisfied all validation criteria and was tested on the real samples with satisfactory results. Therefore, this analytical approach has been proven to be a tool for measuring endogenous levels of ATCA in post mortem specimens. To conclude, a novel, accurate and sensitive method of ATCA determination in post mortem blood was developed. The establishment of the method provides new possibilities in the field of forensic science.

  13. Gold Nanoparticle–Mediated Targeted Delivery of Recombinant Human Endostatin Normalizes Tumour Vasculature and Improves Cancer Therapy

    PubMed Central

    Li, Wei; Zhao, Xiaoxu; Du, Bin; Li, Xin; Liu, Shuhao; Yang, Xiao-Yan; Ding, Hui; Yang, Wende; Pan, Fan; Wu, Xiaobo; Qin, Li; Pan, Yunlong

    2016-01-01

    Tumour vasculature is generally disordered because of the production of excessive angiogenic factors by tumour cells, which results in tumour progression and reduces the effectiveness of radiotherapy or chemotherapy. Transient anti-angiogenic therapies that regulate tumour vascular morphology and function and improve the efficiency of antitumour therapy are under investigation. Recombinant human endostatin (Endostar/rhES) is a vascular angiogenesis–disrupting agent that has been used to treat non-small cell lung cancer (NSCLC) in the clinical setting. In this study, we used gold nanoparticles (AuNPs) as a drug-delivery system (DDS) for targeted tumour delivery of rhES for short therapy, which resulted in transient tumour vascular normalization, reduced permeability and hypoxia, strengthened blood vessel integrity, and increased blood-flow perfusion. Moreover, combination therapy with 5-FU over this timeframe was substantially more effective than 5-FU monotherapy. In conclusion, our research demonstrates the potential use of AuNPs as a drug-delivery platform for transporting rhES into a tumour to induce transient tumour vascular normalization and enhance the antitumour efficacy of cytotoxic drugs. PMID:27470938

  14. Carbogen-induced changes in rat mammary tumour oxygenation reported by near infrared spectroscopy

    PubMed Central

    Hull, E L; Conover, D L; Foster, T H

    1999-01-01

    We have evaluated the ability of steady-state, radially-resolved, broad-band near infrared diffuse reflectance spectroscopy to measure carbogen-induced changes in haemoglobin oxygen saturation (SO2) and total haemoglobin concentration in a rat R3230 mammary adenocarcinoma model in vivo. Detectable shifts toward higher saturations were evident in all tumours (n = 16) immediately after the onset of carbogen breathing. The SO2 reached a new equilibrium within 1 min and remained approximately constant during 200–300 s of administration. The return to baseline saturation was more gradual when carbogen delivery was stopped. The degree to which carbogen increased SO2 was variable among tumours, with a tendency for tumours with lower initial SO2 to exhibit larger changes. Tumour haemoglobin concentrations at the time of peak enhancement were also variable. In the majority of cases, haemoglobin concentration decreased in response to carbogen, indicating that increased tumour blood volume was not responsible for the observed elevation in SO2. We observed no apparent relationship between the extent of the change in tumour haemoglobin concentration and the magnitude of the change in the saturation. Near infrared diffuse reflectance spectroscopy provides a rapid, non-invasive means of monitoring spatially averaged changes in tumour haemoglo