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Sample records for blood tumour marker

  1. Surface markers of small lymphocytes appearing in the mouse Ehrlich ascites tumour, host spleen and blood

    PubMed Central

    Garnis, Sylvia; Lala, P. K.

    1978-01-01

    Small lymphocytes sampled from intraperitoneally growing Ehrlich ascites tumour in CBA/H-T6 mice as well as host spleen and blood at different days of tumour development were characterized radioautographically on the basis of two surface markers, IgM for B cells and θ antigen for T cells. A direct binding of 125I-labelled anti-IgM detected natural surface IgM, while an indirect binding following a prior exposure to anti-θ antibody detected θ antigen. Cells remaining unlabelled with the latter procedure were considered to lack both markers (double negative). While the incidence of IgM+ve small lymphocytes within the tumour declined, their absolute numbers increased with tumour growth. Low levels of antiglobulin binding shown by these cells were considered to reflect low levels of maturation, because (1) our previous studies indicated that they were newly formed, and (2) the extent of antiglobulin binding by B lymphocytes in the marrow is known to increase with increasing post-mitotic age. The proportions and the absolute numbers of θ+ve as well as the double negative small lymphocytes increased within the growing tumours. Within the host spleen, the incidence of IgM+ve small lymphocytes remained unchanged but their absolute numbers increased because of splenomegaly. The degree of antiglobulin binding by these cells was comparable to that of the normal splenic population. The incidence of θ+ve cells dropped but their absolute numbers remained unchanged in the spleen during tumour growth. In contrast, the incidence as well as the absolute numbers of double negative cells increased markedly. This cell category increased also in the blood, possibly in transit to the tumour site and other lymphoid organs from the bone marrow, where they were most prevalent. Their bone marrow origin was further suggested by a preponderance of marrow derived small lymphocytes at the tumour site as well as in the host spleens found in our earlier studies. Double negative population in

  2. Evaluation of immunohistochemical markers of lymphatic and blood vessels in canine mammary tumours.

    PubMed

    Sleeckx, N; Van Brantegem, L; Fransen, E; Van den Eynden, G; Casteleyn, C; Veldhuis Kroeze, E; Van Ginneken, C

    2013-05-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Bitches with spontaneously arising CMTs represent a promising animal model for human breast cancer research. The aim of the present study was to develop an immunohistochemical protocol for the identification of blood and lymphatic vessels in CMTs. Antibodies specific for human lymphatic vessels (prox-1, lyve-1, podoplanin and D2-40) and blood vessels (von Willebrand factor [vWf], CD31 and CD34) were utilized. Serial sections of 18 samples (eight samples of normal canine mammary tissue, five benign and five malignant CMTs) were examined. Antibodies specific for podoplanin, D2-40 and CD34 showed no immunoreactivity with canine tissue. Prox-1 and CD31 were determined to be the most suitable markers for lymphatic and blood vessels, respectively. PMID:23123127

  3. 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

  4. 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

  5. Clinical tumour markers in ovarian cancer.

    PubMed

    Mazurek, A; Nikliński, J; Laudański, T; Pluygers, E

    1998-02-01

    Within past few years, the measurement of serological, histochemical and molecular genetic markers has had an increasing influence on clinical decisions about initial treatment and follow-up. This review presents data concerning the most studied and interesting markers in ovarian cancer. CA 125, CA 19.9, TATI, CASA, CEA, TPA, TPS and CYFRA21-1 are now the most widely used serological tumour markers for management of ovarian cancer patients. Ras oncogenes, C-erb2 proto-oncogene, p53 suppressor gene and Bcl-2 oncogene are examples of currently used molecular genetic markers. As histochemical markers-proliferation markers, flow cytometric analysis, thymidine labelling index, Ki-67 nuclear antigen or differentiation markers are nowadays the ones most often determined. Some of these markers might be useful adjuncts for monitoring response to therapy, including early detection of tumour reactivation to allow curative therapy and rapid detection of treatment failure. The study of these markers may also lead to a better understanding of the biological characteristics of ovarian cancer. Numerous tumour markers characterized in this paper have been recognized as promising prognostic factors. The information derived from studies of these markers also represents the most promising avenue towards new treatment strategies; nevertheless to validate these factors, prospective studies of a large patient population are needed. PMID:9511849

  6. Tumour angiogenesis-Origin of blood vessels.

    PubMed

    Krishna Priya, S; Nagare, R P; Sneha, V S; Sidhanth, C; Bindhya, S; Manasa, P; Ganesan, T S

    2016-08-15

    The conventional view of tumour vascularization is that tumours acquire their blood supply from neighbouring normal stroma. Additional methods of tumour vascularization such as intussusceptive angiogenesis, vasculogenic mimicry, vessel co-option and vasculogenesis have been demonstrated to occur. However, the origin of the endothelial cells and pericytes in the tumour vasculature is not fully understood. Their origin from malignant cells has been shown indirectly in lymphoma and neuroblastoma by immuno-FISH experiments. It is now evident that tumours arise from a small population of cells called cancer stem cells (CSCs) or tumour initiating cells. Recent data suggest that a proportion of tumour endothelial cells arise from cancer stem cells in glioblastoma. This was demonstrated both in vitro and in vivo. The analysis of chromosomal abnormalities in endothelial cells showed identical genetic changes to those identified in tumour cells. However, another report contradicted these results from the earlier studies in glioblastoma and had shown that CSCs give rise to pericytes and not endothelial cells. The main thrust of this review is the critical analysis of the conflicting data from different studies and the remaining questions in this field of research. The mechanism by which this phenomenon occurs is also discussed in detail. The transdifferentiation of CSCs to endothelial cells/pericytes has many implications in the progression and metastasis of the tumours and hence it would be a novel target for antiangiogenic therapy. PMID:26934471

  7. 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

  8. Tumour markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines for clinical use.

    PubMed

    Duffy, M J; van Dalen, A; Haglund, C; Hansson, L; Holinski-Feder, E; Klapdor, R; Lamerz, R; Peltomaki, P; Sturgeon, C; Topolcan, O

    2007-06-01

    The aim of this article is to present updated guidelines for the use of serum, tissue and faecal markers in colorectal cancer (CRC). Lack of specificity and sensitivity preclude the use of all existing serum markers for the early detection of CRC. For patients with stage II or stage III CRC who may be candidates for either liver resection or systemic treatment should recurrence develop, CEA should be measured every 2-3 months for at least 3 years after diagnosis. Insufficient evidence exists to recommend routine use of tissue factors such as thymidylate synthase, microsatellite instability (MSI), p53, K-ras and deleted in colon cancer (DCC) for either determining prognosis or predicting response to therapy in patients with CRC. Microsatellite instability, however, may be used as a pre-screen for patients with suspected hereditary non-polyposis colorectal cancer. Faecal occult blood testing but not faecal DNA markers may be used to screen asymptomatic subjects 50 years or older for early CRC. PMID:17512720

  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. 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.

  11. Parkia pendula lectin as histochemistry marker for meningothelial tumour.

    PubMed

    Beltrão, E I C; Medeiros, P L; Rodrigues, O G; Figueredo-Silva, J; Valença, M M; Coelho, L C B B; Carvalho, L B

    2003-01-01

    Lectins have been intensively used in histochemical techniques for cell surface characterization. These proteins are involved in several biological processes and their use as histochemical markers have been evaluated since they can indicate differences in cell surfaces. Parkia pendula lectin (PpeL) was evaluated as histochemical marker for meningothelial meningioma biopsies. Tissue slices were incubated with PpeL conjugated to horseradish peroxidase (PpeL-HRP) and Concanavalin A-HRP (ConA-HPR) and the binding visualized with diaminobenzidine and hydrogen peroxide. The lectin-tissue binding was inhibited with D-glucose. PpeL showed to be a useful tool for the characterization of meningothelial tumour and clinico-pathological diagnosis. PMID:12777210

  12. Big endothelin-1 as a tumour marker for canine haemangiosarcoma.

    PubMed

    Fukumoto, Shinya; Miyasho, Taku; Hanazono, Kiwamu; Saida, Kaname; Kadosawa, Tsuyoshi; Iwano, Hidetomo; Uchide, Tsuyoshi

    2015-06-01

    Haemangiosarcoma (HSA) is an important malignant neoplasm of dogs that originates from vascular endothelial cells. This study explored the suitability of using serum big endothelin-1 (ET-1) as a tumour marker for canine spontaneous HSA. Serum big ET-1 was measured in dogs with splenic HSA (n = 14), splenic malignant tumours other than HSA (n = 10), benign splenic lesions (n = 11) and normal healthy dogs (n = 17) by ELISA. Serum big ET-1 levels in dogs with HSA were significantly (P < 0.01) higher than in other dogs. High sensitivity (100%, 95% confidence interval 86-100%) and specificity (95%, 95% confidence interval 86-95%) for HSA diagnosis were obtained using a cut-off of 17 pg/mL according to receiver operating characteristic (ROC) curves (area under ROC curve 0.93). PPET1, ETA, VEGF and Hif1-α mRNA expression, measured by real-time PCR, were elevated in HSA compared with normal tissues. These findings suggest that elevated serum big ET-1 could be used as a diagnostic marker for canine HSA. PMID:25920760

  13. Tumour endothelial marker-1 is expressed in canine Haemangiopericytomas.

    PubMed

    Fujii, Y; Tsuchiya, T; Morita, R; Kimura, M; Suzuki, K; Machida, N; Mitsumori, K; Shibutani, M

    2013-01-01

    The aim of this study was to characterize immunohistochemically 18 cases of canine haemangiopericytoma (CHP) using two new candidate markers for pericytes, tumour endothelial marker (TEM)-1 and new glue (NG)-2, as well as the conventional mesenchymal cellular markers, vimentin, α-smooth muscle actin (α-SMA), desmin and von Willebrand factor (vWF). Because pericytes may have the same origin as endothelial or smooth muscle cells or the same differentiation potential as myofibroblasts, 17 cases of leiomyosarcoma (LMS), 20 cases of haemangiosarcoma (HS) and three cases of myofibroblastic sarcoma (MFS) were also examined. Expression of TEM-1 by >10% of the neoplastic population was observed in 94.4% (17/18) of haemangiopericytomas, 23.5% (4/17) of LMSs, 30.0% (6/20) of HSs and 66.7% (2/3) of MFSs. NG-2 expression by >10% of the neoplastic population was observed in 16.7% (3/18) of haemangiopericytomas, 52.9% (9/17) of LMSs, 0% (0/20) of HSs and 33.3% (1/3) of MFSs. Vimentin was expressed by all of tumours. In haemangiopericytoma, the incidence of positive immunoreactivity in >10% of the neoplastic population was 5.6% (1/18) for both α-SMA and desmin and 0% (0/18) for vWF. Considering the phenotypic features of cells expressing TEM-1, CHPs are thought to originate from immature vascular mural cells sharing their phenotype with myofibroblasts. NG-2 expression may be a phenotype of smooth muscle cells rather than pericytes in dogs. PMID:23489680

  14. The tumour hypoxia marker pimonidazole reflects a transcriptional programme associated with aggressive prostate cancer

    PubMed Central

    Ragnum, H B; Vlatkovic, L; Lie, A K; Axcrona, K; Julin, C H; Frikstad, K M; Hole, K H; Seierstad, T; Lyng, H

    2015-01-01

    Background: The hypoxia marker pimonidazole is a candidate biomarker of cancer aggressiveness. We investigated the transcriptional programme associated with pimonidazole staining in prostate cancer. Methods: Index tumour biopsies were taken by image guidance from an investigation cohort of 52 patients, where 43 patients received pimonidazole before prostatectomy. Biopsy location within the index tumour was verified for 46 (88%) patients, who were included for gene expression profiling and immunohistochemistry. Two independent cohorts of 59 and 281 patients were used for validation. Results: Expression of genes in proliferation, DNA repair and hypoxia response was a major part of the transcriptional programme associated with pimonidazole staining. A signature of 32 essential genes was constructed and showed positive correlation to Ki67 staining, confirming the increased proliferation in hypoxic tumours as suggested from the gene data. Positive correlations were also found to tumour stage and lymph node status, but not to blood prostate-specific antigen level, consistent with the findings for pimonidazole staining. The association with aggressiveness was confirmed in validation cohorts, where the signature correlated with Gleason score and had independent prognostic impact, respectively. Conclusions: Pimonidazole staining reflects an aggressive hypoxic phenotype of prostate cancer characterised by upregulation of proliferation, DNA repair and hypoxia response genes. PMID:25461803

  15. An analysis of T lymphocyte subsets in tumour-transplanted mice on the basis of Lyt antigenic markers and functions

    PubMed Central

    Lala, P. K.; McKenzie, I. F. C.

    1982-01-01

    Small lymphocyte subsets were characterized radioautographically on the basis of several surface markers, viz. surface Ig (S-Ig), Thy-1 and Lyt (Ly-1, Ly-2 and 3) antigens in host lymphoid organs (thymus, spleen and blood) as well as at the tumour site at various stages of subcutaneous growth of two different syngeneic tumours—MPC-11 plasmacytoma and WEHI-164 fibrosarcoma in BALB/c mice. In both tumour-host combinations there was a rise in the levels of null (S-Ig-, Thy-1-) small lymphocytes as well as the Ly-23+ subset of T small lymphocytes at all the sites examined. The absolute number of these two subsets also increased excepting the case of null cell rise in the thymus which was relative. The functional potentials of Lyt subsets were explored by employing in vitro and in vivo assays. While no appreciable levels of anti-tumour cytotoxic T cells (Tc) were detectable by a 51Cr release assay in the host spleen or the tumour-draining lymph nodes at any stage of growth of MPC-11 tumour, such Tc was generated in vitro by a co-cultivation of unprimed spleen cells with irradiated MPC-11 cells. These Tc were Thy-1+ and Ly-12+, as noted from antibody+C′ mediated abrogation of cytotoxicity. These results suggested that the generation of anti-tumour Tc in vivo was suppressed in tumour-bearing hosts. The possibility of a cell-mediated suppression was tested by an adoptive transfer of thymocytes or splenocytes from tumour-bearing mice into naive or pre-immunized recipients which then received fresh tumour transplants. This procedure caused a specific enhancement of tumour growth in three tumour-host combinations: MPC-11 or WEHI-164 tumour in BALB/c mice and W-1 fibrosarcoma in CBA mice. The suppressor lineage lymphocytes appearing in vivo were found to be Thy-1+ and Ly-1-, 2+, as noted from antibody +C′ mediated abrogation of their tumour-growth promoting ability. They appeared earlier (7 days) in the thymus and later (>2 weeks) in the spleen and then persisted during

  16. 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

  17. 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

  18. 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

  19. Enhanced immune recognition of cryptic glycan markers in human tumours

    PubMed Central

    Newsom-Davis, Thomas E; Wang, Denong; Steinman, Lawrence; Chen, Paul F-T; Wang, Lai-Xi; Simon, A Katharina; Screaton, Gavin R

    2009-01-01

    Abnormal glycosylation is one of the hallmarks of the cancer cell and is associated with tumour invasion and metastasis. The development of tumour associated carbohydrate antigen (TACA) vaccines has been problematic due to poor immunogenicity. However when appropriate targets can be identified, passive immunisation with monoclonal antibodies (mAbs) directed against TACAs have been shown to have anti-tumour activity. Fas ligand (FasL) is a transmembrane protein which induces apoptosis in cells expressing its receptor, Fas. When grafted into mice, FasL-expressing tumour cells break immunological tolerance to self-antigens and induce antibody mediated tumour immunity. Here, five IgM mAbs were produced from mice vaccinated with FasL-expressing B16F10 mouse melanoma cells. They recognise various syngeneic and allogeneic murine tumour cell lines. One mAb, TM10, recognises a range of human tumour cell lines including melanoma, prostate and ovarian cancer. It does not bind to untransformed cells. The epitopes recognised by all the mAbs were carbohydrates expressed on proteins. Using carbohydrate microarrays, the antigenic targets of TM10 were found to be high-mannose core structures of N-linked glycans. In normal cells high mannose clusters are hidden by extensive saccharide branching but they become exposed in cancer cells as a result of abnormal glycosylation pathways. Vaccination with FasL-expressing tumours therefore enables the immune system to break tolerance to self-antigens, allowing identification of novel TACAs that can form the basis of future humoral anti-cancer therapy. PMID:19223535

  20. Cytosolic thymidine kinase is a specific histopathologic tumour marker for breast carcinomas.

    PubMed

    He, Qimin; Mao, Yongrong; Wu, Jainping; Decker, Catrine; Merza, Malik; Wang, Naining; Eriksson, Staffan; Castro, Juan; Skog, Sven

    2004-10-01

    Thymidine kinase 1 (TK1), an enzyme involved in the synthesis of precursors for DNA, and thus proliferation dependent, has been suggested as a good tumour marker. We have recently developed poly/monoclonal antibodies against TK1, which proved useful for diagnostics in both serum and immunohistochemistry of cancer patients. The anti-TK1 monoclonal antibodies (mAbs) 1D11 and 1E3 were characterized by Western blot, immunoprecipitation and flow cytometry. TK1 mAbs and Ki-67 mAb were then used for immunohistochemistry staining of tumour sections from 54 patients with ductal infiltrated breast carcinoma. Results showed the relative number of patients with positively stained tumours for TK1 (mAb 1D11) and for Ki-67 (mAb MIB-1) were 47 and 41%, respectively, significantly related (p=0.007). Combination of TK1 mAbs 1D11 and 1E3 increased this number to 56%, due to detection of a significantly higher number of patients with grade 2 tumours. Patients with stage II and grade 2 tumours showed significantly higher TK1 staining when compared to stage I and grade 1. Ki-67 staining was significantly higher in stage III and grade 3. The tumours only stained for TK1 represented higher stages and grades, while tumours staining only for Ki-67 were of lower stages and grades. Combining TK1 and Ki-67 increased the number of patients with positively stained tumours to 69%. In conclusion, TK1 is a reliable marker for identification of patients with grade 2 tumours. The highest number of patients with positively stained tumours were obtained when both TK1 and Ki-67 markers were used. PMID:15375544

  1. 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.

  2. 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

  3. 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.

  4. Tumor markers in prostate cancer I: blood-based markers

    PubMed Central

    Shariat, Shahrokh F.; Semjonow, Axel; Lilja, Hans; Savage, Caroline; Vickers, Andrew J.; Bjartell, Anders

    2013-01-01

    INTRODUCTION The introduction of total prostate specific antigen (total PSA) testing in blood has revolutionized the detection and management of men with prostate cancer (PCa). The objective of this review was to discuss the challenges of PCa biomarker research, definition of the type of PCa biomarkers, the statistical considerations for biomarker discovery and validation, and to review the literature regarding total PSA velocity and novel blood-based biomarkers. METHODS An English-language literature review of the Medline database (1990 to August 2010) of published data on blood-based biomarkers and PCa was undertaken. RESULTS The inherent biological variability of total PSA levels affects the interpretation of any single result. Men who will eventually develop PCa have increased total PSA levels years or decades before the cancer is diagnosed. Total PSA velocity improves predictiveness of total PSA only marginally, limiting its value for PCa screening and prognostication. The combination of PSA molecular forms and other biomarkers improve PCa detection substantially. Several novel blood-based biomarkers such as human glandular kallikrein 2 (hK2), urokinase plasminogen activator (uPA) and its receptor (uPAR), transforming growth factor-beta 1 (TGF-β1); interleukin-6 (IL-6) and its receptor (IL-6R) may help PCa diagnosis, staging, prognostication, and monitoring. Panels of biomarkers that capture the biologic potential of PCa are in the process of being validated for PCa prognostication. CONCLUSIONS PSA is a strong prognostic marker for long-term risk of clinically relevant cancer. However, there is a need for novel biomarkers that aid clinical decision making about biopsy and initial treatment. There is no doubt that progress will continue based on the integrated collaboration of researchers, clinicians and biomedical firms. PMID:21604943

  5. Pleural fluid tumour markers in malignant pleural effusion with inconclusive cytologic results

    PubMed Central

    Antonangelo, L.; Sales, R.K.; Corá, A.P.; Acencio, M.M.P.; Teixeira, L.R.; Vargas, F.S.

    2015-01-01

    Background The presence of tumour cells in pleural fluid or tissue defines an effusion as malignant. Cytology analysis of the pleural fluid has about 60% diagnostic sensitivity. Several tests have been proposed to improve diagnosis—among them, the concentrations of tumour markers in pleural fluid. We evaluated whether the concentrations of tumour markers in pleural fluid could improve the diagnosis of malignant pleural effusion (mpe) when cytology is doubtful. Methods Lymphocytic pleural fluids secondary to tuberculosis or malignancy from 156 outpatients were submitted for cytology and tumour marker quantification [carcinoembryonic antigen (cea), cancer antigen 15-3 (ca15-3), carbohydrate antigen 19-9 (ca19-9), cancer antigen 72-4 (ca72-4), cancer antigen 125 (ca125), and cyfra 21-1). Oneway analysis of variance, the Student t-test or Mann–Whitney test, and receiver operating characteristic curves were used in the statistical analysis. Results Concentrations of the tumour markers cea, ca15-3, ca125, and cyfra 21-1 were higher in mpes than they were in the benign effusions (p < 0.001), regardless of cytology results. The markers ca19-9 and ca72-4 did not discriminate malignant from benign effusions. When comparing the concentrations of tumour markers in mpes having positive, suspicious, or negative cytology with concentrations in benign effusions, we observed higher levels of cea, ca15-3, cyfra 21-1, and ca125 in malignant effusions with positive cytology (p = 0.003, p = 0.001, p = 0.002, and p = 0.001 respectively). In pleural fluid, only ca125 was higher in mpes with suspicious or negative cytology (p = 0.001) than in benign effusions. Conclusions Given high specificity and a sensitivity of about 60%, the concentrations of tumour markers in pleural effusions could be evaluated in cases of inconclusive cytology in patients with a high pre-test chance of malignancy or a history of cancer. PMID:26628873

  6. Blood oxidative stress markers after ultramarathon swimming.

    PubMed

    Kabasakalis, Athanasios; Kyparos, Antonios; Tsalis, Georgios; Loupos, Dimitrios; Pavlidou, Anastasia; Kouretas, Dimitrios

    2011-03-01

    Data on redox balance in response to marathon swimming are lacking, whereas findings from studies using other types of ultraendurance exercise are controversial. The aim of the present study was to investigate the effect of ultramarathon swimming on selective blood oxidative stress markers. Five well-trained male swimmers aged 28.8 (6.0) years participated in the study. Blood samples were obtained before and after the ultramarathon swimming, for full blood count analysis and determination of protein carbonyls, thiobarbituric acid-reactive substances (TBARS), and total antioxidant capacity (TAC). The swimmers swam 19.4 (3.4) hours, covering 50.5 (15.0) km. Hematocrit and erythrocyte count, and leukocyte, neutrophil and monocyte counts were significantly elevated after swimming, whereas protein carbonyls, TBARS and TAC did not significantly change. The findings of the present study indicate that well-trained swimmers were able to regulate a redox homeostasis during ultra-long duration swimming. It is also postulated that the relatively low intensity of marathon swimming may not be a sufficient stimulus to induce oxidative stress in well-trained swimmers. The fact that low-intensity long-duration exercise protocols are not associated with oxidative damage is useful knowledge for coaches and athletes in scheduling the content of the training sessions that preceded and followed these exercise protocols. PMID:20613649

  7. 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. PMID:8694552

  8. Commensal bacteria drive endogenous transformation and tumour stem cell marker expression through a bystander effect

    PubMed Central

    Wang, Xingmin; Yang, Yonghong; Huycke, Mark M

    2015-01-01

    Objective Commensal bacteria and innate immunity play a major role in the development of colorectal cancer (CRC). We propose that selected commensals polarise colon macrophages to produce endogenous mutagens that initiate chromosomal instability (CIN), lead to expression of progenitor and tumour stem cell markers, and drive CRC through a bystander effect. Design Primary murine colon epithelial cells were repetitively exposed to Enterococcus faecalis-infected macrophages, or purified trans-4-hydroxy-2-nonenal (4-HNE)—an endogenous mutagen and spindle poison produced by macrophages. CIN, gene expression, growth as allografts in immunodeficient mice were examined for clones and expression of markers confirmed using interleukin (IL) 10 knockout mice colonised by E. faecalis. Results Primary colon epithelial cells exposed to polarised macrophages or 4-hydroxy-2-nonenal developed CIN and were transformed after 10 weekly treatments. In immunodeficient mice, 8 of 25 transformed clones grew as poorly differentiated carcinomas with 3 tumours invading skin and/or muscle. All tumours stained for cytokeratins confirming their epithelial cell origin. Gene expression profiling of clones showed alterations in 3 to 7 cancer driver genes per clone. Clones also strongly expressed stem/progenitor cell markers Ly6A and Ly6E. Although not differentially expressed in clones, murine allografts positively stained for the tumour stem cell marker doublecortin-like kinase 1. Doublecortin-like kinase 1 and Ly6A/E were expressed by epithelial cells in colon biopsies for areas of inflamed and dysplastic tissue from E. faecalis-colonised IL-10 knockout mice. Conclusions These results validate a novel mechanism for CRC that involves endogenous CIN and cellular transformation arising through a microbiome-driven bystander effect. PMID:24906974

  9. Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner

    PubMed Central

    Chauhan, Vikash P.; Stylianopoulos, Triantafyllos; Martin, John D.; Popović, Zoran; Chen, Ou; Kamoun, Walid S.; Bawendi, Moungi G.; Fukumura, Dai; Jain, Rakesh K.

    2012-01-01

    The blood vessels of cancerous tumours are leaky1–3 and poorly organized4–7. This can increase the interstitial fluid pressure (IFP) inside tumours and reduce blood supply to them, which impairs drug delivery8–9. Anti-angiogenic therapies – which “normalize” the abnormal blood vessels in tumours by making them less leaky – have been shown to improve the delivery and effectiveness of chemotherapeutics with low molecular-weights10, but it remains unclear whether normalizing tumour vessels can improve the delivery of nanomedicines. Here we show that repairing the abnormal vessels in mammary tumours, by blocking vascular endothelial growth factor (VEGF) receptor-2, improves the delivery of small nanoparticles (12nm diameter) while hindering the delivery of large nanoparticles (125nm diameter). We utilize a mathematical model to show that reducing vessel wall pore sizes through normalization decreases IFP in tumours, allowing small nanoparticles to enter them more rapidly. However, increased steric and hydrodynamic hindrances, also associated with smaller pores, make it more difficult for large nanoparticles to enter tumours. Our results further suggest that smaller (~12nm) nanomedicines are ideal for cancer therapy, owing to superior tumour penetration. PMID:22484912

  10. 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

  11. 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

  12. 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

  13. Evaluation of Minichromosome Maintenance Protein 7 and c-KIT as Prognostic Markers in Feline Cutaneous Mast Cell Tumours.

    PubMed

    Dobromylskyj, M J; Rasotto, R; Melville, K; Smith, K C; Berlato, D

    2015-11-01

    Mast cell tumours (MCTs) are a common skin tumour in cats, but there is currently no histological grading system or reliable prognostic marker for this species (unlike the situation for dogs). This study utilized a set of 71 feline cutaneous MCTs with known clinical outcomes to assess the potential of various prognostic markers, including the cellular proliferation marker minichromosome maintenance protein (MCM)-7, mitotic index and various KIT labelling characteristics, including KIT positivity, KIT labelling pattern and KIT immunoreactivity score (IS). Of the factors studied, the mitotic index and the KIT labelling pattern were the only features associated significantly with survival times, while the proliferation marker MCM7 and the KIT IS were not. The study also highlights the variability of KIT labelling characteristics between tumours, which may prevent use of this marker as a diagnostic and prognostic tool. PMID:26385324

  14. Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines.

    PubMed

    Duffy, M J; van Dalen, A; Haglund, C; Hansson, L; Klapdor, R; Lamerz, R; Nilsson, O; Sturgeon, C; Topolcan, O

    2003-04-01

    In recent years, numerous serum and cell/tissue-based markers have been described for colorectal cancer (CRC). The aim of this article was to provide guidelines for the routine clinical use of some of these markers. Lack of sensitivity and specificity preclude the use of any available serum markers such as carcinoembryonic antigen (CEA), CA 19-9, CA 242, CA 72-4, tissue polypeptide antigen (TPA) or tissue polypeptide-specific antigen (TPS) for the early detection of CRC. However, preoperative measurement of CEA is desirable as this may give independent prognostic information, help with surgical management and provide a baseline level for subsequent determinations. For patients with stage 2 (Dukes' B) and 3 (Dukes' C) disease who may be candidates for liver resection, CEA levels should be measured every 2-3 months for at least 3 years after diagnosis. For monitoring treatment of advanced disease, CEA should also be tested every 2-3 months. Insufficient evidence is presently available to recommend the routine use of other serum markers for monitoring purposes. Similarly, the new cell and tissue-based markers (e.g, ras, P53) cannot yet be recommended for routine clinical use. PMID:12651195

  15. Nitroimidazole adducts as markers for tissue hypoxia: mechanistic studies in aerobic normal tissues and tumour cells.

    PubMed Central

    Parliament, M. B.; Wiebe, L. I.; Franko, A. J.

    1992-01-01

    Two aspects of the aerobic metabolism of nitroimidazole markers for hypoxia were investigated. Several normal murine tissues which are likely to be well oxygenated bind misonidazole at rates comparable to those of hypoxic regions in tumours. The possibility that this aerobic activation occurs via an oxygen independent process such as an initial two electron reduction was studied. Binding to the oesophageal mucosa of mice which occurred under hypoxia in vitro was inhibited by at least 95% in the presence of 10% oxygen. Dicoumarol, an inhibitor of DT-diaphorase, was shown to cause only small reductions in misonidazole binding to oesophageal epithelium and smooth muscle in vitro and to EMT6 tumours, liver, oesophageal and tracheal epithelium, parotid gland and smooth muscle in vivo. Thus an oxygen-insensitive process is not a major cause of the high binding rate in oesophageal mucosa, and may not contribute significantly to the observed binding in other normal tissues. It has been suggested that metabolism of nitroimidazoles by aerobic cells in tumours might be sufficient to minimise access of these compounds to hypoxic regions, particularly at the micromolar concentrations currently in use clinically. The uptake of 125I-iodoazomycin arabinoside by RIF-1 and EMT6 tumours was found to be directly proportional to injected dose over concentrations between 0.5 and 50 microM. Labelling of hypoxic regions in EMT6 tumours by high specific activity 3H-misonidazole at 1 microM was found to be similar to that obtained at 50 microM. Images Figure 1 PMID:1280990

  16. Differential Expression of Prognostic Proteomic Markers in Primary Tumour, Venous Tumour Thrombus and Metastatic Renal Cell Cancer Tissue and Correlation with Patient Outcome

    PubMed Central

    Laird, Alexander; O’Mahony, Fiach C.; Nanda, Jyoti; Riddick, Antony C. P.; O’Donnell, Marie; Harrison, David J.; Stewart, Grant D.

    2013-01-01

    Renal cell carcinoma (RCC) is the most deadly of urological malignancies. Metastatic disease affects one third of patients at diagnosis with a further third developing metastatic disease after extirpative surgery. Heterogeneity in the clinical course ensures predicting metastasis is notoriously difficult, despite the routine use of prognostic clinico-pathological parameters in risk stratification. With greater understanding of pathways involved in disease pathogenesis, a number of biomarkers have been shown to have prognostic significance, including Ki67, p53, vascular endothelial growth factor receptor 1 (VEGFR1) and ligand D (VEGFD), SNAIL and SLUG. Previous pathway analysis has been from study of the primary tumour, with little attention to the metastatic tumours which are the focus of targeted molecular therapies. As such, in this study a tissue microarray from 177 patients with primary renal tumour, renal vein tumour thrombus and/or RCC metastasis has been created and used with Automated Quantitative Analysis (AQUA) of immunofluorescence to study the prognostic significance of these markers in locally advanced and metastatic disease. Furthermore, this has allowed assessment of differential protein expression between the primary tumours, renal vein tumour thrombi and metastases. The results demonstrate that clinico-pathological parameters remain the most significant predictors of cancer specific survival; however, high VEGFR1 or VEGFD can predict poor cancer specific survival on univariate analysis for locally advanced and metastatic disease. There was significantly greater expression of Ki67, p53, VEGFR1, SLUG and SNAIL in the metastases compared with the primary tumours and renal vein tumour thrombi. With the exception of p53, these differences in protein expression have not been shown previously in RCC. This confirms the importance of proliferation, angiogenesis and epithelial to mesenchymal transition in the pathogenesis and metastasis of RCC. Importantly

  17. Expression pattern of clinically relevant markers in paediatric germ cell- and sex-cord stromal tumours is similar to adult testicular tumours.

    PubMed

    Mosbech, Christiane Hammershaimb; Svingen, Terje; Nielsen, John Erik; Toft, Birgitte Groenkaer; Rechnitzer, Catherine; Petersen, Bodil Laub; Rajpert-De Meyts, Ewa; Hoei-Hansen, Christina Engel

    2014-11-01

    Paediatric germ cell tumours (GCTs) are rare and account for less than 3 % of childhood cancers. Like adult GCTs, they probably originate from primordial germ cells, but the pattern of histopathological types is different, and they occur predominantly in extragonadal sites along the body midline. Because they are rare, histology of paediatric GCTs is poorly documented, and it remains unclear to what extent they differ from adult GCTs. We have analysed 35 paediatric germ cell tumours and 5 gonadal sex-cord stromal tumours from prepubertal patients aged 0-15 years, to gain further knowledge, elaborate on clinical-pathological associations and better understand their developmental divergence. The tumours were screened for expression of stemness-related factors (OCT4, AP-2γ, SOX2), classical yolk sac tumours (YSTs; AFP, SALL4), GCTs (HCG, PLAP, PDPN/D2-40), as well as markers for sex-cord stromal tumour (PDPN, GATA4). All YSTs expressed AFP and SALL4, with GATA4 present in 13/14. The majority of teratomas expressed SOX2 and PDPN, whereas SALL4 was found in 8/13 immature teratomas. Adult seminoma markers AP-2γ, OCT4, SALL4 and PDPN were all expressed in dysgerminoma. We further report a previously unrecognised pathogenetic relationship between AFP and SALL4 in YST in that different populations of YST cells express either SALL4 or AFP, which suggests variable differentiation status. We also show that AP-2γ is expressed in the granulosa layer of ovarian follicles and weakly expressed in immature but not in mature granulosa cell tumours. Our findings indicate that the expression pattern of these antigens is similar between paediatric and adult GCTs, even though they develop along different developmental trajectories. PMID:25074678

  18. 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

  19. 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

  20. In vivo 31P nuclear magnetic resonance spectroscopy of experimental murine tumours and human tumour xenografts: effects of blood flow modification.

    PubMed Central

    Bremner, J. C.; Counsell, C. J.; Adams, G. E.; Stratford, I. J.; Wood, P. J.; Dunn, J. F.; Radda, G. K.

    1991-01-01

    The effect of hydralazine on tumours appears to vary depending on tumour type. Blood flow and radiation sensitivity decrease more in murine tumours than human tumour xenografts. In this study a comparison between various tumour types has been made using in vivo 31P nuclear magnetic resonance spectroscopy (NMRS) to follow the metabolic responses occurring after clamping or intravenous administration of hydralazine (5 mg kg-1). Large increases in the Pi/total phosphate ratio were found with the murine sarcomas, KHT and RIF-1 implanted into C3H/He mice. However little or no effect was seen for the two human xenografted tumours, HX118 and HT29 implanted in MFI nu/nu/01a mice. An intermediate response was observed for KHT tumours grown in nu/nu mice. All tumours showed a large response to clamping. The anaesthetic Hypnorm/Hypnovel has a great influence on the response of the tumour metabolism to hydralazine appearing to both prolong and increase the changes induced. There is evidence to support the theory that the changes in 31P spectra are related to the oxygen status of the tumours. PMID:1931606

  1. Real-time RT-PCR systems for CTC detection from blood samples of breast cancer and gynaecological tumour patients (Review).

    PubMed

    Andergassen, Ulrich; Kölbl, Alexandra C; Mahner, Sven; Jeschke, Udo

    2016-04-01

    Cells, which detach from a primary epithelial tumour and migrate through lymphatic vessels and blood stream are called 'circulating tumour cells'. These cells are considered to be the main root of remote metastasis and are correlated to a worse prognosis concerning progression-free and overall survival of the patients. Therefore, the detection of the minimal residual disease is of great importance regarding therapeutic decisions. Many different detection strategies are already available, but only one method, the CellSearch® system, reached FDA approval. The present review focusses on the detection of circulating tumour cells by means of real-time PCR, a highly sensitive method based on differences in gene expression between normal and malignant cells. Strategies for an enrichment of tumour cells are mentioned, as well as a large panel of potential marker genes. Drawbacks and advantages of the technique are elucidated, whereas, the greatest advantage might be, that by selection of appropriate marker genes, also tumour cells, which have already undergone epithelial to mesenchymal transition can be detected. Finally, the application of real-time PCR in different gynaecological malignancies is described, with breast cancer being the most studied cancer entity. PMID:26848098

  2. Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels

    PubMed Central

    Chauhan, Vikash P.; Martin, John D.; Liu, Hao; Lacorre, Delphine A.; Jain, Saloni R.; Kozin, Sergey V.; Stylianopoulos, Triantafyllos; Mousa, Ahmed S.; Han, Xiaoxing; Adstamongkonkul, Pichet; Popović, Zoran; Huang, Peigen; Bawendi, Moungi G.; Boucher, Yves; Jain, Rakesh K.

    2013-01-01

    Cancer and stromal cells actively exert physical forces (solid stress) to compress tumour blood vessels, thus reducing vascular perfusion. Tumour interstitial matrix also contributes to solid stress, with hyaluronan implicated as the primary matrix molecule responsible for vessel compression because of its swelling behaviour. Here we show, unexpectedly, that hyaluronan compresses vessels only in collagen-rich tumours, suggesting that collagen and hyaluronan together are critical targets for decompressing tumour vessels. We demonstrate that the angiotensin inhibitor losartan reduces stromal collagen and hyaluronan production, associated with decreased expression of profibrotic signals TGF-β1, CCN2 and ET-1, downstream of angiotensin-II-receptor-1 inhibition. Consequently, losartan reduces solid stress in tumours resulting in increased vascular perfusion. Through this physical mechanism, losartan improves drug and oxygen delivery to tumours, thereby potentiating chemotherapy and reducing hypoxia in breast and pancreatic cancer models. Thus, angiotensin inhibitors —inexpensive drugs with decades of safe use — could be rapidly repurposed as cancer therapeutics. PMID:24084631

  3. Canine cutaneous peripheral nerve sheath tumours versus fibrosarcomas can be differentiated by neuroectodermal marker genes in their transcriptome.

    PubMed

    Klopfleisch, R; Meyer, A; Lenze, D; Hummel, M; Gruber, A D

    2013-02-01

    The diagnostic differentiation between canine fibrosarcomas and peripheral nerve sheath tumours (PNSTs) is based on histopathological phenotype. Histological differentiation of these tumours can, however, be challenging and there is a lack of immunohistochemical markers to prove their histogenic origin. To identify possible PNST markers and to further characterize their histogenic origin we compared histologically well-defined canine fibrosarcomas and PNSTs by cDNA microarray analysis. Forty-five annotated gene products were significantly differentially expressed between both tumour types. Seven of these gene products, known to be specifically expressed in neuroectodermal tissues, had higher expression levels in PNSTs: FMN2, KIF1B, GLI1, ROBO1, NMUR2, DOK4 and HMG20B. Conversely, eight genes associated with carcinogenesis had higher expression in fibrosarcomas: FHL2, PLAGL1, FNBP1L, BAG2, HK1, CSK and Cox5A. Comparison of the fibrosarcoma and PNST transcriptome therefore identified PNST phenotype-associated genes involved in neuroectodermal differentiation, which may be useful as diagnostic markers. Furthermore, the genes associated with the fibrosarcoma phenotype may serve as markers to differentiate fibrosarcomas from other tumour types. PMID:22818216

  4. Plasticity of Blood- and Lymphatic Endothelial Cells and Marker Identification

    PubMed Central

    Keuschnigg, Johannes; Karinen, Sirkku; Auvinen, Kaisa; Irjala, Heikki; Mpindi, John-Patrick; Kallioniemi, Olli; Hautaniemi, Sampsa; Jalkanen, Sirpa; Salmi, Marko

    2013-01-01

    The distinction between lymphatic and blood vessels is biologically fundamental. Here we wanted to rigorously analyze the universal applicability of vascular markers and characteristics of the two widely used vascular model systems human microvascular endothelial cell line-1 (HMEC-1) and telomerase-immortalized microvascular endothelial cell line (TIME). Therefore we studied the protein expression and functional properties of the endothelial cell lines HMEC-1 and TIME by flow cytometry and in vitro flow assays. We then performed microarray analyses of the gene expression in these two cell lines and compared them to primary endothelial cells. Using bioinformatics we then defined 39 new, more universal, endothelial-type specific markers from 47 primary endothelial microarray datasets and validated them using immunohistochemistry with normal and pathological tissues. We surprisingly found that both HMEC-1 and TIME are hybrid blood- and lymphatic cells. In addition, we discovered great discrepancies in the previous identifications of blood- and lymphatic endothelium-specific genes. Hence we identified and validated new, universally applicable vascular markers. Summarizing, the hybrid blood-lymphatic endothelial phenotype of HMEC-1 and TIME is indicative of plasticity in the gene expression of immortalized endothelial cell lines. Moreover, we identified new, stable, vessel-type specific markers for blood- and lymphatic endothelium, useful for basic research and clinical diagnostics. PMID:24058540

  5. Plasminogen Activator of the Blood Vessels in Tumours and in Carrageenin-induced Granulomas

    PubMed Central

    Pick, C. R.; Cater, D. B.

    1971-01-01

    Fibrinolytic activity in tumours was studied by the fibrin slide technique. The tumour cells were inactive and fibrinolysis was seen only in areas with young blood vessels. In carrageenin-induced granulomas at 6 days the fibrinolytic activity was small and confined to mature veins, but from 7-14 days activity was high in zones containing young vessels supplying the terminal capillary buds; these latter showed no activity. In old fibrosed granulomas there was no fibrinolytic activity. The vascular permeability changes of inflammation (detected by the colloidal carbon technique) showed no correlation with fibrinolytic activity, and systemic injection of inflammatory agents had no effect on the fibrinolytic activity of the vessels. These findings are discussed in relationship to tumour vascularization. ImagesFigs. 5-8Figs. 1-4 PMID:5547651

  6. Tumour progression of human neuroblastoma cells tagged with a lacZ marker gene: earliest events at ectopic injection sites.

    PubMed Central

    Kleinman, N. R.; Lewandowska, K.; Culp, L. A.

    1994-01-01

    Human Platt neuroblastoma cells were transfected with the marker gene, bacterial lacZ, to track cells at the earliest stages after ectopic injection at two different sites in athymic nude mice. Three clones (LZPt-1,-2 and -3) of differing morphologies were analysed. All clones yielded large primary tumours subcutaneously or intradermally with similar latency. While LZPt-2 and -3 clones generated well-staining primary tumours, LZPt-1 cells yielded many non-staining tumours, indicating greater instability of lacZ expression for this clone in situ (stability of lacZ expression in culture was similar for all three clones). After s.c. or intradermal injections, tumour cells were tracked for 1 h to > 3 weeks (palpable) to evaluate the topology and population expansion characteristics at the earliest times. From 1 h to 2 days, tumour cells were concentrated in central masses with 'crinkly hair' distributions emanating from the periphery. Between 3 and 7 days, these 'crinkly hair' patterns were cleared from the tissue, leaving dense ovoid patterns of tumour cells. These concentrations of cells expanded collectively, not by division of one or a few cells, but by division of many cells. For clone LZPt-1, cells stained well with X-gal for 2-3 days; by 7 days, most cells were non-staining. Evidence suggests that lacZ expression is turned off in these tumour cells, rather than a lacZ- cell type clonally dominating the population. For all three clones, tumour cells remained rounded and did not spread in any tissue environment at all time points, indicating very different matrix adhesion mechanisms operating in situ compared with their distinctive spreading patterns in culture. Angioneogenesis near primary tumours became evident by 2-3 days, leading to extensive vascularisation by 1-2 weeks. Overall, these studies indicate common tumour progression characteristics for three different clones of human neuroblastoma, insight into lacZ instability mechanisms operating in one of these

  7. Early detection of metastatic disease in asymptomatic breast cancer patients with whole-body imaging and defined tumour marker increase

    PubMed Central

    Di Gioia, D; Stieber, P; Schmidt, G P; Nagel, D; Heinemann, V; Baur-Melnyk, A

    2015-01-01

    Background: Follow-up care in breast cancer is still an issue of debate. Diagnostic methods are more sensitive, and more effective therapeutic options are now available. The risk of recurrence is not only influenced by tumour stage but also by the different molecular subtypes. This study was performed to evaluate the use of whole-body imaging combined with tumour marker monitoring for the early detection of asymptomatic metastatic breast cancer (MBC). Methods: This analysis was performed as part of a follow-up study evaluating 813 patients with a median follow-up of 63 months. After primary therapy, all patients underwent tumour marker monitoring for CEA, CA 15-3 and CA 125 at 6-week intervals within an intensified diagnostic aftercare algorithm. A reproducible previously defined increase was considered as a strong indicator of MBC. From 2007 to 2010, 44 patients with tumour marker increase underwent whole-body magnetic resonance imaging and/or an FDG-PET/CT scan. Histological clarification and/or imaging follow-up were done. Results: Metastases were detected in 65.9% (29/44) of patients, 13.6% (6/44) had secondary malignancies besides breast cancer and 20.5% (9/44) had no detectable malignancy. Limited disease was found in 24.1% (7/29) of patients. Median progression-free survival of MBC was 9.2 months and median overall survival was 41.1 months. The 3- and 5-year survival rates were 64.2% and 40.0%, respectively. Conclusions: A reproducible tumour marker increase followed by whole-body imaging is highly effective for early detection. By consequence, patients might benefit from earlier detection and improved therapeutic options with a prolonged survival. PMID:25647014

  8. 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

  9. Acetylcholinesterase: an enzymatic marker of human red blood cell aging.

    PubMed

    Prall, Y G; Gambhir, K K; Ampy, F R

    1998-01-01

    The purpose of this investigation was to determine whether acetylcholinesterase (AChE) can be used as a marker of cell aging in human red blood cells (RBCs). This study used consented subjects; both males and females in an age range of 21-42 years. The blood samples (8-9 mL) were drawn in tubes containing sodium heparin or EDTA as anticoagulants. To avoid contamination with other cells, (lymphocytes, monocytes and reticulocytes), RBCs were purified (PRBC) by Hypaque-Ficoll gradient technique. The PRBCs were subfractionated into young (y) (1.08-1.09), mid (m) (1.09-1.11) and old (o) (1.11-1.12) percoll density (g/mL) fractions using a discontinuous percoll gradient. The mean +/- 1 SD AChE per gram hemoglobin (U/g Hgb) activities in whole blood (WB) purified human red blood cells (PRBCs), young human red blood cells (y-RBCs), mid age human red blood cells (m-RBCs) and old human red blood cells (o-RBCs) were 27.4 +/- 2.98, 26.0 +/- 2.33, 25.5 +/- 1.64, 20.3 +/- 3.84, 14.6 +/- 3.42 in males and 26.3 +/- 4.44, 24.8 /- 4.83, 26.4 +/- 4.59, 24.0 +/- 5.50 and 12.4 +/- 7.09 in females respectively. Although there was variation in the data, the results indicated that old human red blood cells showed significantly (p<.05) lower AChE activity compared to young human red blood cells of both sexes. These preliminary but novel observations suggest that AChE can be an excellent enzymatic marker for RBC aging in man. PMID:9698047

  10. 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

  11. 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

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

    PubMed Central

    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

    2016-01-01

    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

  13. Glucocorticoid-Induced Tumour Necrosis Factor Receptor-Related Protein: A Key Marker of Functional Regulatory T Cells

    PubMed Central

    Ronchetti, Simona; Ricci, Erika; Petrillo, Maria Grazia; Cari, Luigi; Migliorati, Graziella; Nocentini, Giuseppe; Riccardi, Carlo

    2015-01-01

    Glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR, TNFRSF18, and CD357) is expressed at high levels in activated T cells and regulatory T cells (Tregs). In this review, we present data from mouse and human studies suggesting that GITR is a crucial player in the differentiation of thymic Tregs (tTregs), and expansion of both tTregs and peripheral Tregs (pTregs). The role of GITR in Treg expansion is confirmed by the association of GITR expression with markers of memory T cells. In this context, it is not surprising that GITR appears to be a marker of active Tregs, as suggested by the association of GITR expression with other markers of Treg activation or cytokines with suppressive activity (e.g., IL-10 and TGF-β), the presence of GITR+ cells in tissues where Tregs are active (e.g., solid tumours), or functional studies on Tregs. Furthermore, some Treg subsets including Tr1 cells express either low or no classical Treg markers (e.g., FoxP3 and CD25) and do express GITR. Therefore, when evaluating changes in the number of Tregs in human diseases, GITR expression must be evaluated. Moreover, GITR should be considered as a marker for isolating Tregs. PMID:25961057

  14. 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

  15. 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

  16. Gamma-enolase: a well-known tumour marker, with a less-known role in cancer

    PubMed Central

    Vizin, Tjasa; Kos, Janko

    2015-01-01

    Background Gamma-enolase, known also as neuron-specific enolase (NSE), is an enzyme of the glycolytic pathway, which is expressed predominantly in neurons and cells of the neuroendocrine system. As a tumour marker it is used in diagnosis and prognosis of cancer; however, the mechanisms enrolling it in malignant progression remain elusive. As a cytoplasmic enzyme gamma-enolase is involved in increased aerobic glycolysis, the main source of energy in cancer cells, supporting cell proliferation. However, different cellular localisation at pathophysiological conditions, proposes other cellular engagements. Conclusions The C-terminal part of the molecule, which is not related to glycolytic pathway, was shown to promote survival of neuronal cells by regulating neuronal growth factor receptor dependent signalling pathways, resulting also in extensive actin cytoskeleton remodelling. This additional function could be important also in cancer cells either to protect cells from stressful conditions and therapeutic agents or to promote tumour cell migration and invasion. Gamma-enolase might therefore have a multifunctional role in cancer progression: it supports increased tumour cell metabolic demands, protects tumour cells from stressful conditions and promotes their invasion and migration. PMID:26401126

  17. 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

  18. 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

  19. 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

  20. 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

  1. Markers of Hepatitis Viruses by ELISA among Healthy Blood Donors.

    PubMed

    Shil, N; Rahman, A; Sultana, N; Yasmin, F

    2015-10-01

    This cross sectional study was done to have a comprehensive idea about prevalence and distribution of HBsAg and anti-HCV. The present serosurveilance study was done on healthy selected blood donors and conducted in the Department of Transfusion Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh for their relatives and friends and also voluntarily from January 2001 to July 2003. Samples were collected from blood donors (Voluntary and Party) who came for donation of blood. Blood samples taken from 10,200 apparently healthy blood donors with or without the previous history of jaundice in the Transfusion Medicine department of BSMMU was tested for HBsAg and Anti-HCV by standard commercial ELISA method during the period from 1st January 2001 to 30th June 2003. Reactive samples were retested. Samples positive in duplicate tests were taken as positive. Within 10,200 samples 550(5.39%) were found positive for HBsAg and 84(0.823%) positive for anti-HCV. Among 8670(8%) male donors 470(5.42%) was positive for HBaAg and 70(0.91%) positive for anti-HCV. Among 1530(15%) female donors 80(5.29%) found positive for HBsAg and 14(0.807%) positive for anti-HCV. Prevalence of both is more in male than female, young donors below 30 years (80%) are of least prevalence 4.43% for HBsAg and 0.73% for anti-HCV. Markers are raised in prevalence with age, highest among aged donors above 40 years 14.5% and 2.62 respectively. Markers are of least prevalence among students (4.47% and 0.47%), highest among working people (7.90 and 0.91%). Within 10,200 donors no one was found concomitantly positive for HBsAg and anti-HCV, study may help to have a comprehensive idea about prevalence and distribution of HBV and HCV among healthy blood donors/party donors 9,996(98%) and voluntary donors 204(2%). PMID:26620019

  2. 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

  3. Mitogen-activated Tasmanian devil blood mononuclear cells kill devil facial tumour disease cells.

    PubMed

    Brown, Gabriella K; Tovar, Cesar; Cooray, Anne A; Kreiss, Alexandre; Darby, Jocelyn; Murphy, James M; Corcoran, Lynn M; Bettiol, Silvana S; Lyons, A Bruce; Woods, Gregory M

    2016-08-01

    Devil facial tumour disease (DFTD) is a transmissible cancer that has brought the host species, the Tasmanian devil, to the brink of extinction. The cancer cells avoid allogeneic immune recognition by downregulating cell surface major histocompatibility complex (MHC) I expression. This should prevent CD8(+) T cell, but not natural killer (NK) cell, cytotoxicity. The reason why NK cells, normally reactive to MHC-negative cells, are not activated to kill DFTD cells has not been determined. The immune response of wild devils to DFTD, if it occurs, is uncharacterised. To investigate this, we tested 12 wild devils with DFTD, and found suggestive evidence of low levels of antibodies against DFTD cells in one devil. Eight of these devils were also analysed for cytotoxicity, however, none showed evidence for cytotoxicity against cultured DFTD cells. To establish whether mimicking activation of antitumour responses could induce cytotoxic activity against DFTD, Tasmanian devil peripheral blood mononuclear cells (PBMCs) were treated with either the mitogen Concanavalin A, the Toll-like receptor agonist polyinosinic:polycytidylic acid or recombinant Tasmanian devil IL-2. All induced the PBMC cells to kill cultured DFTD cells, suggesting that activation does not occur after encounter with DFTD cells in vivo, but can be induced. The identification of agents that activate cytotoxicity against DFTD target cells is critical for developing strategies to protect against DFTD. Such agents could function as adjuvants to induce functional immune responses capable of targeting DFTD cells and tumours in vivo. PMID:27089941

  4. An enzyme-linked immunosorbent assay for hypoxia marker binding in tumours.

    PubMed Central

    Raleigh, J. A.; La Dine, J. K.; Cline, J. M.; Thrall, D. E.

    1994-01-01

    An enzyme-linked immunosorbent assay (ELISA) has been developed for measuring the in vivo binding of a hexafluorinated 2-nitroimidazole (CCI-103F) in tumour tissue biopsies. The binding of CCI-103F is believed to reflect the presence of hypoxia in tumours. The ELISA provides a sensitive and convenient method of measuring CCI-103F binding which does not require the injection of radioactive reagents. The ELISA is based on reagents prepared from synthetic antigens formed by the reductive activation and binding of CCI-103F to proteins in novel test tube experiments. Calibration of the ELISA involved comparing the ELISA with the radioactivity contained either in protein-CCI-103F adducts formed in vitro with tritiated CCI-103F or in tissues isolated from a tumour-bearing dog which had been injected with tritium-labelled CCI-103F. The two approaches to calibration are compared. The scope and limitation of the ELISA for measuring the binding of CCI-103F is discussed and an example of the application of the ELISA to measuring changes in tumour hypoxia in canine patients undergoing fractionated radiation therapy is presented. Images Figure 3 PMID:8286212

  5. C-kit as a prognostic and therapeutic marker in canine cutaneous mast cell tumours: From laboratory to clinic.

    PubMed

    Gil da Costa, Rui M

    2015-07-01

    Cutaneous mast cell tumours (MCTs) are some of the most common canine neoplasms and their variable and often aggressive biological behaviour makes them particularly challenging for the veterinary practitioner. Over the years, scientists have accumulated a wealth of knowledge on these tumours and developed better prognostic markers and targeted therapies, mostly focused on inhibiting c-kit, a protein that plays a major role in the biopathology of MCTs. Masitinib and toceranib, targeted inhibitors of c-kit and other receptor tyrosine-kinases (RTKs), offer the promise of improving the outcome of patients with aggressive MCTs. Much of the available knowledge on MCTs is dispersed, making it difficult for practitioners to benefit when consulting a pathologist or making therapeutic decisions. This article seeks to bring together current knowledge on the biopathology of MCTs, reviewing prognostic markers and their applications, and the development of c-kit inhibitors in the context of the basic cellular, molecular and pathological features of MCTs. Future perspectives following recent biopathological data and experimental therapeutic approaches are also addressed. PMID:26021891

  6. Multiple Marker Detection in Peripheral Blood for NSCLC Diagnosis

    PubMed Central

    Ulivi, Paola; Mercatali, Laura; Casoni, Gian-Luca; Scarpi, Emanuela; Bucchi, Lauro; Silvestrini, Rosella; Sanna, Stefano; Monteverde, Marco; Amadori, Dino; Poletti, Venerino; Zoli, Wainer

    2013-01-01

    Background Non-invasive early detection of lung cancer could reduce the number of patients diagnosed with advanced disease, which is associated with a poor prognosis. We analyzed the diagnostic accuracy of a panel of peripheral blood markers in detecting non small cell lung cancer (NSCLC). Methods 100 healthy donors and 100 patients with NSCLC were enrolled onto this study. Free circulating DNA, circulating mRNA expression of peptidylarginine deiminase type 4 (PAD4/PADI4), pro-platelet basic protein (PPBP) and haptoglobin were evaluated using a Real-Time PCR-based method. Results Free circulating DNA, PADI4, PPBP and haptoglobin levels were significantly higher in NSCLC patients than in healthy donors (p<0.0001, p<0.0001, p = 0.0002 and p = 0.0001, respectively). The fitted logistic regression model demonstrated a significant direct association between marker expression and lung cancer risk. The odds ratios of individual markers were 6.93 (95% CI 4.15–11.58; p<0.0001) for free DNA, 6.99 (95% CI 3.75–13.03; p<0.0001) for PADI4, 2.85 (95% CI 1.71–4.75; p<0.0001) for PPBP and 1.16 (95% CI 1.01–1.33; p = 0.031) for haptoglobin. Free DNA in combination with PPBP and PADI4 gave an area under the ROC curve of 0.93, 95% CI = 0.90–0.97, with sensitivity and specificity over 90%. Conclusions Free circulating DNA analysis combined with PPBP and PADI4 expression determination appears to accurately discriminate between healthy donors and NSCLC patients. This non-invasive multimarker approach warrants further research to assess its potential role in the diagnostic or screening workup of subjects with suspected lung cancer. PMID:23468981

  7. Identification by a Digital Gene Expression Displayer (DGED) and test by RT-PCR analysis of new mRNA candidate markers for colorectal cancer in peripheral blood.

    PubMed

    Lauriola, Mattia; Ugolini, Giampaolo; Rosati, Giancarlo; Zanotti, Simone; Montroni, Isacco; Manaresi, Alessio; Zattoni, Davide; Rivetti, Stefano; Mattei, Gabriella; Coppola, Domenico; Strippoli, Pierluigi; Taffurelli, Mario; Solmi, Rossella

    2010-08-01

    Evidence from the literature widely supports the efficacy of screening for colorectal cancer (CRC) in reducing mortality. A blood-based assay, potentially, represents a more accessible early detection tool for the identification of circulating tumour cells originating from a primary tumour site in the body. The present work aimed at identifying a set of specific mRNAs expressed in colon tissue but not in blood cells. These mRNAs may represent useful markers for early detection of circulating colon cancer cells by a simple, qualitative RT-PCR assay, following RNA extraction from peripheral blood samples. Using a data-mining tool called cDNA digital gene expression displayer (DGED), based on serial analysis of gene expression (SAGE) from the Cancer Genome Anatomy Project (CGAP) database, 4-colon and 14-blood cDNA libraries were analyzed. We selected 7 genes expressed in colon tissue but not in blood and were able to test 6 of them by RT-PCR in peripheral blood of CRC patients and healthy controls. We present a relatively easy and highly reproducible technique for the detection of mRNA expression of genes as candidate markers of malignancy in blood samples of patients with colon cancer. SAGE DGED provided a list of the best candidate mRNAs predicted to detect colon cells in the blood, namely those encoding the following proteins: hypothetical protein LOC644844 (LOC644844, whose cDNA was not amplifiable), fatty acid binding protein 1 (FABP1), carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), mucin 13 cell surface associated (MUC13), guanylate cyclase activator 2A (GUCA2A), amiloride binding protein 1 (ABP1), galactoside-binding, solute carrier family 26, member 3 (SLC26A3). The mRNA expression of these genes was evaluated in 8 samples from subjects diagnosed with CRC and 9 from healthy controls. We observed the expression of 2 of the 6 investigated genes in the blood samples of the vast majority of patients considered, but also in a subset of the

  8. Evaluation of Uric Acid as a Prognostic Blood-Based Marker in a Large Cohort of Pancreatic Cancer Patients

    PubMed Central

    Stotz, Michael; Szkandera, Joanna; Seidel, Julia; Stojakovic, Tatjana; Samonigg, Hellmut; Reitz, Daniel; Gary, Thomas; Kornprat, Peter; Schaberl-Moser, Renate; Hoefler, Gerald; Gerger, Armin; Pichler, Martin

    2014-01-01

    Background Recently, chemical blood parameters gain more attraction as potential prognostic parameters in pancreatic cancer (PC). In the present study we investigated the prognostic relevance of the uric acid (UA) level in blood plasma at the time of diagnosis for overall survival (OS) in a large cohort of patients with PC. Patients and Methods Data from 466 consecutive patients with ductal adenocarcinoma of the pancreas were evaluated retrospectively. Overall survival (OS) was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of the UA level, univariate and multivariate Cox regression models were calculated. Results None of the clinicopathological parameters (tumour grade, clinical stage, age, CA19-9 level, Karnofski Index (KI) or surgical resection) except gender was associated with UA level. In univariate analysis we observed the elevated UA level (<5.1 versus ≥5.1 mg/dl, p = 0.017) as poor prognostic factor for OS. In the multivariate analysis that included age, gender, tumour grade, tumour stage, surgical resection, CA19-9 level, the KI and UA level we confirmed the UA level as independent prognostic factor for OS (HR = 1.373%; CI = 1.077–1.751; p = 0.011). Conclusion In conclusion, we identified the UA level at time of diagnosis as an independent prognostic factor in PC patients. Our results indicate that the UA level might represent a novel and useful marker for patient stratification in PC management. PMID:25133546

  9. Integrative genomic analyses identify LIN28 and OLIG2 as markers of survival and metastatic potential in childhood central nervous system primitive neuro-ectodermal brain tumours

    PubMed Central

    Picard, Daniel; Miller, Suzanne; Hawkins, Cynthia E; Bouffet, Eric; Rogers, Hazel A; Chan, Tiffany SY; Kim, Seung-Ki; Ra, Young-Shin; Fangusaro, Jason; Korshunov, Andrey; Toledano, Helen; Nakamura, Hideo; Hayden, James T; Chan, Jennifer; Lafay-Cousin, Lucie; Hu, Ping X; Fan, Xing; Muraszko, Karin M; Pomeroy, Scott L; Lau, Ching C; Ng, Ho-Keung; Jones, Chris; Meter, Timothy Van; Clifford, Steven C; Eberhart, Charles; Gajjar, Amar; Pfister, Stefan M; Grundy, Richard G; Huang, Annie

    2013-01-01

    Background Childhood Central Nervous System Primitive Neuro-Ectodermal brain Tumours (CNS-PNETs) are highly aggressive brain tumours for which molecular features and best therapeutic strategy remains unknown. We interrogated a large cohort of these rare tumours in order to identify molecular markers that will enhance clinical management of CNS-PNET. Methods Transcriptional and copy number profiles from primary hemispheric CNS-PNETs were examined using clustering, gene and pathways enrichment analyses to discover tumour sub-groups and group-specific molecular markers. Immuno-histochemical and/or gene expression analyses were used to validate and examine the clinical significance of novel sub-group markers in 123 primary CNS-PNETs. Findings Three molecular sub-groups of CNS-PNETs distinguished by primitive neural (Group 1), oligo-neural (Group 2) and mesenchymal lineage (Group 3) gene expression signature were identified. Tumour sub-groups exhibited differential expression of cell lineage markers, LIN28 and OLIG2, and correlated with distinct demographics, survival and metastatic incidence. Group 1 tumours affected primarily younger females; male: female ratios were respectively 0.61 (median age 2.9 years; 95% CI: 2.4–5.2; p≤ 0.005), 1.25 (median age 7.9 years; 95% CI: 6–9.7) and 1.63 (median age 5.9 years; 95% CI: 4.9–7.8) for group 1, 2 and 3 patients. Overall outcome was poorest in group 1 patients which had a median survival of 0.8 years (95% CI: 0.47–1.2; p=0.019) as compared to 1.8 years (95% CI: 1.4–2.3) and 4.3 years; (95% CI: 0.82–7.8) respectively for group 2 and 3 patients. Group 3 tumours had the highest incidence of metastases at diagnosis; M0: M+ ratio were respectively 0.9 and 3.9 for group 3, versus group 1 and 2 tumours combined (p=0.037). Interpretation LIN28 and OLIG2 represent highly promising, novel diagnostic and prognostic molecular markers for CNS PNET that warrants further evaluation in prospective clinical trials. PMID:22691720

  10. Effects of blood sample handling procedures on measurable inflammatory markers in plasma, serum and dried blood spot samples.

    PubMed

    Skogstrand, Kristin; Ekelund, Charlotte K; Thorsen, Poul; Vogel, Ida; Jacobsson, Bo; Nørgaard-Pedersen, Bent; Hougaard, David M

    2008-07-20

    The interests in monitoring inflammation by immunoassay determination of blood inflammatory markers call for information on the stability of these markers in relation to the handling of blood samples. The increasing use of stored biobank samples for such ventures that may have been collected and stored for other purposes, justifies the study hereof. Blood samples were stored for 0, 4, 24, and 48 h at 4 degrees C, room temperature (RT), and at 35 degrees C, respectively, before they were separated into serum or plasma and frozen. Dried blood spot samples (DBSS) were stored for 0, 1, 2, 3, 7, and 30 days at the same temperatures. 27 inflammatory markers in serum and plasma and 25 markers in DBSS were measured by a previously validated multiplex sandwich immunoassay using Luminex xMAP technology. The measurable concentrations of several cytokines in serum and plasma were significantly increased when blood samples were stored for a period of time before the centrifugation, for certain cytokines more than 1000 fold compared to serum and plasma isolated and frozen immediately after venepuncture. The concentrations in serum generally increased more than in plasma. The measurable concentrations of inflammatory markers also changed in DBSS stored under various conditions compared to controls frozen immediately after preparation, but to a much lesser degree than in plasma or serum. The study demonstrates that trustworthy measurement of several inflammatory markers relies on handling of whole blood samples at low temperatures and rapid isolation of plasma and serum. Effects of different handling procedures for all markers studied are given. DBSS proved to be a robust and convenient way to handle samples for immunoassay analysis of inflammatory markers in whole blood. PMID:18495149

  11. Characterization, Localization and Patterning of Lymphatics and Blood Vessels in Oral Squamous Cell Carcinoma: A Comparative Study Using D2-40 and CD-34 IHC Marker

    PubMed Central

    Agarwal, Deshant; Bajpai, Manas; Gupta, Shailendra; Mathur, Nikunj; Vanaki, S S; Puranik, R S; Mittal, Manoj

    2014-01-01

    Objectives: Lymphatic metastasis has always been regarded as a major prognostic indicator for disease progression and as a guide for therapeutic strategies to oral squamous cell carcinoma (OSCC). Differentiating lymphatic vessels from blood vessels is difficult, partly due to lack of specific method for identifying lymphatics. A new lymphatic vessel reactive antibody D2-40 has been introduced recently. Here we examined immunohistochemical localization of lymphatic vessels and blood vessels using D2-40 and CD-34 respectively in different histological grades of OSCC. Their expression in intra-tumoural and peri-tumoural region was also compared. Materials and Methods: Forty two formalin-fixed paraffin-embedded tissue blocks of excised specimens of OSCC were immunohistochemically evaluated using D2-40 and CD-34 antibodies. Lymphatic vessel density (LVD) (D2-40 positivity) and micro vessel density (MVD) (CD34 positivity) in both intratumoural and peritumoural areas were assessed by hot spot method. Results: Regardless of histopathological differentiation, LVD–– and MVD in peritumoural areas were found greater than intratumoural areas (p>0.05). Interestingly, other than lymphatic vessels, D2-40 positivity was also detected in tumour cells as well as in basal layer of epithelium adjacent to OSCC. Two patterns of distribution of CD34 positive vessel - circumscribing type and penetrating type were also observed in the cancer nest area. Conclusion: D2-40 can be used as a marker to differentiate lymphatic vessels from blood vessels. Lymphatic and blood vessel proliferation might be much more extensive in the peritumoural area. D2-40 expression in epithelium adjacent to tumour indicates its role in the process of differentiation. Further, its expression in potential malignant disorder may provide better insight in predicting prognosis and pathogenesis of these lesions. PMID:25478456

  12. 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

  13. Tumour endothelial marker-8 in wound healing and its impact on the proliferation and migration of keratinocytes

    PubMed Central

    WANG, SHEILA C.; YE, LIN; SANDERS, ANDREW J.; RUGE, FIONA; HARDING, KEITH G.; JIANG, WEN G.

    2016-01-01

    Chronic wound management represents a significant burden on healthcare systems and negatively impacts on the quality of patient life. New strategies to understand and identify wounds that will not heal in a normal manner are required. Tumour endothelial marker-8 (TEM-8) has been implicated in the wound healing and angiogenesis processes. TEM-8 expression was examined at the transcript level in a cohort of acute (n=10) and chronic (n=14) wounds and in normal skin (n=10). Protein analysis of TEM-8 was also undertaken for this cohort using immunohistochemistry (IHC). TEM-8 impact on keratinocyte cell growth and migration was assessed following TEM-8 ribozyme transgene transfection of human HaCaT keratinocytes using cell growth and electric cell-substrate impedance sensing (ECIS)-based assays. Expression of TEM-8 was observed to be increased in acute wounds compared to chronic wounds and normal skin using quantitative polymerase chain reaction transcript analysis and IHC staining of wound tissues. Knockdown of TEM-8 in HaCaT cells, using two independent ribozyme transgenes, resulted in significant decreases in cell growth as well as reductions in the rate of migration assessed using an ECIS-based system. TEM-8 may be differentially expressed between wound types and loss of this molecule impacts HaCaT growth and migration, potentially implicating this molecule as a factor involved in successful progression of wound healing. PMID:26677171

  14. Functional Blood Progenitor Markers in Developing Human Liver Progenitors.

    PubMed

    Goldman, Orit; Cohen, Idan; Gouon-Evans, Valerie

    2016-08-01

    In the early fetal liver, hematopoietic progenitors expand and mature together with hepatoblasts, the liver progenitors of hepatocytes and cholangiocytes. Previous analyses of human fetal livers indicated that both progenitors support each other's lineage maturation and curiously share some cell surface markers including CD34 and CD133. Using the human embryonic stem cell (hESC) system, we demonstrate that virtually all hESC-derived hepatoblast-like cells (Hep cells) transition through a progenitor stage expressing CD34 and CD133 as well as GATA2, an additional hematopoietic marker that has not previously been associated with human hepatoblast development. Dynamic expression patterns for CD34, CD133, and GATA2 in hepatoblasts were validated in human fetal livers collected from the first and second trimesters of gestation. Knockdown experiments demonstrate that each gene also functions to regulate hepatic fate mostly in a cell-autonomous fashion, revealing unprecedented roles of fetal hematopoietic progenitor markers in human liver progenitors. PMID:27509132

  15. 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

  16. 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

  17. 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

  18. New blood markers for staging and prognostics of atherosclerosis

    NASA Astrophysics Data System (ADS)

    Sicchieri, Leticia B.; Silva, Mônica Nascimento; Monteiro, Andrea Moreira; Figueiredo Neto, Antonio Martins; Courrol, Lilia C.

    2014-03-01

    Analysis from the plasmas of rabbits subjected to high-cholesterol diets were performed by fluorescence spectroscopy using three biossensors: Europium-Chlortetracycline (EuCTc), Evans Blue (EB), and Thioflavin T (ThT). For this purpose an animal experimentation was done with New Zealand rabbits divided into two groups: control group of 6 rabbits that received a regular diet for 60 days; and experimental group of 9 rabbits, that were fed with 1% cholesterol for 60 days. The results from spectroscopic analysis have shown that the EuCTc marker emission intensity increases in the presence of plaque formation. The EB emission intensity remained constant for control and experimental groups. The ThT presented an increase in the emission intensity and a modification in the spectra shape with 60 days of diet. The studied biomarkers may not yet be specific in the

  19. Transient finite element analysis of thermal methods used to estimate SAR and blood flow in homogeneously and nonhomogeneously perfused tumour models.

    PubMed

    Wong, T Z; Mechling, J A; Jones, E L; Strohbehn, J W

    1988-01-01

    A two-dimensional time-dependent finite element model was developed to evaluate thermal techniques for estimating blood flow and specific absorption rate (SAR). In these computer simulations, homogeneously and nonhomogeneously perfused tumour models were heated by a 915 MHz interstitial microwave antenna array. Representative blood flow values were assigned within the tumour, and the applied SAR distribution was based on a previously developed antenna theory. SAR values were estimated from the power-on transient temperatures, and blood flow values were estimated from thermal clearance data after power was discontinued. These estimated parameters were then compared to the known 'true' blood flow and SAR values throughout the treatment region. SAR values could be predicted with reasonable accuracy throughout most of the heated region independent of local blood flow. For a homogeneous model, thermal clearance was found to yield reasonably accurate blood flow estimates at high perfusion rates and less accurate estimates at lower perfusion rates. However, for the inhomogeneous model, the blood perfusion estimates were generally poor, and an average blood flow value for the tumour was obtained with little ability to resolve the differences in perfusion between regions. Using temperatures observed early in the cool-down curve resulted in improved spatial resolution, but increased the contribution of thermal conduction to the blood flow estimates. A single time-constant exponential thermal decay curve was found to be a necessary but not sufficient condition for reliable blood flow estimates using this technique. PMID:3171254

  20. Expression of tissue factor in canine mammary tumours and correlation with grade, stage and markers of haemostasis and inflammation.

    PubMed

    Andreasen, E B; Nielsen, O L; Tranholm, M; Knudsen, T; Kristensen, A T

    2016-06-01

    Tissue factor (TF) expression in human cancers has been associated with a procoagulant state and facilitation of metastasis. This study was conducted in order to evaluate if TF was expressed in canine mammary tumours. Forty epithelial mammary tumours from 28 dogs were included. TF expression of the tumours was evaluated by immunohistochemistry using a polyclonal antibody against recombinant canine TF. In addition, thromboelastography, haemostatic and inflammatory parameters were evaluated in the patients. TF was recognized in 44% of benign and 58% of malignant tumours. TF localized to the cytoplasmic membrane of neoplastic luminal epithelial cells and/or diffusely in the cytoplasm. No association was found between TF expression and stage or grade of disease. A significant association between TF expression and antithrombin and plasminogen was found, and extensive TF expression was seen in a lymph node metastasis classified as anaplastic mammary carcinoma from a dog with concomitant disseminated intravascular coagulation (DIC). PMID:24674618

  1. Tumour regression after extracorporeal affinity chromatography of blood plasma across agarose beads containing staphylococcal protein A.

    PubMed

    Håkansson, L; Jonsson, S; Söderberg, M; Eneström, S; Liedén, G; Lindgren, S

    1984-11-01

    The therapeutic effect of absorbing plasma from tumour patients with immobilized staphylococcal protein A was tested. Plasma prepared by centrifugation was passed over protein A-Sepharose and then reinfused into the patient. Five patients were thus treated. One with malignant melanoma and one with renal adenocarcinoma showed measurable regression of metastatic lesions. In another with malignant melanoma a subcutaneous metastasis showed histopathological changes compatible with a therapeutic effect. In two patients, one with malignant melanoma and one with renal adenocarcinoma, no signs of regression were found. No severe adverse effects of the treatment were observed. PMID:6542007

  2. 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

  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. 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

  5. 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

  6. 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.

  7. 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

  8. Putative markers for the detection of breast carcinoma cells in blood.

    PubMed Central

    Eltahir, E. M.; Mallinson, D. S.; Birnie, G. D.; Hagan, C.; George, W. D.; Purushotham, A. D.

    1998-01-01

    The aim of this study was to investigate certain genes for their suitability as molecular markers for detection of breast carcinoma cells using the reverse transcriptase-polymerase chain reaction (RT-PCR). RNA was prepared from MCF-7 breast carcinoma cells and peripheral blood leucocytes of healthy female volunteers. This RNA was screened for mRNA of MUC1, cytokeratin 19 (CK19) and CD44 (exons 8-11) by RT-PCR and the results validated by Southern blots. Variable degrees of expression of MUC1 and CD44 (exons 8-11) were detected in normal peripheral blood, rendering these genes non-specific for epithelial cells and therefore unsuitable for use as markers to detect breast carcinoma cells. Although CK19 mRNA was apparently specific, it was deemed unsuitable for use as a marker of breast cancer cells in light of its limited sensitivity. Furthermore, an attempt at using nested primers to increase sensitivity resulted in CK19 mRNA being detected after two amplification rounds in blood from healthy volunteers. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9579823

  9. 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

  10. 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

  11. Silicon determination in human ventricular whole blood: a possible marker of drowning.

    PubMed

    Maraschi, Federica; Sturini, Michela; Speltini, Andrea; Orio, Francesco; Profumo, Antonella; Pierucci, Giovanni

    2012-07-15

    This article presents the first results demonstrating that total silicon trace concentration in human ventricular whole blood may be used as a further marker in the diagnosis of drowning. The difference in silicon content between the left and right ventricles was significantly higher for drowning cases than that from individuals who had not drowned. These findings were in full agreement with autoptic responses, supporting silicon as a marker of freshwater drowning. The procedure entails an alkaline microwave-assisted digestion using tetramethylammonium hydroxide (TMAH) in the presence of H(2)O(2) followed by dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS) detection, whose accuracy was obtained for Seronorm whole blood reference material. Satisfactory recoveries (91-98%) were gained on whole ventricular blood, with a silicon content lower than the method detection limit (MDL), spiked at 5 to 7μgg(-1) with materials consistent with drowning media constituents, that is, freshwater plankton (CRM [certified reference material] 414), silicon dioxide, diatomaceous earth powder, and a silicon standard solution. Good within-lab reproducibility (4-10%) and sensitivity (MDL=0.46μgg(-1)) were achieved as well. The procedure was applied to blood samples from 18 different real cases of death. PMID:22542976

  12. 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

  13. 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

  14. 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. PMID:25823952

  15. In vitro production of tumour necrosis factor and prostaglandin E2 by peripheral blood mononuclear cells from tuberculosis patients.

    PubMed Central

    Cadranel, J; Philippe, C; Perez, J; Milleron, B; Akoun, G; Ardaillou, R; Baud, L

    1990-01-01

    We investigated the production of tumour necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2) by peripheral blood mononuclear cells (PBMC) from tuberculosis patients and healthy controls. PBMC from tuberculosis patients generated constitutively more TNF-alpha than did control PBMC. This production was significantly higher for patients with high-grade fever and cachexia. The increase of TNF-alpha production by PBMC from tuberculosis patients was associated with a comparatively weaker elevation of PGE2 synthesis which did not parallel fever or weight loss. In vitro treatment of control PBMC with the tuberculin purified protein derivative (PPD) promoted an increased TNF-alpha production which was similar to that of untreated PBMC from tuberculosis patients. Thus, the increased TNF-alpha production in tuberculosis could be explained by the in vivo exposure of PBMC to mycobacterial antigens. In contrast, the concentration of PGE2 was weaker in the medium of untreated PBMC from tuberculosis patients than in the medium of PPD-treated control PBMC, suggesting that PGE2 synthesis by PBMC was limited in tuberculosis by unidentified factors. PMID:2387094

  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 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

  17. 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…

  18. 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

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

    PubMed

    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

  20. 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. PMID:26525643

  1. 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

  2. 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

  3. 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

  4. Soluble tumour necrosis factor alpha receptor 2, a serum marker of resistance to the anabolic actions of growth hormone in subjects with HIV disease.

    PubMed

    Gelato, Marie C; Mynarcik, Dennis; McNurlan, Margaret A

    2002-01-01

    Therapies are still being sought for the prevention of loss of body weight and lean body mass in HIV disease. The purpose of the present study was to identify a serum marker that would help in selecting patients who may be appropriate candidates for the use of anabolic agents, such as growth hormone, to restore lean body mass. This study included 26 HIV-infected patients and nine healthy controls, assessed previously for the effectiveness of 2 weeks of growth hormone administration in the stimulation of protein synthesis in skeletal muscle. Serum levels of interleukins-1beta, -6 and -10 were not useful predictors of the anabolic response to growth hormone. Serum concentrations of tumour necrosis factor alpha (TNFalpha) were significantly elevated (P<0.05) in patients with AIDS and AIDS-related weight loss, and there was a significant correlation between the serum concentration of interleukin-1 receptor antagonist and stage of disease (P=0.03). However, the serum concentration of the soluble TNFalpha receptor type 2 was most predictive of an inability of muscle protein synthesis to respond anabolically to growth hormone (r=-0.42, P=0.01). These data suggest that inflammation impacts on the responsiveness of muscle tissue to an anabolic stimulus, and that the soluble TNFalpha receptor type 2 provides a useful serum marker for metabolic dysfunction in HIV disease, which can be used to identify individuals likely to respond to growth hormone-based anabolic therapy. PMID:11749664

  5. 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

  6. Production of a recombinant antibody specific for i blood group antigen, a mesenchymal stem cell marker.

    PubMed

    Hirvonen, Tia; Suila, Heli; Tiitinen, Sari; Natunen, Suvi; Laukkanen, Marja-Leena; Kotovuori, Annika; Reinman, Mirka; Satomaa, Tero; Alfthan, Kaija; Laitinen, Saara; Takkinen, Kristiina; Räbinä, Jarkko; Valmu, Leena

    2013-10-01

    Multipotent mesenchymal stem/stromal cells (MSCs) offer great promise for future regenerative and anti-inflammatory therapies. Panels of functional and phenotypical markers are currently used in characterization of different therapeutic stem cell populations from various sources. The i antigen (linear poly-N-acetyllactosamine) from the Ii blood group system has been suggested as a marker for MSCs derived from umbilical cord blood (UCB). However, there are currently no commercially available antibodies recognizing the i antigen. In the present study, we describe the use of antibody phage display technology to produce recombinant antibodies recognizing a structure from the surface of mesenchymal stem cells. We constructed IgM phage display libraries from the lymphocytes of a donor with an elevated serum anti-i titer. Antibody phage display technology is not dependent on immunization and thus allows the generation of antibodies against poorly immunogenic molecules, such as carbohydrates. Agglutination assays utilizing i antigen-positive red blood cells (RBCs) from UCB revealed six promising single-chain variable fragment (scFv) antibodies, three of which recognized epitopes from the surface of UCB-MSCs in flow cytometric assays. The amino acid sequence of the VH gene segment of B12.2 scFv was highly similar to the VH4.21 gene segment required to encode anti-i specificities. Further characterization of binding properties revealed that the binding of B12.2 hyperphage was inhibited by soluble linear lactosamine oligosaccharide. Based on these findings, we suggest that the B12.2 scFv we have generated is a prominent anti-i antibody that recognizes i antigen on the surface of both UCB-MSCs and RBCs. This binder can thus be utilized in UCB-MSC detection and isolation as well as in blood group serology. PMID:24083089

  7. High frequency of tumours in Mulibrey nanism.

    PubMed

    Karlberg, Niklas; Karlberg, Susann; Karikoski, Riitta; Mikkola, Sakari; Lipsanen-Nyman, Marita; Jalanko, Hannu

    2009-06-01

    Mulibrey nanism (MUL) is a monogenic disorder with prenatal-onset growth failure, typical clinical characteristics, cardiopathy and tendency for a metabolic syndrome. It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity. In this work, the frequency and pathology of malignant and benign tumours were analysed in a national cohort of 89 Finnish MUL patients aged 0.7-76 years. The subjects had a clinical and radiological evaluation, and histological and immunohistocemical analyses on specimens obtained from biopsy, surgery or autopsy, were performed. The results show that the MUL patients have disturbed architecture with ectopic tissues and a high frequency of both benign and malignant tumours detectable in several internal organs. A total of 210 tumorous lesions were detected in 66/89 patients (74%). Fifteen malignancies occurred in 13 patients (15%), seven of them in the kidney (five Wilms' tumours), three in the thyroid gland, two gynaecological cancers, one gastrointestinal carcinoid tumour, one neuropituitary Langerhans cell histiocytosis and one case of acute lymphoblastic leukaemia (ALL). Tumours detected by radiology in the liver and other organs mainly comprised strongly dilated blood vessels (peliosis), vascularized cysts and nodular lesions. The lesions showed strong expression of the endothelial cell markers CD34 and CD31 as well as the myocyte marker alpha-smooth muscle actin (alpha-SMA). Our findings show that MUL is associated with frequent malignant tumours and benign adenomatous and vascular lesions, as well as disturbed organ development. PMID:19334051

  8. Significance of the tumour markers CA 125 II, CA 72-4, CASA and CYFRA 21-1 in ovarian carcinoma.

    PubMed

    Hasholzner, U; Baumgartner, L; Stieber, P; Meier, W; Hofmann, K; Fateh-Moghadam, A

    1994-01-01

    We compared the tumour marker CA 72-4 and the new markers CASA and CYFRA 21-1 with the established marker CA 125II in follow-up care and control of efficacy of treatment in ovarian cancer in order to determine whether there are differences in recognizing ovarian carcinomas of different histological type. The investigation was done retrospectively on serum samples frozen at -80 degrees C obtained from 262 subjects, among them 50 healthy women, 53 sera with benign gynecological diseases and 159 sera with ovarian cancer, 72 of them at the time of primary diagnosis. We used commercially available kits: CA 125 II: Centocor RIA, CASA: Medac EIA, CA 72-4: Centocor RIA and CYFRA 21-1: Boehringer EnzymunR ELISA. Fixing specificity at 95% versus benign gynecological diseases as a clinically relevant reference group, we found cut-off values of 160 U/mL for CA 125II, 6.5 U/mL for CASA, 6.8 U/mL for CA 72-4 and 2.4 ng/ml for CYFRA 21-1. Based on this specificity we can compare the corresponding sensitivities at the time of primary diagnosis (n = 72): CA 125 II 47%, CA 72-4 47%; CASA 31% and CYFRA 21-1 44%. Regarding histological types of ovarian carcinomas, we found a sensitivity of 50% for CA 125 II and CASA, 36% for CA 72-4 and 33% for CYFRA 21-1 in serous ovarian cancer (n = 53), 21% for CA 125 II and CASA, 36% for CYFRA 21-1 and 43% for CA 72-4 for mucinous ovarian cancer (n = 27). Serous ovarian carcinomas were classified by higher FIGO-stages than mucinous ovarian carcinomas. Additional sensitivities were found at the time of primary diagnosis for the combination of CA 125 II and CA 72-4 and in serous ovarian cancer for CA 125 II and CASA. According to our results, at the time of primary diagnosis the combined determination of CA 125 II and CA 72-4 is useful. If both are negative, determination of CASA can be helpful. For follow-up care and control of efficacy of treatment the preoperative positive or leading marker is sufficient. PMID:7532929

  9. Development and validation of risk index for cognitive decline using blood-derived markers

    PubMed Central

    Ayonayon, Hilsa; Harris, Tamara; Phillips, Caroline; Rosano, Caterina; Satterfield, Suzanne; Yaffe, Kristine

    2015-01-01

    Objective: We sought to develop and validate a risk index for prospective cognitive decline in older adults based on blood-derived markers. Methods: The index was based on 8 markers that have been previously associated with cognitive aging: APOE genotype, plasma β-amyloid 42/40 ratio, telomere length, cystatin C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11 years of follow-up. A total of 1,445 older adults comprised the development sample. An index based on dichotomized markers was divided into low-, medium-, and high-risk categories; the risk categories were validated with the remaining sample (n = 739) using linear regression. Amyloid was measured on a subsample (n = 865) and was included only in a secondary index. Results: The risk categories showed significant differences from each other and were predictive of prospective cognitive decline in the validation sample, even after adjustment for age and baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95% confidence interval [CI]: −0.46, −0.19), the medium-risk group (58.7%) declined 0.55 points/y (95% CI: −0.65, 0.45), and the high-risk group (16.6%) declined 0.69 points/y (95% CI: −0.85, −0.54). Using the secondary index, which included β-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20 points/y (95% CI: −0.42, 0.01), the medium-risk group (61.3%) declined 0.55 points/y (95% CI: −0.72, −0.38), and the high-risk group (11.8%) declined 0.83 points/y (95% CI: −1.14, −0.51). Conclusions: A risk index based on 8 blood-based markers was modestly able to predict cognitive decline over an 11-year follow-up. Further validation in other cohorts is necessary. PMID:25609760

  10. 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.

  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. 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.

  13. 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

  14. Effects of Swedish Massage Therapy on Blood Pressure, Heart Rate, and Inflammatory Markers in Hypertensive Women

    PubMed Central

    Supa'at, Izreen; Zakaria, Zaiton; Maskon, Oteh; Aminuddin, Amilia; Nordin, Nor Anita Megat Mohd

    2013-01-01

    Swedish Massage Therapy (SMT) is known for its therapeutic relaxation effects. Hypertension is associated with stress and elevated endothelial inflammatory markers. This randomized control trial measured the effects of whole body SMT (massage group) or resting (control group) an hour weekly for four weeks on hypertensive women. Blood pressure (BP) and heart rate (HR) were measured before and after each intervention and endothelial inflammatory markers: vascular endothelial adhesion molecules 1 (VCAM-1) and intracellular adhesion molecules 1 (ICAM-1) were measured at baseline and after the last intervention. Massage group (n=8) showed significant systolic BP (SBP) reduction of 12 mmHg (P=0.01) and diastolic BP (DBP) reduction of 5 mmHg (P=0.01) after four sessions with no significant difference between groups. Reductions in HR were also seen in massage group after sessions 1, 3, and 4 with significant difference between groups. VCAM-1 showed significant reduction after four sessions: the massage group showed reduction of 998.05 ng/mL (P=0.03) and the control group of 375.70 ng/mL (P=0.01) with no significant differences between groups. There were no changes in ICAM-1. In conclusion, SMT or resting an hour weekly has effects on reducing BP, HR, and VCAM-1 in hypertensive women. PMID:24023571

  15. Oxidative stress parameters in bitches with mammary gland tumours.

    PubMed

    Szczubiał, M; Kankofer, M; Łopuszyński, W; Dabrowski, R; Lipko, J

    2004-01-01

    The aim of the present study was to describe some of the oxidative stress parameters in bitches suffering from spontaneously occurring mammary gland tumours. The experiment involved 28 bitches which had mammary gland tumours removed surgically (15 bitches with malignant tumour and 13 with benign tumour) as well as 10 clinically healthy bitches. The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined in haemolysates of erythrocytes derived from the animals. The concentrations of thiobarbituric acid reactive substances (TBARS), as well as -SH groups, were determined in blood plasma. GSH-Px activity was significantly higher in the malignant tumour group than in healthy animals. SOD activity was significantly higher in animals with tumours compared with the control group. Activities of both enzymes were higher in animals with malignant tumours than in benign groups, but the differences were not statistically significant. The concentrations of TBARS and -SH groups were similar in all examined groups. The increase of antioxidative enzyme activities in these animals may suggest the activation of antioxidative defence mechanisms in mammary gland carcinogenesis. Moreover, it might indicate the participation of oxidative stress in malignancies. Further experiments involving more animals, with more frequent sample collection and the use of other oxidative stress markers are necessary. PMID:15533114

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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...

  1. 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

  2. Expression of surface markers on the blood cells during the delayed asthmatic response to allergen challenge

    PubMed Central

    2014-01-01

    Patients with bronchial asthma develop various types of asthmatic response to bronchial challenge with allergen, such as immediate/early asthmatic response (IAR), late asthmatic response (LAR) or delayed asthmatic response (DYAR), because of different immunologic mechanisms. The DYAR, occurring between 24 and 56 hours after the bronchial allergen challenge (p < 0.01), differs from IAR and LAR in clinical as well as immunologic features. This study investigates the expression of CD molecules (markers) on the surface of particular cell populations in the peripheral blood and their changes during the DYAR. In 17 patients developing the DYAR (p < 0.01), the bronchial challenge with allergen was repeated 2–6 weeks later. The repeated DYAR (p < 0.001) was combined with recording of CD molecule expression on various types of blood cells by means of flow cytometry up to 72 hours after the challenge. The results were expressed in percent of the mean relative fluorescence intensity. The DYAR was accompanied by (a) increased expression of CD11b, CD11b/18, CD16,CD32, CD35, CD62E, CD62L, CD64, and CD66b on neutrophils; CD203C on basophils; CD25 and CD62L on eosinophils; CD14, CD16, CD64, and CD86 on monocytes; CD3, CD4, CD8, CD11a, CD18, and CD69 on lymphocytes; CD16, CD56, CD57, and CD94 on natural killer (NK) cells; and CD31, CD41, CD61, CD62P, and CD63 on thrombocytes and (b) decreased expression of CD18 and CD62L on eosinophils, CD15 on neutrophils, and CD40 on lymphocytes. These results suggest involvement of cell-mediated hypersensitivity mechanism, on participation of Th1- lymphocytes, neutrophils, monocytes, NK cells, and thrombocytes in the DYAR. PMID:24988283

  3. 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

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

    PubMed Central

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

    2016-01-01

    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

  5. Diabetes Technology: Markers, Monitoring, Assessment, and Control of Blood Glucose Fluctuations in Diabetes

    PubMed Central

    Kovatchev, Boris P.

    2012-01-01

    People with diabetes face a life-long optimization problem: to maintain strict glycemic control without increasing their risk for hypoglycemia. Since the discovery of insulin in 1921, the external regulation of diabetes by engineering means has became a hallmark of this optimization. Diabetes technology has progressed remarkably over the past 50 years—a progress that includes the development of markers for diabetes control, sophisticated monitoring techniques, mathematical models, assessment procedures, and control algorithms. Continuous glucose monitoring (CGM) was introduced in 1999 and has evolved from means for retroactive review of blood glucose profiles to versatile reliable devices, which monitor the course of glucose fluctuations in real time and provide interactive feedback to the patient. Technology integrating CGM with insulin pumps is now available, opening the field for automated closed-loop control, known as the artificial pancreas. Following a number of in-clinic trials, the quest for a wearable ambulatory artificial pancreas is under way, with a first prototype tested in outpatient setting during the past year. This paper discusses key milestones of diabetes technology development, focusing on the progress in the past 10 years and on the artificial pancreas—still not a cure, but arguably the most promising treatment of diabetes to date. PMID:24278682

  6. Evaluation of white blood cell count as a possible prognostic marker for oral cancer

    PubMed Central

    2011-01-01

    Introduction There seems to be increasing evidence that inflammation leads to cancer. For several cancers, an association with white blood cell (WBC) count has been reported. So far, no studies have been performed for cancer of the oral cavity and WBC. Therefore, the aim of the present study was to look at whether WBC count can be used as a prognostic marker for recurrence or metastases for oral cancer. Material and methods For 278 patients with oral cancer, the preoperative WBC count was compared with the clinicopathological information: age, gender, T-status, N-status, recurrence, metastases, follow-up time, and time till recurrence or metastases appeared. Results Out of 278 patients, 48 developed recurrence, 24 second tumors, 46 cervical metastases, and 14 distant metastases. The mean follow-up time was 35.97 months (range: 12-107 months). Significant Pearson correlation at the 0.05 level could be found for the T-status (0.046), but not for the N status (0.121). No significant correlation could be found between WBC count and the development of recurrence or metastases. Conclusion In conclusion, our findings demonstrate that elevated WBC count does not seem to be a predictor for recurrence or for further metastases. Further research is recommended to investigate the WBC count in precancerous lesions and in HPV positive patients with oral SCC. PMID:21352591

  7. Astrocytoma-associated antigens - IL13Rα2, Fra-1, and EphA2 as potential markers to monitor the status of tumour-derived cell cultures in vitro

    PubMed Central

    2014-01-01

    Background The molecular heterogeneity of high-grade astrocytomas underlies the difficulties in the development of representative and valuable in vitro experimental models for their studies. The purpose of our study was to estimate the value of astrocytoma-associated antigens (AAAs) - IL13Rα2, Fra-1, EphA2 - and the most common molecular aberrations typical for astrocytomas as potential markers to screen the status of tumour-derived cell cultures in vitro. Methods The tumour-derived cell cultures were established from high-grade astrocytomas. The expression analyses of the tested genes were performed via semi-quantitative real-time PCR and subsequently verified by immunohistochemical and immunocytochemical technique. The analyses of molecular aberrations at DNA level included gene dosage status evaluation based on real-time PCR, sequencing analysis, and loss of heterozygosity (LOH) assay. Results The expression analyses based on semi-quantitative real-time PCR showed that in the final stage of culture the expression level of all tested AAAs was significantly higher or at least comparable to that of primary tumours; however, two expression patterns were observed during cell culture establishment. Analysis at the single cell level via immunocytochemistry also demonstrated an increase of the level of tested proteins and/or selection of tumour cell populations strongly positive for AAAs vs. other cell types including admixed non-tumoural cells. Confrontation of AAA expression data with the results of molecular analyses at DNA level seems to support the latter, revealing that the expression pattern of astrocytoma-associated antigens in tumour-derived cells in subsequent stages of culture is convergent with changes in the molecular profile of examined cell populations. Conclusions The consistency of the obtained results seems to support the use of the selected AAAs, in particular IL13Rα2 and Fra-1, as tools facilitating the establishment of tumour-derived cultures

  8. Adhesion of tumour-infiltrating lymphocytes to endothelium: a phenotypic and functional analysis.

    PubMed Central

    Adams, D. H.; Yannelli, J. R.; Newman, W.; Lawley, T.; Ades, E.; Rosenberg, S. A.; Shaw, S.

    1997-01-01

    Efficacy of cancer immunotherapy with cultured tumour-infiltrating lymphocytes (TILs) depends upon infused TILs migrating into tumour-bearing tissue, in which they mediate an anti-tumour response. For TILs to enter a tumour, they must first bind to tumour endothelium, and this process depends on TILs expressing and regulating the function of relevant cell-surface receptors. We analysed the cell-surface phenotype and endothelial binding of TILs cultured from human melanoma and compared them with peripheral blood T cells and with allostimulated T cells cultured under similar conditions. Compared with peripheral blood T cells, TILs expressed high levels of five integrins, two other adhesion molecules, including the skin homing molecule CLA, and several activation markers and showed markedly enhanced integrin-mediated adhesion to a dermal microvascular endothelial cell line in vitro. Compared with the allostimulated T cells, TILs expressed higher levels of the cutaneous lymphocyte antigen (CLA), the adhesion molecule CD31 and the activation markers CD30 and CD69, but lower levels of several other adhesion and activation molecules. These phenotypic and functional properties of TILs should have complex effects on their migration in vivo. Expression of CLA, the skin homing receptor, may increase migration to melanoma (a skin cancer), whereas integrin activation may cause non-specific binding of TILs to other endothelium. Manipulation of the culture conditions in which TILs are expanded might result in a phenotype that is more conducive to selective tumour homing in vivo. Images Figure 1 PMID:9166933

  9. 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

  10. Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women

    PubMed Central

    Jayachandran, Muthuvel; Litwiller, Robert D.; Owen, Whyte G.; Heit, John A.; Behrenbeck, Thomas; Mulvagh, Sharon L.; Araoz, Philip A.; Budoff, Matthew J.; Harman, S. Mitchell; Miller, Virginia M.

    2008-01-01

    While the risk for symptomatic atherosclerotic disease increases after menopause, currently recognized risk factors do not identify ongoing disease processes in low-risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by the Framingham risk score. The concentration and phenotype of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry, and coronary artery calcification (CAC) was scored using 64-slice computed tomography scanners. The procoagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, serum lipids, systolic blood pressure (Framingham risk score < 10%, range 1–3%), and high-sensitivity C-reactive protein did not differ significantly among women with low (0 < 35; range, 0.3–32 Agatston units) or high (>50; range, 93–315 Agatston units) CAC compared with women without calcification. The total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. The thrombin-generating capacity of the isolated microparticles correlated with phosphatidylserine expression, which also was greatest in women with high CAC scores. The percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, the characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis. PMID:18621859

  11. 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

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

    PubMed

    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

  13. Tumour-associated eosinophilia: a review.

    PubMed Central

    Lowe, D; Jorizzo, J; Hutt, M S

    1981-01-01

    In a recent study of cervical carcinoma, 13 cases with a marked eosinophil infiltrate around the tumour were found. The histological appearance of the tumours was distinctive and suggested a specific response, similar to the lymphocyte infiltration in medullary carcinoma of the breast and seminoma. A review of published reports shows that tumour-associated tissue eosinophilia (TATE) and tumour-associated blood eosinophilia (TABE) may be seen in tumours of different histological types from different anatomical sites, and may occur together or separately. Tumours with TATE alone appear to have a better prognosis that those without, while TABE is associated with tumor spread and a poor prognosis. Images PMID:7035499

  14. 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

  15. Anti-tumour activity of oncolytic Western Reserve vaccinia viruses in canine tumour cell lines, xenografts, and fresh tumour biopsies.

    PubMed

    Autio, K; Knuuttila, A; Kipar, A; Ahonen, M; Parviainen, S; Diaconu, I; Kanerva, A; Hakonen, T; Vähä-Koskela, M; Hemminki, A

    2014-10-10

    Cancer is one of the most common reasons for death in dogs. One promising approach is oncolytic virotherapy. We assessed the oncolytic effect of genetically modified vaccinia viruses in canine cancer cells, in freshly excised tumour biopsies, and in mice harbouring canine tumour xenografts. Tumour transduction efficacy was assessed using virus expressing luciferase or fluorescent marker genes and oncolysis was quantified by a colorimetric cell viability assay. Oncolytic efficacy in vivo was evaluated in a nude mouse xenograft model. Vaccinia virus was shown to infect most tested canine cancer cell lines and primary surgical tumour tissues. Virus infection significantly reduced tumour growth in the xenograft model. Oncolytic vaccinia virus has antitumour effects against canine cancer cells and experimental tumours and is able to replicate in freshly excised patient tumour tissue. Our results suggest that oncolytic vaccinia virus may offer an effective treatment option for otherwise incurable canine tumours. PMID:25302859

  16. Tumours of the soft (mesenchymal) tissues.

    PubMed

    Weiss, E

    1974-01-01

    This is a classification of tumours of fibrous tissue, fat, muscle, blood and lymph vessels, and mast cells, irrespective of the region of the body in which they arise. Tumours of fibrous tissue are divided into fibroma, fibrosarcoma (including "canine haemangiopericytoma"), other sarcomas, equine sarcoid, and various tumour-like lesions. The histological appearance of the tumours is described and illustrated with photographs. PMID:4371740

  17. Characterization of blood biochemical markers during aging in the Grey Mouse Lemur (Microcebus murinus): impact of gender and season

    PubMed Central

    2012-01-01

    Background Hematologic and biochemical data are needed to characterize the health status of animal populations over time to determine the habitat quality and captivity conditions. Blood components and the chemical entities that they transport change predominantly with sex and age. The aim of this study was to utilize blood chemistry monitoring to establish the reference levels in a small prosimian primate, the Grey Mouse Lemur (Microcebus murinus). Method In the captive colony, mouse lemurs may live 10–12 years, and three age groups for both males and females were studied: young (1–3 years), middle-aged (4–5 years) and old (6–10 years). Blood biochemical markers were measured using the VetScan Comprehensive Diagnostic Profile. Because many life history traits of this primate are highly dependent on the photoperiod (body mass and reproduction), the effect of season was also assessed. Results The main effect of age was observed in blood markers of renal functions such as creatinine, which was higher among females. Additionally, blood urea nitrogen significantly increased with age and is potentially linked to chronic renal insufficiency, which has been described in captive mouse lemurs. The results demonstrated significant effects related to season, especially in blood protein levels and glucose rates; these effects were observed regardless of gender or age and were likely due to seasonal variations in food intake, which is very marked in this species. Conclusion These results were highly similar with those obtained in other primate species and can serve as references for future research of the Grey Mouse Lemur. PMID:23131178

  18. 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...

  19. Phosphatidylethanol in blood as a marker of chronic alcohol use: a systematic review and meta-analysis.

    PubMed

    Viel, Guido; Boscolo-Berto, Rafael; Cecchetto, Giovanni; Fais, Paolo; Nalesso, Alessandro; Ferrara, Santo Davide

    2012-01-01

    The present paper aims at a systematic review of the current knowledge on phosphatidylethanol (PEth) in blood as a direct marker of chronic alcohol use and abuse. In March 2012, the search through "MeSH" and "free-text" protocols in the databases Medline/PubMed, SCOPUS, Web of Science, and Ovid/Embase, combining the terms phosphatidylethanol and alcohol, provided 444 records, 58 of which fulfilled the inclusion criteria and were used to summarize the current evidence on the formation, distribution and degradation of PEth in human blood: (1), the presence and distribution of different PEth molecular species (2), the most diffused analytical methods devoted to PEth identification and quantization (3), the clinical efficiency of total PEth quantification as a marker of chronic excessive drinking (4), and the potential utility of this marker for identifying binge drinking behaviors (5). Twelve papers were included in the meta-analysis and the mean (M) and 95% confidence interval (CI) of total PEth concentrations in social drinkers (DAI ≤ 60 g/die; M = 0.288 μM; CI 0.208-0.367 μM) and heavy drinkers (DAI > 60 g/die; M = 3.897 μM; CI 2.404-5.391 μM) were calculated. The present analysis demonstrates a good clinical efficiency of PEth for detecting chronic heavy drinking. PMID:23203094

  20. Phosphatidylethanol in Blood as a Marker of Chronic Alcohol Use: A Systematic Review and Meta-Analysis

    PubMed Central

    Viel, Guido; Boscolo-Berto, Rafael; Cecchetto, Giovanni; Fais, Paolo; Nalesso, Alessandro; Ferrara, Santo Davide

    2012-01-01

    The present paper aims at a systematic review of the current knowledge on phosphatidylethanol (PEth) in blood as a direct marker of chronic alcohol use and abuse. In March 2012, the search through “MeSH” and “free-text” protocols in the databases Medline/PubMed, SCOPUS, Web of Science, and Ovid/Embase, combining the terms phosphatidylethanol and alcohol, provided 444 records, 58 of which fulfilled the inclusion criteria and were used to summarize the current evidence on the formation, distribution and degradation of PEth in human blood: (1), the presence and distribution of different PEth molecular species (2), the most diffused analytical methods devoted to PEth identification and quantization (3), the clinical efficiency of total PEth quantification as a marker of chronic excessive drinking (4), and the potential utility of this marker for identifying binge drinking behaviors (5). Twelve papers were included in the meta-analysis and the mean (M) and 95% confidence interval (CI) of total PEth concentrations in social drinkers (DAI ≤ 60 g/die; M = 0.288 μM; CI 0.208–0.367 μM) and heavy drinkers (DAI > 60 g/die; M = 3.897 μM; CI 2.404–5.391 μM) were calculated. The present analysis demonstrates a good clinical efficiency of PEth for detecting chronic heavy drinking. PMID:23203094

  1. 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

  2. The Effects of Probiotic Supplementation on Markers of Blood Lipids, and Blood Pressure in Patients with Prediabetes: A Randomized Clinical Trial

    PubMed Central

    Mahboobi, Sepideh; Iraj, Bijan; Maghsoudi, Zahra; Feizi, Awat; Ghiasvand, Reza; Askari, Gholamreza; Maayeshi, Najmeh

    2014-01-01

    Background: Prediabetes is a high-risk condition for type 2 diabetes mellitus. The growing prevalence of diabetes emphasizes on the necessity of concentrating on various strategies to prediabetes prevention and management. Probiotics as a group of functional foods might exert antidiabetic effects. This study aimed to assess the effects of probiotic administration on blood lipid profile and blood pressure in patients with prediabetes. Methods: This randomized controlled trial consisted of 60 prediabetic patients, aged 25-65 years old, that were randomly assigned to the intervention (receiving 500 mg probiotic capsules, n = 30) or control group (receiving placebo, n = 30) for 8-week period. Demographic and anthropometric data were collected at baseline. Blood samples were collected at baseline and after 8 weeks for biochemical measurements. Blood pressure was measured at the baseline an after 8 weeks of intervention. Data regarding dietary intakes and physical activity were also collected during the study. We used SPSS software version 16 (SPSS Inc. Chicago, USA) for data analyzing. Results: Probiotic supplementation did not contribute to significant changes in total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, Triglycerides (TG), TG/LDL and LDL/HDL ratios, after 8 weeks. After adjusting for potential confounders, HDL-cholesterol reduced significantly in the placebo group compared with probiotic group. Percent change in systolic blood pressure was significantly different in the probiotic group in comparison with a placebo group (–3.10 ± 2.22 vs. 3.24 ± 1.96, P = 0.01), although this significance did not exist anymore after adjusting for confounders (P > 0.05). Conclusions: Our study showed that probiotics did not have significant effects on lipid markers although they had positive effects on systolic blood pressure. PMID:25400881

  3. Simple blood tests as predictive markers of disease severity and clinical condition in patients with venous insufficiency.

    PubMed

    Karahan, Oguz; Yavuz, Celal; Kankilic, Nazim; Demirtas, Sinan; Tezcan, Orhan; Caliskan, Ahmet; Mavitas, Binali

    2016-09-01

    Chronic venous insufficiency (CVI) is a progressive inflammatory disease. Because of its inflammatory nature, several circulating markers were investigated for predicting disease progression. We aimed to investigate simple inflammatory blood markers as predictors of clinical class and disease severity in patients with CVI. Eighty patients with CVI were divided into three groups according to clinical class (grade 1, 2 and 3) and score of disease severity (mild, moderate and severe). The basic inflammatory blood markers [neutrophil, lymphocyte, mean platelet volume (MPV), white blood cell (WBC), platelet, albumin, D-dimer, fibrinogen, fibrinogen to albumin ratio, and neutrophil to lymphocyte ratio] were investigated in each group. Serum neutrophil, lymphocyte, MPV, platelet count, D-dimer and neutrophil to lymphocyte ratio levels were similar among the groups (P > 0.05). Although the serum WBC levels were significant in the clinical severity groups (P < 0.05), it was useless to separate each severity class. However, albumin, fibrinogen and the fibrinogen to albumin ratio were significant predictors of clinical class and disease severity. Especially, the fibrinogen to albumin ratio was detected as an independent indicator for a clinical class and disease severity with high sensitivity and specificity (75% sensitivity and 87.5% specificity for clinical class and 90% sensitivity and 88.3% specificity for disease severity). Serum fibrinogen and albumin levels can be useful parameters to determine clinical class and disease severity in patients with CVI. Moreover, the fibrinogen to albumin ratio is a more sensitive and specific predictor of the progression of CVI. PMID:26650463

  4. 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

  5. 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

  6. 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

  7. Evaluation of blood, buccal swabs, and hair follicles for DNA profiling technique using STR markers

    PubMed Central

    Chaudhary, Garima; Dogra, T D; Raina, Anupuma

    2015-01-01

    Aim To study the short tandem repeat (STR) pattern of DNA from the blood, buccal swabs, and hair follicles of the recipients of allogenic hematopoietic stem cell transplantation to examine whether these tissues contain donor derived cells. Methods The study enrolled 25 patients who sustained engraftment. Peripheral blood, buccal swabs, and hair follicles were collected on days 21-30, 90, and 180 after transplantation and the chimeric status of the recipients was evaluated. Results Donor derived cells existed in the blood and buccal swabs, but not in hair follicles, which can be used to obtain the pre-transplant sample of the recipient after transplant. Conclusion Peripheral blood and buccal swab do not serve as a reliable source of recipient’s origin for DNA analysis of individuals who underwent allogenic hematopoietic stem cell transplantation at least within 6 months after transplant. PMID:26088848

  8. 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

  9. 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

  10. 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

  11. 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

  12. Quantitative assessment of regulatory proteins in blood as markers of radiation effects in the late period after occupational exposure.

    PubMed

    Kirillova, Evgenia N; Zakharova, Maria L; Muksinova, Klara N; Drugova, Elena D; Pavlova, Olga S; Sokolova, Svetlana N

    2012-07-01

    The objective of this research was quantitative assessment of serum and membrane regulatory proteins in blood from nuclear workers as markers of radiation-induced alterations in immune homeostasis in the late period after protracted exposure of nuclear workers with different doses. The effector and regulatory lymphocytes were measured using a flow cytofluorometer in workers from the main facilities of the Mayak PA (aged ∼60 y up to 80 y) in the late period after combined exposure to external gamma-rays and internal alpha-radiation from incorporated 239Pu. The control group included non-occupationally exposed members of the Ozyorsk population matched by gender and age to the group of Mayak workers. Thirty serum proteins involved in regulation of immune homeostasis, such as growth factors, multifunctional interleukins, pro- and anti-inflammatory cytokines, and their receptors, were measured using ELISA in blood serum specimens from the Radiobiology Human Tissue Repository. The dosimetry estimates were obtained using Doses-2005. The correlation analysis revealed a statistically significant direct relationship of T-killers and plutonium body burden and a decreasing level of T-helpers with accumulated external dose in exposed individuals. There were differences in expression of membrane markers in young regulatory cells (double null T-lymphocytes, NKT-lymphocytes, regulatory T-cells, and an increase of activated forms of T-lymphocytes), which indicated an active role of regulatory cells in maintaining immune homeostasis in terms of protracted exposure. The assessment of regulatory proteins in blood indicated that growth factors (EGF, TGF-β1, PDGF), multifunctional interleukins (IL-17A, IL-18), and pro-inflammatory cytokines (IL-1β and INF-γ) could be potential markers of radiation-induced alterations in protein status. An imbalance of pro- and antiinflammatory proteins in blood and variations of protein profiles at the lower exposure levels (gamma-ray dose <1 Gy

  13. 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. PMID:19915570

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

    PubMed Central

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

    2012-01-01

    The spread of cancer cells between organs, a process known as metastasis, is the cause of most cancer deaths1,2. Detecting circulating tumour cells—a common marker for the development of metastasis3,4—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 analysed5–7. 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. PMID:19915570

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

    NASA Astrophysics Data System (ADS)

    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.

  16. Blood Translation Elongation Factor-1δ Is a Novel Marker for Cadmium Exposure

    PubMed Central

    Lu, Qian; Lei, Yi-Xiong; He, Chao-Cai; Lei, Zi-Ning

    2013-01-01

    Translation elongation factor-1δ (TEF-1δ) has been identified as a novel cadmium-responsive proto-oncogene. However, it is still unclear whether TEF-1δ could be a potential biomarker of cadmium exposure. Rats were treated with CdCl2 at different concentrations (high dose 1.225, mid-dose 0.612 and low dose 0.306 mg/kg body weight, respectively) for 14 weeks, and the cadmium levels, weight coefficients, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), serum creatinine (SCR), 24-h urine protein (24hPro), urinary creatinine (Cr) and pathological features were determined. The TEF-1δ expression in white blood cells and multiple organs were examined by reverse transcription polymerase chain reaction (PCR) and were also confirmed with fluorescence quantitative PCR. A cadmium dose-dependent increase (p < 0.05) of cadmium levels in blood, urine, liver, kidney, heart and lung, and the weight coefficients was observed. The liver and renal function indictors including AST, ALT, SCR, BUN and 24hPro, were elevated in a cadmium dose-dependent manner (p < 0.05). Significant pathological changes in liver, kidney, heart and lung were indicated. The TEF-1δ expression was up-regulated in both blood and organs (p < 0.05). Moreover, the expression level of blood TEF-1δ was positively correlated to TEF-1δ expression level, cadmium level and toxicity in the organs (p < 0.01). This study indicates that blood TEF-1δ is a novel valuable biomarker for cadmium exposure and its organ toxicity. PMID:23459232

  17. Developmental validation studies of epigenetic DNA methylation markers for the detection of blood, semen and saliva samples.

    PubMed

    Silva, Deborah S B S; Antunes, Joana; Balamurugan, Kuppareddi; Duncan, George; Alho, Clarice S; McCord, Bruce

    2016-07-01

    Determining the type and origin of body fluids in a forensic investigation can provide important assistance in reconstructing crime scenes. A set of epigenetic markers, ZC3H12D, BCAS4 and cg06379435, have been developed to produce unique and specific patterns of DNA methylation that can be used to identify semen, saliva, and blood, respectively. To ensure the efficacy of these markers, developmental validation studies were performed to determine the conditions and limitations of this new tool for forensic analysis. DNA was extracted from human samples and bisulfite modified using commercial bisulfite modification kits. Specific primers were used to amplify the region of interest and the methylation profile of the CpG sites were determined by pyrosequencing. The percent methylation values at each CpG site were determined in multiple samples and averaged for each tissue type. The versatility of these new markers is presented by showing the results of validation studies on sensitivity, human specificity, stability and mixture resolution. When testing the markers using different organisms, we did obtain positive results for certain non-human primate samples, however, all other tested species were negative. The lowest concentration consistently detected varied from 0.1 to 10ng, depending on the locus, indicating the importance of primer design and sequence in the assay. The method also proved to be effective when inhibitors were present in the samples or when samples were degraded by heat. Simulated case- samples were also tested. In the case of mixtures of different cell types, the overall methylation values varied in a consistent and predictable manner when multiple cell types were present in the same sample. Overall, the validation studies demonstrate the robustness and effectiveness of this new tool for body fluid identification. PMID:27010659

  18. Cells Expressing Early Cardiac Markers Reside in the Bone Marrow and Are Mobilized Into the Peripheral Blood After Myocardial Infarction

    PubMed Central

    Kucia, Magda; Dawn, Buddhadeb; Hunt, Greg; Guo, Yiru; Wysoczynski, Marcin; Majka, Marcin; Ratajczak, Janina; Rezzoug, Francine; Ildstad, Suzanne T.; Bolli, Roberto; Ratajczak, Mariusz Z.

    2013-01-01

    The concept that bone marrow (BM)– derived cells participate in cardiac regeneration remains highly controversial and the identity of the specific cell type(s) involved remains unknown. In this study, we report that the postnatal BM contains a mobile pool of cells that express early cardiac lineage markers (Nkx2.5/Csx, GATA-4, and MEF2C). These cells are present in significant amounts in BM harvested from young mice but their abundance decreases with age; in addition, the responsiveness of these cells to gradients of motomorphogens SDF-1, HGF, and LIF changes with age. FACS analysis, combined with analysis of early cardiac markers at the mRNA and protein levels, revealed that cells expressing these markers reside in the nonadherent, nonhematopoietic CXCR4+/Sca-1+/lin−/CD45− mononuclear cell (MNC) fraction in mice and in the CXCR4+/CD34+/AC133+/CD45− BMMNC fraction in humans. These cells are mobilized into the peripheral blood after myocardial infarction and chemoattracted to the infarcted myocardium in an SDF-1-CXCR4 −, HGF-c-Met−, and LIF-LIF-R− dependent manner. To our knowledge, this is the first demonstration that the postnatal BM harbors a nonhematopoietic population of cells that express markers for cardiac differentiation. We propose that these potential cardiac progenitors may account for the myocardial regenerative effects of BM. The present findings provide a novel paradigm that could reconcile current controversies and a rationale for investigating the use of BM-derived cardiac progenitors for myocardial regeneration. PMID:15550692

  19. 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

  20. 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 ...

  1. Lymphocyte subpopulations in peripheral blood of healthy persons. Characterization by surface markers and lack of selection during purification

    PubMed Central

    Holm, G.; Pettersson, D.; Mellstedt, H.; Hedfors, E.; Bloth, B.

    1975-01-01

    Lymphocytes were isolated at 99% purity from peripheral blood of healthy persons by defibrination, gelatine sedimentation, treatment with carbonyl iron powder and centrifugation on Ficoll–Isopaque. Subpopulations were identified by three surface markers: cells forming rosettes with sheep red blood cells (SRBC) (E-binding lymphocytes) as a measure of T lymphocytes; lymphocytes with surface immunoglobulin identified by indirect immunofluorescence (B lymphocytes); lymphocytes with receptors for C3 observed by the rosette method using SRBC treated with rabbit antiserum and human complement (EAC-binding lymphocytes). The yield of lymphocytes after purification varied from 15 to 65%. No selection of lymphocytes was observed either by counting immunoglobulin-bearing and EAC-binding lymphocytes in whole blood and in purified cells from the same sample, or by statistical analysis of lymphocytes in subpopulations as a function of the yields from twenty-six experiments. In the absence of selection during purification the total numbers of T and B lymphocytes could be calculated from the percentages and the total numbers of lymphocytes. Our normal values are close to those reported using other non-selective methods of purification. When lymphocytes were simultaneously stained for immunoglobulin and rosetted with EAC, cells bearing either or both markers were found. In total, 27–35% cells were identified by these markers. Since about 70% of the cells were E-binding, practically all lymphocytes could be identified. A small overlap between E-binding and immunoglobulin-bearing/EAC-binding lymphocytes may occur. Either the IgM or the IgG-containing fractions obtained after fractionation of rabbit anti-SRBC serum on Sephadex G-200 could be used for sensitization of SRBC with complement. Formation of rosettes was not prevented by pretreating the lymphocytes with aggregated IgG, while rosettes formed with EA prepared by high concentrations of IgG antibody (Fc-binding lymphocytes

  2. 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.

  3. Blood Protein Markers of Neocortical Amyloid-β Burden: A Candidate Study Using SOMAscan Technology

    PubMed Central

    Voyle, Nicola; Baker, David; Burnham, Samantha C.; Covin, Antonia; Zhang, Zhanpan; Sangurdekar, Dipen P.; Tan Hehir, Cristina A.; Bazenet, Chantal; Lovestone, Simon; Kiddle, Steven; Dobson, Richard J.B.

    2015-01-01

    Abstract Background: Four previously reported studies have tested for association of blood proteins with neocortical amyloid-β burden (NAB). If shown to be robust, these proteins could have utility as a blood test for enrichment in clinical trials of Alzheimer’s disease (AD) therapeutics. Objective: This study aimed to investigate whether previously identified blood proteins also show evidence for association with NAB in serum samples from the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL). The study considers candidate proteins seen in cohorts other than AIBL and candidates previously discovered in the AIBL cohort. Methods: Our study used the SOMAscan platform for protein quantification in blood serum. Linear and logistic regressions were used to model continuous NAB and dichotomized NAB respectively using single proteins as a predictor. Multiple protein models were built using stepwise regression techniques and support vectors machines. Age and APOE ɛ4 carriage were used as covariates for all analysis. Results: Of the 41 proteins previously reported, 15 AIBL candidates and 20 non-AIBL candidates were available for testing. Of these candidates, pancreatic polypeptide (PPY) and IgM showed a significant association with NAB. Notably, IgM was found to associate with continuous NAB across cognitively normal control subjects. Conclusions: We have further demonstrated the association of PPY and IgM with NAB, despite technical differences between studies. There are several reasons for a lack of significance for the other candidates including platform differences and the use of serum rather than plasma samples. To investigate the possibility of technical differences causing lack of replication, further studies are required. PMID:25881911

  4. 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

  5. Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers

    PubMed Central

    Zoledziewska, Magdalena; Mulas, Antonella; Pistis, Giorgio; Steri, Maristella; Danjou, Fabrice; Kwong, Alan; Ortega del Vecchyo, Vicente Diego; Chiang, Charleston W. K.; Bragg-Gresham, Jennifer; Pitzalis, Maristella; Nagaraja, Ramaiah; Tarrier, Brendan; Brennan, Christine; Uzzau, Sergio; Fuchsberger, Christian; Atzeni, Rossano; Reinier, Frederic; Berutti, Riccardo; Huang, Jie; Timpson, Nicholas J; Toniolo, Daniela; Gasparini, Paolo; Malerba, Giovanni; Dedoussis, George; Zeggini, Eleftheria; Soranzo, Nicole; Jones, Chris; Lyons, Robert; Angius, Andrea; Kang, Hyun M.; Novembre, John; Sanna, Serena; Schlessinger, David; Cucca, Francesco; Abecasis, Gonçalo R

    2015-01-01

    We report ~17.6M genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from prior sequencing-based compilations and enriched for predicted functional consequence. Furthermore, ~76K variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. Fourteen signals, including two major new loci, were observed for lipid levels, and 19, including two novel loci, for inflammatory markers. New associations would be missed in analyses based on 1000 Genomes data, underlining the advantages of large-scale sequencing in this founder population. PMID:26366554

  6. Genome sequencing elucidates Sardinian genetic architecture and augments association analyses for lipid and blood inflammatory markers.

    PubMed

    Sidore, Carlo; Busonero, Fabio; Maschio, Andrea; Porcu, Eleonora; Naitza, Silvia; Zoledziewska, Magdalena; Mulas, Antonella; Pistis, Giorgio; Steri, Maristella; Danjou, Fabrice; Kwong, Alan; Ortega Del Vecchyo, Vicente Diego; Chiang, Charleston W K; Bragg-Gresham, Jennifer; Pitzalis, Maristella; Nagaraja, Ramaiah; Tarrier, Brendan; Brennan, Christine; Uzzau, Sergio; Fuchsberger, Christian; Atzeni, Rossano; Reinier, Frederic; Berutti, Riccardo; Huang, Jie; Timpson, Nicholas J; Toniolo, Daniela; Gasparini, Paolo; Malerba, Giovanni; Dedoussis, George; Zeggini, Eleftheria; Soranzo, Nicole; Jones, Chris; Lyons, Robert; Angius, Andrea; Kang, Hyun M; Novembre, John; Sanna, Serena; Schlessinger, David; Cucca, Francesco; Abecasis, Gonçalo R

    2015-11-01

    We report ∼17.6 million genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from previous sequencing-based compilations and are enriched for predicted functional consequences. Furthermore, ∼76,000 variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. We observe 14 signals, including 2 major new loci, for lipid levels and 19 signals, including 2 new loci, for inflammatory markers. The new associations would have been missed in analyses based on 1000 Genomes Project data, underlining the advantages of large-scale sequencing in this founder population. PMID:26366554

  7. 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

  8. [Blood DNA Radiosensitivity May Be Predictive Marker for Efficacy of Radiation Therapy in Glioma Tumorbearing Individuals].

    PubMed

    Ivanov, S D; Korytova, L I; Yamshanov, V A; Zhabina, R M; Semenov, A L; Krasnikova, V G

    2015-01-01

    Animal and clinical studies were conducted to evaluate the association between the blood DNA radiosensitivity, assessed by determining the original S-index ex vivo, and the response of gliomas to irradiation in vivo. Possible modifications of the latter after administration of iron-containing water (ICW) in rats were also explored. The study was performed on the rats with subcutaneously implanted experimental glioma-35. The tumors were locally X-irradiated with a single 15 Gy dose as a radiation therapy (RT). ICW (60-63 mg · Fe 2+/l) was administered as a drinking water for 3 days before treatment. The animals underwent blood sampling for analysis of the DNA concentration and leukocyte count. The DNA index was estimated 24 h after RT. The S-index was evaluated within 4 h before RT. The mean initial S-index in the blood samples of glioma-bearing rats was 0.73 ± 0.05. Addition of ICW ex vivo resulted in a significantly increased S-index in a half of the samples. In general, the irradiated rats, which had been given pretreatment with ICW and demonstrated an ex vivo increase of the S-index to > 1.0, showed the most marked inhibition of tumor progression and the smallest tumor volume 25 days after irradiation. They also exhibited the lowest rate of growth and the longest survival. Determination of the biochemical S-index and evaluation of its changes ex vivo caused by ICW may be predictive of the response of experimental glioma to irradiation with radiomodification. The S-index may serve as a predictive indicator in clinic of the efficient evaluation of RT in patients with glioma. PMID:26863781

  9. CD45+/CD133+ positive cells expanded from umbilical cord blood expressing PDX-1 and markers of pluripotency.

    PubMed

    Pessina, Augusto; Bonomi, Arianna; Sisto, Francesca; Baglio, Carolina; Cavicchini, Loredana; Ciusani, Emilio; Coccé, Valentina; Gribaldo, Laura

    2010-08-01

    UCB (human umbilical cord blood) contains cells able to differentiate into non-haematopoietic cell lineages. It also contains cells similar to primitive ESCs (embryonic stem cells) that can differentiate into pancreatic-like cells. However, few data have been reported regarding the possibility of expanding these cells or the differential gene expression occurring in vitro. In this study, we expanded formerly frozen UCB cells by treatment with SCF (stem cell factor) and GM-CSF (granulocyte-macrophage colony stimulating factor) in the presence of VPA (valproic acid). Gene expression profiles for beta cell differentiation and pluripotency (embryo stem cell phenotype) were analysed by RT-PCR and immunocytochemistry. The results show a dramatic expansion (>150-fold) of haematopoietic progenitors (CD45+/CD133+) which also expressed embryo markers of pluripotency (nanog, kfl-4, sox-2, oct-3/4 and c-myc), nestin, and pancreatic markers such as pax-4, ngn-3, pdx-1 and syt-1 (that is regulated by pdx-1 and provides the cells with a Ca++ regulation mechanism essential for insulin exocytosis). Our results show that UCB cells can be expanded to produce large numbers of cells of haematopoietic lineage that naturally (without the need of retroviral vectors or transposons) express a gene pattern compatible with endocrine pancreatic precursors and markers of pluripotency. Further investigations are necessary to clarify, first, whether in this context, the embryogenes expressed are functional or not, and secondly, since these cells are safer than cells transfected with retroviral vectors or transposons, whether they would represent a potential tool for clinical application. PMID:20397976

  10. The Potential Utility of Blood-Derived Biochemical Markers as Indicators of Early Clinical Trends Following Severe Traumatic Brain Injury

    PubMed Central

    DeFazio, Michael; Rammo, Richard; Robles, Jaime R.; Bramlett, Helen M.; Dietrich, W. Dalton; Bullock, M. Ross

    2016-01-01

    OBJECTIVE Severe traumatic brain injury (TBI) is a dynamic neuropathologic process in which a substantial proportion of patients die within the first 48-hours. The assessment of injury severity and prognosis are of primary concern in the initial management of severe TBI. Supplemental testing that aids in the stratification of patients at high risk for deterioration may significantly improve posttraumatic management in the acute setting. METHODS This retrospective study assessed the utility of both single-marker and multimarker models as predictive indicators of acute clinical status after severe TBI. Forty-four patients who sustained severe TBI (admission Glasgow Coma Scale [GCS] score ≤8) were divided into two cohorts according to a dichotomized clinical outcome at 72 hours after admission: Poor status (death or GCS score ≤8) and improved status (GCS score improved to >8). Threshold values for clinical status prediction were calculated for serum S-100B, matrix metalloproteinase-9, and plasma D-dimer, upon admission and at 24 hours after TBI by the use of receiver operating characteristic analysis. Performance characteristics of these single-marker predictors were compared with those derived from a multimarker logistic regression analysis. RESULTS Biomarkers with the greatest predictive value for poor status at 72 hours included serum S-100B on admission, as well as plasma D-dimer and serum S-100B at 24 hours, for which, associations were strongly significant. Multimarker analysis indicated no substantial improvement in prediction accuracy over the best single predictors during this time frame. CONCLUSION In conjunction with other clinical, physical, and radiologic evidence, blood-derived biochemical markers may serve to enhance prediction of early clinical trends after severe TBI. PMID:23313262

  11. Mitochondrial activity and oxidative stress markers in peripheral blood mononuclear cells of patients with bipolar disorder, schizophrenia, and healthy subjects.

    PubMed

    Gubert, Carolina; Stertz, Laura; Pfaffenseller, Bianca; Panizzutti, Bruna Schilling; Rezin, Gislaine Tezza; Massuda, Raffael; Streck, Emilio Luiz; Gama, Clarissa Severino; Kapczinski, Flávio; Kunz, Maurício

    2013-10-01

    Evidence suggests that mitochondrial dysfunction is involved in the pathophysiology of psychiatric disorders such as schizophrenia (SZ) and bipolar disorder (BD). However, the exact mechanisms underlying this dysfunction are not well understood. Impaired activity of electron transport chain (ETC) complexes has been described in these disorders and may reflect changes in mitochondrial metabolism and oxidative stress markers. The objective of this study was to compare ETC complex activity and protein and lipid oxidation markers in 12 euthymic patients with BD type I, in 18 patients with stable chronic SZ, and in 30 matched healthy volunteers. Activity of complexes I, II, and III was determined by enzyme kinetics of mitochondria isolated from peripheral blood mononuclear cells (PBMCs). Protein oxidation was evaluated using the protein carbonyl content (PCC) method, and lipid peroxidation, the thiobarbituric acid reactive substances (TBARS) assay kit. A significant decrease in complex I activity was observed (p = 0.02), as well as an increase in plasma levels of TBARS (p = 0.00617) in patients with SZ when compared to matched controls. Conversely, no significant differences were found in complex I activity (p = 0.17) or in plasma TBARS levels (p = 0.26) in patients with BD vs. matched controls. Our results suggest that mitochondrial complex I dysfunction and oxidative stress play important roles in the pathophysiology of SZ and may be used in potential novel adjunctive therapy for SZ, focusing primarily on cognitive impairment and disorder progression. PMID:23870796

  12. 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. PMID:21286851

  13. White blood cell and platelet indices as prognostic markers in patients with invasive ductal breast carcinoma

    PubMed Central

    Mantas, Dimitrios; Kostakis, Ioannis D.; Machairas, Nikolaos; Markopoulos, Christos

    2016-01-01

    A growing body of evidence suggests that oncogenesis is associated with systemic inflammation. The present study investigated white blood cell and platelet indices, whose values change during the inflammatory response, in women with invasive ductal breast carcinoma. Preoperatively obtained white blood cell and platelet counts from 53 patients with early breast cancer, who developed systemic metastases over a mean follow-up period of 65 months, were analyzed and compared with those of a matching control group formed of 37 patients with the same characteristics, who remained recurrence-free during the same time period. Patients who developed distant metastasis had a significantly higher mean platelet volume and lower neutrophil count than patients who did not present with distant metastasis. Furthermore, time to distant metastasis development was longer in patients with a lower mean platelet volume, whilst patients with a lower neutrophil count had a shorter systemic disease-free time interval. However, receiver operating characteristic curve analysis demonstrated that these parameters provided moderate accuracy in predicting which patients may develop distant metastasis. No differences were detected between patient groups regarding additional parameters. Patients who developed systemic disease during a mean follow-up period of 65 months were observed to have an increased mean platelet volume and decreased neutrophil count preoperatively. These results indicate that such parameters may be of prognostic value in patients with breast cancer. Studies with a larger number of patients are required to further investigate this hypothesis. PMID:27446480

  14. 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

  15. In vivo detection of small tumour lesions by multi-pinhole SPECT applying a (99m)Tc-labelled nanobody targeting the Epidermal Growth Factor Receptor.

    PubMed

    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 (99m)Tc-D10 for visualizing small tumour lesions with volumes below 100 mm(3) 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 (99m)Tc-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 mm(3) ± 21.2 and 26.6 mm(3) ± 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 (99m)Tc-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 (99m)Tc-D10. PMID:26912069

  16. 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

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

    PubMed Central

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

    2010-01-01

    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. PMID:19884327

  18. 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

  19. Lenalidomide treatment induced the normalization of marker protein levels in blood plasma of patients with 5q-myelodysplastic syndrome.

    PubMed

    Messingerová, Lucia; Jonášová, Anna; Barančik, Miroslav; Poleková, Lenka; Šereš, Mário; Gibalová, Lenka; Breier, Albert; Sulová, Zdena

    2015-10-01

    A specific type of myelodysplastic syndrome (MDS) is associated with isolated deletion on the long arm of chromosome 5, i.e., 5q-syndrome (del(5q)). The treatment approaches for MDS del(5q) include the immunomodulating drug lenalidomide (LEN). Thirteen MDS del(5q) patients were included in this study. We found elevated activities of lactate dehydrogenase (LDH) and matrix metalloproteinase 9 (MMP-9) in the blood plasma of MDS del(5q) patients as compared with healthy controls. This was stabilized to control values after LEN treatment. Similar behavior we registered also for the thioredoxin and calnexin contents in BP. Peripheral blood mononuclear cells (PBMC) from patients with MDS del(5q) prior to and after treatment with LEN did not exhibit any detectable amount of P-glycoprotein (P-gp) gene transcript. However, we detected a measurable amount of multidrug resistance associated protein 1 (MRP1) mRNA in PBMCs from three patients prior to LEN treatment and in one patient during LEN treatment but it was not present prior to treatment. These data indicated on usefulness of applied protein markers estimation for monitoring of MDS del(5q) patient treatment effectiveness by LEN. Expression of MRP1 seems to be independent on LEN treatment and reflects probably the molecular variability in the ethiopathogenesis of MDS del(5q). PMID:26001289

  20. Isolation and characterization of 48 polymorphic microsatellite markers for the blood clam Scapharca broughtonii (Arcidae).

    PubMed

    Tian, J-T; Liu, Z-H; Zhou, L-Q; Wu, B; Liu, P; Yang, A-G

    2012-01-01

    Blood clams (Scapharca broughtonii) are widely cultivated and consumed in noutheast Asia. Forty-eight polymorphic microsatellite loci were developed for this clam using magnetic-bead hybridization enrichment. The number of alleles per locus ranged from 2 to 14. Polymorphism of these loci was assessed in 30 individuals from a population collected from coastal areas of Qingdao, China. The values of observed heterozygosity, expected heterozygosity and polymorphism information content per locus ranged from 0.1034 to 0.9655, from 0.1831 to 0.9208, and from 0.1638 to 0.8964, respectively. Forty-three of 48 loci conformed to Hardy-Weinberg equilibrium. These microsatellite loci would be useful for molecular genetic breeding, population genetics, genome mapping, and other relevant research on S. broughtonii. PMID:23096914

  1. 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

  2. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD.

    PubMed

    Barnes, Neil C; Sharma, Raj; Lettis, Sally; Calverley, Peter M A

    2016-05-01

    Identification of a biomarker that predicts response to inhaled corticosteroids (ICS) would help evaluate the risk/benefit profile of ICS in chronic obstructive pulmonary disease (COPD) and guide treatment.The ISOLDE study randomised 751 patients (mean post-bronchodilator forced expiratory volume in 1 s (FEV1) 1.4 L: 50% predicted normal) to fluticasone propionate 500 μg twice daily or placebo for 3 years, finding no difference in FEV1 rate of decline between treatments (p=0.16) and a significant reduction in median exacerbation rate with fluticasone propionate versus placebo (p=0.026). We re-analysed ISOLDE results by baseline blood eosinophil count to investigate whether eosinophil level predicts ICS benefit.Patients with eosinophils <2% (n=456) had a similar rate of post-bronchodilator FEV1 decline with fluticasone propionate as placebo (-2.9 mL·year(-1); p=0.688). With eosinophils ≥2% (n=214), the rate of decline decreased by 33.9 mL·year(-1) with fluticasone propionate versus placebo (p=0.003). Exacerbation rate reduction on ICS for fluticasone propionate versus placebo was higher in the eosinophil <2% group compared with the ≥2% group; time-to-first moderate/severe exacerbation was not different between treatments in either group.A baseline blood eosinophil count of ≥2% identifies a group of COPD patients with slower rates of decline in FEV1 when treated with ICS: prospective testing of this hypothesis is now warranted. PMID:26917606

  3. 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

  4. Neutrophil left shift and white blood cell count as markers of bacterial infection.

    PubMed

    Honda, Takayuki; Uehara, Takeshi; Matsumoto, Go; Arai, Shinpei; Sugano, Mitsutoshi

    2016-06-01

    Neutrophil left shift and white blood cell (WBC) count are routine laboratory tests used to assess neutrophil state, which depends on supply from the bone marrow and consumption in the tissues. If WBC count is constant, the presence of left shift indicates an increase of neutrophil consumption that is equal to an increase of production. A decrease in WBC count indicates that neutrophil consumption surpasses supply. During a bacterial infection, large numbers of neutrophils are consumed. Thus, from onset of infection to recovery, dynamic changes occur in WBC count and left shift data, reflecting the mild to serious condition of the bacterial infection. Although various stimuli in healthy and pathological conditions also cause left shift, a change as sudden and significant is only seen in bacterial infection. Left shift does not occur in the extremely early or late phases of infection; therefore, assessing data from a single time point is unsuitable for diagnosing a bacterial infection. We argue that time-series data of left shift and WBC count reflect real-time neutrophil consumption during the course of a bacterial infection, allowing more accurate evaluation of patient condition. PMID:27034055

  5. 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

  6. Subjective food hypersensitivity: assessment of enterochromaffin cell markers in blood and gut lavage fluid

    PubMed Central

    Gregersen, Kine; Valeur, Jørgen; Lillestøl, Kristine; Frøyland, Livar; Araujo, Pedro; Lied, Gülen Arslan; Berstad, Arnold

    2011-01-01

    Background: Food hypersensitivity is commonly suspected, but seldom verified. Patients with subjective food hypersensitivity suffer from both intestinal and extraintestinal health complaints. Abnormalities of the enterochromaffin cells may play a role in the pathogenesis. The aim of this study was to investigate enterochromaffin cell function in patients with subjective food hypersensitivity by measuring serum chromogranin A (CgA) and 5-hydroxytryptamine (5-HT, serotonin) in gut lavage fluid. Methods: Sixty-nine patients with subjective food hypersensitivity were examined. Twenty-three patients with inflammatory bowel disease and 35 healthy volunteers were included as comparison groups. CgA was measured in serum by enzyme-linked immunosorbent assay. Gut lavage fluid was obtained by administering 2 L of polyethylene glycol solution intraduodenally. The first clear fluid passed per rectum was collected and 5-HT was analyzed by liquid chromatography tandem mass spectrometry. Results: Serum levels of CgA were significantly lower in patients with subjective food hypersensitivity than in healthy controls (P = 0.04). No differences were found in 5-HT levels in gut lavage fluid between patients with subjective food hypersensitivity and the control groups. There was no correlation between serum CgA and gut lavage 5-HT. Conclusion: Decreased blood levels of CgA suggest neuroendocrine alterations in patients with subjective food hypersensitivity. However, 5-HT levels in gut lavage fluid were normal. PMID:21887108

  7. Quantitative trait locus mapping in chickens by selective DNA pooling with dinucleotide microsatellite markers by using purified DNA and fresh or frozen red blood cells as applied to marker-assisted selection.

    PubMed

    Lipkin, E; Fulton, J; Cheng, H; Yonash, N; Soller, M

    2002-03-01

    Many large, half-sib sire families are an integral component of chicken genetic improvement programs. These family structures include a sufficient number of individuals for mapping quantitative trait loci (QTL) at high statistical power. However, realizing this statistical power through individual or selective genotyping is yet too costly to be feasible under current genotyping methodologies. Genotyping costs can be greatly reduced through selective DNA pooling, involving densitometric estimates of marker allele frequencies in pooled DNA samples. When using dinucleotide microsatellite markers, however, such estimates are often confounded by overlapping "shadow" bands and can be confounded further by differential amplification of alleles. In the present study a shadow correction procedure provided accurate densitometric estimates of allele frequency for dinucleotide microsatellite markers in pools made from chicken purified DNA samples, fresh blood samples, and frozen-thawed blood samples. In a retrospective study, selective DNA pooling with thawed blood samples successfully identified two QTL previously shown by selective genotyping to affect resistance in chickens to Marek's disease. It is proposed that use of selective DNA pooling can provide relatively low-cost mapping and use in marker-assisted selection of QTL that affect production traits in chickens. PMID:11902402

  8. Quantification of tumour vasculature and hypoxia by immunohistochemical staining and HbO2 saturation measurements.

    PubMed

    Fenton, B M; Paoni, S F; Lee, J; Koch, C J; Lord, E M

    1999-02-01

    Despite the possibility that tumour hypoxia may limit radiotherapeutic response, the underlying mechanisms remain poorly understood. A new methodology has been developed in which information from several sophisticated techniques is combined and analysed at a microregional level. First, tumour oxygen availability is spatially defined by measuring intravascular blood oxygen saturations (HbO2) cryospectrophotometrically in frozen tumour blocks. Second, hypoxic development is quantified in adjacent sections using immunohistochemical detection of a fluorescently conjugated monoclonal antibody (ELK3-51) to a nitroheterocyclic hypoxia marker (EF5), thereby providing information relating to both the oxygen consumption rates and the effective oxygen diffusion distances. Third, a combination of fluorescent (Hoechst 33342 or DiOC7(3)) and immunohistological (PECAM-1/CD31) stains is used to define the anatomical vascular densities and the fraction of blood vessels containing flow. Using a computer-interfaced microscope stage, image analysis software and a 3-CCD colour video camera, multiple images are digitized, combined to form a photo-montage and revisited after each of the three staining protocols. By applying image registration techniques, the spatial distribution of HbO2 saturations is matched to corresponding hypoxic marker intensities in adjacent sections. This permits vascular configuration to be related to oxygen availability and allows the hypoxic marker intensities to be quantitated in situ. PMID:10027314

  9. Growth factors and metabolic markers in cord blood: relationship to birth weight and length.

    PubMed

    Napoli, F; Di Iorgi, N; Bagnasco, F; Cangemi, G; D'Amico, B; Boschetti, M; Allegri, A E M; Bruzzone Ichim, I A; Traggiai, C; Allodi, A; Polo Perucchin, P; Ghezzi, M; Noli, S; Giaccardi, M; Roviglione, B; De Miglio, L; Calcagno, A; Lorini, R; Maghnie, M

    2014-01-01

    Low birth weight and length for gestational age are associated with a high risk of short stature and metabolic syndrome in adulthood. The mechanisms that link prenatal growth to adult stature and metabolic syndrome have not yet been entirely clarified. The aim of our study was to evaluate the relationship between standardized anthropometric measures at birth and insulin-like growth factor (IGF)-I, IGF-II, insulin, adiponectin, and non-esterified fatty acid (NEFA) cord blood levels in the general population. One hundred fifty-eight random newborn subjects (77F, 81M) from Genoa, Italy, were analyzed. Anthropometric parameters were measured and standardized according to standard Italian tables. Insulin values were treated as categorical, since in several cases the results fell below detection cut-off. Mean birth weight was 3,214.23∓488.99 gr and mean length was 49.82∓2.17 cm. Females had higher mean IGF-I (p=0.04), and were more likely to have insulin values either <2 μU/ml or >4.5μU/ml (p= 0.04) compared to males. Weight and length SD scores (SDS) were higher in subjects with elevated insulin levels (p=0.002). A moderate correlation was found between weight and IGF-II (r=0.354). Multivariable analysis demonstrated that standardized birth weight was associated with IGFII and insulin values. Our data highlight the importance of IGF-II in fetal growth and suggest that gender differences should be taken into consideration when evaluating prenatal growth. PMID:25001656

  10. Effect of major burns on early and late activating markers of peripheral blood T lymphocytes.

    PubMed

    Sayed, S; Bakry, R; El-Shazly, M; El-Oteify, M; Terzaki, S; Fekry, M

    2012-03-31

    It is known that lymphocytes immunophenotype is a reflection of the functional level of the immune system. The immunosuppressive effect of major burns is also known for many years. T lymphocytes of 50 major burn patients were analyzed in base line (BL) samples at 24 hours and at 1 week and 2 weeks after burn, using monoclonal antibodies of CD3, CD4, CD8, CD25 (IL2R) and HLA-DR by flow cytometry and β2-microglobulin (β2-m) by ELISA. Recorded values were compared with those of 50 healthy donors. There was statistically significant reduction in absolute number of CD3 positive cells (CD3+) (p<0.000) and CD4/CD8 ratio (p=0.01) in the first 24 hours in comparison with controls. CD25 (IL-2R) shows insignificant upregulation on T lymphocytes after burn with significant upregulation of HLA-DR. The absolute number of CD3+ cells began to increase after 2 weeks (p=0.03) but remained less than controls (p=0.08). CD4/CD8 ratio was more or less same as healthy controls after 2 weeks. Upregulation of CD25 was insignificantly increased and that of HLA-DR was markedly increased after 2 weeks (p=0.001). Significant negative correlations were detected between mean values of β2-m and both absolute numbers of CD3 and CD4 positive cells in BL and one week samples. In addition there was significant correlation between mean values of β2-m and values of CD25 expression in the BL samples. The obtained data is suggestive of persistent activation of T lymphocytes two weeks after major burns whereas early shedding of β2-m is related to activation of lymphocytes increasing their susceptibility to apoptosis, both indicative of altered immune response. Burn intensivists and surgeons should be keen to support the patients' immune system in the first hours following major burns. This support will ensure free-bacteremic blood with a consequent better prognosis. PMID:23012611

  11. 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

  12. Blood

    MedlinePlus

    ... fight infection and are part of your body's defense system. Platelets help blood to clot when you have a cut or wound. Bone marrow, the spongy material inside your bones, makes new blood cells. Blood cells ...

  13. Novel Molecular Tumor Cell Markers in Regional Lymph Nodes and Blood Samples from Patients Undergoing Surgery for Non-Small Cell Lung Cancer

    PubMed Central

    Nordgård, Oddmund; Singh, Gurpartap; Solberg, Steinar; Jørgensen, Lars; Halvorsen, Ann Rita; Smaaland, Rune; Brustugun, Odd Terje; Helland, Åslaug

    2013-01-01

    Introduction Recent evidence suggests that microscopic lymph node metastases and circulating tumor cells may have clinical importance in lung cancer. The purpose of this study was to identify new molecular markers for tumor cells in regional lymph nodes (LNs) and peripheral blood (PB) from patients with non-small cell lung cancer (NSCLC). Methods Candidate markers were selected based on digital transcript profiling and previous literature. KRT19, CEACAM5, EPCAM, DSG3, SFTPA, SFTPC and SFTPB mRNA levels were initially validated by real-time reverse transcription PCR-based quantification in 16 NSCLC tumors and 22 LNs and 12 PB samples from individuals without known cancer. Five of the candidate markers were selected for secondary validation by quantification in parallel tumor biopsies, regional LNs and PB samples from 55 patients undergoing surgery for NSCLC. LN and PB marker status were compared to clinicopathological patient data. Results All selected markers except DSG3 were present at high levels in the primary tumors and at very low or non-detectable levels in normal LNs and PB in the first round of validation, indicating a potential for detecting tumor cells in NSCLC patients. The expression profiles of KRT19, CEACAM5, DSG3, SFTPA and SFTPC mRNA were confirmed in the larger group during the secondary validation. Using the highest normal LN level of each marker as threshold, 39 (71%) of the 55 patients had elevated levels of at least one marker in regional LNs. Similarly, 26 (47%) patients had elevated levels of at least one marker in PB. A significantly higher number of patients with adenocarcinomas had positive LN status for these markers, compared with other histological types (P = 0.004). Conclusions Several promising molecular tumor cell markers in regional LNs and PB were identified, including the new SFTPA and SFTPC mRNAs. Clinical follow-up in a larger cohort is needed to elucidate their prognostic value. PMID:23671585

  14. Nilotinib and bosutinib modulate pre-plaque alterations of blood immune markers and neuro-inflammation in Alzheimer's disease models.

    PubMed

    Lonskaya, I; Hebron, M L; Selby, S T; Turner, R S; Moussa, C E-H

    2015-09-24

    Alzheimer's disease (AD) brains exhibit plaques and tangles in association with inflammation. The non-receptor tyrosine kinase Abl is linked to neuro-inflammation in AD. Abl inhibition by nilotinib or bosutinib facilitates amyloid clearance and may decrease inflammation. Transgenic mice that express Dutch, Iowa and Swedish APP mutations (TgAPP) and display progressive Aβ plaque deposition were treated with tyrosine kinase inhibitors (TKIs) to determine pre-plaque effects on systemic and CNS inflammation using milliplex® ELISA. Plaque Aβ was detected at 4months in TgAPP and pre-plaque intracellular Aβ accumulation (2.5months) was associated with changes of cytokines and chemokines prior to detection of glial changes. Plaque formation correlated with increased levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1α, IL-1β) and markers of immunosuppressive and adaptive immunity, including, IL-4, IL-10, IL-2, IL-3, Vascular Endothelial Growth Factor (VEGF) and IFN-γ. An inverse relationship of chemokines was observed as CCL2 and CCL5 were lower than WT mice at 2months and significantly increased after plaque appearance, while soluble CX3CL1 decreased. A change in glial profile was only robustly detected at 6months in Tg-APP mice and TKIs reduced astrocyte and dendritic cell number with no effects on microglia, suggesting alteration of brain immunity. Nilotinib decreased blood and brain cytokines and chemokines and increased CX3CL1. Bosutinib increased brain and blood IL-10 and CX3CL1, suggesting a protective role for soluble CX3CL1. Taken together these data suggest that TKIs regulate systemic and CNS immunity and may be useful treatments in early AD through dual effects on amyloid clearance and immune modulation. PMID:26235435

  15. 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

  16. Functional canine dendritic cells can be generated in vitro from peripheral blood mononuclear cells and contain a cytoplasmic ultrastructural marker.

    PubMed

    Ibisch, C; Pradal, G; Bach, J M; Lieubeau, B

    2005-03-01

    For physiological and practical reasons the dog is a large animal model used increasingly to study the pathogenesis of human diseases and new therapeutic approaches, in particular for immune disorders. However, some immunological resources are lacking in this model, especially concerning dendritic cells. The aim of our study was to develop an efficient method to generate dendritic cells (DC) in vitro from dog peripheral blood mononuclear cells (PBMC) and to characterize their functional, structural and ultrastructural properties. PBMC were cultured in vitro with IL-4 and GM-CSF. After 1 week of culture, a great proportion of non-adherent cells displayed typical cytoplasmic processes, as evidenced both by optical and electron microscopy. Cytometric analysis revealed the presence of 41.7+/-24.6% CD14+ cells expressing both CD11c and MHC class II molecules. Allogeneic mixed lymphocyte reactions confirmed the ability of these cultures to stimulate the proliferation of allogeneic lymphocytes as already reported as a characteristic of DC in other species. In addition, we describe for the first time the presence in canine DC of cytoplasmic periodic microstructures (PMS) that could represent ultrastructural markers of canine DC. In conclusion, our study provides an easy method to generate DC from PBMC in sufficient numbers for immunological in vitro investigations in dogs, a pre-clinical model for many human diseases. PMID:15847807

  17. Blood Viscosity and the Expression of Inflammatory and Adhesion Markers in Homozygous Sickle Cell Disease Subjects with Chronic Leg Ulcers

    PubMed Central

    Bowers, Andre S.; Reid, Harvey L.; Greenidge, Andre; Landis, Clive; Reid, Marvin

    2013-01-01

    Objective To determine differences in TNF-α, IL-1β, IL-10, sICAM-1 concentrations, leg hypoxia and whole blood viscosity (WBV) at shear rates of 46 sec-1 and 230 sec-1 in persons with homozygous S sickle cell disease (SCD) with and without chronic leg ulceration and in AA genotype controls. Design & Methods: fifty-five age-matched participants were recruited into the study: 31 SS subjects without leg ulcers (SSn), 24 SS subjects with leg ulcers (SSu) and 18 AA controls. Haematological indices were measured using an AC.Tron Coulter Counter. Quantification of inflammatory, anti-inflammatory and adhesion molecules was performed by ELISA. Measurement of whole blood viscosity was done using a Wells Brookfield cone-plate viscometer. Quantification of microvascular tissue oxygenation was done by Visible Lightguide spectrophotometry. Results TNF-α and whole blood viscosity at 46 sec-1 and 230 sec-1 (1.75, 2.02 vs. 0.83, 1.26, p<0.05) were significantly greater in sickle cell disease subjects than in controls. There were no differences in plasma concentration of sICAM-1, IL-1β and IL-10 between SCD subjects and controls. IL-1β (median, IQR: 0.96, 1.7 vs. 0, 0.87; p<0.01) and sICAM-1 (226.5, 156.48 vs. 107.63, 121.5, p<0.005) were significantly greater in SSu group compared with SSn. However there were no differences in TNF-α (2, 3.98 vs. 0, 2.66) and IL-10 (13.34, 5.95 vs. 11.92, 2.99) concentrations between SSu and SSn. WBV in the SSu group at 46 sec-1 and at 230 Sec 1 were 1.9 (95%CI; 1.2, 3.1) and 2.3 (1.2, 4.4) times greater than in the SSn group. There were no differences in the degree of tissue hypoxia as determined by lightguide spectrophotometry. Conclusion Inflammatory, adhesion markers and WBV may be associated with leg ulceration in sickle cell disease by way of inflammation-mediated vasoocclusion/vasoconstriction. Impaired skin oxygenation does not appear to be associated with chronic ulcers in these subjects with sickle cell disease. PMID:23922670

  18. Investigating the role of tumour cell derived iNOS on tumour growth and vasculature in vivo using a tetracycline regulated expression system.

    PubMed

    Papaevangelou, Efthymia; Whitley, Guy S; Johnstone, Alan P; Robinson, Simon P; Howe, Franklyn A

    2016-06-01

    Nitric oxide (NO) is a free radical signalling molecule involved in various physiological and pathological processes, including cancer. Both tumouricidal and tumour promoting effects have been attributed to NO, making its role in cancer biology controversial and unclear. To investigate the specific role of tumour-derived NO in vascular development, C6 glioma cells were genetically modified to include a doxycycline regulated gene expression system that controls the expression of an antisense RNA to inducible nitric oxide synthase (iNOS) to manipulate endogenous iNOS expression. Xenografts of these cells were propagated in the presence or absence of doxycycline. Susceptibility magnetic resonance imaging (MRI), initially with a carbogen (95% O2 /5% CO2 ) breathing challenge and subsequently an intravascular blood pool contrast agent, was used to assess haemodynamic vasculature (ΔR2 *) and fractional blood volume (fBV), and correlated with histopathological assessment of tumour vascular density, maturation and function. Inhibition of NO production in C6 gliomas led to significant growth delay and inhibition of vessel maturation. Parametric fBV maps were used to identify vascularised regions from which the carbogen-induced ΔR2 * was measured and found to be positively correlated with vessel maturation, quantified ex vivo using fluorescence microscopy for endothelial and perivascular cell staining. These data suggest that tumour-derived iNOS is an important mediator of tumour growth and vessel maturation, hence a promising target for anti-vascular cancer therapies. The combination of ΔR2 * response to carbogen and fBV MRI can provide a marker of tumour vessel maturation that could be applied to non-invasively monitor treatment response to iNOS inhibitors. PMID:26756734

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

    PubMed

    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. 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

  1. Tumour-associated hypoglycaemia in a murine cachexia model.

    PubMed Central

    McDevitt, T. M.; Tisdale, M. J.

    1992-01-01

    Animals bearing a cachexia-inducing tumour, the MAC16 adenocarcinoma, showed a progressive decrease in blood glucose levels with increasing weight loss, while animals bearing a histologically similar tumour, the MAC13 adenocarcinoma, showed no change in either body weight or blood glucose levels with growth of the tumour. The effect of the MAC16 tumour on blood glucose levels appeared to be unrelated to food intake, glucose consumption by the tumour, or to the production of increased levels of IGF-I and IGF-II mRNA by the tumour cells. The relationship between the induction of cachexia and alteration in blood glucose levels remains unknown. Images Figure 4 Figure 5 PMID:1358167

  2. White Blood Cell Counts as Risk Markers of Developing Metabolic Syndrome and Its Components in the Predimed Study

    PubMed Central

    Babio, Nancy; Ibarrola-Jurado, Núria; Bulló, Mònica; Martínez-González, Miguel Ángel; Wärnberg, Julia; Salaverría, Itziar; Ortega-Calvo, Manuel; Estruch, Ramón; Serra-Majem, Lluís; Covas, Maria Isabel; Sorli, José Vicente; Salas-Salvadó, Jordi

    2013-01-01

    Background The Metabolic Syndrome (MetS) is a cluster of metabolic abnormalities that includes hyperglucemia, hypertension, dyslipidemia and central obesity, conferring an increased risk of cardiovascular disease. The white blood cell (WBC) count has been proposed as a marker for predicting cardiovascular risk. However, few prospective studies have evaluated the relationship between WBC subtypes and risk of MetS. Methods Participants were recruited from seven PREDIMED study centers. Both a baseline cross-sectional (n = 4,377) and a prospective assessment (n = 1,637) were performed. Participants with MetS at baseline were excluded from the longitudinal analysis. The median follow-up was 3.9 years. Anthropometric measurements, blood pressure, fasting glucose, lipid profile and WBC counts were assessed at baseline and yearly during the follow-up. Participants were categorized by baseline WBC and its subtype count quartiles. Adjusted logistic regression models were fitted to assess the risk of MetS and its components. Results Of the 4,377 participants, 62.6% had MetS at baseline. Compared to the participants in the lowest baseline sex-adjusted quartile of WBC counts, those in the upper quartile showed an increased risk of having MetS (OR, 2.47; 95%CI, 2.03–2.99; P-trend<0.001). This association was also observed for all WBC subtypes, except for basophils. Compared to participants in the lowest quartile, those in the top quartile of leukocyte, neutrophil and lymphocyte count had an increased risk of MetS incidence. Leukocyte and neutrophil count were found to be strongly associated with the MetS components hypertriglyceridemia and low HDL-cholesterol. Likewise, lymphocyte counts were found to be associated with the incidence of the MetS components low HDL-cholesterol and high fasting glucose. An increase in the total WBC during the follow-up was also associated with an increased risk of MetS. Conclusions Total WBC counts, and some subtypes, were positively

  3. 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

  4. Peculiarities of hyperlipidaemia in tumour patients.

    PubMed Central

    Dilman, V. M.; Berstein, L. M.; Ostroumova, M. N.; Tsyrlina, Y. V.; Golubev, A. G.

    1981-01-01

    The study group included 684 cases: 258 patients with breast carcinoma, 113 males with lung cancer, 42 patients with rectal tumours, 42 patients with stomach tumours, 59 patients with fibroadenomatosis, and 170 healthy subjects of varying age (male and female). A relatively high blood triglyceride level was found in patients with breast, lung, rectal (females), and stomach (female) tumours. The blood concentration of high-density lipoprotein-cholesterol in patients with breast, lung, and stomach (female) tumours was relatively low. The elimination of tumour (breast carcinoma) did not lead to significant changes in lipid metabolism. There was no correlation between degree of lipidaemia and stage of tumour progression except in the cases of rectal cancer. Preliminary results are presented on the tentative classification of hyperlipoproteinaemia in tumour patients, using the lipid concentration threshold values advocated by Carlson et al. (1977); an increased frequency of Type IV hyperlipoproteinaemia proved to be the most characteristic feature of tumour patients. The results are discussed in terms of the concept of the importance of lipid metabolic disturbances, primarily those due to ageing, in the genesis of the syndrome of "cancerophilia" (predisposition to cancer). PMID:7248149

  5. 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

  6. The mRNA level of Charcot-Leyden crystal protein/galectin-10 is a marker for CRTH2 activation in human whole blood in vitro.

    PubMed

    Lin, Tai-An; Kourteva, Galina; Hilton, Holly; Li, Hongli; Tare, Nadine S; Carvajal, Valerie; Hang, Julie S; Wei, Xin; Renzetti, Louis M

    2010-11-01

    CRTH2 is one of the prostaglandin D₂ receptors and plays a proinflammatory role in allergic diseases. Gene expression markers in whole blood induced by CRTH2 activation have not previously been reported. Using microarray analyses of 54 675 genes, we revealed modest gene expression changes in human whole blood stimulated in vitro by a selective CRTH2 agonist, DK-PGD₂. Five genes were found to exhibit 1.5- to 2.6-fold changes in expression. The expression of Charcot-Leyden crystal protein/galectin-10 (CLC/Gal-10) in particular was consistently enhanced in human whole blood stimulated by DK-PGD₂, as confirmed by quantitative real-time polymerase chain reaction analyses. DK-PGD(2)-induced increases in blood CLC/Gal-10 mRNA levels were largely attenuated by the CRTH2 antagonist CAY10471.Thus, the DK-PGD₂-induced CLC/Gal-10 mRNA level can serve as a potential marker for monitoring pharmacodynamic effects of blood exposure to CRTH2 modulating agents. PMID:20858065

  7. 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

  8. 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

  9. The use of novel lymphatic endothelial cell-specific immunohistochemical markers to differentiate cutaneous angiosarcomas in dogs.

    PubMed

    Halsey, C H C; Worley, D R; Curran, K; Charles, J B; Ehrhart, E J

    2016-09-01

    Lymphangiosarcomas are uncommon vascular neoplasms that arise from lymphatic endothelial cells (LECs). They efface and replace normal subcutaneous tissue and are characterised by arborising, vascular channels lined by a single layer of pleomorphic endothelial cells and a paucity of erythrocytes. Lymphangiosarcomas are architecturally similar to hemangiosarcomas, a common malignancy of vascular origin arising from blood vascular endothelial cells. Common immunohistochemical markers for vascular endothelium, such as Factor VIII-related antigen (F8RA) and CD31, have traditionally been used to confirm the diagnosis of tumours of vascular origin. However, these markers fail to differentiate between lymphangiosarcoma and hemangiosarcoma, which often show overlapping morphologic features, disparate clinical behaviour and require different treatment modalities. Here we describe the use of two novel LEC-specific markers, lymphatic vessel endothelial receptor-1 (LYVE-1) and prospero-related homeobox gene-1 (PROX-1), to further differentiate between vascular tumours of lymphatic (lymphangiosarcoma) and blood (hemangiosarcoma) endothelial cell origin in the dog. PMID:24593773

  10. 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

  11. Systematic pan-cancer analysis of tumour purity

    PubMed Central

    Aran, Dvir; Sirota, Marina; Butte, Atul J.

    2015-01-01

    The tumour microenvironment is the non-cancerous cells present in and around a tumour, including mainly immune cells, but also fibroblasts and cells that comprise supporting blood vessels. These non-cancerous components of the tumour may play an important role in cancer biology. They also have a strong influence on the genomic analysis of tumour samples, and may alter the biological interpretation of results. Here we present a systematic analysis using different measurement modalities of tumour purity in >10,000 samples across 21 cancer types from the Cancer Genome Atlas. Patients are stratified according to clinical features in an attempt to detect clinical differences driven by purity levels. We demonstrate the confounding effect of tumour purity on correlating and clustering tumours with transcriptomics data. Finally, using a differential expression method that accounts for tumour purity, we find an immunotherapy gene signature in several cancer types that is not detected by traditional differential expression analyses. PMID:26634437

  12. 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

    2016-01-01

    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

  13. Evaluation of surrogate markers for human immunodeficiency virus infection among blood donors at the blood bank of "Hospital Universitário Regional Norte do Paraná", Londrina, PR, Brazil.

    PubMed

    Reiche, Edna Maria Vissoci; Vogler, Ingridt Hildegard; Morimoto, Helena Kaminami; Bortoliero, André Luis; Matsuo, Tiemi; Yuahasi, Kátia Kioko; Cancian, Sanderson Júnior; Koguichi, Roberto Setsuo

    2003-01-01

    This study evaluated the usefulness of the anti-HBc, hepatitis C virus antibodies (anti-HCV), human T cell lymphotropic virus I and II antibodies (anti-HTLV I/II), serologic tests for syphilis, and surface antigen of hepatitis B virus (HBsAg) as surrogate markers for the risk for HIV infection in 80,284 serum samples from blood donors from the Blood Bank of "Hospital Universitário Regional Norte do Paraná", Londrina, Paraná State, Brazil, analyzed from July 1994 to April 2001. Among 39 blood donors with positive serology for HIV, 12 (30.8%) were anti-HBc positive, 10 (25.6%) for anti-HCV, 1 (2.6%) for anti-HTLV I/I, 1 (2.6%) was positive for syphilis, and 1 (2.6%) for HBsAg. Among the donors with negative serology for HIV, these markers were detected in 8,407 (10.5%), 441 (0.5%), 189 (0.2%), 464 (0.6%), and 473 (0.6%) samples, respectively. The difference was statistically significant (p < 0.001) for anti-HBc and anti-HCV. Although the predictive positive values for these surrogate markers were low for HIV infection, the results confirmed the anti-HBc and anti-HCV as useful surrogate markers for HIV infection thus reinforcing the maintenance of them in the screening for blood donors contributing to the prevention of the small number of cases in which HIV is still transmitted by transfusion. PMID:12751318

  14. Eicosapentaenoic Acid and Docosahexaenoic Acid in Whole Blood Are Differentially and Sex-Specifically Associated with Cardiometabolic Risk Markers in 8–11-Year-Old Danish Children

    PubMed Central

    Damsgaard, Camilla T.; Eidner, Maj B.; Stark, Ken D.; Hjorth, Mads F.; Sjödin, Anders; Andersen, Malene R.; Andersen, Rikke; Tetens, Inge; Astrup, Arne; Michaelsen, Kim F.; Lauritzen, Lotte

    2014-01-01

    n-3 long-chain polyunsaturated fatty acids improve cardiovascular risk markers in adults. These effects may differ between eicosapentaenoic acid (EPA, 20∶5n-3) and docosahexaenoic acid (DHA, 22∶6n-3), but we lack evidence in children. Using baseline data from the OPUS School Meal Study we 1) investigated associations between EPA and DHA in whole blood and early cardiometabolic risk markers in 713 children aged 8–11 years and 2) explored potential mediation through waist circumference and physical activity and potential dietary confounding. We collected data on parental education, pubertal stage, 7-day dietary records, physical activity by accelerometry and measured anthropometry, blood pressure, and heart rate. Blood samples were analyzed for whole blood fatty acid composition, cholesterols, triacylglycerol, insulin resistance by the homeostatic model of assessment (HOMA-IR), and inflammatory markers. Whole blood EPA was associated with a 2.7 mmHg (95% CI 0.4; 5.1) higher diastolic blood pressure per weight% EPA, but only in boys. Heart rate was negatively associated with both EPA and DHA status (P = 0.02 and P = 0.002, respectively). Whole blood EPA was negatively associated with triacylglycerol (P = 0.003) and positively with total cholesterol, low density and high density lipoprotein (HDL) cholesterol and HDL:triacylglycerol (all P<0.01) whereas DHA was negatively associated with insulin and HOMA-IR (P = 0.003) and tended to be negatively associated with a metabolic syndrome-score (P = 0.05). Adjustment for waist circumference and physical activity did not change the associations. The association between DHA and HOMA-IR was attenuated but remained after adjustment for fiber intake and none of the other associations were confounded by dietary fat, protein, fiber or energy intake. This study showed that EPA status was negatively associated with triacylglycerol and positively with cholesterols whereas DHA was negatively associated with

  15. A practical approach to immunohistochemical diagnosis of ovarian germ cell tumours and sex cord-stromal tumours.

    PubMed

    Rabban, Joseph T; Zaloudek, Charles J

    2013-01-01

    Immunohistochemistry can be useful in the diagnosis of ovarian germ cell tumours and sex cord-stromal tumours. A wide variety of markers are available, including many that are novel. The aim of this review is to provide a practical approach to the selection and interpretation of these markers, emphasizing an understanding of their sensitivity and specificity in the particular differential diagnosis in question. The main markers discussed include those for malignant germ cell differentiation (SALL4 and placental alkaline phosphatase), dysgerminoma (OCT4, CD117, and D2-40), yolk sac tumour (α-fetoprotein and glypican-3), embryonal carcinoma (OCT4, CD30, and SOX2), sex cord-stromal differentiation (calretinin, inhibin, SF-1, FOXL2) and steroid cell tumours (melan-A). In addition, the limited role of immunohistochemistry in determining the primary site of origin of an ovarian carcinoid tumour is discussed. PMID:23240671

  16. 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

  17. Interaction of blood lead and delta-aminolevulinic acid dehydratase genotype on markers of heme synthesis and sperm production in lead smelter workers.

    PubMed

    Alexander, B H; Checkoway, H; Costa-Mallen, P; Faustman, E M; Woods, J S; Kelsey, K T; van Netten, C; Costa, L G

    1998-04-01

    The gene that encodes gamma-aminolevulinic acid dehydratase (ALAD) has a polymorphism that may modify lead toxicokinetics and ultimately influence individual susceptibility to lead poisoning. To evaluate the effect of the ALAD polymorphism on lead-mediated outcomes, a cross-sectional study of male employees from a lead-zinc smelter compared associations between blood lead concentration and markers of heme synthesis and semen quality with respect to ALAD genotype. Male employees were recruited via postal questionnaire to donate blood and urine for analysis of blood lead, zinc protoporphyrin (ZPP), urinary coproporphyrin (CPU), and ALAD genotype, and semen samples for semen analysis. Of the 134 workers who had ALAD genotypes completed, 114 (85%) were ALAD1-1 (ALAD1) and 20 (15%) were ALAD1-2 (ALAD2). The mean blood lead concentrations for ALAD1 and ALAD2 were 23.1 and 28.4 microg/dl (p = 0.08), respectively. ZPP/heme ratios were higher in ALAD1 workers (68.6 vs. 57.8 micromol/ml; p = 0.14), and the slope of the blood lead ZPP linear relationship was greater for ALAD1 (2.83 vs. 1.50, p = 0.06). No linear relationship between CPU and blood lead concentration was observed for either ALAD1 or ALAD2. The associations of blood lead concentration with ZPP, CPU, sperm count, and sperm concentration were more evident in workers with the ALAD1 genotype and blood lead concentrations >/= 40 microg/dl. The ALAD genetic polymorphism appears to modify the association between blood lead concentration and ZPP. However, consistent modification of effects were not found for CPU, sperm count, or sperm concentration. PMID:9495797

  18. Electrochemotherapy on liver tumours in rabbits.

    PubMed Central

    Ramirez, L. H.; Orlowski, S.; An, D.; Bindoula, G.; Dzodic, R.; Ardouin, P.; Bognel, C.; Belehradek, J.; Munck, J. N.; Mir, L. M.

    1998-01-01

    Electrochemotherapy (ECT) is a new therapeutic approach combining the effects of a low-permeant cytotoxic drug, bleomycin (BLM), administered i.v. and cell-permeabilizing electric pulses (EPs) locally delivered to tumours. The transient permeabilization of the cell membrane by the EPs allows free access of BLM to its intracellular targets, largely enhancing BLM's cytotoxic effects. ECT efficacy has been proved so far on transplanted subcutaneous murine tumours and on subcutaneous metastases in humans. Here, we present the first study of the effects of ECT on tumours transplanted to livers in rabbits. We used a recently developed EP applicator consisting of an array of parallel and equidistant needles to be inserted in tissues. Effects of EPs alone or of ECT were assessed by histological analysis, tumour growth rates and survival of the treated animals. A transient blood hypoperfusion was seen in the electropulsed areas, with or without BLM, related to EP-dependent vasoconstriction but this had no major effects on cell survival. Long-term effects depended on the presence of BLM at the time of EP delivery. Almost complete tumour necrosis was observed after ECT, resulting from both BLM direct cytotoxic effects on electropermeabilized tumour cells and indirect effects on the tumour vessels. A large reduction in tumour growth rate and significantly longer survival times were scored in comparison with control rabbits. Moreover, ECT of liver tumours was well tolerated and devoid of systemic side-effects. When ECT was associated with a local interleukin 2-based immunotherapy, increased local anti-tumour effectiveness as well as a large decrease in the number of metastases were observed. Thus, ECT could become a novel treatment modality for liver tumours and other solid internal malignancies. Images Figure 1 Figure 2 PMID:9649121

  19. Imaging tumour hypoxia with positron emission tomography

    PubMed Central

    Fleming, I N; Manavaki, R; Blower, P J; West, C; Williams, K J; Harris, A L; Domarkas, J; Lord, S; Baldry, C; Gilbert, F J

    2015-01-01

    Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers. PMID:25514380

  20. Cystic lesions accompanying extra-axial tumours.

    PubMed

    Lohle, P N; Wurzer, H A; Seelen, P J; Kingma, L M; Go, K G

    1999-01-01

    We examined the mechanism of cyst formation in extra-axial tumours in the central nervous system (CNS). Cyst fluid, cerebrospinal fluid (CSF) and blood plasma were analysed in eight patients with nine peritumoral cysts: four with meningiomas, two with intracranial and two spinal intradural schwannomas. Measuring concentrations of various proteins [albumin, immunoglobulin G (IgG), IgA, alpha 2-macroglobulin and IgM] in cyst fluid, CSF and blood plasma provides insight into the state of the semipermeability of the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier. Peritumoral cysts accompanying intra-axial brain tumours are the end result of disruption of the BBB and oedema formation. Unlike intra-axial tumours which lie embedded within nervous tissue, extra-axial tumours tend to be separated from nervous tissue by arachnoid and pia mater. High concentrations of proteins were measured in the cyst fluid, approaching blood plasma levels, suggesting a local barrier disruption, and passage across the arachnoid, pia mater and cortical/medullary layer into the CNS parenchyma, leaving the protein concentrations of CSF practically unchanged. We confirmed that very high concentrations of protein are to be found in tumour cysts, plasma proteins forming almost 90% of the total protein in the cyst. We review current hypotheses on the pathogenesis of cysts accompanying neoplasms, particularly meningiomas and schwannomas, and conclude that the majority of proteins in cyst fluid in extra-axial, intradural meningiomas and schwannomas are plasma proteins. This provides a strong argument for pathogenesis of extra-axial intradural tumour cysts in favour of leakage of plasma proteins out of the tumour vessels into the nervous tissue. PMID:9987761

  1. Assessment of immunological markers and booster effects of Ag85B peptides, Ag85B, and BCG in blood of BCG vaccinated children: a preliminary report

    PubMed Central

    2016-01-01

    Purpose In the present study, the protective immunological markers in serum and peripheral blood mononuclear cells (PBMCs) of bacillus Calmette–Guérin (BCG) vaccinated and unvaccinated children were evaluated after vaccination. Further, PBMCs of children with low protective levels were boosted with BCG, Ag85B, and Ag85B peptides to study their booster effects to increase waning BCG induced immunity. Materials and Methods Fifty children from 1 month to 18 years of age were randomized for the study. Blood samples were collected from 27 participants with/without BCG vaccination. Immunological markers (anti-BCG, interferon γ [IFN-γ], and adenosine deaminase activity) were assessed in both serum and PBMCs of children. Children with low levels of protective immunological markers were further recruited and their PBMCs were boosted with BCG, Ag85B, and Ag85B peptides. Results Children in age group of 4-6 years were associated with significantly (p<0.05) higher BCG-specific IgG and IFN-γ levels compared to those in age group greater than 10 years. Vaccinated children had greater repertoire of immunological memory which on in vitro stimulation with BCG showed increase in BCG-specific response compared to unvaccinated controls. Assessment of booster effects of BCG, Ag85B, and Ag85B peptides in PBMCs of children revealed greater potential of peptides to boost BCG induced immunity compared to BCG and Ag85B. Conclusion To conclude, children within age 4-6 years are associated with high immunological markers which eventually diminish with age thereby suggesting need for booster dose in later years. Mycobacterium tuberculosis peptides along with BCG may be used as attractive candidates to boost such waning BCG induced immunity in children. PMID:26866022

  2. Determination of fatty acid ethyl esters in dried blood spots by LC-MS/MS as markers for ethanol intake: application in a drinking study.

    PubMed

    Luginbühl, Marc; Schröck, Alexandra; König, Stefan; Schürch, Stefan; Weinmann, Wolfgang

    2016-05-01

    The forensic utility of fatty acid ethyl esters (FAEEs) in dried blood spots (DBS) as short-term confirmatory markers for ethanol intake was examined. An LC-MS/MS method for the determination of FAEEs in DBS was developed and validated to investigate FAEE formation and elimination in a drinking study, whereby eight subjects ingested 0.66-0.84 g/kg alcohol to reach blood alcohol concentrations (BAC) of 0.8 g/kg. Blood was taken every 1.5-2 h, BAC was determined, and dried blood spots were prepared, with 50 μL of blood, for the determination of FAEEs. Lower limits of quantitation (LLOQ) were between 15 and 37 ng/mL for the four major FAEEs. Validation data are presented in detail. In the drinking study, ethyl palmitate and ethyl oleate proved to be the two most suitable markers for FAEE determination. Maximum FAEE concentrations were reached in samples taken 2 or 4 h after the start of drinking. The following mean peak concentrations (c̅ max) were reached: ethyl myristate 14 ± 4 ng/mL, ethyl palmitate 144 ± 35 ng/mL, ethyl oleate 125 ± 55 ng/mL, ethyl stearate 71 ± 21 ng/mL, total FAEEs 344 ± 91 ng/mL. Detectability of FAEEs was found to be on the same time scale as BAC. In liquid blood samples containing ethanol, FAEE concentrations increase post-sampling. This study shows that the use of DBS fixation prevents additional FAEE formation in blood samples containing ethanol. Positive FAEE results obtained by DBS analysis can be used as evidence for the presence of ethanol in the original blood sample. Graphical Abstract Time courses for fatty acid ethyl ester (FAEE) concentrations in DBS and ethanol concentrations for subject 1 over a period of 7 h. Ethanol ingestion occured during the first hour of the time course. PMID:26968564

  3. Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study

    PubMed Central

    Morrow, C. J.; Trapani, F.; Metcalf, R. L.; Bertolini, G.; Hodgkinson, C. L.; Khandelwal, G.; Kelly, P.; Galvin, M.; Carter, L.; Simpson, K. L.; Williamson, S.; Wirth, C.; Simms, N.; Frankliln, L.; Frese, K. K.; Rothwell, D. G.; Nonaka, D.; Miller, C. J.; Brady, G.; Blackhall, F. H.; Dive, C.

    2016-01-01

    Background Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, ‘liquid biopsies’ such as circulating tumour cells (CTCs) are minimally invasive and easier to obtain. Here, we present a clinical case study of a NSCLC patient with advanced metastatic disease, a never smoker whose primary tumour was EGFR and ALK wild-type. We demonstrate for the first time, tumorigenicity of their CTCs to generate a patient CTC-derived eXplant (CDX). Patients and methods CTCs were enriched at diagnosis and again 2 months later during disease progression from 10 ml blood from a 48-year-old NSCLC patient and implanted into immunocompromised mice. Resultant tumours were morphologically, immunohistochemically, and genetically compared with the donor patient's diagnostic specimen. Mice were treated with cisplatin and pemetrexed to assess preclinical efficacy of the chemotherapy regimen given to the donor patient. Results The NSCLC CDX expressed lung lineage markers TTF1 and CK7 and was unresponsive to cisplatin and pemetrexed. Examination of blood samples matched to that used for CDX generation revealed absence of CTCs using the CellSearch EpCAM-dependent platform, whereas size-based CTC enrichment revealed abundant heterogeneous CTCs of which ∼80% were mesenchymal marker vimentin positive. Molecular analysis of the CDX, mesenchymal and epithelial CTCs revealed a common somatic mutation confirming tumour origin and showed CDX RNA and protein profiles consistent with the predominantly mesenchymal phenotype. Conclusions This study shows that the absence of NSCLC CTCs detected by CellSearch (EpCAM+) does not preclude CDX generation

  4. 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

  5. [Occult stromal tumour of the small intestine: a cause of chronic intestinal blood loss in a 70 year-old woman].

    PubMed

    Pentimone, F; Gerini, A; Moncini, C; Di Stefano, S; Pagni, V; Pastine, F; Del Corso, L

    1999-03-01

    The case of a 70 year-old woman with a chronic gastrointestinal blood loss due to a stromal tumor located in the middle third of the small intestine is reported. The peculiarities of the case are the characteristic immunohistochemistry of the neoplasm and, particularly, the mimetic clinical presentation, a kind of ''phantom tumor'' confirmed only with celiotomy and surgical excision. PMID:16498316

  6. Molecular identification of blood meal sources of ticks (Acari, Ixodidae) using cytochrome b gene as a genetic marker

    PubMed Central

    Che Lah, Ernieenor Faraliana; Yaakop, Salmah; Ahamad, Mariana; Md Nor, Shukor

    2015-01-01

    Abstract Blood meal analysis (BMA) from ticks allows for the identification of natural hosts of ticks (Acari: Ixodidae). The aim of this study is to identify the blood meal sources of field collected on-host ticks using PCR analysis. DNA of four genera of ticks was isolated and their cytochrome b (Cyt b) gene was amplified to identify host blood meals. A phylogenetic tree was constructed based on data of Cyt b sequences using Neighbor Joining (NJ) and Maximum Parsimony (MP) analysis using MEGA 5.05 for the clustering of hosts of tick species. Twenty out of 27 samples showed maximum similarity (99%) with GenBank sequences through a Basic Local Alignment Search Tool (BLAST) while 7 samples only showed a similarity range of between 91–98%. The phylogenetic trees showed that the blood meal samples were derived from small rodents (Leopoldamys sabanus, Rattus tiomanicus and Sundamys muelleri), shrews (Tupaia glis) and mammals (Tapirus indicus and Prionailurus bengalensis), supported by 82–88% bootstrap values. In this study, Cyt b gene as a molecular target produced reliable results and was very significant for the effective identification of ticks’ blood meal. The assay can be used as a tool for identifying unknown blood meals of field collected on-host ticks. PMID:25685009

  7. Brain and spinal tumour.

    PubMed

    Goh, C H; Lu, Y Y; Lau, B L; Oy, J; Lee, H K; Liew, D; Wong, A

    2014-12-01

    This study reviewed the epidemiology of brain and spinal tumours in Sarawak from January 2009 till December 2012. The crude incidence of brain tumour in Sarawak was 4.6 per 100,000 population/year with cumulative rate 0.5%. Meningioma was the most common brain tumour (32.3%) and followed by astrocytoma (19.4%). Only brain metastases showed a rising trend and cases were doubled in 4 years. This accounted for 15.4% and lung carcinoma was the commonest primary. Others tumour load were consistent. Primitive neuroectodermal tumour (PNET) and astrocytoma were common in paediatrics (60%). We encountered more primary spinal tumour rather than spinal metastases. Intradural schwannoma was the commonest and frequently located at thoracic level. The current healthcare system in Sarawak enables a more consolidate data collection to reflect accurate brain tumours incidence. This advantage allows subsequent future survival outcome research and benchmarking for healthcare resource planning. PMID:25934956

  8. 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

  9. 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

  10. 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.

  11. Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function.

    PubMed

    Reddy, Manjula; Eirikis, Edward; Davis, Cuc; Davis, Hugh M; Prabhakar, Uma

    2004-10-01

    Activation of lymphocytes is a complex, yet finely regulated cascade of events that results in the expression of cytokine receptors, production and secretion of cytokines and expression of several cell surface molecules that eventually lead to divergent immune responses. Assessing the qualitative and quantitative nature of lymphocyte function following immunotherapy provides valuable information about the immune responses mediated by a therapeutic agent. To facilitate evaluation of the immunomodulatory activity of therapeutic agents, we have established a platform of in vitro immunoassays with normal human peripheral blood mononuclear cells (PBMCs) treated with several polyclonal activators that are known to exhibit different modes of action. We evaluated the kinetics of cell surface marker expression and cytokine release from PBMCs stimulated in parallel with various activating agents over a time course. These stimulating agents induced early (CD69 and CD71) and late (CD25 and HLA-DR) activation markers to varying antigen densities, indicated different cytokine profiles, and showed differential inhibition with dexamethasone (DEX), an inhibitor of early signaling events. Based on the association or correlation of the kinetics of activation marker expression and secreted cytokines, the results of our study indicate the appropriate time points for the simultaneous measurement of both these activation products. This study defines the kinetics for both measures of T cell activation and provides a comprehensive review with various polyclonal activators that can serve as a reference for monitoring lymphocyte function in clinical study samples. PMID:15541283

  12. Changes in circulating immune complexes in tumour patient serum after in vitro or ex vivo affinity chromatography of blood plasma or whole blood over immunoglobulin-binding staphylococcal protein A-Sepharose.

    PubMed

    Håkansson, L; Hed, J; Baldetorp, L; Eneström, S; Jonsson, S; Liedén, G

    1984-01-01

    Circulating immune complexes (CIC) were determined in tumour patient sera using three methods. One is based on PEG-precipitation, one on C1q-reactivity, and one on protein A-reactivity. About 25-30% of the sera were positive in at least one of the tests. Incubation of serum with protein A-Sepharose in vitro removed PEG-precipitable CIC from most sera, whereas C1q-reactive CICs had a much lower affinity to protein A. The protein A-reactive complexes showed considerable variation in their binding to protein A-Sepharose, and in some sera the amount of these CICs was actually increased. Similar changes in protein A-reactive CIC were also found during ex vivo treatment of tumour patients with immune adsorption. It is proposed that the binding of immune complexes to protein A can result in remodelling of protein A itself. Results from ultracentrifugation and fractionated PEG-precipitation support this hypothesis. PMID:6365797

  13. A Module of Human Peripheral Blood Mononuclear Cell Transcriptional Network Containing Primitive and Differentiation Markers Is Related to Specific Cardiovascular Health Variables

    PubMed Central

    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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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. PMID:26913068

  20. 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

  1. Effects of polyphenol-rich extract from berries of Aronia melanocarpa on the markers of oxidative stress and blood platelet activation.

    PubMed

    Olas, Beata; Kedzierska, Magdalena; Wachowicz, Barbara; Stochmal, Anna; Oleszek, Wieslaw

    2010-01-01

    Bioactive substances found in numerous foods can be successfully and safely used to modify various cellular functions and affect the oxidative stress. Aronia melanocarpa fruits (Rosaceae) are one of the richest plant sources of phenolic substances shown to have anti-inflammatory, antitumor, antioxidative and antiplatelet activities. We investigated antioxidant properties of the extract from berries of A. melanocarpa by the estimation of the selected and other biomarkers of oxidative stress, i.e. the level of 8-epi-prostaglandin F(2) (8-EPI) (by immunoassay kit) and the amount of glutathione (by HPLC method) in control platelets and platelets treated with H(2)O(2). The expression of alpha(IIb)beta(3) (a marker of platelet activation) was measured by flow cytometer. The antioxidative and antiplatelet properties of the tested extract were also compared with the action of a well characterized antioxidative and antiplatelet commercial monomeric polyphenol-resveratrol. The extract from berries of A. melanocarpa (at the highest tested concentration -100 microg/ml) decreased the production of 8-EPI (a marker of lipid peroxidation) in control blood platelets and platelets treated with H(2)O(2) (2 mM). A combined action of the tested plant extract and H(2)O(2) evoked a significant increase of reduced form of glutathione in platelets compared with cells treated with H(2)O(2) only. Moreover, the tested plant extract (at the highest used concentration -100 microg/ml) reduced the expression of alpha(IIb)beta(3) on blood platelets. Comparative studies indicate that the tested plant extract was found to be more reactive in blood platelets than the solution of pure resveratrol. PMID:20218910

  2. 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

  3. 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

  4. Clonality analysis of combined Brenner and mucinous tumours of the ovary reveals their monoclonal origin.

    PubMed

    Wang, Yihong; Wu, Ren-chin; Shwartz, Lauren Ende; Haley, Lisa; Lin, Ming-tse; Shih, Ie-ming; Kurman, Robert J

    2015-10-01

    The derivation of ovarian intestinal-type mucinous tumours is not well established. Some are derived from teratomas but the origin of the majority is not clear. It has been recently proposed that the non-germ cell group may be derived from Brenner tumours, as the association of a mucinous tumour with a Brenner tumour is frequently observed. In order to explore the histogenesis of these neoplasms, we undertook a clonality analysis of the two components of ten combined Brenner and mucinous tumours using a human androgen receptor gene (HUMARA) assay. All eight informative cases of ten showed a concordant X-chromosome inactivation pattern between the two tumour components, indicative of a shared clonal origin (p = 0.0039). Microsatellite genotyping in five of the combined tumours displayed an identical heterozygous pattern with paired Fallopian tube tissue, indicative of a somatic cell origin. In addition, paired box protein 8, a highly sensitive Müllerian epithelial marker, was not detected by immunohistochemistry in either tumour component in any of the ten tumours, suggesting that this subset of mucinous tumours does not originate from Müllerian-derived epithelium. In conclusion, this study demonstrates that in combined mucinous and Brenner tumours, there is a shared clonal relationship between the two different tumour components and suggests that some pure mucinous tumours may develop from a Brenner tumour in which the Brenner tumour component becomes compressed and obliterated by an expanding mucinous neoplasm. PMID:26095692

  5. Tumours of the lung

    PubMed Central

    Stünzi, H.; Head, K. W.; Nielsen, S. W.

    1974-01-01

    Lung tumours are not common in domestic animals; there has not been the increase in epidermoid carcinomas and anaplastic small-cell carcinomas that has occurred in man this century. Adenocarcinoma is the most common type in animals. The biological behaviour of each type of tumour in animals seems to be much the same as in man. The tumours are described histologically, the main categories being: epidermoid carcinoma, anaplastic carcinoma, adenocarcinoma, combined epidermoid and adenocarcinoma, carcinoid tumours, bronchial gland tumours, benign tumours, and sarcomas. ImagesFig. 13Fig. 14Fig. 15Fig. 16Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12 PMID:4371738

  6. 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

  7. 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

  8. 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

  9. 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

  10. Biological evaluation of new potential anticancer agent for tumour imaging and radiotherapy by two methods: 99mTc-radiolabelling and EPR spectroscopy

    PubMed Central

    Karamalakova, Yanka; Chuttani, Krishna; Sharma, Rakesh; Zheleva, Antoaneta; Gadjeva, Veselina; Mishra, Anil

    2014-01-01

    Recently, a new class of in vitro and ex vivo radiotracers/radioprotectors, the nitroxyl-labelled agent 1-ethyl-1-nitroso–3-[4-(2,2,6,6–tetramethylpiperidine-1-oxyl)]-urea (SLENU), has been discovered. Our previous investigations demonstrated that SLENU is a low-molecular-weight stable free radical which is freely membrane permeable, easily crosses the blood brain barrier and exhibited in/ex vivo the lowest general toxicity and higher anticancer activity against some experimental tumour models. Further investigation was aimed to develop a 99mTc-labelled SLENU (97%) as a chelator and evaluate its labelling efficiency and potential use as a tumour seeking agent and for early diagnosis. Tissue biodistribution of 99mTc-SLENU was determined in normal mice at 1, 2 and 24 h (n = 4/time interval, route of administration i.v.). The distribution data were compared using male albino non-inbred mice and electron paramagnetic resonance investigation. The imaging characteristics of 99mTc-SLENU conjugate examined in BALB/c mice grafted with Ehrlich Ascitis tumour in the thigh of hind leg demonstrated major accumulation of the radiotracer in the organs and tumour. Planar images and auto-radiograms confirmed that the tumours could be visualized clearly with 99mTc-SLENU. Blood kinetic study of radio-conjugate showed a bi-exponential pattern, as well as quick reduced duration in the blood circulation. This study establishes nitroxyls as a general class of new spin-labelled diagnostic markers that reduce the negative lateral effects of radiotherapy and drug damages, and are appropriate for tumour-localization. PMID:26019604

  11. 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

  12. Tumour ablation: technical aspects

    PubMed Central

    Bodner, Gerd; Bale, Reto

    2009-01-01

    Abstract Image-guided percutaneous radiofrequency ablation (RFA) is a minimally invasive, relatively low-risk procedure for tumour treatment. Local recurrence and survival rates depend on the rate of complete ablation of the entire tumour including a sufficient margin of surrounding healthy tissue. Currently a variety of different RFA devices are available. The interventionalist must be able to predict the configuration and extent of the resulting ablation necrosis. Accurate planning and execution of RFA according to the size and geometry of the tumour is essential. In order to minimize complications, individualized treatment strategies may be necessary for tumours close to vital structures. This review examines the state-of-the art of different device technologies, approaches, and treatment strategies for percutaneous RFA of liver tumours. PMID:19965296

  13. 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

  14. 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

  15. 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

  16. Cord Blood Vγ2Vδ2 T Cells Provide a Molecular Marker for the Influence of Pregnancy-Associated Malaria on Neonatal Immunity

    PubMed Central

    Cairo, Cristiana; Longinaker, Nyaradzo; Cappelli, Giulia; Leke, Rose G. F.; Ondo, Manuel Mve; Djokam, Rosine; Fogako, Josephine; Leke, Robert J.; Sagnia, Bertrand; Sosso, Samuel; Colizzi, Vittorio; Pauza, C. David

    2014-01-01

    Background. Plasmodium falciparum placental infection primes the fetal immune system and alters infant immunity. Mechanisms leading to these outcomes are not completely understood. We focused on Vγ2Vδ2 cells, which are part of the immune response against many pathogens, including P. falciparum. These unconventional lymphocytes respond directly to small, nonpeptidic antigens, independent of major histocompatibility complex presentation. We wondered whether placental malaria, which may increase fetal exposure to P. falciparum metabolites, triggers a response by neonatal Vγ2Vδ2 lymphocytes that can be a marker for the extent of fetal exposure to malarial antigens. Methods. Cord blood mononuclear cells were collected from 15 neonates born to mothers with P. falciparum infection during pregnancy (8 with placental malaria) and 25 unexposed neonates. Vγ2Vδ2 cell phenotype, repertoire, and proliferative responses were compared between newborns exposed and those unexposed to P. falciparum. Results. Placental malaria–exposed neonates had increased proportions of central memory Vγ2Vδ2 cells in cord blood, with an altered Vγ2 chain repertoire ex vivo and after stimulation. Conclusion. Our results suggest that placental malaria affects the phenotype and repertoire of neonatal Vγ2Vδ2 lymphocytes. Placental malaria may lower the capacity for subsequent Vγ2Vδ2 cell responses and impair the natural resistance to infectious diseases or the response to pediatric vaccination. PMID:24325967

  17. 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

  18. 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. PMID:24869977

  19. Predicting High-Grade Cancer at Ten-Core Prostate Biopsy Using Four Kallikrein Markers Measured in Blood in the ProtecT Study

    PubMed Central

    Bryant, Richard J.; Sjoberg, Daniel D.; Vickers, Andrew J.; Robinson, Mary C.; Kumar, Rajeev; Marsden, Luke; Davis, Michael; Scardino, Peter T.; Donovan, Jenny; Neal, David E.; Hamdy, Freddie C.

    2015-01-01

    Background: Many men with elevated prostate-specific antigen (PSA) levels in serum do not have aggressive prostate cancer and undergo unnecessary biopsy. Retrospective studies using cryopreserved serum suggest that four kallikrein markers can predict biopsy outcome. Methods: Free, intact and total PSA, and kallikrein-related peptidase 2 were measured in cryopreserved blood from 6129 men with elevated PSA (≥3.0ng/mL) participating in the prospective, randomized trial Prostate Testing for Cancer and Treatment. Marker levels from 4765 men providing anticoagulated plasma were incorporated into statistical models to predict any-grade and high-grade (Gleason score ≥7) prostate cancer at 10-core biopsy. The models were corrected for optimism by 10-fold cross validation and independently validated using markers measured in serum from 1364 men. All statistical tests were two-sided. Results: The four kallikreins enhanced prostate cancer detection compared with PSA and age alone. Area under the curve (AUC) for the four kallikreins was 0.719 (95% confidence interval [CI] = 0.704 to 0.734) vs 0.634 (95% CI = 0.617 to 0.651, P < .001) for PSA and age alone for any-grade cancer, and 0.820 (95% CI = 0.802 to 0.838) vs 0.738 (95% CI = 0.716 to 0.761) for high-grade cancer. Using a 6% risk of high-grade cancer as an illustrative cutoff, for 1000 biopsied men with PSA levels of 3.0ng/mL or higher, the model would reduce the need for biopsy in 428 men, detect 119 high-grade cancers, and delay diagnosis of 14 of 133 high-grade cancers. Models exhibited excellent discrimination on independent validation among men with only serum samples available for analysis. Conclusions: A statistical model based on kallikrein markers was validated in a large prospective study and reduces unnecessary biopsies while delaying diagnosis of high-grade cancers in few men. PMID:25863334

  20. [Analysis of Cases with Elevated Blood (1->3)-β-D-glucan in Relation to an Infection Marker, Neutrophil CD64 Expression].

    PubMed

    Hashimoto, Atsushi; Matsui, Toshihiro

    2015-11-01

    (1->3)-β-D-glucan (BDG) is a constituent of the fungal cell wall and its blood level is known as a marker of fungal infection including pneumocystis pneumonia (PCP). Meanwhile, peripheral blood neutrophil CD64 expression (CD64) is upregulated in various infections. We analyzed patients with positive BDG (cut off 11.0 pg/mL) and those whose CD64 was measured simultaneously. In patients who visited our hospital from 2005 to 2011, BDG was measured in 3,960 samples. The number of positive samples were 441 obtained from 185 patients. In patients with positive BDG, the initial BDG was 24.3 [16.4-70.5] pg/mL (median [interquartile range]). Positive BDG samples were derived mainly from the department of Rheumatology or that of Allergy and Respirology. Common primary diseases were rheumatoid arthritis (RA) or other connective tissue diseases, followed by malignancy, none (only abnormal chest X-ray) and bronchial asthma. The rates of afebrile patients, patients on immunosuppressive therapy and those with a normal range of white blood cell count were 63.7%, 50.9% and 40.8%, respectively. The main causes of positive BDG were PCP (n = 38, 20.5%) and non-PCP mycosis (n = 48, 25.9%, including 26 cases of aspergillosis). Others (99 patients, 53.6%) had positive BDG of unknown origin and 53 of them ameliorated spontaneously, most of whom could have been examples of pseudo-positive BDG. The number of deceased patients was 57 (30.8%) consisting of 9 PCP, 16 non-PCP mycosis and others. The median initial positive BDG levels in patients with PCP, non-PCP mycosis and others were 49.9, 28.9 and 19.7pg/mL, respectively. The positive rate of CD64 (cut off 2,000 molecules/cell) measured simultaneously with initial positive BDG was 77.8%. In RA patients with PCP, 94.7% of them had positive CD64 and the levels of CD64 were significantly higher than those in RA patients with bacterial pneumonia (median 9,386 vs 4,399 molecules/cell) in that same period. The positive rate of CD64 was lower in

  1. A cross-shift study of lung function, exhaled nitric oxide and inflammatory markers in blood in Norwegian cement production workers

    PubMed Central

    Notø, Hilde; Skogstad, Marit; Nordby, Karl-Christian; Eduard, Wijnand; Svendsen, Martin Veel; Øvstebø, Reidun; Trøseid, Anne Marie Siebke; Kongerud, Johny

    2011-01-01

    Objectives To study possible effects of aerosol exposure on lung function, fractional exhaled nitric oxide (FeNO) and inflammatory markers in blood from Norwegian cement production workers across one work shift (0 to 8 h) and again 32 h after the non-exposed baseline registration. Methods 95 workers from two cement plants in Norway were included. Assessment of lung function included spirometry and gas diffusion pre- and post-shift (0 and 8 h). FeNO concentrations were measured and blood samples collected at 0, 8 and 32 h. Blood analysis included cell counts of leucocytes and mediators of inflammation. Results The median respirable aerosol level was 0.3 mg/m3 (range 0.02–6.2 mg/m3). FEV1, FEF25–75% and DLCO decreased by 37 ml (p=0.04), 170 ml/s (p<0.001) and 0.17 mmol/min/kPa (p=0.02), respectively, across the shift. A 2 ppm reduction in FeNO between 0 and 32 h was detected (p=0.01). The number of leucocytes increased by 0.6×109 cells/l (p<0.001) across the shift, while fibrinogen levels increased by 0.02 g/l (p<0.001) from 0 to 32 h. TNF-α level increased and IL-10 decreased across the shift. Baseline levels of fibrinogen were associated with the highest level of respirable dust, and increased by 0.39 g/l (95% CI 0.06 to 0.72). Conclusions We observed small cross-shift changes in lung function and inflammatory markers among cement production workers, indicating that inflammatory effects may occur at exposure levels well below 1 mg/m3. However, because the associations between these acute changes and personal exposure measurements were weak and as the long-term consequences are unknown, these findings should be tested in a follow-up study. PMID:21297153

  2. Tumour promotion versus tumour suppression in chronic hepatic iron overload.

    PubMed

    Bloomer, Steven A; Brown, Kyle E

    2015-06-01

    Although iron-catalysed oxidative damage is presumed to be a major mechanism of injury leading to cirrhosis and hepatocellular carcinoma in hemochromatosis, these events have been difficult to recapitulate in an animal model. In this study, we evaluated regulators of hepatocarcinogenesis in a rodent model of chronic iron overload. Sprague-Dawley rats were iron loaded with iron dextran over 6 months. Livers were harvested and analysed for markers of oxidative stress, as well as the following proteins: p53, murine double minute 2, the Shc proteins p66, p52, p46; β-catenin, CHOP, C/EBPα and Yes-associated protein. In this model, iron loading is associated with hepatocyte proliferation, and indices of oxidative damage are mildly increased in tandem with augmented antioxidant defenses. Alterations potentially favouring carcinogenesis included a modest but significant decrease in p53 levels and increases in p52, p46 and β-catenin levels compared with control livers. Countering these factors, the iron-loaded livers demonstrated a significant decrease in CHOP, which has recently been implicated in the development of hepatocellular carcinoma, as well as a reciprocal increase in C/EBPα and decrease in Yes-associated protein. Our results suggest that chronic iron overload elicits both tumour suppressive as well as tumour-promoting mechanisms in rodent liver. PMID:26059599

  3. Determination of carcinoembryonic antigen and cancer antigen (CA 15-3) in bitches with tumours on mammary gland: preliminary report.

    PubMed

    Valencakova-Agyagosova, A; Frischova, Z; Sevcikova, Z; Hajurka, J; Lepej, J; Szakallova, I; Kredatusova, G; Nagy, V; Ledecky, V

    2014-09-01

    The aim of this work was to determine levels of carcinoembryonic antigen (CEA) and cancer antigen (CA 15-3) in the blood serum of 45 bitches. A modified procedure was used to determine the CEA and CA 15-3 markers with the human kits using the radioimmunoassay method. Samples collected from extirpated tumour of mammary glands were histologically processed and classified as per WHO guidelines. The average age of animals with tumour was 10.00 ± 2.2 years; for healthy bitches average age was 4.2 ± 3.2 years. Values of CEA and CA 15-3 were considered positive, if they exceeded 0.23 ng mL(-1) and 7 IU mL(-1) , respectively. Average levels of CEA in the tumour group were 0.25 ± 0.06 versus 0.20 ± 0.03 in healthy bitches (P = 0.0001). The average CA 15-3 value in bitches with tumour was 8.58 ± 1.27 versus 5.14 ± 1.34 in healthy animals (P < 0.0001). PMID:22947252

  4. 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. PMID:23828904

  5. Markers of antioxidant defence system and lipid peroxidation in peripheral blood of female patients with chronic idiopathic urticaria.

    PubMed

    Kasperska-Zajac, Alicja; Brzoza, Zenon; Polaniak, Renata; Rogala, Barbara; Birkner, Ewa

    2007-03-01

    Oxidative stress is an important event in lesional skin of patients with chronic idiopathic urticaria (CIU). In the present study, we assessed blood oxidant/antioxidant status of patients suffering from CIU with positive response to autologous serum skin test (ASST) and with negative ASST, to improve our understanding of biological processes and the part of oxidative stress in this disease. Activities of manganese superoxide dismutase (MnSOD), copper-zinc superoxide dismutase (Cu/ZnSOD), glutathione peroxidase (GSH-PX), and catalase (CAT) as indices of enzymatic antioxidant capacity, as well as malondialdehyde (MDA) level as a maker of lipid peroxidation were measured in plasma and erythrocytes from 14 CIU female patients showing positive ASST, 31 CIU female patients with negative ASST and in 19 sex- and age-matched healthy subjects. The antioxidant enzyme activity in plasma and in erythrocytes did not differ significantly among the three groups. Also, the plasma and erythrocytes MDA levels were similar in the three groups. Based on our results, it seems that systemic activity of the enzymatic antioxidants (CuZn/SOD, MnSOD, GSH-Px, and CAT) as well as level of lipid peroxidation determined by MDA may not be increased in the course of immune-inflammatory processes associated with CIU. We also suggest that the systemic oxidant/antioxidant status of CIU patients, showing positive response to ASST, may not be different from that of CIU patients with negative ASST. PMID:17171548

  6. 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

  7. 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. PMID:27325270

  8. 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

  9. Assessment of tumour hypoxia for prediction of response to therapy and cancer prognosis

    PubMed Central

    Jubb, Adrian M; Buffa, Francesca M; Harris, Adrian L

    2010-01-01

    Abstract Tumour cells exploit both genetic and adaptive means to survive and proliferate in hypoxic microenvironments, resulting in the outgrowth of more aggressive tumour cell clones. Direct measurements of tumour oxygenation, and surrogate markers of the hypoxic response in tumours (for instance, hypoxia inducible factor-1α, carbonic anhydrase 9 and glucose transporter-1) are well-established prognostic markers in solid cancers. However, individual markers do not fully capture the complex, dynamic and heterogeneous hypoxic response in cancer. To overcome this, expression profiling has been employed to identify hypoxia signatures in cohorts or models of human cancer. Several of these hypoxia signatures have demonstrated prognostic significance in independent cancer datasets. Nevertheless, individual hypoxia markers have been shown to predict the benefit from hypoxia-modifying or anti-angiogenic therapies. This review aims to discuss the clinical impact of translational work on hypoxia markers and to explore future directions for research in this area. PMID:19840191

  10. Five-Day Whole-Body Cryostimulation, Blood Inflammatory Markers, and Performance in High-Ranking Professional Tennis Players

    PubMed Central

    Ziemann, Ewa; Olek, Robert Antoni; Kujach, Sylwester; Grzywacz, Tomasz; Antosiewicz, Jędrzej; Garsztka, Tomasz; Laskowski, Radosław

    2012-01-01

    Context Tournament season can provoke overreaching syndrome in professional tennis players, which may lead to deteriorated performance. Thus, appropriate recovery methods are crucial for athletes in order to sustain high-level performance and avoid injuries. We hypothesized that whole-body cryostimulation could be applied to support the recovery process. Objective To assess the effects of 5 days of whole-body cryostimulation combined with moderate-intensity training on immunologic, hormonal, and hematologic responses; resting metabolic rate; and tennis performance in a posttournament season. Design Controlled laboratory study. Setting National Olympic Sport Centre. Patients or Other Participants Twelve high-ranking professional tennis players. Intervention(s) Participants followed a moderate-intensity training program. A subgroup was treated with the 5-day whole-body cryostimulation (−120°C) applied twice a day. The control subgroup participated in the training only. Main Outcome Measure(s) Pretreatment and posttreatment blood samples were collected and analyzed for tumor necrosis factor α, interleukin 6, testosterone, cortisol, and creatine kinase. Resting metabolic rate and performance of a tennis drill were also assessed. Results Proinflammatory cytokine (tumor necrosis factor α) decreased and pleiotropic cytokine (interleukin 6) and cortisol increased in the group exposed to cryostimulation. In the same group, greater stroke effectiveness during the tennis drill and faster recovery were observed. Neither the training program nor cryostimulation affected resting metabolic rate. Conclusions Professional tennis players experienced an intensified inflammatory response after the completed tournament season, which may lead to overreaching. Applying whole-body cryostimulation in conjunction with moderate-intensity training was more effective for the recovery process than the training itself. The 5-day exposure to cryostimulation twice a day ameliorated the

  11. 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

  12. LINE-1 Hypomethylation in Blood and Tissue Samples as an Epigenetic Marker for Cancer Risk: A Systematic Review and Meta-Analysis

    PubMed Central

    Barchitta, Martina; Quattrocchi, Annalisa; Maugeri, Andrea; Vinciguerra, Manlio; Agodi, Antonella

    2014-01-01

    Objective A systematic review and a meta-analysis were carried out in order to summarize the current published studies and to evaluate LINE-1 hypomethylation in blood and other tissues as an epigenetic marker for cancer risk. Methods A systematic literature search in the Medline database, using PubMed, was conducted for epidemiological studies, published before March 2014. The random-effects model was used to estimate weighted mean differences (MDs) with 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by sample type (tissue or blood samples), cancer types, and by assays used to measure global DNA methylation levels. The Cochrane software package Review Manager 5.2 was used. Results A total of 19 unique articles on 6107 samples (2554 from cancer patients and 3553 control samples) were included in the meta-analysis. LINE-1 methylation levels were significantly lower in cancer patients than in controls (MD: −6.40, 95% CI: −7.71, −5.09; p<0.001). The significant difference in methylation levels was confirmed in tissue samples (MD −7.55; 95% CI: −9.14, −65.95; p<0.001), but not in blood samples (MD: −0.26, 95% CI: −0.69, 0.17; p = 0.23). LINE-1 methylation levels were significantly lower in colorectal and gastric cancer patients than in controls (MD: −8.33; 95% CI: −10.56, −6.10; p<0.001 and MD: −5.75; 95% CI: −7.75, −3.74; p<0.001) whereas, no significant difference was observed for hepatocellular cancer. Conclusions The present meta-analysis adds new evidence to the growing literature on the role of LINE-1 hypomethylation in human cancer and demonstrates that LINE-1 methylation levels were significantly lower in cancer patients than in control samples, especially in certain cancer types. This result was confirmed in tissue samples, both fresh/frozen or FFPE specimens, but not in blood. Further studies are needed to better clarify the role of LINE-1 methylation in specific subgroups, considering both cancer

  13. Gastrointestinal stromal tumour.

    PubMed

    Joensuu, Heikki; Hohenberger, Peter; Corless, Christopher L

    2013-09-14

    Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms that arise in the gastrointestinal tract, usually in the stomach or the small intestine and rarely elsewhere in the abdomen. They can occur at any age, the median age being 60-65 years, and typically cause bleeding, anaemia, and pain. GISTs have variable malignant potential, ranging from small lesions with a benign behaviour to fatal sarcomas. Most tumours stain positively for the mast/stem cell growth factor receptor KIT and anoctamin 1 and harbour a kinase-activating mutation in either KIT or PDGFRA. Tumours without such mutations could have alterations in genes of the succinate dehydrogenase complex or in BRAF, or rarely RAS family genes. About 60% of patients are cured by surgery. Adjuvant treatment with imatinib is recommended for patients with a substantial risk of recurrence, if the tumour has an imatinib-sensitive mutation. Tyrosine kinase inhibitors substantially improve survival in advanced disease, but secondary drug resistance is common. PMID:23623056

  14. Transport processes in tumours.

    PubMed

    Quastel, J H

    1965-12-01

    The characteristic features of transport systems controlling influx into tumour cells of nutrients and other chemicals are briefly described. Two notable features of transport of amino acids into tumour cells have been observed: extensive accumulation against a concentration gradient and equal accumulations, whether conditions are aerobic or anaerobic, provided glucose is present. This combination of features has not been observed in the majority of normal mammalian tissues so far examined. Important for considerations of chemotherapy is the ability of tumour transport carriers to transfer substances related in structure to amino acids and other nutrients. Amino acid analogues, for example, can either block transport of natural amino acids or can be transported into the cell where they may interfere with various aspects of amino acid metabolism. The study of transport carriers is essential for an understanding of tumour-host relationships and for considerations of chemotherapy. PMID:5842595

  15. Breast tumour angiogenesis

    PubMed Central

    Fox, Stephen B; Generali, Daniele G; Harris, Adrian L

    2007-01-01

    The central importance of tumour neovascularization has been emphasized by clinical trials using antiangiogenic therapy in breast cancer. This review gives a background to breast tumour neovascularization in in situ and invasive breast cancer, outlines the mechanisms by which this is achieved and discusses the influence of the microenvironment, focusing on hypoxia. The regulation of angiogenesis and the antivascular agents that are used in an antiangiogenic dosing schedule, both novel and conventional, are also summarized. PMID:18190723

  16. [Tumours and liver transplants].

    PubMed

    Mejzlík, Vladimír; Husová, Libuše; Kuman, Milan; Štěpánková, Soňa; Ondrášek, Jiří; Němec, Petr

    2015-01-01

    Liver transplantation as a curative treatment method can be used for selected primary liver tumours, in particular for hepatocellular carcinoma and rather rare semi-malignant tumours such as epithelioid hemangioendothelioma, further for infiltration of liver by metastatic neuroendocrine tumours (provided that metastases are only located in the liver and the primary tumour was removed) and for benign tumours (hemangiomas and adenomas) with oppression symptoms and size progression. Cholangiocarcinoma is not indicated for liver transplantation at the CKTCH Brno. In recent years liver transplants for hepatocellular carcinoma have increased and hepatocellular carcinoma has also been more frequently found ex post, in the explanted livers. Liver transplantation is indicated in selected patients with a good chance of long-term survival after liver transplantation (a generally accepted limit is 5 year survival of 50 % after transplantation). By 20 March 2015 there were liver transplants carried out on 38 patients - in 25 of them was hepatocellular carcinoma diagnosed before transplantation and in 13 it was found in the liver explants. 5 year survival following transplantation is reached by 53 % of this cohort. 32 % patients suffered from chronic hepatitis C. The longest surviving (32 years) patient at CKTCH Brno had liver transplanted for a big fibrolamellar hepatocellular carcinoma, which points to the prognostic significance of tumour histology: the criterion only considered in some indication schemes for practical reasons. Benign liver tumours (adenomatosis, cystadenoma, hemangioma with oppression symptoms) are rather rare indications and the transplantation results are favourable. 4 patients underwent transplantation for infiltration of liver by carcinoid, tumour recurrence occurred in one. PMID:26375706

  17. Testicular germ cell tumours.

    PubMed

    Rajpert-De Meyts, Ewa; McGlynn, Katherine A; Okamoto, Keisei; Jewett, Michael A S; Bokemeyer, Carsten

    2016-04-23

    Testicular germ cell tumours are at the crossroads of developmental and neoplastic processes. Their cause has not been fully elucidated but differences in incidences suggest that a combination of genetic and environment factors are involved, with environmental factors predominating early in life. Substantial progress has been made in understanding genetic susceptibility in the past 5 years on the basis of the results of large genome-wide association studies. Testicular germ cell tumours are highly sensitive to radiotherapy and chemotherapy and hence have among the best outcomes of all tumours. Because the tumours occur mainly in young men, preservation of reproductive function, quality of life after treatment, and late effects are crucial concerns. In this Seminar, we provide an overview of advances in the understanding of the epidemiology, genetics, and biology of testicular germ cell tumours. We also summarise the consensus on how to treat testicular germ cell tumours and focus on a few controversies and improvements in the understanding of late effects of treatment and quality of life for survivors. PMID:26651223

  18. Serum markers of intrahepatic cholangiocarcinoma.

    PubMed

    Malaguarnera, Giulia; Paladina, Isabella; Giordano, Maria; Malaguarnera, Michele; Bertino, Gaetano; Berretta, Massimiliano

    2013-01-01

    Cholangiocarcinoma (CCA) is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9), Carcinogenic Embryonic antigen (CEA), and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1) Mucins, Tumour Markers_{2} pyruvate-Kinase (TuM_{2-} PK) and metalloproteinase-7 (MMP-7) have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value. PMID:23396291

  19. 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

  20. Rapid Detection of Dendritic Cell and Monocyte Disorders Using CD4 as a Lineage Marker of the Human Peripheral Blood Antigen-Presenting Cell Compartment

    PubMed Central

    Jardine, Laura; Barge, Dawn; Ames-Draycott, Ashley; Pagan, Sarah; Cookson, Sharon; Spickett, Gavin; Haniffa, Muzlifah; Collin, Matthew; Bigley, Venetia

    2013-01-01

    Dendritic cells (DCs) and monocytes are critical regulators and effectors of innate and adaptive immune responses. Monocyte expansion has been described in many pathological states while monocyte and DC deficiency syndromes are relatively recent additions to the catalog of human primary immunodeficiency disorders. Clinically applicable screening tests to diagnose and monitor these conditions are lacking. Conventional strategies for identifying human DCs and monocytes have been based on the use of a lineage gate to exclude lymphocytes, thus preventing simultaneous detection of DCs, monocytes, and lymphocyte subsets. Here we demonstrate that CD4 is a reliable lineage marker for the human peripheral blood antigen-presenting cell compartment that can be used to identify DCs and monocytes in parallel with lymphocytes. Based on this principle, simple modification of a standard lymphocyte phenotyping assay permits simultaneous enumeration of four lymphocyte and five DC/monocyte populations from a single sample. This approach is applicable to clinical samples and facilitates the diagnosis of DC and monocyte disorders in a wide range of clinical settings, including genetic deficiency, neoplasia, and inflammation. PMID:24416034

  1. Repeated measurements of cerebral blood flow in the left superior temporal gyrus reveal tonic hyperactivity in patients with auditory verbal hallucinations: a possible trait marker

    PubMed Central

    Homan, Philipp; Kindler, Jochen; Hauf, Martinus; Walther, Sebastian; Hubl, Daniela; Dierks, Thomas

    2013-01-01

    Background: The left superior temporal gyrus (STG) has been suggested to play a key role in auditory verbal hallucinations (AVH) in patients with schizophrenia. Methods: Eleven medicated subjects with schizophrenia and medication-resistant AVH and 19 healthy controls underwent perfusion magnetic resonance (MR) imaging with arterial spin labeling (ASL). Three additional repeated measurements were conducted in the patients. Patients underwent a treatment with transcranial magnetic stimulation (TMS) between the first 2 measurements. The main outcome measure was the pooled cerebral blood flow (CBF), which consisted of the regional CBF measurement in the left STG and the global CBF measurement in the whole brain. Results: Regional CBF in the left STG in patients was significantly higher compared to controls (p < 0.0001) and to the global CBF in patients (p < 0.004) at baseline. Regional CBF in the left STG remained significantly increased compared to the global CBF in patients across time (p < 0.0007), and it remained increased in patients after TMS compared to the baseline CBF in controls (p < 0.0001). After TMS, PANSS (p = 0.003) and PSYRATS (p = 0.01) scores decreased significantly in patients. Conclusions: This study demonstrated tonically increased regional CBF in the left STG in patients with schizophrenia and auditory hallucinations despite a decrease in symptoms after TMS. These findings were consistent with what has previously been termed a trait marker of AVH in schizophrenia. PMID:23805093

  2. Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs.

    PubMed

    Rajpert-De Meyts, Ewa; Nielsen, John E; Skakkebaek, Niels E; Almstrup, Kristian

    2015-01-01

    This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCT), with focus on the most common testicular GCT (TGCT). GCT are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic differentiation. TGCT that occur in young men are divided into two main types, seminoma and nonseminoma, both derived from a pre-invasive germ cell neoplasia in situ (GCNIS), which originates from transformed foetal gonocytes. In severely dysgenetic gonads, a GCNIS-resembling lesion is called gonadoblastoma. GCT occur rarely in young children (infantile GCT) in whom the pathogenesis is different (no GCNIS/gonadoblastoma stage) but the histopathological features are similar to the adult GCT. The rare spermatocytic tumour of older men is derived from post-pubertal spermatogonia that clonally expand due to gain-of function mutations in survival-promoting genes (e.g. FGFR3, HRAS), thus this tumour has a different expression profile than GCNIS-derived TGCT. Clinically most informative immunohistochemical markers for GCT, except teratoma, are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related factors, such as placental-like alkaline phosphatase (PLAP), OCT4 (POU5F1), NANOG, AP-2γ (TFAP2C) and LIN28, which are not expressed in normal adult germ cells. Some of these markers can also be used for immunocytochemistry to detect GCNIS or incipient tumours in semen samples. Gene expression in GCT is regulated in part by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation, except nonseminomas. In addition, a recently discovered mechanism of post-genomic gene expression regulation involves small non-coding RNAs, predominantly micro-RNA (miR). Testicular GCT display micro-RNA profiles similar to embryonic stem cells. Targeted miRNA-based blood tests for miR-371-3 and miR-367 clusters are

  3. Surgical implications of tumour immunology.

    PubMed Central

    Somers, S. S.

    1996-01-01

    The presence of immune infiltration of tumour deposits and the existence of effective in vitro anti-tumour immune responses would suggest the possibility of therapeutic manipulation against tumour cells. However, clinical immunotherapy has shown little promise as a cancer treatment. Numerous explanations for this inefficacy have been proposed, one of which involves the elaboration of immunosuppressive moieties from tumour cells. The results of studies presented below show that serum from patients with gastrointestinal and other tumours have immunosuppressive influences on normal lymphocytes. The degree of this in vitro inhibition is related to tumour 'bulk' and may reflect a systemic immunosuppressive influence of the tumour. Isolation and culture of lymphocytes from gastrointestinal tumour deposits demonstrated that these immune cells are functionally inert, suggesting the existence of an immunosuppressive tumour microenvironment. The isolation and partial purification of an immunosuppressive moiety from conditioned culture medium of a variety of human tumour cell lines further supports the hypothesis of tumour-mediated immunosuppression. A number of protein tumour cell products have been described with potent immunosuppressive properties. These include transforming growth factor-beta, interleukin-10, and the retroviral envelope protein p15E. The surgical implications of the proposed tumour-host immune relationship includes the hypothesis that clinically apparent disease may not be amenable to immune attack owing to tumour-mediated immune suppression. The use of immunostimulatory strategies as adjuvant perioperative therapy would seem a more effective environment for the activation of antitumour immune responses in the surgical patient. PMID:8678441

  4. FGFs: crucial factors that regulate tumour initiation and progression.

    PubMed

    Jing, Qian; Wang, Yuanyuan; Liu, Hao; Deng, Xiaowei; Jiang, Lin; Liu, Rui; Song, Haixing; Li, Jingyi

    2016-08-01

    Fibroblast growth factors (FGFs) are crucial signalling molecules involved in normal cell growth, differentiation and proliferation. Over the past few decades, a large body of research has illustrated effects of individual FGFs on tumour initiation and progression. Tumour development is commonly accompanied with generation of new blood and lymph vessels, which support enhanced cell proliferation. Moreover, acquisition of tumour cells of the epithelial-mesenchymal transition (EMT) phenotype, enhances tumour cell migration and invasion potentials, crucial steps in tumour metastasis. This review summarizes recent findings concerning roles of FGFs in angiogenesis, lymphangiogenesis and EMT. PMID:27383016

  5. The role of myeloid cells in the promotion of tumour angiogenesis.

    PubMed

    Murdoch, Craig; Muthana, Munitta; Coffelt, Seth B; Lewis, Claire E

    2008-08-01

    The use of various transgenic mouse models and analysis of human tumour biopsies has shown that bone marrow-derived myeloid cells, such as macrophages, neutrophils, eosinophils, mast cells and dendritic cells, have an important role in regulating the formation and maintenance of blood vessels in tumours. In this Review the evidence for each of these cell types driving tumour angiogenesis is outlined, along with the mechanisms regulating their recruitment and activation by the tumour microenvironment. We also discuss the therapeutic implications of recent findings that specific myeloid cell populations modulate the responses of tumours to agents such as chemotherapy and some anti-angiogenic therapies. PMID:18633355

  6. 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

  7. Tumours of the ovary

    PubMed Central

    Nielsen, Svend W.; Misdorp, W.; McEntee, Kenneth

    1976-01-01

    Ovarian tumours are common in animals, the majority occurring in bitches and cows. The two most important germ cell tumours were dysgerminoma and teratoma; these morphologically resemble their counterparts in women, with the exception that teratomas in animals tend less to malignancy. The granulosa cell tumour is the most frequent sex cord-stromal tumour in all six species and it may contain luteinized areas or show differentiation towards a Sertoli cell pattern. The canine papillary adenoma and papillary adenocarcinoma, which are as common as granulosa tumours, have several features in common with their counterparts in women: they are of similar histological appearance, are frequently bilateral, and the adenocarcinomas have a great propensity for peritoneal implantation metastasis. Ovarian cysts are frequent in the bitch, sow, and cow and may originate from five different anatomical structures in the ovary. ImagesFig. 1Fig. 2 and 3Fig. 20-22Fig. 8-10Fig. 15 and 16Fig. 23Fig. 24Fig. 25Fig. 26Fig. 17-19Fig. 4 and 5Fig. 6 and 7Fig. 11Fig. 12Fig. 13 and 14 PMID:1086151

  8. Two unusual tumours in a ferret (Mustela putorius furo).

    PubMed

    Eatwell, K

    2004-09-01

    This case report describes the clinical history, diagnosis and treatment of a ferret with a tumour of the right adrenal gland and insulinomas of the pancreas. Histopathology of both lesions confirmed the diagnoses. Clinical signs of the adrenal gland tumour were a swollen vulva, overgrooming, sexual activity and pruritus. The clinical signs suggesting insulinomas were collapse of the ferret, disorientation and ptyalism. A low blood glucose level assisted the diagnosis of insulinomas. This is believed to be the first reported case of concurrent insulinomas and adrenal gland tumour in a ferret in the United Kingdom. PMID:15460204

  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. 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

  11. Fecal Occult Blood and Fecal Calprotectin as Point-of-Care Markers of Intestinal Morbidity in Ugandan Children with Schistosoma mansoni Infection

    PubMed Central

    Bustinduy, Amaya L.; Sousa-Figueiredo, José C.; Adriko, Moses; Betson, Martha; Fenwick, Alan; Kabatereine, Narcis; Stothard, J. Russell

    2013-01-01

    Background Calprotectin is a calcium-binding cytoplasmic protein found in neutrophils and increasingly used as a marker of bowel inflammation. Fecal occult blood (FOB) is also a dependable indicator of bowel morbidity. The objective of our study was to determine the applicability of these tests as surrogate markers of Schistosoma mansoni intestinal morbidity before and after treatment with praziquantel (PZQ). Methods 216 children (ages 3–9 years old) from Buliisa District in Lake Albert, Uganda were examined and treated with PZQ at baseline in October 2012 with 211 of them re-examined 24 days later for S. mansoni and other soil transmitted helminths (STH). POC calprotectin and FOB assays were performed at both time points on a subset of children. Associations between the test results and infection were analysed by logistic regression. Results Fecal calprotectin concentrations of 150–300 µg/g were associated with S. mansoni egg patent infection both at baseline and follow up (OR: 12.5 P = 0.05; OR: 6.8 P = 0.02). FOB had a very strong association with baseline anemia (OR: 9.2 P = 0.03) and medium and high egg intensity schistosomiasis at follow up (OR: 6.6 P = 0.03; OR: 51.3 P = 0.003). Both tests were strongly associated with heavy intensity S. mansoni infections. There was a significant decrease in FOB and calprotectin test positivity after PZQ treatment in those children who had egg patent schistosomiasis at baseline. Conclusions Both FOB and calprotectin rapid assays were found to correlate positively and strongly with egg patent S. mansoni infection with a positive ameloriation response after PZQ treatment indicative of short term reversion of morbidity. Both tests were appropriate for use in the field with excellent operational performance and reliability. Due to its lower-cost which makes its scale-up of use affordable, FOB could be immediately adopted as a monitoring tool for PC campaigns for efficacy evaluation before and after

  12. 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

  13. 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

  14. Radiotherapy for ocular tumours.

    PubMed

    Stannard, C; Sauerwein, W; Maree, G; Lecuona, K

    2013-02-01

    Ocular tumours present a therapeutic challenge because of the sensitive tissues involved and the necessity to destroy the tumour while minimising visual loss. Radiotherapy (RT) is one of several modalites used apart from surgery, laser, cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106 (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare most of the eye. Alternatively, an I-125 interstitial implant can be used with shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue lymphoma can be treated with an anterior electron field with lens shielding and 25-30 Gray (Gy) in 2 Gy fractions. Discrete retinoblastoma (RB), too large for cryotherapy or thermolaser, or recurrent after these modalities, can be treated with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with vacuum contact lenses to fix the eyes in the required position. Post-enucleated orbits at risk for recurrent RB can be treated with an I-125 implant with shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be treated with plaque or proton therapy with excellent local control. Preservation of vision will depend on the initial size and location of the tumour. PMID:23174750

  15. Radiotherapy for ocular tumours

    PubMed Central

    Stannard, C; Sauerwein, W; Maree, G; Lecuona, K

    2013-01-01

    Ocular tumours present a therapeutic challenge because of the sensitive tissues involved and the necessity to destroy the tumour while minimising visual loss. Radiotherapy (RT) is one of several modalites used apart from surgery, laser, cryotherapy, and chemotherapy. Both external beam RT (EBRT) and brachytherapy are used. Tumours of the bulbar conjunctiva, squamous carcinoma and malignant melanoma, can be treated with a radioactive plaque: strontium-90, ruthenium-106 (Ru-106), or iodine-125 (I-125), after excision. If the tumour involves the fornix or tarsal conjunctiva, proton therapy can treat the conjunctiva and spare most of the eye. Alternatively, an I-125 interstitial implant can be used with shielding of the cornea and lens. Conjunctival mucosal-associated lymphoid tissue lymphoma can be treated with an anterior electron field with lens shielding and 25–30 Gray (Gy) in 2 Gy fractions. Discrete retinoblastoma (RB), too large for cryotherapy or thermolaser, or recurrent after these modalities, can be treated with plaque therapy, I-125, or Ru-106. For large RB, multiple tumours, or vitreous seeds the whole eye can be treated with an I-125 applicator, sparing the bony orbit, or with EBRT, under anaesthetic, using X-rays or proton therapy with vacuum contact lenses to fix the eyes in the required position. Post-enucleated orbits at risk for recurrent RB can be treated with an I-125 implant with shielding to reduce the dose to the bony orbit. Uveal malignant melanomas can be treated with plaque or proton therapy with excellent local control. Preservation of vision will depend on the initial size and location of the tumour. PMID:23174750

  16. An unusual tumour of the lung.

    PubMed

    Ayadi, L; Abid, N; Makni, S; Bahri, I; Frikha, I; Sellami-Boudawara, T

    2015-03-01

    We report a case of a 51-year-old woman with a solitary mast cell tumour of the lung, a rare neoplasm with only three previously-reported cases reported in the literature. Unlike previous cases, the tumour in the present case was bulky, measuring 14 cm in diameter and budding into the segmental bronchus. Histologically, it showed proliferation of typical metachromatic mast cells intermingled with undifferentiated cells with a ratio of 3:1. The neoplastic mast cells stained strongly with tryptase, CD117, CD68 and CD45, CD14 and CD33; whereas the undifferentiated cells lacked all these markers and expressed EMA and cytokeratin. Histological examination of bone marrow and laboratory data were unremarkable. To our knowledge, this is the fourth case of solitary extracutaneous mastocytoma of the lung. The differentiating features of this neoplasm and a review of literature are presented. PMID:26591626

  17. Immunology of naturally transmissible tumours.

    PubMed

    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

  18. 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

  19. 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

  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.

  1. [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

  2. Novel association between microglia and stem cells in human gliomas: A contributor to tumour proliferation?

    PubMed Central

    Noorani, Imran; Petty, Gareth; Grundy, Paul L; Sharpe, Geoff; Willaime‐Morawek, Sandrine; Harris, Scott; Thomas, Gareth J; Nicoll, James AR

    2015-01-01

    Abstract Brain tumour stem cells and microglia both promote the growth of astrocytomas, the commonest form of primary brain tumour, with recent emerging evidence that these cell types may interact in glioma models. It is unclear whether microglia and stem cells are associated in human gliomas. To investigate this question, we used the technique of tissue microarrays to perform a correlative study of a large number of tumour samples. We quantified immunostaining of human astrocytic tumour tissue microarrays (86 patients; World Health Organisation grade II–IV) for microglia Ionized calcium binding adaptor molecule 1 (Iba1) and CD68, and stem cell nestin, SOX2 and CD133. Ki67 was used to assess proliferation and GFAP for astrocytic differentiation. Immunoreactivity for both microglial markers and stem cell markers nestin and SOX2 significantly increased with increasing tumour grade. GFAP was higher in low grade astrocytomas. There was a positive correlation between: (i) both microglial markers and nestin and CD133, (ii) nestin and tumour cell proliferation Ki67 and (iii) both microglial markers and Ki67. SOX2 was not associated with microglia or tumour proliferation. To test the clinical relevance, we investigated the putative association of these markers with clinical outcomes. High expression for nestin and Iba1 correlated with significantly shorter survival times, and high expression for nestin, Iba1, CD68 and Ki67 was associated with faster tumour progression on univariate analysis. On multivariate analysis, nestin, CD133 and Ki67 remained significant predictors of poorer survival, after adjustment for other markers. These results confirm previous in vitro findings, demonstrating their functional relevance as a therapeutic target in humans. This is the first report of a novel correlation between microglia and stem cells that may drive human astrocytic tumour development.

  3. 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...

  4. 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

  5. Serum endostatin levels are elevated in colorectal cancer and correlate with invasion and systemic inflammatory markers

    PubMed Central

    Kantola, T; Väyrynen, J P; Klintrup, K; Mäkelä, J; Karppinen, S M; Pihlajaniemi, T; Autio-Harmainen, H; Karttunen, T J; Mäkinen, M J; Tuomisto, A

    2014-01-01

    Background: Endostatin, a fragment of collagen XVIII, is an endogenous angiogenesis inhibitor with anti-tumour functions. However, elevated circulating endostatin concentrations have been found in several human cancers including colorectal cancer (CRC). Methods: Serum endostatin levels were measured by enzyme-linked immunoassay from a series of 143 patients with CRC and from 84 controls, and correlated with detailed clinicopathological features of CRC, serum leukocyte differential count and C-reactive protein (CRP) levels. Results: Patients with CRC had higher serum endostatin levels than the controls (P=0.005), and high levels associated with age, tumour invasion through the muscularis propria and poor differentiation, but not with metastases. Endostatin levels showed a positive correlation with the markers of systemic inflammatory response and a negative correlation with the densities of tumour-infiltrating mast cells and dendritic cells. Collagen XVIII was expressed in tumour stroma most strikingly in blood vessels and capillaries, and in the muscle layer of the bowel wall. Conclusions: Elevated endostatin levels in CRC correlate with systemic inflammation and invasion through the muscularis propria. Increased endostatin level may be a result of invasion-related cleavage of collagen XVIII expressed in the bowel wall. The negative correlations between serum endostatin and intratumoural mast cells and immature dendritic cells may reflect angiogenesis inhibition by endostatin. PMID:25137019

  6. Targeting of cancer stem cell marker EpCAM by bispecific antibody EpCAMxCD3 inhibits pancreatic carcinoma

    PubMed Central

    Salnikov, Alexei V; Groth, Ariane; Apel, Anja; Kallifatidis, Georgios; Beckermann, Benjamin M; Khamidjanov, Akmal; Ryschich, Eduard; Büchler, Markus W; Herr, Ingrid; Moldenhauer, Gerhard

    2009-01-01

    Patients with pancreatic cancer have a poor survival rate, and new therapeutic strategies are needed. Epithelial cell adhesion molecule (EpCAM), suggested as a marker for cancer stem cells, is over-expressed on most pancreatic tumour cells but not on normal cells and may be an ideal therapeutic target. We evaluated the anti-tumour efficiency of bispecific EpCAMxCD3 antibody linking tumour cells and T lymphocytes. In NOD SCID mice, EpCAMxCD3 had a long serum half-life (t1/2∼ 7 days). EpCAMxCD3 significantly retarded growth of BxPC-3 pancreatic carcinoma xenografts. For mimicking a pancreatic cancer microenvironment in vitro, we used a three-dimensional tumour reconstruct system, in which lymphocytes were co-cultured with tumour cells and fibroblasts in a collagen matrix. In this in vivo–like system, EpCAMxCD3 potently stimulated production of the effector cytokines IFN-γ and TNF-α by extracorporally pre-activated lymphocytes. Moreover, compared with a bivalent anti-CD3 antibody, EpCAMxCD3 more efficiently activated the production of TNF-α and IFN-γ by non-stimulated peripheral blood mononuclear cells. Most excitingly, we demonstrate for the first time that EpCAMxCD3 induces prolonged contacts between lymphocytes and tumour cells, which may be the main reason for the observed anti-tumour effects. As an important prerequisite for future use in patients, EpCAMxCD3 did not alter lymphocyte migration as measured by time-lapse video microscopy. Our data may open a way to improve the immune response and treatment outcome in patients with pancreatic cancer. PMID:20196789

  7. Fatty tumours of the uterus.

    PubMed Central

    Pounder, D J

    1982-01-01

    Uterine fatty tumours (UFT) are uncommon and have received little attention in the English literature. They have aroused interest as a consequence of occasional diagnostic confusion with sarcomas and the continuing unresolved dispute as to their histogenesis. Three cases of UFT are described and the pathological features of note discussed. The viewpoint that these tumours are hamartomas/choristomas is rejected. UFT most probably represent tumour metaplasia within a leiomyoma. There is no uniform accepted nomenclature for such tumours and it is suggested that they be designated "uterine fatty tumours" and subdivided into "lipoma" and "mixed lipoma/leiomyoma" (synonym lipoleiomyoma). Images PMID:7174848

  8. Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

    PubMed Central

    Lunt, Sarah Jane; Kalliomaki, Tuula MK; Brown, Allison; Yang, Victor X; Milosevic, Michael; Hill, Richard P

    2008-01-01

    Background High tumour interstitial fluid pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread. Methods KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m), sub-cutaneously (s/c) or orthotopically. Polyoma middle-T (MMTV-PyMT) transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging. Results Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion between ME180 tumours grown

  9. Glomus tumour of the stomach.

    PubMed

    Troller, Rebekka; Soll, Christopher; Breitenstein, Stefan

    2016-01-01

    Glomus tumours are benign tumours typically arising from the glomus bodies and primarily found under the fingernails or toenails. These rare neoplasms account for <2% of all soft tissue tumours and are generally not found in the gastrointestinal tract. We report a case of a 40-year-old man presenting with recurrent epigastric pain and pyrosis. Endoscopy revealed a solitary tumour in the antrum of the stomach. Fine-needle aspiration biopsy was suspicious for a gastrointestinal stroma tumour. After CT indicated the resectability of the tumour, showing neither lymphatic nor distant metastases, a laparoscopic-assisted gastric wedge resection was performed. Surprisingly, histology revealed a glomus tumour of the stomach. PMID:27343282

  10. Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours.

    PubMed

    Braekeveldt, Noémie; Wigerup, Caroline; Tadeo, Irene; Beckman, Siv; Sandén, Caroline; Jönsson, Jimmie; Erjefält, Jonas S; Berbegall, Ana P; Börjesson, Anna; Backman, Torbjörn; Øra, Ingrid; Navarro, Samuel; Noguera, Rosa; Gisselsson, David; Påhlman, Sven; Bexell, Daniel

    2016-06-01

    Treatment of high-risk childhood neuroblastoma is a clinical challenge which has been hampered by a lack of reliable neuroblastoma mouse models for preclinical drug testing. We have previously established invasive and metastasising patient-derived orthotopic xenografts (PDXs) from high-risk neuroblastomas that retained the genotypes and phenotypes of patient tumours. Given the important role of the tumour microenvironment in tumour progression, metastasis, and treatment responses, here we analysed the tumour microenvironment of five neuroblastoma PDXs in detail. The PDXs resembled their parent tumours and retained important stromal hallmarks of aggressive lesions including rich blood and lymphatic vascularisation, pericyte coverage, high numbers of cancer-associated fibroblasts, tumour-associated macrophages, and extracellular matrix components. Patient-derived tumour endothelial cells occasionally formed blood vessels in PDXs; however, tumour stroma was, overall, of murine origin. Lymphoid cells and lymphatic endothelial cells were found in athymic nude mice but not in NSG mice; thus, the choice of mouse strain dictates tumour microenvironmental components. The murine tumour microenvironment of orthotopic neuroblastoma PDXs reflects important hallmarks of aggressive and metastatic clinical neuroblastomas. Neuroblastoma PDXs are clinically relevant models for preclinical drug testing. PMID:27000989

  11. Tumour biology: Herceptin acts as an anti-angiogenic cocktail

    NASA Astrophysics Data System (ADS)

    Izumi, Yotaro; Xu, Lei; di Tomaso, Emmanuelle; Fukumura, Dai; Jain, Rakesh K.

    2002-03-01

    Malignant tumours secrete factors that enable them to commandeer their own blood supply (angiogenesis), and blocking the action of these factors can inhibit tumour growth. But because tumours may become resistant to treatments that target individual angiogenic factors by switching over to other angiogenic molecules, a cocktail of multiple anti-angiogenic agents should be more effective. Here we show that herceptin, a monoclonal antibody against the cell-surface receptor HER2 (for human epidermal growth factor receptor-2; ref. 4), induces normalization and regression of the vasculature in an experimental human breast tumour that overexpresses HER2 in mice, and that it works by modulating the effects of different pro- and anti-angiogenic factors. As a single agent that acts against multiple targets, herceptin, or drugs like it, may offer a simple alternative to combination anti-angiogenic treatments.

  12. 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.

  13. Borderline ovarian tumours.

    PubMed

    Tropé, Claes Göran; Kaern, Janne; Davidson, Ben

    2012-06-01

    Borderline ovarian tumours account for 10-20% of all epithelial ovarian cancer. Historically, standard primary surgery has included borderline ovarian tumours, omentectomy, peritoneal washing and multiple biopsies. As one-third of borderline ovarian tumours are diagnosed in women under the age of 40 years, fertility-sparing treatment has been more frequently used in the past 10 years. Fertility drugs are well tolerated in women with infertility after fertility-sparing surgery. Careful selection of candidates is necessary. Laparoscopic techniques can be used, but should be reserved for oncologic surgeons. This conservative treatment increases the rate of recurrence, albeit with no effect on survival. The pregnancy rate is nearly 50%, and most are achieved spontaneously. These women should be closely followed up. The question is whether this is acceptable from a gynaecologic oncologic point of view. For this reason, we will discuss recently published studies and gynaecologic oncologic concerns about the mode of fertility-sparing surgery and its consequences. PMID:22321906

  14. Tumours of the kidney

    PubMed Central

    Nielsen, Svend W.; Mackey, L. J.; Misdorp, W.

    1976-01-01

    The most frequent renal tumours of animals are renal cell carcinoma and nephroblastoma. Renal cell carcinomas are seen mainly in dogs and cattle and nephroblastoma is encountered in pigs, puppies, and calves. Renal cell carcinomas are usually papillary in the dog. They show a marked propensity for vascular invasion, penetration of the posterior vena cava, and subsequent pulmonary metastasis. Nephroblastoma, which is morphologically identical to Wilms' tumour of children, is almost always a benign tumour in animals. It is one of the most frequent neoplasms of pigs, possibly owing to the fact that most pigs are slaughtered (and examined) when a few months old. Lymphosarcoma involving the kidney is particularly frequent in the cat, but is also seen in other species as part of a generalized disease. ImagesFig. 5,6Fig. 7Fig. 8Fig. 1,2Fig. 3,4Fig. 16,17,18,19Fig. 9,10Fig. 11Fig. 12Fig. 13Fig. 14,15 PMID:1086154

  15. Adaptation to statins restricts human tumour growth in Nude mice

    PubMed Central

    2011-01-01

    Background Statins have long been used as anti-hypercholesterolemia drugs, but numerous lines of evidence suggest that they may also bear anti-tumour potential. We have recently demonstrated that it was possible to isolate cancer cells adapted to growth in the continuous presence of lovastatin. These cells grew more slowly than the statin-sensitive cells of origin. In the present study, we compared the ability of both statin-sensitive and statin-resistant cells to give rise to tumours in Nude mice. Methods HGT-1 human gastric cancer cells and L50 statin-resistant derivatives were injected subcutaneously into Nude mice and tumour growth was recorded. At the end of the experiment, tumours were recovered and marker proteins were analyzed by western blotting, RT-PCR and immunohistochemistry. Results L50 tumours grew more slowly, showed a strong decrease in cyclin B1, over-expressed collagen IV, and had reduced laminin 332, VEGF and CD34 levels, which, collectively, may have restricted cell division, cell adhesion and neoangiogenesis. Conclusions Taken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years. PMID:22107808

  16. 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

  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. Biophysical models of tumour growth

    NASA Astrophysics Data System (ADS)

    Tracqui, P.

    2009-05-01

    Tumour growth is a multifactorial process, which has stimulated in recent decades the development of numerous models trying to figure out the mechanisms controlling solid tumours morphogenesis. While the earliest models were focusing on cell proliferation kinetics, modulated by the availability of supplied nutrients, new modelling approaches emphasize the crucial role of several biophysical processes, including local matrix remodelling, active cell migration and traction, and reshaping of host tissue vasculature. After a brief presentation of this experimental background, this review will outline a number of representative models describing, at different scales, the growth of avascular and vascularized tumours. Special attention will be paid to the formulation of tumour-host tissue interactions that selectively drive changes in tumour size and morphology, and which are notably mediated by the mechanical status and elasticity of the tumour microenvironment. Emergence of invasive behaviour through growth instabilities at the tumour-host interface will be presented considering both reaction-diffusion and mechano-cellular models. In the latter part of the review, patient-oriented implications of tumour growth modelling are outlined in the context of brain tumours. Some conceptual views of the adaptive strategies and selective barriers that govern tumour evolution are presented in conclusion as potential guidelines for the development of future models.

  19. Quantifying the Effects of Radiation on Tumour Vasculature with High-Frequency Three-Dimensional Power Doppler Ultrasound

    NASA Astrophysics Data System (ADS)

    Hupple, Clinton

    Recent evidence suggests that radiation may have a significant effect on tumour vasculature in addition to damaging tumour cell DNA. It is well established that endothelial cells are among the first cells to respond after administration of ionizing radiation in both normal and tumour tissues. It has also been suggested that microvascular dysfunction may regulate tumour response to radiotherapy at high doses. However, due to limitations in imaging the microcirculation this response is not well characterized. Advances in high-frequency ultrasound and computation methods now make it possible to acquire and analyze 3-D ultrasound data of tumour blood flow in tumour microcirculation. This thesis outlines the work done to test the hypothesis that single dose 8 Gy radiotherapy produces changes in tumour blood vessels which can be quantified using high-frequency power Doppler ultrasound. In addition, the issue of reproducibility of power Doppler measurements and the relationship between histopathology and power Doppler measurements have been examined.

  20. Acute vascular response to cediranib treatment in human non-small-cell lung cancer xenografts with different tumour stromal architecture

    PubMed Central

    Jiang, Yanyan; Allen, Danny; Kersemans, Veerle; Devery, Aoife M.; Bokobza, Sivan M.; Smart, Sean; Ryan, Anderson J.

    2015-01-01

    Objectives Tumours can be categorised based on their stromal architecture into tumour vessel and stromal vessel phenotypes, and the phenotypes have been suggested to define tumour response to chronic treatment with a VEGFR2 antibody. However, it is unclear whether the vascular phenotypes of tumours associate with acute vascular response to VEGFR tyrosine kinase inhibitors (TKI), or whether the early changes in vascular function are associated with subsequent changes in tumour size. This study was sought to address these questions by using xenograft models of human non-small cell lung cancer (NSCLC) representing stromal vessel phenotype (Calu-3) and tumour vessel phenotype (Calu-6), respectively. Methods For dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), nude mice bearing established Calu-3 or Calu-6 xenografts were treated with a potent pan-VEGFR TKI, cediranib (6 mg/kg), at 0 h and 22 h. DCE-MRI was performed 2 h before the first dose and 2 h after the second dose of cediranib to examine acute changes in tumour vessel perfusion. Tumours were harvested for hypoxia detection by CA9 immunohistochemistry. For tumour growth study, mice carrying established Calu-3 or Calu-6 tumours were treated with cediranib once daily for 5 days. Results Twenty-four hours after cediranib administration, the perfusion of Calu-3 tumours was markedly reduced, with a significant increase in hypoxia. In contrast, neither perfusion nor hypoxia was significantly affected in Calu-6 tumours. Tumour regressions were induced in Calu-3 xenografts, but not in Calu-6 xenografts, although there was a trend towards tumour growth inhibition after 5 days of cediranib treatment. Conclusion These findings suggest that tumour stromal architecture may associate with acute tumour vascular response to VEGFR TKI, and this acute tumour vascular response may be a promising early predictive marker of response to VEGFR TKI in NSCLC. PMID:26323213

  1. Use of faecal markers in screening for colorectal neoplasia: a European group on tumor markers position paper.

    PubMed

    Duffy, Michael J; van Rossum, Leo G M; van Turenhout, Sietze T; Malminiemi, Outi; Sturgeon, Catherine; Lamerz, Rolf; Nicolini, Andrea; Haglund, Caj; Holubec, Lubos; Fraser, Callum G; Halloran, Stephen P

    2011-01-01

    Several randomized controlled trials have shown that population-based screening using faecal occult blood testing (FOBT) can reduce mortality from colorectal neoplasia. Based on this evidence, a number of countries have introduced screening for colorectal cancer (CRC) and high-risk adenoma and many others are considering its introduction. The aim of this article is to critically review the current status of faecal markers as population-based screening tests for these neoplasia. Most of the available faecal tests involve the measurement of either occult blood or a panel of DNA markers. Occult blood may be measured using either the guaiac faecal occult blood test (gFOBT) or a faecal immunochemical test (iFOBT). Although iFOBT may require a greater initial investment, they have several advantages over gFOBT, including greater analytical sensitivity and specificity. Their use results in improved clinical performance and higher uptake rates. Importantly for population screening, some of the iFOBTs can be automated and provide an adjustable cutoff for faecal haemoglobin concentration. However, samples for iFOBT, may be less stable after collection than for gFOBT. For new centres undertaking FOBT for colorectal neoplasia, the European Group on Tumour Markers recommends use of a quantitative iFOBT with an adjustable cutoff point and high throughput analysis. All participants with positive FOBT results should be offered colonoscopy. The panel recommends further research into increasing the stability of iFOBT and the development of improved and affordable DNA and proteomic-based tests, which reduce current false negative rates, simplify sample transport and enable automated analysis. PMID:20824704

  2. 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

  3. Effects of tumour cells on angiogenesis and vasoconstrictor responses in sponge implants in mice.

    PubMed

    Andrade, S P; Bakhle, Y S; Hart, I; Piper, P J

    1992-11-01

    The effects of tumour cells (Colon 26) on the development and response of new blood vessels to different vasoconstrictors (platelet activating factor; PAF, endothelin-1, angiotensin II, adrenalin and 5-hydroxytryptamine) have been investigated. Sponge implants in mice were used to host tumour cells while washout of 133Xe was employed to assess local blood flow in the implanted sponges. By 14 days after implantation the response of vessels in tumour-bearing implants to the various vasoconstrictors generally was decreased compared to that obtained in control sponge implants or adjacent normal skin. Thus at this time point the t1/2 for 133Xe washout from control sponges treated with adrenalin (0.5 micrograms) was 30 +/- 4 min whereas in tumour-bearing sponges it was 5 +/- 1 min. This decreased sensitivity in tumour vessels was probably not due to a complete lack of contractile elements since actin was demonstrated by immunohistochemistry around blood vessels in both types of implant. The results of the present study have shown that the pharmacological responses of blood vessels in a growing tumour, Colon 26, differed from the responses of vessels of a similar age in non-neoplastic tissue. These results appear to suggest that the different angiogenic stimuli released from tumour tissue may markedly influence pharmacological reactivity of newly formed blood vessels. PMID:1384642

  4. NHEXAS PHASE I REGION 5 STUDY--STANDARD OPERATING PROCEDURE--HUMAN BIOLOGICAL MARKERS:BLOOD AND URINE SAMPLE COLLECTION AND ANALYSES (EOHSI-AP-209-040)

    EPA Science Inventory

    This procedure describes the process for collecting and analyzing blood and urine samples. The presence of chemical contaminants in biological specimens such as blood, urine, and hair represent a measure of the internal dose or body burden for a given individual derived from the ...

  5. 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

  6. Cell Surface Markers in Colorectal Cancer Prognosis

    PubMed Central

    Belov, Larissa; Zhou, Jerry; Christopherson, Richard I.

    2011-01-01

    The classification of colorectal cancers (CRC) is currently based largely on histologically determined tumour characteristics, such as differentiation status and tumour stage, i.e., depth of tumour invasion, involvement of regional lymph nodes and the occurrence of metastatic spread to other organs. These are the conventional prognostic factors for patient survival and often determine the requirement for adjuvant therapy after surgical resection of the primary tumour. However, patients with the same CRC stage can have very different disease-related outcomes. For some, surgical removal of early-stage tumours leads to full recovery, while for others, disease recurrence and metastasis may occur regardless of adjuvant therapy. It is therefore important to understand the molecular processes that lead to disease progression and metastasis and to find more reliable prognostic markers and novel targets for therapy. This review focuses on cell surface proteins that correlate with tumour progression, metastasis and patient outcome, and discusses some of the challenges in finding prognostic protein markers in CRC. PMID:21339979

  7. Role of tumour angiogenesis in haematological malignancies.

    PubMed

    Medinger, Michael; Passweg, Jakob

    2014-01-01

    Tumour angiogenesis plays a key role in the pathogenesis and progression of haematological malignancies. Thereby, pro- and anti-angiogenic growth factors and cytokines regulate the angiogenic process. The most important growth factor, vascular endothelial growth factor (VEGF) and its signaling through its receptors 1 and 2, is not only involved in solid tumours, but there is also emerging evidence that tumour progression in haematological malignancies also depends on the induction of new blood vessel formation. The evidence supporting this theory includes the finding of increased bone marrow microvessel density and increased levels of plasma pro-angiogenic cytokines. Leukaemia cells interact with surrounding host cells and extracellular matrix, this crosstalk affecting the most important aspects of the malignant phenotype. The pathophysiology of leukaemia induced angiogenesis involves both direct production of angiogenic cytokines by leukaemia cells and their interaction with bone marrow microenvironment. The inhibition of VEGF signalling by monoclonal antibodies or small molecules (kinase inhibitors) has already been successfully used for the treatment of different cancer entities, and multiple new drugs are being tested. This review summarises recent advances in the basic understanding of the role of angiogenesis in haematological malignancies and the translation of such basic findings into clinical studies. PMID:25375891

  8. 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 ...

  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. Direct evidence that hydralazine can induce hypoxia in both transplanted and spontaneous murine tumours.

    PubMed Central

    Horsman, M. R.; Nordsmark, M.; Høyer, M.; Overgaard, J.

    1995-01-01

    Hydralazine can substantially decrease blood flow and increase hypoxia in transplanted tumours. Previous indirect studies have suggested that hydralazine does not induce such effects in spontaneous tumours. We have now directly investigated the ability of hydralazine to increase hypoxia in both transplanted and spontaneous murine tumours by measuring tumour oxygen partial pressure (pO2) distributions using an Eppendorf oxygen electrode. Spontaneous tumours arose at different sites in CDF1 mice, while transplanted tumours were produced by implanting a C3H mouse mammary carcinoma on the backs of the same mouse strain. Measurements of pO2 were made in anaesthetised mice immediately before and 45 min after an intravenous injection of 5 mg kg-1 hydralazine. In the transplanted tumours hydralazine significantly decreased tumour oxygenation, such that the percentage of pO2 values < or = 5 mmHg increased from 45% to 87%, and median pO2 decreased from 5 to 3 mmHg. Similar significant changes were induced by hydralazine in the spontaneous tumours, the percentage of pO2 values < or = 5 mmHg increasing from 60% to 94% while the median pO2 values decreased from 8 to 2 mmHg. These results clearly show that there is no difference in the response of transplanted and spontaneous mouse tumours to hydralazine. PMID:8519662

  11. Familial predisposition to Wilms' tumour does not map to the short arm of chromosome 11.

    PubMed

    Grundy, P; Koufos, A; Morgan, K; Li, F P; Meadows, A T; Cavenee, W K

    1988-11-24

    Wilms' tumour of the kidney usually occurs sporadically, but can also segregate as an autosomal dominant trait with incomplete penetrance. Patients with the WAGR syndrome of aniridia, genitourinary anomalies, mental retardation and high risk of Wilms' tumour have overlapping deletions of chromosome 11p13 which has suggested a possible location for a Wilms' tumour locus. Moreover, many sporadic tumours have lost a portion of chromosome 11p. A second locus at 11p15 is implicated by association of the tumour with the Wiedemann-Beckwith syndrome and by tumour-specific losses of chromosome 11 confined to 11p15. Here we report a multipoint linkage analysis of a family segregating for Wilms' tumour, using polymorphic DNA markers mapped to chromosome 11p. The results exclude the predisposing mutation from both locations. In a second family, the 11p15 alleles lost in the tumour were derived from the affected parent, thus precluding this region as the location of the inherited mutation. These findings imply an aetiological heterogeneity for Wilms' tumour and raise questions concerning the general applicability of the carcinogenesis model that has been useful in the understanding of retinoblastoma. PMID:2848199

  12. One very rare and one new tracheal tumour found by electron microscopy: glomus tumour and acinic cell tumour resembling carcinoid tumours by light microscopy.

    PubMed Central

    Heard, B E; Dewar, A; Firmin, R K; Lennox, S C

    1982-01-01

    Tracheal tumours were removed surgically from two patients and diagnosed as carcinoid tumours by routine light microscopy. At a later date, electron microscopy was performed on stored tumour tissue and no neurosecretory granules were found in either case. One showed features of a glomus tumour and the other of an acinic cell tumour. Only two glomus tumours appear to have been reported previously in the trachea, and no acinic cell tumours. Electron microscopy is thus sometimes of great assistance in diagnosing accurately unusual tumours of the lower respiratory tract. Images PMID:6281934

  13. Metabolic reprogramming of the tumour microenvironment.

    PubMed

    Xing, Yazhi; Zhao, Shimin; Zhou, Binhua P; Mi, Jun

    2015-10-01

    Tumour cells, stromal cells and the stroma comprise the tumour microenvironment. The metabolism of both tumour cells and several types of tumour stromal cells, such as cancer-associated fibroblasts and tumour-associated macrophages, is reprogrammed. Current studies have found that stromal cells promote tumour progression and metastasis, through not only the paracrine secretion of cytokines or chemokines, but also intermediate metabolites. Here, we summarize the latest insights into the mechanism of metabolic reprogramming in cancer cells, cancer-associated fibroblasts and tumour-associated macrophages, and their potential roles in tumour progression and metastasis. PMID:26255648

  14. Intra-Abdominal Desmoid Tumour (DT) with Pelvic Extension-A Case Report

    PubMed Central

    Kumar, Sathish Selva; Ramachandran, Padmini; G, Veena; Madhusudhan, Napa; Kumbhar, Uday

    2014-01-01

    Desmoid Tumour (DT) is a rare benign, myofibroblastic tumour originating from muscle fascia with tendency to recur but, it rarely metastasizes. We are reporting here a case of DT that presented as an intra-abdominal mass with pelvic extension in a patient who underwent hysterectomy for fibroid uterus seventeen years ago. A clinical diagnosis of ovarian malignancy was made. Ovarian tumour markers for surface epithelial and germ cell tumours were negative. Imaging studies suggested DT and the same was excised surgically. A histopathological diagnosis of DT was made and confirmed with immunohistochemistry (IHC) markers. DT should always be considered especially in female patients with previous history of surgery. A complete surgical excision is the treatment of choice with recurrent cases requiring radiotherapy. A differential diagnosis like sarcoma and further toxic chemotherapy can be avoided with careful histopathological evaluation and IHC confirmation of DTs. PMID:24596759

  15. Serially heterotransplanted human prostate tumours as an experimental model

    PubMed Central

    Lopez-Barcons, Lluis-A

    2010-01-01

    Abstract Preclinical research on prostate cancer (PC) therapies uses several models to represent the human disease accurately. A common model uses patient prostate tumour biopsies to develop a cell line by serially passaging and subsequent implantation, in immunodeficient mice. An alternative model is direct implantation of patient prostate tumour biopsies into immunodeficient mice, followed by serial passage in vivo. The purpose of this review is to compile data from the more than 30 years of human PC serial heterotransplantation research. Serially heterotransplanted tumours are characterized by evaluating the histopathology of the resulting heterotransplants, including cellular differentiation, karyotype, marker expression, hormone sensitivity, cellular proliferation, metastatic potential and stromal and vascular components. These data are compared with the initial patient tumour specimen and, depending on available information, the patient’s clinical outcome was compared with the heterotransplanted tumour. The heterotansplant model is a more accurate preclinical model than older generation serially passaged or genetic models to investigate current and newly developed androgen-deprivation agents, antitumour compounds, anti-angiogenic drugs and positron emission tomography radiotracers, as well as new therapeutic regimens for the treatment of PC. PMID:19874422

  16. Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster.

    PubMed Central

    Leunig, M.; Richert, C.; Gamarra, F.; Lumper, W.; Vogel, E.; Jocham, D.; Goetz, A. E.

    1993-01-01

    In this study the localisation of porphyrinoid photosensitizers in tumours was investigated. To determine if tumour selectivity results from a preferential uptake or prolonged retention of photosensitizers, intravital fluorescence microscopy and chemical extraction were used. Amelanotic melanoma (A-Mel-3) were implanted in a skin fold chamber in Syrian Golden hamsters. Distribution of the porphyrin mixture Photofrin and three porphycenes, pure porphyrinoid model compounds, was studied quantitatively by intravital fluorescence microscopy. Extraction of tissue and blood samples was performed to verify and supplement intravital microscopic results. Photofrin accumulated in melanomas reaching a maximum tumour:skin tissue ratio of 1.7:1. Localisation of the different porphycenes was found to be highly tumour selective (3.2:1), anti-tumour selective (0.2:1), and non-selective (1:1) with increasing polarity of the porphycenes. The two non-tumour selective porphycenes had distinctly accelerated serum and tissue kinetics; serum halflife times being as short as 1 min. The specific localisation of the slowly distributed, tumour selective photosensitizers, occurred exclusively during the distribution from serum and uptake into tissues. For the most selective porphycene, the tumour selection process had a halflife of 260 +/- 150 min and led to a strongly fluorescent tumour edge edema. Accumulation of porphyrines by the amelanotic melanoma (A-Mel-3) can be attributed to an enhanced uptake rate for lipophilic molecules in this subcutaneously growing neoplasm. The slow distribution of the two tumour specific photosensitizers and the strong fluorescence of these hydrophobic molecules in the tumour compartment with a high water content indicate a carrier role of serum proteins in the selection process. Enhanced permeability of the tumour vasculature to macromolecules appears to be the most probable reason for the tumour selectivity of these two sensitisers. Images Figure 6 PMID

  17. Recurrent hyperphosphatemic tumoural calcinosis

    PubMed Central

    Amit, Sonal; Agarwal, Asha; Nigam, Anand; Rao, Yashwant Kumar

    2012-01-01

    Tumoural calcinosis (TC) is a benign gradually developing disorder that can occur in a variety of clinical settings, characterised by subcutaneous deposition of calcium phosphate with or without giant cell reaction. We describe a case of 11-year-old girl presenting with recurrent hard swellings in the vicinity of shoulder and hip joints associated with elevated serum phosphate and normal serum calcium levels. TC has been mainly reported from Africa, with very few cases reported from India. After the diagnosis of hyperphosphatemic TC was established, the patient was treated with oral sevelamer and is under constant follow-up to detect recurrence, if any. The present case highlights the fact that although an uncommon lesion, TC must be considered in the differential diagnosis of subcutaneous hard lump in the vicinity of a joint. PMID:23010461

  18. 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

  19. Tumour-initiating cells vs. cancer 'stem' cells and CD133: What's in the name?

    SciTech Connect

    Neuzil, Jiri; E-mail: j.neuzil@griffith.edu.au; Stantic, Marina; Zobalova, Renata; Chladova, Jaromira; Wang, Xiufang; Prochazka, Lubomir; Dong, Lanfeng; Andera, Ladislav; Ralph, Stephen J.

    2007-04-20

    Recent evidence suggests that a subset of cells within a tumour have 'stem-like' characteristics. These tumour-initiating cells, distinct from non-malignant stem cells, show low proliferative rates, high self-renewing capacity, propensity to differentiate into actively proliferating tumour cells, resistance to chemotherapy or radiation, and they are often characterised by elevated expression of the stem cell surface marker CD133. Understanding the molecular biology of the CD133{sup +} cancer cells is now essential for developing more effective cancer treatments. These may include drugs targeting organelles, such as mitochondria or lysosomes, using highly efficient and selective inducers of apoptosis. Alternatively, agents or treatment regimens that enhance sensitivity of these therapy-resistant 'tumour stem cells' to the current or emerging anti-tumour drugs would be of interest as well.

  20. Circulating tumour cells in patients with urothelial tumours: Enrichment and in vitro culture

    PubMed Central

    Kolostova, Katarina; Cegan, Martin; Bobek, Vladimir

    2014-01-01

    Introduction: Results of clinical trials have demonstrated that circulating tumour cells (CTCs) are frequently detected in patients with urothelial tumours. The monitoring of CTCs has the potential to improve therapeutic management at an early stage and also to identify patients with increased risk of tumour progression or recurrence before the onset of clinically detected metastasis. In this study, we report a new effectively simplified methodology for a separation and in vitro culturing of viable CTCs from peripheral blood. Method: We include patients diagnosed with 3 types of urothelial tumours (prostate cancer, urinary bladder cancer, and kidney cancer). A size-based separation method for viable CTC - enrichment from unclothed peripheral blood has been introduced (MetaCell, Ostrava, Czech Republic). The enriched CTCs fraction was cultured directly on the separation membrane, or transferred from the membrane and cultured on any plastic surface or a microscopic slide. Results: We report a successful application of a CTCs isolation procedure in patients with urothelial cancers. The CTCs captured on the membrane are enriched with a remarkable proliferation potential. This has enabled us to set up in vitro cell cultures from the viable CTCs unaffected by any fixation buffers, antibodies or lysing solutions. Next, the CTCs were cultured in vitro for a minimum of 10 to 14 days to enable further downstream analysis (e.g., immunohistochemistry). Conclusion: We demonstrated an efficient CTCs capture platform, based on a cell size separation principle. Furthermore, we report an ability to culture the enriched cells – a critical requirement for post-isolation cellular analysis. PMID:25408812

  1. 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

  2. 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

  3. [Drug therapy for neuroendocrine tumours].

    PubMed

    Tóth, Miklós

    2013-09-29

    The author aims to review the established medical treatment options of neuroendocrine tumours, which have expanded greatly in recent years and present the most important aspects to be considered in planning patients' management. Medical treatment is usually considered in advanced stages of these tumours, as well as in cases of hormone overproduction. Somatostatin analogues have been known to be effective in alleviating hormone excess syndromes, especially carcinoid syndrome for the past 25 years. There is a convincing evidence that the somatostatin analogue octreotide is useful as an antitumor agent, at least in well-differentiated small intestinal neuroendocrine tumours and probably also in those of pancreatic origin. Interferons may be also used and the indications for their use may be almost the same. Optimal patient selection is mandatory for the use of cytotoxic chemotherapy. Streptozotocin- and, recently, temozolomide-based chemotherapies should be considered in progressive phases of well differentiated (G1/G2) pancreatic neuroendocrine tumours. A cisplatin-etoposide combination is the first choice for the treatment of G3 neuroendocrine carcinomas of any origin. Recently, the mammalian target of rapamycin inhibitor everolimus and the combined tyrosine kinase inhibitor sunitinib were registered for the treatment of G1/G2 pancreatic neuroendocrine tumours. The most recent drug treatment recommendations and therapeutic algorithms to improve systemic therapy in patients with neuroendocrine tumours are summarized and novel drug candidates with particular potential for future management of these tumours are outlined. PMID:24058101

  4. Tumours of bones and joints

    PubMed Central

    Misdorp, W.; Van Der Heul, R. O.

    1976-01-01

    Tumours of bones and joints are not infrequent in dogs but are rare in other domestic animals. In the dog, most bone tumours are malignant; osteosarcomas are by far the most frequently encountered tumours, especially in giant breeds and boxers. The following main categories of bone tumour are described: bone-forming, cartilage-forming, giant cell, marrow, vascular, miscellaneous, metastatic, unclassified, and tumour-like lesions. The tumours of joints and related structures are classified as synovial sarcomas, fibroxanthomas, and malignant giant cell tumour of soft tissues. ImagesFig. 21Fig. 22Fig. 23Fig. 24Fig. 17Fig. 18Fig. 19Fig. 20Fig. 29Fig. 30Fig. 31Fig. 32Fig. 33Fig. 34Fig. 35Fig. 36Fig. 25Fig. 26Fig. 27Fig. 28Fig. 1Fig. 2Fig. 3Fig. 4Fig. 37Fig. 38Fig. 39Fig. 40Fig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16Fig. 9Fig. 10Fig. 11Fig. 12 PMID:1086157

  5. 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

  6. 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

  7. Mixed Germ Cell Tumour in an Infertile Male Having Unilateral Cryptorchidism: A Rare Case Report.

    PubMed

    Singla, Anand; Kaur, Navneet; Sandhu, Gunjeet; Nagori, Rupesh

    2016-02-01

    Mixed germ cell tumours with multiple components occur more frequently than the pure varieties of germ cell tumours. Embryonal carcinoma and teratoma together form the most common components of the mixed germ cell tumour but the yolk sac tumour is usually seen as a minor component in patients presenting with mixed germ cell tumour. We report a rare case of 27-year-old Hepatitis C positive male presenting with pain in left lower abdomen with associated history of same sided undescended testis and infertility. Right sided testis lying in scrotal sac appeared normal on ultrasonography but patient was azoospermic. He had raised levels of serum markers, alpha feto protein and beta HCG. Examination showed a large mass in left lower abdomen involving the sigmoid colon with the absence of left testis in left scrotum which was confirmed on CT scan. Excision of the mass was done and histopathology examination revealed it as a malignant mixed germ cell tumour composed predominantly of a yolk sac tumour, with minor component as seminoma and embryonal carcinoma in an undescended testis. Following this, the level of serum markers came down. The patient is now undergoing adjuvant chemotherapy and is doing well. PMID:27042527

  8. Mixed Germ Cell Tumour in an Infertile Male Having Unilateral Cryptorchidism: A Rare Case Report

    PubMed Central

    Kaur, Navneet; Sandhu, Gunjeet; Nagori, Rupesh

    2016-01-01

    Mixed germ cell tumours with multiple components occur more frequently than the pure varieties of germ cell tumours. Embryonal carcinoma and teratoma together form the most common components of the mixed germ cell tumour but the yolk sac tumour is usually seen as a minor component in patients presenting with mixed germ cell tumour. We report a rare case of 27-year-old Hepatitis C positive male presenting with pain in left lower abdomen with associated history of same sided undescended testis and infertility. Right sided testis lying in scrotal sac appeared normal on ultrasonography but patient was azoospermic. He had raised levels of serum markers, alpha feto protein and beta HCG. Examination showed a large mass in left lower abdomen involving the sigmoid colon with the absence of left testis in left scrotum which was confirmed on CT scan. Excision of the mass was done and histopathology examination revealed it as a malignant mixed germ cell tumour composed predominantly of a yolk sac tumour, with minor component as seminoma and embryonal carcinoma in an undescended testis. Following this, the level of serum markers came down. The patient is now undergoing adjuvant chemotherapy and is doing well. PMID:27042527

  9. Studies on canine mammary tumours. I. Age, seasonal and breed distribution.

    PubMed

    Boldizsár, H; Szenci, O; Muray, T; Csenki, J

    1992-01-01

    The incidence as well as age, seasonal and breed distribution of canine mammary tumours (n = 521) were studied at the Clinic of Obstetrics and Gynaecology of the University of Veterinary Science, Budapest, between 1985 and 1989. In 39 cases of mammary tumour, blood plasma oestradiol (E2) and progesterone (P) concentrations were also determined. Of all dogs referred to the clinics of the University in 1985, 0.7% had mammary tumour. On the average, 104 +/- 9.3 cases of mammary tumour were recorded at the Clinic of Obstetrics per year. This number did not increase after the Chernobyl atomic reactor catastrophe of 1986. The age distribution of canine mammary tumour found in this study shows good agreement with earlier data of the literature: mammary tumour showed the highest incidence in 10 years old dogs. The incidence of mammary tumour kept increasing with age until the 14th year of life (as expressed in per cent of animals of identical age). The number of mammary tumours was markedly higher in the spring (April-May) and autumn (September). This seasonality was demonstrable in 11 to 16 years old bitches, too. On the basis of the blood plasma E2 and P profiles, 61.5% of the clinically anoestrous animals were found to be cycling. The strikingly high ratio of pulis among dogs with mammary cancer was suggestive of a breed disposition. PMID:1476093

  10. 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.

  11. 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

  12. Tumours of the urinary bladder

    PubMed Central

    Pamukcu, A. M.

    1974-01-01

    Tumours of the urinary bladder are uncommon in all domestic animals except cattle in certain regions. Where cattle eat bracken (Pteridium aquilinum) there is a high incidence of these tumours. Epithelial tumours are the most frequently encountered neoplasms in cattle and in dogs—the two species most studied. They are described under the following names: papilloma, adenoma, transitional cell carcinoma (with variants), squamous cell carcinoma, adenocarcinoma, and undifferentiated carcinoma. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15Fig. 16 PMID:4371741

  13. Distribution of Photofrin between tumour cells and tumour associated macrophages.

    PubMed Central

    Korbelik, M.; Krosl, G.; Olive, P. L.; Chaplin, D. J.

    1991-01-01

    Photofrin levels in cells derived from SCCVII tumours, excised from mice that previously received the drug, were measured using a fluorescence activated cell sorter (FACS). Concomitantly, in the same cells the FACS was used to measure fluorescein isothiocyanate (FITC) fluorescence that originated from FITC-conjugated antimouse IgG added to the cell suspension before sorting. This later measurement enabled discrimination between IgG negative tumour malignant cells and IgG positive host cells (primarily macrophages). In addition, cellular Photofrin content in 'tumour' and 'host' cells sorted by FACS was determined by chemical extraction. The measurements were performed for the time intervals 1-96 h post Photofrin administration. The data showed consistently higher Photofrin levels in the 'host cells', i.e., tumour associated macrophages (TAM), than in 'tumour' cells. On a per cell basis, at any time point studied there was a minimum of 1.7 times more Photofrin in 'host' than in 'tumour cells', while at 4-12 h postadministration, ratios of up to 3.0 times were observed. This corresponds to ratio values greater than 9, when based on Photofrin content per micrograms cell protein. PMID:1832927

  14. Paramagnetic changes in cancer: DMBA-induced tumours studied in non-lyophilized and lyophilized tissues.

    PubMed Central

    Gutierrez, P. L.; Swartz, H. M.; Wilkinson, E. J.

    1979-01-01

    Electron spin resonance (ESR) studies were made on frozen samples of 7,12 dimethylbenzanthracene (DMBA)-induced rat breast tumours both before and after lyophilization. The primary purpose of these studies was to determine the relationship between ESR spectra under these two conditions and thereby hopefully resolve an apparent conflict as to the experimental findings and clinical implications of these findings. In contrast to the other system (Walker 256 carcinosarcoma) which we studied by a similar method, in the DMBA-induced tumours we found a close parallel between the ESR spectra before and after lyophilization. In both cases free-radical levels were elevated about two-fold in all tumours and showed little dependence on the age of the tumour. Studies of blood and liver before the development of tumours showed no change in free radicals levels in either nonlyophilized or lyophilized samples. In animals with tumours, the level of free radicals in the liver increased approximately 17%. Manganese (2+) levels were increased in breast tumours but the changes did not closely follow those of free radicals and were much more variable in the lyophilized samples. We conclude that: (1) there seems to be no general relationship between ESR spectra of tumours before and after lyophilization; (2) there appears to be no general pattern of ESR changes in lyophilized samples of tumours. PMID:223619

  15. Acute changes in liver tumour perfusion measured non-invasively with arterial spin labelling

    PubMed Central

    Johnson, S Peter; Ramasawmy, Rajiv; Campbell-Washburn, Adrienne E; Wells, Jack A; Robson, Mathew; Rajkumar, Vineeth; Lythgoe, Mark F; Pedley, R Barbara; Walker-Samuel, Simon

    2016-01-01

    Background: Non-invasive measures of tumour vascular perfusion are desirable, in order to assess response to vascular targeting (or modifying) therapies. In this study, hepatic arterial spin labelling (ASL) magnetic resonance imaging (MRI) was investigated to measure acute changes in perfusion of colorectal cancer in the liver, in response to vascular disruption therapy with OXi4503. Methods: SW1222 and LS174T tumours were established in the liver of MF1 nu/nu mice via intrasplenic injection. Perfusion and R2* MRI measurements were acquired with an Agilent 9.4T horizontal bore scanner, before and at 90 min after 40 mg kg−1 OXi4503. Results: A significant decrease in SW1222 tumour perfusion was observed (−43±33%, P<0.005). LS174T tumours had a significantly lower baseline level of perfusion. Intrinsic susceptibility MRI showed a significant increase in R2* in LS174T tumours (28±25%, P<0.05). An association was found between the change in tumour perfusion and the proximity to large vessels, with pre-treatment blood flow predictive of subsequent response. Histological evaluation confirmed the onset of necrosis and evidence of heterogeneous response between tumour deposits. Conclusions: Hepatic ASL-MRI can detect acute response to targeted tumour vascular disruption entirely non-invasively. Hepatic ASL of liver tumours has potential for use in a clinical setting. PMID:27031853

  16. 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

  17. Appropriate use of tumour biomarkers for treatment with innovative drugs: A retrospective study

    PubMed Central

    MASSA, ILARIA; NANNI, ORIANA; GUIDOBONI, MASSIMO; FRASSINETI, GIOVANNI LUCA; ROCCA, ANDREA; BURGIO, MARCO ANGELO; VALMORRI, LINDA; MARRI, MATTIA; PIANCASTELLI, ALESSANDRA; FAEDI, MARINA; LEONI, MAURIZIO; TAMBERI, STEFANO; ALTINI, MATTIA; AMADORI, DINO

    2016-01-01

    Performing randomised clinical trials to address the clinical usefulness of predictive and prognostic tumour markers is a complex process for several reasons, and observational experiences may thus play an important role. The present study performed an observational retrospective analysis in Area Vasta Romagna, Italy, collecting information on tumour marker determination in 760 consecutive patients who started a new line of anticancer therapy between January and June 2010. The determination of well-known biomarkers was requested for all gastrointestinal stromal tumour (GIST) patients (n=13) and for almost all breast cancer patients (n=369), and targeted therapies were consequently prescribed. Conversely, Kirsten rat sarcoma viral oncogene homolog (KRAS) determination in colon cancer patients (n=177) was requested in ~50% of advanced cases, while epidermal growth factor receptor (EGFR) determination was required in slightly more than 30% of the same patients. EGFR and KRAS determinations were requested in only 15% and 7.5% of non-small cell lung cancer (NSCLC) patients (n=201), respectively. There would appear to be greater appropriateness of tumour marker determination for breast cancer and GISTs than for colon cancer and NSCLC. Resources can be further optimised by standardising tumour marker determinations in terms of the timing of requests and the consequent use of the results for tailored treatment planning. PMID:26870292

  18. Quantifying tumour heterogeneity with CT

    PubMed Central

    Miles, Kenneth A.

    2013-01-01

    Abstract Heterogeneity is a key feature of malignancy associated with adverse tumour biology. Quantifying heterogeneity could provide a useful non-invasive imaging biomarker. Heterogeneity on computed tomography (CT) can be quantified using texture analysis which extracts spatial information from CT images (unenhanced, contrast-enhanced and derived images such as CT perfusion) that may not be perceptible to the naked eye. The main components of texture analysis can be categorized into image transformation and quantification. Image transformation filters the conventional image into its basic components (spatial, frequency, etc.) to produce derived subimages. Texture quantification techniques include structural-, model- (fractal dimensions), statistical- and frequency-based methods. The underlying tumour biology that CT texture analysis may reflect includes (but is not limited to) tumour hypoxia and angiogenesis. Emerging studies show that CT texture analysis has the potential to be a useful adjunct in clinical oncologic imaging, providing important information about tumour characterization, prognosis and treatment prediction and response. PMID:23545171

  19. 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

  20. 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

  1. 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.

  2. Mathematical and computational models of drug transport in tumours

    PubMed Central

    Groh, C. M.; Hubbard, M. E.; Jones, P. F.; Loadman, P. M.; Periasamy, N.; Sleeman, B. D.; Smye, S. W.; Twelves, C. J.; Phillips, R. M.

    2014-01-01

    The ability to predict how far a drug will penetrate into the tumour microenvironment within its pharmacokinetic (PK) lifespan would provide valuable information about therapeutic response. As the PK profile is directly related to the route and schedule of drug administration, an in silico tool that can predict the drug administration schedule that results in optimal drug delivery to tumours would streamline clinical trial design. This paper investigates the application of mathematical and computational modelling techniques to help improve our understanding of the fundamental mechanisms underlying drug delivery, and compares the performance of a simple model with more complex approaches. Three models of drug transport are developed, all based on the same drug binding model and parametrized by bespoke in vitro experiments. Their predictions, compared for a ‘tumour cord’ geometry, are qualitatively and quantitatively similar. We assess the effect of varying the PK profile of the supplied drug, and the binding affinity of the drug to tumour cells, on the concentration of drug reaching cells and the accumulated exposure of cells to drug at arbitrary distances from a supplying blood vessel. This is a contribution towards developing a useful drug transport modelling tool for informing strategies for the treatment of tumour cells which are ‘pharmacokinetically resistant’ to chemotherapeutic strategies. PMID:24621814

  3. Anti-tumour immunity in malignant melanoma assay by tube leucocyte adherence inhibition.

    PubMed Central

    Marti, J. H.; Thomson, D. M.

    1976-01-01

    Tumour antigen-induced inhibition of leucocyte adherence was modified for use in glass test tubes (Tube LAI assay) for the study of cell-mediated anti-tumour immunity to human malignant melanoma. Peripheral blood leucocytes (PBL) of 20 out of 25 patients (80%) with active malignant melanoma responded to an extract of malignant melanoma with LAI, whereas only 4-5% of 475 control subjects showed a response. The malignant melanoma patients reacted to both allogeneic and autologous extracts of malignant melanoma which indicates a common cross-reacting antigen. Malignant melanoma patients did not respond to unrelated tumour extracts. The LAI was mediated by PBL (monocytes) "armed" with cytophilic anti-tumour antibody specific for the sensitizing tumour antigen. The anti-tumour response of the malignant melanoma patients was dependent on the stage of the cancer, and 11 out of 13 Stage I patients had a positive NAI, whereas patients with disseminated cancer had decreased response. The diminished LAI in patients with large tumour burdens appeared to be the result of release of tumour antigen systemically. Also, surgery and chemotherapy depressed LAI. Although LAI was depressed after surgical excision of the cutaneous melanoma, most patients showed LAI 1-3 months later. Tumour-free melanoma patients monitored for one year by the Tube LAI assay showed a decline in their anti-tumour immunity 5-6 months after surgery. The NAI was low or negative after the 8th post-surgical month in tumour-free patients. Patients with residual malignant melanoma showed persistent or recurrent LAI after the 8th post-surgical month. LAI reactivity monitored after "curative" surgery for malignant melanoma may assist in determining whether the patient is tumour-free or has a recurrence. PMID:962991

  4. Expression of endothelin-1 and endothelin-1 receptor A in canine mammary tumours.

    PubMed

    Restucci, B; Martano, M; Maiolino, P

    2015-06-01

    Endothelins and their receptors have been implicated in numerous diseases and have recently emerged as relevant players in a variety of malignancies. Tumours overexpress the Endothelin-1 (ET-1) and the Endothelin-A receptors (ETAR) and their interaction enhances tumour growth and metastasis by promoting tumour cell survival, proliferation and angiogenesis. In this study we have evaluated the expression of ET-1 and ETAR in 50 canine mammary tumours, compared to normal controls. Results demonstrated a progressive increase in ET-1 and ETAR expression from benign tumour to grade 1 and to grade 2 malignant mammary tumours with a decrease of expression in grade 3 carcinomas. Co-localization of ET-1 and ETAR was observed in benign mammary tumours and in G1 and G2 carcinomas, while absent in G3 carcinomas. Concluding, ET-1/ETAR can be considered reliable markers for evaluating malignancy of canine mammary tumours and could have importance for the development of specific anticancer therapies. PMID:25816929

  5. Steroid receptors in canine and human female genital tract tumours with smooth muscle differentiation.

    PubMed

    Millán, Y; Gordon, A; de los Monteros, A Espinosa; Reymundo, C; de las Mulas, J Martín

    2007-01-01

    The expression of oestrogen receptor-alpha (ERalpha) and progesterone receptor (PR) was examined in 32 canine genital tract tumours diagnosed as smooth muscle tumours (benign or malignant, pure or mixed). The immunohistochemical expression of calponin was used to assess the smooth muscle differentiation of the tumours. Nineteen human uterine leiomyomas were also examined. Calponin expression was detected in 89.3% of canine and 100% of human genital tract tumours diagnosed as leiomyomas, as well as in the majority of other tumours examined (canine or human, genital or extragenital, benign or malignant) with the exception of canine negative control tumours (cutaneous fibroma and hepatoid gland adenoma). ERalpha was found in 56.3% of canine and 52.6% of human leiomyomas, while PR was found in 84.4% of canine and 94.7% of human tumours. These results indicate that calponin is a good marker for differentiating neoplasia of the canine genital system of uncertain origin, as in human patients. They also show that canine tumours with smooth muscle differentiation of the genital tract of the bitch express steroid hormone receptors, a finding that opens up the possibility of hormone therapy. PMID:17362977

  6. Canine mammary tumours, an overview.

    PubMed

    Sleeckx, N; de Rooster, H; Veldhuis Kroeze, E J B; Van Ginneken, C; Van Brantegem, L

    2011-12-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs. PMID:21645126

  7. 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. PMID:27330416

  8. A simple, optimized method for the determination of sulphide in whole blood by GC-mS as a marker of bowel fermentation processes.

    PubMed

    Hyspler, Radomír; Tichá, Alena; Indrová, Monika; Zadák, Zdenek; Hysplerová, Lidmila; Gasparic, Jirí; Churácek, Jaroslav

    2002-04-25

    Hydrogen sulphide is produced in human large intestine by anaerobic fermentation and may play a pathogenic role. An analytical method for determination of sulphide in whole blood using an extractive alkylation technique was optimised and validated for this purpose. The sample was mixed with organic phase containing pentafluorobenzyl bromide as an alkylating agent. The benzalkonium chloride was used as a phase-transfer catalyst. The quantitative determination was performed using GC-MS technique in selected ion monitoring mode. The blood levels of sulphide of healthy controls were measured (35-80 microM/l). The method is versatile, reproducible (RSD=2.7%) and suitable for research of anaerobic fermentation in vivo. PMID:12013234

  9. Vitamins C and E treatment combined with exercise modulates oxidative stress markers in blood of patients with fibromyalgia: a controlled clinical pilot study.

    PubMed

    Nazıroğlu, Mustafa; Akkuş, Selami; Soyupek, Feray; Yalman, Kadir; Çelik, Ömer; Eriş, Sevilay; Uslusoy, Gökçen Ay

    2010-11-01

    We aimed to investigate effects of vitamins C and E (VCE) supplementation with exercise (EX) on antioxidant vitamin and lipid peroxidation (LP) levels in blood of patients with fibromyalgia (FM). A controlled study was performed on blood samples from 32 female FM patients and 30 age-matched controls. The patients were divided into three groups namely EX (n = 10), VCE (n = 11), and EX plus VCE (n = 11) after taking basal blood samples. After 12 weeks of EX and VCE supplementation, blood samples were taken once more from the patients. LP levels in plasma and erythrocytes were higher in the patients at baseline than those in controls, whereas LP levels were lower in the VCE and EX groups at the end of 12 weeks than those at baseline. Plasma concentrations of vitamins A and E and reduced glutathione were lower in the patients than those in controls and their concentrations were increased by VCE and EX. Glutathione peroxidase activity in erythrocytes was increased by VCE supplementation, with or without EX. Concentrations of β-carotene in the groups did not change with treatment. Despite the measured effects on anti-oxidative mechanisms, FM symptoms were not improved by the treatments. In conclusion, VCE with EX may protect against FM-induced oxidative stress by up-regulation of an antioxidant redox system in the plasma and erythrocytes of patients with FM. Such protective effects of VCE in the patients seemed to be greater in combination with EX than EX alone. PMID:20666654

  10. 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

  11. Pulse wave velocity as marker of preclinical arterial disease: reference levels in a uruguayan population considering wave detection algorithms, path lengths, aging, and blood pressure.

    PubMed

    Farro, Ignacio; Bia, Daniel; Zócalo, Yanina; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Alallón, Walter; Lluberas, Ricardo; Armentano, Ricardo L

    2012-01-01

    Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American) population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV) disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender); asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n = 429) were categorized according to the age decade and the blood pressure levels (at study time). All subjects represented the "reference population"; the group of subjects with optimal/normal blood pressures levels at study time represented the "normal population." Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes. PMID:22666551

  12. Pulse Wave Velocity as Marker of Preclinical Arterial Disease: Reference Levels in a Uruguayan Population Considering Wave Detection Algorithms, Path Lengths, Aging, and Blood Pressure

    PubMed Central

    Farro, Ignacio; Bia, Daniel; Zócalo, Yanina; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Alallón, Walter; Lluberas, Ricardo; Armentano, Ricardo L.

    2012-01-01

    Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard for non-invasive evaluation of aortic stiffness; absence of standardized methodologies of study and lack of normal and reference values have limited a wider clinical implementation. This work was carried out in a Uruguayan (South American) population in order to characterize normal, reference, and threshold levels of PWV considering normal age-related changes in PWV and the prevailing blood pressure level during the study. A conservative approach was used, and we excluded symptomatic subjects; subjects with history of cardiovascular (CV) disease, diabetes mellitus or renal failure; subjects with traditional CV risk factors (other than age and gender); asymptomatic subjects with atherosclerotic plaques in carotid arteries; patients taking anti-hypertensives or lipid-lowering medications. The included subjects (n = 429) were categorized according to the age decade and the blood pressure levels (at study time). All subjects represented the “reference population”; the group of subjects with optimal/normal blood pressures levels at study time represented the “normal population.” Results. Normal and reference PWV levels were obtained. Differences in PWV levels and aging-associated changes were obtained. The obtained data could be used to define vascular aging and abnormal or disease-related arterial changes. PMID:22666551

  13. [CONTENT OF OXIDATIVE STRESS MARKERS IN BLOOD PLASMA UNDER THE ACTION OF EXTRACTS OF GRATIOLA OFFICINALIS L., HELICHRYSUM ARENARIUM (L.) MOENCH, AND ANTHOCYANIN FORMS OF ZEA MAYS L].

    PubMed

    Durnova, N A; Afanas'eva, G A; Kurchatova, M N; Zaraeva, N V; Golikov, A G; Bucharskaya, A B; Golikov, A G; Bucharskaya, A B; Plastun, V O; Andreeva, N V

    2015-01-01

    The effect of aqueous solutions of dry ethanol extracts of Gratiola officinalis L., Helichrysum arenarium (L.) Moench, and anthocyanin forms of Zea mays L. on the dioxidin-induced lipid peroxidation in blood has been studied on rats. It is established that all these extracts are capable of reducing the amount of avera- ge-mass (AM) molecules and malonic dialdehyde (MDA) in rat blood plasma. The extract of Gratiola officinalis L. reduces the concentration of AM and MDA moleules by 43%. The extract of Helichrysum arenarium (L.) Moench reduces the concentration of AM molecules on the average by 18.66% (within 9.22 -34.81%) and MDA by 49.36% (within 34.12-79.75%). The Extract of anthocyanin forms of Zea mays L. does not reduce the concentration of AM mo- lecules, but reduces the amount of MDA in the blood of rats on average by 27.88% (within 21.58-37.82%) (p < 0.01). PMID:26591206

  14. 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 ...

  15. 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

  16. 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

  17. Intralymphatic mRNA vaccine induces CD8 T-cell responses that inhibit the growth of mucosally located tumours.

    PubMed

    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

  18. Hprt mutants in a transplantable murine tumour arise more frequently in vivo than in vitro.

    PubMed Central

    Wilkinson, D.; Sandhu, J. K.; Breneman, J. W.; Tucker, J. D.; Birnboim, H. C.

    1995-01-01

    A model system was developed to allow investigation of the frequency at which clastogenic and/or mutagenic events occur in situ in a transplantable murine fibrosarcoma tumour (MC1A-C1) compared with in vitro culture. The marker selected for detecting these events was the X-linked hprt (hypoxanthine-guanine phosphoribosyltransferase) gene. We found that the hprt gene in MC1A-C1 was not suitable for this purpose, most likely because multiple active copies were present. To circumvent the problem, HPRT- [6-thioguanine (6-TG)-resistant] clones were isolated by inactivating all hprt genes with methylnitrosourea. Spontaneous revertants to hypoxanthine/aminopterin/thymidine resistance (HATR) were isolated and found to be approximately 1000 times more sensitive than the parental tumour to induction of 6-TGR mutants by cobalt-60 gamma-rays. This sensitivity is expected for a heterozygous marker, these revertants may therefore possess only one functional hprt locus but two or more active X chromosomes. A clone with a stable hprt gene was identified and a neo gene was introduced. The resulting cell line (MN-11) could be grown as a subcutaneous tumour in syngeneic C57BL/6 animals. The frequency of mutations arising in vivo in the marker hprt gene could be estimated by culturing explanted tumour cells in the presence of 6-TG, using G418 selection to distinguish tumour from host cells. The frequency of mutants in MN-11 cells grown as tumours was found to be 3.4-fold higher than in tissue culture for an equivalent period of time. These data provide the first direct evidence for the existence of mutagenic factors in a tumour environment that might contribute to tumour progression. Images Figure 1 PMID:7577474

  19. Soluble fms-like tyrosine kinase-1 and endothelial adhesion molecules (intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1) as predictive markers for blood pressure reduction after renal sympathetic denervation.

    PubMed

    Dörr, Oliver; Liebetrau, Christoph; Möllmann, Helge; Gaede, Luise; Troidl, Christian; Rixe, Johannes; Hamm, Christian; Nef, Holger

    2014-05-01

    Renal sympathetic denervation (RSD) is a treatment option for patients with resistant arterial hypertension, but in some patients it is not successful. Predictive parameters on the success of RSD remain unknown. The angiogenic factors soluble fms-like tyrosine kinase-1 (sFLT-1), intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) are known to be associated with endothelial dysfunction, vascular remodeling, and hypertension. We evaluated whether sFLT-1, ICAM-1, and VCAM-1 are predictive markers for blood pressure reduction after RSD. Consecutive patients (n=55) undergoing renal denervation were included. Venous serum samples for measurement of sFlt-1, ICAM-1, and VCAM-1 were collected before and 6 months after RSD. A therapeutic response was defined as an office systolic blood pressure reduction of >10 mm Hg 6 months after RSD. A significant mean office systolic blood pressure reduction of 31.2 mm Hg was observed in 46 patients 6 months after RSD. Nine patients were classified as nonresponders, with a mean systolic blood pressure reduction of 4.6 mm Hg. At baseline, sFLT-1 levels were significantly higher in responders than in nonresponders (P<0.001) as were ICAM-1 (P<0.001) and VCAM-1 levels (P<0.01). The areas under the curve for sFLT-1, ICAM-1, and VCAM-1 were 0.82 (interquartile range, 0.718-0.921; P<0.001), 0.754 (0.654-0.854; P<0.001), and 0.684 (0.564-804; P=0.01), respectively, demonstrating prediction of an RSD response. Responders showed significantly higher serum levels of sFLT-1, ICAM-1, and VCAM-1 at baseline compared with nonresponders. Thus, this study identified for the first time potential biomarkers with a predictive value indicating a responder or nonresponder before renal denervation. PMID:24470464

  20. 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

  1. 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

  2. Small intestinal ulceration secondary to carcinoid tumour arising in a Meckel's diverticulum.

    PubMed Central

    McCluggage, W G; McConnell, L; Sloan, J M; Ellis, P K; Irwin, S T

    1999-01-01

    A solitary small intestinal ulcer associated with a carcinoid tumour in a nearby Meckel's diverticulum was found in a 77 year old man presenting with massive rectal bleeding. Angiography and a radioisotope study localised the bleeding to the ileum. At operation, the Meckel's diverticulum was identified, with bleeding from an ulcer just distal to it. Pathological examination revealed a small carcinoid tumour confined to the Meckel's diverticulum. Close to the opening of the diverticulum, within the ileum, a well demarcated ulcer was present. Histology showed a non-specific ulcer which eroded a large blood vessel. This is the first documented occurrence of solitary small intestinal ulceration in association with a carcinoid tumour. Carcinoid tumour should be added to the list of possible causes of small intestinal ulceration. The ulceration may be secondary to release of cytokines by the tumour. Images PMID:10343617

  3. 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

  4. Epidemiological and pathological features of primary cardiac tumours in dogs from Poland in 1970-2014.

    PubMed

    Janus, Izabela; Nowak, Marcin; Noszczyk-Nowak, Agnieszka; Ciaputa, Rafał; Kandefer-Gola, Małgorzata; Pasławska, Urszula; Sapierzyński, Rafał; Łopuszyński, Wojciech; Otrocka-Domagała, Iwona

    2016-03-01

    Primary heart tumours affect less than 1% of dogs. Due to their rare incidence, every research showing the frequency of cardiac tumours is valuable. Routine diagnostics is often complemented with immunohistochemical analysis. This study was conducted on 110 patient records from all veterinary faculties in Poland from dogs diagnosed with heart tumours between 1970 and 2014. The dogs' age, breed and sex with tumour localisation and histopathological diagnosis were analysed. Because of its most common incidence, samples of haemangiosarcoma underwent further examination with assessment of the expression of cell markers that have not been evaluated earlier (i.e. minichromosome maintenance proteins and beta-catenin). We noted 111 tumours including 88.3% malignant and 10.8% benign ones. Haemangiosarcoma and aortic body tumour were the most frequent cardiac neoplasms in the dogs examined (45.9% and 27.9% of all tumours, respectively). Immunohistochemical analysis of haemangiosarcoma showed a positive expression of all markers examined. CD31, vimentin, and beta-catenin showed a positive reaction in all 11 samples examined. At least one proliferative marker (Ki-67, MCM-3 or MCM-7) showed a positive reaction in each sample. MCM-3 showed a higher expression than the two other proliferative markers (P = 0.006), but only Ki-67 showed a positive correlation with the mitotic index (P > 0.05, r = 0.89). Although beta-catenin, MCM-3 and MCM-7 showed a positive reaction in the haemangiosarcomas examined, their usefulness as diagnostic and prognostic factors should be a topic of further research. PMID:26919146

  5. Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis

    PubMed Central

    Mei, Z; Liu, Y; Liu, C; Cui, A; Liang, Z; Wang, G; Peng, H; Cui, L; Li, C

    2014-01-01

    Background: The role of tumour-infiltrating inflammation in the prognosis of patients with colorectal cancer (CRC) has not been fully evaluated. The primary objective of our meta-analysis was to determine the impact of tumour-infiltrating inflammation on survival outcomes. Methods: Ovid MEDLINE and EMBASE were searched to identify studies reporting the prognostic significance of tumour-infiltrating inflammation for patients with CRC. The primary outcome measures were overall survival (OS), cancer-specific survival (CS) and disease-free survival (DFS). Results: A total of 30 studies involving 2988 patients were identified. Studies were subdivided into those considering the associations between CRC survival and generalised tumour inflammatory infiltrate (n=12) and T lymphocyte subsets (n=18). Pooled analyses revealed that high generalised tumour inflammatory infiltrate was associated with good OS (HR, 0.59; 95% CI, 0.48–0.72), CS (HR, 0.40; 95% CI, 0.27–0.61) and DFS (HR, 0.72; 95% CI, 0.57–0.91). Stratification by location and T lymphocyte subset indicated that in the tumour centre, CD3+, CD8+ and FoxP3+ infiltrates were not statistically significant prognostic markers for OS or CS. In the tumour stroma, high CD8+, but not CD3+ or FoxP3+ cell infiltrates indicated increased OS. Furthermore, high CD3+ cell infiltrate was detected at the invasive tumour margin in patients with good OS and DFS; and high CCR7+ infiltrate was also indicated increased OS. Conclusion: Overall, high generalised tumour inflammatory infiltrate could be a good prognostic marker for CRC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes to increase the robustness of the analyses. PMID:24504370

  6. Plasma haemostatic markers, endothelial function and ambulatory blood pressure changes with home versus hospital cardiac rehabilitation: the Birmingham Rehabilitation Uptake Maximisation Study

    PubMed Central

    Lee, K W; Blann, A D; Jolly, K; Lip, G Y H

    2006-01-01

    Background Cardiac rehabilitation is an accepted therapeutic intervention in patients after myocardial infarction or coronary revascularisation. The effects of cardiac rehabilitation programmes, whether home based or hospital based, on haemostatic indices (as reflected by fibrinogen, plasma viscosity, fibrin D‐dimer (an index of thrombogenesis), von Willebrand factor (vWf, an index of endothelial damage/dysfunction), soluble P‐selectin (an index of platelet activation)), vasomotor function (using flow‐mediated dilatation (FMD)) and ambulatory blood pressure (ABP) in patients with coronary heart disease are unknown. Methods 81 patients (66 men, mean (SD) 59 (11) years) after myocardial infarction or coronary revascularisation were randomised to comprehensive hospital‐based (n = 40) or home‐based (n = 41) cardiac rehabilitation. Plasma levels of vWf, D‐dimer, fibrinogen, soluble P‐selectin and plasma viscosity, as well as FMD and 24‐h ABP, were measured at baseline and after 3 months of cardiac rehabilitation. Results In patients who completed cardiac rehabilitation, levels of vWf, fibrinogen and D‐dimer were significantly lower and FMD improved (all p⩽0.001), whereas levels were unchanged in controls. Significant reductions were also observed in 24‐h mean systolic blood pressure, diastolic blood pressure and mean aortic pressure after completion of cardiac rehabilitation (all p<0.05). No significant differences were observed between the hospital‐based and home‐based cardiac rehabilitation programmes on these indices. Conclusions Cardiac rehabilitation improves haemostasis, endothelial function and ABP in patients with coronary heart disease, with no significant differences between home‐based and hospital‐based cardiac rehabilitation programmes. These effects may contribute to the beneficial effects of cardiac rehabilitation programmes on CV outcomes. PMID:16807272

  7. Repeated measurements of blood lactate concentration as a prognostic marker in horses with acute colitis evaluated with classification and regression trees (CART) and random forest analysis.

    PubMed

    Petersen, M B; Tolver, A; Husted, L; Tølbøll, T H; Pihl, T H

    2016-07-01

    The objective of this study was to investigate the prognostic value of single and repeated measurements of blood l-lactate (Lac) and ionised calcium (iCa) concentrations, packed cell volume (PCV) and plasma total protein (TP) concentration in horses with acute colitis. A total of 66 adult horses admitted with acute colitis (<24 h) to a referral hospital in the 2002-2011 period were included. The prognostic value of Lac, iCa, PCV and TP recorded at admission and 6 h post admission was analysed with univariate analysis, logistic regression, classification and regression trees, as well as random forest analysis. Ponies and Icelandic horses made up 59% of the population, whilst the remaining 41% were horses. Blood lactate concentration at admission was the only individual parameter significantly associated with probability of survival to discharge (P < 0.001). In a training sample, a Lac cut-off value of 7 mmol/L had a sensitivity of 0.66 and a specificity of 0.92 in predicting survival. In independent test data, the sensitivity was 0.69 and the specificity was 0.76. At the observed survival rate (38%), the optimal decision tree identified horses as non-survivors when the Lac at admission was ≥4.3 mmol/L and the Lac 6 h post admission stayed at >2 mmol/L (sensitivity, 0.72; specificity, 0.8). In conclusion, blood lactate concentration measured at admission and repeated 6 h later aided the prognostic evaluation of horses with acute colitis in this population with a very high mortality rate. This should allow clinicians to give a more reliable prognosis for the horse. PMID:27240909

  8. The radiation response of cells from 9L gliosarcoma tumours is correlated with [F18]-EF5 uptake

    PubMed Central

    KOCH, CAMERON J.; SHUMAN, ANNE L.; JENKINS, WALTER T.; KACHUR, ALEXANDER V.; KARP, JOEL S.; FREIFELDER, RICHARD; DOLBIER, WILLIAM R.; EVANS, SYDNEY M.

    2014-01-01

    Purpose Tumour hypoxia affects cancer biology and therapy-resistance in both animals and humans. The purpose of this study was to determine whether EF5 ([2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide]) binding and/or radioactive drug uptake correlated with single-dose radiation response in 9L gliosarcoma tumours. Materials and methods Twenty-two 9L tumours were grown in male Fischer rats. Rats were administered low specific activity 18F-EF5 and their tumours irradiated and assessed for cell survival and hypoxia. Hypoxia assays included EF5 binding measured by antibodies against bound-drug adducts and gamma counts of 18F-EF5 tumour uptake compared with uptake by normal muscle and blood. These assays were compared with cellular radiation response (in vivo to in vitro assay). In six cases, uptake of tumour versus muscle was also assayed using images from a PET (positron emission tomography) camera (PENN G-PET). Results The intertumoural variation in radiation response of 9L tumour-cells was significantly correlated with uptake of 18F-labelled EF5 (i.e., including both bound and non-bound drug) using either tumour to muscle or tumour to blood gamma count ratios. In the tumours where imaging was performed, there was a significant correlation between the image analysis and gamma count analysis. Intertumoural variation in cellular radiation response of the same 22 tumours was also correlated with mean flow cytometry signal due to EF5 binding. Conclusion To our knowledge, this is the first animal model/drug combination demonstrating a correlation of radioresponse for tumour-cells from individual tumours with drug metabolism using either immunohistochemical or non-invasive techniques. PMID:19995239

  9. Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

    PubMed Central

    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. PMID:27009516

  10. 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

  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. PMID:26838446

  13. 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.

  14. AFP mRNA level in enriched circulating tumor cells from hepatocellular carcinoma patient blood samples is a pivotal predictive marker for metastasis.

    PubMed

    Jin, Junhua; Niu, Xiaojuan; Zou, Lihui; Li, Lin; Li, Shugang; Han, Jingli; Zhang, Peiying; Song, Jinghai; Xiao, Fei

    2016-08-01

    Circulating tumor cells (CTCs) quantification may be helpful for evaluating cancer dissemination, predicting prognosis and assessing therapeutic effectiveness and safety. In the present study, CTCs from blood samples of 72 patients with hepatocellular carcinoma (HCC) were enriched with anti-EpCAM nanoparticles. AFP mRNA level was detected by nested polymerase chain reaction (PCR) after enrichment of CTCs from HCC blood samples at 0, 3, 6, 9 and 12 months after hepatectomy, respectively. AFP mRNA expression in CTCs was positive in 43 patients (59.7%) and negative in 29 patients (40.3%) before hepatectomy. Among 43 patients with positive AFP mRNA expression in CTCs before hepatectomy, 10 and 11 were diagnosed as intrahepatic/extrahepatic metastasis before and after hepatectomy, respectively. In addition, these 21 patients with metastasis had persisting positive AFP mRNA of CTCs during the whole tested year. Specifically, 3 patients with AFP mRNA negative in CTCs before hepatectomy changed to be positive at 6 and 9 months, and 2 of them were diagnosed as metastasis 12 months after hepatectomy. We conclude that the positive AFP mRNA of CTCs can be a pivotal predictor for HCC metastasis before and after hepatectomy. The release of AFP expression from hepatocellular carcinoma cells into circulation must be a major source of HCC metastasis. PMID:27160647

  15. The peritoneal tumour microenvironment of high-grade serous ovarian cancer.

    PubMed

    Leinster, D Andrew; Kulbe, Hagen; Everitt, Gemma; Thompson, Richard; Perretti, Mauro; Gavins, Felicity N E; Cooper, Dianne; Gould, David; Ennis, Darren P; Lockley, Michelle; McNeish, Iain A; Nourshargh, Sussan; Balkwill, Frances R

    2012-06-01

    High-grade serous ovarian cancer (HGSC) disseminates early and extensively throughout the peritoneal space, causing multiple lesions that are a major clinical problem. The aim of this study was to investigate the cellular composition of peritoneal tumour deposits in patient biopsies and their evolution in mouse models using immunohistochemistry, intravital microscopy, confocal microscopy, and 3D modelling. Tumour deposits from the omentum of HGSC patients contained a prominent leukocyte infiltrate of CD3(+) T cells and CD68(+) macrophages, with occasional neutrophils. Alpha-smooth muscle actin(+) (α-SMA(+) ) pericytes and/or fibroblasts surrounded these well-vascularized tumour deposits. Using the murine bowel mesentery as an accessible mouse peritoneal tissue that could be easily imaged, and two different transplantable models, we found multiple microscopic tumour deposits after i.p. injection of malignant cells. Attachment to the peritoneal surface was rapid (6-48 h) with an extensive CD45(+) leukocyte infiltrate visible by 48 h. This infiltrate persisted until end point and in the syngeneic murine ID8 model, it primarily consisted of CD3(+) T lymphocytes and CD68(+) macrophages with α-SMA(+) cells also involved from the earliest stages. A majority of tumour deposits developed above existing mesenteric blood vessels, but in avascular spaces new blood vessels tracked towards the tumour deposits by 2-3 weeks in the IGROV-1 xenografts and 6 weeks in the ID8 syngeneic model; a vigorous convoluted blood supply was established by end point. Inhibition of tumour cell cytokine production by stable expression of shRNA to CXCR4 in IGROV-1 cells did not influence the attachment of cells to the mesentery but delayed neovascularization and reduced tumour deposit size. We conclude that the multiple peritoneal tumour deposits found in HGSC patients can be modelled in the mouse. The techniques described here may be useful for assessing treatments that target the disseminated

  16. Tumours of the upper alimentary tract.

    PubMed

    Head, K W

    1976-01-01

    Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals. PMID:1086147

  17. Histone modifications patterns in tissues and tumours from acute promyelocytic leukemia xenograft model in response to combined epigenetic therapy.

    PubMed

    Valiulienė, Giedrė; Treigytė, Gražina; Savickienė, Jūratė; Matuzevičius, Dalius; Alksnė, Milda; Jarašienė-Burinskaja, Rasa; Bukelskienė, Virginija; Navakauskas, Dalius; Navakauskienė, Rūta

    2016-04-01

    Xenograft models are suitable for in vivo study of leukemia's pathogenesis and the preclinical development of anti-leukemia agents but understanding of epigenetic regulatory mechanisms linking to adult cell functions in pathological conditions during different in vivo treatments is yet unknown. In this study, for the first time epigenetic chromatin modifications were characterized in tissues and tumours from murine xenograft model generated using the human acute promyelocytic leukemia (APL) NB4 cells engrafted in immunodeficient NOG mice. Xenografts were subjected to combined epigenetic treatment by histone deacetylase inhibitor Belinostat, histone methyltransferase inhibitor 3-DZNeaplanocin A and all-trans-retinoic acid based on in vitro model, where such combination inhibited NB4 cell growth and enhanced retinoic acid-induced differentiation to granulocytes. Xenotransplantation was assessed by peripheral blood cells counts, the analysis of cell surface markers (CD15, CD33, CD45) and the expression of certain genes (PML-RAR alpha, CSF3, G-CSFR, WT1). The combined treatment prolonged APL xenograft mice survival and prevented tumour formation. The analysis of the expression of histone marks such as acetylation of H4, trimethylation of H3K4, H3K9 and H3K27 in APL xenograft mice tumours and tissues demonstrated tissue-specific changes in the level of histone modifications and the APL prognostic mark, WT1 protein. In summary, the effects of epigenetic agents used in this study were positive for leukemia prevention and linked to a modulation of the chromatin epigenetic environment in adult tissues of malignant organism. PMID:27044813

  18. Spectrin repeat containing nuclear envelope 1 and forkhead box protein E1 are promising markers for the detection of colorectal cancer in blood.

    PubMed

    Melotte, Veerle; Yi, Joo Mi; Lentjes, Marjolein H F M; Smits, Kim M; Van Neste, Leander; Niessen, Hanneke E C; Wouters, Kim A D; Louwagie, Joost; Schuebel, Kornel E; Herman, James G; Baylin, Stephen B; van Criekinge, Wim; Meijer, Gerrit A; Ahuja, Nita; van Engeland, Manon

    2015-02-01

    Identifying biomarkers in body fluids may improve the noninvasive detection of colorectal cancer. Previously, we identified N-Myc downstream-regulated gene 4 (NDRG4) and GATA binding protein 5 (GATA5) methylation as promising biomarkers for colorectal cancer in stool DNA. Here, we examined the utility of NDRG4, GATA5, and two additional markers [Forkhead box protein E1 (FOXE1) and spectrin repeat containing nuclear envelope 1 (SYNE1)] promoter methylation as biomarkers in plasma DNA. Quantitative methylation-specific PCR was performed on plasma DNA from 220 patients with colorectal cancer and 684 noncancer controls, divided in a training set and a test set. Receiver operating characteristic analysis was performed to measure the area under the curve of GATA5, NDRG4, SYNE1, and FOXE1 methylation. Functional assays were performed in SYNE1 and FOXE1 stably transfected cell lines. The sensitivity of NDRG4, GATA5, FOXE1, and SYNE1 methylation in all stages of colorectal cancer (154 cases, 444 controls) was 27% [95% confidence interval (CI), 20%-34%), 18% (95% CI, 12%-24%), 46% (95% CI, 38%-54%), and 47% (95% CI, 39%-55%), with a specificity of 95% (95% CI, 93%-97%), 99% (95% CI, 98%-100%), 93% (95% CI, 91%-95%), and 96% (95% CI, 94%-98%), respectively. Combining SYNE1 and FOXE1, increased the sensitivity to 56% (95% CI, 48%-64%), while the specificity decreased to 90% (95% CI, 87%-93%) in the training set and to 58% sensitivity (95% CI, 46%-70%) and 91% specificity (95% CI, 80%-100%) in a test set (66 cases, 240 controls). SYNE1 overexpression showed no major differences in cell proliferation, migration, and invasion compared with controls. Overexpression of FOXE1 significantly decreased the number of colonies in SW480 and HCT116 cell lines. Overall, our data suggest that SYNE1 and FOXE1 are promising markers for colorectal cancer detection. PMID:25538088

  19. HCG blood test - qualitative

    MedlinePlus

    ... qualitative Images Blood test References Lee P, Pincus MR, McPherson RA. Diagnosis and management of cancer using serologic tumor markers. In: McPherson RA, Pincus MR, eds. Henry's Clinical Diagnosis and Management by Laboratory ...

  20. Cord Blood Adiponectin and Visfatin Concentrations in relation to Oxidative Stress Markers in Neonates Exposed and Nonexposed In Utero to Tobacco Smoke

    PubMed Central

    Ambroszkiewicz, Jadwiga; Gajewska, Joanna; Rowicka, Grażyna; Maciejewski, Tomasz M.; Mazur, Joanna

    2016-01-01

    Aims. Maternal smoking is considered as a source of oxidative stress, which has been implicated to disrupted adipokines expression in adipose tissue. We examined the relationship between selected adipokines and markers of oxidative stress/antioxidant defence in the umbilical cord of neonates exposed and nonexposed in utero to tobacco smoke. Methods. Subjects including 85 healthy neonates (born to 41 smokers and 44 nonsmokers) were tested for adiponectin, visfatin, oxidized low density lipoprotein (ox-LDL), total oxidant capacity (TOC), and total antioxidant capacity (TAC). Results. Cord serum visfatin, ox-LDL, and TOC were significantly higher (p < 0.001) but adiponectin and TAC were lower (p < 0.001 and p < 0.05, resp.) in smoking group than in tobacco abstinents. In whole group of children (adjusted for smoking status, gender, and birth weight) adiponectin showed negative and visfatin positive correlations with ox-LDL. In the model estimated separately for smokers ox-LDL explained 36% of adiponectin and 35.5% of visfatin variance, while in the model of nonsmokers it explained 36.8% and 69.4%, respectively. Conclusion. Maternal smoking enhances oxidative status and depletes antioxidant potential in newborns. Lower level of adiponectin and higher visfatin concentration seem to be related with a less beneficial oxidative stress profile and higher level of lipid peroxidation in neonates exposed and nonexposed in utero to tobacco smoke. PMID:27525051

  1. Kinetics of /sup 13/N-ammonia uptake in myocardial single cells indicating potential limitations in its applicability as a marker of myocardial blood flow

    SciTech Connect

    Rauch, B.; Helus, F.; Grunze, M.; Braunwell, E.; Mall, G.; Hasselbach, W.; Kuebler, W.

    1985-02-01

    To study kinetics and principles of cellular uptake of /sup 13/N-ammonia, a marker of coronary perfusion in myocardial scintigraphy, heart muscle cells of adult rats were isolated by perfusion with collagenase and hyaluronidase. Net uptake of /sup 13/N, measured by flow dialysis, reached equilibrium within 20 sec in the presence of sodium bicarbonate and carbon dioxide (pH 7.4, 37 degrees C). Total extraction, 80 sec after the reaction start, was 786 +/- 159 mumol/ml cell volume. Cells destroyed by calcium overload were unable to extract /sup 13/N-ammonia. Omission of bicarbonate and carbon dioxide reduced total extraction to 36% of control. /sup 13/N-Ammonia uptake could also be reduced by 50 muM 4,4' diisothiocyanostilbene 2,2' disulfonic acid, by 100 micrograms/ml 1-methionine sulfoximine, and by preincubation with 5 muM free oleic acid. These results indicate that in addition to metabolic trapping by glutamine synthetase, the extraction of /sup 13/N-ammonia by myocardial cells is influenced by cell membrane integrity, intracellular-extracellular pH gradient, and possibly an anion exchange system for bicarbonate. For this reason, the uptake of /sup 13/N-ammonia may not always provide a valid measurement of myocardial perfusion.

  2. Oncoprotein stability after tumour resection.

    PubMed Central

    Ong, G.; Gullick, W.; Sikora, K.

    1990-01-01

    The means by which oncogenes and their products activate malignant transformation are currently under intense investigation. However, published papers on experiments using human tumour material do not always report in detail their methods of collection or storage of the specimens. In order to assess the stability of oncogene encoded proteins following collection or storage of human tumour biopsies, we have examined the rate of decay of the c-myc, neu and EGF-receptor proteins. Solid tumours, containing amplified copies of each oncogene, were established in nude mice and the stability of the oncogene protein in portions of each tumour, left in phosphate buffered saline at room temperature for varying time intervals, was examined by immunoblotting. Intact EGF-receptor and neu oncoproteins were present even after 24 h under these conditions while the c-myc protein was apparently rapidly degraded after 20 min. These data demonstrate that oncogene products decay at different rates after tumour resection and that collection of human biopsies should take this into account in order to provide the basis for consistent measurements of protein expression. Images Figure 1 Figure 2 Figure 3 PMID:2139576

  3. Expression of Merozoite Surface Protein Markers by Plasmodium falciparum-Infected Erythrocytes in Peripheral Blood and Tissues of Children with Fatal Malaria▿

    PubMed Central

    Dobaño, Carlota; Rogerson, Stephen J.; Taylor, Terrie E.; McBride, Jana S.; Molyneux, Malcolm E.

    2007-01-01

    Sequestration of Plasmodium falciparum-infected erythrocytes is a pathological feature of fatal cerebral malaria. P. falciparum is genetically diverse among, and often within, patients. Preferential sequestration of certain genotypes might be important in pathogenesis. We compared circulating parasites with parasites sequestered in the brain, spleen, liver, and lung in the same Malawian children with fatal malaria, classifying serotypes using antibodies to merozoite surface proteins 1 and 2 and immunofluorescence in order to differentiate parasites and to quantify the proportions of each serotype. We found (i) similar distributions of various serotypes in different tissues and (ii) concordance between parasite serotypes in peripheral blood and parasite serotypes in tissues. No serotypes predominated in the brain in cerebral malaria, and parasites belonging to a single serotype did not cluster within individual vessels or within single tissues. These findings do not support the hypothesis that cerebral malaria is caused by cerebral sequestration of certain virulent types. PMID:17118989

  4. γ-Herpesvirus Load as Surrogate Marker of Early Death in HIV-1 Lymphoma Patients Submitted to High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation

    PubMed Central

    Pratesi, Chiara; Zanussi, Stefania; Tedeschi, Rosamaria; Bortolin, Maria Teresa; Talamini, Renato; Rupolo, Maurizio; Scaini, Chiara; Basaglia, Giancarlo; Di Maso, Matteo; Mazzucato, Mario; Zanet, Ernesto; Tirelli, Umberto; Michieli, Mariagrazia; Carbone, Antonino; De Paoli, Paolo

    2015-01-01

    Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12135 copies/mL) and 18 patients (median 417 copies/106 PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11–98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient’s therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT. PMID:25668032

  5. γ-Herpesvirus load as surrogate marker of early death in HIV-1 lymphoma patients submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation.

    PubMed

    Pratesi, Chiara; Zanussi, Stefania; Tedeschi, Rosamaria; Bortolin, Maria Teresa; Talamini, Renato; Rupolo, Maurizio; Scaini, Chiara; Basaglia, Giancarlo; Di Maso, Matteo; Mazzucato, Mario; Zanet, Ernesto; Tirelli, Umberto; Michieli, Mariagrazia; Carbone, Antonino; De Paoli, Paolo

    2015-01-01

    Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12,135 copies/mL) and 18 patients (median 417 copies/10(6) PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT. PMID:25668032

  6. Canine Mammary Mixed Tumours: A Review

    PubMed Central

    Dantas Cassali, Geovanni; Cavalheiro Bertagnolli, Angélica; Ferreira, Enio; Araújo Damasceno, Karine; de Oliveira Gamba, Conrado; Bonolo de Campos, Cecília

    2012-01-01

    Mammary mixed tumours are the most frequent neoplasias in female dogs. In humans, mixed tumours are frequently found in the salivary glands and are known as pleomorphic adenomas. In addition to their histomorphologic similarities, mixed tumours and pleomorphic adenomas have the potential to become malignant and give rise to carcinomas in mixed tumours and carcinomas ex-pleomorphic adenoma, respectively. The factors associated with malignant transformation are still poorly known in the case of canine mixed tumours. However, this form of neoplasia tends to be associated with a better prognosis than other malignant histological types. This paper discusses the main features associated with female canine mammary mixed tumours. PMID:23193497

  7. Identification of prognostic factors in canine mammary malignant tumours: a multivariable survival study

    PubMed Central

    2013-01-01

    Background Although several histopathological and clinical features of canine mammary gland tumours have been widely studied from a prognostic standpoint, considerable variations in tumour individual biologic behaviour difficult the definition of accurate prognostic factors. It has been suggested that the malignant behaviour of tumours is the end result of several alterations in cellular physiology that culminate in tumour growth and spread. Accordingly, the aim of this study was to determine, using a multivariable model, the independent prognostic value of several immunohistochemically detected tumour-associated molecules, such as MMP-9 and uPA in stromal cells and Ki-67, TIMP-2 and VEGF in cancer cells. Results Eighty-five female dogs affected by spontaneous malignant mammary neoplasias were followed up for a 2-year post-operative period. In univariate analysis, tumour characteristics such as size, mode of growth, regional lymph node metastases, tumour cell MIB-1 LI and MMP-9 and uPA expressions in tumour-adjacent fibroblasts, were associated with both survival and disease-free intervals. Histological type and grade were related with overall survival while VEGF and TIMP-2 were not significantly associated with none of the outcome parameters. In multivariable analysis, only a MIB-1 labelling index higher than 40% and a stromal expression of MMP-9 higher than 50% retained significant relationships with poor overall and disease-free survival. Conclusions The results of this study indicate that MMP-9 and Ki-67 are independent prognostic markers of canine malignant mammary tumours. Furthermore, the high stromal expressions of uPA and MMP-9 in aggressive tumours suggest that these molecules are potential therapeutic targets in the post-operative treatment of canine mammary cancer. PMID:23289974

  8. Dietary Zinc Deficiency Affects Blood Linoleic Acid: Dihomo-γ-linolenic Acid (LA:DGLA) Ratio; a Sensitive Physiological Marker of Zinc Status in Vivo (Gallus gallus)

    PubMed Central

    Reed, Spenser; Qin, Xia; Ran-Ressler, Rinat; Brenna, James Thomas; Glahn, Raymond P.; Tako, Elad

    2014-01-01

    Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio. Diets identical in composition were formulated and two groups of birds (n = 12) were randomly separated upon hatching into two diets, Zn(+) (zinc adequate control, 42.3 μg/g zinc), and Zn(−) (zinc deficient, 2.5 μg/g zinc). Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn(+) control versus Zn(−) group (p < 0.05). Hepatic TNF-α, IL-1β, and IL-6 gene expression were higher in the Zn(+) control group (p < 0.05), and hepatic Δ6 desaturase was significantly higher in the Zn(+) group (p < 0.001). The LA:DGLA ratio was significantly elevated in the Zn(−) group compared to the Zn(+) group (22.6 ± 0.5 and 18.5 ± 0.5, % w/w, respectively, p < 0.001). This study suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc adequate and zinc deficient birds, and may be a sensitive biomarker to assess dietary zinc manipulation. PMID:24658588

  9. Dietary zinc deficiency affects blood linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio; a sensitive physiological marker of zinc status in vivo (Gallus gallus).

    PubMed

    Reed, Spenser; Qin, Xia; Ran-Ressler, Rinat; Brenna, James Thomas; Glahn, Raymond P; Tako, Elad

    2014-01-01

    Zinc is a vital micronutrient used for over 300 enzymatic reactions and multiple biochemical and structural processes in the body. To date, sensitive and specific biological markers of zinc status are still needed. The aim of this study was to evaluate Gallus gallus as an in vivo model in the context of assessing the sensitivity of a previously unexplored potential zinc biomarker, the erythrocyte linoleic acid: dihomo-γ-linolenic acid (LA:DGLA) ratio. Diets identical in composition were formulated and two groups of birds (n = 12) were randomly separated upon hatching into two diets, Zn⁺ (zinc adequate control, 42.3 μg/g zinc), and Zn⁻ (zinc deficient, 2.5 μg/g zinc). Dietary zinc intake, body weight, serum zinc, and the erythrocyte fatty acid profile were measured weekly. At the conclusion of the study, tissues were collected for gene expression analysis. Body weight, feed consumption, zinc intake, and serum zinc were higher in the Zn⁺ control versus Zn⁻ group (p < 0.05). Hepatic TNF-α, IL-1β, and IL-6 gene expression were higher in the Zn⁺ control group (p < 0.05), and hepatic Δ⁶ desaturase was significantly higher in the Zn⁺ group (p < 0.001). The LA:DGLA ratio was significantly elevated in the Zn⁻ group compared to the Zn⁺ group (22.6 ± 0.5 and 18.5 ± 0.5, % w/w, respectively, p < 0.001). This study suggests erythrocyte LA:DGLA is able to differentiate zinc status between zinc adequate and zinc deficient birds, and may be a sensitive biomarker to assess dietary zinc manipulation. PMID:24658588

  10. 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

  11. Brown tumour of the jaw

    PubMed Central

    Nair, Preeti P; Gharote, Harshkant P; Thomas, Shaji; R, Guruprasad; Singh, Neha

    2011-01-01

    Brown tumours are classic bony lesions that arise as a result of the effect of parathyroid hormone on bone tissue in some patients with hyperparathyroidism. They are erosive bony lesions caused by rapid osteolysis and peritrabecular fibrosis, resulting in a local destructive phenomenon. Facial skeleton is involved in about 2% of all cases of which the mandible is frequently affected. A 35-year-old female who was diagnosed with osteomalacia and brown tumour in posterior mandible as the sign of secondary hyperparathyroidism secondary to vitamin D deficiency is presented. PMID:22669885

  12. A rare urinary bladder tumour

    PubMed Central

    Haddad-Lacle, Judella Edwina Maria; Haddad, Charles Joseph; Villas, Bruce

    2014-01-01

    This case report describes a 54-year-old man who presented to his primary care physician with low back pain. During his workup, an incidental finding of a bladder mass was diagnosed. He underwent transurethral resection of the bladder tumour and the resulting pathology was consistent with extra nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). Presentation of MALT lymphoma in the urinary bladder is rare. This malignancy is more commonly found in the stomach. The prognosis for this rare tumour is excellent. Our patient showed no sign of recurrence with transurethral excision and radiation alone. PMID:24835803

  13. Survival in rectal cancer is predicted by T cell infiltration of tumour-associated lymphoid nodules

    PubMed Central

    McMullen, T P W; Lai, R; Dabbagh, L; Wallace, T M; de Gara, C J

    2010-01-01

    Lymphoid nodules are a normal component of the mucosa of the rectum, but little is known about their function and whether they contribute to the host immune response in malignancy. In rectal cancer specimens from patients with local (n = 18), regional (n = 12) and distant (n = 10) disease, we quantified T cell (CD3, CD25) and dendritic cell (CD1a, CD83) levels at the tumour margin as well as within tumour-associated lymphoid nodules. In normal tissue CD3+, but not CD25+, T cells are concentrated at high levels within lymphoid nodules, with significantly fewer cells found in surrounding normal mucosa (P = 0·001). Mature (CD83), but not immature (CD1a), dendritic cells in normal tissue are also found clustered almost exclusively within lymphoid nodules (P = < 0·0001). In rectal tumours, both CD3+ T cells (P = 0·004) and CD83+ dendritic cells (P = 0·0001) are also localized preferentially within tumour-associated lymphoid nodules. However, when comparing tumour specimens to normal rectal tissue, the average density of CD3+ T cells (P = 0·0005) and CD83+ dendritic cells (P = 0·0006) in tumour-associated lymphoid nodules was significantly less than that seen in lymphoid nodules in normal mucosa. Interestingly, regardless of where quantified, T cell and dendritic cell levels did not depend upon the stage of disease. Increased CD3+ T cell infiltration of tumour-associated lymphoid nodules predicted improved survival, independent of stage (P = 0·05). Other T cell (CD25) markers and different levels of CD1a+ or CD83+ dendritic cells did not predict survival. Tumour-associated lymphoid nodules, enriched in dendritic cells and T cells, may be an important site for antigen presentation and increased T cell infiltration may be a marker for improved survival. PMID:20408858

  14. Elevated tissue Cr levels, increased plasma oxidative markers, and global hypomethylation of blood DNA in male Sprague-Dawley rats exposed to potassium dichromate in drinking water.

    PubMed

    Wang, Yu; Wu, Wei; Yao, Chunji; Lou, Jianlin; Chen, Riping; Jin, Lingzhi; Wu, Nanxiang; Gao, Ming; Song, Peng; Tan, Yufeng; Liu, Kecheng

    2016-09-01

    Hexavalent chromium [Cr (VI)] is prevalent in ground water in some areas, but evidence on the toxic effects of Cr (VI) via ingestion through drinking water remains insufficient. The aims of our study were to investigate the toxic effects of Cr (VI) through oral water ingestion on oxidative stress and DNA methylation. Thirty-two Sprague-Dawley rats were randomly divided into four groups, and exposed to porassium dichromate (K2 Cr2 O7 ; 0, 30, 100, and 300 mg/L) in drinking water for 4 weeks. Mean body weight gain, mean water consumption, clinical chemistry determinations, and oxidative stress levels in plasma were measured. Global DNA methylation changes and DNA methylation status at the promoter of p16 gene were also detected. After 4 weeks, mild anemic effects and increased plasma malondialdehyde (MDA) levels occurred in rats exposed to 100 mg/L or 300 mg/L of Cr (VI). Plasma glutathione peroxidase (GSH-Px) activity decreased in all exposed groups. Global DNA methylation levels were reduced in 100 mg/L and 300 mg/L exposure groups. However, DNA methylation status at the promoter of P16 gene remained unchanged in all K2 Cr2 O7- treated groups. The correlation analysis indicated that increased MDA levels were closely correlated to global DNA hypomethylation. Our results indicated that oral ingestion of Cr (VI) through drinking water caused not only oxidative stress in plasma, but also global DNA hypomethylation in blood cells from male rats, and a good correlation was found between increased MDA levels and reduced global DNA methylation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1080-1090, 2016. PMID:25846368

  15. Low body weight gain, low white blood cell count and high serum ferritin as markers of poor nutrition and increased risk for preterm delivery.

    PubMed

    Hsu, Wen-Yin; Wu, Cheng-Hsuan; Hsieh, Charles Tsung-Che; Lo, Hui-Chen; Lin, Jen-Shiou; Kao, Mei-Ding

    2013-01-01

    This study determined factors of preterm delivery in Taiwan. Healthy women (n=520, age 29.1±4.2 y) at 8-12 weeks of pregnancy were recruited from prenatal clinics. Background information, anthropometrics, biochemical parameters, and dietary intake, collected by 24 h-recall were obtained from the first, second, and third trimesters to delivery. Clinical outcomes of neonates were also collected. The results show that 53.7% of women were primiparous and that the incidence of preterm delivery was 6.2%. Body weight gains in the first trimester and throughout pregnancy were significantly lower in mothers with preterm delivery (preterm group) than in mothers with term delivery (term group, p<0.05). Maternal cholesterol intake, circulating white blood cell counts (WBC) and serum albumin were significantly lower and that serum magnesium and ferritin were significantly higher in the preterm group than in the term group. Maternal weight gain was positively correlated with caloric and nutrient intake (p<0.05). Neonatal birth weight was positively correlated with maternal weight gain and intakes of protein and phosphate during pregnancy; with intakes of calories, vitamin B-1 and B-2 in the first trimester; and with intakes of calcium, magnesium, iron and zinc, as well as circulating WBC in the third trimester. However, neonatal birth weight was negatively correlated with serum iron in the third trimester and with serum iron and ferritin at the time of delivery. In conclusion, maternal weight gain in early pregnancy and WBC, mineral intake and iron status in late pregnancy seem to be major factors affecting delivery and neonatal outcomes. PMID:23353616

  16. Reduction of weight loss and tumour size in a cachexia model by a high fat diet.

    PubMed Central

    Tisdale, M. J.; Brennan, R. A.; Fearon, K. C.

    1987-01-01

    An attempt has been made to reverse cachexia and to selectively deprive the tumour of metabolic substrates for energy production by feeding a ketogenic regime, since ketone bodies are considered important in maintaining homeostasis during starvation. As a model we have used a transplantable mouse adenocarcinoma of the colon (MAC 16) which produces extensive weight loss without a reduction in food intake. When mice bearing the MAC16 tumour were fed on diets in which up to 80% of the energy was supplied as medium chain triglycerides (MCT) with or without arginine 3-hydroxybutyrate host weight loss was reduced in proportion to the fat content of the diet, and there was also a reduction in the percentage contribution of the tumour to the final body weight. The increase in carcass weight in tumour-bearing mice fed high levels of MCT was attributable to an increase in both the fat and the non-fat carcass mass. Blood levels of free fatty acids (FFA) were significantly reduced by MCT addition. The levels of both acetoacetate and 3-hydroxybutyrate were elevated in mice fed the high fat diets, and tumour-bearing mice fed the normal diet did not show increased plasma levels of ketone bodies over the non-tumour-bearing group despite the loss of carcass lipids. Both blood glucose and plasma insulin levels were reduced in mice bearing the MAC16 tumour and this was not significantly altered by feeding the high fat diets. The elevation in ketone bodies may account for the retention of both the fat and the non-fat carcass mass. This is the first example of an attempt to reverse cachexia by a diet based on metabolic differences between tumour and host tissues, which aims to selectively feed the host at the expense of the tumour. PMID:3620317

  17. Structural Adaptation of Normal and Tumour Vascular Networks

    PubMed Central

    Secomb, Timothy W.; Dewhirst, Mark W.; Pries, Axel R.

    2012-01-01

    Vascular networks are dynamic structures, adapting to changing conditions by structural remodelling of vessel diameters and by growth of new vessels and regression of existing vessels. The vast number of blood vessels in the circulatory system, more than 109, implies that vessels’ arrangement and structure are not under individual genetic control but emerge as a result of generic responses of each segment to the various stimuli that it experiences. To obtain insight into the types of response that are needed, a network-oriented approach has been used, in which theoretical models are used to simulate structural adaptation in vascular networks, and the results are compared with experimental observations. With regard to the structural control of vessel diameters, this approach shows that responses to both haemodynamic and metabolic stimuli are needed for the formation of functionally adequate and efficient network structures. Furthermore, information transfer in both upstream and downstream directions is essential for balancing flows between long and short flow pathways. Otherwise, functional shunting occurs, that is, short pathways become enlarged and flow bypasses longer pathways. Information transfer in the upstream direction is achieved by conducted responses communicated along vessel walls. Simulations of structural adaptation in tumour microvascular networks indicate that impaired vascular communication, resulting in functional shunting, may be an important factor causing the dysfunctional microcirculation and local hypoxia typically observed in tumours. Anti-angiogenic treatment of tumours may restore vascular communication and thereby improve or normalize flow distribution in tumour vasculature. PMID:21995550

  18. Brain tumour mortality in immigrants.

    PubMed

    Neutel, C I; Quinn, A; Brancker, A

    1989-03-01

    All Canadian deaths due to malignant brain tumour for the years 1970-73 were identified and analysed for country of birth. The years 1970-73 were chosen since in later years country of birth was no longer available for each death. The brain tumour population consisted of 1551 male and 1058 female deaths and matched controls were chosen from deaths due to other causes. Americans who died of brain tumour in Canada had a standardized mortality ratio (SMR) of 1.0 compared to their fellow Americans in the USA. Italian, German, Dutch and British immigrants had SMR between 1.5 and 2.6 compared to rates in their home countries and between 1.24 and 2.09 when compared to Canadian rates. A series of graphs shows the increased risk for male immigrants quite dramatically, and indicates that for females the increases were less pronounced. Further analysis showed that the excess risk is confined to those who were born in Western Europe while their Canadian-born children experienced the same rates as all Canadians. Based on the limited information available, occupation could not be shown to play a role in establishing risk. An attempt was made to pinpoint the years of immigration which showed the greatest risk. It is concluded that the determination of risk of brain tumour has a strong environmental component. The possibilities for identification of this component are discussed. PMID:2722385

  19. 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

  20. 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

  1. Radical surgical resection for giant primary mediastinal endodermal sinus tumour with pulmonary metastasis after chemotherapy: can be curative

    PubMed Central

    Chaudhry, Ikram Ulhaq; Rahhal, Mohammed; Khurshid, Imtiaz; Mutairi, Hadi

    2014-01-01

    Primary non-seminomatous germ cell tumours of anterior mediastinum are uncommon. Endodermal sinus tumour of the anterior mediastinum (yolk sac) is a rare but lethal neoplasm. We present a case of an 18-year-old man who presented with chest pain, cough and haemosputum with markedly raised serum α-fetoprotein (AFP) levels above 112 000 ng/mL. Chest roentgenogram and CT showed a giant anterior mediastinal mass. CT guided biopsy revealed a diagnosis of endodermal sinus tumour. After the completion of chemotherapy, extensive surgical resection was carried out along with the right lung metastastectomy. Five years postresection follow-up the patient is disease free with normal serum tumour markers. This is the longest survival ever reported of such tumours with highest AFP level (>112 000 ng/mL) and lung metastasis. PMID:24939455

  2. A Multicenter Pilot Study Examining the Role of Circulating Tumor Cells as a Blood-Based Tumor Marker in Patients with Extensive Small-Cell Lung Cancer

    PubMed Central

    Huang, Chao H.; Wick, Jo A.; Sittampalam, Gurusingham Sitta; Nirmalanandhan, Victor Sanjit; Ganti, Apar Kishor; Neupane, Prakash C.; Williamson, Stephen K.; Godwin, Andrew K.; Schmitt, Sarah; Smart, Nora J.; Spencer, Sarah; Van Veldhuizen, Peter J.

    2014-01-01

    Background: Small-cell lung cancer (SCLC), a variant of lung cancer marked by early metastases, accounts for 13% of all lung cancers diagnosed in US. Despite high response rates to treatment, it is an aggressive disease with a median survival of 9–11 months for patients with extensive stage (EX-SCLC). Detection of circulating tumor cells (CTCs) is a novel laboratory technique currently in use to determine response to therapy and to predict prognosis in breast, colorectal, and prostate cancer. We initiated a pilot study to analyze the role of CTCs as a biomarker of response and relapse in patients with EX-SCLC. Methods: We collected blood samples from chemotherapy naïve patients with EX-SCLC prior to initiation of therapy, after completion of systemic therapy, and follow-up every 6–8 weeks and at relapse. The number of CTCs was determined using the cell search system in a central laboratory. The study was conducted in four different sites, and it was reviewed and approved by respective research review committees and IRBs. Results: We enrolled 26 patients with EX-SCLC, 1 was excluded due to ineligibility, all were treated with platinum and etoposide. We observed partial response in 16 patients, stable disease in 3 patients, 1 patient with disease progression, and 6 patients were not assessed (5 deceased, 1 not available). The overall median number of CTCs in 24 patients measured at baseline and post-tx was 75 (range 0–3430) and 2 (range 0–526), respectively. A significant reduction in CTCs from baseline to post-treatment was identified for 15 subjects; the median reduction was 97.4% (range −100 to +100%, p < 0.001). Higher baseline CTCs and percentage change in post-treatment CTCs were associated with decreased survival. Conclusion: We demonstrated that it is feasible to detect CTCs in EX-SCLC. If validated in other prospective studies, CTCs could be a useful biomarker in the management of EX-SCLC by predicting patients’ clinical responses to

  3. Role of senescence marker p16 INK4a measured in peripheral blood T-lymphocytes in predicting length of hospital stay after coronary artery bypass surgery in older adults.

    PubMed

    Pustavoitau, Aliaksei; Barodka, Viachaslau; Sharpless, Norman E; Torrice, Chad; Nyhan, Daniel; Berkowitz, Dan E; Shah, Ashish S; Bandeen Roche, Karen J; Walston, Jeremy D

    2016-02-01

    Adults older than 65 years undergo more than 120,000 coronary artery bypass (CAB) procedures each year in the United States. Chronological age alone, though commonly used in prediction models of outcomes after CAB, does not alone reflect variability in aging process; thus, the risk of complications in older adults. We performed a prospective study to evaluate a relationship between senescence marker p16(INK4a) expression in peripheral blood T-lymphocytes (p16 levels in PBTLs) with aging and with perioperative outcomes in older CAB patients. We included 55 patients age 55 and older, who underwent CAB in Johns Hopkins Hospital between September 1st, 2010 and March 25th, 2013. Demographic, clinical and laboratory data following outline of the Society of Thoracic Surgeons data collection form was collected, and p16 mRNA levels in PBTLs were measured using TaqMan® qRT-PCR. Associations between p16 mRNA levels in PBTLs with length of hospital stay, frailty status, p16 protein levels in the aortic and left internal mammary artery tissue, cerebral oxygen saturation, and augmentation index as a measure of vascular stiffness were measured using regression analyses. Length of hospital stay was the primary outcome of interest, and major organ morbidity, mortality, and discharge to a skilled nursing facility were secondary outcomes. In secondary analysis, we evaluated associations between p16 mRNA levels in PBTLs and interleukin-6 levels using regression analyses. Median age of enrolled patients was 63.5 years (range 56-81 years), they were predominantly male (74.55%), of Caucasian descent (85.45%). Median log2(p16 levels in PBTLs) were 4.71 (range 1.10-6.82). P16 levels in PBTLs were significantly associated with chronological age (mean difference 0.06 for each year increase in age, 95% CI 0.01-0.11) and interleukin 6 levels (mean difference 0.09 for each pg/ml increase in IL-6 levels, 95% CI 0.01-0.18). There were no significant associations with frailty status, augmentation

  4. Malignancy markers in the cerebrospinal fluid.

    PubMed

    Koskiniemi, M

    1988-10-01

    The specificity and sensitivity of malignancy marker determinations in cerebrospinal fluid (CSF) are often insufficient. Even at the subclinical stage of the disease the marker should be present. The effect of therapy should be monitored and relapses noted. Thus high standards of methodology are required. There are many substances that may indicate a malignant process in the central nervous system. However, there are many pitfalls in their determination. Malignant cells may occur in CSF via processes involving leptomeningeal structures such as metastases and leukaemia, but primary brain tumours seldom show cells in CSF. Human chorionic gonadotrophin and alpha-fetoprotein determinations assist in the early detection of cerebral germ cell tumours and of relapses, even in the subclinical stage. Desmosterol may aid in the diagnosis of medulloblastomas and malignant gliomas and in monitoring therapy. Putrescine levels are elevated in CSF of patients with medulloblastoma and correlate with the clinical state, and serial analyses may reveal relapses. Fibronectin, when determined in CSF at the time of diagnosis, appears to be of great significance for the prognosis of acute lymphoblastic leukaemia. Ferritin and beta-2-microglobulin may help in some well-defined conditions. Brain-specific proteins and antibodies to them are non-specific markers whereas tumour-specific antigens and growth factors may be more significant. PMID:3058481

  5. Extramedullary myeloid cell tumours--the NIMS experience.

    PubMed

    Paul, T Roshni; Sundaram, C; Gayathri, K; Prayaga, Aruna; Rao, D Raghunadha

    2005-07-01

    Extramedullary myeloid cell tumours are rare clinical entities, which often pose diagnostic problems. From the pathology record files of Nizam's Institute of Medical Sciences, Hyderabad, 16 cases of EMCTs were traced, over a period of 14 years. The clinical details, follow-up were noted and morphology re-evaluated, and immunohistochemistry with LCA was performed. Of the 16 cases, the distribution was as follows--skin and subcutaneous nodules, lymph nodes, extradural masses presenting with cord compression and one case each with eyelid, orbital and breast masses. The problems in diagnosis are presented and a panel of immunohistochemical markers suggested for proper diagnosis and treatment. PMID:16761741

  6. Endothelial CD276 (B7-H3) expression is increased in human malignancies and distinguishes between normal and tumour-derived circulating endothelial cells

    PubMed Central

    Kraan, J; van den Broek, P; Verhoef, C; Grunhagen, D J; Taal, W; Gratama, J W; Sleijfer, S

    2014-01-01

    Background: Mature circulating endothelial cells (CEC) are surrogate markers of endothelial damage. CEC measured in patients with advanced cancer are thought not only to derive from damaged normal vasculature (n-CEC), but also from damaged (t-CEC). Therefore, assays that allow the discrimination between these two putative types of CEC are thought to improve the specificity of the enumeration of CEC in cancer. Methods: Identification of tumour-associated endothelial markers (TEM) by comparing antigen expression on normal vs t-CEC and assess the presence of t-CEC in peripheral blood of cancer patients by incorporating TEM in our novel flow cytometry-based CEC detection assay. Results: No difference in antigen expression between normal and malignant endothelial cells (ECs) was found for CD54, CD109, CD137, CD141, CD144 and CXCR7. In contrast, overexpression for CD105, CD146, CD276 and CD309 was observed in tumour ECs compared with normal ECs. CD276 was most differentially expressed and chosen as a marker for further investigation. CD276-expressing CEC were significantly higher in 15 patients with advanced colorectal cancer (median 9 (range 1–293 cell per 4 ml); P<0.005), in 83 patients with a glioblastoma multiforme (median 10 (range 0–804); P<0.0001) and in 14 patients with advanced breast cancer (median 14 (range 0–390) P<0.05) as compared with 24 healthy individuals (median 3 (range 0–11)). Of all patients with malignancies, 58% had CD276+ CEC counts above the ULN (8 cell per 4 ml). Conclusions: The present study shows that CD276 can be used to discriminate ECs from malignant tissue from ECs from normal tissue. In addition, CD276+ CEC do occur in higher frequencies in patients with advanced cancer. PMID:24892449

  7. 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

  8. Newly-derived neuroblastoma cell lines propagated in serum-free media recapitulate the genotype and phenotype of primary neuroblastoma tumours.

    PubMed

    Bate-Eya, Laurel T; Ebus, Marli E; Koster, Jan; den Hartog, Ilona J M; Zwijnenburg, Danny A; Schild, Linda; van der Ploeg, Ida; Dolman, M Emmy M; Caron, Huib N; Versteeg, Rogier; Molenaar, Jan J

    2014-02-01

    Recently protocols have been devised for the culturing of cell lines from fresh tumours under serum-free conditions in defined neural stem cell medium. These cells, frequently called tumour initiating cells (TICs) closely retained characteristics of the tumours of origin. We report the isolation of eight newly-derived neuroblastoma TICs from six primary neuroblastoma tumours and two bone marrow metastases. The primary tumours from which these TICs were generated have previously been fully typed by whole genome sequencing (WGS). Array comparative genomic hybridisation (aCGH) analysis showed that TIC lines retained essential characteristics of the primary tumours and exhibited typical neuroblastoma chromosomal aberrations such as MYCN amplification, gain of chromosome 17q and deletion of 1p36. Protein analysis showed expression for neuroblastoma markers MYCN, NCAM, CHGA, DBH and TH while haematopoietic markers CD19 and CD11b were absent. We analysed the growth characteristics and confirmed tumour-forming potential using sphere-forming assays, subcutaneous and orthotopic injection of these cells into immune-compromised mice. Affymetrix mRNA expression profiling of TIC line xenografts showed an expression pattern more closely mimicking primary tumours compared to xenografts from classical cell lines. This establishes that these neuroblastoma TICs cultured under serum-free conditions are relevant and useful neuroblastoma tumour models. PMID:24321263

  9. Animal models of tumour-associated epilepsy.

    PubMed

    Kirschstein, Timo; Köhling, Rüdiger

    2016-02-15

    Brain tumours cause a sizeable proportion of epilepsies in adulthood, and actually can be etiologically responsible also for childhood epilepsies. Conversely, seizures are often first clinical signs of a brain tumour. Nevertheless, several issues of brain-tumour associated seizures and epilepsies are far from understood, or clarified regarding clinical consensus. These include both the specific mechanisms of epileptogenesis related to different tumour types, the possible relationship between malignancy and seizure emergence, the interaction between tumour mass and surrounding neuronal networks, and - not least - the best treatment options depending on different tumour types. To investigate these issues, experimental models of tumour-induced epilepsies are necessary. This review concentrates on the description of currently used models, focusing on methodological aspects. It highlights advantages and shortcomings of these models, and identifies future experimental challenges. PMID:26092434

  10. Haemangioleiomyomatous tumour of the lung.

    PubMed Central

    Soorae, A S; Bharucha, H

    1980-01-01

    A case of haemangioleiomyomatous tumour of the lung, occurring as a peripheral, solitary nodule in an asymptomatic 54-year-old man is presented. The tumour was well-demarcated and microscopically it was characterised by the presence of vascular spaces with endothelial, pericytic, and, predominantly, smooth muscle proliferation. Islands of cartilage and slit-like spaces lined by bronchial epithelium make this a hamartomatous lesion of a quite distinctive and unusual variety, which does not fit any of the well-recognised patterns of hamartomas previously described. The long-term prognosis after limited excision is considered to be favourable. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7358861

  11. Interferon regulatory factor-8 modulates the development of tumour-induced CD11b+Gr-1+ myeloid cells.

    PubMed

    Stewart, Trina J; Greeneltch, Kristy M; Reid, Julia E; Liewehr, David J; Steinberg, Seth M; Liu, Kebin; Abrams, Scott I

    2009-09-01

    Tumour-induced myeloid-derived suppressor cells (MDSC) promote immune suppression and mediate tumour progression. However, the molecular basis for the generation of MDSC, which in mice co-express the CD11b(+) and Gr-1(+) cell surface markers remains unclear. Because CD11b(+)Gr-1(+) cells expand during progressive tumour growth, this suggests that tumour-induced events alter signalling pathways that affect normal myeloid cell development. Interferon regulatory factor-8 (IRF-8), a member of the IFN-gamma regulatory factor family, is essential for normal myelopoiesis. We therefore examined whether IRF-8 modulated tumour-induced CD11b(+)Gr-1(+) cell development or accumulation using both implantable (4T1) and transgenic (MMTV-PyMT) mouse models of mammary tumour growth. In the 4T1 model, both splenic and bone marrow-derived CD11b(+)Gr-1(+) cells of tumour-bearing mice displayed a marked reduction in IRF-8 expression compared to control populations. A causal link between IRF-8 expression and the emergence of tumour-induced CD11b(+)Gr-1(+) cells was explored in vivo using a double transgenic (dTg) mouse model designed to express transgenes for both IRF-8 and mammary carcinoma development. Despite the fact that tumour growth was unaffected, splenomegaly, as well as the frequencies and absolute numbers of CD11b(+)Gr-1(+) cells were significantly lower in dTg mice when compared with single transgenic tumour-bearing mice. Overall, these data reveal that IRF-8 plays an important role in tumour-induced development and/or accumulation of CD11b(+)Gr-1(+) cells, and establishes a molecular basis for the potential manipulation of these myeloid populations for cancer therapy. PMID:20196788

  12. Hypoxia-mediated tumour targeting.

    PubMed

    Binley, K; Askham, Z; Martin, L; Spearman, H; Day, D; Kingsman, S; Naylor, S

    2003-04-01

    Hypoxia is a common physiological feature of tumours. It activates a signalling cascade that culminates in the stabilization of the HIF-1 transcription factor and activation of genes that possess a hypoxia response element (HRE). We have used an optimized hypoxia responsive promoter (OBHRE) to investigate hypoxia-targeted gene expression in vivo in the context of an adenovirus vector. The OBHRE promoter showed limited activity in the liver or spleen such that expression was 1000-fold lower than that driven by the strong CMV/IE promoter. However, in the context of the tumour microenvironment, the OBHRE promoter achieved expression levels comparable to that of the CMV/IE promoter. Next, we showed that an adenovirus expressing the human cytochrome P450 (CYP2B6) regulated by the OBHRE promoter delays tumour growth in response to the prodrug cyclophosphamide (CPA). Finally, we exploited the hepatotropism of adenovirus to investigate whether the OBHRE promoter could mitigate the hepatotoxicity of a recombinant adenovirus expressing thymidine kinase (TK) in the context of the prodrug ganciclovir (GCV). High-dose Ad.CMVTK/GCV treatment caused significant liver necrosis whereas the same dose of Ad.HRETK was well tolerated. These in vivo data demonstrate that hypoxia-targeted gene expression via the OBHRE promoter can be used to increase the therapeutic window of cytotoxic cancer gene therapy. PMID:12646859

  13. Arteriolar oxygenation in tumour and subcutaneous arterioles: effects of inspired air oxygen content.

    PubMed Central

    Dewhirst, M. W.; Ong, E. T.; Rosner, G. L.; Rehmus, S. W.; Shan, S.; Braun, R. D.; Brizel, D. M.; Secomb, T. W.

    1996-01-01

    Carbogen is thought to be more effective than normobaric oxygen in reducing tumour hypoxia because it may reduce hyperoxic vasoconstriction. In this study, tumour and normal arteriolar diameters were measured simultaneously with perivascular pO2 during air breathing followed by either carbogen or 100% oxygen to determine whether the action of carbogen is the result of alterations in feeding vessel diameter. Fischer-344 rats bearing dorsal flap window chambers, with or without implanted R3230AC tumours, were the experimental subjects. Arteriolar diameters were measured using optical techniques and perivascular pO2 was measured using recessed-tip electrodes (3-6 microns tip diameter). Baseline arteriolar pO2 averaged 30-50% of blood gas pO2 (mean = 97 mmHg). Both hyperoxic gases increased blood gas pO2 by 4-to 5-fold, but relative improvements in arteriolar pO2 were < or = 2.5 for all arterioles studied. This means that these normobaric high O2 gases are not very efficient in increasing O2 delivery to tumours. In addition, improvements in tumour arteriolar pO2 were transient for both hyperoxic gases. Oxygen and carbogen caused no change and mild vasodilatory responses in tumour arterioles, respectively. Normal arterioles on the other hand, tended toward vasoconstriction by carbogen breathing. Peri-arteriolar pO2 in tumours increased within the first 5 min of breathing either hyperoxic gas, followed by a decline back toward values seen with air-breathing. These results suggest that temporal changes in tumour oxygenation after exposure to carbogen or O2 may not be due to changes in perfusion. Other factors, such as changes in O2 consumption rate may be involved. PMID:8763889

  14. Sensitive capture of circulating tumour cells by functionalized graphene oxide nanosheets

    NASA Astrophysics Data System (ADS)

    Yoon, Hyeun Joong; Kim, Tae Hyun; Zhang, Zhuo; Azizi, Ebrahim; Pham, Trinh M.; Paoletti, Costanza; Lin, Jules; Ramnath, Nithya; Wicha, Max S.; Hayes, Daniel F.; Simeone, Diane M.; Nagrath, Sunitha

    2013-10-01

    The spread of cancer throughout the body is driven by circulating tumour cells (CTCs). These cells detach from the primary tumour and move from the bloodstream to a new site of subsequent tumour growth. They also carry information about the primary tumour and have the potential to be valuable biomarkers for disease diagnosis and progression, and for the molecular characterization of certain biological properties of the tumour. However, the limited sensitivity and specificity of current methods for measuring and studying these cells in patient blood samples prevents the realization of their full clinical potential. The use of microfluidic devices is a promising method for isolating CTCs. However, the devices are reliant on three-dimensional structures, which limits further characterization and expansion of cells on the chip. Here we demonstrate an effective approach to isolating CTCs from blood samples of pancreatic, breast and lung cancer patients, by using functionalized graphene oxide nanosheets on a patterned gold surface. CTCs were captured with high sensitivity at a low concentration of target cells (73 +/- 32.4% at 3-5 cells per ml blood).

  15. Proteomics of thyroid tumours provides new insights into their molecular composition and changes associated with malignancy

    PubMed Central

    Martínez-Aguilar, Juan; Clifton-Bligh, Roderick; Molloy, Mark P.

    2016-01-01

    Around 5% of the general population have palpable thyroid nodules. Although most thyroid tumours are benign, thyroid cancer represents the most common malignancy of the endocrine system, comprising mainly follicular and papillary thyroid carcinomas. Previous studies have shed some light on the molecular pathogenesis of thyroid cancer but there have not been any comprehensive mass spectrometry-based proteomic studies of large scale to reveal protein expression differences between thyroid tumours and the molecular alterations associated with tumour malignancy. We applied data-independent acquisition mass spectrometry which enabled quantitative expression analysis of over 1,600 proteins from 32 specimens to compare normal thyroid tissue with the three most common tumours of the thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma. In follicular tumours, we found marked reduction of the tumour suppressor and therapeutic target extracellular protein decorin. We made the novel observation that TGFβ-induced protein ig-h3 (TGFBI) was found frequently overexpressed in follicular carcinoma compared with follicular adenoma. Proteomic pathway analysis showed changes in papillary carcinoma were associated with disruption of cell contacts (loss of E-cadherin), actin cytoskeleton dynamics and loss of differentiation markers, all hallmarks of an invasive phenotype. PMID:27025787

  16. Proteomics of thyroid tumours provides new insights into their molecular composition and changes associated with malignancy.

    PubMed

    Martínez-Aguilar, Juan; Clifton-Bligh, Roderick; Molloy, Mark P

    2016-01-01

    Around 5% of the general population have palpable thyroid nodules. Although most thyroid tumours are benign, thyroid cancer represents the most common malignancy of the endocrine system, comprising mainly follicular and papillary thyroid carcinomas. Previous studies have shed some light on the molecular pathogenesis of thyroid cancer but there have not been any comprehensive mass spectrometry-based proteomic studies of large scale to reveal protein expression differences between thyroid tumours and the molecular alterations associated with tumour malignancy. We applied data-independent acquisition mass spectrometry which enabled quantitative expression analysis of over 1,600 proteins from 32 specimens to compare normal thyroid tissue with the three most common tumours of the thyroid gland: follicular adenoma, follicular carcinoma and papillary carcinoma. In follicular tumours, we found marked reduction of the tumour suppressor and therapeutic target extracellular protein decorin. We made the novel observation that TGFβ-induced protein ig-h3 (TGFBI) was found frequently overexpressed in follicular carcinoma compared with follicular adenoma. Proteomic pathway analysis showed changes in papillary carcinoma were associated with disruption of cell contacts (loss of E-cadherin), actin cytoskeleton dynamics and loss of differentiation markers, all hallmarks of an invasive phenotype. PMID:27025787

  17. Lungs and subcutaneous metastases from a solitary fibrous tumour of the pancreas

    PubMed Central

    Tesfom, Meron F.; Caldwell, Carole; Hanasoge, Raveesh; Bramhall, Simon R.

    2015-01-01

    Solitary fibrous tumour is an uncommon mesenchymal neoplasm previously thought to only originate from the pleura; it is seen only rarely in an extra-pleural location. We report the first case of pancreatic solitary fibrous tumour in an 87-year-old woman that has metastasized to the lungs and subcutaneous tissue. We have identified a solitary mass excised from the groin region, which is positive for CD34 and vimentic marker with high proliferative rate, nuclear atypia and cellular necrosis. Imaging studies confirmed a slow-growing solitary mass in the uncinate lobe of the pancreas with evidence of lung metastasis. PMID:26612261

  18. Targeting breast to brain metastatic tumours with death receptor ligand expressing therapeutic stem cells

    PubMed Central

    Bagci-Onder, Tugba; Du, Wanlu; Figueiredo, Jose-Luiz; Martinez-Quintanilla, Jordi

    2015-01-01

    Characterizing clinically relevant brain metastasis models and assessing the therapeutic efficacy in such models are fundamental for the development of novel therapies for metastatic brain cancers. In this study, we have developed an in vivo imageable breast-to-brain metastasis mouse model. Using real time in vivo imaging and subsequent composite fluorescence imaging, we show a widespread distribution of micro- and macro-metastasis in different stages of metastatic progression. We also show extravasation of tumour cells and the close association of tumour cells with blood vessels in the brain thus mimicking the multi-foci metastases observed in the clinics. Next, we explored the ability of engineered adult stem cells to track metastatic deposits in this model and show that engineered stem cells either implanted or injected via circulation efficiently home to metastatic tumour deposits in the brain. Based on the recent findings that metastatic tumour cells adopt unique mechanisms of evading apoptosis to successfully colonize in the brain, we reasoned that TNF receptor superfamily member 10A/10B apoptosis-inducing ligand (TRAIL) based pro-apoptotic therapies that induce death receptor signalling within the metastatic tumour cells might be a favourable therapeutic approach. We engineered stem cells to express a tumour selective, potent and secretable variant of a TRAIL, S-TRAIL, and show that these cells significantly suppressed metastatic tumour growth and prolonged the survival of mice bearing metastatic breast tumours. Furthermore, the incorporation of pro-drug converting enzyme, herpes simplex virus thymidine kinase, into therapeutic S-TRAIL secreting stem cells allowed their eradication post-tumour treatment. These studies are the first of their kind that provide insight into targeting brain metastasis with stem-cell mediated delivery of pro-apoptotic ligands and have important clinical implications. PMID:25910782

  19. Photodynamic therapy augments the efficacy of oncolytic vaccinia virus against primary and metastatic tumours in mice

    PubMed Central

    Gil, M; Bieniasz, M; Seshadri, M; Fisher, D; Ciesielski, M J; Chen, Y; Pandey, R K; Kozbor, D

    2011-01-01

    Background: Therapies targeted towards the tumour vasculature can be exploited for the purpose of improving the systemic delivery of oncolytic viruses to tumours. Photodynamic therapy (PDT) is a clinically approved treatment for cancer that is known to induce potent effects on tumour vasculature. In this study, we examined the activity of PDT in combination with oncolytic vaccinia virus (OVV) against primary and metastatic tumours in mice. Methods: The effect of 2-[1-hexyloxyethyl-]-2-devinyl pyropheophorbide-a (HPPH)-sensitised-PDT on the efficacy of oncolytic virotherapy was investigated against subcutaneously implanted syngeneic murine NXS2 neuroblastoma and human FaDu head and neck squamous cell carcinoma xenografts in nude mice. Treatment efficacy was evaluated by monitoring tumour growth and survival. The effects of combination treatment on vascular function were examined using magnetic resonance imaging (MRI) and immunohistochemistry, whereas viral replication in tumour cells was analysed by a standard plaque assay. Normal tissue phototoxicity following PDT-OV treatment was studied using the mouse foot response assay. Results: Combination of PDT with OVV resulted in inhibition of primary and metastatic tumour growth compared with either monotherapy. PDT-induced vascular disruption resulted in higher intratumoural viral titres compared with the untreated tumours. Five days after delivery of OVV, there was a loss of blood flow to the interior of tumour that was associated with infiltration of neutrophils. Administration of OVV did not result in any additional photodynamic damage to normal mouse foot tissue. Conclusion: These results provide evidence into the usefulness of PDT as a means of enhancing intratumoural replication and therapeutic efficacy of OV. PMID:21989183

  20. Quantitative RT-PCR assessment of melanoma cells in peripheral blood during immunotherapy for metastatic melanoma.

    PubMed

    Schmidt, H; Sørensen, B S; von der Maase, H; Bang, C; Agger, R; Hokland, M; Nexo, E

    2002-12-01

    Circulating malignant cells in peripheral blood are thought to be precursors and surrogate markers of distant metastases and hence markers of a poor clinical outcome. In this study, we used the detection of MART-1 and tyrosinase (TYR) mRNA with a quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay to identify circulating melanoma cells. Blood samples were obtained from 35 patients with metastatic melanoma before, during and after treatment with interleukin-2, interferon-alpha and cisplatin. In addition, MART-1 and TYR protein was identified by immunohistochemistry in consecutive biopsies from 15 of the patients. Analysis of three daily blood samples for 3 days demonstrated that four out of 11 patients examined were negative for both markers on all occasions, and two patients were positive for both markers on all occasions but one. The remaining five patients showed sporadic low positive results for one or the other of the two markers. By comparing the immunohistochemistry results from consecutive biopsies with the RT-PCR results, we demonstrated that patients with MART-1 and TYR protein in their tumour cells had circulating MART-1 and TYR mRNA in 77% and 54% of the cases, respectively. During treatment, the majority of patients who were positive for MART-1 and TYR mRNA converted to being negative. However, these conversions did not significantly correlate with objective response. The presence of TYR mRNA in one of the first two samples showed a trend towards being an independent prognostic factor for poor survival. PMID:12459648

  1. Fertility sparing treatment in borderline ovarian tumours

    PubMed Central

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10–15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  2. Fertility sparing treatment in borderline ovarian tumours.

    PubMed

    Alvarez, Rosa Maria; Vazquez-Vicente, Daniel

    2015-01-01

    Borderline ovarian tumours are low malignant potential tumours. They represent 10-15% of all epithelial ovarian malignancies. Patients with this type of tumour are younger at the time of diagnosis than patients with invasive ovarian cancer. Most of them are diagnosed in the early stages and have an excellent prognosis. It has been quite clearly established that the majority of borderline ovarian tumours should be managed with surgery alone. Because a high proportion of women with this malignancy are young and the prognosis is excellent, the preservation of fertility is an important issue in the management of these tumours. In this systemic review of the literature, we have evaluated in-depth oncological safety and reproductive outcomes in women with borderline ovarian tumours treated with fertility-sparing surgery, reviewing the indications, benefits, and disadvantages of each type of conservative surgery, as well as new alternative options to surgery to preserve fertility. PMID:25729420

  3. Photodynamic therapy using intravenous delta-aminolaevulinic acid-induced protoporphyrin IX sensitisation in experimental hepatic tumours in rats.

    PubMed Central

    Svanberg, K.; Liu, D. L.; Wang, I.; Andersson-Engels, S.; Stenram, U.; Svanberg, S.

    1996-01-01

    The efficacy of photodynamic therapy (PDT) using delta-aminolaevulinic acid (ALA)-induced protoporphyrin IX (PpIX) sensitisation and laser light at 635 nm was investigated in the treatment of experimental hepatic tumours. The model of liver tumours was induced either by local inoculation or by administration of tumour cells through the portal vein in rats. ALA at a dose of 60 mg kg(-1) b.w. was intravenously administered 60 min before PDT. PpIX accumulation in tumour, normal liver and abdominal wall muscle was detected by means of laser-induced fluorescence (LIF). Laser Doppler imaging (LDI) was used to determine changes in the superficial blood flow in connection with PDT. Histopathological examinations were performed to evaluate the PDT effects on the tumour and the surrounding liver tissue, including pathological features in the microvascular system. The accumulation of PpIX, as monitored by LIF, showed high fluorescence intensities at about 635 nm in both the hepatic tumour tissue and normal liver and low values in the abdominal wall. LDI demonstrated that the blood flow in the treated tumour and its surrounding normal liver tissue decreased immediately after the PDT, indicating an effect on the vascular system. A large number of thrombi in the irradiated tumour were found microscopically 3 h after the PDT. The tumour growth rate showed a marked decrease when evaluated 3 and 6 days after the treatment. These results show that the ALA-PDT is effective in the inhibition of growth of experimental hepatic tumours. Images Figure 4 Figure 5 Figure 7 Figure 9 PMID:8932330

  4. Malignant Leydig cell tumour of the testis.

    PubMed

    Powari, Manish; Kakkar, Nandita; Singh, S K; Rai, R S; Jogai, Sanjay

    2002-01-01

    A case of malignant Leydig cell tumour is presented. It is a rare primary malignant tumour of the testis and occurs exclusively in adults. The present case is of interest because it occurred at the young age of 25 years which is rare. Histologically it showed almost all features which suggest malignancy and also had metastases to the lungs and liver. The clinical details and pathology of this tumour are discussed. PMID:11803271

  5. Tumours of the liver and biliary system

    PubMed Central

    Ponomarkov, V.; Mackey, L. J.

    1976-01-01

    In this histological classification of liver and gall bladder tumours the tumour types largely correspond to those found in man. The most common tumours in this group are liver cell adenoma, hepatocellular carcinoma, and cholangiocarcinoma. ImagesFig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 1Fig. 2Fig. 3Fig. 4Fig. 9Fig. 10Fig. 11Fig. 12 PMID:1086149

  6. Vaginal canine transmissible venereal tumour associated with intra-tumoural Leishmania spp. amastigotes in an asymptomatic female dog.

    PubMed

    Kegler, K; Habierski, A; Hahn, K; Amarilla, S P; Seehusen, F; Baumgärtner, W

    2013-01-01

    A 2-year-old female boxer dog was presented with a vaginal serosanguineous discharge not associated with oestrus. There was a friable mass occupying the upper caudal part of the vagina. Cytological and histological examination revealed a monomorphic population of neoplastic round cells consistent with canine transmissible venereal tumour (TVT). In addition, Leishmania spp. amastigotes were found within the neoplastic tissue. In order to characterize whether the amastigotes were present inside macrophages and/or neoplastic cells, a co-localization study using cell- and pathogen-specific markers was performed. To detect Leishmania spp. a 5.8S ribosomal RNA (rRNA) parasite-specific sequence was used for in-situ hybridization and Mac387 was used as a macrophage marker for immunohistochemistry. Leishmania spp. rRNA was detected inside Mac387(+) macrophages and within the cytoplasm of some neoplastic cells. DNA isolation and polymerase chain reaction using specific primers and sequencing analysis identified the organism as Leishmania infantum (syn. Leishmania chagasi). This is the first report describing infection of tumour cells by L. infantum in a genital TVT from an asymptomatic bitch. Transplantation of Leishmania-laden neoplastic cells could represent an alternative route of venereal transmission of leishmaniasis among dogs. PMID:23348016

  7. Human Immunoglobulin (Ig)M+IgD+ Peripheral Blood B Cells Expressing the CD27 Cell Surface Antigen Carry Somatically Mutated Variable Region Genes: CD27 as a General Marker for Somatically Mutated (Memory) B Cells

    PubMed Central

    Klein, Ulf; Rajewsky, Klaus; Küppers, Ralf

    1998-01-01

    Immunoglobulin (Ig)M+IgD+ B cells are generally assumed to represent antigen-inexperienced, naive B cells expressing variable (V) region genes without somatic mutations. We report here that human IgM+IgD+ peripheral blood (PB) B cells expressing the CD27 cell surface antigen carry mutated V genes, in contrast to CD27-negative IgM+IgD+ B cells. IgM+IgD+CD27+ B cells resemble class-switched and IgM-only memory cells in terms of cell phenotype, and comprise ∼15% of PB B lymphocytes in healthy adults. Moreover, a very small population (<1% of PB B cells) of highly mutated IgD-only B cells was detected, which likely represent the PB counterpart of IgD-only tonsillar germinal center and plasma cells. Overall, the B cell pool in the PB of adults consists of ∼40% mutated memory B cells and 60% unmutated, naive IgD+CD27− B cells (including CD5+ B cells). In the somatically mutated B cells, VH region genes carry a two- to threefold higher load of somatic mutation than rearranged Vκ genes. This might be due to an intrinsically lower mutation rate in κ light chain genes compared with heavy chain genes and/or result from κ light chain gene rearrangements in GC B cells. A common feature of the somatically mutated B cell subsets is the expression of the CD27 cell surface antigen which therefore may represent a general marker for memory B cells in humans. PMID:9802980

  8. Localization of a breast cancer tumour-suppressor gene to a 3-cM interval within chromosomal region 16q22.

    PubMed

    Iida, A; Isobe, R; Yoshimoto, M; Kasumi, F; Nakamura, Y; Emi, M

    1997-01-01

    Allelic losses on chromosome 16q in tumour cells are frequent in a variety of malignancies, suggesting the presence of one or more tumour-suppressor genes in the region. Among 210 sporadic breast cancers we examined using 15 microsatellite markers on the long arm of chromosome 16, heterozygosity for at least one locus was lost in 141 (67%). Detailed deletion mapping revealed two distinct commonly deleted regions. One region was defined as a 3-cM interval flanked by markers D16S512 and D16S515 at 16q22; the second consisted of a 9.5-cM interval flanked by markers D16S498 and D16S303 at q24.3. Allelic loss on 16q was observed frequently in small tumours, tumours without lymph node metastasis and tumours of the non-invasive histological type as well as in tumours of more advanced phenotype, suggesting that inactivation of one of at least two tumour-suppressor genes on 16q plays a role in early stage breast carcinogenesis. PMID:9010036

  9. Tumours of the upper alimentary tract

    PubMed Central

    Head, K. W.

    1976-01-01

    Tumours of the oropharynx of domestic animals are common in most parts of the world, but squamous cell carcinoma of the upper alimentary tract shows differences in prevalence in different geographical areas and occurs at different sites in the various species. Oral tumours of the melanogenic system are more common in dogs than in man. The following main histological categories, which broadly correspond to those used in the classification of tumours of man, are described: papilloma; squamous cell carcinoma; salivary gland tumours; malignant melanoma; tumours of soft (mesenchymal) tissues; tumours of the facial bones; tumours of haematopoietic and related tissues; and odontogenic tumours and jaw cysts. Papilloma, squamous cell carcinoma, malignant melanoma, fibroma, and fibrosarcoma account for about 80% of the tumours that occur in the upper alimentary tract of domestic animals. ImagesFig. 6Fig. 7Fig. 8Fig. 9Fig. 34Fig. 35Fig. 36Fig. 37Fig. 2Fig. 3Fig. 4Fig. 5Fig. 22Fig. 23Fig. 24Fig. 25Fig. 26Fig. 27Fig. 28Fig. 29Fig. 14Fig. 15Fig. 16Fig. 17Fig. 30Fig. 31Fig. 32Fig. 33Fig. 18Fig. 19Fig. 20Fig. 21Fig. 10Fig. 11Fig. 12Fig. 13Fig. 1 PMID:1086147

  10. [Pancreatic tumour in a child].

    PubMed

    Schouenborg Schultz, Thea; Thyssen Vestergaard, Esben

    2014-07-28

    Abdominal pain is a common symptom in children and recurrent abdominal pain (RAP) has a prevalence of 8.4% in childhood. In 90-95% of RAPs no organic disease is identified. Thus, it is important that the few of somatic origin are diagnosed. We describe a case concerning a 12-year-old girl, diagnosed with a solid pseudopapillary tumour of the pancreas. The symptoms were RAP and postprandial vomiting. The purpose of this article is to increase the knowledge of "alarm findings" indicating an organic disease in children with RAP. PMID:25292323

  11. Markers of metastatic carcinoma of breast origin.

    PubMed

    Gown, Allen M; Fulton, Regan S; Kandalaft, Patricia L

    2016-01-01

    This review summarizes the three major breast-associated markers that can be of assistance in evaluating metastatic carcinomas for which a breast primary diagnosis is entertained. These markers include gross cystic disease fluid protein-15 (GCDFP-15), mammaglobin, and GATA3. The first two are cytoplasmic markers that show comparable sensitivities for breast cancer, although relatively few of the published studies have employed the same antibodies against the target molecule, making direct comparisons challenging. GATA3 is a nuclear transcription factor that shows superior sensitivity to GCDFP-15 and mammaglobin. However, the specificity of GATA3 can pose challenges, inasmuch as carcinomas of the bladder and other sites can show significant levels of positivity. Determination of the optimal panel of antibodies employed in a given clinical setting will thus depend on the non-breast tumours included in the differential diagn