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Sample records for cancer antigen ca

  1. CA 19-9 (Cancer Antigen 19-9)

    Science.gov (United States)

    ... called Lewis antigen that is similar to the ABO antigens that are used in blood typing for ... Guidelines for the Use of Tumor Markers in Breast and Colorectal Cancer [On-line guidelines]. Available online at http://www. ...

  2. CA 19-9 (Cancer Antigen 19-9)

    Science.gov (United States)

    ... antigen negative (about 30% in people of African ancestry) and do not produce CA 19-9. The ... are slightly more likely to have it than women), family history, diabetes , chronic pancreatitis , and workplace exposure ...

  3. Interpretation of sequential measurements of cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) based on analytical imprecision and biological variation in the monitoring of ovarian cancer

    DEFF Research Database (Denmark)

    Tuxen, Malgorzata K.; Sölétormos, G; Petersen, P H

    2001-01-01

    The main objective with cancer antigen 125 (CA 125), carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) monitoring of ovarian cancer patients is to detect an early change of disease activity with high reliability. We hypothesized that a monitoring scheme for ovarian cancer patie...

  4. Luminoimmunometric Assay of Tissue Polypeptide Antigen (Tpa and Cancer Antigen 125 (Ca-125 in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    O. El-Ahmady

    1993-01-01

    Full Text Available Serum TPA and CA-125 were determined in 86 individuals (66 with breast cancer representing the different stages and grades of the disease and 20 normal healthy controls. TPA and CA-125 were estimated using the L1A reagents supplied by BYK Sangtec. TPA showed sensitivity rates of 31.8%, 42.4% and 51.5% while CA-125 showed sensitivities of 16.3%, 18.6% and 25.6% at specificity levels of 100%, 95% and 90% respectively. Combined determination of the two markers resulted in some improvement in sensitivity. For follow-up of breast cancer patients after surgery both markers were of value and showed near-identical patterns.

  5. The CA19-9 and Sialyl-TRA Antigens Define Separate Subpopulations of Pancreatic Cancer Cells.

    Science.gov (United States)

    Barnett, Daniel; Liu, Ying; Partyka, Katie; Huang, Ying; Tang, Huiyuan; Hostetter, Galen; Brand, Randall E; Singhi, Aatur D; Drake, Richard R; Haab, Brian B

    2017-06-22

    Molecular markers to detect subtypes of cancer cells could facilitate more effective treatment. We recently identified a carbohydrate antigen, named sTRA, that is as accurate a serological biomarker of pancreatic cancer as the cancer antigen CA19-9. We hypothesized that the cancer cells producing sTRA are a different subpopulation than those producing CA19-9. The sTRA glycan was significantly elevated in tumor tissue relative to adjacent pancreatic tissue in 3 separate tissue microarrays covering 38 patients. The morphologies of the cancer cells varied in association with glycan expression. Cells with dual staining of both markers tended to be in well-to-moderately differentiated glands with nuclear polarization, but exclusive sTRA staining was present in small clusters of cells with poor differentiation and large vacuoles, or in small and ill-defined glands. Patients with higher dual-staining of CA19-9 and sTRA had statistically longer time-to-progression after surgery. Patients with short time-to-progression (<2 years) had either low levels of the dual-stained cells or high levels of single-stained cells, and such patterns differentiated short from long time-to-progression with 90% (27/30) sensitivity and 80% (12/15) specificity. The sTRA and CA19-9 glycans define separate subpopulations of cancer cells and could together have value for classifying subtypes of pancreatic adenocarcinoma.

  6. The value of cancer antigen 125 (CA 125) during treatment and follow-up of patients with ovarian cancer

    NARCIS (Netherlands)

    deBruijn, HWA; vanderZee, AGJ; Aalders, JG

    Although the nature of the cancer antigen 125 leaves many questions unanswered, the use of serum measurements as a means to assess the response to surgery and chemotherapy in ovarian cancer is now well documented. Good prognostic significance is attributed to a rapid decline in cancer antigen 125

  7. The Potential Ability of Plaster to Cause Breast Cancer as Indicated by CA15-3 and CEA Antigens in Women Working in Gypsum Factory

    Directory of Open Access Journals (Sweden)

    Ali Abdul Hussein S. AL-Janabi

    2017-07-01

    Full Text Available Plaster is an important form of gypsum that mainly used in building construction. Breast cancer was investigated among women exposure to the dust of such material. The levels of CA15-3 and carcinoembryonic antigens (CEA as indicators for breast cancer were measured in the serum of 120 women working in a plaster factory. All of involved women showed a normal level of CEA, while 12.5% of them had moderately elevated levels of CA15-3. In conclusion; plaster dust has no significant effect to cause breast cancer in working women. Moderately high levels of CA15-3 in some of exposed women may relate to liver diseases. Key words: Breast Cancer, Plaster, CA15-3, CEA

  8. Preoperative sensitivity and specificity for early-stage ovarian cancer when combining cancer antigen CA-125II, CA 15-3, CA 72-4, and macrophage colony-stimulating factor using mixtures of multivariate normal distributions

    NARCIS (Netherlands)

    Skates, S.J.; Horick, N.; Yu, Y.H.; Xu, F.J.; Berchuck, A.; Havrilesky, L.J.; de Bruijn, H.W.A.; van der Zee, A.G.J.; Woolas, R.P.; Jacobs, I.J.; Zhang, 27727; Bast, R.C.; Zhang, Z

    2004-01-01

    Purpose In CA-125–based ovarian cancer screening trials, overall specificity and screening sensitivity of ultrasound after an elevated CA-125 exceeded 99.6% and 70%, respectively, thereby yielding a positive predictive value (PPV) exceeding 10%. However, sensitivity for early-stage disease was only

  9. Cancer vaccine--Antigenics.

    Science.gov (United States)

    2002-01-01

    Antigenics is developing a therapeutic cancer vaccine based on heat-shock proteins (HSPs). The vaccine [HSPPC-96, Oncophage] is in a pivotal phase III clinical trial for renal cancer at 80 clinical sites worldwide. The trial is enrolling at least 500 patients who are randomised to receive surgical removal of the primary tumour followed by out-patient treatment with Oncophage((R)) or surgery only. This study was initiated on the basis of results from a pilot phase I/II study and preliminary results from a phase II study in patients with renal cell cancer. In October 2001, Oncophage was designated as a fast-track product by the Food and Drug Administration in the US for the treatment of renal cell carcinoma. Oncophage is in phase I/II trials in Italy for colorectal cancer (30 patients) and melanoma. The trials in Italy are being conducted at the Istituto dei Tumouri, Milan (in association with Sigma-Tau). Preliminary data from the phase II trial for melanoma was presented at the AACR-NCI-EORTC International Conference in Florida, USA, in October 2001. Oncophage is also in a phase I/II (42 patients) and a phase II trial (84 patients) in the US for renal cell cancer, a phase II trial in the US for non-Hodgkin's lymphoma (35 patients), a phase II trial in the US for sarcoma (20-35 patients), a phase I/II trial in the US for melanoma (36 patients), and phase I/II trials in Germany for gastric (30 patients) and pancreatic cancers. A pilot phase I trial in patients with pancreatic cancer began in the US in 1997 with 5 patients enrolled. In November 2000, Antigenics announced that this trial had been expanded to a phase I/II study which would now include survival as an endpoint and would enroll 5 additional patients. The US trials are being performed at Memorial Sloan-Kettering Cancer Center and the M.D. Anderson Cancer Center. The trials in Germany are being carried out at Johannes Gutenberg-University Hospital, Mainz. Oncophage is an autologous vaccine consisting of

  10. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J

    2015-01-01

    immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic...... functions, including support of growth, survival and metastasis. This novel insight into the function of cancer/testis antigens has the potential to deliver more effective cancer vaccines. Moreover, immune targeting of oncogenic cancer/testis antigens in combination with conventional cytotoxic therapies...

  11. Unexpected distribution of CA19.9 and other type 1 chain Lewis antigens in normal and cancer tissues of colon and pancreas: Importance of the detection method and role of glycosyltransferase regulation.

    Science.gov (United States)

    Aronica, Adele; Avagliano, Laura; Caretti, Anna; Tosi, Delfina; Bulfamante, Gaetano Pietro; Trinchera, Marco

    2017-01-01

    CA19.9 antigen has been assumed as an abundant product of cancer cells, due to the reactivity found by immunohistochemical staining of cancer tissues with anti-CA19.9 antibody. Expression and biosynthesis of type 1 chain Lewis antigens in the colon and the pancreas were studied by immunodetection in tissue sections and lysates, quantification of glycosyltransferase transcripts, bisulfite sequencing, and chromatin immunoprecipitation assays. CA19.9 was poorly detectable in normal colon mucosa and almost undetectable in colon cancer, while it was easily detected in the pancreatic ducts, together with Lewis b antigen, under both normal and cancer conditions. B3GALT5 transcripts were down-regulated in colon cancer, while they remained expressed in pancreatic cancer. Even ST3GAL3 transcript appeared well expressed in the pancreas but poorly in the colon, irrespective of normal or cancer conditions. CpG islands flanking B3GALT5 native promoter presented an extremely low degree of methylation in pancreatic cancer with respect to colon cancer. In a DNA region about 1kb away from the B3GALT5 retroviral promoter, a stretch of CG dinucleotides presented a methylation pattern potentially associated with transcription. Such a DNA region and the transcription factor binding site provided overlapping results by chromatin immunoprecipitation assays, corroborating the hypothesis. CA19.9 appears as a physiological product whose synthesis strongly depends on the tissue specific and epigenetically-regulated expression of B3GALT5 and ST3GAL3. CA19.9 and other Lewis antigens acquire tumor marker properties in the pancreas due to mechanisms giving rise to reabsorption into vessels and elevation in circulating levels. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Cancer antigen 125 and prognosis

    DEFF Research Database (Denmark)

    Høgdall, Estrid Vilma Solyom

    2008-01-01

    PURPOSE OF REVIEW: This review addresses recently reported progress in cancer antigen 125 as a prognostic marker in patients with ovarian cancer. RECENT FINDINGS: Serum cancer antigen 125 levels measured preoperatively in both early and late stage ovarian cancer may be of prognostic value. Before...... cancer antigen 125 determination may be implemented into clinical practice, cut-off levels must be evaluated and internationally defined. Studies examining serum cancer antigen 125 levels after surgery but before, during, or after treatment confirmed that changes in serum levels are of prognostic value....... Furthermore, recent studies have shown that the level of expression of cancer antigen 125 in tissue may be an independent prognostic indicator in late stage ovarian cancer. SUMMARY: Prognostic markers may potentially help to individualize treatment within subgroups of patients. In a recent study the level...

  13. CA 15-3, Ceruloplasmin and tissue polypeptide specific antigen as a ...

    African Journals Online (AJOL)

    Objective: To examine the value of CA 15-3, ceruloplasmin and tissue polypeptide specific antigen (TPS) panel in the monitoring of breast cancer. Subjects: Serum concentrations of CA 15-3, ceruloplasmin and TPS were measured in 90 women: Fifteen controls, sixteen patients with benign breast disease (BBD), thirty one ...

  14. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J

    2015-01-01

    Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer....../testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor...... or novel immunotherapies such as checkpoint blockade or adoptive transfer, represents a highly synergistic approach with the potential to improve patient survival....

  15. HE4 and CA125 levels in the preoperative assessment of endometrial cancer patients

    DEFF Research Database (Denmark)

    Antonsen, Sofie L; Høgdall, Estrid; Christensen, Ib J

    2013-01-01

    To evaluate whether human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) correlated to known high-risk prognostic factors for endometrial cancer.......To evaluate whether human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) correlated to known high-risk prognostic factors for endometrial cancer....

  16. Predictors of pretreatment CA125 at ovarian cancer diagnosis

    DEFF Research Database (Denmark)

    Babic, Ana; Cramer, Daniel W; Kelemen, Linda E

    2017-01-01

    in CA125 between studies and linear regression to estimate the association between epidemiologic factors and tumor characteristics and pretreatment CA125 levels. RESULTS: In age-adjusted models, older age, history of pregnancy, history of tubal ligation, family history of breast cancer, and family......PURPOSE: Cancer antigen 125 (CA125) is a glycoprotein expressed by epithelial cells of several normal tissue types and overexpressed by several epithelial cancers. Serum CA125 levels are mostly used as an aid in the diagnosis of ovarian cancer patients, to monitor response to treatment and detect...... cancer recurrence. Besides tumor characteristics, CA125 levels are also influenced by several epidemiologic factors, such as age, parity, and oral contraceptive use. Identifying factors that influence CA125 levels in ovarian cancer patients could aid in the interpretation of CA125 values for individuals...

  17. Enhanced discrimination of malignant from benign pancreatic disease by measuring the CA 19-9 antigen on specific protein carriers.

    Directory of Open Access Journals (Sweden)

    Tingting Yue

    Full Text Available The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenocarcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage cancer, owing to diversity among patients in their CA 19-9 protein carriers. However, a subset of cancer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 antigen specifically on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of cancer detection was improved relative to CA 19-9 alone in each sample set, achieving 67-80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glycans on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic cancer could have important applications for improving the treatment and management of patients suffering from this disease.

  18. CA125 in ovarian cancer

    DEFF Research Database (Denmark)

    Duffy, M J; Bonfrer, J M; Kulpa, J

    2005-01-01

    CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little...... value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal...... women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease...

  19. Monitoring different stages of breast cancer using tumour markers CA 15-3, CEA and TPA

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V

    2004-01-01

    The ability of the tumour markers Cancer Antigen 15-3 (CA 15-3), Carcinoembryonic Antigen (CEA), and Tissue Polypeptide Antigen (TPA) to signal progression in breast cancer patients was investigated in this study. Marker interpretation considered the analytical variation, intra-individual biologi...

  20. Comparison of two different methods for CA19-9 antigen determination.

    Science.gov (United States)

    Deinzer, Martina; Faissner, Ralf; Metzger, Tobias; Kaminski, Wolfgang E; Löhr, Mathias; Neumaier, Michael; Brinkmann, Thomas

    2010-01-01

    This study was designed to investigate the clinical performance of the Access GI Monitor (Beckman Coulter) on the UniCel DxI 800, a method for CA19-9 antigen determination, and to compare with CA19-9 assay on the AxSYM system (Abbott). 1,063 serum samples from unselected patients with different underlying diagnoses were tested with both methods. Passing-Bablok regression analysis and Bland Altman analysis was performed. In addition, using ROC analysis, the distribution of Access GI Monitor and AxSYM CA19-9 antigen levels was tested in patients with pancreatic cancer (n = 50), acute inflammatory disease (n = 20), and with chronic inflammation of the pancreatic gland (n = 18). Furthermore, four patients with pancreatic cancer were monitored individually in their courses of the disease (before, during, and after therapeutic procedures) to compare their CA19-9 values with regard to inter-method concordance. Passing-Bablok analysis showed a systematic difference with R = 0.93, slope 0.75, and intercept -1.0. Bland Altman analysis showed a wide scatter of relative differences between both methods, especially in the low end measuring range. In the selected group of patients with pancreatic diseases the analysis of concordance revealed 95.5 % agreement between both methods with a comparable area under the ROC curves (0.73 vs. 0.76). A clear concordance was found for all four selected patients. Although we found significant systematic measuring variations in the global analysis, the two different automated methods for the quantitative determination of CA19-9 antigen were comparable with respect to their clinical accuracy and applicability to support decision making in the management of pancreatic cancer.

  1. Comparison of breast cancer mucin (BCM) and CA 15-3 in human breast cancer

    NARCIS (Netherlands)

    Garcia, M.B.; Blankenstein, M.A.; Wall, E. van der; Nortier, J.W.R.; Schornagel, J.H.; Thijssen, J.H.H.

    1990-01-01

    The Breast Cancer Mucin (BCM) enzyme immunoassay utilizes two monoclonal antibodies (Mab), M85/34 and F36/22, for the identification of a mucin-like glycoprotein in serum of breast cancer patients. We have compared BCM with CA 15-3, another member of the human mammary epithelial antigen

  2. Diagnostic Values of Carcinoembryonic Antigen, Cancer Antigen 15-3 and Cancer Antigen 125 Levels in Nipple Discharge.

    Science.gov (United States)

    Zhao, Song; Gai, Xiaodong; Wang, Yongmei; Liang, Weili; Gao, Haidong; Zhang, Kai; Wang, Huimin; Liu, Yanhong; Wang, Jianli; Ma, Rong

    2015-12-31

    An expedient and cost-effective diagnostic tool is needed to complement galactography and exfoliative cytology for detection of benign or malignant breast diseases with nipple discharge. The aim of this prospective study is to explore the utility of carcinoembryonic antigen, cancer antigen 15-3 and cancer antigen 125 levels in nipple discharge for the diagnosis of various breast diseases. We evaluated the pre-operative tumor marker levels in 153 nipple discharge samples collected from one or both breasts of 142 women undergoing surgery. Patients with nipple discharge underwent auxiliary examination (ultrasonography, exfoliative cytology, ductoscopy and galactography). Statistically higher levels of carcinoembryonic antigen and cancer antigen 15-3 were found in patients in the malignant group as compared to those in the benign group. No statistically significant difference in the level of cancer antigen 125 (P = 0.895). Sensitivities of carcinoembryonic antigen and cancer antigen 15-3 for diagnosing breast cancer were 74.42% and 58.14%, and specificities were 87.27% and 80.00% where as the cutoff values with max-sum of sensitivity and specificity were 224.3 ng/ml and 1368.2 U/ml, respectively. The following sensitivities for telling malignant from benign could be determined: exfoliative cytology 46.67%, ultrasonography 76.74%, galactography 75.00%, and ductoscopy 0%. Exfoliative cytology was found to be a valuable alternative method for differentiating benign from malignancy. Thus, tumor marker analysis of nipple discharge fluid for carcinoembryonic antigen and cancer antigen 15-3 would enhance the accurate assessment and treatment planning for patients with nipple discharge.

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

    Science.gov (United States)

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

    2017-07-01

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

  4. CANCER-ASSOCIATED ANTIGEN CA-195 IN PATIENTS WITH MUCINOUS OVARIAN-TUMORS - A COMPARATIVE-ANALYSIS WITH CEA, TATI AND CA-125 IN SERUM SPECIMENS AND CYST FLUIDS

    NARCIS (Netherlands)

    DEBRUIJN, HWA; TENHOOR, KA; MARRINK, J; KRANS, M; AALDERS, JG; Boonstra, J.

    1993-01-01

    The CA 195 levels in ovarian cyst fluids from malignant mucinous tumours (median 2,300,000 U/ml) were significantly higher than the levels in benign mucinous tumours and malignant non-mucinous tumours (medians of 26,800 and 1,700 U/ml, respectively, p = 0.039 and 0.011). Also, the carcinoembryonic

  5. Ovarian Cancer Early Detection by Circulating CA125 in the context of Anti-CA125 Autoantibody Levels

    DEFF Research Database (Denmark)

    Fortner, Renée T; Schock, Helena; Le Cornet, Charlotte

    2018-01-01

    CA125 is the best ovarian cancer early detection marker to date; however, sensitivity is limited and complementary markers are required to improve discrimination between ovarian cancer cases and non-cases. Anti-CA125 autoantibodies are observed in circulation. Our objective was to evaluate whether......-cases. We investigated these objectives using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (EPIC) including 250 cases diagnosed within 4 years of blood collection and up to 4 matched controls. Circulating CA125 antigen and antibody levels were...... the first evidence of potentially synergistic discrimination effects of CA125 and anti-CA125 antibodies in ovarian early detection. If these findings are replicated, evaluating CA125 in the context of its antibody may improve ovarian cancer early detection. This article is protected by copyright. All rights...

  6. Diagnostic Difficulties in Woman with Crohn’s Disease, Ascites, and Elevated Value of Serum CA125 Antigen

    Directory of Open Access Journals (Sweden)

    Maria Kłopocka

    2014-01-01

    Full Text Available Variety of symptoms and atypical clinical course of Crohn’s disease (CD often create the need for additional diagnostic procedures. In the described case of woman with CD, there was a suspicion of coexistence of ovarian cancer. This issue is particularly important in patients treated with immunosuppressants and biological agents. The discussion focused on the usefulness of CA125 (cancer antigen 125, mucin 16 serum level estimation in clinical practice and draws attention to the possible reasons for the increase of its value which is not associated to ovarian cancer.

  7. Diverse monoclonal antibodies against the CA 19-9 antigen show variation in binding specificity with consequences for clinical interpretation.

    Science.gov (United States)

    Partyka, Katie; Maupin, Kevin A; Brand, Randall E; Haab, Brian B

    2012-07-01

    The CA 19-9 antigen is currently the best individual marker for the detection of pancreatic cancer. In order to optimize the CA 19-9 assay and to develop approaches to further improve cancer detection, it is important to understand the specificity differences between CA 19-9 antibodies and the consequential affect on biomarker performance. Antibody arrays enabled multiplexed comparisons between five different CA 19-9 antibodies used in the analysis of plasma samples from pancreatic cancer patients and controls. Major differences were observed between antibodies in their detection of particular patient samples. Glycan array analysis revealed that certain antibodies were highly specific for the canonical CA 19-9 epitope, sialyl-Lewis A, while others bound sialyl-Lewis A in addition to a related structure called sialyl-Lewis C and modification with Nue5Gc. In a much larger patient cohort, we confirmed the binding of sialyl-Lewis C glycan by one of the antibodies and showed that the broader specificity led to the detection of an increased number of cancer patients without increasing detection of pancreatitis patient samples. This work demonstrates that variation between antibody specificity for cancer-associated glycans can have significant implications for biomarker performance and highlights the value of characterizing and detecting the range of glycan structures that are elevated in cancer. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Cancer-germline antigen vaccines and epigenetic enhancers

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Burns, Jorge; Ditzel, Henrik Jorn

    2010-01-01

    can be achieved using epigenetic modifiers. AREAS COVERED IN THIS REVIEW: We provide an overview of the potential of CG antigens as targets for cancer immunotherapy, including advantages and disadvantages. We also discuss the current state of development of CG antigen vaccines, and the potential...... antigen vaccines may be a useful approach for treating cancer....

  9. T cell recognition of breast cancer antigens

    DEFF Research Database (Denmark)

    Petersen, Nadia Viborg; Andersen, Sofie Ramskov; Andersen, Rikke Sick

    Recent studies are encouraging research of breast cancer immunogenicity to evaluate the applicability ofimmunotherapy as a treatment strategy. The epitope landscape in breast cancer is minimally described, thus it is necessary to identify T cell targets to develop immune mediated therapies.......This project investigates four proteins commonly upregulated in breast cancer and thus probable tumor associated antigens (TAAs). Aromatase, prolactin, NEK3, and PIAS3 contribute to increase growth, survival, and motility of malignant cells. Aspiring to uncover novel epitopes for cytotoxic T cells, a reverse...... immunology approach is applied. Via in silico screening of the protein sequences, 415 peptides were predicted as HLA-A*0201 and HLA-B*0702 binders. Subsequent in vitro binding analysis in a MHC ELISA platform confirmed binding for 147 of the 415 predicted binders. The 147 peptides were evaluated for T cell...

  10. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

    DEFF Research Database (Denmark)

    Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel

    2018-01-01

    BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PS...

  11. Predictors of pretreatment CA125 at ovarian cancer diagnosis: a pooled analysis in the Ovarian Cancer Association Consortium.

    Science.gov (United States)

    Babic, Ana; Cramer, Daniel W; Kelemen, Linda E; Köbel, Martin; Steed, Helen; Webb, Penelope M; Johnatty, Sharon E; deFazio, Anna; Lambrechts, Diether; Goodman, Marc T; Heitz, Florian; Matsuo, Keitaro; Hosono, Satoyo; Karlan, Beth Y; Jensen, Allan; Kjær, Susanne K; Goode, Ellen L; Pejovic, Tanja; Moffitt, Melissa; Høgdall, Estrid; Høgdall, Claus; McNeish, Iain; Terry, Kathryn L

    2017-05-01

    Cancer antigen 125 (CA125) is a glycoprotein expressed by epithelial cells of several normal tissue types and overexpressed by several epithelial cancers. Serum CA125 levels are mostly used as an aid in the diagnosis of ovarian cancer patients, to monitor response to treatment and detect cancer recurrence. Besides tumor characteristics, CA125 levels are also influenced by several epidemiologic factors, such as age, parity, and oral contraceptive use. Identifying factors that influence CA125 levels in ovarian cancer patients could aid in the interpretation of CA125 values for individuals. We evaluated predictors of pretreatment CA125 in 13 studies participating in the Ovarian Cancer Association Consortium. This analysis included a total of 5,091 women with invasive epithelial ovarian cancer with pretreatment CA125 measurements. We used probit scores to account for variability in CA125 between studies and linear regression to estimate the association between epidemiologic factors and tumor characteristics and pretreatment CA125 levels. In age-adjusted models, older age, history of pregnancy, history of tubal ligation, family history of breast cancer, and family history of ovarian cancer were associated with higher CA125 levels while endometriosis was associated with lower CA125 levels. After adjusting for tumor-related characteristics (stage, histology, grade), body mass index (BMI) higher than 30 kg/m2 was associated with 10% (95% CI 2, 19%) higher CA125 levels, while race (non-white vs. white) was associated with 15% (95% CI 4, 27%) higher CA125 levels. Our results suggest that high BMI and race may influence CA125 levels independent of tumor characteristics. Validation is needed in studies that use a single assay for CA125 measurement and have a diverse study population.

  12. Cancer-testis antigen expression is shared between epithelial ovarian cancer tumors.

    Science.gov (United States)

    Garcia-Soto, Arlene E; Schreiber, Taylor; Strbo, Natasa; Ganjei-Azar, Parvin; Miao, Feng; Koru-Sengul, Tulay; Simpkins, Fiona; Nieves-Neira, Wilberto; Lucci, Joseph; Podack, Eckhard R

    2017-06-01

    Cancer-testis (CT) antigens have been proposed as potential targets for cancer immunotherapy. Our objective was to evaluate the expression of a panel of CT antigens in epithelial ovarian cancer (EOC) tumor specimens, and to determine if antigen sharing occurs between tumors. RNA was isolated from EOC tumor specimens, EOC cell lines and benign ovarian tissue specimens. Real time-PCR analysis was performed to determine the expression level of 20 CT antigens. A total of 62 EOC specimens, 8 ovarian cancer cell lines and 3 benign ovarian tissues were evaluated for CT antigen expression. The majority of the specimens were: high grade (62%), serous (68%) and advanced stage (74%). 58 (95%) of the EOC tumors analyzed expressed at least one of the CT antigens evaluated. The mean number of CT antigen expressed was 4.5 (0-17). The most frequently expressed CT antigen was MAGE A4 (65%). Antigen sharing analysis showed the following: 9 tumors shared only one antigen with 62% of the evaluated specimens, while 37 tumors shared 4 or more antigens with 82%. 5 tumors expressed over 10 CT antigens, which were shared with 90% of the tumor panel. CT antigens are expressed in 95% of EOC tumor specimens. However, not a single antigen was universally expressed across all samples. The degree of antigen sharing between tumors increased with the total number of antigens expressed. These data suggest a multi-epitope approach for development of immunotherapy for ovarian cancer treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Correlation of serum and salivary CA15-3 levels in patients with breast cancer.

    Science.gov (United States)

    Agha-Hosseini, Farzaneh; Mirzaii-Dizgah, Iraj; Rahimi, Asieh

    2009-10-01

    The aim of this study was to assess the relationship between serum and saliva levels of cancer antigen (CA) 15-3 and to compare them between women with and without breast cancer. A case-control study was carried out on 61 women aged 28-69 years, including women with and without breast cancer (26 as part of the case study and 35 as part of the control group) conducted at the Emam Khomeini Hospital, Tehran University of Medical Sciences. CA 15-3 levels were assayed in serum and unstimulated whole saliva by EIA. Unpaired t-test, one-way ANOVA and Pearson correlation were used as statistical analysis. The salivary and serological levels of CA 15-3 in the cancer patients were significantly higher (P cancer patients. However, the saliva flow rate was significantly lower in the cancer patients (P cancer in women.

  14. Technical evaluation of the Beckman Coulter OV-Monitor (CA 125 antigen) immunoassay.

    Science.gov (United States)

    Yagmur, Eray; Driesch, Reinhard; Gressner, Axel M; Kiefer, Paul

    2006-01-01

    The CA 125 antigen is a large (200-1000 kDa) glycoprotein, present within normal and benign ovarian tissue. We evaluated the analytical performance of the newly available Beckman Coulter OV-Monitor (CA 125 antigen) immunoassay on the Beckman Coulter UniCel DxI 800 analyzer. The evaluation was performed according to NCCLS recommendations. The lowest level of CA 125 antigen detectable was 0.374 U/mL. Serial dilution of two pooled CA 125 antigen-rich samples provided a linear response (pUniCel DxI 800 showed linear regression values of r=0.961 vs. the Bayer ADVIA Centaur system and r=0.981 vs. the Abbott AxSYM system. Considering the limited number of serum samples analyzed, our data indicate that the Beckman Coulter OV-Monitor immunoassay has excellent analytical performance and shows satisfactory correlation with automated immunoassays on the Abbott AxSYM and Bayer ADVIA Centaur systems. It is easy to perform, accurate and suitable for measurements in routine clinical laboratories.

  15. Monitoring performance of progression assessment criteria for cancer antigen 125 among patients with ovarian cancer compared by computer simulation

    DEFF Research Database (Denmark)

    Abu Hassan, Suher Othman; Petersen, Per Hyltoft; Lund, Flemming

    2015-01-01

    BACKGROUND: Cancer antigen 125 (CA125) is used to monitor tumor burden among patients with advanced serous epithelial ovarian cancer. The purpose is to compare the monitoring performance of seven previously proposed criteria. MATERIALS & METHODS: The CA125 assessment criteria were applied....... For baseline concentrations below cut-off, the best performing criterion was based on a confirmed increment from ≤ cut-off to >two-times cut-off. DISCUSSION: Computer simulation models may be useful for a preclinical validation of criteria to be investigated in clinical trials....

  16. [Biological function of cancer-associated carbohydrate antigens].

    Science.gov (United States)

    Kannagi, R

    1996-06-01

    An important outcome of the monoclonal antibody approach for cancer-associated antigens is that cell-surface carbohydrates have been shown to be very important cancer-associated antigens. These antigens are currently classified into several groups. The first group has the sugar determinant carried by so-called type 1 chain carbohydrates, with a backbone structure composed of the Gal beta 1-->3GlcNAc beta repeating unit. The antigens in this group are utilized mainly for the diagnosis of cancers in the pancreas, biliary tract and other digestive organs. This group includes the well-known serum tumor marker, the 2 -->3 sialyl Le(a) antigen, which is detected by N19-9 and other antibodies. This group also includes DU-PAN-2, which was recently confirmed to be the sialyl Lec. The second group has the polysaccharide determinant carried by so-called type 2 chain carbohydrates, the characteristic feature of which is a backbone structure composed of the Gal beta1 -->4GlcNAc beta repeating unit. This group includes the tumor markers, sialyl SSEA-1, CSLEX-1 or sialyl Lewis X, and is used for the diagnosis of cancers originating in the lung, ovary and digestive organs. The third group has the antigenic determinant carried by the innermost core structures in O-linked carbohydrate side chains. The example of this group is the sialyl Tn antigen, which is detected in ovarian cancers. This group also includes the recently described carbohydrate determinant called Fl alpha antigen, which is frequently expressed in gastric cancer cells. Some of the antigens in the first and second groups such as sialyl Le(a) and sialyl Le(x), serve as ligands for E-selectin, a cell adhesion molecule expressed on activated human endothelial cells, and play significant roles in hematogenous metastasis of cancer.

  17. Clinical Significance of Serum HE4, CA125, CA724, and CA19-9 in Patients With Endometrial Cancer.

    Science.gov (United States)

    Bian, Jing; Sun, Xiaoxu; Li, Bo; Ming, Liang

    2017-08-01

    Serum markers with increased sensitivity and specificity for endometrial cancer are required. To date, no good marker has met this standard. The aims of our study were to evaluate the utility of tumor markers HE4, CA125, CA724, and CA19-9 as potential markers in patients diagnosed with endometrial cancer. Blood samples from 105 patients with endometrial cancer and 87 healthy women were analyzed by Roche electrochemiluminescent immunoassay, and serum values were measured for the following biomarkers: HE4, CA125, CA724, and CA19-9. Serum HE4, CA125, CA724, and CA19-9 concentrations were significantly higher in patients with endometrial cancer, compared with controls ( P endometrial cancer, HE4 had higher sensitivity (58%), positive predictive value (60%), and negative predictive value (67%) than any other single tumor marker, and in the combination of HE4, CA125, CA724, and CA19-9, the sensitivity and positive predictive values reached 59.1% and 88%, respectively. Meanwhile, the receiver operating characteristic area under the curve of the combination of the 4 markers was significantly increased than any other group, either in stage I or in stage II to IV cases. HE4 and CA125 both correlate with advanced age; in addition, HE4 was related to pathology subtypes and positive adnexal involvement, CA125 was related to International Federation of Gynecology and Obstetrics stage, CA19-9 was related to International Federation of Gynecology and Obstetrics stage, and CA724 was correlated with positive lymph node. Combination of HE4, CA125, CA724, and CA19-9 has the highest value in diagnosing endometrial cancer, and they can be a useful tissue immune marker for patients with endometrial cancer.

  18. Cancer antigen 125 after delivery in women with a normal pregnancy

    DEFF Research Database (Denmark)

    Szecsi, Pal B; Andersen, Malene R; Bjørngaard, Brian

    2014-01-01

    OBJECTIVE: To establish reference intervals for cancer antigen 125 (CA-125) in women with expected normal pregnancy, delivery, and early postpartum period. DESIGN: Prospective observational study. SETTING: Department of Clinical Biochemistry and Obstetrics, Copenhagen University Hospital, Gentofte...... the gestational period and around delivery. RESULTS: CA-125 was fairly stable below 35 U/mL during pregnancy but increased markedly during vaginal delivery, to a minor degree during emergency cesarean section, and only slightly during elective cesarean section. In the early postpartum period, CA-125 decreased...... it unlikely that small fluctuations in CA-125 can be clinically useful for identifying other conditions. Measuring CA-125 around the time of delivery is not recommended. Gestational age-specific reference intervals during normal pregnancy are not needed....

  19. Early decline in cancer antigen 125 as a surrogate for progression-free survival in recurrent ovarian cancer

    DEFF Research Database (Denmark)

    Lee, Chee K; Friedlander, Michael; Brown, Chris

    2011-01-01

    We used data from 886 patients from the CAELYX in Platinum Sensitive Ovarian Patients (CALYPSO) trial, recruited between April 2005 and September 2007, to examine the role of early decline in cancer antigen 125 (CA125) and early tumor response as prognostic factors and surrogates for superiority...... response as surrogates for CPLD treatment benefit compared with CP. All statistical tests were two-sided. Early decline (defined as rate of CA125 decrease of at least 50% per month) was associated with improved PFS (adjusted hazard ratio [HR] for progression = 0.81, 95% confidence interval [CI] = 0.67 to 0...

  20. Dialysate cancer antigen 125 concentration as marker of peritoneal membrane status in patients treated with chronic peritoneal dialysis

    NARCIS (Netherlands)

    Krediet, R. T.

    2001-01-01

    OBJECTIVE: This study reviews publications on the history of cancer antigen 125 (CA125), the background of its use as a marker of mesothelial cell mass, determination in peritoneal effluent, and its practical use in both the follow-up of peritoneal dialysis (PD) patients and as a marker of in vivo

  1. Factors related to serum level of carbohydrate antigen 19-9 and cancer antigen 125 in healthy rural populations in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S. K.; Yoo, K. Y.; Park, S. K.; Kang, D. H.; Kim, J. K.; Jeong, Z. K.; Lee, M. C. [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    1998-01-01

    This study examines the levels of carbohydrate antigen 19-9(CA 19-9) and cancer antigen 125(CA125) in serum and its related factors in healthy Korean population. Although CA19-9 and CA125 have been widely used tumor markers for gastroenteric cancers and ovarian cancer in Western countries, there are no information available on the serum levels of CA19-9 and CA125 in healthy population and the factors affecting the levels of these tumor markers in Korea. A cross-sectional study was performed to measure CA19-9 and CA125 among 76 healthy males and 95 healthy females in Korea. CA19-9 and CA125 were quantitated using solid-phase radioimmunoassay kits. Informations on the factors which might be related to the levels of these markers were collected by questionnaire(e.g., smoking, alcohol consumption, menstruation, oral pill use, breast-feeding history, etc.). There was no statistically significant difference in the mean of CA19-9 concentration between men(10.4 u/ml) and women (10.1 u/ml), whereas the mean of CA125 levels (11.2 u/ml) was higher in women than that(2.5 u/ml) in men. Although there was a statistically significant association between CA19-9 and average number of cigarette consumed per day (r=0.59, p=0.026) and total number of cigarettes consumed in women (r=0.74, p=0.003), the significance disappeared by multiple regression analysis after adjusting age and body mass index. Later age of menopause(p=0.035) and longer duration of breast-feeding(p=0.050) were significant predictors for CA125 levels in women by multiple regression analysis after adjusting age and body mass index. In conclusion, CA19-9 can be used as a stable tumor marker in clinical practices, however, menstruation and breast-feeding should be considered when CA125 is used in women.

  2. Clinical Significance and Prognostic Value of CA72-4 Compared with CEA and CA19-9 in Patients with Gastric Cancer

    Directory of Open Access Journals (Sweden)

    M. Ychou

    2000-01-01

    Full Text Available Carcinoembryonic antigen (CEA and CA 19-9 are both widely used in the follow up of patients with gastrointestinal cancer. More recently another tumor marker, named CA 72-4 has been identified and characterized using two different monoclonal antibodies B72.3 and CC49. Several reports evaluated CA 72-4 as a serum tumor marker for gastric cancer and compared its clinical utility with that of CEA or CA 19-9; few reports concerned its prognostic value. In the present study, CA 72-4 is evaluated and compared with CEA and CA 19-9 in various populations of patients with gastric cancer and benign disease; for 52 patients with gastric adenocarcinoma and 57 patients without neoplastic disease CEA, CA 19-9 and CA 72-4 were evaluated before treatment. Sensitivity of the tumor markers CA 72-4, CA 19-9 and CEA at the recommended cut-off level in all 52 patients were 58%, 50% the sensitivity increased to 75%. of these markers, for non metastatic patients, multivariate analyses indicated that none of the markers were significant, when adjusted for gender and age (which were indicators of poor prognosis; patients with abnormal values of CA72-4 tended to have shorter survival than patients with normal values (p < 0.07. In the metastatic population, only high values of CA19-9 (p < 0.02 and gender (women (p < 0.03 were indicators of poor prognosis in univariate analysis; multivariate analysis revealed that both CA72-4 (p = 0.034 and CA19-9 p = 0.009, adjusted for gender were independent prognostic factors. However, CA72-4 lost significance (p = 0.41 when adjusted for CA19-9 and gender, indicating that CA19-9 provides more prognostic information than CA72-4.

  3. Decline in CA19-9 during chemotherapy predicts survival in four independent cohorts of patients with inoperable bile duct cancer

    DEFF Research Database (Denmark)

    Grunnet, Mie; Christensen, Ib J.; Lassen, Ulrik

    2015-01-01

    Background: Carbohydrate associated antigen (CA19-9) has been approved by the FDA as a biomarker for monitoring treatment effect in pancreatic cancer. However, the value of serum CA19-9 as a biomarker of response to chemotherapy in bile duct cancer is unclear. The aim of this study was to determi...

  4. Specificity and affinity of 26 monoclonal antibodies against the CA 125 antigen : First report from the ISOBM TD-1 workshop

    NARCIS (Netherlands)

    Nustad, K; Bast, RC; OBrien, TJ; Nilsson, O; Seguin, P; Suresh, MR; Saga, T; Nozawa, S; Bormer, OP; deBruijn, HWA; Vitali, A; Gadnell, M; Clark, J; Shigemasa, K; Karlsson, B; Kreutz, FT; Jette, D; Sakahara, H; Endo, K; Paus, E; Warren, D; Hammarstrom, S; Kenemans, P; Hilgers, J

    1996-01-01

    The specificity of 26 monoclonal antibodies against the CA 125 antigen was investigated in two phases of the ISOBM TD-1 workshop. The binding specificity was studied using CA 125 immunoextracted by specific antibodies immobilized on various solid phases, or on the surface of human cell lines.

  5. Tumor markers cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen for monitoring metastatic breast cancer during first-line chemotherapy and follow-up

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V

    1996-01-01

    We investigated whether model systems integrating stochastic variation into criteria for marker assessment could be used for monitoring metastatic breast cancer. A total of 3989 serum samples was obtained from 204 patients receiving first-line chemotherapy and from 112 of these patients during...... follow-up. Each sample was analyzed for cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen. The efficiency for identifying progression and nonprogression was 94% during therapy and 85% during follow-up, with no false-positive marker results for progressive disease. At clinical...... unnecessary toxicity. Marker information may also be useful in studies investigating whether early treatment during follow-up will alter the prognosis of metastatic breast cancer....

  6. Predictive value of prostate-specific antigen for prostate cancer

    DEFF Research Database (Denmark)

    Shepherd, Leah; Borges, Alvaro Humberto; Ravn, Lene

    2014-01-01

    INTRODUCTION: Although prostate cancer (PCa) incidence is lower in HIV+ men than in HIV- men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV- men. We aimed to describe the kinetics and predict...

  7. Metastatic prostate cancer with elevated serum levels of CEA and CA19-9

    Directory of Open Access Journals (Sweden)

    Guang-Dar Juang

    2014-03-01

    Full Text Available Prostate-specific antigen (PSA is well known as a specific tumor marker for prostate cancer, but carcinoembryonic antigen (CEA- and carbohydrate antigen 19-9 (CA19-9-elevating adenocarcinomas originating in the prostate gland are rare. We report a case of metastatic adenocarcinoma of the prostate gland with a high serum level of CEA and CA19-9 in a 78-year-old man in whom prostate cancer (T3N1M1 had been diagnosed 2 years ago and who was treated with androgen deprivation therapy. He visited the emergency department because of a loss of appetite and abdominal pain. The serum CEA and CA19-9 levels were increased to 218.9 ng/mL (normal, <5 ng/mL and 212 ng/mL (normal, <27 ng/mL, respectively. The serum PSA level was slightly elevated (4.41 ng/mL. Computed tomography demonstrated multiple liver metastases, para-aortic lymph node enlargement, and lung metastases. A liver biopsy was performed and the specimen showed high-grade adenocarcinoma with focal positive staining for PSA. Despite chemotherapy with docetaxel, the patient died 3 months after treatment. Based on this case and a review of the literature, an aggressive variant of prostatic carcinoma with a high serum level of CEA and CA19-9 and a low PSA level was shown to progress rapidly with a poor prognosis.

  8. Tumor subtype-specific cancer-testis antigens as potential biomarkers and immunotherapeutic targets for cancers

    OpenAIRE

    Yao, Jun; Caballero, Otavia L.; Yung, W.K. Alfred; Weinstein, John N.; Riggins, Gregory J.; Strausberg, Robert L.; Zhao, Qi

    2013-01-01

    Cancer-testis (CT) antigens are potential targets for cancer immunotherapy because of their restricted expression in immune-privileged germ cells and various malignancies. Current application of CT-based immunotherapy has been focused on CT expression-rich tumors such as melanoma and lung cancers. In this study, we surveyed CT expression using the Cancer Genome Atlas (TCGA) datasets for ten common cancer types. We show that, CT expression is specific and enriched within certain cancer molecul...

  9. Antibody profiling with protein antigen microarrays in early stage cancer.

    Science.gov (United States)

    Liu, Brian C-S; Dijohnson, Daniel A; O'Rourke, Dennis J

    2012-05-01

    Proteins not present in normal cells, that is, cancer cells, may elicit a host immune response that leads to the generation of antibodies that might react with these tumor-associated proteins. In recent years, a growing number of reports have showed that autoantibody profiling may provide an alternative approach for the detection of cancer. However, most studies of antigen-autoantibody reactivity have relied on recombinant proteins. Recombinant proteins lack the proper post-translational modifications present in native proteins. Because of this limitation, native or natural protein antigen microarrays are gaining popularity for profiling antibody responses. i) To illustrate some examples of autoantibodies as signatures for early stage cancer; ii) to briefly outline the various protein antigen microarray platforms; iii) to illustrate the use of native or natural protein microarrays in the discovery of potential biomarkers and iv) to discuss the advantages of native protein antigen microarrays over other approaches. The nature of protein microarray platforms is conducive to multiplexing, which amplifies the potential for uncovering effective biomarkers for many significant diseases. However, the major challenge will be in integrating microarray platforms into multiplexed clinical diagnostic tools, as the main drawback is the reproducibility and coefficient of variation of the results from array to array, and the transportability of the array platform to a more automatable platform.

  10. Comparison of survival outcomes after recurrence detected by cancer antigen 125 elevation versus imaging study in epithelial ovarian cancer.

    Science.gov (United States)

    Paik, E Sun; Kim, Tae Joong; Lee, Yoo Young; Choi, Chel Hun; Lee, Jeong Won; Kim, Byoung Gie; Bae, Duk Soo

    2016-09-01

    The aim of this study was to compare survival outcomes in two groups of patients with recurrent epithelial ovarian cancer (EOC) with initial recurrence detection by cancer antigen 125 (CA-125) elevation or imaging, and underwent secondary cytoreductive surgery (SCS). A retrospective review of the medical records was performed on 99 recurrent EOC patients who underwent SCS at the Samsung Medical Center between January 2002 and December 2013. For follow-up after primary treatment, patients were routinely assessed by CA-125 levels every 3 months and computed tomography (CT) scan (or magnetic resonance imaging [MRI]) every 6 months for first 3 years, and by CA-125 every 6 months and CT scan (or MRI) every 12 months thereafter. The first recurrence was initially identified by either CA-125 elevation (n=41, 41.4%) or by imaging study (n=58, 58.6%). None of the patients showed the symptoms as initial sign of recurrence. There were higher percentages of extra-pelvic recurrence (87.8%) and multiple recurrences (78.0%) in the group diagnosed by CA-125 elevation. The proportion of no residual disease after SCS was comparably lower in the CA-125 group (22.0% vs. 72.4%). There were 19 cancer-associated deaths (19.2%) within a median follow-up period of 67 months. The group diagnosed by imaging had better overall survival from initial diagnosis (OS1), overall survival after SCS (OS2), progression-free survival after the initial treatment (PFS1) and progression-free survival after SCS compared to those of the CA-125 group (PFS2). EOC patients with recurrence initially detected by imaging study showed better survival outcomes than patients diagnosed by CA-125 elevation.

  11. Clinicopathological characteristics of patients of certain molecular subtypes and elevated postoperative cancer antigen 15.3 levels and its correlation with menopausal status

    OpenAIRE

    Soumi Saha; Suvro Ganguly; Diptendra Kumar Sarkar; Avijit Hazra

    2016-01-01

    Context: It is well established that breast cancer subtypes differ in their outcome and treatment response. Aim: To observe tumor characteristics of different molecular subgroup and patients with postoperative (PO) raised cancer antigen 15.3 (CA 15.3) group and variation of tumor nature between pre- and post-menopausal breast cancer patients. Materials and Methods: Blood samples and tumor blocks were collected from 95 nonmetastatic female breast cancer patients. Immunohistochemical stains for...

  12. Immunohistochemical evaluation of a new epithelial antigen, BER-EP4 in ovarian cancer: a propos of 62 cases.

    Science.gov (United States)

    Capobianco, G; Marras, V; Battista Meloni, G; Dessole, S; Ashqar, N; Cherchi, C; Dessole, F; Cherchi, P L

    2012-01-01

    To assess the immunohistochemical expression of BerEP4, a new epithelial antigen in ovarian cancer. We studied 62 cases of ovarian cancer in which BerEP4, CEA and CA-125 were investigated by an immunohistochemical method. We evaluated the correlations among immunohistochemical positivity and the grading, histotype and stage of disease. BerEP4 was positive in 45 out of 62 cases (72.58%), CA-125 in 36 out of 62 cases (58.06%) and CEA in ten out of 62 cases (16.13%). BerEP4 was present both in serous and in mucinous tumors (80.96% vs. 80.77%). CA-125 was mainly expressed in serous vs mucinous tumors (66.67% vs. 57.69%). CEA was more prevalent in mucinous vs. serous tumors. Ber-EP4 was mainly expressed in G1 (75%) and G2 (77.27%). CA-125 was more present in G1 and G3 (both 62.50%) than G2 (50%), whereas CEA showed positivity in G1: 12.50%, G2: 22.73% and G3: 12.50%. There were no differences among the three antigens studied with regard to clinical stage. In our study Ber-EP4 was positive in 45 out of 62 cases (72.58%) of primary epithelial ovarian cancers. The presence of this antigen seemed to be related to the histotype and grading but not to clinical stage.

  13. Prostate-specific antigen, prostate cancer, and disorders of hemostasis.

    Science.gov (United States)

    Lippi, Giuseppe; Plebani, Mario; Franchini, Massimo; Guidi, Gian Cesare; Favaloro, Emmanuel J

    2009-10-01

    Prostate cancer is the most prevalent malignancy in men and the third leading cause of cancer deaths worldwide. Disorders of hemostasis are commonplace in patients with prostate cancer and include disseminated intravascular coagulation, venous thromboembolism, acute coronary syndrome, and postsurgical bleeding. These hemostatic disorders contribute to the mortality and morbidity of prostate cancer. The leading mechanisms proposed to underlie prostate cancer-related coagulopathies are thought to be a hyperexpression of tissue factor, cancer procoagulant, and platelet-activating factor, which is then accompanied by release of large amounts of both prothrombotic and profibrinolytic substances into the bloodstream. Given the generally accepted notion that prostate-specific antigen (PSA) represents an important biomarker in prostate cancer diagnostics, large population screenings were initiated for early detection of cancer. However, recent clinical and economic drawbacks have been recently raised, including evidence that screening exposes patients to a significant risk of both overdiagnosis and overtreatment. Nevertheless, several lines of evidence suggest that PSA may have tumor-suppressing activities. Despite being a member of the vast kallikrein family, which actively interplays with the coagulation cascade, the role of PSA in the pathogenesis of hemostatic disorders observed in prostate cancer patients remains circumstantial and speculative. However, observations that the levels of this cancer marker tend to correlate positively with those of several markers of thrombin generation, and with postsurgical bleeding as well as with coronary atherosclerosis and negative outcomes of myocardial infarction, raise a new and intriguing scenario regarding the pathophysiological role of this serine protease. (c) Thieme Medical Publishers.

  14. Urine antibody against human cancer antigen NY-ESO-1

    OpenAIRE

    Jäger, Dirk; Stockert, Elisabeth; Karbach, Julia; Herrlinger, Kristina; Atmaca, Akin; Arand, Michael; Chen, Yao-Tseng; Gnjatic, Sacha; Old, Lloyd J; Knuth, Alexander; Jäger, Elke

    2002-01-01

    NY-ESO-1 is one of the most immunogenic tumor antigens known to date. Spontaneous humoral and cellular immune responses against NY-ESO-1 are detected in a substantial proportion of patients with NY-ESO-1 positive cancers. NY-ESO-1 serum antibody is dependent on the presence of NY-ESO-1+ cancer cells, and antibody titers correlate with the clinical development of the disease. NY-ESO-1 serum antibody is associated with detectable NY-ESO-1-specific CD8+ T cell reactivity. High titers of NY-ESO-1...

  15. Cancer Antigen 72-4 for the Monitoring of Advanced Tumors of the Gastrointestinal Tract, Lung, Breast and Ovaries.

    Science.gov (United States)

    Mariampillai, Anusiyanthan Isaac; Cruz, Josephine Pineda Dela; Suh, Jason; Sivapiragasam, Abirami; Nevins, Kyle; Hindenburg, Alexander A

    2017-07-01

    Cancer antigen CA72-4 is a tumor marker found to be elevated in a variety of human adenocarcinomas. Using the DRG TM-CA72-4, we quantified the elevation of CA72-4 compared to current United States Food And Drug Administration-approved tumor markers in various cancer types. We conducted a prospective, single-center study enrolling 96 patients between March 2013 and August 2016 with different locally advanced, unresectable or metastatic cancer known to express CA72-4. Quantification of CA72-4 was performed according to the manufacturer's instructions using the DRG TM-CA72-4 enzyme-linked immunosorbent assay kit and the positivity rates were calculated. CA72-4 expression varied with tumoral site of origin, with the highest positivity rates found in pancreatic and ovarian malignancies. Correlation with clinical activity was also noted in some patients. CA72-4 may have a potential role as an adjunct to conventional biomarkers in disease monitoring of pancreatic, ovarian and colorectal carcinomas. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. The Vibrio cholerae O139 O-antigen polysaccharide is essential for Ca2+-dependent biofilm development in sea water

    OpenAIRE

    Kierek, Katharine; Watnick, Paula I.

    2003-01-01

    Vibrio cholerae is both an inhabitant of estuarine environments and the etiologic agent of the diarrheal disease cholera. Previous work has demonstrated that V. cholerae forms both an exopolysaccharide-dependent biofilm and a Ca2+-dependent biofilm. In this work, we demonstrate a role for the O-antigen polysaccharide of V. cholerae in Ca2+-dependent biofilm development in model and true sea water. Interestingly, V. cholerae biofilms, as well as the biofilms of several other Vibrio species, di...

  17. Colorectal carcinoma: nucleosomes, carcinoembryonic antigen and ca 19-9 as apoptotic markers; a comparative study

    Directory of Open Access Journals (Sweden)

    Mahgoub Samir S

    2011-07-01

    Full Text Available Abstract Background Colorectal carcinoma is a common and often fatal disease in which methods of early detection and monitoring are essential. The present study was conducted for measuring serum levels of nucleosomes, carcinoembryonic antigen (CEA and CA 19-9 in patients newly diagnosed with colorectal carcinoma and confirmed by clinicopathological study. Method Thirty subjects were included in the current study: six normal subjects as a control group with mean age (45.6 ± 7.9 and twenty four colorectal carcinoma patients with mean age (46.9 ± 15.6, which were classified pathologically according to the degree of malignant cell differentiation into well differentiated (group I, moderately differentiated (group II and poorly differentiated (group III. Fasting venous blood samples were collected preoperative. Results The results revealed a significant increase in serum level of nucleosomes in patients with poorly differentiated tumors versus patients with well differentiated tumors (p = 0.041. The levels of CEA and CA19-9 showed no significant increase (p = 0.569 and 0.450, respectively. Conclusion In conclusion, serum level of nucleosomes provides a highly sensitive and specific apoptotic marker for colorectal carcinoma.

  18. Universal Breast Cancer Antigens as Targets Linking Early Detection and Therapeutic Vaccination

    National Research Council Canada - National Science Library

    Domchek, Susan M

    2005-01-01

    This grant supports studies to understand the potential of universal tumor antigens for cancer immunotherapy, with a particular focus on the characterization of the human telomerase reverse transcriptase (hTERT) as tumor antigen...

  19. Overdetection, overtreatment and costs in prostate-specific antigen screening for prostate cancer

    NARCIS (Netherlands)

    E.A.M. Heijnsdijk (Eveline); A. der Kinderen (Arno); E.M. Wever (Elisabeth); G. Draisma (Gerrit); M.J. Roobol-Bouts (Monique); H.J. de Koning (Harry)

    2009-01-01

    textabstractBackground:Prostate cancer screening with prostate-specific antigen (PSA) has shown to reduce prostate cancer mortality in the European Randomised study of Screening for Prostate Cancer (ERSPC) trial. Overdetection and overtreatment are substantial unfavourable side effects with

  20. 78 FR 11895 - Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer...

    Science.gov (United States)

    2013-02-20

    ... Rights for development of Pox-virus based vaccines for bladder cancer, breast cancer, colorectal cancer...-1 Tumor Associated Antigens as Cancer Vaccines for Bladder Cancer, Breast Cancer, Colorectal Cancer, Gastric Cancer, Kidney Cancer, Liver Cancer, Lung Cancer, Ovarian Cancer, Prostate Cancer and Pancreatic...

  1. CA1 contributes to microcalcification and tumourigenesis in breast cancer.

    Science.gov (United States)

    Zheng, Yabing; Xu, Bing; Zhao, Yan; Gu, He; Li, Chang; Wang, Yao; Chang, Xiaotian

    2015-10-12

    Although mammary microcalcification is frequently observed and has been associated with poor survival in patients with breast cancer, the genesis of calcification remains unclear. Carbonic anhydrase I (CA1) has been shown to promote calcification by catalysing the hydration of CO2. This study aimed to determine whether CA1 was correlated with microcalcification and with other processes that are involved in breast cancer tumourigenesis. CA1 expression in breast cancer tissues and blood samples was detected using western blotting, real-time PCR, immunohistochemistry and ELISA. Calcification was induced in the cultured 4T1 cell line originating from mouse breast tumours, using ascorbic acid and β-glycerophosphate. Acetazolamide, a chemical inhibitor of CA1, was also added to the culture to determine the role of CA1 in calcification. The MCF-7 human breast cancer cell line was treated with anti-CA1 siRNA and was assessed using a CCK-8 cell proliferation assay, an annexin V cell apoptosis assay, transwell migration assay and a human breast cancer PCR array. The tag SNP rs725605, which is located in the CA1 locus, was genotyped using TaqMan® genotyping. Increased CA1 expression was detected in samples of breast carcinoma tissues and blood obtained from patients with breast cancer. A total of 15.3 % of these blood samples exhibited a 2.1-fold or higher level of CA1 expression, compared to the average level of CA1 expression in samples from healthy controls. Following the induction of calcification of 4T1 cells, both the number of calcium-rich deposits and the expression of CA1 increased, whereas the calcification and CA1 expression were significantly supressed in the presence of acetazolamide. Increased migration and apoptosis were observed in MCF-7 cells that were treated with anti-CA1 siRNA. The PCR array detected up-regulation of the androgen receptor (AR) and down-regulation of X-box binding protein 1 (XBP1) in the treated MCF-7 cells. Significant differences in

  2. Cancer vaccines: an update with special focus on ganglioside antigens.

    Science.gov (United States)

    Bitton, Roberto J; Guthmann, Marcel D; Gabri, Mariano R; Carnero, Ariel J L; Alonso, Daniel F; Fainboim, Leonardo; Gomez, Daniel E

    2002-01-01

    Vaccine development is one of the most promising and exciting fields in cancer research; numerous approaches are being studied to developed effective cancer vaccines. The aim of this form of therapy is to teach the patient's immune system to recognize the antigens expressed in tumor cells, but not in normal tissue, to be able to destroy these abnormal cells leaving the normal cells intact. In other words, is an attempt to teach the immune system to recognize antigens that escaped the immunologic surveillance and are by it, therefore able to survive and, in time, disseminate. However each research group developing a cancer vaccine, uses a different technology, targeting different antigens, combining different carriers and adjuvants, and using different immunization schedules. Most of the vaccines are still experimental and not approved by the US or European Regulatory Agencies. In this work, we will offer an update in the knowledge in cancer immunology and all the anticancer vaccine approaches, with special emphasis in ganglioside based vaccines. It has been demonstrated that quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Malignant transformation appears to activate enzymes associated with ganglioside glycosylation, resulting in altered patterns of ganglioside expression in tumors. Direct evidence of the importance of gangliosides as potential targets for active immunotherapy has been suggested by the observation that human monoclonal antibodies against these glycolipids induce shrinkage of human cutaneous melanoma metastasis. Thus, the cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, therefore representing a new target for anticancer therapy. Since 1993 researchers at the University of Buenos Aires and the University of Quilmes (Argentina), have taken part in a project carried out by

  3. Updates of prostate cancer staging: Prostate-specific membrane antigen

    Directory of Open Access Journals (Sweden)

    Niranjan J Sathianathen

    2016-12-01

    Full Text Available The ability to accurately stage prostate cancer in both the primary and secondary staging setting can have a major impact on management. Until recently radiological staging has relied on computer tomography, magnetic resonance imaging, and nuclear bone scans to evaluate the extent of disease. However, the utility of these imaging technologies has been limited by their sensitivity and specificity especially in detecting early recurrence. Functional imaging using positron-emission tomography with a radiolabeled ligand targeted to prostate-specific membrane antigen has transformed the prostate cancer imaging landscape. Initial results suggest that it is a substantial improvement over conventional imaging in the setting of recurrence following primary therapy by having a superior ability to detect disease and to do so at an earlier stage. Additionally, it appears that the benefits seen in the secondary staging setting may also exist in the primary staging setting.

  4. The role of GAGE cancer/testis antigen in metastasis

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Terp, Mikkel Green; Hansen, Malene Bredahl

    2016-01-01

    BACKGROUND: GAGE cancer/testis antigens are frequently expressed in various types of malignancies and represent attractive targets for immunotherapy, however their role in cancer initiation and progression has remained elusive. GAGE proteins are expressed in normal cells during early development...... lines, which are equally tumorigenic in immunodeficient mice, but differ with their ability to generate metastases in the lungs and lymph nodes. RESULTS: Although GAGE proteins were strongly upregulated in the highly metastatic clone (CL16) compared to non-metastatic (NM2C5), weakly metastatic (M4A4......) and moderately metastatic clones (LM3), stable downregulation of GAGE expression did not affect the ability of CL16 cells to establish primary tumors and form metastasis in the lungs of immunodeficient mice. CONCLUSIONS: These results suggest that GAGE proteins per se do not support metastasis and that further...

  5. CA72-4 antigen levels in serum and peritoneal washing in gastric cancer: correlation with morphological aspects of neoplasia Níveis sérico e no lavado peritonial do antígeno CA 72-4 no câncer gástrico: correlação com aspectos morfológicos da neoplasia

    Directory of Open Access Journals (Sweden)

    Leonardo Landim Fernandes

    2007-09-01

    Full Text Available BACKGROUND: Determining levels of tumor markers in peritoneal washing enables likelihood of peritoneal recurrence to be ascertained in patients with high marker levels, thereby allowing provision of more accurate adjuvant treatment and postoperative follow up. AIM: To analyze the relationship between levels of tumor marker CA72-4 in serum and peritoneal washing, and morphological aspects of gastric carcinoma. METHOD: This study analyzed 32 consecutively-operated patients with gastric carcinoma, who underwent subtotal, total or palliative gastrectomy. The variables studied were CA72-4 levels in serum and peritoneal washing, lesion site, stage, degree of cell differentiation, operation performed, and number of extirpated and involvement lymph nodes. Of the 32 patient sample, 21 (65.6% were male and 11 (34.4% female. Mean age was 62.6 ± 14.2 years (29 to 91 years. Following anesthetic induction, peripherical venous blood was collected through percutaneous punction of an upper limb vein. After the procedure, 50 mL of physiologic solution at 37ºC was introduced into the cul-de-sac. A 10 mL volume of this liquid was aspirated from the cavity and the peritoneal washing tested for CA72-4 levels. Normal values for CA72-4 levels in serum were considered 7U/mL, whilst for the peritoneal washing normal levels were 0.61 U/mL. RESULTS: Mean pre-operative serum levels for CA72-4 were 6.55 U/mL ± 15.30 (0.3 to 75.30 U/mL whilst the mean level of CA72-4 in peritoneal washing was 8.50 U/mL ± 26.72 (0.3 to 142.00 U/mL; correlation between these levels was significant. Lymph nodes involvement by the gastric carcinoma correlated significantly with higher CA72-4 levels in both serum and peritoneal wash. There was no statistically significant correlation between serum level of CA72-4 and invasion into serosa by the gastric carcinoma. There was however, significant correlation between peritoneal washing levels of CA72-4 and involvement of serosa by gastric

  6. Inhibiting DNA methylation activates cancer testis antigens and expression of the antigen processing and presentation machinery in colon and ovarian cancer cells.

    Science.gov (United States)

    Siebenkäs, Cornelia; Chiappinelli, Katherine B; Guzzetta, Angela A; Sharma, Anup; Jeschke, Jana; Vatapalli, Rajita; Baylin, Stephen B; Ahuja, Nita

    2017-01-01

    Innovative therapies for solid tumors are urgently needed. Recently, therapies that harness the host immune system to fight cancer cells have successfully treated a subset of patients with solid tumors. These responses have been strong and durable but observed in subsets of patients. Work from our group and others has shown that epigenetic therapy, specifically inhibiting the silencing DNA methylation mark, activates immune signaling in tumor cells and can sensitize to immune therapy in murine models. Here we show that colon and ovarian cancer cell lines exhibit lower expression of transcripts involved in antigen processing and presentation to immune cells compared to normal tissues. In addition, treatment with clinically relevant low doses of DNMT inhibitors (that remove DNA methylation) increases expression of both antigen processing and presentation and Cancer Testis Antigens in these cell lines. We confirm that treatment with DNMT inhibitors upregulates expression of the antigen processing and presentation molecules B2M, CALR, CD58, PSMB8, PSMB9 at the RNA and protein level in a wider range of colon and ovarian cancer cell lines and treatment time points than had been described previously. In addition, we show that DNMTi treatment upregulates many Cancer Testis Antigens common to both colon and ovarian cancer. This increase of both antigens and antigen presentation by epigenetic therapy may be one mechanism to sensitize patients to immune therapies.

  7. Serological identification of Tektin5 as a cancer/testis antigen and its immunogenicity

    Directory of Open Access Journals (Sweden)

    Hanafusa Tadashi

    2012-11-01

    Full Text Available Abstract Background Identification of new cancer antigens is necessary for the efficient diagnosis and immunotherapy. A variety of tumor antigens have been identified by several methodologies. Among those antigens, cancer/testis (CT antigens have became promising targets. Methods The serological identification of antigens by the recombinant expression cloning (SEREX methodology has been successfully used for the identification of cancer/testis (CT antigens. We performed the SEREX analysis of colon cancer. Results We isolated a total of 60 positive cDNA clones comprising 38 different genes. They included 2 genes with testis-specific expression profiles in the UniGene database, such as TEKT5 and a CT-like gene, A kinase anchoring protein 3 (AKAP3. Quantitative real-time RT-PCR analysis showed that the expression of TEKT5 was restricted to the testis in normal adult tissues. In malignant tissues, TEKT5 was aberrantly expressed in a variety of cancers, including colon cancer. A serological survey of 101 cancer patients with different cancers by ELISA revealed antibodies to TEKT5 in 13 patients, including colon cancer. None of the 16 healthy donor serum samples were reactive in the same test. Conclusion We identified candidate new CT antigen of colon cancer, TEKT5. The findings indicate that TEKT5 is immunogenic in humans, and suggest its potential use as diagnostic as well as an immunotherapeutic reagent for cancer patients.

  8. The Vibrio cholerae O139 O-antigen polysaccharide is essential for Ca2+-dependent biofilm development in sea water.

    Science.gov (United States)

    Kierek, Katharine; Watnick, Paula I

    2003-11-25

    Vibrio cholerae is both an inhabitant of estuarine environments and the etiologic agent of the diarrheal disease cholera. Previous work has demonstrated that V. cholerae forms both an exopolysaccharide-dependent biofilm and a Ca2+-dependent biofilm. In this work, we demonstrate a role for the O-antigen polysaccharide of V. cholerae in Ca2+-dependent biofilm development in model and true sea water. Interestingly, V. cholerae biofilms, as well as the biofilms of several other Vibrio species, disintegrate when Ca2+ is removed from the bathing medium, suggesting that Ca2+ is interacting directly with the O-antigen polysaccharide. In the Bay of Bengal, cholera incidence has been correlated with increased sea surface height. Because of the low altitude of this region, increases in sea surface height are likely to lead to transport of sea water, marine particulates, and marine biofilms into fresh water environments. Because fresh water is Ca2+-poor, our results suggest that one potential outcome of an increase is sea surface height is the dispersal of marine biofilms with an attendant increase in planktonic marine bacteria such as V. cholerae. Such a phenomenon may contribute to the correlation of increased sea surface height with cholera.

  9. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

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    Hao Hong

    2008-01-01

    Full Text Available Carcinoembryonic antigen (CEA, highly expressed in many cancer types, is an important target for cancer diagnosis and therapy. Radionuclide-based imaging techniques (gamma camera, single photon emission computed tomography [SPECT] and positron emission tomography [PET] have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically. Briefly, these studies can be divided into three major categories: antibody-based, antibody fragment-based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the earliest among the three categories, typically gave suboptimal tumor contrast due to the prolonged circulation life time of intact antibodies. Subsequently, a number of engineered anti-CEA antibody fragments (e.g. Fab’, scFv, minibody, diabody and scFv-Fc have been labeled with a variety of radioisotopes for CEA imaging, many of which have entered clinical investigation. CEA-Scan (a 99mTc-labeled anti-CEA Fab’ fragment has already been approved by the United States Food and Drug Administration for cancer imaging. Meanwhile, pretargeting strategies have also been developed for CEA imaging which can give much better tumor contrast than the other two methods, if the system is designed properly. In this review article, we will summarize the current state-of-the-art of radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short half-lives (e.g. 18F and 99mTc are more suitable for labeling small engineered antibody fragments while the isotopes with longer half-lives (e.g. 123I and 111In are needed for antibody labeling to match its relatively long circulation half-life. With further improvement in tumor targeting efficacy and radiolabeling strategies, novel CEA-targeted agents may play an important role in cancer patient management, paving the way to “personalized medicine”.

  10. Prostate-specific antigen screening and mortality from prostate cancer.

    Science.gov (United States)

    Marcella, Stephen W; Rhoads, George G; Carson, Jeffrey L; Merlino, Frances; Wilcox, Homer

    2008-03-01

    There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55-79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2-29.2% of cases and 21.8-26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality.

  11. Tumor subtype-specific cancer-testis antigens as potential biomarkers and immunotherapeutic targets for cancers.

    Science.gov (United States)

    Yao, Jun; Caballero, Otavia L; Yung, W K Alfred; Weinstein, John N; Riggins, Gregory J; Strausberg, Robert L; Zhao, Qi

    2014-04-01

    Cancer-testis (CT) antigens are potential targets for cancer immunotherapy because of their restricted expression in immune-privileged germ cells and various malignancies. Current application of CT-based immunotherapy has been focused on CT expression-rich tumors such as melanoma and lung cancers. In this study, we surveyed CT expression using The Cancer Genome Atlas (TCGA) datasets for ten common cancer types. We show that CT expression is specific and enriched within certain cancer molecular subtypes. For example, HORMAD1, CXorf61, ACTL8, and PRAME are highly enriched in the basal subtype of breast cancer; MAGE and CSAG are most frequently activated in the magnoid subtype of lung adenocarcinoma; and PRAME is highly upregulated in the ccB subtype of clear cell renal cell carcinoma. Analysis of CT gene expression and DNA methylation indicates that some CTs are regulated epigenetically, whereas others are controlled primarily by tissue- and subtype-specific transcription factors. Our results suggest that although for some CT expression is associated with patient outcome, not many are independent prognostic markers. Thus, CTs with shared expression pattern are heterogeneous molecules with distinct activation modes and functional properties in different cancers and cancer subtypes. These data suggest a cancer subtype-orientated application of CT antigen as biomarkers and immunotherapeutic targets.

  12. Prognostic impact of prechemotherapy serum levels of HER2, CA125, and HE4 in ovarian cancer patients

    DEFF Research Database (Denmark)

    Steffensen, Karina Dahl; Waldstrøm, Marianne; Brandslund, Ivan

    2011-01-01

    Human epididymis protein 4 (HE4) has attracted a lot of interest as a relatively novel biomarker for ovarian carcinoma. Research focus has been directed at HE4 as a diagnostic tool with potential for better triage of women with adnexal masses but the prognostic aspect of HE4 in ovarian cancer pat...... patients remains to be elucidated. The aim of the present study was to investigate the prognostic value of prechemotherapy serum HER2, cancer antigen 125 (CA125), and HE4 levels in ovarian cancer patients receiving standard combination chemotherapy....

  13. Exploration of the value of MRCP combined with tumor marker CA19-9 in the diagnosis of pancreatic cancer.

    Science.gov (United States)

    Ma, Shaojun; Duan, Jutao; Li, Weizhi; Zhang, He; Hou, Zhenyu

    2016-01-01

    This paper aims to provide an effective, accurate, and specific diagnostic method for the diagnosis of pancreatic cancer. It discusses the diagnostic value of magnetic res retrograde cholangiopancreatography (MRCP) combined with the detection of tumor marker carbohydrate antigen 19-9 (CA19-9) for pancreatic cancer. A group of confirmed cases of pancreatic cancer in some hospitals were randomly selected and subjected to an MRCP examination as well as serological CA19-9 detection. In addition, a group of patients whose pancreatic cancer was confirmed by surgery and pathology, and who underwent MRCP without the detection of the tumor marker CA19-9, were also selected for research. The experiment found that the rate of accuracy for the group that underwent MRCP combined with CA19-9 detection showed a higher positive value in the diagnosis of pancreatic cancer than in the group that underwent MRCP alone. Therefore, this paper proposes that MRCP combined with CA19-9 detection can be taken as the reliable and effective means for diagnosis of pancreatic cancer.

  14. Multiple cancer/testis antigens are preferentially expressed in hormone-receptor negative and high-grade breast cancers.

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    Yao-Tseng Chen

    Full Text Available BACKGROUND: Cancer/testis (CT antigens are protein antigens normally expressed only in germ cells of testis, and yet are expressed in a proportion of a wide variety of human cancers. CT antigens can elicit spontaneous immune responses in cancer patients with CT-positive cancers, and CT antigen-based therapeutic cancer vaccine trials are ongoing for "CT-rich" tumors. Although some previous studies found breast cancer to be "CT-poor", our recent analysis identified increased CT mRNA transcripts in the ER-negative subset of breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we performed a comprehensive immunohistochemical study to investigate the protein expression of eight CT genes in 454 invasive ductal carcinomas, including 225 ER/PR/HER2-negative (triple-negative carcinomas. We found significantly more frequent expression of all eight CT antigens in ER-negative cancers, and five of them--MAGEA, CT7, NY-ESO-1, CT10 and CT45, were expressed in 12-24% of ER-negative cancers, versus 2-6% of ER-positive cancers (p2 cm. CONCLUSIONS/SIGNIFICANCE: CT antigens are preferentially expressed in hormone receptor-negative and high-grade breast cancer. Considering the limited treatment options for ER/PR/HER2 triple-negative breast cancer, the potential of CT-based immunotherapy should be explored.

  15. Lack of ADAM2, CALR3 and SAGE1 Cancer/Testis Antigen Expression in Lung and Breast Cancer

    DEFF Research Database (Denmark)

    Maheswaran, Emeaga; Pedersen, Christina B; Ditzel, Henrik J

    2015-01-01

    cancers. Staining for the well-characterized MAGE-A proteins was included for comparison. Immunohistochemical staining confirmed previous mRNA analysis demonstrating that ADAM2, CALR3 and SAGE1 proteins are confined to testis in normal individuals. Negative tissues included plancenta, which express many...... inhibitors has been proposed as an attractive strategy to increase the expression of cancer/testis antigens in tumors before immunotargeting; however, neither ADAM2, CALR3 nor SAGE1 could be significantly induced in lung and breast cancer cell lines using this strategy. Our results suggest that ADAM2, CALR3...... and antigenic properties, but the expression patterns of most of the more than 200 identified cancer/testis antigens in various cancers remain largely uncharacterized. In this study, we investigated the expression of the cancer/testis antigens ADAM2, CALR3 and SAGE1 in lung and breast cancer, the two most...

  16. Value of detection of serum human epididymis secretory protein 4 and carbohydrate antigen 125 in diagnosis of early endometrial cancer of different pathological subtypes.

    Science.gov (United States)

    Liu, Xingui; Zhao, Fengting; Hu, Linli; Sun, Yingpu

    2015-01-01

    This study explored the value of detection of human epididymis secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) from serum in diagnosis of early endometrial cancer of different pathological subtypes and discussed the mechanism of HE4 and CA125 in diagnosis. In this study, enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to detect HE4 and CA125 from serum in endometrial cancer and control groups. Besides, the concentration of HE4 and CA125 was compared in these two groups, and the expression of CA125 and HE4 and clinicopathological characteristics in patients with endometrial cancer were also analyzed. Compared with the control group, the expression of HE4 was much higher in serum of patients with endometrial cancer, while there was no obvious change in the expression of CA125. The threshold detection value was acquired by receiver operating characteristic analysis method, that is, 141.5 pmol/L and 54.5 U/L, respectively. When comparing the concentration of HE4 in patients with endometrial cancer at the early stage (stage I) with healthy people, the difference therein had statistical significance, but there was no obvious difference in CA125. HE4 and CA125 in diagnosis of endometrial cancer in the stages I and II were found with no statistically significant difference. The difference of HE4 in the stages II and III had statistical significance while the difference of CA125 had no statistical significance. The specificity of both HE4 and CA125 was 95%, and the sensitivity of HE4 to uterine papillary serous carcinomas was higher than that to endometrioid adenocarcinoma. Thus, the serum HE4 is much better than CA125 in detecting the endometrial cancer at an early stage.

  17. Double blind comparison of T-antigen and ABO(H) cell surface antigens in bladder cancer.

    Science.gov (United States)

    Vafier, J A; Javadpour, N; Worsham, G F; O'Connell, K J

    1984-04-01

    Transitional cell carcinoma of the bladder is a major cause of cancer deaths. Recently, much attention has been focused on ABO(H) antigen deletion in terms of prediction of prognosis. Furthermore, several studies have shown a correlation between T-antigen (a precursor of blood MN glycoprotein) expression in carcinomas of the breast, colon, and stomach. We have studied 56 specimens from 41 patients with transitional cell carcinoma of the bladder for T-antigen expression and ABO(H) antigen deletion. Results were analyzed with respect to tumor grade, tumor stage, and clinical course. The data indicate that T-antigen expression was not completely useful prognostically; it did not correlate with grade, stage, or clinical course. ABO(H) antigen expression or deletion was found to be a better predictor of tumor behavior than tumor grade, despite a false negative rate of 20 to 30 per cent in blood group O patients. We suggest that use of immunoperoxidase techniques will increase the sensitivity in group O patients, thus making ABO(H) deletion a useful predictive parameter of tumor aggressiveness. This is currently being evaluated in our patients.

  18. Delayed radiation-induced inflammation accompanying a marked carbohydrate antigen 19-9 elevation in a patient with resected pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mattes, Malcolm D.; Cardinal, Jon S.; Jacobson, Geraldine M. [West Virginia University School of Medicine, Morgantown (United States)

    2016-06-15

    Although carbohydrate antigen (CA) 19-9 is a useful tumor marker for pancreatic cancer, it can also become elevated from a variety of benign and malignant conditions. Herein we describe an unusual presentation of elevated CA 19-9 in an asymptomatic patient who had previously undergone adjuvant chemotherapy and radiation therapy for resected early stage pancreatic cancer. The rise in CA 19-9 might be due to delayed radiation-induced inflammation related to previous intra-abdominal radiation therapy with or without radiation recall induced by gemcitabine. After treatment with corticosteroids the CA 19-9 level decreased to normal, and the patient has not developed any evidence of recurrent cancer to date.

  19. Role of Antigen Spread and Distinctive Characteristics of Immunotherapy in Cancer Treatment.

    Science.gov (United States)

    Gulley, James L; Madan, Ravi A; Pachynski, Russell; Mulders, Peter; Sheikh, Nadeem A; Trager, James; Drake, Charles G

    2017-04-01

    Immunotherapy is an important breakthrough in cancer. US Food and Drug Administration-approved immunotherapies for cancer treatment (including, but not limited to, sipuleucel-T, ipilimumab, nivolumab, pembrolizumab, and atezolizumab) substantially improve overall survival across multiple malignancies. One mechanism of action of these treatments is to induce an immune response against antigen-bearing tumor cells; the resultant cell death releases secondary (nontargeted) tumor antigens. Secondary antigens prime subsequent immune responses (antigen spread). Immunotherapy-induced antigen spread has been shown in clinical studies. For example, in metastatic castration-resistant prostate cancer patients, sipuleucel-T induced early immune responses to the immunizing antigen (PA2024) and/or the target antigen (prostatic acid phosphatase). Thereafter, most patients developed increased antibody responses to numerous secondary proteins, several of which are expressed in prostate cancer with functional relevance in cancer. The ipilimumab-induced antibody profile in melanoma patients shows that antigen spread also occurs with immune checkpoint blockade. In contrast to chemotherapy, immunotherapy often does not result in short-term changes in conventional disease progression end points (eg, progression-free survival, tumor size), which may be explained, in part, by the time taken for antigen spread to occur. Thus, immune-related response criteria need to be identified to better monitor the effectiveness of immunotherapy. As immunotherapy antitumor effects take time to evolve, immunotherapy in patients with less advanced cancer may have greater clinical benefit vs those with more advanced disease. This concept is supported by prostate cancer clinical studies with sipuleucel-T, PSA-TRICOM, and ipilimumab. We discuss antigen spread with cancer immunotherapy and its implications for clinical outcomes. © The Author 2017. Published by Oxford University Press. All rights reserved. For

  20. Cancer/testis antigen PASD1 silences the circadian clock

    Science.gov (United States)

    Michael, Alicia K.; Harvey, Stacy L.; Sammons, Patrick J.; Anderson, Amanda P.; Kopalle, Hema M.; Banham, Alison H.; Partch, Carrie L.

    2015-01-01

    SUMMARY The circadian clock orchestrates global changes in transcriptional regulation on a daily basis via the bHLH-PAS transcription factor CLOCK:BMAL1. Pathways driven by other bHLH-PAS transcription factors have a homologous repressor that modulates activity on a tissue-specific basis, but none have been identified for CLOCK:BMAL1. We show here that the cancer/testis antigen PASD1 fulfills this role to suppress circadian rhythms. PASD1 is evolutionarily related to CLOCK and interacts with the CLOCK:BMAL1 complex to repress transcriptional activation. Expression of PASD1 is restricted to germline tissues in healthy individuals, but can be induced in cells of somatic origin upon oncogenic transformation. Reducing PASD1 in human cancer cells significantly increases the amplitude of transcriptional oscillations to generate more robust circadian rhythms. Our results describe a function for a germline-specific protein in regulation of the circadian clock and provide a molecular link from oncogenic transformation to suppression of circadian rhythms. PMID:25936801

  1. Ca2+ Receptor, Prostate Cancer, and Bone Metastases

    Science.gov (United States)

    2005-03-01

    the skeletal complications of metastatic niurie hyperealcemia andother syndromes ofaltered respansive- breast cancer and on the incidence of new... dhat an hicrease in extra.ehlinlar Ca42 resulted :in delayed activation of exlracellular signal-regulated kinwse (ERK) in PC-3 cells. Pre-intcubation

  2. Analysis of PIK3CA mutations in breast cancer subtypes.

    Science.gov (United States)

    Arsenic, Ruza; Lehmann, Annika; Budczies, Jan; Koch, Ines; Prinzler, Judith; Kleine-Tebbe, Anke; Schewe, Christiane; Loibl, Sibylle; Dietel, Manfred; Denkert, Carsten

    2014-01-01

    Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA) is a central element of a signaling pathway involved in cell proliferation, survival, and growth. Certain mutations in this pathway result in enhanced PI3K signaling, which is associated with oncogenic cellular transformation and cancer. The aims of this study were to characterize different types of PIK3CA mutations in exons 9 and 20 in a series of primary breast carcinomas and to correlate the results with clinicopathologic parameters and survival. We used frozen tissue samples and sequenced exons 9 and 20 for a series of 241 patients with a diagnosis of breast carcinoma. We found that 15.8% of the primary breast carcinomas possessed PIK3CA mutations in either exon 9 or exon 20. The rate of PIK3CA mutations was increased in HR(+)/HER2(-) tumors (18.6%), but this difference did not reach a statistical significance. The lowest rate of mutations was observed in HR(+)/HER2(+) tumors (5.3%). No statistically significant association was found between the presence of PIK3CA mutations and the prognostic/clinical features of breast cancer, including histologic subtype, Her2 status, axillary lymph node involvement, tumor grade, and tumor stage. However, the presence of the H1047R mutation in 10 samples was associated with a statistically significantly worse overall survival. PIK3CA mutation was found to be a frequent genetic change in all breast cancer subtypes but occurred with the highest rate in HR(+)/HER2(-) tumors. Further studies are needed to validate the prognostic impact of different PIK3CA mutations.

  3. Comparison of circulating MMP-9, TIMP-1 and CA19-9 in the detection of pancreatic cancer

    DEFF Research Database (Denmark)

    Joergensen, Maiken Thyregod; Brünner, Nils; De Muckadell, Ove B Schaffalitzky

    2010-01-01

    adenocarcinoma. PATIENTS AND METHODS: The patients had symptoms of pancreatic cancer. The discriminative strength of MMP-9 and TIMP-1 were compared to that of CA19-9 using receiver operating characteristics curves, area under the curves (AUC), specificity and sensitivity. RESULTS: The sensitivities of MMP-9......Background/Aim: The performance of the circulating tumor markers carbohydrate antigen 19-9 (CA19-9), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were evaluated separately and in combination for their potential value in detecting pancreatic ductal......, TIMP-1 and CA19-9 in detecting pancreatic ductal adenocarcinoma were 58.82%, 47.1% and 86%, respectively, with specificities of 34.6%, 69.2% and 73%. The AUCs of MMP-9, TIMP-1 and CA19-9 were 0.50, 0.64 and 0.84, respectively. Combining the three markers did not significantly improve detection...

  4. Clinical performance of LOCI™-based tumor marker assays for tumor markers CA 15-3, CA 125, CEA, CA 19-9 and AFP in gynecological cancers.

    Science.gov (United States)

    Dolscheid-Pommerich, Ramona C; Keyver-Paik, Mignon; Hecking, Thomas; Kuhn, Walther; Hartmann, Gunther; Stoffel-Wagner, Birgit; Holdenrieder, Stefan

    2017-10-01

    Evidence is sparse regarding the clinical performance of luminescent oxygen channeling immunoassays-based tumor marker assays in gynecological cancer. Analyzing serum samples of 336 patients with Dimension™Vista1500, we investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein in patients suffering from different types of gynecological cancer and precancerous gynecological diseases and compared findings to appropriate control groups. The cohort comprised 177 female patients with gynecological cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4 cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24 healthy controls. Discriminative power was assessed by areas under the curve in receiver operating characteristic curves, and sensitivities were determined at a fixed specificity of 95%. Levels of biomarkers in healthy controls were in the expected ranges and a discriminative power between gynecological cancers and healthy controls was observed for several tumor markers. Established tumor type-associated markers were elevated in specific gynecological cancers and benign controls as well as within precancerous gynecological diseases and healthy control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate antigen 15-3 were significantly elevated compared to the respective benign diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer, carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher than in the respective benign diseases. Carcinoembryonic antigen achieved the most conclusive area under the curve (0.65) with 31.5% sensitivity at 95% specificity. None of the investigated markers was found to be of

  5. African Americans' Perceptions of Prostate-Specific Antigen Prostate Cancer Screening

    Science.gov (United States)

    Hunter, Jaimie C.; Vines, Anissa I.; Carlisle, Veronica

    2015-01-01

    Background: In 2012, the U.S. Preventive Services Task Force released a hotly debated recommendation against prostate-specific antigen testing for all men. The present research examines African Americans' beliefs about their susceptibility to prostate cancer (PCa) and the effectiveness of prostate-specific antigen testing in the context of the…

  6. TISSUE POLYPEPTIDE-SPECIFIC ANTIGEN - A DISCRIMINATIVE PARAMETER BETWEEN PROSTATE-CANCER AND BENIGN PROSTATIC HYPERTROPHY

    NARCIS (Netherlands)

    MARRINK, J; OOSTEROM, R; BONFRER, HMG; SCHRODER, FH; MENSINK, HJA

    1993-01-01

    The serum concentration of the cell proliferation marker TPS (tissue polypeptide-specific antigen) was compared with the tumour marker PSA (prostate specific antigen). PSA was found elevated in 50% of the benign prostatic hypertrophy (BPH) patients, in 88% of the patients with active prostate cancer

  7. Comparison of Plasma Tu-M2-PK and CA19-9 in Pancreatic Cancer

    DEFF Research Database (Denmark)

    Joergensen, Maiken Thyregod; Heegaard, Niels H H; Schaffalitzky de Muckadell, Ove B

    2009-01-01

    because of suspicion of pancreatic cancer. Of these, 51 patients had their conditions diagnosed as PDAC, whereas this diagnosis was ruled out in 52 after 12 months of follow-up. The performance of Tu-M2-PK was compared with that of CA19-9 using cutoff values 15 and 37 U/mL, respectively. RESULTS......OBJECTIVES:: The performance of the 2 tumor markers carbohydrate antigen 19-9 (CA19-9) and tumor M2 pyruvate kinase (Tu-M2-PK) separately and in combination detecting pancreatic ductal adenocarcinoma (PDAC) was evaluated in a prospective study. METHODS:: The study comprised 103 patients referred...... alone. The presence of chronic pancreatitis or jaundice causes increased levels of CA19-9 but does not influence Tu-M2-PK. CONCLUSIONS:: Tu-M2-PK was inferior to CA19-9 as marker of PDAC. Tu-M2-PK may have a role in diagnosing PDAC because it is not affected by cholestasis or Lewis phenotype. Neither...

  8. CA125-related measures of tumor kinetics and outcome of patients with recurrent ovarian cancer receiving chemotherapy: a retrospective evaluation.

    Science.gov (United States)

    Colloca, Giuseppe; Venturino, Antonella; Addamo, Gianfranco; Coccorullo, Zaira; Ratti, Riccardo; Caltabiano, Graziano; Guarneri, Domenico

    2013-12-01

    Defining the reliability of cancer antigen-125-related kinetics criteria versus Gynecologic Cancer Inter Group criteria in predicting the tumor outcome after chemotherapy in patients with recurrent ovarian cancer. A retrospective monoinstitutional assessment of CA125-related versus Gynecologic Cancer Inter Group-related parameters was performed after cytotoxic chemotherapy in patients with metastatic ovarian cancer treated from 2006 to 2011. A correlation analysis between the response and progression measurements has been performed, and the outcome has been reported. Among 42 eligible patients, tumor response and progression calculated by CA125 kinetics, with tumor response at 8 weeks and specific growth rate at progression, exhibited a significant correlation with progression-free and overall survival, similar to tumor response and progression by Gynecologic Cancer Inter Group criteria. The tumor response at 8 weeks higher than 1.77 appears to be a good surrogate of clinical response, whereas the definition of progression when CA125 increases above a value double than the nadir suggests a similar performance of growth rate at progression versus Gynecologic Cancer Inter Group criteria and warrants further investigation.

  9. Localization of CaSR antagonists in CaSR-expressing medullary thyroid cancer.

    Science.gov (United States)

    Ding, Haiming; Yusof, Adlina Mohd; Kothandaraman, Shankaran; Saji, Motoyasu; Wang, Chaojie; Kumar, Krishan; Milum, Keisha; Carleton, Michelle; Pan, Xueliang; Ringel, Matthew D; Tweedle, Michael F; Phay, John E

    2013-11-01

    Image-based localization of medullary thyroid cancer (MTC) and parathyroid glands would improve the surgical outcomes of these diseases. MTC and parathyroid glands express high levels of calcium-sensing receptor (CaSR). The aim of this study was to prove the concept that CaSR antagonists specifically localize to CaSR-expressing tumors in vivo. We synthesized two isomers of a known CaSR calcilytic, Calhex 231, and four new analogs, which have a favorable structure for labeling. Their antagonistic activity was determined using immunoblots demonstrating decreased ERK1/2 phosphorylation after calcium stimulation in human embryonic kidney cells overexpressing CaSR. Compound 9 was further radiolabeled with (125)I and evaluated in nude mice with and without heterotransplanted xenografts of MTC cell lines, TT and MZ-CRC-1, that do and do not express CaSR, respectively. Two newly synthesized compounds, 9 and 11, exhibited better antagonistic activity than Calhex 231. The half-life of (125)I-compound 9 in nude mice without xenografts was 9.9 hours. A biodistribution study in nude mice bearing both tumors demonstrated that the uptake of radioactivity in TT tumors was higher than in MZ-CRC-1 tumors at 24 hours: 0.39 ± 0.24 vs 0.18 ± 0.12 percentage of injected dose per gram of tissue (%ID/g) (P = .002), with a ratio of 2.25 ± 0.62. Tumor-to-background ratios for TT tumors, but not MZ-CRC-1 tumors, increased with time. Tumor-to-blood values increased from 2.02 ± 0.52 at 1 hour to 3.29 ± 0.98 at 24 hour (P = .015) for TT tumors, and 1.7 ± 0.56 at 1 hour to 1.48 ± 0.33 at 24 hour (P = .36) for MZ-CRC-1 tumors. Our new CaSR antagonists specifically inhibit CaSR function in vitro, preferentially localize to CaSR-expressing tumors in vivo, and therefore have the potential to serve as scaffolds for further development as imaging pharmaceuticals.

  10. Diagnostic and prognostic value of carcinoembryonic antigen in pancreatic cancer: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Meng Q

    2017-09-01

    Full Text Available Qingcai Meng,1–3,* Si Shi,1–3,* Chen Liang,1–3,* Dingkong Liang,1–3 Wenyan Xu,1–3 Shunrong Ji,1–3 Bo Zhang,1–3 Quanxing Ni,1–3 Jin Xu,1–3 Xianjun Yu1–3 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, 3Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Carcinoembryonic antigen (CEA is one of the most widely used tumor markers and is increased in 30%–60% of patients with pancreatic cancer. Although carbohydrate antigen 19-9 (CA19-9 is the most important serum biomarker in pancreatic cancer, the diagnostic and prognostic value of CEA is gradually being recognized.Materials and methods: The MEDLINE, EMBASE, and Web of Science databases were searched for related literature published until January 2017. Diagnostic accuracy variables were pooled using the Meta-Disc software. The pooled hazard ratios (HRs for prognostic data were calculated and analyzed using Stata software.Results: A total of 3,650 participants enrolled in 19 studies met our inclusion criteria. The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of a CEA-based panel were 0.45 (95% confidence interval [CI], 0.41–0.50, 0.89 (95% CI, 0.86–0.91, 5.39 (95% CI, 3.16–9.18, and 0.55 (95% CI, 0.41–0.72, respectively. The area under the curve (AUC, 0.90 and Q-value (0.84 of the CEA-based panel indicated a significantly higher diagnostic accuracy compared with CEA or CA19-9 alone. Moreover, there was also a significant association between high levels of CEA and worse overall survival (HR, 1.43; 95% CI, 1.31–1.56.Conclusion: Our meta-analysis indicated that elevated serum CEA level, as a vital supplementary to CA19-9, can play an important role in the clinical diagnosis of pancreatic cancer patients and predict poor prognosis. Keywords: carcinoembryonic

  11. Lewis Y Antigen as a Target for Breast Cancer Therapy

    Science.gov (United States)

    1997-09-01

    is noteworthy that patients thus far who developed high titers of anti-sLe antigen ILM showed no evidence of hematologic toxicity (hemolysis, anuria ...siaylated Lewis (sLe) antigen IgM showed no evidence of hematologic toxicity (hemolysis, anuria or granulocytopenia) (6). In summary, these studies

  12. Design of universal cancer vaccines using natural tumor vessel-specific antigens (SANTAVAC).

    Science.gov (United States)

    Lokhov, Petr G; Balashova, Elena E

    2015-01-01

    Vaccination against endothelial cells (ECs) lining the tumor vasculature represents one of the most attractive potential cancer immunotherapy options due to its ability to prevent solid tumor growth. Using this approach, target antigens can be derived from ECs and used to develop a universal cancer vaccine. Unfortunately, direct immunization with EC preparations can elicit autoimmune vasculitis in normal tissues. Recently, tumor-induced changes to the human EC surface were described that provided a basis for designing efficient EC-based vaccines capable of eliciting immune responses that targeted the tumor endothelium directly. This review examines these data from the perspective of designing EC-based cancer vaccines for the treatment of all solid tumors, including the antigen composition of vaccine formulations, the selection ECs for antigen derivation, the production and control of antigens, and the method for estimating vaccine efficacy and safety. As the vaccine preparation requires a specifically derived set of natural cell surface antigens, a new vaccine preparation concept was formulated. Antigen compositions prepared according to this concept were named SANTAVAC (Set of All Natural Target Antigens for Vaccination Against Cancer).

  13. Alternative antibody for the detection of CA15-3 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access BR Monitor assay on the UniCel Dxl 800 Immunoassay System.

    Science.gov (United States)

    Molina, Rafael; Gion, Massimo; Gressner, Axel; Troalen, Frédéric; Auge, Jose Maria; Holdenrieder, Stefan; Zancan, Matelda; Wycislo, Matthias; Stieber, Petra

    2008-01-01

    Cancer antigen CA15-3 antigen is known as a valuable marker for the management of breast cancer. The analytical and clinical performance of the Access BR Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA15-3 on the Elecsys System (Roche Diagnostics). Total imprecision (% CV) of the BR Monitor ranged between 5.5% and 11.7%, and inter-laboratory reproducibility between 3.4% and 5.1%. Linearity upon dilution showed a mean recovery of 98.5% (SD + 9.1%). Endogenous interferents had no influence on BR Monitor levels (mean recoveries: hemoglobin 112%, bilirubin 111%, triglycerides 108%). There was no high-dose hook effect up to 13,540 kU/L. Clinical performance investigated in sera from individuals showed a general correlation between the Access BR Monitor and Elecsys CA15-3 (R = 0.797), with a slope of 1.383. CA15-3 serum levels, as measured by the BR Monitor, were low in healthy individuals (n = 267, median = 11.9 kU/L, 95th percentile = 23.5 kU/L), higher in individuals with various benign diseases (n = 549, medians = 11.3-15.6 kU/L, 95th percentiles = 21.6-54.6 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians = 11.2-22.8 kU/L, 95th percentiles = 30.0-429.7 kU/L). Best diagnostic accuracy for cancer detection against the relevant benign control group by the BR Monitor was found for locoregional and metastatic breast cancer, as well as for ovarian cancer [area under the curve (AUC) 0.619, 0.897 and 0.774]. Results for the reference CA15-3 assay were comparable (AUC 0.611, 0.887 and 0.818). The Access BR Monitor provides accurate methodological characteristics and demonstrates an analytical and clinical correlation with Elecsys CA15-3. Best diagnostic accuracy for the BR Monitor was found in breast and ovarian cancer. Our results also suggest a clinical value of the BR Monitor in other cancers.

  14. A Panel of Cancer Testis Antigens and Clinical Risk Factors to Predict Metastasis in Colorectal Cancer

    Science.gov (United States)

    Molania, Ramyar; Mahjoubi, Frouzandeh; Mirzaei, Rezvan; Khatami, Saeed-Reza; Mahjoubi, Bahar

    2014-01-01

    Colorectal cancer (CRC) is the third common carcinoma with a high rate of mortality worldwide and several studies have investigated some molecular and clinicopathological markers for diagnosis and prognosis of its malignant phenotypes. The aim of this study is to evaluate expression frequency of PAGE4, SCP-1, and SPANXA/D cancer testis antigen (CTA) genes as well as some clinical risk markers to predict liver metastasis of colorectal cancer patients. The expression frequency of PAGE4, SCP-1, and SPANXA/D cancer/testis antigen (CTA) genes was obtained using reverse transcription polymerase chain reaction (RT-PCR) assay in 90 colorectal tumor samples including both negative and positive liver metastasis tumors. Statistical analysis was performed to assess the association of three studied genes and clinical risk factors with CRC liver metastasis. The frequency of PAGE4 and SCP-1 genes expression was significantly higher in the primary tumours with liver metastasis when statistically compared with primary tumors with no liver metastasis (P < 0.05). Among all clinical risk factors studied, the lymph node metastasis and the depth of invasion were statistically correlated with liver metastasis of CRC patients. In addition, using multiple logistic regression, we constructed a model based on PAGE4 and lymph node metastasis to predict liver metastasis of CRC. PMID:26317029

  15. A Panel of Cancer Testis Antigens and Clinical Risk Factors to Predict Metastasis in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Ramyar Molania

    2014-01-01

    Full Text Available Colorectal cancer (CRC is the third common carcinoma with a high rate of mortality worldwide and several studies have investigated some molecular and clinicopathological markers for diagnosis and prognosis of its malignant phenotypes. The aim of this study is to evaluate expression frequency of PAGE4, SCP-1, and SPANXA/D cancer testis antigen (CTA genes as well as some clinical risk markers to predict liver metastasis of colorectal cancer patients. The expression frequency of PAGE4, SCP-1, and SPANXA/D cancer/testis antigen (CTA genes was obtained using reverse transcription polymerase chain reaction (RT-PCR assay in 90 colorectal tumor samples including both negative and positive liver metastasis tumors. Statistical analysis was performed to assess the association of three studied genes and clinical risk factors with CRC liver metastasis. The frequency of PAGE4 and SCP-1 genes expression was significantly higher in the primary tumours with liver metastasis when statistically compared with primary tumors with no liver metastasis (P<0.05. Among all clinical risk factors studied, the lymph node metastasis and the depth of invasion were statistically correlated with liver metastasis of CRC patients. In addition, using multiple logistic regression, we constructed a model based on PAGE4 and lymph node metastasis to predict liver metastasis of CRC.

  16. Cancer testis antigen Sperm Protein 17 as a new target for triple negative breast cancer immunotherapy.

    Science.gov (United States)

    Mirandola, Leonardo; Pedretti, Elisa; Figueroa, Jose A; Chiaramonte, Raffaella; Colombo, Michela; Chapman, Caroline; Grizzi, Fabio; Patrinicola, Federica; Kast, W Martin; Nguyen, Diane D; Rahman, Rakhshanda Layeequr; Daver, Naval; Ruvolo, Peter; Post, Sean M; Bresalier, Robert S; Chiriva-Internati, Maurizio

    2017-09-26

    Breast carcinoma is a major health issue for millions of women. Current therapies have serious side effects, and are only partially effective in patients with metastatic tumors. Thus, the need for novel and less toxic therapies is urgent. Moreover, hormonal and antibody therapies effective in other subtypes are not effective in Triple Negative Breast Cancer (TNBC). Immunotherapeutic strategies directed against specific tumor-associated antigens (TAAs) and mediated by specific cytotoxic T lymphocytes (CTL) have been largely underexplored in this disease. Cancer-testis antigens (CTA) are a group of TAAs displaying the ideal characteristics of promising vaccine targets, i.e. strong immunogenicity and cancer specificity. The CTA, Sperm Protein 17 (SP17), has been found to be aberrantly expressed in different neoplasms, including ovarian and esophageal cancers, nervous system tumors and multiple myeloma, and has been suggested as a candidate target for immunotherapy. Here, we evaluated SP17 expression levels in breast cancer cell lines, invasive ductal breast carcinoma, including patients with TNBC, and adjacent non-neoplastic breast tissue, and determined whether SP17 was capable of generating SP17-specific cytotoxic T lymphocytes in vitro. We showed that SP17 is expressed in breast cancer cell lines and primary breast tumors and importantly in TNBC subtype, but not in adjacent non-tumoral breast tissue or unaffected tissues, except in male germinal cells. Furthermore, we detected specific anti-SP17 antibodies in patients' sera and we generated SP17-specific, HLA class I-restricted, cytotoxic T lymphocytes capable of efficiently killing breast cancer cells.

  17. Differences in plasma gastrin, CEA, and CA 19-9 concentration in patients with proximal and distal colorectal cancer.

    Science.gov (United States)

    Bombski, Grzegorz; Gasiorowska, Anita; Orszulak-Michalak, Daria; Neneman, Beata; Kotynia, Justyna; Strzelczyk, Janusz; Janiak, Adam; Malecka-Panas, Ewa

    2002-01-01

    We investigated whether there are differences in plasma gastrin, as compared with carcinoembryonic antigen (CEA) and cancer antigen (CA) 19-9 between patients with proximal and distal colorectal cancer. Gastrin concentration has also been analyzed, dependent on the tumor stage, in order to evaluate the possible prognostic role of this measurement. In 50 patients with colon cancer-fasting gastrin, CA 19-9 and CEA levels were evaluated. Mean plasma-gastrin level in patients with distal tumor yielded 105.31 +/- 12.5 microU/L and was significantly higher than in patients with the proximal tumor site (42.2 +/- 3.1 microU/L) as well as in controls (p < 0.001). No significant difference was observed between mean plasma gastrin in patients with proximal tumors and the control group. The mean CEA plasma level was significantly higher (p < 0.01) in patients with distal tumors (9.1 +/- 1.1 ng/mL) than in those with proximal tumors (1.48 +/- 0.1 ng/mL). Similarly, the mean CA 19-9 plasma level was significantly higher (p < 0.01) in patients with distal tumor (19.9 +/- 2.1 U/mL) than in those with proximal tumor: 1.8 +/- 0.2 U/mL. The mean gastrin plasma, CA 19-9, and CEA level was significantly higher in group of Duke's stage C and D as compared to A and B. We speculate that observed differences in gastrin concentration in patients with distal and proximal tumors may contribute to the distinct pathogenesis and biological properties of those cancers. The significance of gastrin as a marker for diagnostic or prognostic purposes in colorectal cancer requires further study.

  18. Progression criteria for cancer antigen 15.3 and carcinoembryonic antigen in metastatic breast cancer compared by computer simulation of marker data

    DEFF Research Database (Denmark)

    Sölétormos, G; Hyltoft Petersen, P; Dombernowsky, P

    2000-01-01

    BACKGROUND: We investigated the utility of computer simulation models for performance comparisons of different tumor marker assessment criteria to define progression or nonprogression of metastatic breast cancer. METHODS: Clinically relevant values for progressive cancer antigen 15...... of progression. CONCLUSIONS: The computer simulation model is a fast, effective, and inexpensive approach for comparing the diagnostic potential of assessment criteria during clinically relevant conditions of steady-state and progressive disease. The model systems can be used to generate tumor marker assessment...

  19. Prostate specific antigen levels and prostate cancer detection rates in patients with end stage renal disease.

    Science.gov (United States)

    Chen, Catherine J; Heldt, Jonathan P; Anderson, Kirk M; Ruckle, Herbert C; Agarwal, Gautum; Smith, Damien L; Schlaifer, Amy E; Richards, Gideon D; Arnold, Don C; Baldwin, D Duane

    2012-06-01

    Patients with end stage renal disease plus prostate cancer are ineligible to receive a renal transplant at most centers until an acceptable cancer-free period is demonstrated. To our knowledge previously established prostate specific antigen reference ranges have not been validated in patients with end stage renal disease. We determined age stratified 95th percentile prostate specific antigen reference ranges and the prostate cancer detection rate at specific prostate specific antigen intervals for patients with end stage renal disease. We retrospectively reviewed the records of 775 male patients with end stage renal disease on the waiting list for a renal transplant who had undergone a serum prostate specific antigen test. Prostate specific antigen was stratified by age at the time of the blood test and 95th percentile reference ranges were calculated for each decade. A total of 80 patients underwent prostate biopsy for increased prostate specific antigen and/or abnormal digital rectal examination. The cancer detection rate was calculated for specific prostate specific antigen reference ranges. The age specific 95th percentile prostate specific antigen references ranges were 0 to 4.0 ng/ml for ages 40 to 49 in 137 patients, 0 to 5.3 ng/ml for ages 50 to 59 in 257, 0 to 10.5 ng/ml for ages 60 to 69 in 265 and 0 to 16.6 ng/ml for ages 70 to 79 years in 69. The cancer detection rate was 44%, 38% and 67% for prostate specific antigen 2.5 to 4.0, 4 to 10 and greater than 10 ng/ml, respectively. In our study population of patients with end stage renal disease age stratified prostate specific antigen was higher than in the general population. The cancer detection rate was increased in our patients with end stage renal disease compared to that in patients with normal renal function at specific prostate specific antigen intervals. Lower prostate specific antigen cutoffs may be appropriate to recommend prostate biopsy in patients with end stage renal disease. Copyright

  20. Prostate cancer in the Baby Boomer generation: results from CaPSURE.

    Science.gov (United States)

    Scales, Charles D; Moul, Judd W; Curtis, Lesley H; Elkin, Eric P; Hughes, M E; Carroll, Peter R

    2007-12-01

    Baby Boomers (those born in 1946 to 1964) are thought to place a high value on quality of life, and have a higher propensity to consume healthcare services than previous generations. We sought to characterize prostate cancer (CaP) presentation among this group, and determine whether treatment patterns differ between Baby Boomers and the preceding generation. We defined two birth cohorts: men born in 1927 to 1945 (pre-Boomers) and Baby Boomers. Our study cohort included men less than 65 years old, diagnosed with CaP between 1999 and 2003 (Baby Boomers, n = 812; pre-Boomers, n = 1843). We compared the two groups for clinical presentation, sociodemographics, and primary treatment, controlling for age effects. The primary endpoint was selection of radical prostatectomy as primary treatment. Most Baby Boomers were diagnosed with stage T1 disease (466, 61%), biopsy Gleason sums less than 7 (572, 73%), and prostate-specific antigen levels of 4.1 to 10.0 (509, 66%). This presentation was not clinically different from pre-Boomers. Baby Boomers had higher socioeconomic status than pre-Boomers. On multivariate analysis, Baby Boomers were more likely to undergo radical prostatectomy as primary therapy (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.13 to 2.35). Controlling for age effects, however, there were no significant differences in treatment choice (OR 0.86, 95% CI 0.40 to 1.87) or sociodemographics between these groups. Differences in CaP presentation and treatment between Baby Boomers and pre-Boomers may be related to age at diagnosis rather than innate differences in behavior. As more Baby Boomers are diagnosed with CaP, further research will be required to characterize this generation's impact on CaP care.

  1. Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine

    NARCIS (Netherlands)

    Weinert, Brian T.; Krishnadath, Kausilia K.; Milano, Francesca; Pedersen, Ayako W.; Claesson, Mogens H.; Zocca, Mai-Britt

    2009-01-01

    Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated

  2. Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen

    NARCIS (Netherlands)

    A.J. Vickers (Andrew); D. Sjoberg (Daniel); D. Ulmert (David); E. Vertosick (Emily); M.J. Roobol-Bouts (Monique); I.M. Thompson (Ian); E.A.M. Heijnsdijk (Eveline); H.J. de Koning (Harry); C. Atoria-Swartz (Coral); P.T. Scardino (Peter); H. Lilja (Hans)

    2014-01-01

    textabstractBackground: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing

  3. NY-ESO-1 cancer testis antigen demonstrates high immunogenicity in triple negative breast cancer.

    Science.gov (United States)

    Ademuyiwa, Foluso O; Bshara, Wiam; Attwood, Kristopher; Morrison, Carl; Edge, Stephen B; Karpf, Adam R; James, Smith A; Ambrosone, Christine B; O'Connor, Tracey L; Levine, Ellis G; Miliotto, Anthony; Ritter, Erika; Ritter, Gerd; Gnjatic, Sacha; Odunsi, Kunle

    2012-01-01

    NY-ESO-1 cancer testis (CT) antigen is an attractive candidate for immunotherapy as a result of its high immunogenicity. The aim of this study was to explore the potential for NY-ESO-1 antigen directed immunotherapy in triple negative breast cancer (TNBC) by determining the frequency of expression by immunohistochemistry (IHC) and the degree of inherent immunogenicity to NY-ESO-1. 168 TNBC and 47 ER+/HER2- primary breast cancer specimens were used to determine NY-ESO-1 frequency by IHC. As previous studies have shown that patients with a robust innate humoral immune response to CT antigens are more likely to develop CD8 T-cell responses to NY-ESO-1 peptides, we evaluated the degree to which patients with NY-ESO-1 expression had inherent immunogenicity by measuring antibodies. The relationship between NY-ESO-1 expression and CD8+ T lymphocytes was also examined. The frequency of NY-ESO-1 expression in the TNBC cohort was 16% versus 2% in ER+/HER2- patients. A higher NY-ESO-1 score was associated with a younger age at diagnosis in the TNBC patients with NY-ESO-1 expression (p = 0.026). No differences in OS (p = 0.278) or PFS (p = 0.238) by NY-ESO-1 expression status were detected. Antibody responses to NY-ESO-1 were found in 73% of TNBC patients whose tumors were NY-ESO-1 positive. NY-ESO-1 positive patients had higher CD8 counts than negative patients (p = 0.018). NY-ESO-1 is expressed in a substantial subset of TNBC patients and leads to a high humoral immune response in a large proportion of these individuals. Given these observations, patients with TNBC may benefit from targeted therapies directed against NY-ESO-1.

  4. Exosomes derived from tumor cells genetically modified to express Mycobacterium tuberculosis antigen: a novel vaccine for cancer therapy.

    Science.gov (United States)

    Koyama, Yoshiyuki; Ito, Tomoko; Hasegawa, Aya; Eriguchi, Masazumi; Inaba, Toshio; Ushigusa, Takahiro; Sugiura, Kikuya

    2016-11-01

    To examine the potential of exosomes derived from the tumor cells, which had been genetically modified to express a Mycobacterium tuberculosis antigen, as a cancer vaccine aimed at overcoming the weak immunogenicity of tumor antigens. We transfected B16 melanoma cells with a plasmid encoding the M. tuberculosis antigen, early secretory antigenic target-6 (ESAT-6). The secreted exosomes bearing both tumor-associated antigens and the pathogenic antigen (or their epitopes) were collected. When the exosomes were injected into foot pads of mice, they significantly (p exosomes significantly suppressed (p exosomes derived from the non-transfected B16 cells showed no effect on tumor growth, although both exosomes should have similar tumor antigens. Exosomes bearing both tumor antigens and the M. tuberculosis antigen (or their epitopes) have a high potential as a candidate for cancer vaccine to overcome the immune escape by tumor cells.

  5. Turning tumour cells into antigen presenting cells: The next step to improve cancer immunotherapy?

    Science.gov (United States)

    de Charette, Marie; Marabelle, Aurélien; Houot, Roch

    2016-11-01

    Downregulation/loss of the antigen presentation is a major immune escape mechanism in cancer. It allows tumour cells to become 'invisible' and avoid immune attack by antitumour T cells. In tumour harbouring properties of professional antigen presenting cells (i.e. tumour B cells in lymphoma), downregulation/loss of the antigen presentation may also prevent direct priming of naïve T cells by tumour cells. Here, we review treatments that may induce/restore antigen presentation by the tumour cells. These treatments may increase the generation of antitumour T cells and/or their capacity to recognise and eliminate tumour cells. By forcing tumour cells to present their antigens, these treatments may sensitise patients to T cell-based immunotherapies, including checkpoint inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Antigen-specific immunotherapy in ovarian cancer and p53 as tumor antigen

    NARCIS (Netherlands)

    Vermeij, Renee; Leffers, Ninke; Melief, Cornelis J.; Daemen, Toos; Nijman, Hans W.

    This review discusses the results of different immunization strategies, identifies possible drawbacks in study design and provides potential solutions for augmentation of clinical efficacy. A potential target for cancer immunotherapy is p53, as approximately 50% of ovarian cancer cells carry p53

  7. Immunologic aspect of ovarian cancer and p53 as tumor antigen

    Directory of Open Access Journals (Sweden)

    van der Burg SH

    2005-09-01

    Full Text Available Abstract Ovarian cancer represents the fifth leading cause of death from all cancers for women. During the last decades overall survival has improved due to the use of new chemotherapy schedules. Still, the majority of patients die of this disease. Research reveals that ovarian cancer patients exhibit significant immune responses against their tumor. In this review the knowledge obtained thus far on the interaction of ovarian cancer tumor cells and the immune system is discussed. Furthermore the role of p53 as tumor antigen and its potential role as target antigen in ovarian cancer is summarized. Based on the increased knowledge on the role of the immune system in ovarian cancer major improvements are to be expected of immunotherapy based treatment of this disease.

  8. Cancer testis antigen SPAG9 is a promising marker for the diagnosis and treatment of lung cancer.

    Science.gov (United States)

    Ren, Biqiong; Wei, Xiaobin; Zou, Guoying; He, Junyu; Xu, Guofeng; Xu, Fei; Huang, Yiran; Zhu, Haowen; Li, Yong; Ma, Guoan; Yu, Ping

    2016-05-01

    Cancer testis antigen sperm-associated antigen 9 (SPAG9) is highly expressed in many types of cancers. In the present study, to obtain a better understanding of the relevance of SPAG9 in cancer diagnosis and treatment, the expression of SPAG9 mRNA and protein in lung cancer specimens was evaluated by RT-PCR, western blotting and immunohistochemistry. ELISA was used to quantify the SPAG9 autoantibody in the peripheral blood of lung cancer patients. The results showed that the expression of SPAG9 mRNA and protein in the lung cancer tissues was significantly higher than that in the adjacent non-cancerous tissues (Plung cancer patients was significantly higher than the level in the healthy controls (Plung cancer patients than these levels in the untreated patients (P=0.006, P=0.026, respectively), while no statistical difference was found between treated and untreated squamous cell carcinoma patients. Our results suggest that the SPAG9 antibody in serum is a promising marker for the diagnosis of lung cancer, and the level of the humoral immune response to this antigen appears to be related to the type of lung cancer.

  9. ca 15-3, ceruloplasmin and tissue polypeptide specific antigen as a ...

    African Journals Online (AJOL)

    hi-tech

    2000-06-01

    Jun 1, 2000 ... out of 59 patients with breast cancer had metastatic disease or relapse while the remaining 31 were in remission. Twelve of the. 15 patients in remission were on adjuvant therapy (chemo- or hormonal) at the time of this study following a radical or modified radical mastectomy with or without radiotherapy.

  10. Cancer testis antigen vaccination affords long-term protection in a murine model of ovarian cancer.

    Directory of Open Access Journals (Sweden)

    Maurizio Chiriva-Internati

    Full Text Available Sperm protein (Sp17 is an attractive target for ovarian cancer (OC vaccines because of its over-expression in primary as well as in metastatic lesions, at all stages of the disease. Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 cells, following prophylactic and therapeutic treatments. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17 was shown to be expressed in an OC mouse model, and that vaccination against this antigen significantly controlled tumor growth. Our study shows that the CpG-adjuvated Sp17 vaccine overcomes the issue of immunologic tolerance, the major barrier to the development of effective immunotherapy for OC. Furthermore, this study provides a better understanding of OC biology by showing that Th-17 cells activation and contemporary immunosuppressive T-reg cells inhibition is required for vaccine efficacy. Taken together, these results indicate that prophylactic and therapeutic vaccinations can induce long-standing protection against OC and delay tumor growth, suggesting that this strategy may provide additional treatments of human OC and the prevention of disease onset in women with a family history of OC.

  11. Prostate-specific antigen doubling time and response to cabazitaxel in a hormone-resistant metastatic prostate cancer patient

    OpenAIRE

    Ghosn, Marwan; Dagher, Alain; El-Karak, Fadi

    2014-01-01

    Abstract We report a case of metastatic castration-resistant prostate cancer, who received prior treatment with docetaxel and was then given cabazitaxel as salvage therapy. The patient was monitored by prostate-specific antigen doubling time and prostate-specific antigen absolute value. The prostate-specific antigen doubling time was found to be a good response predictor in the patient.

  12. Prostate-specific antigen doubling time and response to cabazitaxel in a hormone-resistant metastatic prostate cancer patient.

    Science.gov (United States)

    Ghosn, Marwan; Dagher, Alain; El-Karak, Fadi

    2015-09-01

    We report a case of metastatic castration-resistant prostate cancer, who received prior treatment with docetaxel and was then given cabazitaxel as salvage therapy. The patient was monitored by prostate-specific antigen doubling time and prostate-specific antigen absolute value. The prostate-specific antigen doubling time was found to be a good response predictor in the patient.

  13. Decline in CA19-9 during chemotherapy predicts survival in four independent cohorts of patients with inoperable bile duct cancer.

    Science.gov (United States)

    Grunnet, Mie; Christensen, Ib J; Lassen, Ulrik; Jensen, Lars H; Lydolph, Magnus; Knox, Jennifer J; McNamara, Mairead G; Jitlal, Mark; Wasan, Harpreet; Bridgewater, John; Valle, Juan W; Mau-Sorensen, Morten

    2015-07-01

    Carbohydrate associated antigen (CA19-9) has been approved by the FDA as a biomarker for monitoring treatment effect in pancreatic cancer. However, the value of serum CA19-9 as a biomarker of response to chemotherapy in bile duct cancer is unclear. The aim of this study was to determine if a decline in CA19-9 (CA19-9 response) during chemotherapy is predictive of survival in patients with inoperable bile duct cancer. Consecutive patients with inoperable bile duct cancer treated at a University Hospital were retrospectively included in an investigational cohort (n = 212). Three validation cohorts were established including patients 1) participating in phase I/II trials at a Danish Hospital (n = 71), 2) identified retrospectively in a Canadian cohort (n = 196) and 3) randomized in the ABC-02 trial (n = 410). Patients with a baseline CA19-9 and at least one CA19-9 value measured 10-12 weeks after the start of chemotherapy were included. Multivariate Cox regression analyses were performed. Patients meeting the criteria to be included were 54 in the investigational cohort and 34, 68 and 148 in the three validation sets, respectively. Multivariate analysis included radiological response, performance status, bilirubin, gender, site of cancer, extend of disease, CA19-9 at baseline and age. A hazard ratio (HR) of 0.60 (95%CI: 0.44-0.80, p = 0.0005) for death in CA19-9 responders was reached in the investigational cohort. The predictive value of CA 19-9 response was confirmed in all three validation cohorts. CA19-9 response is a robust predictor of survival in patients with inoperable bile duct cancer in four independent data sets. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Systematic review: Tumor-associated antigen autoantibodies and ovarian cancer early detection.

    Science.gov (United States)

    Fortner, Renée Turzanski; Damms-Machado, Antje; Kaaks, Rudolf

    2017-11-01

    Tumor-associated autoantibodies (AAbs), produced as an immune response to tumor-associated antigens (TAAs), are a novel pathway of early detection markers. We conducted a systematic review on AAbs and ovarian cancer to summarize the diagnostic performance of individual AAbs and AAb panels. A total of 29 studies including 85 AAbs were included; 27 of the studies were conducted in prevalent cases and cancer-free controls and 2 investigations included pre-diagnosis samples. The majority of studies were hypothesis-driven, evaluating AAbs to target TAAs; 10 studies used screening approaches such as serological expression cloning (SEREX) and nucleic acid-programmable protein arrays (NAPPA). The highest sensitivities for individual AAbs were reported for RhoGDI-AAbs (89.5%) and TUBA1C-AAbs (89%); however, specificity levels were relatively low (80% and 75%, respectively). High sensitivities at high specificities were reported for HOXA7-AAbs for detection of moderately differentiated ovarian tumors (66.7% sensitivity at 100% specificity) and IL8-AAbs in stage I-II ovarian cancer (65.5% sensitivity at 98% specificity). A panel of 11 AAbs (ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3) provided 45% sensitivity at 98% specificity for serous ovarian cancer, when at least 2 AAbs were above a threshold of 95% specificity. Twelve of the AAbs identified in this review were investigated in more than one study. Data on diagnostic discrimination by tumor histology and stage at diagnosis are sparse. Limited data suggest select AAb markers improve diagnostic discrimination when combined with markers such as CA125 and HE4. AAbs for ovarian cancer early detection is an emerging area, and large-scale, prospective investigations considering histology and stage are required for discovery and validation. However, data to date suggests panels of AAbs may eventually reach sufficient diagnostic discrimination to allow earlier detection of disease as a complement to

  15. Identification of salt-inducible kinase 3 as a novel tumor antigen associated with tumorigenesis of ovarian cancer.

    Science.gov (United States)

    Charoenfuprasert, S; Yang, Y-Y; Lee, Y-C; Chao, K-C; Chu, P-Y; Lai, C-R; Hsu, K-F; Chang, K-C; Chen, Y-C; Chen, L-T; Chang, J-Y; Leu, S-J; Shih, N-Y

    2011-08-18

    Existence of humoral immunity has been previously demonstrated in malignant ascitic fluids. However, only a limited number of immunogenic tumor-associated antigens (TAAs) were identified, and few of which are associated with ovarian cancer. Here, we identified salt-inducible kinase 3 (SIK3) as a TAA through screening of a random peptide library in the phage display system. Overexpression of SIK3 markedly promoted cell proliferation, attenuated p21(Waf/Cip1) and p27(Kip) expressions in low-grade OVCAR3 cells, and permitted the cells to grow in mice. Decrease in SIK3 expression in high-grade SK-OV3 cells consistently demonstrated its tumorigenic potency by modulating the protein levels of cell cycle regulators. When the expressions of SIK3 and CA125 were compared in cancer tissues, immunohistochemical (IHC) studies indicated that cytoplasm-localized SIK3 was highly expressed in 55% of the ovarian cancer samples. In contrast, it was rarely detected in adenomyosis, leiomyoma and normal ovary tissues, showing its higher specificity (97%) to CA125 (65%) in ovarian cancer. Moreover, experiments using pharmacological inhibitors to block SIK3-induced p21(Waf/Cip1) expression revealed that activation of c-Src and phosphoinositide-3-kinase were critically required for its biological activity, suggesting that they are the downstream signaling mediators of SIK3. These data were further supported by IHC studies, showing coexpression of c-Src with SIK3 in 85% of the ovarian tumor samples stained positive for SIK3. Collectively, our findings indicate that SIK3 is a novel ovarian TAA. Overexpression of SIK3 promotes G1/S cell cycle progression, bestows survival advantages to cancer cells for growth and correlates the clinicopathological conditions of patients with ovarian cancer.

  16. Activation of Cdc42 is necessary for sustained oscillations of Ca2+ and PIP2 stimulated by antigen in RBL mast cells

    Directory of Open Access Journals (Sweden)

    Marcus M. Wilkes

    2014-07-01

    Full Text Available Antigen stimulation of mast cells via FcεRI, the high-affinity receptor for IgE, triggers a signaling cascade that requires Ca2+ mobilization for exocytosis of secretory granules during the allergic response. To characterize the role of Rho GTPases in FcεRI signaling, we utilized a mutant RBL cell line, B6A4C1, that is deficient in antigen-stimulated Cdc42 activation important for these processes. Recently the importance of stimulated intracellular oscillations has emerged, and we find that B6A4C1 cells exhibit severely attenuated Ca2+ oscillations in response to antigen, which are restored to wild-type RBL-2H3 levels by expression of constitutively active Cdc42 G12V or by a GEF for Cdc42, DOCK7, but not when the C-terminal di-arginine motif of active Cdc42 is mutated to di-glutamine. We found that antigen-stimulated FcεRI endocytosis, which occurs independently of Ca2+ mobilization, is also defective in B6A4C1 cells, and Cdc42 G12V reconstitutes this response as well. Thus, activation of Cdc42 occurs prior to and is critical for antigen-stimulated pathways leading separately to both Ca2+ mobilization and receptor endocytosis. Accounting for these downstream functional consequences, we show that Cdc42 G12V reconstitutes antigen-stimulated oscillations of phosphatidylinositol 4,5-bisphosphate (PIP2 at the plasma membrane in mutant B6A4C1 cells, pointing to Cdc42 participation in the regulation of stimulated PIP2 synthesis.

  17. Prostate-specific antigen-activated thapsigargin prodrug as targeted therapy for prostate cancer

    DEFF Research Database (Denmark)

    Denmeade, Samuel R; Jakobsen, Carsten M; Janssen, Samuel

    2003-01-01

    Standard anti-proliferative chemotherapy is relatively ineffective against slowly proliferating androgen-independent prostate cancer cells within metastatic sites. In contrast, the lipophilic cytotoxin thapsigargin, which causes apoptosis by disrupting intracellular free Ca2+ levels, is effective...

  18. Expression of the cancer-testis antigen BORIS correlates with prostate cancer.

    Science.gov (United States)

    Cheema, Zubair; Hari-Gupta, Yukti; Kita, Georgia-Xanthi; Farrar, Dawn; Seddon, Ian; Corr, John; Klenova, Elena

    2014-02-01

    BORIS, a paralogue of the transcription factor CTCF, is a member of the cancer-testis antigen (CT) family. BORIS is normally present at high levels in the testis; however it is aberrantly expressed in various tumors and cancer cell lines. The main objectives of this study were to investigate BORIS expression together with sub-cellular localization in both prostate cell lines and tumor tissues, and assess correlations between BORIS and clinical/pathological characteristics. We examined BORIS mRNA expression, protein levels and cellular localization in a panel of human prostate tissues, cancer and benign, together with a panel prostate cell lines. We also compared BORIS levels and localization with clinical/pathological characteristics in prostate tumors. BORIS was detected in all inspected prostate cancer cell lines and tumors, but was absent in benign prostatic hyperplasia. Increased levels of BORIS protein positively correlated with Gleason score, T-stage and androgen receptor (AR) protein levels in prostate tumors. The relationship between BORIS and AR was further highlighted in prostate cell lines by the ability of ectopically expressed BORIS to activate the endogenous AR mRNA and protein. BORIS localization in the nucleus plus cytoplasm was also associated with higher BORIS levels and Gleason score. Detection of BORIS in prostate tumors suggests potential applications of BORIS as a biomarker for prostate cancer diagnosis, as an immunotherapy target and, potentially, a prognostic marker of more aggressive prostate cancer. The ability of BORIS to activate the AR gene indicates BORIS involvement in the growth and development of prostate tumors. © 2013 Wiley Periodicals, Inc.

  19. Effect of [10]-Gingerol on [Ca2+]i and Cell Death in Human Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chung-Yi Chen

    2009-03-01

    Full Text Available The effect of [10]-gingerol on cytosol free Ca2+ concentration ([Ca2+]i and viability is large unknown. This study examines the early signaling effects of [10]-gingerol on human colorectal cancer cells. It was found that this compound caused a slow and sustained rise of [Ca2+]i in a concentration-dependent manner. [10]-Gingerol also induced a [Ca2+]i rise when extracellular Ca2+ was removed, but the magnitude was reduced by 38%. In a Ca2+-free medium, the [10]-gingerol-induced [Ca2+]i rise was partially abolished by depleting stored Ca2+ with thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor. The elevation of [10]-gingerol-caused [Ca2+]i in a Ca2+-containing medium was not affected by modulation of protein kinase C activity. The [10]-gingerol-induced Ca2+ influx was insensitive to L-type Ca2+ channel blockers. At concentrations of 10-100 mM, [10]-gingerol killed cells in a concentration-dependent manner. These findings suggest that [10]-gingerol induces [Ca2+]i rise by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx from non-L-type Ca2+ channels in SW480 cancer cells.

  20. Effect of [10]-Gingerol on [Ca2+]i and Cell Death in Human Colorectal Cancer Cells

    OpenAIRE

    Chung-Yi Chen; Yi-Wen Li; Soong-Yu Kuo

    2009-01-01

    The effect of [10]-gingerol on cytosol free Ca2+ concentration ([Ca2+]i) and viability is large unknown. This study examines the early signaling effects of [10]-gingerol on human colorectal cancer cells. It was found that this compound caused a slow and sustained rise of [Ca2+]i in a concentration-dependent manner. [10]-Gingerol also induced a [Ca2+]i rise when extracellular Ca2+ was removed, but the magnitude was reduced by 38%. In a Ca2+-free medium, the [10]-gingerol-induced [Ca2+]i rise w...

  1. caGrid 1.0: a Grid enterprise architecture for cancer research.

    Science.gov (United States)

    Oster, Scott; Langella, Stephen; Hastings, Shannon; Ervin, David; Madduri, Ravi; Kurc, Tahsin; Siebenlist, Frank; Covitz, Peter; Shanbhag, Krishnakant; Foster, Ian; Saltz, Joel

    2007-10-11

    caGrid is the core Grid architecture of the NCI-sponsored cancer Biomedical Informatics Grid (caBIG) program. The current release, caGrid version 1.0, is developed as the production Grid software infrastructure of caBIG. Based on feedback from adopters of the previous version (caGrid 0.5), it has been significantly enhanced with new features and improvements to existing components. This paper presents an overview of caGrid 1.0, its main components, and enhancements over caGrid 0.5.

  2. Association between expression levels of CA 19-9 and N-acetylglucosamine-beta;1,3-galactosyltransferase 5 gene in human pancreatic cancer tissue.

    Science.gov (United States)

    Hayashi, Nobuyasu; Nakamori, Shoji; Okami, Jiro; Nagano, Hiroaki; Dono, Keizo; Umeshita, Koji; Sakon, Masato; Narimatsu, Hisashi; Monden, Morito

    2004-01-01

    CA 19-9, equivalent to Sialyl Lewis antigen, is a well-known tumor marker in pancreatic cancer. At the initial step of the biosynthesis of CA 19-9, N-acetylglucosamine-beta1,3-galactosyltransferase (beta3Gal-T) transfers galactose to N-acetylglucosamine (GlcNAc). Recently, beta3Gal-T5 has been presumed to be related to the formation of the type 1 chain in an in vitro experiment in terms of kinetic enzyme characterization. The purpose of this study was to investigate which beta3Gal-T is related to the synthesis of CA 19-9 in human pancreatic cancer tissues. We examined beta;3Gal-T1, T2, T3, T4, and beta;3Gal-T5 mRNA expressions in 13 noncancerous and cancerous tissues of the human pancreas using real-time polymerase chain reaction, and compared those gene expression levels with the immunoreactivity of CA 19-9 and its precursor DUPAN-2 in cancerous tissues. Beta;3Gal-T5 gene expression significantly augmented in cancerous tissues, when compared with the adjacent noncancerous tissues. Additionally, there was a good correlation between BETA;3GAL-T5 gene transcription levels and immunohistochemical grades of CA 19-9 or its precursor DUPAN-2 in cancerous tissues. However, no correlation was observed between beta;3Gal-T1, T2, T3, and beta;3Gal-T4 gene expression levels and CA 19-9 or DUPAN-2 immunoreactive grades in cancerous tissue. beta3Gal-T5 is presumed to be responsible for the synthesis of CA 19-9 in pancreatic cancer tissue. Copyright 2004 S. Karger AG, Basel

  3. Pretreatment prostate specific antigen doubling time as prognostic factor in prostate cancer patients

    OpenAIRE

    Zharinov, Gennady M.; Bogomolov, Oleg A.; Neklasova, Natalia N.; Anisimov, Vladimir N.

    2017-01-01

    Despite the prostate-specific antigen (PSA) serum level commonly uses as tumor marker in diagnosis of prostate cancer, it seems that PSA doubling time (PSADT) could be more useful indicator of tumor behavior and of prognosis for patients. The results of hormone and radiation therapy were evaluated for 912 prostate cancer having at least 2 PSA tests before the treatment was started. Clustering procedure (selection of homogenous group) was performed by using PSADT as the classification marker. ...

  4. Frequent High Expression of Kita-Kyushu Lung Cancer Antigen-1 (KK-LC-1) in Gastric Cancer.

    Science.gov (United States)

    Shida, Akiko; Futawatari, Nobue; Fukuyama, Takashi; Ichiki, Yoshinobu; Takahashi, Yoshihito; Nishi, Yatsushi; Kobayashi, Noritada; Yamazaki, Hitoshi; Watanabe, Masahiko

    2015-06-01

    The tumor-associated antigen Kita-Kyushu lung cancer antigen-1 (KK-LC-1) has been reported as not being expressed in normal tissues, except for the testis, and in the setting of non-small cell lung cancer. The present study demonstrated that KK-LC-1 is expressed in gastric cancer. We analyzed the expression of KK-LC-1 and cancer/testis antigens (CTAs) in surgical specimens of 49 gastric carcinomas. The expression of KK-LC-1 and CTAs was assessed using reverse transcription-polymerase chain reaction. KK-LC-1 expression was observed in gastric carcinomas. The number of lesions with expression of KK-LC-1, Melanoma antigen gene encoding-A1 (MAGE-A1), MAGE-A3 and New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) was 40 (81.6%), 17 (34.7%), 22 (44.9%) and 8 (16.3%) out of the 49 specimens, respectively. KK-LC-1 should be categorized as a CTA. The frequency of KK-LC-1 expression was higher than that of the other CTAs. KK-LC-1 might be a useful target for immunotherapy and in diagnosis of gastric cancer. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. The SSX Family of Cancer-Testis Antigens as Target Proteins for Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Heath A. Smith

    2010-01-01

    Full Text Available Cancer-testis antigens (CTAs represent an expanding class of tumor-associated proteins defined on the basis of their tissue-restricted expression to testis or ovary germline cells and frequent ectopic expression in tumor tissue. The expression of CTA in MHC class I-deficient germline cells makes these proteins particularly attractive as immunotherapeutic targets because they serve as essentially tumor-specific antigens for MHC class I-restricted CD8+ T cells. Moreover, because CTAs are expressed in many types of cancer, any therapeutic developed to target these antigens might have efficacy for multiple cancer types. Of particular interest among CTAs is the synovial sarcoma X chromosome breakpoint (SSX family of proteins, which includes ten highly homologous family members. Expression of SSX proteins in tumor tissues has been associated with advanced stages of disease and worse patient prognosis. Additionally, both humoral and cell-mediated immune responses to SSX proteins have been demonstrated in patients with tumors of varying histological origin, which indicates that natural immune responses can be spontaneously generated to these antigens in cancer patients. The current review will describe the history and identification of this family of proteins, as well as what is known of their function, expression in normal and malignant tissues, and immunogenicity.

  6. Chemoresistance Is Associated with MUC1 and Lewis y Antigen Expression in Ovarian Epithelial Cancers

    Directory of Open Access Journals (Sweden)

    Danye Zhang

    2013-05-01

    Full Text Available Objective: The aim of this study was to analyze the correlation and clinical significance between the expression of Mucin-1 (MUC1 and the Lewis y antigen with chemoresistance in ovarian epithelial cancers. Methods: Ovarian cancer patients (n = 92 treated at our hospital from May 2005 to July 2009 were divided, according to their treatment and follow-up outcomes, into a resistant group (n = 37 or sensitive group (n = 55. The expression of MUC1 and Lewis y antigen in ovarian cancer tissues was detected using immunohistochemistry and correlated with chemoresistance. Results: The positive rates of MUC1 and Lewis y antigen in the resistant group were both 91.89%, significantly higher than their positive rates in the sensitive group (65.45% and 69.09%, respectively, and both p < 0.05. MUC1 or Lewis y expression and the pathological stage of the tissue were independent risk factors for chemoresistance (all p < 0.05. Conclusion: The increased expression of MUC1 and the Lewis y antigen is a significant risk factor for chemoresistance in patients with ovarian epithelial cancer.

  7. Carbohydrate antigen 549 in metastatic breast cancer during cytostatic treatment and follow-up

    DEFF Research Database (Denmark)

    Sölétormos, G; Nielsen, D; Schiøler, V

    1992-01-01

    This study was designed to investigate whether the serum tumour marker CA 549 gave early and reliable information about disease activity among metastatic breast cancer patients during cytostatic treatment and follow-up. 50 females with metastatic breast cancer were monitored clinically...... among 91% by marker progression. Clinical progression was excluded among 93% without marker progression. In conclusion, monitoring of metastatic breast cancer patients could include CA 549 if standardised criteria for marker evaluation are used....... and with the tumour marker CA 549. Response evaluation was based upon clinical (World Health Organization) and elaborated CA 549 criteria, respectively. In 113 blindly and matched evaluations, concordance appeared in 73/113 and discordance in 40/113 evaluations. In 27, discordance concerned degree of response, in 2...

  8. Prostate-specific antigen: does the current evidence support its use in prostate cancer screening?

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Although widely used, the value of prostate-specific antigen (PSA) in screening asymptomatic men for prostate cancer is controversial. Reasons for the controversy relate to PSA being less than an ideal marker in detecting early prostate cancer, the possibility that screening for prostate cancer may result in the overdetection and thus overtreatment of indolent disease and the lack of clarity as to the definitive or best treatment for men diagnosed with localized prostate cancer. Although the results from some randomized prospective trials suggest that screening with PSA reduces mortality from prostate cancer, the overall benefit was modest. It is thus currently unclear as to whether the modest benefit of reduced mortality outweighs the harms of overdetection and overtreatment. Thus, prior to undergoing screening for prostate cancer, men should be informed of the risks and benefits of early detection. Newly emerging markers that may complement PSA in the early detection of prostate cancer include specific isoforms of PSA and PCA3.

  9. Interfering Effect of Black Tea Consumption on Diagnosis of Pancreatic Cancer by CA 19-9.

    Science.gov (United States)

    Al-Janabi, Ali Abdul Hussein S; Tawfeeq, Ekhlas F

    2017-06-01

    The study aims to determine the possible effects of black tea consumption on the level of CA 19-9 antigen in the human body. The level of CA 19-9 was measured in 270 healthy individuals who consumed heavy amounts of black tea. About 43.3 % of involved individuals were revealed to have elevated levels of CA 19-9. Males with high values of CA 19-9 represented the greatest number of involved individuals. The cutoff value of high levels of CA 19-9 in all individuals was ranged 69-105 U/ml. Consuming heavy amounts of black tea could be considered an important interfering factor that affects the levels of CA 19-9. The cutoff or predictive value of CA 19-9 in heavy-consuming people of black tea was determined.

  10. The role of GAGE cancer/testis antigen in metastasis

    DEFF Research Database (Denmark)

    Gjerstorff, Morten Frier; Terp, Mikkel Green; Hansen, Malene Bredahl

    2016-01-01

    with migratory and invasive properties and were found to be upregulated in cancer cells with metastasizing potential in a gastric cancer model. METHODS: We have addressed the direct role of GAGE proteins in supporting metastasis using an isogenic metastasis model of human cancer, consisting of 4 isogenic cell......) and moderately metastatic clones (LM3), stable downregulation of GAGE expression did not affect the ability of CL16 cells to establish primary tumors and form metastasis in the lungs of immunodeficient mice. CONCLUSIONS: These results suggest that GAGE proteins per se do not support metastasis and that further...

  11. Extracellular Ca(2+)-dependent enhancement of cytocidal potency of zoledronic acid in human oral cancer cells.

    Science.gov (United States)

    Inoue, Sayaka; Arai, Naoya; Tomihara, Kei; Takashina, Michinori; Hattori, Yuichi; Noguchi, Makoto

    2015-08-15

    Direct antitumor effects of bisphosphonates (BPs) have been demonstrated in various cancer cells in vitro. However, the effective concentrations of BPs are typically much higher than their clinically relevant concentrations. Oral cancers frequently invade jawbone and may lead to the release of Ca(2+) in primary lesions. We investigated the effects of the combined application of zoledronic acid (ZA) and Ca(2+) on proliferation and apoptosis of oral cancer cells. Human oral cancer cells, breast cancer cells, and colon cancer cells were treated with ZA at a wide range of concentrations in different Ca(2+) concentration environments. Under a standard Ca(2+) concentration (0.6mM), micromolar concentrations of ZA were required to inhibit oral cancer cell proliferation. Increasing extracellular Ca(2+) concentrations greatly enhanced the potency of the ZA cytocidal effect. The ability of Ca(2+) to enhance the cytocidal effects of ZA was negated by the Ca(2+)-selective chelator EGTA. In contrast, the cytocidal effect of ZA was less pronounced in breast and colon cancer cells regardless of whether extracellular Ca(2+) was elevated. In oral cancer cells incubated with 1.6mM Ca(2+), ZA up-regulated mitochondrial Bax expression and increased mitochondrial Ca(2+) uptake. This was associated with decreased mitochondrial membrane potential and increased release of cytochrome c. We suggest that ZA can specifically produce potent cytocidal activity in oral cancer cells in an extracellular Ca(2+)-dependent manner, implying that BPs may be useful for treatment of oral squamous cell carcinoma with jawbone invasion leading to the hypercalcemic state. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Cancer/Testis antigens as potential predictors of biochemical recurrence of prostate cancer following radical prostatectomy

    Directory of Open Access Journals (Sweden)

    Trock Bruce

    2011-09-01

    Full Text Available Abstract Background The Cancer/Testis Antigens (CTAs are an important group of proteins that are typically restricted to the testis in the normal adult but are aberrantly expressed in several types of cancers. As a result of their restricted expression patterns, the CTAs could serve as unique biomarkers for cancer diagnosis/prognosis. The aim of this study was to identify promising CTAs that are associated with prostate cancer (PCa recurrence following radical prostatectomy (RP. Methods The expression of 5 CTAs was measured by quantitative multiplex real-time PCR using prostate tissue samples obtained from 72 patients with apparently clinically localized PCa with a median of two years follow-up (range, 1 to 14 years. Results The expression of CTAs namely, CEP55, NUF2, PBK and TTK were significantly higher while PAGE4 was significantly lower in patients with recurrent disease. All CTAs with the exception of TTK were significantly correlated with the prostatectomy Gleason score, but none were correlated with age, stage, or preoperative PSA levels. In univariate proportional hazards models, CEP55 (HR = 3.59, 95% CI: 1.50-8.60, p = 0.004; NUF2 (HR = 2.28, 95% CI: 1.11-4.67, p = 0.024; and PAGE4 (HR = 0.44, 95% CI: 0.21-0.93, p = 0.031 were significantly associated with the risk of PCa recurrence. However, the results were no longer significant after adjustment for prostatectomy Gleason score. Conclusions To our knowledge, this is the first study to identify CTAs as biomarkers that can differentiate patients with recurrent and non-recurrent disease following RP and underscores its potential impact on PCa prognosis and treatment.

  13. Carcinoembryonic antigen (CEA) as tumor marker in lung cancer

    DEFF Research Database (Denmark)

    Knudsen, Mie Grunnet; Sorensen, J B

    2012-01-01

    The use of CEA as a prognostic and predictive marker in patients with lung cancer is widely debated. The aim of this review was to evaluate the results from studies made on this subject. Using the search words "CEA", "tumor markers in lung cancer", "prognostic significance", "diagnostic...... and risk of death measured over time. No studies found CEA levels useful as a diagnostic marker for lung cancer. With regard to NSCLC the level of CEA measured in tumor tissue in NSCLC patients, were not of prognostic, diagnostic or predictive significance for OS or recurrence after treatment. In one study...... significance" and "predictive significance", a search was carried out on PubMed. Exclusion criteria was articles never published in English, articles before 1981 and articles evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles were found, and 34 were left after selecting those...

  14. Can preoperative CEA and CA19-9 serum concentrations suggest metastatic disease in colorectal cancer patients?

    Science.gov (United States)

    Stojkovic Lalosevic, Milica; Stankovic, Sanja; Stojkovic, Mirjana; Markovic, Velimir; Dimitrijevic, Ivan; Lalosevic, Jovan; Petrovic, Jelena; Brankovic, Marija; Pavlovic Markovic, Aleksandra; Krivokapic, Zoran

    2017-01-01

    This study was designed to investigate the efficiency of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate cancer antigen (CA19-9) levels for diagnosing synchronous liver metastases and lymph node in colorectal carcinoma (CRC) patients. A total of 300 patients with histologically diagnosed CRC were included in this study between May 2014 and March 2015. The data were obtained prospectively from patient's medical records: medical history, demographics, tumor location, differentiation (grade), depth of the tumor (T), lymph node metastases (N), distant metastases (M), lymphatics, venous and perineural invasion, and disease stage. Tumor markers were measured with an electrochemiluminescent assay and the reference value was 5ng/ml for CEA and for Ca19-9, 37u/ml. There was A high statistically significant difference in the levels of serum CEA and CA19-9 between different disease stages of CRC (P<0.001). Regarding different T stages of CRC, We noticed a significant statistical difference in CEA (stage I 3.76±8.73; II 5.68±17.27, III 7.56±14.81, and IV 70.90±253.23) and CA 19-9 levels (stage I 9.65±11.03, II 9.83±11.09; III 19.58±36.91, and IV 228.9±985.38, respectively). The mean CEA and CA19-9 serum levels were significantly higher in patients with regional lymph nodes involvement (CEA 37.21±177.85 vs 4.79±9.90, CA19-9 119.51±687.71 VS 12.24±17.69, respectively, P<0.05) and in liver metastases (CEA 86.56±277.65 vs. 5.98±12.98, and CA19-9 273.27±1073.46 vs. 4.98±3142, respectively, with P<0.001) in comparison to patients without lymph node involvement and liver metastases. We noticed a cut-off value for lymph nodes involvement, for CEA and CA 19-9, 3.5 ng/mL and 7.5 U/mL, respectively. While, a cut-off value for the presence of synchronous liver metastases of these two markers was 3.5ng/mL AND 5.5 U/mL. Our study showed that tumor makers, CEA and CA19-9, can be used as diagnostic factors regarding the severity of CRC specifically to

  15. CdSe/ZnS Quantum Dot-Labeled Lateral Flow Strips for Rapid and Quantitative Detection of Gastric Cancer Carbohydrate Antigen 72-4.

    Science.gov (United States)

    Yan, Xinyu; Wang, Kan; Lu, Wenting; Qin, Weijian; Cui, Daxiang; He, Jinghua

    2016-12-01

    Carbohydrate antigen 72-4 (CA72-4) is an important biomarker associated closely with diagnosis and prognosis of early gastric cancer. How to realize quick, sensitive, specific, and quantitative detection of CA72-4 in clinical specimens has become a great requirement. Herein, we reported a CdSe/ZnS quantum dot-labeled lateral flow test strip combined with a charge-coupled device (CCD)-based reader was developed for rapid, sensitive, and quantitative detection of CA72-4. Two mouse monoclonal antibodies (mAbs) against CA72-4 were employed. One of them was coated as a test line, while another mAb was labeled with quantum dots and coated onto conjugate pad. The goat anti-mouse IgG was immobilized as a control line. After sample was added, a sandwich structure was formed with CA72-4 and these two mAbs. The fluorescent signal from quantum dots (QD)-labeled mAb in sandwich structure was related to the amount of detected CA72-4. A CCD-based reader was used to realize quantitative detection of CA72-4. Results showed that developed QD-labeled lateral flow strips to detect CA72-4 biomarker with the sensitivity of 2 IU/mL and 10 min detection time. One hundred sera samples from clinical patients with gastric cancer and healthy people were used to confirm specificity of this strip method; results showed that established strip method own 100 % reproducibility and 100 % specificity compared with Roche electrochemiluminescence assay results. In conclusion, CdSe/ZnS quantum dot-labeled lateral flow strips for detection of CA72-4 could realize rapid, sensitive, and specific detection of clinical samples and could own great potential in clinical translation in near future.

  16. CdSe/ZnS Quantum Dot-Labeled Lateral Flow Strips for Rapid and Quantitative Detection of Gastric Cancer Carbohydrate Antigen 72-4

    Science.gov (United States)

    Yan, Xinyu; Wang, Kan; Lu, Wenting; Qin, Weijian; Cui, Daxiang; He, Jinghua

    2016-03-01

    Carbohydrate antigen 72-4 (CA72-4) is an important biomarker associated closely with diagnosis and prognosis of early gastric cancer. How to realize quick, sensitive, specific, and quantitative detection of CA72-4 in clinical specimens has become a great requirement. Herein, we reported a CdSe/ZnS quantum dot-labeled lateral flow test strip combined with a charge-coupled device (CCD)-based reader was developed for rapid, sensitive, and quantitative detection of CA72-4. Two mouse monoclonal antibodies (mAbs) against CA72-4 were employed. One of them was coated as a test line, while another mAb was labeled with quantum dots and coated onto conjugate pad. The goat anti-mouse IgG was immobilized as a control line. After sample was added, a sandwich structure was formed with CA72-4 and these two mAbs. The fluorescent signal from quantum dots (QD)-labeled mAb in sandwich structure was related to the amount of detected CA72-4. A CCD-based reader was used to realize quantitative detection of CA72-4. Results showed that developed QD-labeled lateral flow strips to detect CA72-4 biomarker with the sensitivity of 2 IU/mL and 10 min detection time. One hundred sera samples from clinical patients with gastric cancer and healthy people were used to confirm specificity of this strip method; results showed that established strip method own 100 % reproducibility and 100 % specificity compared with Roche electrochemiluminescence assay results. In conclusion, CdSe/ZnS quantum dot-labeled lateral flow strips for detection of CA72-4 could realize rapid, sensitive, and specific detection of clinical samples and could own great potential in clinical translation in near future.

  17. Alternative antibody for the detection of CA19-9 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access GI Monitor assay on the UniCel Dxl 800 Immunoassay System.

    Science.gov (United States)

    Stieber, Petra; Molina, Rafael; Gion, Massimo; Gressner, Axel; Troalen, Frédéric; Holdenrieder, Stefan; Auge, Jose Maria; Zancan, Matelda; Wycislo, Matthias; Jarrige, Véronique

    2008-01-01

    Gastrointestinal cancer antigen CA19-9 is known as a valuable marker for the management of patients with pancreatic cancer. The analytical and clinical performance of the Access GI Monitor assay (Beckman Coulter) was evaluated on the UniCel Dxl 800 Immunoassay System at five different European sites and compared with a reference method, defined as CA19-9 on the Elecsys System (Roche Diagnostics). Total imprecision (%CV) of the GI Monitor ranged between 3.4% and 7.7%, and inter-laboratory reproducibility between 3.6% and 4.0%. Linearity upon dilution showed a mean recovery of 97.4% (SD + 7.2%). Endogenous interferents had no influence on GI Monitor levels (mean recoveries: hemoglobin 103%, bilirubin 106%, triglycerides 106%). There was no high-dose hook effect up to 115,000 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access GI Monitor and Elecsys CA19-9 (R = 0.959, slope = 1.004, intercept = +0.17). GI Monitor serum levels were low in healthy individuals (n = 267, median = 6.0 kU/L, 95th percentile=23.1 kU/L), higher in individuals with various benign diseases (n = 550, medians = 5.8-13.4 kU/L, 95th percentiles = 30.1-195.5 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians = 8.4-233.8 kU/L, 95th percentiles = 53.7-13,902 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the GI Monitor was found for pancreatic cancer [area under the curve (AUC) 0.83]. Results for the reference CA19-9 assay were comparable (AUC 0.85). The Access GI Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with the Elecsys CA19-9. The GI Monitor shows the best diagnostic accuracy in pancreatic cancer. Our results also suggest a clinical value of the GI Monitor in other cancers.

  18. Alternative antibody for the detection of CA125 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access OV Monitor assay on the UniCel Dxl 800 Immunoassay System.

    Science.gov (United States)

    Holdenrieder, Stefan; Molina, Rafael; Gion, Massimo; Gressner, Axel; Troalen, Frédéric; Auge, Jose Maria; Zancan, Matelda; Wycislo, Matthias; Stieber, Petra

    2008-01-01

    Cancer antigen CA125 is known as a valuable marker for the management of ovarian cancer. The analytical and clinical performance of the Access OV Monitor Immunoassay System (Beckman Coulter) was evaluated at five different European sites and compared with a reference system, defined as CA125 on the Elecsys System (Roche Diagnostics). Total imprecision (% CV) of the OV Monitor ranged between 3.1% and 8.8%, and inter-laboratory reproducibility between 4.7% and 5.0%. Linearity upon dilution showed a mean recovery of 100% (SD + 8.1%). Endogenous interferents had no influence on OV Monitor levels (mean recoveries: hemoglobin 107%, bilirubin 103%, triglycerides 103%). There was no high-dose hook effect up to 27,193 kU/L. Clinical performance investigated in sera from 1811 individuals showed a good correlation between the Access OV Monitor and Elecsys CA125 (R = 0.982, slope = 0.921, intercept = +1.951). OV Monitor serum levels were low in healthy individuals (n = 267, median = 9.7 kU/L, 95th percentile = 30.8 kU/L), higher in individuals with various benign diseases (n = 549, medians = 10.9-16.4 kU/L, 95th percentiles = 44.2-355 kU/L) and even higher in individuals suffering from various cancers (n = 995, medians = 12.4-445 kU/L; 95th percentiles = 53.4-4664 kU/L). Optimal diagnostic accuracy for cancer detection against the relevant benign control group by the OV Monitor was found for ovarian cancer [area under the curve (AUC) 0.898]. Results for the reference CA125 assay were comparable (AUC 0.899). The Access OV Monitor provides very good methodological characteristics and demonstrates an excellent analytical and clinical correlation with Elecsys CA125. The best diagnostic accuracy for the OV Monitor was found in ovarian cancer. Our results also suggest a clinical value of the OV Monitor in other cancers.

  19. Towards efficient cancer immunotherapy: advances in developing artificial antigen-presenting cells

    Science.gov (United States)

    Eggermont, Loek J.; Paulis, Leonie E.; Tel, Jurjen; Figdor, Carl G.

    2014-01-01

    Active anti-cancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells (APCs). Therapy with autologous natural APCs is costly and time-consuming and results in variable outcomes in clinical trials. Therefore, development of artificial APCs (aAPCs) has attracted significant interest as an alternative. We discuss the characteristics of various types of acellular aAPCs, and their clinical potential in cancer immunotherapy. The size, shape, and ligand mobility of aAPCs and their presentation of different immunological signals can all have significant effects on cytotoxic T cell activation. Novel optimized aAPCs, combining carefully tuned properties, may lead to efficient immunomodulation and improved clinical responses in cancer immunotherapy. PMID:24998519

  20. Expression of PIK3CA, PTEN mRNA and PIK3CA mutations in primary breast cancer

    DEFF Research Database (Denmark)

    Palimaru, Irina; Brügmann, Anja; Wium-Andersen, Marie Kim

    2013-01-01

    PURPOSE: High activity of the intracellular phosphatidylinositol-3 kinase (PI3K) pathway is common in breast cancer. Here, we explore differences in expression of important PI3K pathway regulators: the activator, phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA), and the tumour...

  1. TanCAR: A Novel Bispecific Chimeric Antigen Receptor for Cancer Immunotherapy.

    Science.gov (United States)

    Grada, Zakaria; Hegde, Meenakshi; Byrd, Tiara; Shaffer, Donald R; Ghazi, Alexia; Brawley, Vita S; Corder, Amanda; Schönfeld, Kurt; Koch, Joachim; Dotti, Gianpietro; Heslop, Helen E; Gottschalk, Stephen; Wels, Winfried S; Baker, Matthew L; Ahmed, Nabil

    2013-07-09

    Targeted T cells are emerging as effective non-toxic therapies for cancer. Multiple elements, however, contribute to the overall pathogenesis of cancer through both distinct and redundant mechanisms. Hence, targeting multiple cancer-specific markers simultaneously could result in better therapeutic efficacy. We created a functional chimeric antigen receptor-the TanCAR, a novel artificial molecule that mediates bispecific activation and targeting of T cells. We demonstrate the feasibility of cumulative integration of structure and docking simulation data using computational tools to interrogate the design and predict the functionality of such a complex bispecific molecule. Our prototype TanCAR induced distinct T cell reactivity against each of two tumor restricted antigens, and produced synergistic enhancement of effector functions when both antigens were simultaneously encountered. Furthermore, the TanCAR preserved the cytolytic ability of T cells upon loss of one of the target molecules and better controlled established experimental tumors by recognition of both targets in an animal disease model. This proof-of-concept approach can be used to increase the specificity of effector cells for malignant versus normal target cells, to offset antigen escape or to allow for targeting the tumor and its microenvironment.Molecular Therapy-Nucleic Acids (2013) 2, e105; doi:10.1038/mtna.2013.32; published online 9 July 2013.

  2. Assessment of cancer and virus antigens for cross-reactivity in human tissues.

    Science.gov (United States)

    Jaravine, Victor; Raffegerst, Silke; Schendel, Dolores J; Frishman, Dmitrij

    2017-01-01

    Cross-reactivity (CR) or invocation of autoimmune side effects in various tissues has important safety implications in adoptive immunotherapy directed against selected antigens. The ability to predict CR (on-target and off-target toxicities) may help in the early selection of safer therapeutically relevant target antigens. We developed a methodology for the calculation of quantitative CR for any defined peptide epitope. Using this approach, we performed assessment of 4 groups of 283 currently known human MHC-class-I epitopes including differentiation antigens, overexpressed proteins, cancer-testis antigens and mutations displayed by tumor cells. In addition, 89 epitopes originating from viral sources were investigated. The natural occurrence of these epitopes in human tissues was assessed based on proteomics abundance data, while the probability of their presentation by MHC-class-I molecules was modelled by the method of Keşmir et al. which combines proteasomal cleavage, TAP affinity and MHC-binding predictions. The results of these analyses for many previously defined peptides are presented as CR indices and tissue profiles. The methodology thus allows for quantitative comparisons of epitopes and is suggested to be suited for the assessment of epitopes of candidate antigens in an early stage of development of adoptive immunotherapy. Our method is implemented as a Java program, with curated datasets stored in a MySQL database. It predicts all naturally possible self-antigens for a given sequence of a therapeutic antigen (or epitope) and after filtering for predicted immunogenicity outputs results as an index and profile of CR to the self-antigens in 22 human tissues. The program is implemented as part of the iCrossR webserver, which is publicly available at http://webclu.bio.wzw.tum.de/icrossr/ CONTACT: d.frishman@wzw.tum.deSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press

  3. Description of a computer program to assess cancer antigen 15.3, carcinoembryonic antigen, and tissue polypeptide antigen information during monitoring of metastatic breast cancer

    DEFF Research Database (Denmark)

    Sölétormos, G; Schiøler, V

    2000-01-01

    It is time-consuming to process and compare the clinical and marker information registered during monitoring of breast cancer patients. To facilitate the assessment, we developed a computer program for interpreting consecutive measurements. The intraindividual biological variation, the analytical...... of individual breast cancer patients with tumor marker measurements. It may also be implemented in trials investigating the utility of potential new markers in breast cancer as well as in other malignancies....

  4. Prostate Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0595 TITLE: Prostate-Specific Membrane Antigen (PSMA) Targeted Bio-orthogonal Therapy for Metastatic Prostate Cancer ... Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0595 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Dmitri Artemov, Ph.D. 5e...excellent targeting of PSMA- expressing prostate cancer cells both in vitro and in vivo. We investigated details of the mAb and therapeutic complexes

  5. Prostataspecifikt antigen, sure fosfataser og rektaleksploration i diagnostik af cancer prostatae

    DEFF Research Database (Denmark)

    Andersen, B R; Knorr, U B; Brasso, K

    1997-01-01

    Eleven hundred and seven patients referred for urological evaluation including measurement of serumprostate specific antigen (PSA) measurement are reviewed. Prostate cancer was diagnosed in 105 patients. PSA was found to be superior to prostatic acid phosphatase in the discrimination between...... prostate cancer and benign prostatic conditions. In 105 patients with newly diagnosed prostate cancer, scintigraphic evidence of osseous metastases was found in thirty-seven. No patients with a serum PSA value less than three times the upper normal limit of the assay had a positive bone scan. Isotope bone...

  6. Stage-specific embryonic antigen: determining expression in canine glioblastoma, melanoma, and mammary cancer cells.

    Science.gov (United States)

    Lin, Weiming; Modiano, Jaime F; Ito, Daisuke

    2017-03-30

    The expression of stage-specific embryonic antigens (SSEAs) was determined in several types of canine cancer cells. Flow cytometry showed SSEA-1 expression in glioblastoma, melanoma, and mammary cancer cells, although none expressed SSEA-3 or SSEA-4. Expression of SSEA-1 was not detected in lymphoma, osteosarcoma, or hemangiosarcoma cell lines. Relatively stable SSEA-1 expression was observed between 24 and 72 h of culture. After 8 days in culture, sorted SSEA-1(-) and SSEA-1(+) cells re-established SSEA-1 expression to levels comparable to those observed in unsorted cells. Our results document, for the first time, the expression of SSEA-1 in several canine cancer cell lines.

  7. Dietary Lycopene, Angiogenesis, and Prostate Cancer: A Prospective Study in the Prostate-Specific Antigen Era

    Science.gov (United States)

    2014-01-01

    Background The role of lycopene in prostate cancer prevention remains controversial. We examined the associations between dietary lycopene intake and prostate cancer, paying particular attention to the influence of prostate-specific antigen screening, and evaluated tissue biomarkers in prostate cancers in relation to lycopene intake. Methods Among 49898 male health professionals, we obtained dietary information through questionnaires and ascertained total and lethal prostate cancer cases from 1986 through January 31, 2010. Cox regression was used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). Tissue microarrays and immunohistochemistry were used to assess tumor biomarker expression in a subset of men. Two-sided χ2 tests were used to calculate the P values. Results Higher lycopene intake was inversely associated with total prostate cancer and more strongly with lethal prostate cancer (top vs bottom quintile: HR = 0.72; 95% CI = 0.56 to 0.94; P trend = .04). In a restricted population of screened participants, the inverse associations became markedly stronger (for lethal prostate cancer: HR = 0.47; 95% CI = 0.29 to 0.75; P trend = .009). Comparing different measures of dietary lycopene, early intake, but not recent intake, was inversely associated with prostate cancer. Higher lycopene intake was associated with biomarkers in the cancer indicative of less angiogenic potential. Conclusions Dietary intake of lycopene was associated with reduced risk of lethal prostate cancer and with a lesser degree of angiogenesis in the tumor. Because angiogenesis is a strong progression factor, an endpoint of lethal prostate cancer may be more relevant than an endpoint of indolent prostate cancer for lycopene in the era of highly prevalent prostate-specific antigen screening. PMID:24463248

  8. Study on IL-2 and CA 15-3 level as combined biomarkers in monitoring chemotherapeutic response among invasive breast cancer patients

    Science.gov (United States)

    Hameed, Ahmed Muthanna Abdul; Hamid, Auni Fatin Abdul; Shahfiza Noor, Nurul; Appalanaido, Gokula Kumar; Bariyah Sahul Hamid, Shahrul

    2017-05-01

    In Malaysia, breast cancer is the most frequent type of disease among women. This study was designed to determine the clinical usefulness of carbohydrate antigen (CA 15-3) and interleukin 2 (IL-2) levels as combined biomarkers in monitoring breast cancer patient’s response to chemotherapy. Ethical approval was obtained to recruit patients with histologically confirmed invasive ductal carcinoma (IDC) attending Oncology Clinic at Advanced Medical and Dental Institute. Whole blood was collected from 10 IDC breast cancer patients’ pre and post primary chemotherapy. Plasma was separated from the whole blood to determine the CA 15-3 level and IL-2 level using enzyme-linked immunosorbent assay (ELISA) pre and post-treatment. In addition, the histological findings, tumour stage and other patients’ data were obtained from the medical record. Findings showed that IL-2 had borderline significant changes between pre- and post-chemotherapy (p = 0.074) whereas for CA 15-3, there was insignificant differences of CA 15-3 level between pre and post-chemotherapy (p > 0.05). It was noted that only CA 15-3 level had significant correlation with tumour size. This study demonstrates that IL-2 level requires further investigation in a larger sample size to correlate its potential use as combined biomarker with CA 15-3 in monitoring response to chemotherapy.

  9. Serum tumour marker CA 125 in monitoring of ovarian cancer during first-line chemotherapy

    DEFF Research Database (Denmark)

    Tuxen, M K; Sölétormos, G; Dombernowsky, P

    2001-01-01

    The value of the serum tumour marker CA 125 to date has been in the monitoring of ovarian cancer patients for response to therapy and for recurrence of disease. However, despite the availability of serial data on CA 125, the problem of interpreting a change over time is still unsolved. The aim...... of this study was to assess the ability of CA 125 to monitor patients with ovarian cancer during postoperative chemotherapy. 255 patients with stage IC-IV ovarian cancer were allocated to the tumour marker monitoring study. The evaluation of CA 125 information was based on the analytical imprecision, the normal...... intra-individual biological variation, the sampling interval, and the cut-off value. Additionally, a new assessment criterion based upon an increment of 2.5 times the baseline CA 125 concentration confirmed by a third measurement was elaborated and the utility investigated. The efficiency of CA 125...

  10. Microarray Glycoprofiling of CA125 Improves Differential Diagnosis of Ovarian Cancer

    DEFF Research Database (Denmark)

    Chen, Kowa; Gentry-Maharaj, Aleksandra; Burnell, Matthew

    2013-01-01

    for profiling specific aberrant glycoforms, such as Neu5Aca2,6GalNAc (STn) and GalNAc (Tn), present on CA125 (MUC16) and CA15-3 (MUC1). In a blinded cohort study of patients with an elevated CA125 levels (30-500 kU/L) and a pelvic mass from the UK Ovarian Cancer Population Study (UKOPS), we measured STn-CA125......The CA125 biomarker assay plays an important role in the diagnosis and management of primary invasive epithelial ovarian/tubal cancer (iEOC). However, a fundamental problem with CA125 is that it is not cancer-specific and may be elevated in benign gynecological conditions such as benign ovarian...

  11. Change in carbohydrate antigen 19-9 level as a prognostic marker of overall survival in locally advanced pancreatic cancer treated with concurrent chemoradiotherapy.

    Science.gov (United States)

    Kim, Yi-Jun; Koh, Hyeon Kang; Chie, Eui Kyu; Oh, Do-Youn; Bang, Yung-Jue; Nam, Eun Mi; Kim, Kyubo

    2017-12-01

    To investigate the significance of carbohydrate antigen 19-9 (CA19-9) levels for survival in locally advanced pancreatic cancer (LAPC) treated with concurrent chemoradiotherapy (CCRT). We retrospectively reviewed data from 97 LAPC patients treated with CCRT between 2000 and 2013. CA19-9 levels (initial and post-CCRT) and their changes [{(post-CCRT CA19-9 level - initial CA19-9 level)/(initial CA19-9 level)} × 100] were analyzed for overall survival. A cut-off point of 37 U/mL was used to analyze initial and post-CCRT CA19-9 levels. In order to define an optimal cut-off point for change in CA19-9 level, the maxstat package of R was applied. Median overall survival was 14.7 months (95% CI 13.4-16.0), and the 2-year survival rate was 16.5%. The estimated optimal cut-off point of CA19-9 level change was 94.4%. On univariate analyses, CA19-9 level change between initial and post-CCRT was significantly correlated with overall survival (median survival time 9.7 vs 16.3 months, p 94.4% might serve as a surrogate marker for poor survival in patients with LAPC undergoing CCRT, and the prognostic power surpassed other CA19-9 variables including initial and post-CCRT values.

  12. Molecular characterisation and expression analysis of SEREX-defined antigen NUCB2 in gastric epithelium, gastritis and gastric cancer

    Directory of Open Access Journals (Sweden)

    Z Kalnina

    2009-08-01

    Full Text Available NUCB2 is an EF-hand Ca2+ binding protein that has been implicated in various physiological processes like calcium homeostasis, hypothalamic regulation of feeding and TNF receptor shedding. In our previous study we identified NUCB2 as a potential tumour antigen eliciting autoantibody responses in 5.4% of gastric cancer patients but not in the healthy individuals. The current study aimed to elucidate the molecular mechanism underlying NUCB2 immunogenicity and to gain an insight into the physiological functions of NUCB2 in the stomach. mRNA expression analysis demonstrated that NUCB2 is ubiquitously expressed in normal tissues, including lymphoid tissues, and downregulated in gastric tumours when compared with the adjacent relatively normal stomach tissues. The search for molecular alterations resulted in the identification of novel mRNA variants transcribed from an alternative promoter and expressed predominantly in gastric cancers. Western blot analysis demonstrated that the protein levels correspond to mRNA levels and revealed that NUCB2 is phosphorylated in gastric mucosa. Furthermore, a 55 kDa isoform, generated presumably by yet an unidentified post-translational modification was detected in gastric tumours and AGS gastric cancer cells but was absent in the relatively normal gastric mucosa and thereby might have served as a trigger for the immune response against NUCB2. Staining of stomach tissue microarray with anti-NUCB2 antibody revealed that it is expressed in the secretory granules of chief cells and in the cytoplasm of parietal cells in the functioning gastric glands which are lost in atrophic glands and tumour cells. Hence we propose that NUCB2 may be implicated in gastric secretion by establishing an agonist-releasable Ca2+ store in ER or Golgi apparatus, signalling via heterotrimeric Ga proteins and/or mediating the exocytosis of the secretory granules.

  13. Cancer associated aberrant protein O-glycosylation can modify antigen processing and immune response.

    Directory of Open Access Journals (Sweden)

    Caroline B Madsen

    Full Text Available Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing, and presentation on MHC class I and II molecules. The effect of GalNAc O-glycosylation was monitored with a model system based on ovalbumin (OVA-MUC1 fusion peptides (+/- glycosylation loaded onto dendritic cells co-cultured with IL-2 secreting OVA peptide-specific T cell hybridomas. To evaluate the in vivo response to a cancer related tumor antigen, Balb/c or B6.Cg(CB-Tg(HLA-A/H2-D2Enge/J (HLA-A2 transgenic mice were immunized with a non-glycosylated or GalNAc-glycosylated MUC1 derived peptide followed by comparison of T cell proliferation, IFN-γ release, and antibody induction. GalNAc-glycosylation promoted presentation of OVA-MUC1 fusion peptides by MHC class II molecules and the MUC1 antigen elicited specific Ab production and T cell proliferation in both Balb/c and HLA-A2 transgenic mice. In contrast, GalNAc-glycosylation inhibited the presentation of OVA-MUC1 fusion peptides by MHC class I and abolished MUC1 specific CD8+ T cell responses in HLA-A2 transgenic mice. GalNAc glycosylation of MUC1 antigen therefore facilitates uptake, MHC class II presentation, and antibody response but might block the antigen presentation to CD8+ T cells.

  14. Improving Antigenic Peptide Vaccines for Cancer Immunotherapy Using a Dominant Tumor-specific T Cell Receptor*

    Science.gov (United States)

    Buhrman, Jonathan D.; Jordan, Kimberly R.; Munson, Daniel J.; Moore, Brandon L.; Kappler, John W.; Slansky, Jill E.

    2013-01-01

    Vaccines that incorporate peptide mimics of tumor antigens, or mimotope vaccines, are commonly used in cancer immunotherapy and function by eliciting increased numbers of T cells that cross-react with the native tumor antigen. Unfortunately, they often elicit T cells that do not cross-react with or that have low affinity for the tumor antigen. Using a high affinity tumor-specific T cell clone, we identified a panel of mimotope vaccines for the dominant peptide antigen from a mouse colon tumor that elicits a range of tumor protection following vaccination. The TCR from this high affinity T cell clone was rarely identified in ex vivo evaluation of tumor-specific T cells elicited by mimotope vaccination. Conversely, a low affinity clone found in the tumor and following immunization was frequently identified. Using peptide libraries, we determined if this frequently identified TCR improved the discovery of efficacious mimotopes. We demonstrated that the representative TCR identified more protective mimotopes than the high affinity TCR. These results suggest that targeting a dominant fraction of tumor-specific T cells generates potent immunity and that consideration of the available T cell repertoire is necessary for targeted T cell therapy. These results have important implications when optimizing mimotope vaccines for cancer immunotherapy. PMID:24106273

  15. Comparison of plasma amino acid profile-based index and CA125 in the diagnosis of epithelial ovarian cancers and borderline malignant tumors.

    Science.gov (United States)

    Miyagi, Etsuko; Maruyama, Yasuyo; Mogami, Tae; Numazaki, Reiko; Ikeda, Atsuko; Yamamoto, Hiroshi; Hirahara, Fumiki

    2017-02-01

    We previously developed a new plasma amino acid profile-based index (API) to detect ovarian, cervical, and endometrial cancers. Here, we compared API to serum cancer antigen 125 (CA125) for distinguishing epithelial ovarian malignant tumors from benign growths. API and CA125 were measured preoperatively in patients with ovarian tumors, which were later classified into 59 epithelial ovarian cancers, 21 epithelial borderline malignant tumors, and 97 benign tumors including 40 endometriotic cysts. The diagnostic accuracy and cutoff points of API were evaluated using receiver operating characteristic (ROC) curves. The area under the ROC curves showed the equivalent performance of API and CA125 to discriminate between malignant/borderline malignant and benign tumors (both 0.77), and API was superior to CA125 for discrimination between malignant/borderline malignant lesions and endometriotic cysts (API, 0.75 vs. CA125, 0.59; p borderline malignancies (API, 0.71 vs. CA125, 0.74; p = 0.84) or cancers alone (API, 0.73 vs. CA125, 0.85; p = 0.12). However, API had a significantly lower detection rate of benign endometriotic cysts (0.35; 95 % CI, 0.21-0.52) compared with that of CA125 (0.65; 95 % CI, 0.48-0.79) (p borderline malignancies with a low false-positive rate for endometriosis. A large-scale prospective clinical study using the cutoff value of API determined in this study is warranted to validate API for practical clinical use.

  16. Chimeric antigen receptor (CAR)-directed adoptive immunotherapy: a new era in targeted cancer therapy

    OpenAIRE

    Chen, Yamei; Liu, Delong

    2014-01-01

    As a result of the recent advances in molecular immunology, virology, genetics, and cell processing, chimeric antigen receptor (CAR)-directed cancer therapy has finally arrived for clinical application. CAR-directed adoptive immunotherapy represents a novel form of gene therapy, cellular therapy, and immunotherapy, a combination of three in one. Early phase clinical trial was reported in patients with refractory chronic lymphoid leukemia with 17p deletion. Accompanying the cyto...

  17. Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy

    Science.gov (United States)

    Min, Yuanzeng; Roche, Kyle C.; Tian, Shaomin; Eblan, Michael J.; McKinnon, Karen P.; Caster, Joseph M.; Chai, Shengjie; Herring, Laura E.; Zhang, Longzhen; Zhang, Tian; Desimone, Joseph M.; Tepper, Joel E.; Vincent, Benjamin G.; Serody, Jonathan S.; Wang, Andrew Z.

    2017-09-01

    Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+T/Treg and CD8+T/Treg ratios (Treg, regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology.

  18. Regional Delivery of Chimeric Antigen Receptor (CAR T-Cells for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Praveen Sridhar

    2017-07-01

    Full Text Available Chimeric Antigen Receptor (CAR T-cells are T-cells with recombinant receptors targeted to tumor antigens. CAR-T cell therapy has emerged as a mode of immunotherapy and is now being extensively explored in hematologic cancer. In contrast, CAR-T cell use in solid tumors has been hampered by multiple obstacles. Several approaches have been taken to circumvent these obstacles, including the regional delivery of CAR-T cells. Regional CAR-T cell delivery can theoretically compensate for poor T-cell trafficking and tumor antigen specificity while avoiding systemic toxicity associated with intravenous delivery. We reviewed completed clinical trials for the treatment of glioblastoma and metastatic colorectal cancer and examined the data in these studies for safety, efficacy, and potential advantages that regional delivery may confer over systemic delivery. Our appraisal of the available literature revealed that regional delivery of CAR-T cells in both glioblastoma and hepatic colorectal metastases was generally well tolerated and efficacious in select instances. We propose that the regional delivery of CAR-T cells is an area of potential growth in the solid tumor immunotherapy, and look towards future clinical trials in head and neck cancer, mesothelioma, and peritoneal carcinomatosis as the use of this technique expands.

  19. Prostate-specific antigen-based prostate cancer screening: Past and future.

    Science.gov (United States)

    Alberts, Arnout R; Schoots, Ivo G; Roobol, Monique J

    2015-06-01

    Prostate-specific antigen-based prostate cancer screening remains a controversial topic. Up to now, there is worldwide consensus on the statement that the harms of population-based screening, mainly as a result of overdiagnosis (the detection of clinically insignificant tumors that would have never caused any symptoms), outweigh the benefits. However, worldwide opportunistic screening takes place on a wide scale. The European Randomized Study of Screening for Prostate Cancer showed a reduction in prostate cancer mortality through prostate-specific antigen based-screening. These population-based data need to be individualized in order to avoid screening in those who cannot benefit and start screening in those who will. For now, lacking a more optimal screening approach, screening should only be started after the process of shared decision-making. The focus of future research is the reduction of unnecessary testing and overdiagnosis by further research to better biomarkers and the value of the multiparametric magnetic resonance imaging, potentially combined in already existing prostate-specific antigen-based multivariate risk prediction models. © 2015 The Japanese Urological Association.

  20. 68Ga Prostate-Specific Membrane Antigen Uptake in Renal Cell Cancer Lymph Node Metastases.

    Science.gov (United States)

    Einspieler, Ingo; Tauber, Robert; Maurer, Tobias; Schwaiger, Markus; Eiber, Matthias

    2016-05-01

    Ga prostate-specific membrane antigen (PSMA)-HBED-CC PET/CT in a patient with a history of both prostate cancer (PC) and renal cell cancer (RCC) shows high PSMA expression in the residual right seminal vesicle suggestive of local recurrence of PC as well as suspected PSMA-positive mediastinal, retroperitoneal, and iliac lymph nodes. Regarding the latter, biopsy revealed lymph node metastases from RCC excluding PC metastases. This case exemplarily demonstrates that high PSMA expression in RCC metastases can potentially mimic PC metastases. Thus, for accurate interpretation of imaging results in PC patients with additional primary tumors, knowledge of PSMA expression of non-PC tissue is necessary.

  1. Prostate-specific antigen and long-term prediction of prostate cancer incidence and mortality in the general population

    DEFF Research Database (Denmark)

    Orsted, David D; Nordestgaard, Børge G; Jensen, Gorm B

    2012-01-01

    It is largely unknown whether prostate-specific antigen (PSA) level at first date of testing predicts long-term risk of prostate cancer (PCa) incidence and mortality in the general population.......It is largely unknown whether prostate-specific antigen (PSA) level at first date of testing predicts long-term risk of prostate cancer (PCa) incidence and mortality in the general population....

  2. Pancreatic cancer and predictors of survival: comparing the CA 19-9/bilirubin ratio with the McGill Brisbane Symptom Score.

    Science.gov (United States)

    Dumitra, Sinziana; Jamal, Mohammad H; Aboukhalil, Jad; Doi, Suhail A; Chaudhury, Prosanto; Hassanain, Mazen; Metrakos, Peter P; Barkun, Jeffrey S

    2013-12-01

    Few tools predict survival from pancreatic cancer (PAC). The McGill Brisbane Symptom Score (MBSS) based on symptoms at presentation (weight loss, pain, jaundice and smoking) was recently validated. The present study compares the ability of four strategies to predict 9-month survival: MBSS, carbohydrate antigen 19-9 (CA 19-9) alone, CA19-9-to-bilirubin ratio and a combination of MBSS and the CA19-9-to-bilirubin ratio. A retrospective review of 133 patients diagnosed with PAC between 2005 and 2011 was performed. Survival was determined from the Quebec civil registry. Blood CA 19-9 and bilirubin values were collected (n = 52) at the time of diagnosis. Receiver-operating characteristic (ROC) curves were used to determine a cutoff for optimal test characteristics of CA 19-9 and CA19-9-to-total bilirubin ratio in predicting survival at 9 months. Predictive characteristics were then calculated for the four strategies. Of the four strategies, the one with the greatest negative predictive value was the MBSS: negative predictive value (NPV) was 90.2% (76.9-97.3%) and the positive likelihood ratio (LR) was the greatest. The ability of CA 19-9 levels alone, at baseline, to predict survival was low. For the CA19-9-to-bilirubin ratio, the test characteristics improved but remained non-significant. The best performing strategy according to likelihood ratios was the combined MBSS and CA19-9 to the bilirubin ratio. CA19-9 levels and the CA19-9-to-bilirubin ratio are poor predictors of survival for PAC, whereas the MBSS is a far better predictor, confirming its clinical value. By adding the CA19-9-to-bilirubin ratio to the MBSS the predictive characteristics improved. © 2013 International Hepato-Pancreato-Biliary Association.

  3. PIK3CA mutations may be discordant between primary and corresponding metastatic disease in Breast Cancer

    DEFF Research Database (Denmark)

    Dupont Jensen, Jeanette; Laenkholm, Anne-Vibeke; Knoop, Ann

    2011-01-01

    PURPOSE: PIK3CA mutations are frequent in breast cancer and activate the PI3K/Akt pathway. Unexpectedly, PIK3CA mutation appears in general to be associated with better outcome. In a cohort of patients where both primary and metastatic lesions were available the objective was to assess changes...... recurrence than wild type cases (p=0.03). CONCLUSIONS: PIK3CA mutations occur at high frequency in primary and metastatic breast cancer; these may not necessarily confer increased aggressiveness as mutants had a longer time to recurrence. Because PIK3CA status quite frequently changes between primary...... metastatic breast tumors. Samples were analysed for PIK3CA mutations (exon 9 and 20) as well as immunohistochemical evaluation for PTEN, pAKT, Ki67, ER and HER2. RESULTS: PIK3CA mutation was detected in 45 % of the primary tumors. Overall there was a net gain in mutation in metastatic disease, to 53...

  4. Preoperative CA125 as a prognostic factor in stage I epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Høgdall, Estrid; Christensen, Ib Jarle

    2006-01-01

    The purpose of the present study was to evaluate preoperative CA125 as a prognostic factor in stage I epithelial ovarian cancer (EOC). Preoperative serum CA125 levels from 118 women with FIGO (International Federation of Gynaecology and Obstetrics) stage I EOC were analysed and the prognostic value...... was evaluated and compared with other prognostic factors (age, grade, substages, histologic type). By the Kaplan-Meier estimate we demonstrated that patients with stage I EOC and preoperative serum CA125 levels

  5. Surface-Engineering of Red Blood Cells as Artificial Antigen Presenting Cells Promising for Cancer Immunotherapy.

    Science.gov (United States)

    Sun, Xiaoqi; Han, Xiao; Xu, Ligeng; Gao, Min; Xu, Jun; Yang, Rong; Liu, Zhuang

    2017-10-01

    The development of artificial antigen presenting cells (aAPCs) to mimic the functions of APCs such as dendritic cells (DCs) to stimulate T cells and induce antitumor immune responses has attracted substantial interests in cancer immunotherapy. In this work, a unique red blood cell (RBC)-based aAPC system is designed by engineering antigen peptide-loaded major histocompatibility complex-I and CD28 activation antibody on RBC surface, which are further tethered with interleukin-2 (IL2) as a proliferation and differentiation signal. Such RBC-based aAPC-IL2 (R-aAPC-IL2) can not only provide a flexible cell surface with appropriate biophysical parameters, but also mimic the cytokine paracrine delivery. Similar to the functions of matured DCs, the R-aAPC-IL2 cells can facilitate the proliferation of antigen-specific CD8+ T cells and increase the secretion of inflammatory cytokines. As a proof-of-concept, we treated splenocytes from C57 mice with R-aAPC-IL2 and discovered those splenocytes induced significant cancer-cell-specific lysis, implying that the R-aAPC-IL2 were able to re-educate T cells and induce adoptive immune response. This work thus presents a novel RBC-based aAPC system which can mimic the functions of antigen presenting DCs to activate T cells, promising for applications in adoptive T cell transfer or even in direct activation of circulating T cells for cancer immunotherapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. A potential role for immunotherapy in thyroid cancer by enhancing NY-ESO-1 cancer antigen expression.

    Science.gov (United States)

    Gunda, Viswanath; Frederick, Dennie T; Bernasconi, Maria J; Wargo, Jennifer A; Parangi, Sareh

    2014-08-01

    NY-ESO-1 is one of the most immunogenic members of the cancer/testis antigen family and its levels can be increased after exposure to demethylating and deacetylating agents. This cytoplasmic antigen can serve as a potent target for cancer immunotherapy and yet has not been well studied in differentiated thyroid cancer cells. We studied the baseline expression of NY-ESO-1 messenger RNA and protein before and after exposure to 5-aza-2'-deoxycytidine (DAC) (72 hours) in a panel of thyroid cancer cell lines using quantitative polymerase chain reaction and Western blot. HLA-A2+, NY-ESO-1+ thyroid cell lines were then co-cultured with peripheral blood lymphocytes transduced with NY-ESO-1 specific T-cell receptor (TCR) and assayed for interferon-gamma and Granzyme-B release in the medium. SCID mice injected orthotopically with BCPAP cells were treated with DAC to evaluate for NY-ESO-1 gene expression in vivo. None of the thyroid cancer cell lines showed baseline expression of NY-ESO-1. Three cell lines, BCPAP, TPC-1, and 8505c, showed an increase in NY-ESO-1 gene expression with DAC treatment and were found to be HLA-A2 positive. DAC-treated target BCPAP and TPC-1 tumor cells with up-regulated NY-ESO-1 levels were able to mount an appropriate interferon-gamma and Granzyme-B response upon co-culture with the NY-ESO-1-TCR-transduced peripheral blood lymphocytes. In vivo DAC treatment was able to increase NY-ESO-1 expression in an orthotopic mouse model with BCPAP cells. Our data suggest that many differentiated thyroid cancer cells can be pressed to express immune antigens, which can then be utilized in TCR-based immunotherapeutic interventions.

  7. Endoplasmic Reticulum–Mitochondrial Ca2+ Fluxes Underlying Cancer Cell Survival

    Directory of Open Access Journals (Sweden)

    Hristina Ivanova

    2017-05-01

    Full Text Available Calcium ions (Ca2+ are crucial, ubiquitous, intracellular second messengers required for functional mitochondrial metabolism during uncontrolled proliferation of cancer cells. The mitochondria and the endoplasmic reticulum (ER are connected via “mitochondria-associated ER membranes” (MAMs where ER–mitochondria Ca2+ transfer occurs, impacting the mitochondrial biology related to several aspects of cellular survival, autophagy, metabolism, cell death sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted to these constitutive ER–mitochondrial Ca2+ fluxes for their survival, since they drive the tricarboxylic acid cycle and the production of mitochondrial substrates needed for nucleoside synthesis and proper cell cycle progression. In addition to this, the mitochondrial Ca2+ uniporter and mitochondrial Ca2+ have been linked to hypoxia-inducible factor 1α signaling, enabling metastasis and invasion processes, but they can also contribute to cellular senescence induced by oncogenes and replication. Finally, proper ER–mitochondrial Ca2+ transfer seems to be a key event in the cell death response of cancer cells exposed to chemotherapeutics. In this review, we discuss the emerging role of ER–mitochondrial Ca2+ fluxes underlying these cancer-related features.

  8. Human leukocyte antigen-G (HLA-G polymorphism and expression in breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Seri Jeong

    Full Text Available Human leukocyte antigen-G (HLA-G is known to be implicated in a tumor-driven immune escape mechanism in malignancies. The purpose of this study was to investigate HLA-G polymorphism and expression in breast cancer. HLA-G alleles were determined by direct DNA sequencing procedures from blood samples of 80 breast cancer patients and 80 healthy controls. Soluble HLA-G (sHLA-G was measured by enzyme-linked immunosorbent assay (ELISA from serum specimens. HLA-G expression in breast cancer lesions was also analyzed by immunohistochemistry staining. The presence of HLA-G 3' untranslated region (UTR 14-bp sequence was analyzed and found to be associated with reduced risk of breast cancer susceptibility based on HLA-G expression in tissues (P = 0.0407. Levels of sHLA-G were higher in the breast cancer group (median 117.2 U/mL compared to the control group (median 10.1 U/mL, P<0.001. The area under the receiver operating characteristic curve (AU-ROC values of sHLA-G for differentiating breast cancer from normal controls and for detecting metastasis from other stages of breast cancer were 0.89 and 0.79, respectively. HLA-G polymorphism and expression may be involved in breast carcinogenesis and sHLA-G concentrations could be used as a diagnostic marker for detecting breast cancer.

  9. Quantitation of human mammary epithelial antigens in cells cultured from normal and cancerous breast tissues.

    Science.gov (United States)

    Sasaki, M; Peterson, J A; Ceriani, R L

    1981-02-01

    A sensitive radioimmunoassay technique was developed to quantitate the level of human breast celltype specific antigens on cells from normal breast and from various established cell lines of breast and nonbreast origins. Polyacrylamide gel electrophoresis revealed four major proteinaceous components (150,000; 75,000; 60,000; and 48,000) in human milk fat globule membranes that were used to immunize rabbits in order to elicit antimammary epithelial cell antibody. Antisera obtained were rendered specific by absorptions and were able to recognize three specific mammary epithelial components of the breast epithelial cell. Human mammary epithelial (HME) antigen expression was highest (1290 ng/10(6) cells) in normal breast epithelial cells from primary cultures of normal breasts. Lower levels (range: 955 to 330 ng/10(6) cells) were found in breast epithelial cells from cell lines established from cancerous breast tissue. Cells of nonbreast origins as well as fibroblasts from breast gave much lower values (less than 30 ng/10(6) cells). On treatment, with trypsin, of two breast epithelial cell lines (MDA-MB-157 and MCF-7) 80 to 85% of their HME antigen expression was lost, suggesting that a majority of these breast antigens reside on the cell surface.

  10. CA 15–3 cell lines and tissue expression in canine mammary cancer and the correlation between serum levels and tumour histological grade

    Directory of Open Access Journals (Sweden)

    Manuali Elisabetta

    2012-06-01

    Full Text Available Abstract Background Mammary tumours are the most common malignancy diagnosed in female dogs and a significant cause of mortality and morbidity in this species. Carbohydrate antigen (CA 15–3 is a mucinous glycoprotein aberrantly over-expressed in human mammary neoplasms and one of the most widely used serum tumour markers in women with breast cancer. The aim of this study was to investigate the antigenic analogies of human and canine CA 15–3 and to assess its expression in canine mammary cancer tissues and cell lines. Immunohistochemical expression of CA 15–3 was evaluated in 7 canine mammary cancer cell lines and 50 malignant mammary tumours. As a positive control, the human breast carcinoma cell line MCF7 and tissue were used. To assess CA 15–3 staining, a semi-quantitative method was applied. To confirm the specificity and cross-reactivity of an anti-human CA 15–3 antibody to canine tissues, an immunoblot analysis was performed. We also investigated serum CA 15–3 activity to establish whether its expression could be assigned to several tumour characteristics to evaluate its potential use as a serum tumour marker in the canine mammary oncology field. Results Immunocytochemical analysis revealed CA 15–3 expression in all examined canine mammary cancer cell lines, whereas its expression was confirmed by immunoblot only in the most invasive cells (CMT-W1, CMT-W1M, CMT-W2 and CMT-W2M. In the tissue, an immunohistochemical staining pattern was observed in 34 (68% of the malignant tumours. A high statistical correlation (p = 0.0019 between serum CA 15–3 levels and the degree of tumour proliferation and differentiation was shown, which indicates that the values of this serum marker increase as the tumour stage progresses. Conclusions The results of this study reveal that CA 15–3 is expressed in both canine mammary tumour cell lines and tissues and that serum levels significantly correlate with the histological grade of the

  11. An Evaluation of Usefulness of Prostate Specific Antigen and Digital ...

    African Journals Online (AJOL)

    Objective: To evaluate the usefulness of prostate specific antigen (PSA) and digital rectal examination (DRE) in the diagnosis of cancer of the prostate (CaP) amongst unscreened patients. Patients, Materials ans Methods: A prospective study168 unscreened men who were referred for evaluation for CaP. They all had a ...

  12. Prognostic significance of serum squamous cell carcinoma antigen in surgically treated lung cancer.

    Science.gov (United States)

    Takeuchi, Susumu; Nonaka, Makoto; Kadokura, Mitsutaka; Takaba, Toshihiro

    2003-04-01

    The serum concentrations of squamous cell carcinoma antigen (SCC-Ag) obtained from 124 surgically treated primary non-small cell lung cancer patients, including 75 adenocarcinomas (AD) and 49 squamous cell carcinomas (SQ), were studied. The changes in the SCC-Ag concentration, which were obtained before and one month after surgery, were analyzed. The 5-year survival rate of the patients with AD who were positive for SCC-Ag preoperatively (32%) was lower than that for those who were negative for SCC-Ag preoperatively (57%, p<0.05). Meanwhile, in those with SQ, the 5-year survival rate of those who were positive for SCC-Ag preoperatively (59%) was not different when compared with those who were negative for SCC-Ag preoperatively (73%). The 5-year survival rate of patients with AD who were positive for SCC-Ag preoperatively and negative postoperatively was 53% versus 17% for those who remained positive postoperatively (p<0.05). In those with SQ, the 5-year survival rate of those who were positive for SCC-Ag preoperatively and negative postoperatively was 76% while it was 0% for those who remained positive postoperatively (p<0.01). In patients with negative SCC-Ag postoperatively, 5-year survival rates were not different between the patients who had positive antigen preoperatively and the patients who had negative antigen preoperatively both in AD (53% and 57%, respectively) and SQ (76% and 75%, respectively). In conclusion, though SCC-Ag is widely used for SQ, preoperative SCC-Ag did not reflect the prognosis. In AD, the survival rate was lower in antigen-positive than antigen-negative patients. Survival rate was higher in antigen-positive patients who became antigen-negative following resection than in patients who remained antigen-positive for both AD and SQ. In the patients who were negative for SCC-Ag postoperatively, survival was the same regardless of the preoperative SCC-Ag positivity in both AD and SQ.

  13. Lewis Y antigen modified CD47 is an independent risk factor for poor prognosis and promotes early ovarian cancer metastasis

    Science.gov (United States)

    Tan, Mingzi; Zhu, Liancheng; Zhuang, Huiyu; Hao, Yingying; Gao, Song; Liu, Shuice; Liu, Qing; Liu, Dawo; Liu, Juanjuan; Lin, Bei

    2015-01-01

    CD47 is a membrane receptor that belongs to the immunoglobulin superfamily and plays an important role in the mechanisms of tumor immune escape. CD47 participates in tumor immune escape by combining with SIRPα to reduce the phagocytic activity of macrophages. There are six potential N-glycosylation sites on CD47, and glycosylation is known to be necessary for its membrane localization. However, it is still unknown to what extent glycosylation influences CD47 ligand binding properties and subsequent signaling. By using immunoprecipitation and confocal laser scanning microscopy, we showed that CD47 contains Lewis y antigen. Immunohistochemical analysis demonstrated that both the positive expression and the overexpression of CD47 and Lewis y antigen in cancer tissues and borderline tumors were significantly higher than those in benign ovarian tumors and normal ovarian tissues (P CD47 and Lewis y antigen was evident (r = 0.47, P CD47 and Lewis y antigen showed significant correlations with the clinical pathological parameters of ovarian cancer [International Federation of Gynecology and Obstetrics (FIGO) standards, lymph node metastasis, and degree of differentiation] (P CD47 was an independent adverse risk factor for the prognosis of ovarian cancer. Cases with both high CD47 and Lewis y antigen expression had poor prognoses. Our study demonstrates that Lewis y antigens of CD47 may play a crucial role in the development of ovarian cancer, and could be new targets for immunotherapy for ovarian cancer. PMID:26609483

  14. PIK3CA Mutation in Colorectal Cancer: Relationship with Genetic and Epigenetic Alterations

    Directory of Open Access Journals (Sweden)

    Katsuhiko Nosho

    2008-06-01

    Full Text Available Somatic PIK3CA mutations are often present in colorectal cancer. Mutant PIK3CA activates AKT signaling, which up-regulates fatty acid synthase (FASN. Microsatellite instability (MSI and CpG island methylator phenotype (CIMP are important molecular classifiers in colorectal cancer. However, the relationship between PIK3CA mutation, MSI and CIMP remains uncertain. Using Pyrosequencing technology, we detected PIK3CA mutations in 91 (15% of 590 population-based colorectal cancers. To determine CIMP status, we quantified DNA methylation in eight CIMP-specific promoters [CACNA1G, CDKN2A (p16, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1] by real-time polymerase chain reaction (MethyLight. PIK3CA mutation was significantly associated with mucinous tumors [P = .0002; odds ratio (OR = 2.44], KRAS mutation (P < .0001; OR = 2.68, CIMP-high (P = .03; OR = 2.08, phospho–ribosomal protein S6 expression (P = .002; OR = 2.19, and FASN expression (P = .02; OR = 1.85 and inversely with p53 expression (P = .01; OR = 0.54 and β-catenin (CTNNB1 alteration (P = .004; OR = 0.43. In addition, PIK3CA G-to-A mutations were associated with MGMT loss (P = .001; OR = 3.24 but not with MGMT promoter methylation. In conclusion, PIK3CA mutation is significantly associated with other key molecular events in colorectal cancer, and MGMT loss likely contributes to the development of PIK3CA G>A mutation. In addition, Pyrosequencing is useful in detecting PIK3CA mutation in archival paraffin tumor tissue. PIK3CA mutational data further emphasize heterogeneity of colorectal cancer at the molecular level.

  15. Chimeric antigen receptor T-cell therapy for cancer: a basic research-oriented perspective.

    Science.gov (United States)

    Han, Chungyong; Kwon, Byoung S

    2018-03-01

    Chimeric antigen receptor (CAR) T cells have outstanding therapeutic potential for treating blood cancers. The prospects for this technology have accelerated basic research, clinical translation and Big Pharma's investment in the field of T-cell therapeutics. This interest has led to the discovery of key factors that affect CAR T-cell efficacy and play pivotal roles in T-cell immunology. Herein, we introduce advances in adoptive immunotherapy and the birth of CAR T cells, and review CAR T-cell studies that focus on three important features: CAR constructs, target antigens and T-cell phenotypes. At last, we highlight novel strategies that overcome the tumor microenvironment and circumvent CAR T-cell side effects, and consider the future direction of CAR T-cell development.

  16. Prostate-specific antigen-positive extramammary Paget's disease--association with prostate cancer

    DEFF Research Database (Denmark)

    Hammer, Anne; Hager, Henrik; Steiniche, Torben

    2008-01-01

    Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma that primarily affects the anogenital region. Cases of EMPD reacting with PSA (prostate-specific antigen) have previously been associated with underlying prostate cancer. However, a recent case of EMPD in our department has...... led us to question the value of PSA as an indicator of underlying prostate cancer. Clinical and pathological data were obtained for 16 cases of EMPD. Formalin-fixed, paraffin-embedded tissue blocks from the primary skin lesions were investigated using PSA and other immunohistochemical markers. 5...... of the 16 cases of EMPD stained positive for PSA (2 women and 3 men). However, no reactivity was seen for the prostatic marker P501S. Three of the five patients had been diagnosed with internal malignant disease-two with prostate cancer, stage 1. Immunohistochemical investigations of the tumour specimens...

  17. BCL-2, Ca, and Apoptosis in Breast Cancer

    National Research Council Canada - National Science Library

    Machen, Terry

    1998-01-01

    The central hypothesis of this project is that bcl-2 controls PCD and oncogenesis by altering Ca permeability by the ER/nuclear membranes, mitochondria and/or plasma membrane of mammary epithelial cells...

  18. Baseline prostate-specific antigen measurements and subsequent prostate cancer risk in the Danish Diet, Cancer and Health cohort

    DEFF Research Database (Denmark)

    Larsen, Signe Benzon; Brasso, Klaus; Iversen, Peter

    2013-01-01

    AIM: Although prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer. METHODS...... AND MATERIAL: Case-control study nested within the Danish 'Diet, Cancer and Health' cohort of 27,179 men aged 50-64 at enrolment. PSA measured in serum collected at cohort entry in 1993-1997 was used to evaluate prostate cancer risk diagnosed up to 14years after. We identified 911 prostate cancer cases...... in the Danish Cancer Registry through 31st December 2007 1:1 age-matched with cancer-free controls. Aggressive cancer was defined as ⩾T3 or Gleason score ⩾7 or N1 or M1. Statistical analyses were based on conditional logistic regression with age as underlying time axis. RESULTS: Total PSA and free-to-total PSA...

  19. Early gastric cancer frequently has high expression of KK-LC-1, a cancer-testis antigen.

    Science.gov (United States)

    Futawatari, Nobue; Fukuyama, Takashi; Yamamura, Rui; Shida, Akiko; Takahashi, Yoshihito; Nishi, Yatsushi; Ichiki, Yoshinobu; Kobayashi, Noritada; Yamazaki, Hitoshi; Watanabe, Masahiko

    2017-12-14

    To assess cancer-testis antigens (CTAs) expression in gastric cancer patients and examined their associations with clinicopathological factors. Eighty-three gastric cancer patients were evaluated in this study. Gastric cancer specimens were evaluated for the gene expression of CTAs, Kitakyushu lung cancer antigen-1 (KK-LC-1), melanoma antigen (MAGE)-A1, MAGE-A3 and New York esophageal cancer-1 (NY-ESO-1), by reverse transcription PCR. Clinicopathological background information, such as gender, age, tumor size, macroscopic type, tumor histology, depth of invasion, lymph node metastasis, lymphatic invasion, venous invasion, and pathological stage, was obtained. Statistical comparisons between the expression of each CTA and each clinicopathological background were performed using the χ2 test. The expression rates of KK-LC-1, MAGE-A1, MAGE-A3, and NY-ESO-1 were 79.5%, 32.5%, 39.8%, and 15.7%, respectively. In early stage gastric cancer specimens, the expression of KK-LC-1 was 79.4%, which is comparable to the 79.6% observed in advanced stage specimens. The expression of KK-LC-1 was not significantly associated with clinicopathological factors, while there were considerable differences in the expression rates of MAGE-A1 and MAGE-A3 with vs without lymphatic invasion (MAGE-A1, 39.3% vs 13.6%, P = 0.034; MAGE-A3, 47.5% vs 18.2%, P = 0.022) and/or vascular invasion (MAGE-A1, 41.5% vs 16.7%, P = 0.028; MAGE-A3, 49.1% vs 23.3%, P = 0.035) and, particularly, MAGE-A3, in patients with early vs advanced stage (36.5% vs 49.0%, P = 0.044), respectively. Patients expressing MAGE-A3 and NY-ESO-1 were older than those not expressing MAGE-A3 and NY-ESO-1 (MAGE-A3, 73.7 ± 7.1 vs 67.4 ± 12.3, P = 0.009; NY-ESO-1, 75.5 ± 7.2 vs 68.8 ± 11.2, P = 0.042). The KK-LC-1 expression rate was high even in patients with stage I cancer, suggesting that KK-LC-1 is a useful biomarker for early diagnosis of gastric cancer.

  20. Cholesterol masks membrane glycosphingolipid tumor-associated antigens to reduce their immunodetection in human cancer biopsies.

    Science.gov (United States)

    Novak, Anton; Binnington, Beth; Ngan, Bo; Chadwick, Karen; Fleshner, Neil; Lingwood, Clifford A

    2013-11-01

    Glycosphingolipids (GSLs) are neoplastic and normal/cancer stem cell markers and GSL/cholesterol-containing membrane rafts are increased in cancer cell plasma membranes. We define a novel means by which cancer cells can restrict tumor-associated GSL immunoreactivity. The GSL-cholesterol complex reorients GSL carbohydrate to a membrane parallel, rather than perpendicular conformation, largely unavailable for antibody recognition. Methyl-β-cyclodextrin cholesterol extraction of all primary human tumor frozen sections tested (ovarian, testicular, neuroblastoma, prostate, breast, colon, pheochromocytoma and ganglioneuroma), unmasked previously "invisible" membrane GSLs for immunodetection. In ovarian carcinoma, globotriaosyl ceramide (Gb3), the GSL receptor for the antineoplastic Escherichia coli-derived verotoxin, was increased throughout the tumor. In colon carcinoma, Gb3 detection was vastly increased within the neovasculature and perivascular stroma. In tumors considered Gb3 negative (neuroblastoma, Leydig testicular tumor and pheochromocytoma), neovascular Gb3 was unmasked. Tumor-associated GSL stage-specific embryonic antigen (SSEA)-1, SSEA-3, SSEA-4 and globoH were unmasked according to tumor: SSEA-1 in prostate/colon; SSEA-3 in prostate; SSEA-4 in pheochromocytoma/some colon tumors; globoH in prostate/some colon tumors. In colon, anti-SSEA-1 was tumor cell specific. Within the GSL-cholesterol complex, filipin-cholesterol binding was also reduced. These results may relate to the ill-defined benefit of statins on cancer prognosis, for example, prostate carcinoma. We found novel anti-tumor GSL antibodies circulating in 3/5 statin-treated, but not untreated, prostate cancer patients. Lowering tumor membrane cholesterol may permit immune recognition of otherwise unavailable tumor-associated GSL carbohydrate, for more effective immunosurveillance and active/passive immunotherapy. Our results show standard immunodetection of tumor GSLs significantly under assesses

  1. Asia prostate cancer study (A-CaP Study launch symposium

    Directory of Open Access Journals (Sweden)

    Hideyuki Akaza

    2016-09-01

    Full Text Available The Asian Prostate Cancer (A-CaP Study is an Asia-wide initiative that has been developed over the course of 2 years. The A-CaP Study is scheduled to begin in 2016, when each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognosis investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. The inaugural Board Meeting of A-CaP was held on December 11, 2015 at the Research Center for Advanced Science and Technology, The University of Tokyo, attended by representatives of all participating countries and regions, who signed a memorandum of understanding concerning registration for A-CaP. Following the Board Meeting an A-CaP Launch Symposium was held. The symposium was attended by representatives of countries and regions participating in A-CaP, who gave presentations. Presentations and a keynote address were also delivered by representatives of the University of California San Francisco, USA, and the Peter MacCallum Cancer Centre, Australia, who provided insight and experience on similar databases compiled in their respective countries.

  2. CA 15-3: uses and limitation as a biomarker for breast cancer.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    CA 15-3 which detects soluble forms of MUC-1 protein is the most widely used serum marker in patients with breast cancer. Its main use is for monitoring therapy in patients with metastatic disease. In monitoring therapy in this setting, CA 15-3 should not be used alone but measured in conjunction with diagnostic imaging, clinical history and physical examination. CA 15-3 is particularly valuable for treatment monitoring in patients that have disease that cannot be evaluated using existing radiological procedures. CA 15-3 may also be used in the postoperative surveillance of asymptomatic women who have undergone surgery for invasive breast cancer. In this setting, serial determination can provide median lead-times of 5-6 months in the early detection of recurrent\\/metastatic breast cancer. It is unclear however, whether administering systemic therapy based on this lead-time improves patient outcome. Consequently, expert panels disagree on the utility of regularly measuring CA 15-3 in the postoperative surveillance of asymptomatic women following a diagnosis of breast cancer. The main limitation of CA 15-3 as a marker for breast cancer is that serum levels are rarely increased in patients with early or localized disease.

  3. Real-time PCR analysis of genes encoding tumor antigens in esophageal tumors and a cancer vaccine

    DEFF Research Database (Denmark)

    Weinert, Brian T; Krishnadath, Kausilia K; Milano, Francesca

    2009-01-01

    Tumor antigens are the primary target of therapeutic cancer vaccines. We set out to define and compare the expression pattern of tumor antigen genes in esophagus carcinoma biopsies and in an allogeneic tumor lysate-based cancer vaccine, MelCancerVac. Cells used for vaccine production were treated...... in the production of the vaccine. Quantitative PCR was used to assay 74 tumor antigen genes in patients with squamous cell carcinoma of the esophagus. 81% (13/16) of tumors expressed more than five cancer/testis (CT) antigens. A total of 96 genes were assayed in the tumor cell clone (DDM1.7) used to make tumor cell...... lysate for vaccine preparation. Gene expression in DDM1.7 cells was compared with three normal tissues; 16 tumor antigen genes were induced more than ten-fold relative to normal tissues. Treatment with 5-aza-CdR induced expression of an additional 15 tumor antigens to a total of 31. MAGE-A protein...

  4. A new insight in chimeric antigen receptor-engineered T cells for cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Erhao Zhang

    2017-01-01

    Full Text Available Abstract Adoptive cell therapy using chimeric antigen receptor (CAR-engineered T cells has emerged as a very promising approach to combating cancer. Despite its ability to eliminate tumors shown in some clinical trials, CAR-T cell therapy involves some significant safety challenges, such as cytokine release syndrome (CRS and “on-target, off-tumor” toxicity, which is related to poor control of the dose, location, and timing of T cell activity. In the past few years, some strategies to avoid the side effects of CAR-T cell therapy have been reported, including suicide gene, inhibitory CAR, dual-antigen receptor, and the use of exogenous molecules as switches to control the CAR-T cell functions. Because of the advances of the CAR paradigm and other forms of cancer immunotherapy, the most effective means of defeating the cancer has become the integration therapy with the combinatorial control system of switchable dual-receptor CAR-T cell and immune checkpoint blockade.

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

    Science.gov (United States)

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

    2016-07-01

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

  6. Solubilized antigen of Blastocystis hominis facilitates the growth of human colorectal cancer cells, HCT116.

    Science.gov (United States)

    Chandramathi, Samudi; Suresh, Kumar; Kuppusamy, Umah Rani

    2010-03-01

    Blastocystis hominis is one of the most common intestinal protozoan parasites in humans, and reports have shown that blastocystosis is coupled with intestinal disorders. In the past, researchers have developed an in vitro model using B. hominis culture filtrates to investigate its ability in triggering inflammatory cytokine responses and transcription factors in human colonic epithelial cells. Studies have also correlated the inflammation by parasitic infection with cancer. The present study provides evidence of the parasite facilitating cancer cell growth through observing the cytopathic effect, cellular immunomodulation, and apoptotic responses of B. hominis, especially in malignancy. Here we investigated the effect of solubilized antigen from B. hominis on cell viability, using peripheral blood mononuclear cells (PBMCs) and human colorectal carcinoma cells (HCT116). The gene expressions of cytokines namely interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha, interferon gamma, nuclear factor kappa light-chain enhancer of activated B cells (a gene transcription factor), and proapoptotic genes namely protein 53 and cathepsin B were also studied. Results exhibited favor the fact that antigen from B. hominis, at a certain concentration, could facilitate the growth of HCT116 while having the ability to downregulate immune cell responses (PBMCs). Therefore, there is a vital need to screen colorectal cancer patients for B. hominis infection as it possesses the ability to enhance the tumor growth.

  7. NEDDylation in liver cancer: The regulation of the RNA binding protein Hu antigen R.

    Science.gov (United States)

    Fernández-Ramos, David; Martínez-Chantar, María L

    2015-07-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer death. The current view of cancer progression and malignancy supports the notion that cancer cells must undergo through a post-translational modification (PTM) regulation and a metabolic switch or reprogramming in order to progress in an unfriendly environment. NEDDylation is a post-translational modification of the proteins involved in several processes such as cell growth, viability and development. A ground-breaking knowledge on a new critical aspect of HCC research has been to identify that NEDDylation plays a role in HCC by regulating the liver oncogenic driver Hu antigen R (HuR). HuR is a RNA-binding protein that stabilizes target mRNAs involved in cell dedifferentiation, proliferation, and survival, all well-established hallmarks of cancer. And importantly, HuR levels were found to be highly representative in liver and colon cancer. These findings open a completely new area of research, exploring the impact that NEDDylation plays in liver diseases and paving the way for novel therapeutical approaches. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  8. Pretreatment prostate specific antigen doubling time as prognostic factor in prostate cancer patients.

    Science.gov (United States)

    Zharinov, Gennady M; Bogomolov, Oleg A; Neklasova, Natalia N; Anisimov, Vladimir N

    2017-01-01

    Despite the prostate-specific antigen (PSA) serum level commonly uses as tumor marker in diagnosis of prostate cancer, it seems that PSA doubling time (PSADT) could be more useful indicator of tumor behavior and of prognosis for patients. The results of hormone and radiation therapy were evaluated for 912 prostate cancer having at least 2 PSA tests before the treatment was started. Clustering procedure (selection of homogenous group) was performed by using PSADT as the classification marker. The rate of PSADT was estimated for different dissemination rate, age, Gleasons's score and education level. PSADT index inversely correlated with the rate of prostate cancer dissemination, Gleason's score and the level of education were directly correlated with the age of patients. Survival time was longer and PSADT index was higher in "slow" tumor growing subgroups in local, local-advanced and metastatic prostate cancer patients than these in "fast" subgroups. The study confirmed the prognostic value of pretreatment PSADT in prostate cancer patients independently of cancer progression. No significant relationship exists between the authors and the companies/organizations whose products or services may be referenced in this article.

  9. Tumor Radiation Therapy Creates Therapeutic Vaccine Responses to the Colorectal Cancer Antigen GUCY2C

    Energy Technology Data Exchange (ETDEWEB)

    Witek, Matthew [Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Blomain, Erik S.; Magee, Michael S.; Xiang, Bo; Waldman, Scott A. [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States); Snook, Adam E., E-mail: adam.snook@jefferson.edu [Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania (United States)

    2014-04-01

    Purpose: Radiation therapy (RT) is thought to produce clinical responses in cancer patients, not only through direct toxicity to cancer cells and supporting tumor stroma cells, but also through activation of immunologic effectors. More recently, RT has potentiated the local and systemic effects of cancer immunotherapy (IT). However, combination regimens that maximize immunologic and clinical efficacy remain undefined. Methods and Materials: We evaluated the impact of local RT on adenoviral-mediated vaccination against the colorectal cancer antigen GUCY2C (Ad5-GUCY2C) in a murine subcutaneous tumor model using mouse CT26 colon cancer cells (CT26-GUCY2C). Immune responses were assessed by ELISpot, and clinical responses were assessed by tumor size and incidence. Results: The specific sequence of tumor-directed RT preceding Ad5-GUCY2C IT transformed inactive therapeutic Ad5-GUCY2C vaccination into a curative vaccine. GUCY2C-specific T cell responses were amplified (P<.05), tumor eradication was maximized (P<.01), and tumor volumes were minimized (P<.001) in mice whose tumors were irradiated before, compared with after, Ad5-GUCY2C vaccination. The immunologic and antitumor efficacy of Ad5-GUCY2C was amplified comparably by unfractionated (8 Gy × 1), or biologically equivalent doses of fractionated (3.5 Gy × 3), RT. The antitumor effects of sequential RT and IT (RT-IT) depended on expression of GUCY2C by tumor cells and the adenoviral vaccine vector, and tumor volumes were inversely related to the magnitude of GUCY2C-specific T cell responses. Moreover, mice cured of CT26-GUCY2C tumors by RT-IT showed long-lasting antigen-dependent protection, resisting tumors formed by GUCY2C-expressing 4T1 breast cancer cells inoculated 50 days after CT26 cells. Conclusions: Optimal sequencing of RT and IT amplifies antigen-specific local and systemic immune responses, revealing novel acute and long-term therapeutic antitumor protection. These observations underscore the importance

  10. An overview of the GAGE cancer/testis antigen family with the inclusion of newly identified members

    DEFF Research Database (Denmark)

    Gjerstorff, M F; Ditzel, H J

    2008-01-01

    GAGE cancer/testis antigens are frequently expressed in many different types of cancer, whereas their expression in normal tissues is limited to the germ cells of the immune-privileged organs, testis and ovary. Thus, GAGE proteins may be attractive candidates for immunotherapy of cancer. This rev......GAGE cancer/testis antigens are frequently expressed in many different types of cancer, whereas their expression in normal tissues is limited to the germ cells of the immune-privileged organs, testis and ovary. Thus, GAGE proteins may be attractive candidates for immunotherapy of cancer....... This review describes the structure and phylogeny of the GAGE family members and presents a revised nomenclature, which will enable a more clear distinction of genes and gene products. The GAGE gene locus at chromosome X p11.23 consists of at least 16 genes, each of which is located in one of an equal number...

  11. Study on 41Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

    Science.gov (United States)

    Shen, Hongtao; Pang, Fangfang; Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang; Pang, Yijun; Yang, Xianlin; Ruan, Xiangdong; Liu, Manjun; Xia, Chunbo

    2015-10-01

    The annual incidence of new cancer patients in China is about 2 million, 30-40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of 41Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague-Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl2 solution (containing 1.4 mg Ca and 5nCi 41Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for 41Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of 41Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that 41Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

  12. Outcome of elevated CA125 values from primary care following implementation of ovarian cancer guidelines.

    Science.gov (United States)

    Crawford, S Michael; Evans, Colin

    2017-09-28

    Ovarian cancer presents later in the UK compared to economically similar countries. National guidance suggests measuring CA125 in primary care as a means of bringing patients to specialist attention. To investigate the outcome of CA125 values measured in accordance with this policy. Examination of the laboratory records of female patients from the usual catchment population of one general hospital in whom CA125 was measured from primary care in a calendar year. Those with values >35 u/ml were identified. Electronic records within the hospital were interrogated to identify what further evaluation had been undertaken whether ovarian or primary peritoneal cancer had been diagnosed or what other pathology was identified. We also reviewed the CA125 measurement history of patients diagnosed over 3 years by any route. One hundred and sixty-four new cases of CA125 ≥35 u/ml were found. Further information was available for 152 of them. Sixteen had ovarian or primary peritoneal cancer and 16 had other cancers. In 50 no cause for the abnormality was found. The remainder had various non-malignant conditions. The specificity for carcinoma of ovary/primary peritoneal carcinoma was 95.4% [95% confidence interval: 94.8-96.0). In a 3-year period, 65 patients were diagnosed with ovarian or primary peritoneal cancer, 5 had values of CA125 between 20 and 35 u/ml shortly before diagnosis. The CA125 level is a useful diagnostic test for ovarian cancer which has been embraced by primary care but higher sensitivity for earlier disease will require strategies to improve the specificity.

  13. Prostate cancer and prostate-specific antigen testing in New South Wales.

    Science.gov (United States)

    Smith, David P; Supramaniam, Rajah; Marshall, Villis R; Armstrong, Bruce K

    2008-09-15

    To describe trends in prostate-specific antigen (PSA) testing, prostate cancer incidence and mortality in New South Wales. Descriptive analysis using routinely collected data of observed trends in PSA testing from 1989 to 2006, and prostate cancer cases and deaths from 1972 to 2005 in NSW. Age-standardised and age-specific rates and joinpoint regression to identify changes in trends; projected trends observed before the introduction of PSA testing to quantify its impact on incidence and mortality rates. The number of PSA tests per year more than doubled between 1994 and 2006. Age-standardised incidence of prostate cancer peaked in 1994, fell by 10.0% per year to 1998 and then increased by 4.9% per year from 2001 to 2005. An estimated 19 602 (43%) more men than expected from preceding trends were diagnosed with prostate cancer between 1989 and 2005 after PSA testing was introduced. The incidence of recorded advanced prostate cancer at diagnosis fell from 13.0 per 100,000 men in 1987-1991 to 7.0 per 100,000 men in 2002-2005. The age-standardised mortality from prostate cancer increased by 3.6% per year between 1984 and 1990 and then fell by 2.0% per year to 2005. There was a sustained increase in prostate cancer incidence in NSW after PSA testing was introduced. While falls in the incidence of advanced disease at diagnosis and mortality from prostate cancer after 1993 are consistent with a benefit from PSA testing, other explanations cannot be excluded.

  14. Cytomegalovirus and cancer after kidney transplantation: Role of the human leukocyte antigen system?

    Science.gov (United States)

    Wong, Germaine; Chakera, Aron; Chapman, Jeremy R; Chadban, Steve C; Pilmore, Helen; Craig, Jonathan C; Lim, Wai H

    2017-02-01

    The role of cytomegalovirus (CMV) in cancer development after transplantation remains uncertain. We aimed to determine the association between donor and recipient CMV serological status and the risk of cancer development after kidney transplantation. Using data from the Australian and New Zealand Dialysis and Transplant (ANZDATA) Registry, we assessed the association between CMV donor/recipient (D/R) serological status and the risk of solid organ cancers in primary adult deceased-donor kidney transplant patients between 1990 and 2012. Of 8140 recipients, a total of 895 (11%) recipients developed incident cancers during a follow-up time of 51 555 person-years. Human leukocyte antigen (HLA) mismatches was an effect modifier between CMV serological status and cancer (P=.03 for interaction). In recipients who have received 0-2 HLA-ABDR mismatched kidneys, the adjusted hazard ratios for cancer incidence among those with CMV D-/R-, CMV D-/R+, and CMV D+/R- were 0.47 (95% confidence interval [CI]: 0.24-0.91), 1.42 (95% CI: 0.97-2.07), and 1.02 (95% CI: 0.67-1.57), respectively compared with the reference of CMV D+/R+. A similar association was not observed in those with >2 HLA-ABDR mismatches. CMV D-/R- status was associated with a reduced risk of cancer in kidney transplant recipients who have received well-matched renal allografts, suggesting a potential role of HLA matching in cancer development. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Human Leukocyte Antigen-G Polymorphisms Association With Cancer Post-Heart Transplantation.

    Science.gov (United States)

    Lazarte, Julieta; Goldraich, Livia; Manlhiot, Cedric; Kozuszko, Stella; Rao, Vivek; Delgado, Diego

    2016-09-01

    Post transplantation, a major complication is the development of malignancies. Human Leukocyte Antigen (HLA)-G is a molecule that inhibits the immune system and it is utilized by malignant cells to hide from the immune system. Expression of HLA-G from the donor and recipient cells in transplant patients is regulated by gene variations however, the association between genotype and cancer remains unknown. Our objective was to determine the association between genotype and outcome. Heart transplant recipients (251) and available corresponding donors (196) samples were genotyped for polymorphisms and the association of polymorphisms to outcome was evaluated with parametric hazard regression models. Risk of cancer was 22% at 10years post-transplantation. The mean follow-up was of 4.9±3.6years. In a multivariable analysis, donor-recipient SNP 3187 matching was identified as a protective factor for cancer (hazard ratio 0.43; 95% confidence interval 0.19-0.93; p=0.03). While coding region allele (haplotype 6) was identified as an independent risk factor (hazard ratio 3.7; 95% confidence interval 1.36-10.06; p=0.01). In this investigation, we identified an association between cancer post-transplantation and HLA-G polymorphisms, which may reveal a pathway for potential diagnostic and therapeutic strategies for cancer post-transplantation. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  16. Correlation Between Preoperative Serum Carcinoembryonic Antigen Levels and Expression on Pancreatic and Rectal Cancer Tissue

    Directory of Open Access Journals (Sweden)

    LSF Boogerd

    2017-05-01

    Full Text Available Carcinoembryonic antigen (CEA–targeted imaging and therapeutic agents are being tested in clinical trials. If CEA overexpression in malignant tissue corresponds with elevated serum CEA, serum CEA could assist in selecting patients who may benefit from CEA-targeted agents. This study aims to assess the relationship between serum CEA and CEA expression in pancreatic (n = 20 and rectal cancer tissues (n = 35 using histopathology. According to local laboratory standards, a serum CEA >3 ng/mL was considered elevated. In pancreatic cancer patients a significant correlation between serum CEA and percentage of CEA-expressing tumor cells was observed ( P  = .04, ρ = .47. All 6 patients with homogeneous CEA expression in the tumor had a serum CEA >3 ng/mL. Most rectal cancer tissues (32/35 showed homogeneous CEA expression, independent of serum CEA levels. This study suggests that selection of pancreatic cancer patients for CEA-targeted agents via serum CEA appears adequate. For selection of rectal cancer patients, serum CEA levels are not informative.

  17. Prostate specific membrane antigen (PSMA) ligands for diagnosis and therapy of prostate cancer.

    Science.gov (United States)

    Barrio, Martin; Fendler, Wolfgang P; Czernin, Johannes; Herrmann, Ken

    2016-11-01

    Prostate specific membrane antigen (PSMA) has become an attractive diagnostic and therapeutic target for small molecule ligands. Radionuclide-chelating ligands can be labeled with either 68Ga for positron-emission-tomography (PET) or 177Lu for radionuclide therapy. Areas covered: In this literature review we evaluate the diagnostic value of 68Ga PSMA PET/CT and the therapeutic potential of 177Lu PSMA radioligand therapy (RLT) in patients with prostate cancer. 68Ga PSMA PET/CT is more accurate than CT for nodal staging and superior to conventional imaging in patients with biochemical recurrence, translating into major changes in clinical management. The preliminary data for 177Lu PSMA indicates >50% reduction of PSA levels in up to 59% of patients. Severe adverse events occurred <10% of patients after RLT. Expert commentary: PSMA ligands for diagnostic and therapeutic purpose will significantly impact the management of patients with prostate cancer.

  18. Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1.

    Science.gov (United States)

    Iura, Kunio; Maekawa, Akira; Kohashi, Kenichi; Ishii, Takeaki; Bekki, Hirofumi; Otsuka, Hiroshi; Yamada, Yuichi; Yamamoto, Hidetaka; Harimaya, Katsumi; Iwamoto, Yukihide; Oda, Yoshinao

    2017-03-01

    Synovial sarcoma (SS) is regarded as a relatively chemosensitive sarcoma, but the prognosis of advanced SSs remains poor. Here we identified highly expressed cancer-testis antigens that could be promising immunotherapy targets for SS, using a previously conducted cDNA microarray, and we assessed the clinicopathological or prognostic relationships of these antigens in SS. We compared the gene expression profiles of 11 SSs with those of 3 normal adipose tissues. Among the up-regulated cancer-testis antigens, we analyzed PRAME, MAGEA1, and MAGEA4 and another cancer-testis antigen (NY-ESO-1) together, by immunohistochemistry and real-time polymerase chain reaction in 108 SSs. Immunohistochemically, NY-ESO-1, PRAME, MAGEA4, and MAGEA1 were positive in 66 (61%), 93 (86%), 89 (82%), and 16 (15%) of 108 SSs, respectively, and 104 (96%) of 108 SSs showed the immunohistochemical expression of at least 1 of NY-ESO-1, PRAME, and MAGEA4. Moreover, the high expression of at least 1 of these 3 antigens was observed in 83% of the SSs. High expression of NY-ESO-1 and MAGEA4 was significantly correlated with the presence of necrosis and advanced clinical stage. The immunohistochemical expression of these cancer-testis antigens was not correlated with prognosis, but the coexpression of NY-ESO-1, PRAME, and MAGEA4 was significantly associated with adverse prognosis. The real-time polymerase chain reaction results were closely related to the immunohistochemical results: NY-ESO-1 (P = .0019), PRAME (P = .039), MAGEA4 (P = .0149), and MAGEA1 (P = .0766). These data support the potential utility of NY-ESO-1, PRAME, and MAGEA4 as immunotherapy targets and ancillary prognostic parameters, suggesting the possible benefit of the combined use of these cancer-testis antigens as an SS immunotherapy target. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro.

    Directory of Open Access Journals (Sweden)

    Tatsuya Moutai

    Full Text Available Immunotherapies such as adoptive transfer of T cells or natural killer cells, or monoclonal antibody (MoAb treatment have recently been recognized as effective means to treat cancer patients. However, adoptive transfer of B cells or plasma cells producing tumor-specific antibodies has not been applied as a therapy because long-term culture and selective expansion of antigen-specific B cells has been technically very difficult. Here, we describe a novel cancer immunotherapy that uses B-cell adoptive transfer. We demonstrate that germinal-center-like B cells (iGB cells induced in vitro from mouse naïve B cells become plasma cells and produce IgG antibodies for more than a month in the bone marrow of non-irradiated recipient mice. When transferred into mice, iGB cells producing antibody against a surrogate tumor antigen suppressed lung metastasis and growth of mouse melanoma cells expressing the same antigen and prolonged survival of the recipients. In addition, we have developed a novel culture system called FAIS to selectively expand antigen-specific iGB cells utilizing the fact that iGB cells are sensitive to Fas-induced cell death unless their antigen receptors are ligated by membrane-bound antigens. The selected iGB cells efficiently suppressed lung metastasis of melanoma cells in the adoptive immunotherapy model. As human blood B cells can be propagated as iGB cells using culture conditions similar to the mouse iGB cell cultures, our data suggest that it will be possible to treat cancer-bearing patients by the adoptive transfer of cancer-antigen-specific iGB cells selected in vitro. This new adoptive immunotherapy should be an alternative to the laborious development of MoAb drugs against cancers for which no effective treatments currently exist.

  20. caREMOTE: the design of a cancer reporting and monitoring telemedicine system for domestic care.

    Science.gov (United States)

    Cheng, Chihwen; Stokes, Todd H; Wang, May D

    2011-01-01

    After receiving cancer treatment, patients often experience a decline of HRQoL (health-related quality of life). Physicians typically evaluate HRQoL during periodic clinical visits. However, out-patient reporting of vital signals between two visits could be used to interpret the decline of HRQoL. Considering that the vast majority of patients recovering from cancer are not in hospitals, it is often impractical for the care providers to collect these data. In this paper, we design and prototype caREMOTE, a cancer reporting and monitoring telemedicine system, which can be used in domestic cancer care. By extending a standard clinical trial informatics model, we build a prototype on cloud computing services that can be accessed by a mobile application. We aim to maximize the potential of caREMOTE to help medical practitioners efficiently monitor discharged patients' HRQoL and vital signals, and facilitate data reusability and system interoperability in future collaborative cancer research.

  1. Transcription factor Fos-related antigen 1 is an effective target for a breast cancer vaccine

    Science.gov (United States)

    Luo, Yunping; Zhou, He; Mizutani, Masato; Mizutani, Noriko; Reisfeld, Ralph A.; Xiang, Rong

    2003-07-01

    Protection against breast cancer was achieved with a DNA vaccine against murine transcription factor Fos-related antigen 1, which is overexpressed in aggressively proliferating D2F2 murine breast carcinoma. Growth of primary s.c. tumor and dissemination of pulmonary metastases was markedly suppressed by this oral DNA vaccine, carried by attenuated Salmonella typhimurium, encoding murine Fos-related antigen 1, fused with mutant polyubiquitin, and cotransformed with secretory murine IL-18. The life span of 60% of vaccinated mice was tripled in the absence of detectable tumor growth after lethal tumor cell challenge. Immunological mechanisms involved activation of T, natural killer, and dendritic cells, as indicated by up-regulation of their activation markers and costimulatory molecules. Markedly increased specific target cell lysis was mediated by both MHC class I-restricted CD8+ T cells and natural killer cells isolated from splenocytes of vaccinated mice, including a significant release of proinflammatory cytokines IFN- and IL-2. Importantly, fluorescence analysis of fibroblast growth factor 2 and tumor cell-induced vessel growth in Matrigel plugs demonstrated marked suppression of angiogenesis only in vaccinated animals. Taken together, this multifunctional DNA vaccine proved effective in protecting against growth and metastases of breast cancer by combining the action of immune effector cells with suppression of tumor angiogenesis. vaccine | tumor | metastases | antiangiogenesis

  2. SoyCaP: Soy and Prostate Cancer Prevention

    National Research Council Canada - National Science Library

    Hamilton-Reeves, Jill M; Kurzer, Mindy S; Slaton, Joel

    2007-01-01

    The main objective of this project is to evaluate the effects of soy phytoestrogens on reproductive hormones and prostate tissue markers of cell proliferation and androgen action in men at high risk of prostate cancer...

  3. Ca2 Receptor, Prostate Cancer, and Bone Metastases

    National Research Council Canada - National Science Library

    Brown, Edward M

    2006-01-01

    14. ABSTRACT While bony metastases of prostate cancer are often osteoblastic, excessive bone resorption also occurs in the sites of metastases, which contributes to skeletal complications (e.g., pain, fractures...

  4. Ca2+ Receptor, Prostate Cancer, and Bone Metastases

    National Research Council Canada - National Science Library

    Brown, Edward M

    2005-01-01

    While bony metastases of prostate cancer are often osteoblastic, excessive bone resorption also occurs in the sites of metastases, which contributes to skeletal complications (e.g., pain, fractures...

  5. Preoperative Serum Carcinoembryonic Antigen as a Marker for Predicting the Outcome of Three Cancers

    Directory of Open Access Journals (Sweden)

    Jingzhu Nan

    2017-02-01

    Full Text Available Background: Serum levels of carcinoembryonic antigen (CEA are associated with a variety of tumors. Objective: This study evaluated the prognostic value of pretreatment serum CEA levels in predicting the outcomes of multiple tumors subjected to treatment. Methods: Prior to therapy, serum samples from 71 prostate, 46 breast, 77 gastric, and 31 pancreatic cancer patients were collected to examine serum CEA levels. The cutoff value for CEA was set as determined by the maximum Youden index. The data were analyzed by the Kaplan-Meier curves generated by the log-rank test and Cox multivariate analysis. Results: The overall survival rate for all the patients was 71.11%. The 3-year survival rate of patients with prostate, breast, gastric, and pancreatic cancers was 81.69%, 95.65%, 54.55%, and 51.61%, respectively. The 3-year survival rate showed significant statistical differences between patients with serum CEA levels <2.885 µg/L and those with serum CEA levels ⩾2.885 µg/L ( P  < .001. The statistical differences of the 3-year survival rate also existed in the men ( P  = .010 or women group ( P  < .001, as well as in the 3 different types of cancer, which include breast cancer ( P  = .025, gastric cancer ( P  = .001, and pancreatic cancer ( P  = .047. Conclusions: Serum CEA levels can provide additional prognostic information and may be useful in treatment implementation for patients with breast, gastric, or pancreatic cancer.

  6. Mutation distributions and clinical correlations of PIK3CA gene mutations in breast cancer.

    Science.gov (United States)

    Dirican, Ebubekir; Akkiprik, Mustafa; Özer, Ayşe

    2016-06-01

    Breast cancer (BCa) is the most common cancer and the second cause of death among women. Phosphoinositide 3-kinase (PI3K) signaling pathway has a crucial role in the cellular processes such as cell survival, growth, division, and motility. Moreover, oncogenic mutations in the PI3K pathway generally involve the activation phosphatidylinositol-4,5-bisphosphate 3-kinase-catalytic subunit alpha (PIK3CA) mutation which has been identified in numerous BCa subtypes. In this review, correlations between PIK3CA mutations and their clinicopathological parameters on BCa will be described. It is reported that PIK3CA mutations which have been localized mostly on exon 9 and 20 hot spots are detected 25-40 % in BCa. This relatively high frequency can offer an advantage for choosing the best treatment options for BCa. PIK3CA mutations may be used as biomarkers and have been major focus of drug development in cancer with the first clinical trials of PI3K pathway inhibitors currently in progress. Screening of PIK3CA gene mutations might be useful genetic tests for targeted therapeutics or diagnosis. Increasing data about PIK3CA mutations and its clinical correlations with BCa will help to introduce new clinical applications in the near future.

  7. Study of Serum Carcinoembryonic Antigen's Profile for Breast Cancer in Western Algeria: 100 cases.

    Science.gov (United States)

    Tahari, Zenib; Medjdoub, Asmahane; Sahraoui, Tewfik; Belhabri, Leila; El Kebir, Fatima Zohra

    2017-01-01

    Breast cancer is the most common cancer in women worldwide. Biology contributes to the early diagnosis and monitoring of breast cancer with several categories of markers such as prognostic markers (ER, PR, HER2), proliferative markers (Ki67), and tumor markers such as CEA and CA 15-3. CEA can be detected at a high concentration in serum of patients with malignant tumors. The aim of our study was to evaluate the concentrations of CEA in serum of women with breast cancer and to verify the existence of a possible link between the average rates of CEA and SBR grade. Serum samples from 100 patients with breast cancer and 100 controls was recovered and examined with an AxSYM analyzer (Abbott Laboratories, USA) to measure CEA using Microparticle Enzyme Immunoassay (MEIA) technology. In our clinical study, the mean age of patients and controls were 52.7 and 50.3 years respectively. The results revealed an elevation in the CEA levels from patients with an average value of 16.61 ± 0.2 ng/ml. Positive correlation was found between CEA concentrations and SBR grade, it has found with 45,7 ± 1 ng/ml in grade III. CEA represents an excellent marker for breast cancer development. Changes in its concentration reflect the effectiveness or ineffectiveness of treatment.

  8. Immunohistochemical characterization of 22 monoclonal antibodies against the CA125 antigen : 2nd report from the ISOBM TD-1 workshop

    NARCIS (Netherlands)

    Vitali, A; Nustad, K; Bast, RC; OBrien, TJ; Nilsson, O; Seguin, P; Suresh, MR; Bormer, OP; Saga, T; deBruijn, HWA; Nozawa, S; Kreutz, FT; Jette, D; Sakahara, H; Gadnell, M; Endo, K; Barlow, EH; Warren, D; Paus, E; Hammarstrom, S; Kenemans, P; Hilgers, J

    1996-01-01

    We evaluated the immunohistological (IH) characteristics of 22 different antibodies that were submitted for study in the frame of the TD-1 ISOBM Workshop on monoclonal antibodies against CA125. Information on relative affinities and epitope similarities was obtained from a parallel immunochemical

  9. Using serum CA125 to assess the activity of potential cytostatic agents in ovarian cancer.

    Science.gov (United States)

    Hall, Marcia R; Petruckevitch, Ann; Pascoe, Joanna; Persic, Mojca; Tahir, Saad; Morgan, Jamie S; Gourley, Charlie; Stuart, Nick; Crawford, S Michael; Kornbrot, Diana E; Qian, Wendi; Rustin, Gordon J

    2014-05-01

    New strategies are required to rapidly identify novel cytostatic agents before embarking on large randomized trials. This study investigates whether a change in rate of rise (slope) of serum CA125 from before to after starting a novel agent could be used to identify cytostatic agents. Tamoxifen was used to validate this hypothesis. Asymptomatic patients with relapsed ovarian cancer who had responded to chemotherapy were enrolled and had CA125 measurements taken every 4 weeks, then more frequently when rising. Once levels reached 4 times the upper limit of normal or nadir, they started continuous tamoxifen 20 mg daily, as well as fortnightly CA125 measurements until symptomatic progression. Because of the potentially nonlinear relationship of CA125 over time, it was felt that to enable normal approximations to be utilized a natural logarithmic standard transformation [ln(CA125)] was the most suitable to improve linearity above the common logarithmic transformation to base 10. From 235 recruited patients, 81 started tamoxifen and had at least 4 CA125 measurements taken before and 4 CA125 measurements taken after starting tamoxifen, respectively. The mean regression slopes from using at least 4 1n(CA125) measurements immediately before and after starting tamoxifen were 0·0149 and 0·0093 [ln(CA125)/d], respectively. This difference is statistically significant, P = 0·001. Therefore, in a future trial with a novel agent, at least as effective as tamoxifen, using this effect size, the number of evaluable patients needed, at significance level of 5% and power of 80%, is 56. Further validation of this methodology is required, but there is potential to use comparison of mean regression slopes of ln(CA125) as an interim analysis measure of efficacy for novel cytostatic agents in relapsed ovarian cancer.

  10. Human Cancer Antigen Globo H Is a Cell-Surface Ligand for Human Ribonuclease 1.

    Science.gov (United States)

    Eller, Chelcie H; Chao, Tzu-Yuan; Singarapu, Kiran K; Ouerfelli, Ouathek; Yang, Guangbin; Markley, John L; Danishefsky, Samuel J; Raines, Ronald T

    2015-07-22

    Pancreatic-type ribonucleases are secretory enzymes that catalyze the cleavage of RNA. Recent efforts have endowed the homologues from cow (RNase A) and human (RNase 1) with toxicity for cancer cells, leading to a clinical trial. The basis for the selective toxicity of ribonuclease variants for cancerous versus noncancerous cells has, however, been unclear. A screen for RNase A ligands in an array of mammalian cell-surface glycans revealed strong affinity for a hexasaccharide, Globo H, that is a tumor-associated antigen and the basis for a vaccine in clinical trials. The affinity of RNase A and RNase 1 for immobilized Globo H is in the low micromolar-high nanomolar range. Moreover, reducing the display of Globo H on the surface of human breast adenocarcinoma cells with a small-molecule inhibitor of biosynthesis or a monoclonal antibody antagonist decreases the toxicity of an RNase 1 variant. Finally, heteronuclear single quantum coherence (HSQC) NMR spectroscopy showed that RNase 1 interacts with Globo H by using residues that are distal from the enzymic active site. The discovery that a systemic human ribonuclease binds to a moiety displayed on human cancer cells links two clinical paradigms and suggests a mechanism for innate resistance to cancer.

  11. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yihui [Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin (China); Tang, Qingchao [Cancer Center, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150086 Harbin (China); Li, Mingqi; Jiang, Shixiong [Department of Colorectal Surgery, The Third Affiliated Hospital of Harbin Medical University, 150 Haping Road, 150081 Harbin (China); Wang, Xishan, E-mail: wxshan12081@163.com [Cancer Center, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, 150086 Harbin (China)

    2014-02-07

    Highlights: • miR-375 is downregulated in colorectal cancer cell lines and tissues. • miR-375 inhibits colorectal cancer cell growth by targeting PIK3CA. • miR-375 inhibits colorectal cancer cell growth in xenograft nude mice model. - Abstract: Colorectal cancer (CRC) is the second most common cause of death from cancer. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by triggering RNA degradation or interfering with translation. Aberrant miRNA expression is involved in human disease including cancer. Herein, we showed that miR-375 was frequently down-regulated in human colorectal cancer cell lines and tissues when compared to normal human colon tissues. PIK3CA was identified as a potential miR-375 target by bioinformatics. Overexpression of miR-375 in SW480 and HCT15 cells reduced PIK3CA protein expression. Subsequently, using reporter constructs, we showed that the PIK3CA untranslated region (3′-UTR) carries the directly binding site of miR-375. Additionally, miR-375 suppressed CRC cell proliferation and colony formation and led to cell cycle arrest. Furthermore, miR-375 overexpression resulted in inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. SiRNA-mediated silencing of PIK3CA blocked the inhibitory effect of miR-375 on CRC cell growth. Lastly, we found overexpressed miR-375 effectively repressed tumor growth in xenograft animal experiments. Taken together, we propose that overexpression of miR-375 may provide a selective growth inhibition for CRC cells by targeting PI3K/Akt signaling pathway.

  12. Effect of rabdosia rubescens combined with new assistant chemotherapy on serum CA199, CEA, CA15-3 and T lymphocyte subsets in patients with breast cancer

    Directory of Open Access Journals (Sweden)

    Lei Xi

    2018-07-01

    Full Text Available Objective: To study the effects of Rabdosia rubescens combined with neoadjuvant chemotherapy on serum CA199, CEA, CA15-3 levels and T lymphocyte subsets in patients with breast cancer. Methods: A total of 70 patients with breast cancer in our hospital were enrolled as the subjects of this study. The subjects were divided into control group (n=35 and treatment group (n=35 randomly. Patients in the control group were treated with new assistant chemotherapy, while those who were in the treatment group were treated with rabdosia rubescens combined with new assistant chemotherapy. The two groups of patients were treated for 3 periods. The serum CA199, CEA, CA15-3 levels and peripheral blood CD4+, CD8+, CD4+/CD8+ cells of the two groups before and after treatment were compared. Results: There were no significantly differences among the serum CA199, CEA, CA15-3 levels and peripheral blood CD4+, CD8+, CD4+/CD8+ cells of the two groups before treatment. The serum CA199, CEA and CA15-3 levels of the two groups after treatment were significantly lower than those before treatment, besides, the serum CA199, CEA and CA15-3 levels of the treatment group were significantly lower than those of the control group. The peripheral blood CD4+, CD4+/ CD8+ cells of the control group after treatment were significantly lower than before treatment, and the peripheral blood CD4+, CD4+/CD8+ cells of the treatment group after treatment were significantly higher than those of the control group. Conclusion: Rabdosia rubescens combined with new assistant chemotherapycan can significantly reduce the serum CA199, CEA and CA15-3 levels, and improve peripheral blood CD4+, CD8+, CD4+/CD8+ levels of patients with breast cancer. It is worthy of clinical application.

  13. Predicting Lymph Node Metastasis in Endometrial Cancer Using Serum CA125 Combined with Immunohistochemical Markers PR and Ki67, and a Comparison with Other Prediction Models.

    Directory of Open Access Journals (Sweden)

    Bingyi Yang

    Full Text Available We aimed to evaluate the value of immunohistochemical markers and serum CA125 in predicting the risk of lymph node metastasis (LNM in women with endometrial cancer and to identify a low-risk group of LNM. The medical records of 370 patients with endometrial endometrioid adenocarcinoma who underwent surgical staging in the Obstetrics & Gynecology Hospital of Fudan University were collected and retrospectively reviewed. Immunohistochemical markers were screened. A model using serum cancer antigen 125 (CA125 level, the immunohistochemical markers progesterone receptor (PR and Ki67 was created for prediction of LNM. A predicted probability of 4% among these patients was defined as low risk. The developed model was externally validated in 200 patients from Shanghai Cancer Center. The efficiency of the model was compared with three other reported prediction models. Patients with serum CA125 50% and Ki67 < 40% in cancer lesion were defined as low risk for LNM. The model showed good discrimination with an area under the receiver operating characteristic curve of 0.82. The model classified 61.9% (229/370 of patients as being at low risk for LNM. Among these 229 patients, 6 patients (2.6% had LNM and the negative predictive value was 97.4% (223/229. The sensitivity and specificity of the model were 84.6% and 67.4% respectively. In the validation cohort, the model classified 59.5% (119/200 of patients as low-risk, 3 out of these 119 patients (2.5% has LNM. Our model showed a predictive power similar to those of two previously reported prediction models. The prediction model using serum CA125 and the immunohistochemical markers PR and Ki67 is useful to predict patients with a low risk of LNM and has the potential to provide valuable guidance to clinicians in the treatment of patients with endometrioid endometrial cancer.

  14. Functionally Active Fc Mutant Antibodies Recognizing Cancer Antigens Generated Rapidly at High Yields

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    Kristina M. Ilieva

    2017-09-01

    Full Text Available Monoclonal antibodies find broad application as therapy for various types of cancer by employing multiple mechanisms of action against tumors. Manipulating the Fc-mediated functions of antibodies that engage immune effector cells, such as NK cells, represents a strategy to influence effector cell activation and to enhance antibody potency and potentially efficacy. We developed a novel approach to generate and ascertain the functional attributes of Fc mutant monoclonal antibodies. This entailed coupling single expression vector (pVitro1 antibody cloning, using polymerase incomplete primer extension (PIPE polymerase chain reaction, together with simultaneous Fc region point mutagenesis and high yield transient expression in human mammalian cells. Employing this, we engineered wild type, low (N297Q, NQ, and high (S239D/I332E, DE FcR-binding Fc mutant monoclonal antibody panels recognizing two cancer antigens, HER2/neu and chondroitin sulfate proteoglycan 4. Antibodies were generated with universal mutagenic primers applicable to any IgG1 pVitro1 constructs, with high mutagenesis and transfection efficiency, in small culture volumes, at high yields and within 12 days from design to purified material. Antibody variants conserved their Fab-mediated recognition of target antigens and their direct anti-proliferative effects against cancer cells. Fc mutations had a significant impact on antibody interactions with Fc receptors (FcRs on human NK cells, and consequently on the potency of NK cell activation, quantified by immune complex-mediated calcium mobilization and by antibody-dependent cellular cytotoxicity (ADCC of tumor cells. This strategy for manipulation and testing of Fc region engagement with cognate FcRs can facilitate the design of antibodies with defined effector functions and potentially enhanced efficacy against tumor cells.

  15. Carcinoembryonic antigen promotes colorectal cancer progression by targeting adherens junction complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bajenova, Olga, E-mail: o.bazhenova@spbu.ru [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Genetics and Biotechnology, St. Petersburg State University, St. Petersburg 199034 (Russian Federation); Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Chaika, Nina [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); Tolkunova, Elena; Davydov-Sinitsyn, Alexander [Institute of Cytology, Russian Academy of Sciences, St. Petersburg 194064 (Russian Federation); Gapon, Svetlana [Boston Children' s Hospital, Boston, MA 02115 (United States); Thomas, Peter [Department of Surgery and Biomedical Sciences, Creighton University, Omaha, NE 68178 (United States); O’Brien, Stephen [Theodosius Dobzhansky Center for Genome Bioinformatics, St. Petersburg State University, St. Petersburg 199034 (Russian Federation)

    2014-06-10

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

  16. SoyCaP: Soy and Prostate Cancer Prevention

    Science.gov (United States)

    2006-11-01

    an Olympus microscope (BX60) linked to a camera (Diagnostics Instruments Inc.) and computer. The digital images were optimized for quantification ...carotene and retinol efficacy trial. Cancer Epidemiol Biomarkers Prev 2003 Dec;12(12):1410-6. 34. Adlercreutz H. Diet and sex hormone metabolism. In

  17. Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

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    Paolo Cossu-Rocca

    Full Text Available Triple Negative Breast Cancer (TNBC accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data.PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC.Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies.

  18. Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E

    2013-01-01

    NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC....

  19. Utility of Digital Rectal Examination as an Adjunct to Prostate Specific Antigen in the Detection of Clinically Significant Prostate Cancer.

    Science.gov (United States)

    Halpern, Joshua A; Oromendia, Clara; Shoag, Jonathan E; Mittal, Sameer; Cosiano, Michael F; Ballman, Karla V; Vickers, Andrew J; Hu, Jim C

    2017-10-20

    Guidelines from NCCN (National Comprehensive Cancer Network®) advocate digital rectal examination screening only in men with elevated prostate specific antigen. We investigated the effect of prostate specific antigen on the association of digital rectal examination and clinically significant prostate cancer in a large American cohort. We evaluated the records of the 35,350 men who underwent digital rectal examination in the screening arm of the PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening trial for the development of clinically significant prostate cancer (Gleason 7 or greater). Followup was 343,273 person-years. The primary outcome was the rate of clinically significant prostate cancer among men with vs without suspicious digital rectal examination. We performed competing risks regression to evaluate the interaction between time varying suspicious digital rectal examination and prostate specific antigen. A total of 1,713 clinically significant prostate cancers were detected with a 10-year cumulative incidence of 5.9% (95% CI 5.6-6.2). Higher risk was seen for suspicious vs nonsuspicious digital rectal examinations. Increases in absolute risk were small and clinically irrelevant for normal (less than 2 ng/ml) prostate specific antigen (1.5% vs 0.7% risk of clinically significant prostate cancer at 10 years), clinically relevant for elevated (3 ng/ml or greater) prostate specific antigen (23.0% vs 13.7%) and modest clinical relevance for equivocal (2 to 3 ng/ml) prostate specific antigen (6.5% vs 3.5%). Digital rectal examination demonstrated prognostic usefulness when prostate specific antigen was greater than 3 ng/ml, limited usefulness for less than 2 ng/ml and marginal usefulness for 2 to 3 ng/ml. These findings support the restriction of digital rectal examination to men with higher prostate specific antigen as a reflex test to improve specificity. It should not be used as a primary screening modality to improve sensitivity. Copyright

  20. CA-125 response patterns in patients with recurrent ovarian cancer treated with pegylated liposomal doxorubicin (PLD).

    Science.gov (United States)

    Oaknin, Ana; Barretina, Pilar; Pérez, Xavier; Jimenez, Laura; Velasco, Montserrat; Alsina, Maria; Brunet, Joan; Germà, Josep Ramon; Beltran, Miguel

    2010-01-01

    : In recurrent ovarian cancer, CA-125 could be the only objective response criteria. This study analyzes response patterns regarding CA-125 in responders versus nonresponders and determines whether a specific cutoff value for CA-125 could predict clinical response, compared with response evaluation criteria in solid tumors, in patients receiving pegylated liposomal doxorubicin (PLD). : Sixty-eight patients were identified, 78% were platinum resistant. Relative changes in CA-125 values were calculated, and response was defined as higher than 50% reduction in CA-125 from baseline. Receiver operating characteristic (ROC) curves were constructed based on CA-125 value after the first cycle of PLD to evaluate the most precise cutoff point for the decision model predicting response. : Fifty-three patients were assessable for response: 16 patients responded and 37 did not; the median increase of CA-125 was 0.20 (-63; 312) and 52 (-29; 620), respectively. Our ROC curve generated a cutoff value with a sensitivity of 35% (positive test, the proportion of patients who will not respond) and a predictive positive value of 80%. According to the predictive positive value, 20% of the responder patients will be identified as nonresponders; P = 0.025. : Our ROC analysis did not demonstrate any reliable CA-125 cutoff on response. Discontinuation of the therapy before cycle 3 may exclude some patients who will benefit from PLD.

  1. Discoveries and application of prostate-specific antigen, and some proposals to optimize prostate cancer screening

    Directory of Open Access Journals (Sweden)

    Tokudome S

    2016-05-01

    Full Text Available Shinkan Tokudome,1 Ryosuke Ando,2 Yoshiro Koda,3 1Department of Nutritional Epidemiology, National Institute of Health and Nutrition, Shinjuku-ku, Tokyo, 2Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya, 3Department of Forensic Medicine and Human Genetics, Kurume University School of Medicine, Kurume, Japan Abstract: The discoveries and application of prostate-specific antigen (PSA have been much appreciated because PSA-based screening has saved millions of lives of prostate cancer (PCa patients. Historically speaking, Flocks et al first identified antigenic properties in prostate tissue in 1960. Then, Barnes et al detected immunologic characteristics in prostatic fluid in 1963. Hara et al characterized γ-semino-protein in semen in 1966, and it has been proven to be identical to PSA. Subsequently, Ablin et al independently reported the presence of precipitation antigens in the prostate in 1970. Wang et al purified the PSA in 1979, and Kuriyama et al first applied an enzyme-linked immunosorbent assay for PSA in 1980. However, the positive predictive value with a cutoff figure of 4.0 ng/mL appeared substantially low (~30%. There are overdiagnoses and overtreatments for latent/low-risk PCa. Controversies exist in the PCa mortality-reducing effects of PSA screening between the European Randomized Study of Screening for Prostate Cancer (ERSPC and the US Prostate, Lung, Colorectal, and Ovarian (PLCO Cancer Screening Trial. For optimizing PCa screening, PSA-related items may require the following: 1 adjustment of the cutoff values according to age, as well as setting limits to age and screening intervals; 2 improving test performance using doubling time, density, and ratio of free: total PSA; and 3 fostering active surveillance for low-risk PCa with monitoring by PSA value. Other items needing consideration may include the following: 1 examinations of cell proliferation and cell cycle markers

  2. Endoplasmic reticulum Ca2+-homeostasis is altered in small and non-small cell lung cancer cell lines

    Directory of Open Access Journals (Sweden)

    Tufman Amanda

    2009-02-01

    Full Text Available Abstract Background Knowledge of differences in the cellular physiology of malignant and non-malignant cells is a prerequisite for the development of cancer treatments that effectively kill cancer without damaging normal cells. Calcium is a ubiquitous signal molecule that is involved in the control of proliferation and apoptosis. We aimed to investigate if the endoplasmic reticulum (ER Ca2+-homeostasis is different in lung cancer and normal human bronchial epithelial (NHBE cells. Methods The intracellular Ca2+-signaling was investigated using fluorescence microscopy and the expression of Ca2+-regulating proteins was assessed using Western Blot analysis. Results In a Small Cell Lung Cancer (H1339 and an Adeno Carcinoma Lung Cancer (HCC cell line but not in a Squamous Cell Lung Cancer (EPLC and a Large Cell Lung Cancer (LCLC cell line the ER Ca2+-content was reduced compared to NHBE. The reduced Ca2+-content correlated with a reduced expression of SERCA 2 pumping calcium into the ER, an increased expression of IP3R releasing calcium from the ER, and a reduced expression of calreticulin buffering calcium within the ER. Lowering the ER Ca2+-content with CPA led to increased proliferation NHBE and lung cancer cells. Conclusion The significant differences in Ca2+-homeostasis between lung cancer and NHBE cells could represent a new target for cancer treatments.

  3. The construction of cDNA library and the screening of related antigen of ascitic tumor cells of ovarian cancer.

    Science.gov (United States)

    Hou, Q; Chen, K; Shan, Z

    2015-01-01

    To construct the cDNA library of the ascites tumor cells of ovarian cancer, which can be used to screen the related antigen for the early diagnosis of ovarian cancer and therapeutic targets of immune treatment. Four cases of ovarian serous cystadenocarcinoma, two cases of ovarian mucinous cystadenocarcinoma, and two cases of ovarian endometrial carcinoma in patients with ascitic tumor cells which were used to construct the cDNA library. To screen the ovarian cancer antigen gene, evaluate the enzyme, and analyze nucleotide sequence, serological analysis of recombinant tumor cDNA expression libraries (SEREX) and suppression subtractive hybridization technique (SSH) techniques were utilized. The detection method of recombinant expression-based serological mini-arrays (SMARTA) was used to detect the ovarian cancer antigen and the positive reaction of 105 cases of ovarian cancer patients and 105 normal women's autoantibodies correspondingly in serum. After two rounds of serologic screening and glycosides sequencing analysis, 59 candidates of ovarian cancer antigen gene fragments were finally identified, which corresponded to 50 genes. They were then divided into six categories: (1) the homologous genes which related to the known ovarian cancer genes, such as BARD 1 gene, etc; (2) the homologous genes which were associated with other tumors, such as TM4SFI gene, etc; (3) the genes which were expressed in a special organization, such as ILF3, FXR1 gene, etc; (4) the genes which were the same with some protein genes of special function, such as TIZ, ClD gene; (5) the homologous genes which possessed the same source with embryonic genes, such as PKHD1 gene, etc; (6) the remaining genes were the unknown genes without the homologous sequence in the gene pool, such as OV-189 genes. SEREX technology combined with SSH method is an effective research strategy which can filter tumor antigen with high specific character; the corresponding autoantibodies of TM4SFl, ClD, TIZ, BARDI

  4. Beyond the antigen receptor: editing the genome of T-cells for cancer adoptive cellular therapies

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    Angharad eLloyd

    2013-08-01

    Full Text Available Recent early-stage clinical trials evaluating the adoptive transfer of patient CD8+ T-cells re-directed with antigen receptors recognising tumours have shown very encouraging results. These reports provide strong support for further development of the therapeutic concept as a curative cancer treatment. In this respect combining the adoptive transfer of tumour-specific T-cells with therapies that increase their anti-tumour capacity is viewed as a promising strategy to improve treatment outcome. The ex-vivo genetic engineering step that underlies T-cell re-direction offers a unique angle to combine antigen receptor delivery with the targeting of cell intrinsic pathways that restrict T-cell effector functions. Recent progress in genome editing technologies such as protein- and RNA-guided endonucleases raise the possibility of disrupting gene expression in T-cells in order to enhance effector functions or to bypass tumour immune suppression. This approach would avoid the systemic administration of compounds that disrupt immune homeostasis, potentially avoiding autoimmune adverse effects, and could improve the efficacy of T-cell based adoptive therapies.

  5. Synuclein gamma predicts poor clinical outcome in colon cancer with normal levels of carcinoembryonic antigen

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    Xing Xiaofang

    2010-07-01

    Full Text Available Abstract Background Synuclein gamma (SNCG, initially identified as a breast cancer specific gene, is aberrantly expressed in many different malignant tumors but rarely expressed in matched nonneoplastic adjacent tissues. In this study, we investigated the prognostic potential of SNCG in colon cancer particularly in the patients with normal carcinoembryonic antigen (CEA levels. Methods SNCG levels were assessed immunohistochemically in cancer tissues from 229 colon adenocarcinoma patients with a mean follow-up of 44 months. Correlations between SNCG levels and clinicopathologic features, preoperative serum CEA level, and clinical outcome were analyzed statistically using SPSS. Results SNCG levels in colon adenocarcinoma were closely associated with intravascular embolus and tumor recurrence but independent of preoperative serum CEA levels. SNCG expression was an independent prognostic factor of a shorter disease-free survival (DFS and overall survival (OS (P P = 0.001, P = 0.001, 0.002 for 97 patients with normal preoperative serum CEA level. Conclusions Our results suggest for the first time that SNCG is a new independent predicator for poor prognosis in patients with colon adenocarcinoma, including those with normal CEA levels. Combination of CEA with SNCG improves prognostic evaluation for patients with colon adenocarcinoma.

  6. Prognostic value of CA 125 in ovarian cyst fluid of patients with epithelial ovarian cancer.

    NARCIS (Netherlands)

    Kolwijck, E.; Span, P.N.; Thomas, C.M.G.; Bulten, J.; Sweep, F.C.; Massuger, L.F.A.G.

    2010-01-01

    Most ovarian tumors contain ovarian cyst fluid (oCF) which can be easily obtained during surgery. This is the first study that explored if CA 125 in oCF could be of prognostic value for patients with epithelial ovarian cancer (EOC). Of 54 patients with primary EOC, oCF and preoperative serum were

  7. Sensitivity of CA 15-3, CEA and serum HER2 in the early detection of recurrence of breast cancer

    DEFF Research Database (Denmark)

    Eriksen, Ann Christina; Sørensen, Patricia Diana; Jacobsen, Erik Hugger

    2013-01-01

    The aim of this project was to investigate the sensitivity of CA 15-3, CEA and HER2 in the early diagnosis of metastatic breast cancer.......The aim of this project was to investigate the sensitivity of CA 15-3, CEA and HER2 in the early diagnosis of metastatic breast cancer....

  8. Prostate-specific antigen-based population screening for prostate cancer: current status in Japan and future perspective in Asia

    OpenAIRE

    Yasuhide Kitagawa; Mikio Namiki

    2014-01-01

    In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen (PSA) testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the ...

  9. The Basics of Artificial Antigen Presenting Cells in T Cell-Based Cancer Immunotherapies.

    Science.gov (United States)

    Neal, Lillian R; Bailey, Stefanie R; Wyatt, Megan M; Bowers, Jacob S; Majchrzak, Kinga; Nelson, Michelle H; Haupt, Carl; Paulos, Chrystal M; Varela, Juan C

    2017-01-01

    Adoptive T cell transfer (ACT) can mediate objective responses in patients with advanced malignancies. There have been major advances in this field, including the optimization of the ex vivo generation of tumor-reactive lymphocytes to ample numbers for effective ACT therapy via the use of natural and artificial antigen presenting cells (APCs). Herein we review the basic properties of APCs and how they have been manufactured through the years to augment vaccine and T cell-based cancer therapies. We then discuss how these novel APCs impact the function and memory properties of T cells. Finally, we propose new ways to synthesize aAPCs to augment the therapeutic effectiveness of antitumor T cells for ACT therapy.

  10. Seventh Joint Meeting of K-J-CaP and CaPSURE: extending the global initiative to improve prostate cancer management

    Directory of Open Access Journals (Sweden)

    Hideyuki Akaza

    2014-06-01

    Full Text Available This report summarizes the presentations and discussions that took place at the Seventh Joint Meeting of the Korea–Japan Study Group of Prostate Cancer (K-J-CaP and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE held in Seoul, Korea, in September 2013. The original J-CaP and CaPSURE Joint Initiative has now been established since 2007 and since the initial collaboration between research teams in the United States (US and Japan, the project has expanded to include several other Asian countries. The objective of the initiative is to analyze and compare data for prostate cancer patients in the participating countries, looking at similarities and differences in patient management and outcomes. Until now the focus has been primarily on data generated within J-CaP and CaPSURE, both large-scale, longitudinal, observational databases of prostate cancer patients in Japan and the US, respectively. This year's meeting was hosted for the first time in Korea which has recently established its own national database–K-CaP–to add to the wealth of data generated by J-CaP and CaPSURE. As a newly-developed database, K-CaP has also provided a valuable ‘template’ for other countries, such as China and Indonesia, planning to establish their own national databases and this will ultimately allow greater opportunities for international data comparisons. A range of topics was discussed at this Seventh Joint Meeting including comparison of outcomes following androgen deprivation therapy or radical prostatectomy in patients with localized prostate cancer, the use of active surveillance as a treatment option and the triggers for intervention when employing this regimen, patient quality of life during treatment, the impact of comorbidities on outcomes, and a comparison of recent outcomes data between J-CaP and CaPSURE. The participants recognized that prostate cancer was now a global disease and therefore major insights into understanding

  11. Prostate cancer detection and dutasteride: utility and limitations of prostate-specific antigen in men with previous negative biopsies.

    NARCIS (Netherlands)

    Leeuwen, P.J. van; Kolble, K.; Huland, H.; Hambrock, T.; Barentsz, J.O.; Schroder, F.H.

    2011-01-01

    CONTEXT: We addressed the question whether the change of serum prostate-specific antigen (PSA) in men who use 5alpha-reductase inhibitor (5-ARI) dutasteride is sensitive for the detection of aggressive prostate cancer (PCa). OBJECTIVE: The case of a man using dutasteride diagnosed with Gleason 7

  12. Prostate Cancer Detection and Dutasteride : Utility and Limitations of Prostate-Specific Antigen in Men with Previous Negative Biopsies

    NARCIS (Netherlands)

    van Leeuwen, Pim J.; Koelble, Konrad; Huland, Hartwig; Hambrock, Thomas; Barentsz, Jelle; Schroder, Fritz H.

    Context: We addressed the question whether the change of serum prostate-specific antigen (PSA) in men who use 5 alpha-reductase inhibitor (5-ARI) dutasteride is sensitive for the detection of aggressive prostate cancer (PCa). Objective: The case of a man using dutasteride diagnosed with Gleason 7

  13. Prostate-specific antigen screening and prostate cancer treatment in renal transplantation candidates: A survey of U.S. transplantation centers.

    Science.gov (United States)

    Gin, Greg E; Pereira, Jorge F; Weinberg, Alan D; Mehrazin, Reza; Lerner, Susan M; Sfakianos, John P; Phillips, Courtney K

    2016-02-01

    Renal transplantation candidates are a highly screened population. There are currently no guidelines or consensus on prostate cancer (CaP) screening in these patients. In light of the recent United States Preventive Services Task Force recommendations against prostate-specific antigen (PSA) screening, we conducted a survey of transplantation surgeons to gain a better understanding of practice patterns among U.S. centers. A 14-question multiple-choice online survey was e-mailed to 195 U.S. renal transplantation centers. The questionnaire assessed CaP screening and treatment practices. The survey also evaluated characteristics of the respondent's institution. Descriptive statistics were used for each of the responses, and associations were made with program characterization using logistic or linear regression models. A total of 90 surgeons responded, representing 65 of 195 programs (33% response rate). Overall, 89% of respondents reported routinely screening for CaP in renal transplantation candidates and 71% had set guidelines for PSA screening. The most common age to start PSA screening was 50 years (51%) and 79% of respondents reported no age limit to stop PSA screening. Definitive treatment of CaP was required before proceeding to transplantation in 45% of respondents. Active surveillance was a viable option in 67% of responders. Most respondents (73%) replied that the waiting time for eligibility after treatment depended on the CaP stage and risk. Although most programs have guidelines on PSA screening in renal transplantation candidates, there is still variation nationwide in screening and treatment practices. AS is a viable treatment option in most of the programs. Our results suggest a benefit of a consensus panel to recommend guidelines in this population. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Stem Cells Antigen-1 Enriches for a Cancer Stem Cell-Like Subpopulation in Mouse Gastric Cancer.

    Science.gov (United States)

    Park, Jun Won; Park, Jung Min; Park, Dong Min; Kim, Dae-Yong; Kim, Hark Kyun

    2016-05-01

    There is a strong need to identify markers to enrich gastric cancer stem cells (CSCs). However, CSC enrichment markers for mouse gastric cancers have not yet been determined. In our previous study, we generated primary mouse gastric cancer cell line NCC-S1 (S1) established from a Villin-cre;Smad4(F/F) ;Trp53(F/F) ;Cdh1(F/wt) mouse and its metastatic variant cell line NCC-S1M (S1M). Interestingly, S1M cells exhibited CSC-like features, such as increased tumorigenic potential and chemoresistance. By comparing gene expression profiles between S1 and S1M cells, we identified Stem Cells Antigen-1 (Sca-1) as a cell surface marker, which was mostly upregulated in S1M. Sca-1 was upregulated in tumorspheres from S1 cells or after cisplatin treatment in S1 cells. Immunofluorescence (IF) analysis showed that approximately 7% of cancer cells exhibited positivity for Sca-1 in primary mouse gastric cancer tissues. An in vivo-limiting dilution assay showed that Sca-1(high) mouse gastric cancer cells demonstrated increased tumorigenicity compared with Sca-1(negative) cells. The Sca-1 expression was downregulated by TGF-β pathway activation and Wnt pathway inhibition in mouse gastric cancer cells. Sca-1(high) cells showed relatively low TGF-β reporter activity and high TCF/LEF1 reporter activity compared with Sca-1(negative) cells. A chromatin immunoprecipitation analysis demonstrated that Sca-1 was a β-catenin/LEF1 target gene. Sca-1(high) allografts were more resistant to cisplatin/fluorouracil chemotherapy than Sca-1(negative) allografts, and overexpressed Bcl-xL. Eighty-five mouse genes overexpressed in Sca-1(high) S1 cells compared with Sca-1(negative) cells clustered 123 pretreatment gastric cancer patient samples according to survival following chemotherapy. Taken together, Sca-1 is a novel CSC enrichment marker that mediates TGF-β and Wnt/β-catenin signaling in mouse gastric cancer. Stem Cells 2016;34:1177-1187. © 2016 AlphaMed Press.

  15. Autoantibody to tumor antigen, alpha 2-HS glycoprotein: a novel biomarker of breast cancer screening and diagnosis.

    Science.gov (United States)

    Yi, Jae Kyo; Chang, Jong Wook; Han, Wonshik; Lee, Jong Won; Ko, Eunyoung; Kim, Dong Hyun; Bae, Ji-Yeon; Yu, Jonghan; Lee, Cheolju; Yu, Myeong-Hee; Noh, Dong-Young

    2009-05-01

    We sought to identify a new serum biomarker for breast cancer screening and diagnosis using stepwise proteomic analysis of sera from breast cancer patients to detect the presence of autoantibodies that react with urinary protein. Two-dimensional immunoblotting was done for screening autoimmunogenic tumor antigens in the urine of breast cancer patients. Reactive spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Among urinary proteins separated by two-dimensional electrophoresis, 13 spots showed strong reactivity with pooled sera from breast cancer patients or control sera. By mass spectrometry, we identified alpha 2-HS glycoprotein (AHSG) as a tumor antigen. Peripheral blood was obtained from 81 women diagnosed with breast cancer before surgery and 73 female donors without evidence of any malignancy for the individual analysis. In one-dimensional Western blot analysis, AHSG autoantibody was detected in 64 of 81 breast cancer patients (79.1%) and in 7 of 73 controls (9.6%). The sensitivity of this test in breast cancer patients was 79.0%. Our results suggest that AHSG and anti-AHSG autoantibody may be useful serum biomarkers for breast cancer screening and diagnosis.

  16. Experiences in supporting the structured collection of cancer nanotechnology data using caNanoLab

    Science.gov (United States)

    Gaheen, Sharon; Lijowski, Michal; Heiskanen, Mervi; Klemm, Juli

    2015-01-01

    Summary The cancer Nanotechnology Laboratory (caNanoLab) data portal is an online nanomaterial database that allows users to submit and retrieve information on well-characterized nanomaterials, including composition, in vitro and in vivo experimental characterizations, experimental protocols, and related publications. Initiated in 2006, caNanoLab serves as an established resource with an infrastructure supporting the structured collection of nanotechnology data to address the needs of the cancer biomedical and nanotechnology communities. The portal contains over 1,000 curated nanomaterial data records that are publicly accessible for review, comparison, and re-use, with the ultimate goal of accelerating the translation of nanotechnology-based cancer therapeutics, diagnostics, and imaging agents to the clinic. In this paper, we will discuss challenges associated with developing a nanomaterial database and recognized needs for nanotechnology data curation and sharing in the biomedical research community. We will also describe the latest version of caNanoLab, caNanoLab 2.0, which includes enhancements and new features to improve usability such as personalized views of data and enhanced search and navigation. PMID:26425409

  17. Experiences in supporting the structured collection of cancer nanotechnology data using caNanoLab

    Directory of Open Access Journals (Sweden)

    Stephanie A. Morris

    2015-07-01

    Full Text Available The cancer Nanotechnology Laboratory (caNanoLab data portal is an online nanomaterial database that allows users to submit and retrieve information on well-characterized nanomaterials, including composition, in vitro and in vivo experimental characterizations, experimental protocols, and related publications. Initiated in 2006, caNanoLab serves as an established resource with an infrastructure supporting the structured collection of nanotechnology data to address the needs of the cancer biomedical and nanotechnology communities. The portal contains over 1,000 curated nanomaterial data records that are publicly accessible for review, comparison, and re-use, with the ultimate goal of accelerating the translation of nanotechnology-based cancer therapeutics, diagnostics, and imaging agents to the clinic. In this paper, we will discuss challenges associated with developing a nanomaterial database and recognized needs for nanotechnology data curation and sharing in the biomedical research community. We will also describe the latest version of caNanoLab, caNanoLab 2.0, which includes enhancements and new features to improve usability such as personalized views of data and enhanced search and navigation.

  18. Identification of Autoantibodies to Breast Cancer Antigens in Breast Cancer Patients

    Science.gov (United States)

    2011-10-01

    therapies against those targets in patients with breast cancer. Not provided. 80 Leah.Novinger@uvm.edu     Table  of...Develop  Customized  Cancer   Therapies .  UVM  Cell  and   Molecular  Biology  Seminar.  November  30,  2010.     Crossing...J,   Gout ,  I.,  Gordon,  C.  M.,  Williamson,  B.,  Stockert,  E.,  Gure,  A.  O.,  Jäger,  D.,  et  al.

  19. Natural History of Untreated Prostate Specific Antigen Radiorecurrent Prostate Cancer in Men with Favorable Prognostic Indicators

    Directory of Open Access Journals (Sweden)

    Neil E. Martin

    2014-01-01

    Full Text Available Background and Purpose. Life expectancy data could identify men with favorable post-radiation prostate-specific antigen (PSA failure kinetics unlikely to require androgen deprivation therapy (ADT. Materials and Methods. Of 206 men with unfavorable-risk prostate cancer in a randomized trial of radiation versus radiation and ADT, 53 experienced a PSA failure and were followed without salvage ADT. Comorbidity, age and established prognostic factors were assessed for relationship to death using Cox regression analyses. Results. The median age at failure, interval to PSA failure, and PSA doubling time were 76.6 years (interquartile range [IQR]: 71.8–79.3, 49.1 months (IQR: 37.7–87.4, and 25 months (IQR: 13.1–42.8, respectively. After a median follow up of 4.0 years following PSA failure, 45% of men had died, none from prostate cancer and no one had developed metastases. Both increasing age at PSA failure (HR: 1.14; 95% CI: 1.03–1.25; P=0.008 and the presence of moderate to severe comorbidity (HR: 12.5; 95% CI: 3.81–41.0; P2 years following post-radiation PSA failure appear to be good candidates for observation without ADT intervention.

  20. Chimeric antigen receptor (CAR)-directed adoptive immunotherapy: a new era in targeted cancer therapy.

    Science.gov (United States)

    Chen, Yamei; Liu, Delong

    2014-01-01

    As a result of the recent advances in molecular immunology, virology, genetics, and cell processing, chimeric antigen receptor (CAR)-directed cancer therapy has finally arrived for clinical application. CAR-directed adoptive immunotherapy represents a novel form of gene therapy, cellular therapy, and immunotherapy, a combination of three in one. Early phase clinical trial was reported in patients with refractory chronic lymphoid leukemia with 17p deletion. Accompanying the cytokine storm and tumor lysis syndrome was the shocking disappearance of the leukemia cells refractory to chemotherapy and monoclonal antibodies. CAR therapy was reproduced in both children and adults with refractory acute lymphoid leukemia. The CAR technology is being explored for solid tumor therapy, such as glioma. Close to 30 clinical trials are underway in the related fields (www.clinicaltrials.gov). Further improvement in gene targeting, cell expansion, delivery constructs (such as using Sleeping Beauty or Piggyback transposons) will undoubtedly enhance clinical utility. It is foreseeable that CAR-engineered T cell therapy will bring targeted cancer therapy into a new era.

  1. New insights into the role of age and carcinoembryonic antigen in the prognosis of colorectal cancer

    Science.gov (United States)

    Gobbi, P G; Valentino, F; Berardi, E; Tronconi, C; Brugnatelli, S; Luinetti, O; Moratti, R; Corazza, G R

    2007-01-01

    The aim of this study was to verify through relative survival (an estimate of cancer-specific survival) the true prognostic factors of colorectal cancer. The study involved 506 patients who underwent locally radical resection. All the clinical, histological and laboratory parameters were prognostically analysed for both overall and relative survival. This latter was calculated from the expected survival of the general population with identical age, sex and calendar years of observation. Univariate and multivariate analyses were applied to the proportional hazards model. Liver metastases, age, lymph node involvement and depth of bowel wall involvement were independent prognosticators of both overall and relative survival, whereas carcinoembryonic antigen (CEA) was predictive only of relative survival. Increasing age was unfavourably related to overall survival, but mildly protective with regard to relative survival. Three out of the five prognostic factors identified are the cornerstones of the current staging systems, and were confirmed as adequate by the analysis of relative survival. The results regarding age explain the conflicting findings so far obtained from studies considering overall survival only and advise against the adoption of absolute age limits in therapeutic protocols. Moreover, the prechemotherapy CEA level showed a high clinical value. PMID:18026187

  2. Relationship of KRAS and PIK3CA gene mutation in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Fan-Bao Yao; Qian-Yi Kuang; Xi Fu; Shi-Yao Huang

    2016-01-01

    Objective:To analyze the relationship between KRAS/PIK3CA gene mutation and clinicopathologic characteristics such as gender, age, tumor location, pathological pattern, histological grade, TNM stage and lymph node metastasis, especially the relationship with distant metastasis of colorectal cancer.Methods:A total of94 cases of colorectal cancer samples surgically resected in Gastrointestinal Surgery Department of our hospital from January 2012 to August 2015 were collected, DNA was extracted and then KRAS and PIK3CA gene sequencing was carried out; their clinicopathologic characteristics (gender, age, tumor location, pathological pattern, histological grade, TNM stage, lymph node metastasis and distant metastasis) were analyzed, the relationship between KRAS/PIK3CA gene mutation and above factors, especially distant metastasis was analyzed, and statistical analysis processing was conducted; patients received 3-year follow-up, distant metastasis and recurrence were observed, and the number of their cases was counted, statistically analyzed and processed.Results:KRAS gene mutation was not associated with gender, age, tumor location, pathological pattern and histological grade, and significantly associated with distant metastasis, lymph node metastasis and TNM stage; PIK3CA was not associated with gender, age, tumor location, pathological pattern and histological grade, and associated with TNM stage, lymph node metastasis and distant metastasis; 7 cases (7.4%) were with mutation of both KRAS and PIK3CA (double positive), and 55 cases (57.4%) were with no mutation at all (double negative); in double positive cases, 5 cases were with distant metastasis, metastasis rate was 71.4% and higher than that of double negative (16/55, 29.1%), and there were statistical differences; it was found in follow-up that metastasis rate of KRAS mutant type was higher than that of wild type, and differences were statistically significant; recurrence rates of KRAS and PIK3CA mutant type

  3. Cancer/testis antigens: A prospective reagent as diagnostic and immunotherapeutic targets for squamous cell carcinoma of the head and neck

    Directory of Open Access Journals (Sweden)

    Shohei Domae

    2014-11-01

    Full Text Available Numerous tumor antigens have so far been identified from various tumors using the serological identification of antigens by recombinant expression cloning (SEREX method. Among them, cancer/testis (CT antigens are considered promising target molecules for immunotherapy for patients with various cancers. We performed several SEREX analyses of various cancers to identify CT antigens, including gastric adenocarcinoma, lung adenocarcinoma, and colon cancer, and consequently identified additional CT antigens, such as XAGE-1, CCDC62-2, GKAP1, and TEKT5. However, although SEREX analysis of squamous cell carcinoma of the head and neck (HNSCC has been performed several times, only a few CT or HNSCC specific antigens have yet been isolated. Compared with other tumors, a small number of studies have been reported on the antigen proteins specific to HNSCC. We here reported the expression of selected CT antigens and their immunogenicity in patients with HNSCC. The results obtained suggested that CCDC62-2, GKAP1, and TEKT5 are immunogenic in HNSCC and also demonstrated their potencies as diagnostic markers for patients with HNSCC in combination with other CT antigens such as NY-ESO-1, MAGE-A3, and MAGE-A4.

  4. Berbamine inhibits the growth of liver cancer cells and cancer initiating cells by targeting Ca2+/Calmodulin-dependent protein kinase II

    OpenAIRE

    Meng, Zhipeng; Li, Tao; Ma, Xiaoxiao; Wang, Xiaoqiong; Van Ness, Carl; Gan, Yichao; Zhou, Hong; Tang, Jinfen; Lou, Guiyu; Wang, Yafan; Wu, Jun; Yen, Yun; Xu, Rongzhen; Huang, Wendong

    2013-01-01

    Liver cancer is the third leading cause of cancer deaths worldwide but no effective treatment toward liver cancer is available so far. Therefore, there is an unmet medical need to identify novel therapies to efficiently treat liver cancer and improve the prognosis of this disease. Here we report that berbamine (BBM) and one of its derivatives, bbd24, potently suppressed liver cancer cell proliferation and induced cancer cell death by targeting Ca2+/calmodulin-dependent protein kinase II (CAMK...

  5. Xanthohumol Induces Growth Inhibition and Apoptosis in Ca Ski Human Cervical Cancer Cells

    Science.gov (United States)

    2015-01-01

    We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50 values using sulforhodamine B (SRB) assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for cervical cancer. PMID:25949267

  6. Xanthohumol Induces Growth Inhibition and Apoptosis in Ca Ski Human Cervical Cancer Cells

    Directory of Open Access Journals (Sweden)

    Wai Kuan Yong

    2015-01-01

    Full Text Available We investigate induction of apoptosis by xanthohumol on Ca Ski cervical cancer cell line. Xanthohumol is a prenylated chalcone naturally found in hop plants, previously reported to be an effective anticancer agent in various cancer cell lines. The present study showed that xanthohumol was effective to inhibit proliferation of Ca Ski cells based on IC50 values using sulforhodamine B (SRB assay. Furthermore, cellular and nuclear morphological changes were observed in the cells using phase contrast microscopy and Hoechst/PI fluorescent staining. In addition, 48-hour long treatment with xanthohumol triggered externalization of phosphatidylserine, changes in mitochondrial membrane potential, and DNA fragmentation in the cells. Additionally, xanthohumol mediated S phase arrest in cell cycle analysis and increased activities of caspase-3, caspase-8, and caspase-9. On the other hand, Western blot analysis showed that the expression levels of cleaved PARP, p53, and AIF increased, while Bcl-2 and XIAP decreased in a dose-dependent manner. Taken together, these findings indicate that xanthohumol-induced cell death might involve intrinsic and extrinsic apoptotic pathways, as well as downregulation of XIAP, upregulation of p53 proteins, and S phase cell cycle arrest in Ca Ski cervical cancer cells. This work suggests that xanthohumol is a potent chemotherapeutic candidate for cervical cancer.

  7. Oxidative stress activates the TRPM2-Ca2+-CaMKII-ROS signaling loop to induce cell death in cancer cells.

    Science.gov (United States)

    Wang, Qian; Huang, Lihong; Yue, Jianbo

    2017-06-01

    High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca 2+ -permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca 2+ influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca 2+ -CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells. On the other hand, TRPM2 knockdown switched cells from cell death to autophagy for survival in response to oxidative stress. Moreover, we found that oxidative stress activated the TRPM2-CaMKII cascade to further induce intracellular ROS production, which led to mitochondria fragmentation and loss of mitochondrial membrane potential. In summary, our data demonstrated that oxidative stress activates the TRPM2-Ca 2+ -CaMKII-ROS signal loop to inhibit autophagy and induce cell death. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Effect of thymol on Ca²⁺ homeostasis and viability in PC3 human prostate cancer cells.

    Science.gov (United States)

    Yeh, Jeng-Hsien; Chou, Chiang-Ting; Chen, I-Shu; Lu, Ti; Lin, Ko-Long; Yu, Chia-Cheng; Liang, Wei-Zhe; Chang, Hong-Tai; Kuo, Chun-Chi; Ho, Chin-Man; Chang, Wen-Teng; Shieh, Pochuen; Jan, Chung-Ren

    2017-02-28

    Thymol is a phenolic compound that affects physiology in different cell models. However, whether thymol affects Ca²⁺ homeostasis in prostate cancer cells is unknown. The action of this compound on cytosolic Ca²⁺ concentrations ([Ca²⁺]i) and viability in PC3 human prostate cancer cells was explored. The results show that thymol at concentrations of 100-1500 μM caused [Ca²⁺]i rises in a concentration-dependent manner. Removal of extracellular Ca²⁺ reduced thymol’s effect by approximately 80%. Thymol-induced Ca²⁺ entry was confirmed by Mn²⁺ entry-induced quench of fura-2 fluorescence, and was inhibited by approximately 30% by Ca²⁺ entry modulators (nifedipine, econazole, SKF96365), and the protein kinase C (PKC) inhibitor GF109203X. In Ca²⁺-free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin abolished thymol-induced [Ca²⁺]i rises. Treatment with thymol also abolished thapsigargin-induced [Ca²⁺]i rises. Thymol-induced Ca²⁺ release from the endoplasmic reticulum was abolished by the phospholipase C (PLC) inhibitor U73122. Thymol at 100-900 μM decreased cell viability, which was not reversed by pretreatment with the Ca²⁺ chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N’,N’-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). Together, in PC3 cells, thymol induced [Ca²⁺]i rises by inducing PLC-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ entry via PKC-sensitive store-operated Ca²⁺ channels and other unknown channels. Thymol also induced Ca²⁺-dissociated cell death.

  9. Genome Analysis of Latin American Cervical Cancer: Frequent Activation of the PIK3CA Pathway.

    Science.gov (United States)

    Lou, Hong; Villagran, Guillermo; Boland, Joseph F; Im, Kate M; Polo, Sarita; Zhou, Weiyin; Odey, Ushie; Juárez-Torres, Eligia; Medina-Martínez, Ingrid; Roman-Basaure, Edgar; Mitchell, Jason; Roberson, David; Sawitzke, Julie; Garland, Lisa; Rodríguez-Herrera, Maria; Wells, David; Troyer, Jennifer; Pinto, Francisco Castillo; Bass, Sara; Zhang, Xijun; Castillo, Miriam; Gold, Bert; Morales, Hesler; Yeager, Meredith; Berumen, Jaime; Alvirez, Enrique; Gharzouzi, Eduardo; Dean, Michael

    2015-12-01

    Cervical cancer is one of the most common causes of cancer mortality for women living in poverty, causing more than 28,000 deaths annually in Latin America and 266,000 worldwide. To better understand the molecular basis of the disease, we ascertained blood and tumor samples from Guatemala and Venezuela and performed genomic characterization. We performed human papillomavirus (HPV) typing and identified somatically mutated genes using exome and ultra-deep targeted sequencing with confirmation in samples from Mexico. Copy number changes were also assessed in the exome sequence. Cervical cancer cases in Guatemala and Venezuela have an average age of diagnosis of 50 years and 5.6 children. Analysis of 675 tumors revealed activation of PIK3CA and other PI3K/AKT pathway genes in 31% of squamous carcinomas and 24% of adeno- and adenosquamous tumors, predominantly at two sites (E542K, E545K) in the helical domain of the PIK3CA gene. This distribution of PIK3CA mutations is distinct from most other cancer types and does not result in the in vitro phosphorylation of AKT. Somatic mutations were more frequent in squamous carcinomas diagnosed after the age of 50 years. Frequent gain of chromosome 3q was found, and low PIK3CA mutation fractions in many tumors suggest that PI3K mutation can be a late event in tumor progression. PI3K pathway mutation is important to cervical carcinogenesis in Latin America. Therapeutic agents that directly target PI3K could play a role in the therapy of this common malignancy. ©2015 American Association for Cancer Research.

  10. Effects of triptolide on human cervical cancer CaSki cells:an in vitro study

    Directory of Open Access Journals (Sweden)

    Wei-xuan NING

    2011-03-01

    Full Text Available Objective To investigate the effects and mechanism of triptolide(TPL on proliferation and apoptosis of human cervical cancer CaSki cells in vitro.Methods CaSki cells were cultured with 0,5,10 and 20ng/ml TPL for 24,48 and 72 hours,the cell proliferation was then observed by MTT assay,the morphological characteristics were observed by inverted phase contrast microscopy,and the expression of Ki-67 and p53 protein was determined by immunohistochemistry.Results Inverted phase contrast microscopy showed the CaSki cells in TPL treated groups were shrinkage and round,with reduced volume and rough surface,cell number declined,intercellular space dilated,and the changes were aggravated with the time elapsed and the TPL concentration increased.The 5,10 and 20ng/ml TPL showed inhibitory effects on the proliferation of CaSki cells in vitro in a time-and dose-dependent manner.Immunocytochemical staining showed that the expression of Ki-67 and p53 protein decreased in a time-and dose-dependent manner in CaSki cells cultured with TPL(P < 0.01.Conclusion TPL may effectively inhibit the proliferation and induce apoptosis of CaSki cells,and the mechanism may be related to the down-regulation of Ki-67 and p53 protein expression.

  11. Mitochondrial Ca{sup 2+} uniporter is critical for store-operated Ca{sup 2+} entry-dependent breast cancer cell migration

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Shihao [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong (China); Guangzhou No.12 Hospital, Guangzhou (China); Wang, Xubu [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong (China); Shen, Qiang [Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Yang, Xinyi; Yu, Changhui; Cai, Chunqing [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong (China); Cai, Guoshuai [Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX (United States); Meng, Xiaojing, E-mail: xiaojingmeng@smu.edu.cn [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong (China); Zou, Fei, E-mail: zoufei616@163.com [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou, Guangdong (China)

    2015-02-27

    Metastasis of cancer cells is a complicated multistep process requiring extensive and continuous cytosolic calcium modulation. Mitochondrial Ca{sup 2+} uniporter (MCU), a regulator of mitochondrial Ca{sup 2+} uptake, has been implicated in energy metabolism and various cellular signaling processes. However, whether MCU contributes to cancer cell migration has not been established. Here we examined the expression of MCU mRNA in the Oncomine database and found that MCU is correlated to metastasis and invasive breast cancer. MCU inhibition by ruthenium red (RuR) or MCU silencing by siRNA abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or thapsigargin (TG)-induced store-operated Ca2+ entry (SOCE). Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. Our results demonstrate that MCU plays a critical role in breast cancer cell migration by regulating SOCE. - Highlights: • MCU is correlated to metastasis and invasive breast cancer. • MCU inhibition abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or TG-induced SOCE. • Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. • MCU plays a critical role in MDA-MB-231 cell migration by regulating SOCE.

  12. Prostate specific antigen level and Gleason score in predicting the stage of newly diagnosed prostate cancer.

    Science.gov (United States)

    Spencer, J A; Chng, W J; Hudson, E; Boon, A P; Whelan, P

    1998-11-01

    The purpose of this study was to determine the utility of prostate specific antigen (PSA) level and Gleason score in the prediction of disease stage in men with newly diagnosed prostate cancer. 102 consecutive men, newly diagnosed with prostate cancer and candidates for radical therapy, underwent contrast enhanced pelvic CT and skeletal scintigraphy. Staging examinations used the TNM classification and were reported prospectively with the radiologist blinded to the patient's Gleason score and level of PSA. Lymph node metastasis was confirmed by CT guided biopsy, lymphadenectomy or response to therapy in some cases of massive disease. There were significant differences between the mean PSA values of 18 men with and 84 men without skeletal metastases (p = 0.01) and between men with locally confined and non-confined disease (p = 0.02). There was no difference between PSA values of 13 men with and 89 men without lymph node metastasis (p = 0.9). Only one man with CT evidence of nodal metastasis (N + ve) had a PSA value below 20 ng ml-1. Two men with Gleason scores below 6 were N + ve and both had PSA values over 20 ng ml-1. One man with skeletal metastasis had a PSA value below 20 ng ml-1 but had bone pain. For this study group if only those men with PSA values over 20 ng ml-1 had been examined, sensitivity for lymphatic and skeletal metastasis would have been 92%. Using this threshold about one-third would have been spared imaging investigation. In conclusion, pelvic CT and skeletal scintigraphy are unlikely to show metastatic disease in a man newly diagnosed with prostate cancer who has no suggestive clinical features, a PSA level below 20 ng ml-1 and a Gleason score below 6.

  13. Curcumin induces apoptosis by inhibiting sarco/endoplasmic reticulum Ca2+ ATPase activity in ovarian cancer cells.

    Science.gov (United States)

    Seo, Jeong-Ah; Kim, Boyun; Dhanasekaran, Danny N; Tsang, Benjamin K; Song, Yong Sang

    2016-02-01

    Aberrant increase in the expression levels of sarco/endoplasmic reticulum calcium ATPase (SERCA), which regulates Ca(2+) homeostasis, has been observed in ovarian cancers. In this study, we demonstrated that curcumin increases cytosolic Ca(2+) concentration through inhibition of SERCA activity, causing apoptosis in ovarian cancer cells but not in normal cells, including peripheral blood mononuclear cells (PBMCs) and ovarian surface epithelial cells (OSE). Curcumin induced apoptosis in ovarian cancer cells in a concentration- and time-dependent manner. Cytosolic Ca(2+) flux was evident after the curcumin treatment (15 µM). Treatment with Ca(2+) chelator reduced curcumin-induced apoptosis, confirming the possible involvement of increased cytosolic Ca(2+) concentration in this response. Basal mRNA and protein levels of SERCA2 were significantly higher in ovarian cancer cells than in OSE. SERCA activity was suppressed by curcumin, with no effect on protein expression. Forced expression of the SERCA2b gene in ovarian cancer cells prevented curcumin-induced cytosolic Ca(2+) elevation and subsequent apoptosis, supporting an important role of SERCA in curcumin-induced apoptosis of ovarian cancer cells. Taken together, inhibition of SERCA activity by curcumin disrupts the Ca(2+) homeostasis and thereby promotes apoptosis in ovarian cancer cells. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. CARCINOMA-ASSOCIATED MUCIN SERUM MARKERS CA-M26 AND CA-M29 - EFFICACY IN DETECTING AND MONITORING PATIENTS WITH CANCER OF THE BREAST, COLON, OVARY, ENDOMETRIUM AND CERVIX

    NARCIS (Netherlands)

    YEDEMA, KA; KENEMANS, P; WOBBES, T; VANKAMP, GJ; DEBRUIJN, HW; THOMAS, CM; MASSUGER, LF; SCHIJF, CP; BON, GG; VERMORKEN, JB; VOORHORST, F; HILGERS, J

    1991-01-01

    Two recently developed monoclonal antibody (MAb)-based anti-mucin assays, CA M26 and CA M29, were studied in 250 cancer patients and compared to 3 well-established marker tests, viz., CA 125, CA 15.3 and SCC, in order to assess their clinical usefulness as serum tumor markers. Pre-treatment sera

  15. Serum tumor marker CA 125 for monitoring ovarian cancer during follow-up

    DEFF Research Database (Denmark)

    Tuxen, Malgorzata K.; Sölétormos, G; Dombernowsky, P

    2002-01-01

    , and the cut-off value. Additionally, the utility of a new assessment criterion based upon an increment of 2.5 times the baseline CA 125 concentration confirmed by a third measurement was investigated. The efficiency of CA 125 to identify progression and non-progression during follow-up varied between 76.......5 and 79.9%, depending on the applied time limit for an acceptable positive lead time. The median lead time for true positive results was 95-99.5 days. Using the new elaborated criterion, the efficiency of CA 125 for identifying progression and non-progression varied between 75.7 and 78.5%, depending...... utility of serological tumor markers in patients with ovarian cancer....

  16. Review of Cancer Immunotherapy: Application of Chimeric Antigen Receptor T Cells and Programmed Death 1/Programmed Death-ligand 1 Antibodies

    OpenAIRE

    Tengfei Zhang; Ling Cao; Zhen Zhang; Dongli Yue; Yu Ping; Hong Li; Lan Huang; Yi Zhang

    2015-01-01

    Cancer immunotherapy strategies based on chimeric antigen receptor (CAR) transduced T cells or antibodies against immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1), achieved significant successes from bench to clinic in the past 2 years. CARs are artificial engineered receptors that can specifically target tumor cell surface antigen, activate T cell and further enhance T cell function, independent of major histocompatibility complex. CAR T ...

  17. Utility of Preoperative CA125 Assay in the Management Planning of Women Diagnosed with Uterine Cancer

    Directory of Open Access Journals (Sweden)

    N. Povolotskaya

    2014-01-01

    Full Text Available Objective. This study assesses the role of preoperative serum CA125 levels in the planning treatment options for women diagnosed with uterine cancer. Material and Method. Ninety five consecutive patients diagnosed with uterine cancer during a four-year period were identified. Age ranged from 35 to 89 years with a mean age of 69 years. The preoperative CA125 levels were dichotomised at 28 U/mL (using ROC analysis to identify the best discriminating threshold for 5-year survival. This level was then correlated with preoperative prognostic indicators: patient age, tumour grade, and histopathological tumour cell type. Survival data was plotted using Kaplan-Meier curves and analysed using the log-rank test. Univariate and multivariate analysis were performed to identify the predictors of overall survival. Results. The mean age of patients was 69 years (range: 35–89. On univariate analysis, the use of preoperative CA125 levels of greater or less than 28 U/mL correlated significantly with age (P=0.01, the grade of disease (P=0.02 and unfavourable tissue type (P=0.03. This threshold CA125 level had a sensitivity of 75%, specificity of 76%, positive predictive value of 35% and negative predicative value of 96.25%, and a likelihood ratio of 3.12 for predicting nodal disease. Using a threshold of preoperative CA125 level of 28 U/mL (area under curve: 0.60 was also a significant predictor of 5-year survival (log-rank test, P=0.01. Using Cox multivariate survival analysis to identify predictive preoperative factors overall, unfavourable cell type was the strongest predictor of survival (Chi square = 36.5, df = 4, and P=0.001, followed by preoperative CA125 level (CA125 > 28 U/mL, P=0.011 and unfavourable preoperative grade (P=0.017. Amongst patients with a favourable histological tissue type (endometrioid, preoperative CA125 levels predicted overall survival (Chi square = 6.039, df = 2, P=0.02; however unfavourable preoperative

  18. Genome Analysis of Latin American Cervical Cancer: Frequent Activation of the PIK3CA Pathway

    Science.gov (United States)

    Lou, Hong; Villagran, Guillermo; Boland, Joseph F.; Im, Kate M.; Polo, Sarita; Zhou, Weiyin; Odey, Ushie; Juárez-Torres, Eligia; Medina-Martínez, Ingrid; Roman-Basaure, Edgar; Mitchell, Jason; Roberson, David; Sawitzke, Julie; Garland, Lisa; Rodríguez-Herrera, Maria; Wells, David; Troyer, Jennifer; Pinto, Francisco Castillo; Bass, Sara; Zhang, Xijun; Castillo, Miriam; Gold, Bert; Morales, Hesler; Yeager, Meredith; Berumen, Jaime; Alvirez, Enrique; Gharzouzi, Eduardo; Dean, Michael

    2015-01-01

    Purpose Cervical cancer is one of the most common causes of cancer mortality for women living in poverty, causing over 28,000 deaths annually in Latin America and 266,000 worldwide. To better understand the molecular basis of the disease we ascertained blood and tumor samples from Guatemala and Venezuela and performed genomic characterization. Experimental Design We performed HPV typing and identified somatically mutated genes using exome and ultra-deep targeted sequencing with confirmation in samples from Mexico. Copy number changes were also assessed in the exome sequence. Results Cervical cancer cases in Guatemala and Venezuela have an average age-of-diagnosis of 50 years, and 5.6 children. Analysis of 675 tumors revealed activation of PIK3CA and other phosphatidyl inositol (PI3K)/AKT pathway genes in 31% of squamous carcinomas and 24% of adeno- and adenosquamous tumors, predominantly at two sites (E542K, E545K) in the helical domain of the PIK3CA gene. This distribution of PIK3CA mutations is distinct from most other cancer types, and does not result in the in vitro phosphorylation of AKT. Somatic mutations were more frequent in squamous carcinomas diagnosed after age 50. Frequent gain of chromosome 3q was found and low PIK3CA mutation fractions in many tumors suggest that PI3K mutation can be a late event in tumor progression. Conclusions PI3K pathway mutation is important to cervical carcinogenesis in Latin America. Therapeutic agents that directly target PI3K could play a role in the therapy of this common malignancy. PMID:26080840

  19. γ-Radiation promotes immunological recognition of cancer cells through increased expression of cancer-testis antigens in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Anu Sharma

    Full Text Available BACKGROUND: γ-radiation is an effective treatment for cancer. There is evidence that radiotherapy supports tumor-specific immunity. It was described that irradiation induces de novo protein synthesis and enhances antigen presentation, we therefore investigated whether γ-radiation results in increased expression of cancer-testis (CT antigens and MHC-I, thus allowing efficient immunological control. This is relevant because the expression of CT-antigens and MHC-I on tumor cells is often heterogeneous. We found that the changes induced by γ-radiation promote the immunological recognition of the tumor, which is illustrated by the increased infiltration by lymphocytes after radiotherapy. METHODS/FINDINGS: We compared the expression of CT-antigens and MHC-I in various cancer cell lines and fresh biopsies before and after in vitro irradiation (20 Gy. Furthermore, we compared paired biopsies that were taken before and after radiotherapy from sarcoma patients. To investigate whether the changed expression of CT-antigens and MHC-I is specific for γ-radiation or is part of a generalized stress response, we analyzed the effect of hypoxia, hyperthermia and genotoxic stress on the expression of CT-antigens and MHC-I. In vitro irradiation of cancer cell lines and of fresh tumor biopsies induced a higher or de novo expression of different CT-antigens and a higher expression of MHC-I in a time- and dose-dependent fashion. Importantly, we show that irradiation of cancer cells enhances their recognition by tumor-specific CD8+ T cells. The analysis of paired biopsies taken from a cohort of sarcoma patients before and after radiotherapy confirmed our findings and, in addition showed that irradiation resulted in higher infiltration by lymphocytes. Other forms of stress did not have an impact on the expression of CT-antigens or MHC-I. CONCLUSIONS: Our findings suggest that γ-radiation promotes the immunological recognition of the tumor. We therefore propose that

  20. Evaluation of Diagnostic Value in Using a Panel of Multiple Tumor-Associated Antigens for Immunodiagnosis of Cancer

    Directory of Open Access Journals (Sweden)

    Peng Wang

    2014-01-01

    Full Text Available To determine whether a panel of multiple tumor-associated antigens (TAAs would enhance antibody detection, the diagnostic value of autoantibodies to a panel of multiple TAAs in cancer has been evaluated. The TAAs used in this study was composed of eight TAAs including Imp1, p62, Koc, p53, C-myc, Cyclin B1, Survivin, and p16 full-length recombinant proteins. Enzyme-linked immunosorbent assay and immunoblotting were used to detect antibodies in 304 cancer sera and also 58 sera from normal individuals. The antibody frequency to any individual TAA in cancer was variable but rarely exceeded 20%. With the successive addition of TAAs to a final combination of total of eight antigens, there was a stepwise increase of positive antibody reactions reaching a sensitivity of 63.5% and a specificity of 86.2% in the combined cancer group. In different types of cancer, the ranges of positive and negative likelihood ratio were 4.07–4.76 and 0.39–0.51, respectively, and the ranges of positive and negative predictive values were 74.2–88.7% and 58.8–75.8%, respectively. Agreement rate and Kappa value were 67.1% and 0.51, respectively. These results further support our previous hypothesis that detection of anti-TAAs autoantibodies for diagnosis of certain type of cancer can be enhanced by using a miniarray of several TAAs.

  1. REFINEMENT OF AN INDIRECT IMMUNOTOXIN ASSAY OF MONOCLONAL-ANTIBODIES RECOGNIZING THE HUMAN SMALL-CELL LUNG-CANCER CLUSTER-2 ANTIGEN

    NARCIS (Netherlands)

    DERBYSHIRE, EJ; DELEIJ, L; WAWRZYNCZAK, EJ

    Monoclonal antibodies (Mabs) from the Second International Workshop on Small Cell Lung Cancer (SCLC) Antigens that recognise the cluster 2 SCLC-associated antigen mediated potent and selective cytotoxic effects in an indirect assay of immunotoxin cytotoxicity. In this assay, the NCI-H69 cell line

  2. Melanoma-associated antigen expression and the efficacy of tyrosine kinase inhibitors in head and neck cancer

    DEFF Research Database (Denmark)

    Hartmann, Stefan; Brands, Roman C; Küchler, Nora

    2015-01-01

    Melanoma-associated antigen (MAGE) has been identified in a variety of types of cancer. The expression of several MAGE subgroups is correlated with poor prognosis and chemotherapeutic resistance. One target of chemotherapeutic treatment in head and neck cancer is the epidermal growth factor...... receptor (EGFR). The efficacy of tyrosine kinase inhibitors (TKI) in the context of melanoma-associated antigens is discussed in the present study. Five human squamous cell carcinoma cell lines were treated with the EGFR TKIs, erlotinib and gefitinib. The efficacy of these agents was measured using...... a crystal violet assay. Furthermore, the expression levels of MAGE-A1, -A5, -A8, -A9, -A11 and -A12 were determined by reverse transcription-quantitative polymerase chain reaction. The association between TKI efficacy and MAGE-A expression was analyzed by linear regression. The cell lines revealed...

  3. Prognostic Significance of Digital Rectal Examination and Prostate Specific Antigen in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Arm.

    Science.gov (United States)

    Halpern, Joshua A; Shoag, Jonathan E; Mittal, Sameer; Oromendia, Clara; Ballman, Karla V; Hershman, Dawn L; Wright, Jason D; Shih, Ya-Chen Tina; Nguyen, Paul L; Hu, Jim C

    2017-02-01

    The absence of definitive data or explicit guidelines regarding the use of digital rectal examination for prostate cancer screening may lead to confusion for physicians and patients alike. We evaluated the prognostic value of abnormal digital rectal examination and prostate specific antigen following the widespread dissemination of prostate specific antigen testing in the U.S. Collectively, men comprising the screening arm of the PLCO cancer screening trial who underwent digital rectal examination screening (35,350) were followed for 314,033 person-years. Adjusted analyses with competing risks regression were performed to assess the association of suspicious (nodularity, induration, asymmetry) digital rectal examination and abnormal prostate specific antigen (4 ng/ml or greater) with the detection of clinically significant prostate cancer, prostate cancer specific mortality and overall mortality. Among all screening encounters with a suspicious digital rectal examination only 15.4% had a concurrently abnormal prostate specific antigen (McNemar's test p digital rectal examination and abnormal prostate specific antigen were associated with a greater risk of clinically significant prostate cancer (HR 2.21, 95% CI 1.99-2.44 vs HR 5.48, 95% CI 5.05-5.96, p digital rectal examination and abnormal prostate specific antigen on routine screening were independently associated with clinically significant prostate cancer and prostate cancer specific mortality. However, additional research is needed to optimize screening protocols. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. Prostate-specific antigen bounce following stereotactic body radiation therapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    Charles C. Vu

    2014-01-01

    Full Text Available Introduction: Prostate-specific antigen (PSA bounce after brachytherapy has been well-documented. This phenomenon has also been identified in patients undergoing stereotactic body radiation therapy (SBRT. While the parameters that predict PSA bounce have been extensively studied in prostate brachytherapy patients, this study is the first to analyze the clinical and pathologic predictors of PSA bounce in prostate SBRT patients. Materials and Methods: Our institution has maintained a prospective database of patients undergoing SBRT for prostate cancer since 2006. Our study population includes patients between May 2006 and November 2011 who have at least 18 months of follow-up. All patients were treated using the CyberKnife treatment system. The prescription dose was 3500-3625cGy in 5 fractions.Results: 120 patients were included in our study. Median PSA follow-up was 24 months (range 18-78 months. 34 (28% patients had a PSA bounce. The median time to PSA bounce was 9 months, and the median bounce size was 0.50ng/mL. On univariate analysis, only younger age (p = .011 was shown to be associated with an increased incidence of PSA bounce. Other patient factors, including race, prostate size, prior treatment by hormones, and family history of prostate cancer, did not predict PSA bounces. None of the tumor characteristics studied, including Gleason score, pre-treatment PSA, T-stage, or risk classification by NCCN guidelines, was associated with increased incidence of PSA bounces. Younger age was the only statistically significant predictor of PSA bounce on multivariate analysis (OR = 0.937, p = 0.009.Conclusion: PSA bounce, which has been reported after prostate brachytherapy, is also seen in a significant percentage of patients after CyberKnife SBRT. Close observation rather than biopsy can be considered for these patients. Younger age was the only factor that predicted PSA bounce.

  5. Report of the Second Asian Prostate Cancer (A-CaP Study Meeting

    Directory of Open Access Journals (Sweden)

    Choung-Soo Kim

    2017-09-01

    Full Text Available The Asian Prostate Cancer (A-CaP Study is an Asia-wide initiative that has been developed over the course of 2 years. The study was launched in December 2015 in Tokyo, Japan, and the participating countries and regions engaged in preparations for the study during the course of 2016, including patient registration and creation of databases for the purpose of the study. The Second A-CaP Meeting was held on September 8, 2016 in Seoul, Korea, with the participation of members and collaborators from 12 countries and regions. Under the study, each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognostic investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. At the Second Meeting, participating countries and regions discussed the status of preparations and discussed various issues that are being faced. These issues include technical challenges in creating databases, promoting participation in each country or region, clarifying issues relating to data input, addressing institutional issues such as institutional review board requirements, and the need for dedicated data managers. The meeting was positioned as an opportunity to share information and address outstanding issues prior to the initiation of the study. In addition to A-CaP-specific discussions, a series of special lectures was also delivered as a means of providing international perspectives on the latest developments in prostate cancer and the use of databases and registration studies around the world.

  6. Report of the Second Asian Prostate Cancer (A-CaP) Study Meeting.

    Science.gov (United States)

    Kim, Choung-Soo; Lee, Ji Youl; Chung, Byung Ha; Kim, Wun-Jae; Fai, Ng Chi; Hakim, Lukman; Umbas, Rainy; Ong, Teng Aik; Lim, Jasmine; Letran, Jason L; Chiong, Edmund; Wu, Tong-Lin; Lojanapiwat, Bannakij; Türkeri, Levent; Murphy, Declan G; Gardiner, Robert A; Moretti, Kim; Cooperberg, Matthew; Carroll, Peter; Mun, Seong Ki; Hinotsu, Shiro; Hirao, Yoshihiko; Ozono, Seiichiro; Horie, Shigeo; Onozawa, Mizuki; Kitagawa, Yasuhide; Kitamura, Tadaichi; Namiki, Mikio; Akaza, Hideyuki

    2017-09-01

    The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The study was launched in December 2015 in Tokyo, Japan, and the participating countries and regions engaged in preparations for the study during the course of 2016, including patient registration and creation of databases for the purpose of the study. The Second A-CaP Meeting was held on September 8, 2016 in Seoul, Korea, with the participation of members and collaborators from 12 countries and regions. Under the study, each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognostic investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. At the Second Meeting, participating countries and regions discussed the status of preparations and discussed various issues that are being faced. These issues include technical challenges in creating databases, promoting participation in each country or region, clarifying issues relating to data input, addressing institutional issues such as institutional review board requirements, and the need for dedicated data managers. The meeting was positioned as an opportunity to share information and address outstanding issues prior to the initiation of the study. In addition to A-CaP-specific discussions, a series of special lectures was also delivered as a means of providing international perspectives on the latest developments in prostate cancer and the use of databases and registration studies around the world.

  7. Human cell-based artificial antigen-presenting cells for cancer immunotherapy.

    Science.gov (United States)

    Butler, Marcus O; Hirano, Naoto

    2014-01-01

    Adoptive T-cell therapy, where anti-tumor T cells are first prepared in vitro, is attractive since it facilitates the delivery of essential signals to selected subsets of anti-tumor T cells without unfavorable immunoregulatory issues that exist in tumor-bearing hosts. Recent clinical trials have demonstrated that anti-tumor adoptive T-cell therapy, i.e. infusion of tumor-specific T cells, can induce clinically relevant and sustained responses in patients with advanced cancer. The goal of adoptive cell therapy is to establish anti-tumor immunologic memory, which can result in life-long rejection of tumor cells in patients. To achieve this goal, during the process of in vitro expansion, T-cell grafts used in adoptive T-cell therapy must be appropriately educated and equipped with the capacity to accomplish multiple, essential tasks. Adoptively transferred T cells must be endowed, prior to infusion, with the ability to efficiently engraft, expand, persist, and traffic to tumor in vivo. As a strategy to consistently generate T-cell grafts with these capabilities, artificial antigen-presenting cells have been developed to deliver the proper signals necessary to T cells to enable optimal adoptive cell therapy. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Prostate Cancer Detection and Prognosis: From Prostate Specific Antigen (PSA to Exosomal Biomarkers

    Directory of Open Access Journals (Sweden)

    Xavier Filella

    2016-10-01

    Full Text Available Prostate specific antigen (PSA remains the most used biomarker in the management of early prostate cancer (PCa, in spite of the problems related to false positive results and overdiagnosis. New biomarkers have been proposed in recent years with the aim of increasing specificity and distinguishing aggressive from non-aggressive PCa. The emerging role of the prostate health index and the 4Kscore is reviewed in this article. Both are blood-based tests related to the aggressiveness of the tumor, which provide the risk of suffering PCa and avoiding negative biopsies. Furthermore, the use of urine has emerged as a non-invasive way to identify new biomarkers in recent years, including the PCA3 and TMPRSS2:ERG fusion gene. Available results about the PCA3 score showed its usefulness to decide the repetition of biopsy in patients with a previous negative result, although its relationship with the aggressiveness of the tumor is controversial. More recently, aberrant microRNA expression in PCa has been reported by different authors. Preliminary results suggest the utility of circulating and urinary microRNAs in the detection and prognosis of PCa. Although several of these new biomarkers have been recommended by different guidelines, large prospective and comparative studies are necessary to establish their value in PCa detection and prognosis.

  9. Biomarkers for pancreatic cancer: promising new markers and options beyond CA 19-9.

    Science.gov (United States)

    Ballehaninna, Umashankar K; Chamberlain, Ronald S

    2013-12-01

    Pancreatic adenocarcinoma accounts for nearly 90-95% of exocrine malignant tumors of the pancreas. Traditionally, overexpressed proteins/epitopes such as CA 19-9, CA-50, CEA, and many others were being used as pancreatic cancer tumor markers. The main utility of these biomarkers was in the diagnosis of pancreatic cancer as well as to assess response to chemotherapy and to determine prognosis and to predict tumor recurrence. However, these markers had significant limitations such as lack of sensitivity, false-negative results in certain blood groups, as well as false-positive elevation in the presence of obstructive jaundice. To circumvent these limitations, an extraordinary amount of research is being performed to identify an accurate tumor marker or a panel of markers that could aid in the management of the pancreatic cancer. Although this research has identified a large number and different variety of biomarkers, few hold future promise as a preferred marker for pancreatic cancer. This review provides an insight into exciting new areas of pancreatic biomarker research such as salivary, pancreatic juice, and stool markers that can be used as a noninvasive test to identify pancreatic cancer. This manuscript also provides a discussion on newer biomarkers, the role of microRNAs, and pancreatic cancer proteomics, which have the potential to identify a preferred tumor marker for pancreatic adenocarcinoma. This review further elaborates on important genetic changes associated with the development and progression of pancreatic cancer that holds the key for the identification of a sensitive biomarker and which could also serve as a therapeutic target.

  10. Investigating the Functional Role of Prostate-Specific Membrane Antigen and Its Enzymatic Activity in Prostate Cancer Metastasis

    Science.gov (United States)

    2009-11-01

    7E11-C5. Cancer Res. 50: 6423-6429. 1990. 7. Wright GL Jr., Haley C, Beckett ML, Schellhammer PF. Expression of prostate-specific membrane antigen in...normal, benign, and malignant prostate tissues. Urol Oncol. 1:18-28. 1995. 8. Troyer JK, Beckett ML, Wright GL Jr. Detection and characterization of...mixed homogenates (data not shown). Thus, the aggre- gates form in intact cells, not after homogenization. Intracellular abundance of radio -labeled

  11. Prostate cancer detection rate in patients with fluctuating prostate-specific antigen levels on the repeat prostate biopsy

    OpenAIRE

    Park, Yong Hyun; Lee, Jung Keun; Jung, Jin-Woo; Lee, Byung Ki; Lee, Sangchul; Jeong, Seong Jin; Hong, Sung Kyu; Byun, Seok-Soo; Lee, Sang Eun

    2014-01-01

    Purpose: To evaluate whether the risk of prostate cancer was different according to the pattern of fluctuation in prostate-specific antigen (PSA) levels in patients undergoing repeat transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Methods: From March 2003 to December 2012, 492 patients underwent repeat TRUS-Bx. The patients were stratified into 3 groups based on the PSA fluctuation pattern: group 1 (continuous elevation of PSA, n=169), group 2 (PSA fluctuation with PSA velocity [PSAV...

  12. Effect of deoxycholic acid on Ca2+ movement, cell viability and apoptosis in human gastric cancer cells.

    Science.gov (United States)

    Chien, Jau-Min; Chou, Chiang-Ting; Liang, Wei-Zhe; Cheng, Jin-Shiung; Chang, Hong-Tai; Tseng, Hui-Wen; Kuo, Soong-Yu; Kuo, Chun-Chi; Chen, Fu-An; Shieh, Pochuen; Ho, Chin-Man; Lin, Jia-Rong; Kuo, Daih-Huang; Jan, Chung-Ren

    2015-02-01

    Deoxycholic acid (DOA) is one of the secondary bile acids used as a mild detergent for the isolation of membrane associated proteins. This study examined whether the secondary bile acid, DOA, altered Ca(2+) movement, cell viability and apoptosis in SCM1 human gastric cancer cells. The Ca(2+)-sensitive fluorescent dye fura-2 was used to measure [Ca(2+)]i. DOA-evoked [Ca(2+)]i rises concentration dependently. The response was reduced by removing extracellular Ca(2+). DOA-evoked Ca(2+) entry was inhibited by store-operated Ca(2+) channel inhibitors (nifedipine, econazole and SKF96365), the protein kinase C (PKC) activator phorbol 12-myristate 13 acetate (PMA) and the PKC inhibitor GF109203X. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) abolished DOA-evoked [Ca(2+)]i rises. Conversely, treatment with DOA abolished TG-evoked [Ca(2+)]i rises. Inhibition of phospholipase C with U73122 abolished DOA-evoked [Ca(2+)]i rises. At 100-500 μM, DOA decreased cell viability, which was not changed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM). DOA between 100 and 300 μM also induced apoptosis. Collectively, in SCM1 cells, DOA-induced [Ca(2+)]i rises by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via store-operated Ca(2+) channels. DOA also caused Ca(2+)-independent apoptosis.

  13. The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer

    DEFF Research Database (Denmark)

    Jensen, V; Ladekarl, M; Holm-Nielsen, P

    1995-01-01

    The prognostic value of oncogenic antigen 519 (OA-519) expression and tumour proliferative activity was evaluated in a retrospective series of 118 patients with low-risk breast cancer. Low risk was defined as negative axillary nodes, tumour diameter

  14. Human Leukocyte Antigen (HLA) Genotype as a Contributor to Racial/Ethnic Differences in Breast Cancer: A Population-Based, Molecular Epidemiologic Study

    National Research Council Canada - National Science Library

    Glaser, Sally

    2004-01-01

    ... variation. The human leukocyte antigen (HLA) component of the immune system, encoded by highly polymorphic genes that vary across racial/ethnic groups, has been suggested to be a biologically based risk factor for breast cancer and thus...

  15. Human Leukocyte Antigen (HLA) Genotype as a Contributor to Racial/Ethnic Differences in Breast Cancer: A Population-Based, Molecular Epidemiologic Study

    National Research Council Canada - National Science Library

    Glaser, Sally L

    2005-01-01

    .... The human leukocyte antigen (HLA) component of the immune system, coded by highly polymorphic genes whose distribution varies by race/ethnicity, may be a biologically based risk factor for breast cancer and thus may explain...

  16. Immunohistochemical analysis of the expression of MAGE-A and NY-ESO-1 cancer/testis antigens in diffuse large B-cell testicular lymphoma

    OpenAIRE

    Hudolin, Tvrtko; Kaštelan, Željko; Ilić, Ivana; Levarda-Hudolin, Katarina; Bašić-Jukić, Nikolina; Rieken, Malte; Spagnoli, Giulio C; Juretić, Antonio; Mengus, Chantal

    2013-01-01

    BACKGROUND: Primary testicular lymphoma (PTL) is a rare and lethal disease. The most common histological subtype is diffuse large B-cell lymphoma (DLBCL). Standard treatments are frequently ineffective. Thus, the development of novel forms of therapy is urgently required. Specific immunotherapy generating immune responses directed against antigen predominantly expressed by cancer cells such as cancer-testis antigens (CTA) may provide a valid alternative treatment for patients bearing PTL...

  17. Evidence for cytotoxic T lymphocyte response against human lung cancer: reconstitution of antigenic epitope with peptide eluted from lung adenocarcinoma MHC class I.

    Science.gov (United States)

    Calhoun, R F; Naziruddin, B; Enriquez-Rincon, F; Duffy, B F; Ritter, J M; Sundaresan, S; Patterson, G A; Cooper, J D; Mohanakumar, T

    2000-07-01

    Cancer-associated, major histocompatibility complex (MHC)-restricted peptide antigens have been elucidated in human melanomas and ovarian, breast, and renal carcinomas; but relatively little is known about lung cancer antigens. To work toward delineation of lung cancer-associated antigens, we developed tumor infiltrating lymphocytes (TILs), peripheral blood mononuclear cell-derived cytolytic T cell lines (CTL), autologous lung cancer cell lines, and normal lung cell lines from 17 patients undergoing lung cancer resections. The TILs and CTL lines were subsequently evaluated for markers of activation and specific lysis of autologous or allogeneic lung cancer cell lines or both. Freshly isolated TILs contained a more activated T cell population compared with the patients' peripheral blood T cells as evidenced by an increased expression of HLA-DR, CD25, and CD45RO. TILs isolated from 15 patients lysed allogeneic lung cancer lines. TILs lysed autologous lung cancer but not autologous normal lung or Epstein-Barr virus transformed B cell lines (B-LCL) in 4 of 8 cases tested, suggesting tumor specificity. A CTL line (RHPBL57.1) was generated from peripheral blood mononuclear cells of an HLA-A24(+) patient by stimulation against an established HLA-A24(+) allogeneic lung cancer cell line. RHPBL57.1 lysed the lung cancer cell line in an HLA-A24-restricted manner. Moreover, RHPBL57.1 specifically lysed autologous B-LCL pulsed with peptides, eluted from MHC class I and isolated from the HLA-A24(+) lung cancer cell line. TILs isolated from patients with lung cancer are predominantly an activated population of T cells with evidence of tumor and MHC class I-restricted lysis. Furthermore, we provide evidence for a lung cancer-associated, MHC class I-bound peptide antigen(s) that reconstitutes the epitope recognized by a lung cancer specific CD8(+) T cell line derived from a patient with lung cancer.

  18. Impacts of CA9 gene polymorphisms and environmental factors on oral-cancer susceptibility and clinicopathologic characteristics in Taiwan.

    Directory of Open Access Journals (Sweden)

    Ming-Hsien Chien

    Full Text Available BACKGROUND: In Taiwan, oral cancer has causally been associated with environmental carcinogens. Carbonic anhydrase 9 (CA9 is reportedly overexpressed in several types of carcinomas and is generally considered a marker of malignancy. The current study explored the combined effect of CA9 gene polymorphisms and exposure to environmental carcinogens on the susceptibility of developing oral squamous cell carcinoma (OSCC and the clinicopathological characteristics of the tumors. METHODOLOGY AND PRINCIPAL FINDINGS: Four single-nucleotide polymorphisms (SNPs of the CA9 gene from 462 patients with oral cancer and 519 non-cancer controls were analyzed by a real-time polymerase chain reaction (PCR. While the studied SNPs (CA9 rs2071676, rs3829078, rs1048638 and +376 Del were not associated with susceptibility to oral cancer, the GAA haplotype of 3 CA9 SNPs (rs2071676, rs3829078, and rs1048638 was related to a higher risk of oral cancer. Moreover, the four CA9 SNPs combined with betel quid chewing and/or tobacco consumption could robustly elevate susceptibility to oral cancer. Finally, patients with oral cancer who had at least one G allele of CA9 rs2071676 were at higher risk for developing lymph-node metastasis (p = 0.022, compared to those patients homozygous for AA. CONCLUSIONS: Our results suggest that the haplotype of rs2071676, rs3829078, and rs1048638 combined has potential predictive significance in oral carcinogenesis. Gene-environment interactions of CA9 polymorphisms, smoking, and betel-quid chewing might alter oral cancer susceptibility and metastasis.

  19. The efficacy of YKL-40 and CA125 as biomarkers for epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    L. Zou

    2010-12-01

    Full Text Available Our objective was to estimate the efficacy of the measurement of serum YKL-40 alone or with CA125 as biomarkers for the diagnosis of epithelial ovarian cancer (EOC using the YKL-40 ELISA kit. An experimental group of 49 ovarian cancer patients included 42 patients with EOC (53 ± 15 years, range: 19-81 years and 7 patients (48 ± 13 years, range: 29-36 years with borderline epithelial ovarian tumor. A control group of 88 non-malignant cases included 42 patients (43 ± 10 years, range: 26-77 years with benign gynecological disease and 46 healthy women (45 ± 14 years, range: 30-68 years at a teaching hospital. Both YKL-40 (220.1 ± 94.1 vs 61.6 ± 48.4 and 50.1 ± 41.2 ng/mL and CA125 (524.9 ± 972.5 vs 13.4 ± 7.6 and 28.5 ± 29.6 U/mL levels were significantly higher (P < 0.05 in patients with ovarian cancer compared to the healthy and non-malignant groups. YKL-40 had 92.9% sensitivity and 94.4% specificity for the diagnosis of EOC. When YKL-40 and CA125 were tested in parallel, the sensitivity was increased to 98.2%, but the specificity was decreased to 81.3%. The correlations between serum YKL-40 and tumor stage, grade histology, performance status, patient age, and extension of debulking surgery were tested. With increasing stage and grade of EOC, preoperative serum YKL-40 levels were significantly increased (P = 0.029, P = 0.05, respectively. Serum YKL-40 alone or with serum CA125 levels are useful, although with some limitations, to diagnose ovarian cancer. Our study showed that YKL-40 may not be an independent prognostic factor for ovarian cancer. This prospective study may be a new trend in looking for biomarkers that optimize diagnosis of ovarian cancer.

  20. The role of Cancer-Testis antigens as predictive and prognostic markers in non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Thomas John

    Full Text Available BACKGROUND: Cancer-Testis Antigens (CTAs are immunogenic proteins that are poor prognostic markers in non-small cell lung cancer (NSCLC. We investigated expression of CTAs in NSCLC and their association with response to chemotherapy, genetic mutations and survival. METHODS: We studied 199 patients with pathological N2 NSCLC treated with neoadjuvant chemotherapy (NAC; n = 94, post-operative observation (n = 49, adjuvant chemotherapy (n = 47 or unknown (n = 9. Immunohistochemistry for NY-ESO-1, MAGE-A and MAGE-C1 was performed. Clinicopathological features, response to neoadjuvant treatment and overall survival were correlated. DNA mutations were characterized using the Sequenom Oncocarta panel v1.0. Affymetrix data from the JBR.10 adjuvant chemotherapy study were obtained from a public repository, normalised and mapped for CTAs. RESULTS: NY-ESO-1 was expressed in 50/199 (25% samples. Expression of NY-ESO-1 in the NAC cohort was associated with significantly increased response rates (P = 0.03, but not overall survival. In the post-operative cohort, multivariate analyses identified NY-ESO-1 as an independent poor prognostic marker for those not treated with chemotherapy (HR 2.61, 95% CI 1.28-5.33; P = 0.008, whereas treatment with chemotherapy and expression of NY-ESO-1 was an independent predictor of improved survival (HR 0.267, 95% CI 0.07-0.980; P = 0.046. Similar findings for MAGE-A were seen, but did not meet statistical significance. Independent gene expression data from the JBR.10 dataset support these findings but were underpowered to demonstrate significant differences. There was no association between oncogenic mutations and CTA expression. CONCLUSIONS: NY-ESO-1 was predictive of increased response to neoadjuvant chemotherapy and benefit from adjuvant chemotherapy. Further studies investigating the relationship between these findings and immune mechanisms are warranted.

  1. Elevated plasma gastrin, CEA, and CA 19-9 levels decrease after colorectal cancer resection.

    Science.gov (United States)

    Bombski, G; Gasiorowska, A; Orszulak-Michalak, D; Neneman, B; Kotynia, J; Strzelczyk, J; Janiak, A; Malecka-Panas, E

    2003-03-01

    Gastrin stimulates mucosal growth of much of the gastrointestinal tract and has also been implicated in promoting growth of colonic tumors, but its role in colorectal carcinogenesis remains controversial. This study determined fasting serum gastrin levels before and after surgery for colorectal cancer (CRC) and the relationship to the clinical stage of the disease to investigate it possible prognostic role. Fasting radioimmunoassay gastrin, CA 19-9, and CEA levels were measured before and after surgery for CRC. Helicobacter pylori status was also assessed since it causes significant hypergastrinemia. Mean fasting plasma gastrin level was significantly higher in CRC patients than in controls before surgery but not 59 days after surgery. Mean CEA and CA 19-9 levels were significantly higher in patients with CRC before surgery than after tumor resection. There was a significant positive correlation between the plasma gastrin, CEA, and CA 19-9 levels and the CRC stage (Dukes' classification). The significance of gastrin as a marker for diagnosis or prognostic purposes in colorectal cancer needs to be further examined.

  2. Betalains increase vitexin-2-O-xyloside cytotoxicity in CaCo-2 cancer cells.

    Science.gov (United States)

    Farabegoli, F; Scarpa, E S; Frati, A; Serafini, G; Papi, A; Spisni, E; Antonini, E; Benedetti, S; Ninfali, P

    2017-03-01

    Vitexin-2-O-xyloside (XVX) from Beta vulgaris var. cicla L. (BVc) seeds, betaxanthin (R1) and betacyanin (R2) fractions from Beta vulgaris var. rubra L. (BVr) roots were combined and tested for cytotoxicity in CaCo-2 colon cancer cells. XVX was the most cytotoxic molecule, but the combination of XVX with R1 and R2 significantly prolonged its cytotoxicity. Cytotoxicity was mediated by the intrinsic apoptotic pathway, as shown by an increase in Bcl2-like protein 4, cleaved Poly ADP-Ribosyl Polymerase 1 and cleaved Caspase 3 levels with a parallel decrease in anti-apoptotic protein B-cell leukemia/lymphoma 2 levels. R1 and R2, used alone or in combination, reduced oxidative stress triggered by H2O2 in CaCo-2 cells. Betalains dampened cyclooxygenase-2 and interleukin-8 mRNA expression after lipopolysaccharide induction in CaCo-2, showing an anti-inflammatory action. Our results support the use of a cocktail of R1, R2 and XVX as a chemopreventive tool against colon cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Khan, Gazala [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  4. JC Virus T-Antigen in Colorectal Cancer Is Associated with p53 Expression and Chromosomal Instability, Independent of CpG Island Methylator Phenotype

    Directory of Open Access Journals (Sweden)

    Katsuhiko Nosho

    2009-01-01

    Full Text Available JC virus has a transforming gene encoding JC virus T-antigen (JCVT. JCVT may inactivate wild-type p53, cause chromosomal instability (CIN, and stabilize β-catenin. A link between JCVT and CpG island methylator phenotype (CIMP has been suggested. However, no large-scale study has examined the relations of JCVT with molecular alterations, clinical outcome, or prognosis in colon cancer. We detected JCVT expression (by immunohistochemistry in 271 (35% of 766 colorectal cancers. We quantified DNA methylation in eight CIMP-specific promoters (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3, and SOCS1 and eight other loci (CHFR, HIC1, IGFBP3, MGMT, MINT1, MINT31, p14, WRN by MethyLight. We examined loss of heterozygosity in 2p, 5q, 17q, and 18q. JCVT was significantly associated with p53 expression (P < .0001, p21 loss (P < .0001, CIN (≥2 chromosomal segments with LOH; P < .0001, nuclear β-catenin (P = .006, LINE-1 hypomethylation (P = .002, and inversely with CIMP-high (P = .0005 and microsatellite instability (MSI (P < .0001, but not with PIK3CA mutation. In multivariate logistic regression analysis, the associations of JCVT with p53 [adjusted odds ratio (OR, 8.45; P < .0001], CIN (adjusted OR, 2.53; P = .003, cyclin D1 (adjusted OR, 1.57; P = .02, LINE-1 hypomethylation (adjusted OR, 1.97 for a 30% decline as a unit; P = .03, BRAF mutation (adjusted OR, 2.20; P = .04, and family history of colorectal cancer (adjusted OR, 0.64; P = .04 remained statistically significant. However, JCVT was no longer significantly associated with CIMP, MSI, β-catenin, or cyclooxygenase-2 expression in multivariate analysis. JCVT was unrelated with patient survival. In conclusion, JCVT expression in colorectal cancer is independently associated with p53 expression and CIN, which may lead to uncontrolled cell proliferation.

  5. An integrative genomic and proteomic analysis of PIK3CA, PTEN and AKT mutations in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Stemke-Hale, Katherine; Gonzalez-Angulo, Ana Maria; Lluch, Ana; Neve, Richard M.; Kuo, Wen-Lin; Davies, Michael; Carey, Mark; Hu, Zhi; Guan, Yinghui; Sahin, Aysegul; Symmans, W. Fraser; Pusztai, Lajos; Nolden, Laura K.; Horlings, Hugo; Berns, Katrien; Hung, Mien-Chie; van de Vijver, Marc J.; Valero, Vicente; Gray, Joe W.; Bernards, Rene; Mills, Gordon B.; Hennessy, Bryan T.

    2008-05-06

    Phosphatidylinositol-3-kinase (PI3K)/AKT pathway aberrations are common in cancer. By applying mass spectroscopy-based sequencing and reverse phase protein arrays to 547 human breast cancers and 41 cell lines, we determined the subtype specificity and signaling effects of PIK3CA, AKT and PTEN mutations, and the effects of PIK3CA mutations on responsiveness to PI3K inhibition in-vitro and on outcome after adjuvant tamoxifen. PIK3CA mutations were more common in hormone receptor positive (33.8%) and HER2-positive (24.6%) than in basal-like tumors (8.3%). AKT1 (1.4%) and PTEN (2.3%) mutations were restricted to hormone receptor-positive cancers with PTEN protein levels also being significantly lower in hormone receptor-positive cancers. Unlike AKT1 mutations, PIK3CA (39%) and PTEN (20%) mutations were more common in cell lines than tumors, suggesting a selection for these but not AKT1 mutations during adaptation to culture. PIK3CA mutations did not have a significant impact on outcome in 166 hormone receptor-positive breast cancer patients after adjuvant tamoxifen. PIK3CA mutations, in comparison with PTEN loss and AKT1 mutations, were associated with significantly less and indeed inconsistent activation of AKT and of downstream PI3K/AKT signaling in tumors and cell lines, and PTEN loss and PIK3CA mutation were frequently concordant, suggesting different contributions to pathophysiology. PTEN loss but not PIK3CA mutations rendered cells sensitive to growth inhibition by the PI3K inhibitor LY294002. Thus, PI3K pathway aberrations likely play a distinct role in the pathogenesis of different breast cancer subtypes. The specific aberration may have implications for the selection of PI3K-targeted therapies in hormone receptor-positive breast cancer.

  6. Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers.

    Science.gov (United States)

    Kim, Kyungbin; Park, Won Young; Kim, Jee Yeon; Sol, Mee Young; Shin, Dong Hun; Park, Do Youn; Lee, Chang Hun; Lee, Jeong Hee; Choi, Kyung Un

    2012-12-01

    Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis. Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC). CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers. The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy.

  7. Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer.

    Directory of Open Access Journals (Sweden)

    Ian M Smith

    Full Text Available Epigenetic alterations have been implicated in the pathogenesis of solid tumors, however, proto-oncogenes activated by promoter demethylation have been sporadically reported. We used an integrative method to analyze expression in primary head and neck squamous cell carcinoma (HNSCC and pharmacologically demethylated cell lines to identify aberrantly demethylated and expressed candidate proto-oncogenes and cancer testes antigens in HNSCC.We noted coordinated promoter demethylation and simultaneous transcriptional upregulation of proto-oncogene candidates with promoter homology, and phylogenetic footprinting of these promoters demonstrated potential recognition sites for the transcription factor BORIS. Aberrant BORIS expression correlated with upregulation of candidate proto-oncogenes in multiple human malignancies including primary non-small cell lung cancers and HNSCC, induced coordinated proto-oncogene specific promoter demethylation and expression in non-tumorigenic cells, and transformed NIH3T3 cells.Coordinated, epigenetic unmasking of multiple genes with growth promoting activity occurs in aerodigestive cancers, and BORIS is implicated in the coordinated promoter demethylation and reactivation of epigenetically silenced genes in human cancers.

  8. Coordinated activation of candidate proto-oncogenes and cancer testes antigens via promoter demethylation in head and neck cancer and lung cancer.

    Science.gov (United States)

    Smith, Ian M; Glazer, Chad A; Mithani, Suhail K; Ochs, Michael F; Sun, Wenyue; Bhan, Sheetal; Vostrov, Alexander; Abdullaev, Ziedulla; Lobanenkov, Victor; Gray, Andrew; Liu, Chunyan; Chang, Steven S; Ostrow, Kimberly L; Westra, William H; Begum, Shahnaz; Dhara, Mousumi; Califano, Joseph

    2009-01-01

    Epigenetic alterations have been implicated in the pathogenesis of solid tumors, however, proto-oncogenes activated by promoter demethylation have been sporadically reported. We used an integrative method to analyze expression in primary head and neck squamous cell carcinoma (HNSCC) and pharmacologically demethylated cell lines to identify aberrantly demethylated and expressed candidate proto-oncogenes and cancer testes antigens in HNSCC. We noted coordinated promoter demethylation and simultaneous transcriptional upregulation of proto-oncogene candidates with promoter homology, and phylogenetic footprinting of these promoters demonstrated potential recognition sites for the transcription factor BORIS. Aberrant BORIS expression correlated with upregulation of candidate proto-oncogenes in multiple human malignancies including primary non-small cell lung cancers and HNSCC, induced coordinated proto-oncogene specific promoter demethylation and expression in non-tumorigenic cells, and transformed NIH3T3 cells. Coordinated, epigenetic unmasking of multiple genes with growth promoting activity occurs in aerodigestive cancers, and BORIS is implicated in the coordinated promoter demethylation and reactivation of epigenetically silenced genes in human cancers.

  9. Secretory pathway Ca2+-ATPases promote in vitro microcalcifications in breast cancer cells.

    Science.gov (United States)

    Dang, Donna; Prasad, Hari; Rao, Rajini

    2017-11-01

    Calcification of the breast is often an outward manifestation of underlying molecular changes that drive carcinogenesis. Up to 50% of all non-palpable breast tumors and 90% of ductal carcinoma in situ present with radiographically dense mineralization in mammographic scans. However, surprisingly little is known about the molecular pathways that lead to microcalcifications in the breast. Here, we report on a rapid and quantitative in vitro assay to monitor microcalcifications in breast cancer cell lines, including MCF7, MDA-MB-231, and Hs578T. We show that the Secretory Pathway Ca 2+ -ATPases SPCA1 and SPCA2 are strongly induced under osteogenic conditions that elicit microcalcifications. SPCA gene expression is significantly elevated in breast cancer subtypes that are associated with microcalcifications. Ectopic expression of SPCA genes drives microcalcifications and is dependent on pumping activity. Conversely, knockdown of SPCA expression significantly attenuates formation of microcalcifications. We propose that high levels of SPCA pumps may initiate mineralization in the secretory pathway by elevating luminal Ca 2+ . Our new findings offer mechanistic insight and functional implications on a widely observed, yet poorly understood radiographic signature of breast cancer. © 2017 Wiley Periodicals, Inc.

  10. Prostate stem cell antigen (PSCA) expression increases with high gleason score, advanced stage and bone metastasis in prostate cancer.

    Science.gov (United States)

    Gu, Z; Thomas, G; Yamashiro, J; Shintaku, I P; Dorey, F; Raitano, A; Witte, O N; Said, J W; Loda, M; Reiter, R E

    2000-03-02

    Prostate stem cell antigen (PSCA) is a recently defined homologue of the Thy-1/Ly-6 family of glycosylphosphatidylinositol (GPI)-anchored cell surface antigens. PSCA mRNA is expressed in the basal cells of normal prostate and in more than 80% of prostate cancers. The purpose of the present study was to examine PSCA protein expression in clinical specimens of human prostate cancer. Five monoclonal antibodies were raised against a PSCA-GST fusion protein and screened for their ability to recognize PSCA on the cell surface of human prostate cancer cells. Immunohistochemical analysis of PSCA expression was performed on paraffin-embedded sections from 25 normal tissues, 112 primary prostate cancers and nine prostate cancers metastatic to bone. The level of PSCA expression in prostate tumors was quantified and compared with expression in adjacent normal glands. The antibodies detect PSCA expression on the cell surface of normal and malignant prostate cells and distinguish three extracellular epitopes on PSCA. Prostate and transitional epithelium reacted strongly with PSCA. PSCA staining was also seen in placental trophoblasts, renal collecting ducts and neuroendocrine cells in the stomach and colon. All other normal tissues tested were negative. PSCA protein expression was identified in 105/112 (94%) primary prostate tumors and 9/9 (100%) bone metastases. The level of PSCA expression increased with higher Gleason score (P=0.016), higher tumor stage (P=0.010) and progression to androgen-independence (P=0. 021). Intense, homogeneous staining was seen in all nine bone metastases. PSCA is a cell surface protein with limited expression in extraprostatic normal tissues. PSCA expression correlates with tumor stage, grade and androgen independence and may have prognostic utility. Because expression on the surface of prostate cancer cells increases with tumor progression, PSCA may be a useful molecular target in advanced prostate cancer.

  11. Human Leukocyte Antigen (HLA) Genotype as a Contributor to Racial/Ethnic Differences in Breast Cancer: A Population-Based Molecular Epidemiologic Study

    Science.gov (United States)

    2006-05-01

    P, Talamini R, Franceschi S. Population attributable risk for breast cancer: diet , nutrition, and physical exercise. J Natl Cancer Inst 1998;90(5...human leukocyte antigen: distinct DQ and DR alleles are associated with development of gastric cancer and infection by Helicobacter pylori. Cancer Res...2001;61:2684-9. 20 Li Z, Chen D, Zhang C, Li Y, Cao B, Ning T, et al. HLA polymorphisms are associated with Helicobacter pylori infected gastric

  12. The prostate cancer immunome: In silico functional analysis of antigenic proteins from microarray profiling with IgG.

    Science.gov (United States)

    Luna-Coronell, Johana A; Vierlinger, Klemens; Gamperl, Magdalena; Hofbauer, Johann; Berger, Ingrid; Weinhäusel, Andreas

    2016-04-01

    The study of the immunome of prostate cancer (PCa) and characterization of autoantibody signature from differentially reactive antigens can uncover disease stage proteins, reveal enriched networks and even expose aberrant cellular mechanisms during the disease process. By conducting plasma IgG profiling on protein microarrays presenting 5449 unique human proteins expressed in 15 417 E. coli human cDNA expression clones, we elucidated 471 (21 higher reactive in PCa) differentially reactive antigens in 50 PCa versus 49 patients with benign prostate hyperplasia (BPH) at initial diagnosis. Functional analyzes show that the immune-profile of PCa compared to BPH control samples is significantly enriched in features targeting Cellular assembly, Cell death and pathways involved in Cell cycle, translation, and assembly of proteins as EIF2 signaling, PCa related genes as AXIN1 and TP53, and ribosomal proteins (e.g. RPS10). An overlap of 61 (out of 471) DIRAGs with the published 1545 antigens from the SEREX database has been found, however those were higher reactive in BPH. Clinical relevance is shown when antibody-reactivities against eight proteins were significantly (p < 0.001) correlated with Gleason-score. Herewith we provide a biological and pathophysiological characterization of the immunological layer of cancerous (PCa) versus benign (BPH) disease, derived from antibody profiling on protein microarrays. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Centrosomal localisation of the cancer/testis (CT antigens NY-ESO-1 and MAGE-C1 is regulated by proteasome activity in tumour cells.

    Directory of Open Access Journals (Sweden)

    Anna Pagotto

    Full Text Available The Cancer/Testis (CT antigen family of genes are transcriptionally repressed in most human tissues but are atypically re-expressed in many malignant tumour types. Their restricted expression profile makes CT antigens ideal targets for cancer immunotherapy. As little is known about whether CT antigens may be regulated by post-translational processing, we investigated the mechanisms governing degradation of NY-ESO-1 and MAGE-C1 in selected cancer cell lines. Inhibitors of proteasome-mediated degradation induced the partitioning of NY-ESO-1 and MAGE-C1 into a detergent insoluble fraction. Moreover, this treatment also resulted in increased localisation of NY-ESO-1 and MAGE-C1 at the centrosome. Despite their interaction, relocation of either NY-ESO-1 or MAGE-C1 to the centrosome could occur independently of each other. Using a series of truncated fragments, the regions corresponding to NY-ESO-1(91-150 and MAGE-C1(900-1116 were established as important for controlling both stability and localisation of these CT antigens. Our findings demonstrate that the steady state levels of NY-ESO-1 and MAGE-C1 are regulated by proteasomal degradation and that both behave as aggregation-prone proteins upon accumulation. With proteasome inhibitors being increasingly used as front-line treatment in cancer, these data raise issues about CT antigen processing for antigenic presentation and therefore immunogenicity in cancer patients.

  14. Centrosomal localisation of the cancer/testis (CT) antigens NY-ESO-1 and MAGE-C1 is regulated by proteasome activity in tumour cells.

    Science.gov (United States)

    Pagotto, Anna; Caballero, Otavia L; Volkmar, Norbert; Devalle, Sylvie; Simpson, Andrew J G; Lu, Xin; Christianson, John C

    2013-01-01

    The Cancer/Testis (CT) antigen family of genes are transcriptionally repressed in most human tissues but are atypically re-expressed in many malignant tumour types. Their restricted expression profile makes CT antigens ideal targets for cancer immunotherapy. As little is known about whether CT antigens may be regulated by post-translational processing, we investigated the mechanisms governing degradation of NY-ESO-1 and MAGE-C1 in selected cancer cell lines. Inhibitors of proteasome-mediated degradation induced the partitioning of NY-ESO-1 and MAGE-C1 into a detergent insoluble fraction. Moreover, this treatment also resulted in increased localisation of NY-ESO-1 and MAGE-C1 at the centrosome. Despite their interaction, relocation of either NY-ESO-1 or MAGE-C1 to the centrosome could occur independently of each other. Using a series of truncated fragments, the regions corresponding to NY-ESO-1(91-150) and MAGE-C1(900-1116) were established as important for controlling both stability and localisation of these CT antigens. Our findings demonstrate that the steady state levels of NY-ESO-1 and MAGE-C1 are regulated by proteasomal degradation and that both behave as aggregation-prone proteins upon accumulation. With proteasome inhibitors being increasingly used as front-line treatment in cancer, these data raise issues about CT antigen processing for antigenic presentation and therefore immunogenicity in cancer patients.

  15. Bioimpedance and chronoamperometry as an adjunct to prostate-specific antigen screening for prostate cancer

    Directory of Open Access Journals (Sweden)

    Abreu DS

    2011-04-01

    Full Text Available Darci Schiavon de AbreuDepartment of Urology, Hospital Unimed de Limeira, Sao Paulo, BrazilBackground: Bioimpedance is an electrical property of living tissue that has been shown to be a safe technique when used in a number of biomedical applications. The aim of this research was to assess the utility of bioimpedance measurement as a rapid, cost-effective, and noninvasive adjunct to digital rectal examination and PSA in differentiating tumor from normal prostatic tissue.Methods: Three hundred men were examined for signs and symptoms of prostate disorders. 147 patients with a digital rectal examination indicating a positive result underwent a prostate-specific antigen (PSA test. A biopsy was advised for 103 of the men, of whom 50 completed the study. Before undergoing biopsy, an examination with the EIS (electro interstitial scan system using bioimpedance and chronoamperometry was performed. In reference to the biopsy results (negative or positive, a statistical analysis of the EIS data and PSA was conducted using receiver operating characteristic curves to determine the specificity and sensitivity of each test.Results: The PSA test had a sensitivity of 73.9% and specificity of 51.9% using a cutoff value >4 and a sensitivity of 52.2% and specificity of 81.5% using a cutoff value ≥5.7 and P = 0.03. The delta of the electrical conductivity (DE of the left foot-right foot pathway had a sensitivity of 62.5% and specificity of 85.2%, with a cutoff value ≤-5 and P = 0.0001. Algorithms comprising the delta of electrical conductivity and PSA showed a sensitivity of 91.5% and a specificity of 59.3%, with a cutoff value ≤-10.52 and P = 0.0003.Conclusion: The EIS system had a very good specificity of 85.2%. However, the sensitivity of 62.5% would be a problem. Using a PSA reference >4.1 ng/mL, the adjunctive use of bioimpedance and chronoamperometry provided by EIS technology could raise the sensitivity from 73.9% to 91.5% and the specificity from 51

  16. Mass screening of prostate cancer in a Chinese population: the relationship between pathological features of prostate cancer and serum prostate specific antigen.

    Science.gov (United States)

    Gao, Hong-Wen; Li, Yu-Lin; Wu, Shan; Wang, Yi-Shu; Zhang, Hai-Feng; Pan, Yu-Zhuo; Zhang, Ling; Tateno, Hiroo; Sato, Ikuro; Kuwahara, Masaaki; Zhao, Xue-Jian

    2005-06-01

    To investigate the pathological features of the prostate biopsy through mass screening for prostate cancer in a Chinese cohort and their association with serum prostate specific antigen (PSA). A total of 12027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen tPSA test (by Elisa assay). Transrectal ultrasound-guided systematic six-sextant biopsies were performed on those whose serum tPSA value was > 4.0 ng/mL and those who had obstructive symptoms (despite their tPSA value) and were subject to subsequent pathological analysis with the aid of the statistic software SPSS 10.0 (SPSS. Inc., Chicago. USA). Of the 12027 cases, 158 (including 137 patients whose serum tPSA values were 4.0 ng/mL and 21 patients [serum tPSA sextant biopsies was established (r = 0.406, P first to conduct mass screening for prostate cancer by testing for serum tPSA values and the first to investigate the pathological features of prostate cancer in a cohort of Chinese men. Our results reveal that the moderately differentiated carcinoma is the most common type of prostate cancer. This study also has shown that the serum tPSA value in prostate cancer is associated with the Gleason score and the size of tumor.

  17. Current status of chimeric antigen receptor engineered T cell-based and immune checkpoint blockade-based cancer immunotherapies.

    Science.gov (United States)

    Hegde, Upendra P; Mukherji, Bijay

    2017-05-11

    Adoptive cell therapies with chimeric antigen receptor (CAR) engineered T cells (CAR-T) and immune checkpoint inhibition (ICI)-based cancer immunotherapies have lately shown remarkable success in certain tumor types. CAR-T cell-based therapies targeting CD19 can now induce durable remissions as well as prolong disease-free survival of patients with CD19 positive treatment refractory B cell malignancies and ICI-based therapies with humanized monoclonal antibodies against the T cell inhibitory receptors CTLA-4 and PD-1 as well as against the PD-1 ligand, PD-L1, can now achieve durable remissions as well as prolongation of life of a sizeable fraction of patients with melanoma and Hodgkin's lymphoma and non-small cell cancers. Most importantly, these immuno-therapeutic treatment modalities have raised the possibility of achieving long-term "containment" as well as "cures" for certain types of cancer. While this represents major advances in cancer immunotherapy, both modalities come with considerable toxicities, including fatalities. Although more work will be needed to bring CAR-T cell-based therapies to the bedside for most major cancers and a good deal more will be needed to make ICI-alone or in combination with other treatment modalities-work more consistently and across most major cancers, these two treatment modalities stand out as superb examples of successful translation of bench research to the bedside as well as represent real progress in the field of cancer immunotherapy.

  18. Specific Colon Cancer Cell Cytotoxicity Induced by Bacteriophage E Gene Expression under Transcriptional Control of Carcinoembryonic Antigen Promoter

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    Ana R. Rama

    2015-06-01

    Full Text Available Colorectal cancer is one of the most prevalent cancers in the world. Patients in advanced stages often develop metastases that require chemotherapy and usually show a poor response, have a low survival rate and develop considerable toxicity with adverse symptoms. Gene therapy may act as an adjuvant therapy in attempts to destroy the tumor without affecting normal host tissue. The bacteriophage E gene has demonstrated significant antitumor activity in several cancers, but without any tumor-specific activity. The use of tumor-specific promoters may help to direct the expression of therapeutic genes so they act against specific cancer cells. We used the carcinoembryonic antigen promoter (CEA to direct E gene expression (pCEA-E towards colon cancer cells. pCEA-E induced a high cell growth inhibition of human HTC-116 colon adenocarcinoma and mouse MC-38 colon cancer cells in comparison to normal human CCD18co colon cells, which have practically undetectable levels of CEA. In addition, in vivo analyses of mice bearing tumors induced using MC-38 cells showed a significant decrease in tumor volume after pCEA-E treatment and a low level of Ki-67 in relation to untreated tumors. These results suggest that the CEA promoter is an excellent candidate for directing E gene expression specifically toward colon cancer cells.

  19. Prostate-specific antigen-based population screening for prostate cancer: current status in Japan and future perspective in Asia.

    Science.gov (United States)

    Kitagawa, Yasuhide; Namiki, Mikio

    2015-01-01

    In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen (PSA) testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the Asian population. Since the 1990s, screening systems have been administered by each municipal government in Japan, and decreases in the prostate cancer mortality rate are expected in some regions where the exposure rate to PSA screening has increased markedly. A population-based screening cohort revealed that the proportion of metastatic disease in cancer detected by screening gradually decreased according to the increased exposure rate, and a decreasing trend in the proportion of cancer with high serum PSA levels after population screening was started. The prognosis of the prostate cancer detected by population screening was demonstrated to be more favorable than those diagnosed outside of the population screening. Recent results in screening cohorts demonstrated the efficacy of PSA. These recent evidences regarding population-based screening in Japan may contribute to establishing the optimal prostate cancer screening system in Asian individuals.

  20. Prostate-specific antigen-based population screening for prostate cancer: current status in Japan and future perspective in Asia

    Directory of Open Access Journals (Sweden)

    Yasuhide Kitagawa

    2015-06-01

    Full Text Available In Western countries, clinical trials on prostate cancer screening demonstrated a limited benefit for patient survival. In the Asia-Pacific region, including Japan, the rate of prostate-specific antigen (PSA testing remains very low compared with Western countries, and the benefits of population-based screening remain unclear. This review describes the current status of population screening and diagnosis for prostate cancer in Japan and discusses the efficacy of population screening for the Asian population. Since the 1990s, screening systems have been administered by each municipal government in Japan, and decreases in the prostate cancer mortality rate are expected in some regions where the exposure rate to PSA screening has increased markedly. A population-based screening cohort revealed that the proportion of metastatic disease in cancer detected by screening gradually decreased according to the increased exposure rate, and a decreasing trend in the proportion of cancer with high serum PSA levels after population screening was started. The prognosis of the prostate cancer detected by population screening was demonstrated to be more favorable than those diagnosed outside of the population screening. Recent results in screening cohorts demonstrated the efficacy of PSA. These recent evidences regarding population-based screening in Japan may contribute to establishing the optimal prostate cancer screening system in Asian individuals.

  1. Multiplex flow cytometry barcoding and antibody arrays identify surface antigen profiles of primary and metastatic colon cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Kumar Sukhdeo

    Full Text Available Colon cancer is a deadly disease affecting millions of people worldwide. Current treatment challenges include management of disease burden as well as improvements in detection and targeting of tumor cells. To identify disease state-specific surface antigen signatures, we combined fluorescent cell barcoding with high-throughput flow cytometric profiling of primary and metastatic colon cancer lines (SW480, SW620, and HCT116. Our multiplexed technique offers improvements over conventional methods by permitting the simultaneous and rapid screening of cancer cells with reduced effort and cost. The method uses a protein-level analysis with commercially available antibodies on live cells with intact epitopes to detect potential tumor-specific targets that can be further investigated for their clinical utility. Multiplexed antibody arrays can easily be applied to other tumor types or pathologies for discovery-based approaches to target identification.

  2. Prognostic role of KRAS, NRAS, BRAF and PIK3CA mutations in advanced colorectal cancer.

    Science.gov (United States)

    Foltran, Luisa; De Maglio, Giovanna; Pella, Nicoletta; Ermacora, Paola; Aprile, Giuseppe; Masiero, Elena; Giovannoni, Mariella; Iaiza, Emiliana; Cardellino, Giovanni Gerardo; Lutrino, Stefania Eufemia; Mazzer, Micol; Giangreco, Manuela; Pisa, Federica Edith; Pizzolitto, Stefano; Fasola, Gianpiero

    2015-01-01

    To explore the prognostic value of extended mutational profiling for metastatic colorectal cancer (mCRC). We retrospectively reviewed survival results of 194 mCRC patients that were assigned to four molecular subgroups: BRAF mutated; KRAS mutated codons 12-13 only; any of KRAS codons 61-146, PIK3CA or NRAS mutations and all wild-type. Point mutations were investigated by pyrosequencing. BRAF (5.2%) and KRAS 12-13 (31.9%) mutations were associated with poorer survival (HR 2.8 and 1.76, respectively). Presenting with right-sided colon cancer, not resected primary tumor, WBC >10 × 10(9)/l, receiving less chemotherapy or no bevacizumab were all associated with inferior outcome. The all-wild-type subgroup (39.2%) reported the longest survival. Extended mutational profile combined with clinical factors may impact on survival in mCRC.

  3. SSX cancer testis antigens are expressed in most multiple myeloma patients: co-expression of SSX1, 2, 4, and 5 correlates with adverse prognosis and high frequencies of SSX-positive PCs.

    NARCIS (Netherlands)

    Taylor, B.J.; Reiman, T.; Pittman, J.A.; Keats, J.J.; Bruijn, D.R.H. de; Mant, M.J.; Belch, A.R.; Pilarski, L.M.

    2005-01-01

    Cancer testis antigens (CTAs) are tumor-specific antigens that may be useful targets for cancer vaccines. Here, CTA expression was examined in multiple myeloma (MM), a B-cell cancer characterized by malignant plasma cells (PCs) in the bone marrow (BM), and monoclonal gammopathy of undetermined

  4. The prognostic benefit of tumour-infiltrating Natural Killer cells in endometrial cancer is dependent on concurrent overexpression of Human Leucocyte Antigen-E in the tumour microenvironment.

    Science.gov (United States)

    Versluis, M A C; Marchal, S; Plat, A; de Bock, G H; van Hall, T; de Bruyn, M; Hollema, H; Nijman, H W

    2017-11-01

    Human Leucocyte Antigen- E (HLA-E) has been reported as both a positive and negative prognostic marker in cancer. This apparent discrepancy may be due to opposing actions of HLA-E on tumour-infiltrating immune cells. Therefore, we evaluated HLA-E expression and survival in relation to the presence of intratumoural natural killer (NK) cells and cytotoxic T cells (CTLs). Tissue microarrays (TMAs) of endometrial tumours were used for immunohistochemical staining of parameters of interest. The combined impact of clinical, pathological and immune parameters on survival was analysed using log rank testing and Cox regression analyses. Upregulation of HLA-E was associated with an improved disease-free and disease-specific survival in univariate analysis (HR 0.58 95% CI 0.37-0.89; HR 0.42 95% CI 0.25-0.73, respectively). In multivariate analysis, the presence of NK cells predicts survival with a hazard ratio (HR) 0.28 (95% confidence interval (CI) 0.09-0.91) when HLA-E expression is upregulated; but it is associated with a worse prognosis when HLA-E expression is normal (HR 13.43, 95% CI 1.70-106.14). By contrast, the prognostic benefit of T cells was not modulated by HLA-E expression. Taken together, we demonstrate that the prognostic benefit of NK cells, but not T-cells, is influenced by HLA-E expression in endometrial cancer (EC) and propose a model to explain our observations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the Prostate-specific Antigen-era.

    Science.gov (United States)

    Jahn, Jaquelyn L; Giovannucci, Edward L; Stampfer, Meir J

    2015-12-15

    Widespread prostate-specific antigen (PSA) screening detects many cancers that would have otherwise gone undiagnosed. To estimate the prevalence of unsuspected prostate cancer, we reviewed 19 studies of prostate cancer discovered at autopsy among 6,024 men. Among men aged 70-79, tumor was found in 36% of Caucasians and 51% of African-Americans. This enormous prevalence, coupled with the high sensitivity of PSA screening, has led to the marked increase in the apparent incidence of prostate cancer. The impact of PSA screening on clinical practice is well-recognized, but its effect on epidemiologic research is less appreciated. Before screening, a larger proportion of incident prostate cancers had lethal potential and were diagnosed at advanced stage. However, in the PSA era, overall incident prostate cancer mainly is indolent disease, and often reflects the propensity to be screened and biopsied. Studies must therefore focus on cancers with lethal potential, and include long follow-up to accommodate the lead time induced by screening. Moreover, risk factor patterns differ markedly for potentially lethal and indolent disease, suggesting separate etiologies and distinct disease entities. Studies of total incident or indolent prostate cancer are of limited clinical utility, and the main focus of research should be on prostate cancers of lethal potential. © 2014 UICC.

  6. Initial prostate biopsy: development and internal validation of a biopsy-specific nomogram based on the prostate cancer antigen 3 assay

    NARCIS (Netherlands)

    Hansen, J.; Auprich, M.; Ahyai, S.A.; Taille, A. De La; Poppel, H. van; Marberger, M.; Stenzl, A.; Mulders, P.F.A.; Huland, H.; Fisch, M.; Abbou, C.C.; Schalken, J.A.; Fradet, Y.; Marks, L.S.; Ellis, W.; Partin, A.W.; Pummer, K.; Graefen, M.; Haese, A.; Walz, J.; Briganti, A.; Shariat, S.F.; Chun, F.K.

    2013-01-01

    BACKGROUND: Urinary prostate cancer antigen 3 (PCA3) assay in combination with established clinical risk factors improves the identification of men at risk of harboring prostate cancer (PCa) at initial biopsy (IBX). OBJECTIVE: To develop and validate internally the first IBX-specific PCA3-based

  7. Treating cancer as an infectious disease--viral antigens as novel targets for treatment and potential prevention of tumors of viral etiology.

    Directory of Open Access Journals (Sweden)

    Xing Guo Wang

    2007-10-01

    Full Text Available Nearly 20% of human cancers worldwide have an infectious etiology with the most prominent examples being hepatitis B and C virus-associated hepatocellular carcinoma and human papilloma virus-associated cervical cancer. There is an urgent need to find new approaches to treatment and prevention of virus-associated cancers.Viral antigens have not been previously considered as targets for treatment or prevention of virus-associated cancers. We hypothesized that it was possible to treat experimental HPV16-associated cervical cancer (CC and Hepatitis B-associated hepatocellular carcinoma (HCC by targeting viral antigens expressed on cancer cells with radiolabeled antibodies to viral antigens. Treatment of experimental CC and HCC tumors with (188Re-labeled mAbs to E6 and HBx viral proteins, respectively, resulted in significant and dose-dependent retardation of tumor growth in comparison with untreated mice or mice treated with unlabeled antibodies.This strategy is fundamentally different from the prior uses of radioimmunotherapy in oncology, which targeted tumor-associated human antigens and promises increased specificity and minimal toxicity of treatment. It also raises an exciting possibility to prevent virus-associated cancers in chronically infected patients by eliminating cells infected with oncogenic viruses before they transform into cancer.

  8. Comparison of targeted next-generation sequencing and Sanger sequencing for the detection of PIK3CA mutations in breast cancer

    National Research Council Canada - National Science Library

    Arsenic, Ruza; Treue, Denise; Lehmann, Annika; Hummel, Michael; Dietel, Manfred; Denkert, Carsten; Budczies, Jan

    2015-01-01

    Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha, PIK3CA, is one of the most frequently mutated genes in breast cancer, and the mutation status of PIK3CA has clinical relevance...

  9. Prognostic role of PIK3CA mutations of cell-free DNA in early-stage triple negative breast cancer.

    Science.gov (United States)

    Takeshita, Takashi; Yamamoto, Yutaka; Yamamoto-Ibusuki, Mutsuko; Inao, Toko; Sueta, Aiko; Fujiwara, Saori; Omoto, Yoko; Iwase, Hirotaka

    2015-11-01

    PIK3CA is an oncogene that encodes the p110α component of phosphatidylinositol 3-kinase (PI3K); it is the second most frequently mutated gene following the TP53 gene. In the clinical setting, PIK3CA mutations may have favorable prognostic value for hormone receptor-positive breast cancer patients and, during the past few years, PIK3CA mutations of cell-free DNA (cfDNA) have attracted attention as a potential noninvasive biomarker of cancer. However, there are few reports on the clinical implications of PIK3CA mutations for TNBC patients. We investigated the PIK3CA major mutation status of cfDNA as a noninvasive biomarker of cancer using droplet digital polymerase chain reaction (ddPCR), which has high level sensitivity and specificity for cancer mutation, in early-stage 49 triple negative breast cancer (TNBC) patients. A total of 12 (24.4%) of 49 patients had PIK3CA mutations of cfDNA. In a median follow up of 54.4 months, the presence of PIK3CA mutations of cfDNA had significant impacts on relapse-free survival (RFS; P = 0.0072) and breast cancer-specific survival (BCSS; P = 0.016), according to the log-lank test. In a Cox proportional hazards model, the presence of PIK3CA mutations of cfDNA had significant prognostic value in the univariate and multivariate analysis. Additionally, the presence of PIK3CA mutations of cfDNA was significantly correlated with positive androgen receptor phosphorylated form depending on PI3K signaling pathway (pAR) which is independent favorable prognostic factors of TNBC. We demonstrated that the presence of PIK3CA major mutations of cfDNA could be a discriminatory predictor of RFS and BCSS in early-stage TNBC patients and it was associated with PI3K pathway-dependent AR phosphorylation. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

  10. Juzentaihoto Failed to Augment Antigen-Specific Immunity but Prevented Deterioration of Patients’ Conditions in Advanced Pancreatic Cancer under Personalized Peptide Vaccine

    Directory of Open Access Journals (Sweden)

    Shigeru Yutani

    2013-01-01

    Full Text Available Juzentaihoto (JTT is a well-known Japanese herbal medicine, which has been reported to modulate immune responses and enhance antitumor immunity in animal models. However, it is not clear whether JTT has similar effects on humans. In particular, there is little information on the effects of JTT in antigen-specific immunity in cancer patients. Here we conducted a randomized clinical study to investigate whether combined usage of JTT could affect antigen-specific immunity and clinical findings in advanced pancreatic cancer patients undergoing personalized peptide vaccination (PPV, in which HLA-matched vaccine antigens were selected based on the preexisting host immunity. Fifty-seven patients were randomly assigned to receive PPV with (n=28 or without (n=29 JTT. Unexpectedly, JTT did not significantly affect cellular or humoral immune responses specific to the vaccine antigens, which were determined by antigen-specific interferon-γ secretion in T cells and antigen-specific IgG titers in plasma, respectively. Nevertheless, JTT prevented deterioration of patients’ conditions, such as anemia, lymphopenia, hypoalbuminemia, plasma IL-6 elevation, and reduction of performance status, which are frequently observed in advanced cancers. To our knowledge, this is the first clinical study that examined the immunological and clinical effects of JTT in cancer patients undergoing immunotherapy in humans.

  11. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  12. Study on {sup 41}Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Hongtao; Pang, Fangfang [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); China Institute of Atomic Energy, P.O. Box 275-50, Beijing 102413 (China); Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang [China Institute of Atomic Energy, P.O. Box 275-50, Beijing 102413 (China); Pang, Yijun [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); China Institute of Atomic Energy, P.O. Box 275-50, Beijing 102413 (China); Yang, Xianlin [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); Ruan, Xiangdong [College of Physics, Guangxi University, Nanning 530004 (China); Liu, Manjun; Xia, Chunbo [Guiin Medical University, Guilin 541004 (China)

    2015-10-15

    The annual incidence of new cancer patients in China is about 2 million, 30–40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of {sup 41}Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague–Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl{sub 2} solution (containing 1.4 mg Ca and 5nCi {sup 41}Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for {sup 41}Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of {sup 41}Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that {sup 41}Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

  13. Immunogenetic Profiling for Gastric Cancers Identifies Sulfated Glycosaminoglycans as Major and Functional B Cell Antigens in Human Malignancies.

    Science.gov (United States)

    Katoh, Hiroto; Komura, Daisuke; Konishi, Hiroki; Suzuki, Ryohei; Yamamoto, Asami; Kakiuchi, Miwako; Sato, Reiko; Ushiku, Tetsuo; Yamamoto, Shogo; Tatsuno, Kenji; Oshima, Takashi; Nomura, Sachiyo; Seto, Yasuyuki; Fukayama, Masashi; Aburatani, Hiroyuki; Ishikawa, Shumpei

    2017-08-01

    Recent successes in tumor immunotherapies have highlighted the importance of tumor immunity. However, most of the work conducted to date has been on T cell immunity, while the role of B cell immunity in cancer remains more elusive. In this study, immunogenetic repertoire profiling for tumor-infiltrating B and T cells in gastric cancers was carried out to help reveal the architecture of B cell immunity in cancer. Humoral immunity in cancer was shown to involve oligoclonal expansions of tumor-specific and private B cell repertoires. We find that B cell repertoires in cancer are shaped by somatic hypermutation (SHM) either with or without positive selection biases, the latter of which tended to be auto-reactive. Importantly, we identified sulfated glycosaminoglycans (GAGs) as major functional B cell antigens among gastric tumors. Furthermore, natural anti-sulfated GAG antibodies discovered in gastric cancer tissues showed robust growth-suppressive functions against a wide variety of human malignancies of various organs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Enhanced stimulation of anti-breast cancer T cells responses by dendritic cells loaded with poly lactic-co-glycolic acid (PLGA nanoparticle encapsulated tumor antigens

    Directory of Open Access Journals (Sweden)

    Soodabeh Iranpour

    2016-10-01

    Full Text Available Abstract Background Developing safe and effective cancer vaccine formulations is a primary focus in the field of cancer immunotherapy. Dendritic cells (DC are currently employed as cellular vaccine in clinical trials of tumor immunotherapy. Recognizing the critical role of DCs in initiating anti-tumor immunity has resulted in the development of several strategies that target vaccine antigens to DCs to trigger anti-tumor T cell responses. To increase the efficiency of antigen delivery systems for anti-tumor vaccines, encapsulation of tumor-associated antigens in polymer nanoparticles (NPs has been established. Methods In this study, the effect of tumor lysate antigen obtained from three stage III breast cancer tissues encapsulated within PLGA NPs to enhance the DC maturation was investigated. The T-cell immune response activation was then fallowed up. Fresh breast tumors were initially used to generate tumor lysate antigens containing poly lactic-co-glycolic acid (PLGA NP. The encapsulation efficiency and release kinetics were profiled. The efficiency of encapsulation was measured using Bradford protein assays measuring the dissolved NPs. The stability of released antigen from NPs was verified using SDS-PAGE. To evaluate the hypothesis that NPs enhances antigen presentation, including soluble tumor lysate, tumor lysate containing NPs and control NPs the efficiency of NP-mediated tumor lysate delivery to DCs was evaluated by assessing CD3+ T-cell stimulation after T cell/and DCs co-culture. Results The rate of encapsulation was increased by enhancing the antigen concentration of tumor lysate. However, increasing the antigen concentration diminished the encapsulation efficiency. In addition, higher initial protein contenting NPs led to a greater cumulative release. All three patients released variable amounts of IFN-γ, IL-10, IL-12 and IL-4 in response to re-stimulation. T cells stimulated with lysate-pulsed DCs induced a substantial increase in

  15. Bioimpedance and chronoamperometry as an adjunct to prostate-specific antigen screening for prostate cancer.

    Science.gov (United States)

    de Abreu, Darci Schiavon

    2011-01-01

    Bioimpedance is an electrical property of living tissue that has been shown to be a safe technique when used in a number of biomedical applications. The aim of this research was to assess the utility of bioimpedance measurement as a rapid, cost-effective, and noninvasive adjunct to digital rectal examination and PSA in differentiating tumor from normal prostatic tissue. Three hundred men were examined for signs and symptoms of prostate disorders. 147 patients with a digital rectal examination indicating a positive result underwent a prostate-specific antigen (PSA) test. A biopsy was advised for 103 of the men, of whom 50 completed the study. Before undergoing biopsy, an examination with the EIS (electro interstitial scan) system using bioimpedance and chronoamperometry was performed. In reference to the biopsy results (negative or positive), a statistical analysis of the EIS data and PSA was conducted using receiver operating characteristic curves to determine the specificity and sensitivity of each test. The PSA test had a sensitivity of 73.9% and specificity of 51.9% using a cutoff value >4 and a sensitivity of 52.2% and specificity of 81.5% using a cutoff value ≥5.7 and P = 0.03. The delta of the electrical conductivity (DE) of the left foot-right foot pathway had a sensitivity of 62.5% and specificity of 85.2%, with a cutoff value ≤-5 and P = 0.0001. Algorithms comprising the delta of electrical conductivity and PSA showed a sensitivity of 91.5% and a specificity of 59.3%, with a cutoff value ≤-10.52 and P = 0.0003. The EIS system had a very good specificity of 85.2%. However, the sensitivity of 62.5% would be a problem. Using a PSA reference >4.1 ng/mL, the adjunctive use of bioimpedance and chronoamperometry provided by EIS technology could raise the sensitivity from 73.9% to 91.5% and the specificity from 51.9% to 59.3% in prostate cancer screening.

  16. Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies against Prostate Cancer

    Science.gov (United States)

    2000-07-01

    gene. GET FOR GATA TRANSCRIPTION FACTORS. Carlos Perez-Stable, and B. A Roos, Miami VA Med Center/GRECC, Miami, FL, and Univ of Miami Sch of #121...WR, Heston WD: Expression of the prostate- specific membrane antigen. Cancer Res 1994;54:1807-1811. 7. Silver DA, Pellicer I, Fair WR, Heston WD...Prostate: Basic and Clinical Aspects. R. K. Naz, CRC Press: 267-298. 26. Heston, W. D. W. S., D.A. Pellicer , I. Fair, W.R. Cordon-Cardo, C. (1996

  17. Targeting Intracellular Calcium Signaling ([Ca2+]i to Overcome Acquired Multidrug Resistance of Cancer Cells: A Mini-Overview

    Directory of Open Access Journals (Sweden)

    Dietrich Büsselberg

    2017-05-01

    Full Text Available Cancer is a main public health problem all over the world. It affects millions of humans no matter their age, gender, education, or social status. Although chemotherapy is the main strategy for the treatment of cancer, a major problem limiting its success is the intrinsic or acquired drug resistance. Therefore, cancer drug resistance is a major impediment in medical oncology resulting in a failure of a successful cancer treatment. This mini-overview focuses on the interdependent relationship between intracellular calcium ([Ca2+]i signaling and multidrug resistance of cancer cells, acquired upon treatment of tumors with anticancer drugs. We propose that [Ca2+]i signaling modulates gene expression of multidrug resistant (MDR genes which in turn can be modulated by epigenetic factors which in turn leads to modified protein expression in drug resistant tumor cells. A precise knowledge of these mechanisms will help to develop new therapeutic strategies for drug resistant tumors and will improve current chemotherapy.

  18. Vaccination with recombinant adenoviruses and dendritic cells expressing prostate-specific antigens is effective in eliciting CTL and suppresses tumor growth in the experimental prostate cancer.

    Science.gov (United States)

    Kim, Sol; Lee, Jee-Boong; Lee, Geon Kook; Chang, Jun

    2009-06-15

    Prostate cancer is currently the most commonly diagnosed cancer in men and the second leading cause of cancer-related death in men in the US. Immunological approaches may provide an alternative option for prevention and treatment of prostate cancer. To develop vaccine against prostate cancer using mouse model, we constructed three recombinant adenoviruses expressing prostate-specific membrane antigen (rAd/PSMA), prostate stem cell antigen (rAd/PSCA) and six-transmembrane epithelial antigen of the prostate (rAd/STEAP), that were specifically up-regulated in the transgenic murine prostate cancer. Male C57BL/6 mice were immunized by intravenous injection of these recombinant adenoviruses and subsequently by subcutaneous injection of dendritic cells pulsed with TRAMP-C1 tumor lysate. After subcutaneous challenge with TRAMP-C1 cells, tumor growth was significantly delayed in the immunized mice compared to the control group. Surprisingly, significant numbers of STEAP-specific CD8 T cells were detected in the peripheral blood and the spleen of immune mice using MHC I tetramers, and injection of rAd/STEAP alone followed by pulsed DC was sufficient to inhibit tumor growth. Therapeutic vaccination also significantly delayed the growth of pre-established tumors. Our results suggest that STEAP is a good immunologic target antigen against prostate cancer and our vaccination regimen successfully elicits anti-tumor CTL responses and suppresses tumor growth. More studies will expedite the development of this vaccine toward clinical application.

  19. Dutasteride treatment over 2 years delays prostate-specific antigen progression in patients with biochemical failure after radical therapy for prostate cancer: Results from the randomised, placebo-controlled avodart after radical therapy for Prostate Cancer Study (ARTS)

    NARCIS (Netherlands)

    F.H. Schröder (Fritz); C.H. Bangma (Chris); A.F. Angulo; A. Alcaraz (Antonio); J.F. Colombel (Jean Frédéric); T.A. McNicholas (Tom); T.L. Tammela (Teuvo); I.M. Nandy (Indrani); R. Castro (Ramiro)

    2013-01-01

    textabstractBackground: Rising prostate-specific antigen (PSA) levels after radical therapy are indicative of recurrent or residual prostate cancer (PCa). This biochemical recurrence typically predates clinically detectable metastatic disease by several years. Management of patients with biochemical

  20. The CAP cancer protocols – a case study of caCORE based data standards implementation to integrate with the Cancer Biomedical Informatics Grid

    Directory of Open Access Journals (Sweden)

    Warzel Denise B

    2006-06-01

    Full Text Available Abstract Background The Cancer Biomedical Informatics Grid (caBIG™ is a network of individuals and institutions, creating a world wide web of cancer research. An important aspect of this informatics effort is the development of consistent practices for data standards development, using a multi-tier approach that facilitates semantic interoperability of systems. The semantic tiers include (1 information models, (2 common data elements, and (3 controlled terminologies and ontologies. The College of American Pathologists (CAP cancer protocols and checklists are an important reporting standard in pathology, for which no complete electronic data standard is currently available. Methods In this manuscript, we provide a case study of Cancer Common Ontologic Representation Environment (caCORE data standard implementation of the CAP cancer protocols and checklists model – an existing and complex paper based standard. We illustrate the basic principles, goals and methodology for developing caBIG™ models. Results Using this example, we describe the process required to develop the model, the technologies and data standards on which the process and models are based, and the results of the modeling effort. We address difficulties we encountered and modifications to caCORE that will address these problems. In addition, we describe four ongoing development projects that will use the emerging CAP data standards to achieve integration of tissue banking and laboratory information systems. Conclusion The CAP cancer checklists can be used as the basis for an electronic data standard in pathology using the caBIG™ semantic modeling methodology.

  1. Clinical Outcomes of Chemotherapy Naïve Men with Metastatic Castration Resistant Prostate Cancer and Low Baseline Prostate Specific Antigen Treated with Enzalutamide vs Placebo.

    Science.gov (United States)

    Taplin, Mary-Ellen; Armstrong, Andrew J; Lin, Ping; Krivoshik, Andrew; Phung, De; Parli, Teresa; Tombal, Bertrand; Beer, Tomasz M

    2017-12-01

    Metastatic castration resistant prostate cancer with low baseline prostate specific antigen represents an early stage in the natural history of castration resistant prostate cancer progression (low volume disease), low prostate specific antigen producing disease or disease that is less dependent on androgen receptor biology (high volume disease). We analyzed outcomes in men with low prostate specific antigen and a high disease burden who received the oral androgen receptor inhibitor enzalutamide in the PREVAIL (Safety and Efficacy Study of Oral MDV3100 in Chemotherapy-Naive Patients with Progressive Metastatic Prostate Cancer) study. In this exploratory analysis low baseline prostate specific antigen was defined as less than 10 ng/ml. Post hoc analyses included radiographic progression-free and overall survival in the once daily enzalutamide and placebo arms. Patients were stratified post hoc by high volume disease, defined as more than 4 bone metastases and/or visceral disease, and low volume disease, defined as 4 or fewer bone metastases with no visceral disease. Of 1,717 patients enrolled in PREVAIL 242 (14.1%) had low baseline prostate specific antigen, including 110 with high volume disease. Enzalutamide decreased the risk of radiographic progression relative to placebo in patients with low baseline prostate specific antigen (HR 0.20, 95% CI 0.10-0.42). This decrease was irrespective of tumor burden (high volume disease HR 0.17, 95% CI 0.06-0.51 and low volume disease HR 0.25, 95% CI 0.09-0.70). Median overall survival was not reached in patients with low baseline prostate specific antigen in either treatment arm. Chemotherapy naïve men with metastatic castration resistant prostate cancer and low baseline prostate specific antigen irrespective of disease burden may benefit from enzalutamide. This indicates that targeting the androgen receptor signaling pathway is a therapeutic option in similar patients. Copyright © 2017 American Urological Association

  2. The utility of serum CA-125 in predicting extra-uterine disease in apparent early-stage endometrial cancer.

    Science.gov (United States)

    Nicklin, James; Janda, Monika; Gebski, Val; Jobling, Thomas; Land, Russell; Manolitsas, Tom; McCartney, Anthony; Nascimento, Marcelo; Perrin, Lewis; Baker, Jannah F; Obermair, Andreas

    2012-08-15

    Surgical staging in early-stage uterine cancer is controversial. Preoperative serum CA-125 may be of clinical value in predicting the presence of extra-uterine disease in patients with apparent early-stage endometrial cancer. Between October 6, 2005, and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. Of these, 657 patients with endometrial adenocarcinoma had a preoperative serum CA-125 value recorded. Multiple cross-validation analysis was undertaken to correlate preoperative serum CA-125 with stage of disease (Stage I vs. Stage II+) after surgery. Patients' median preoperative serum CA-125 was 14 U/ml. A cutoff point of 30 U/ml was associated with the smallest misclassification error, and using this cutoff, 98 patients (14.9%) had elevated CA-125 levels. Of those, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had an elevated CA-125 level. On univariate and multivariable logistic regression analysis, only preoperative CA-125 level, but no other preoperative clinical characteristics were found to be associated with extra-uterine spread of disease. Utilizing a cutoff point of 30 U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0, 88.5, 36.7 and 85.7%, respectively. Elevated CA-125 above 30 U/ml in patients with apparent early-stage disease is a risk factor for the presence of extra-uterine disease and may assist clinicians in the management of patients with clinical Stage I endometrial cancer. Copyright © 2011 UICC.

  3. The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy

    OpenAIRE

    Dewitte, Heleen; Van Lint, Sandra; Heirman, Carlo; Thielemans, Kris; De Smedt, Stefaan; Breckpot, Karine; Lentacker, Ine

    2014-01-01

    Dendritic cell (DC)-based cancer vaccines, where the patient's own immune system is harnessed to target and destroy tumor tissue, have emerged as a potent therapeutic strategy. In the development of such DC vaccines, it is crucial to load the DCs with tumor antigens, and to simultaneously activate them to become more potent antigen-presenting cells. For this, we report on microbubbles, loaded with both antigen mRNA as well as immunomodulating TriMix mRNA, which can be used for the ultrasound-...

  4. Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma.

    Science.gov (United States)

    Gjerstorff, Morten F; Pøhl, Mette; Olsen, Karen E; Ditzel, Henrik J

    2013-10-08

    The unique expression pattern and immunogenic properties of cancer/testis antigens make them ideal targets for immunotherapy of cancer. The MAGE-A3 cancer/testis antigen is frequently expressed in non-small cell lung cancer (NSCLC) and vaccination with MAGE-A3 in patients with MAGE-A3-positive NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC. Tumor biopsies from normal lung tissue and from a large cohort (n = 169) of NSCLC patients were examined for GAGE, NY-ESO-1 and SP17 protein expression by immunohistochemical analysis. The expression of these antigens was further matched to clinical and pathological features using univariate cox regression analysis. GAGE and NY-ESO-1 cancer/testis antigens were not expressed in normal lung tissue, while SP17 was expressed in ciliated lung epithelia. The frequency of GAGE, NY-ESO-1 and SP17 expression in NSCLC tumors were 26.0% (44/169), 11.8% (20/169) and 4.7% (8/169), respectively, and 33.1% (56/169) of the tumors expressed at least one of these antigens. In general, the expression of GAGE, NY-ESO-1 and SP17 was not significantly associated with a specific histotype (adenocarcinoma vs. squamous cell carcinoma), but high-level GAGE expression (>50%) was more frequent in squamous cell carcinoma (p = 0.02). Furthermore, the frequency of GAGE expression was demonstrated to be significantly higher in stage II-IIIa than stage I NSCLC (17.0% vs. 35.8%; p = 0.02). Analysis of the relation between tumor expression of GAGE and NY-ESO-1 and survival endpoints revealed no significant associations. Our study demonstrates that GAGE, NY-ESO-1 and SP17 cancer/testis antigens are candidate targets for immunotherapy of NSCLC and further suggest that multi-antigen vaccines may be beneficial.

  5. Six-transmembrane epithelial antigen of the prostate as an immunotherapeutic target for renal cell and bladder cancer.

    Science.gov (United States)

    Azumi, Makoto; Kobayashi, Hiroya; Aoki, Naoko; Sato, Keisuke; Kimura, Shoji; Kakizaki, Hidehiro; Tateno, Masatoshi

    2010-05-01

    T-cell based immunotherapy for renal cell and bladder cancer is one of the most promising therapeutic approaches. STEAP is a novel cell surface protein that is over expressed in various cancers, including renal cell and bladder cancer. Recently we induced STEAP specific helper T lymphocytes that recognize the naturally processed STEAP peptide epitopes STEAP(102-116) and STEAP(192-206) arising from STEAP expressing tumor cells. Thus, STEAP may be a useful tumor associated antigen for designing T-cell based immunotherapy. We determined whether STEAP could induce anti-cellular immune responses to urological cancer. We selected 2 previously described STEAP derived epitope peptides, STEAP(102-116) and STEAP(192-206), and examined their ability to elicit helper T-lymphocyte responses by in vitro vaccination of CD4 T lymphocytes from healthy individuals and patients with cancer. STEAP peptides induced helper T-lymphocyte responses using lymphocytes from healthy individuals that directly recognized STEAP expressing, DR positive renal cell and bladder cancer cells, and autologous dendritic cells pulsed with STEAP expressing tumor cell lysates in a major histocompatibility complex class II restricted manner. These peptides also stimulated T-cell responses in patients with renal cell or bladder cancer. Each STEAP peptides behaved as a promiscuous T-cell epitope, in that they stimulated T cells in the context of multiple major histocompatibility complex class II alleles. Results show that STEAP helper T-lymphocyte epitopes could be used to optimize T-cell based immunotherapy against STEAP expressing renal cell and bladder cancer. 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  6. HINT2 triggers mitochondrial Ca2+ influx by regulating the mitochondrial Ca2+ uniporter (MCU) complex and enhances gemcitabine apoptotic effect in pancreatic cancer.

    Science.gov (United States)

    Chen, Linghui; Sun, Qiang; Zhou, Dongkai; Song, Wei; Yang, Qifan; Ju, Bingjie; Zhang, Lufei; Xie, Haiyang; Zhou, Lin; Hu, Zhenhua; Yao, Hangping; Zheng, Shusen; Wang, Weilin

    2017-12-28

    In early studies, it was shown that HINT2, which sensitizes cells to mitochondrial apoptosis, is down-regulated in hepatocellular carcinoma (HCC) cells (Martin et al., 2006). However, the molecular mechanism of this effect is unknown. Immunohistochemistry revealed that HINT2 expression is relatively low in pancreatic cancer tissues, compared to that in adjacent tissues (P cancer patients. Up-regulation of HINT2 was shown to trigger pancreatic cancer cell apoptosis, decrease mitochondrial membrane potential (ΔΨm), promote intracellular reactive oxygen species (ROS) production, and elevate mitochondrial Ca2+ levels. However, co-treatment of HINT2 overexpressing BxPC-3 cells with ruthenium red partially inhibited HINT2-induced apoptosis, which was associated with a reduction in ΔΨm and an increase in intracellular ROS and mitochondrial Ca2+. According to our results, mitochondrial calcium uptake1 and 2 (MICU1 and MICU2) were down-regulated and the essential MCU regulator (EMRE) was up-regulated in cells transduced with Adv-HINT2. Therefore, we deduced that HINT2 triggers apoptosis in pancreatic cancer cells by regulating mitochondrial Ca2+ influx through the mitochondrial calcium uniporter (MCU). In addition, we found that HINT2 can sensitize BxPC-3 and L3.6pl cells to gemcitabine-induced apoptosis and that gemcitabine up-regulates HINT2 expression. This indicates that gemcitabine-induced apoptosis is related to HINT2 levels. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Rapid and ultrasensitive flexible palladium nano-thin film biosensing electrode development for cancer antigen HER2 detection

    Science.gov (United States)

    Huang, Yun-Tzu; Chang, Chia-Yu; Chen, Wei; Su, Chien-Hao; Hsu, Guo-Cheng; Chang, Chia-Ching

    HER2 (human epidermal growth factor receptor 2) is one of the significant surface antigens of breast cancer Trace amount of HER2 protein in human serum is highly correlated to the tumor progression in breast cancers especially in the cases of recurrence. Therefore, HER2 detection of human serum is significant for early detection of cancer recurrence. Conventional HER2 detection approaches may not be sensitive enough or contain highly false positive rate or time consuming for accurate detection. Therefore, a rapid, highly sensitive and specific sensing is highly desired. By using HER2 specific binding peptide functionalized palladium thin film electrochemical electrode the HER2 protein concentration can be determined at sub-nanogram level by electrochemical impedance spectroscopy (EIS) within 10 mins. The Pd nano-film is sputtered on the flexible plastics substrate and reduces the cost of this electrode. Due to the low cost of the electrode, it is designed as a disposable biosensing probe which may reduce the concern of human sample contamination. The self-management after breast cancer operation may be feasible in the near future. Keywords: Electrochemical impedance spectroscopy(EIS), breast cancer, biosensor Corresponding author: ccchang01@faculty.nctu.edu.tw; Cheeshin Technology Co. Collaboration.

  8. MAGE-A1, GAGE and NY-ESO-1 cancer/testis antigen expression during human gonadal development

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Kock, Kirsten; Nielsen, Ole

    2007-01-01

    BACKGROUND: Cancer/testis antigens (CTAs) are expressed in several cancers and during normal adult male germ cell differentiation. Little is known about their role in fetal development of human germ cells. METHODS: We examined expression of the CTAs MAGE-A1, GAGE and NY-ESO-1 in fetal gonads...... by single and double immunohistochemical staining. RESULTS: We found that GAGE was expressed in the primordial germ cells of the gonadal primordium, whereas MAGE-A1 and NY-ESO-1 were first detected in germ cells of both testis and ovary after sexual differentiation was initiated. The number of positive germ...... cells and the staining intensity of all three CTAs peaked during the second trimester and gradually decreased towards birth in both male and female germ cells. In oocytes, MAGE-A1 expression terminated around birth, whereas NY-ESO-1 expression persisted through the neonatal stage and GAGE expression...

  9. Understanding prostate-specific antigen dynamics in monitoring metastatic castration-resistant prostate cancer: implications for clinical practice

    Directory of Open Access Journals (Sweden)

    Atsushi Mizokami

    2017-01-01

    Full Text Available Availability of novel hormonal therapies as well as docetaxel and cabazitaxel treatment for metastatic castration-resistant prostate cancer (CRPC has changed the outlook for this group of patients with improvements in progression-free survival and overall survival. Physicians often diagnose the progression of prostate cancer using serum prostate-specific antigen (PSA. However, serum PSA is not always correlated with the clinical status in CRPC. To evaluate the PSA dynamics with greater precision, understanding of the control of PSA and of the mechanisms of development of CRPC is needed. Moreover, it is necessary to use new hormonal therapies with an appropriate timing to optimally improve the prognosis and the QOL of the patients. In the present review, we ascertain the PSA dynamics and the mechanisms of the development of CRPC to assist in optimal utilization of the new treatments for mCRPC.

  10. pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Yasuyuki; Zhang, Qing [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Akita, Kaoru; Nakada, Hiroshi [Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kita-ku, Kyoto 603-8555 (Japan); Hamamura, Kazunori; Tokuda, Noriyo [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Tsuchida, Akiko [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Noguchi Institute, 1-8-1 Kaga, Itabashi, Tokyo 173-0003 (Japan); Matsubara, Takeshi; Hori, Tomoko; Okajima, Tetsuya [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Furukawa, Keiko [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan); Department of Biomedical Sciences, Chubu University College of Life and Health Sciences, 1200 Matsumoto-cho, Kasugai 487-8501 (Japan); Urano, Takeshi [Department of Biochemistry, Shimane University School of Medicine, Izumo 693-8501 (Japan); Furukawa, Koichi, E-mail: koichi@med.nagoya-u.ac.jp [Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065 (Japan)

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer ppGalNAc-T13 was up-regulated in high metastatic sublines of Lewis lung cancer. Black-Right-Pointing-Pointer ppGalNAc-T13 expression enhanced cell invasion activity in low metastatic sublines. Black-Right-Pointing-Pointer Trimeric Tn antigen was induced in the transfectant cells of ppGalNAc-T13 cDNA. Black-Right-Pointing-Pointer A major protein carrying trimeric Tn structure was identified as Syndecan-1. Black-Right-Pointing-Pointer Silencing of ppGalNAc-T13 resulted in the reduction of invasion and of metastasis.. -- Abstract: In order to analyze the mechanisms for cancer metastasis, high metastatic sublines (H7-A, H7-Lu, H7-O, C4-sc, and C4-ly) were obtained by repeated injection of mouse Lewis lung cancer sublines H7 and C4 into C57BL/6 mice. These sublines exhibited increased proliferation and invasion activity in vitro. Ganglioside profiles exhibited lower expression of GM1 in high metastatic sublines than the parent lines. Then, we established GM1-Si-1 and GM1-Si-2 by stable silencing of GM1 synthase in H7 cells. These GM1-knockdown clones exhibited increased proliferation and invasion. Then, we explored genes that markedly altered in the expression levels by DNA microarray in the combination of C4 vs. C4-ly or H7 vs. H7 (GM1-Si). Consequently, pp-GalNAc-T13 gene was identified as up-regulated genes in the high metastatic sublines. Stable transfection of pp-GalNAc-T13 cDNA into C4 (T13-TF) resulted in increased invasion and motility. Then, immunoblotting and flow cytometry using various antibodies and lectins were performed. Only anti-trimeric Tn antibody (mAb MLS128), showed increased expression levels of trimeric Tn antigen in T13-TF clones. Moreover, immunoprecipitation/immunoblotting was performed by mAb MLS128, leading to the identification of an 80 kDa band carrying trimeric Tn antigen, i.e. Syndecan-1. Stable silencing of endogenous pp-GalNAc-T13 in C4-sc (T13-KD) revealed that primary tumors generated by

  11. The potential of antigen and TriMix sonoporation using mRNA-loaded microbubbles for ultrasound-triggered cancer immunotherapy.

    Science.gov (United States)

    Dewitte, Heleen; Van Lint, Sandra; Heirman, Carlo; Thielemans, Kris; De Smedt, Stefaan C; Breckpot, Karine; Lentacker, Ine

    2014-11-28

    Dendritic cell (DC)-based cancer vaccines, where the patient's own immune system is harnessed to target and destroy tumor tissue, have emerged as a potent therapeutic strategy. In the development of such DC vaccines, it is crucial to load the DCs with tumor antigens, and to simultaneously activate them to become more potent antigen-presenting cells. For this, we report on microbubbles, loaded with both antigen mRNA as well as immunomodulating TriMix mRNA, which can be used for the ultrasound-triggered transfection of DCs. In vivo experiments with in vitro sonoporated DCs show the effective induction of antigen-specific T cells, resulting in specific lysis of antigen-expressing cells. Especially in a therapeutic setting, sonoporation with TriMix has an important added value, resulting in a significant reduction of tumor outgrowth and a marked increase in overall survival. What is more, complete tumor regression was observed in 30% of the antigen+TriMix DC vaccinated animals, which also displayed long-term antigen-specific immunological memory. As a result, DC sonoporation using microbubbles loaded with a combination of antigen and TriMix mRNA can elicit powerful immune responses in vivo, and might serve as a potential tool for further in vivo DC vaccination applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. TMX1 determines cancer cell metabolism as a thiol-based modulator of ER-mitochondria Ca2+ flux.

    Science.gov (United States)

    Raturi, Arun; Gutiérrez, Tomás; Ortiz-Sandoval, Carolina; Ruangkittisakul, Araya; Herrera-Cruz, Maria Sol; Rockley, Jeremy P; Gesson, Kevin; Ourdev, Dimitar; Lou, Phing-How; Lucchinetti, Eliana; Tahbaz, Nasser; Zaugg, Michael; Baksh, Shairaz; Ballanyi, Klaus; Simmen, Thomas

    2016-08-15

    The flux of Ca(2+) from the endoplasmic reticulum (ER) to mitochondria regulates mitochondria metabolism. Within tumor tissue, mitochondria metabolism is frequently repressed, leading to chemotherapy resistance and increased growth of the tumor mass. Therefore, altered ER-mitochondria Ca(2+) flux could be a cancer hallmark, but only a few regulatory proteins of this mechanism are currently known. One candidate is the redox-sensitive oxidoreductase TMX1 that is enriched on the mitochondria-associated membrane (MAM), the site of ER-mitochondria Ca(2+) flux. Our findings demonstrate that cancer cells with low TMX1 exhibit increased ER Ca(2+), accelerated cytosolic Ca(2+) clearance, and reduced Ca(2+) transfer to mitochondria. Thus, low levels of TMX1 reduce ER-mitochondria contacts, shift bioenergetics away from mitochondria, and accelerate tumor growth. For its role in intracellular ER-mitochondria Ca(2+) flux, TMX1 requires its thioredoxin motif and palmitoylation to target to the MAM. As a thiol-based tumor suppressor, TMX1 increases mitochondrial ATP production and apoptosis progression. Copyright © 2016 Raturi et al.

  13. Tumour-associated antigens in systemic sclerosis patients with interstitial lung disease: association with lung involvement and cancer risk.

    Science.gov (United States)

    De Luca, Giacomo; Bosello, Silvia L; Berardi, Giorgia; Rucco, Manuela; Canestrari, Giovanni; Correra, Miriam; Mirone, Luisa; Forni, Franca; Di Mario, Clara; Danza, Francesco M; Pirronti, Tommaso; Ferraccioli, Gianfranco

    2015-11-01

    To evaluate the serum levels of tumour-associated antigens (TAAs) in patients with SSc and interstitial lung disease (ILD) and to define whether their levels mirror the severity and the progression of lung damage. Data from 80 SSc patients with ILD were collected at baseline and after 2 years as well as from 40 SSc controls without ILD. The occurrence of any malignancy was recorded. At baseline, an increase of at least one TAA was present in 35 SSc patients with ILD compared with 6 SSc patients without ILD (P < 0.0001); this was associated with lower forced vital capacity (FVC) and higher interstitial and alveolar scores. Levels of carbohydrate antigen 15-3 and carcinoembryonic antigen inversely correlated with FVC and directly correlated with alveolar and interstitial scores and their levels were higher in patients who presented a progression of lung damage after 2 years. During 4 years of follow-up, a malignancy was detected in seven patients who already had an increase of at least one TAA. Values of TAAs increased over time in patients who developed cancer, while their trend remained stable in the others. At multivariate analysis, to have three or more TAAs emerged as a strong independent predictor of the development of malignancies [relative risk 24.1 (95% CI 1.8, 315.0), P = 0.02]. TAAs can be elevated in the sera of SSc patients and correlate with the degree of lung damage, suggesting a role as severity biomarkers. Close follow-up is necessary in SSc patients because of the increased cancer risk overall in patients with increased TAAs. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Recombinant Lactobacillus plantarum induces immune responses to cancer testis antigen NY-ESO-1 and maturation of dendritic cells.

    Science.gov (United States)

    Mobergslien, Anne; Vasovic, Vlada; Mathiesen, Geir; Fredriksen, Lasse; Westby, Phuong; Eijsink, Vincent G H; Peng, Qian; Sioud, Mouldy

    2015-01-01

    Given their safe use in humans and inherent adjuvanticity, Lactic Acid Bacteria may offer several advantages over other mucosal delivery strategies for cancer vaccines. The objective of this study is to evaluate the immune responses in mice after oral immunization with Lactobacillus (L) plantarum WCFS1 expressing a cell-wall anchored tumor antigen NY-ESO-1. And to investigate the immunostimulatory potency of this new candidate vaccine on human dendritic cells (DCs). L. plantarum displaying NY-ESO-1 induced NY-ESO-1 specific antibodies and T-cell responses in mice. By contrast, L. plantarum displaying conserved proteins such as heat shock protein-27 and galectin-1, did not induce immunity, suggesting that immune tolerance to self-proteins cannot be broken by oral administration of L. plantarum. With respect to immunomodulation, immature DCs incubated with wild type or L. plantarum-NY-ESO-1 upregulated the expression of co-stimulatory molecules and secreted a large amount of interleukin (IL)-12, TNF-α, but not IL-4. Moreover, they upregulated the expression of immunosuppressive factors such as IL-10 and indoleamine 2,3-dioxygenase. Although L. plantarum-matured DCs expressed inhibitory molecules, they stimulated allogeneic T cells in-vitro. Collectively, the data indicate that L. plantarum-NY-ESO-1 can evoke antigen-specific immunity upon oral administration and induce DC maturation, raising the potential of its use in cancer immunotherapies.

  15. Esculetin, a natural coumarin compound, evokes Ca(2+) movement and activation of Ca(2+)-associated mitochondrial apoptotic pathways that involved cell cycle arrest in ZR-75-1 human breast cancer cells.

    Science.gov (United States)

    Chang, Hong-Tai; Chou, Chiang-Ting; Lin, You-Sheng; Shieh, Pochuen; Kuo, Daih-Huang; Jan, Chung-Ren; Liang, Wei-Zhe

    2016-04-01

    Esculetin (6,7-dihydroxycoumarin), a derivative of coumarin compound, is found in traditional medicinal herbs. It has been shown that esculetin triggers diverse cellular signal transduction pathways leading to regulation of physiology in different models. However, whether esculetin affects Ca(2+) homeostasis in breast cancer cells has not been explored. This study examined the underlying mechanism of cytotoxicity induced by esculetin and established the relationship between Ca(2+) signaling and cytotoxicity in human breast cancer cells. The results showed that esculetin induced concentration-dependent rises in the intracellular Ca(2+) concentration ([Ca(2+)]i) in ZR-75-1 (but not in MCF-7 and MDA-MB-231) human breast cancer cells. In ZR-75-1 cells, this Ca(2+) signal response was reduced by removing extracellular Ca(2+) and was inhibited by the store-operated Ca(2+) channel blocker 2-aminoethoxydiphenyl borate (2-APB). In Ca(2+)-free medium, pre-treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin (TG) abolished esculetin-induced [Ca(2+)]i rises. Conversely, incubation with esculetin abolished TG-induced [Ca(2+)]i rises. Esculetin induced cytotoxicity that involved apoptosis, as supported by the reduction of mitochondrial membrane potential and the release of cytochrome c and the proteolytic activation of caspase-9/caspase-3, which were partially reversed by pre-chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM). Moreover, esculetin increased the percentage of cells in G2/M phase and regulated the expressions of p53, p21, CDK1, and cyclin B1. Together, in ZR-75-1 cells, esculetin induced [Ca(2+)]i rises by releasing Ca(2+) from the ER and causing Ca(2+) influx through 2-APB-sensitive store-operated Ca(2+) entry. Furthermore, esculetin activated Ca(2+)-associated mitochondrial apoptotic pathways that involved G2/M cell cycle arrest. Graphical abstract The summary of esculetin

  16. Novel algorithm including CA-125, HE4 and body mass index in the diagnosis of endometrial cancer.

    Science.gov (United States)

    Knific, Tamara; Osredkar, Joško; Smrkolj, Špela; Tonin, Irena; Vouk, Katja; Blejec, Andrej; Frković Grazio, Snježana; Rižner, Tea Lanišnik

    2017-10-01

    To evaluate the diagnostic and prognostic potential of preoperative serum CA-125 and HE4 levels in patients with endometrial cancer. Prospective case-control study of 133 women who underwent surgical treatment at the University Medical Centre Ljubljana (64 patients with endometrial cancer, 69 control patients with prolapsed uterus or myoma). Serum CA-125 and HE4 levels were determined using electrochemiluminescent assays. Serum CA-125 and HE4 levels were significantly higher in patients with endometrial cancer, compared to the controls (p=2.67×10 -4 , 1.36×10 -7 , respectively). A diagnostic model that combines serum CA-125 and HE4 levels and body mass index separated patients with endometrial cancer from controls, with AUC of 0.804, sensitivity of 66.7%, and specificity of 84.6%. Serum HE4 levels showed good prognostic potential and stratified the patients according to presence/absence of deep myometrial invasion (p=0.001) or lymphovascular invasion (p=0.003), with AUCs of 0.78 and 0.81, respectively. In low-risk patients with grade 1 and 2 endometrioid cancer for whom lymphadenectomy can be avoided, HE4 allowed stratification according to deep myometrial invasion (p=3.39×10 -4 ), with AUC of 0.84. Although median HE4 levels were higher in patients with lymphovascular invasion, this difference did not reach significance (p=0.06). A model based on preoperative serum CA-125 and HE4 levels and body mass index has good diagnostic accuracy for separation of patients with endometrial cancer and control patients. In patients with endometrial cancer, serum HE4 levels allow prediction of deep myometrial and lymphovascular invasion. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. PIK3CA and TP53 gene mutations in human breast cancer tumors frequently detected by ion torrent DNA sequencing.

    Science.gov (United States)

    Bai, Xusheng; Zhang, Enke; Ye, Hua; Nandakumar, Vijayalakshmi; Wang, Zhuo; Chen, Lihong; Tang, Chuanning; Li, Jianhui; Li, Huijin; Zhang, Wei; Han, Wei; Lou, Feng; Zhang, Dandan; Sun, Hong; Dong, Haichao; Zhang, Guangchun; Liu, Zhiyuan; Dong, Zhishou; Guo, Baishuai; Yan, He; Yan, Chaowei; Wang, Lu; Su, Ziyi; Li, Yangyang; Jones, Lindsey; Huang, Xue F; Chen, Si-Yi; Gao, Jinglong

    2014-01-01

    Breast cancer is the most common malignancy and the leading cause of cancer deaths in women worldwide. While specific genetic mutations have been linked to 5-10% of breast cancer cases, other environmental and epigenetic factors influence the development and progression of the cancer. Since unique mutations patterns have been observed in individual cancer samples, identification and characterization of the distinctive breast cancer molecular profile is needed to develop more effective target therapies. Until recently, identifying genetic cancer mutations via personalized DNA sequencing was impractical and expensive. The recent technological advancements in next-generation DNA sequencing, such as the semiconductor-based Ion Torrent sequencing platform, has made DNA sequencing cost and time effective with more reliable results. Using the Ion Torrent Ampliseq Cancer Panel, we sequenced 737 loci from 45 cancer-related genes to identify genetic mutations in 105 human breast cancer samples. The sequencing analysis revealed missense mutations in PIK3CA, and TP53 genes in the breast cancer samples of various histologic types. Thus, this study demonstrates the necessity of sequencing individual human cancers in order to develop personalized drugs or combination therapies to effectively target individual, breast cancer-specific mutations.

  18. Vaccines Targeting the Cancer Testis Antigen SSX-2 Elicit HLA-A2 Epitope-Specific Cytolytic T Cells

    Science.gov (United States)

    Smith, Heath A.; McNeel, Douglas G.

    2011-01-01

    The cancer-testis antigen SSX-2 is a potentially attractive target for tumor immunotherapy based upon its tissue-restricted expression to germline cells and its frequent expression in malignancies. The goal of the current study was to evaluate a genetic vaccine encoding SSX-2 to prioritize HLA-A2-specific epitopes and determine if a DNA vaccine can elicit SSX-2-specific cytolytic T lymphocytes (CTL) capable of lysing prostate cancer cells. HLA-A2-restricted epitopes were identified based on their in vitro binding affinity for HLA-A2 and by the ability of a genetic vaccine to elicit peptide-specific CTL in A2/DR1 (HLA-A2.1+/HLA-DR1+/H-2 class I-/class II-knockout) transgenic mice. We found that SSX-2 peptides p41-49 (KASEKIFYV) and p103-111 (RLQGISPKI) had high affinity for HLA-A2 and were immunogenic in vivo, however peptide p103-111 was immunodominant with robust peptide-specific immune responses elicited in mice vaccinated with a plasmid DNA vaccine encoding SSX-2. Furthermore, p103-111-specific CTL were able to lyse an HLA-A2+ prostate cancer cell line. The immunodominance of this epitope was found not to be due to a putative HLA-DR1 epitope (p98-112) flanking p103-111. Finally, we demonstrated that SSX-2 epitope-specific CTL could be detected and cultured from the peripheral blood of HLA-A2+ prostate cancer patients, notably patients with advanced prostate cancer. Overall, we conclude that SSX-2 peptide p103-111 is an immunodominant HLA-A2-restricted epitope, and epitope-specific CD8+ T cells can be detected in patients with prostate cancer, suggesting that tolerance to SSX-2 can be circumvented in vivo. Together, these findings suggest that SSX-2 may be a relevant target antigen for prostate cancer vaccine approaches. PMID:21904219

  19. Detection rate of prostate cancer using prostate specific antigen in patients presenting with lower urinary tract symptoms: A retrospective study

    Directory of Open Access Journals (Sweden)

    Chavan P

    2009-01-01

    Full Text Available Background: Need for undertaking prostate biopsies for detection of prostate cancer is often decided on the basis of serum levels of prostate specific antigen (PSA. Aim: To evaluate the case detection rate of prostate cancer among patients presenting with lower urinary tract symptoms (LUTS on the basis of PSA levels and to assess the scope of prostate biopsy in these patients. Setting and Design: A retrospective study from a tertiary care center. Materials and Methods: The clinical and histopathological data of 922 patients presenting with LUTS in the last five years was obtained from the medical record section. They had been screened for prostate cancer using PSA and /or digital rectal examination examination followed by confirmation with prostate biopsy. Statistical Analysis Used: Detection rate and receiver operating characteristic curve were performed using SPSS 16 and Medcalc softwares. Results: The detection rate of prostate cancer according to the PSA levels was 0.6%, 2.3%, 2.5%, 34.1% and 54.9% in the PSA range of 0-4, 4-10, 10-20, 20-50 and> 50 ng/ml, respectively. Maximum prostate cancer cases were detected beyond a PSA value of 20 ng/ml whereas no significant difference in the detection rate was observed in the PSA range of 0-4, 4-10 and 10-20 ng/ml. Conclusion: A low detection rate of prostate cancer observed in the PSA range of 4-20 ng/ml in LUTS patients indicates the need for use of higher cutoff values of PSA in such cases. Therefore we recommend a cutoff of 20 ng/ml of PSA for evaluation of detection rate of prostate cancer among patients presenting with LUTS.

  20. Increasing level of prostate-specific antigen and prostate cancer risk factors among 193 men examined in screening procedure.

    Science.gov (United States)

    Opalińska, Edyta; Michalak, Anna; Stoma, Filip; Latalski, Maciej; Goniewicz, Mariusz

    2003-01-01

    Prostate cancer is one of the most common cancers in men, therefore has become recently an essential problem of public health. The factors influencing cancer include: androgens metabolism disorders, diabetes mellitus, overweight and obesity, smoking, alcohol and black coffee intake, diet rich in saturated fats and poor in unsaturated, lack of physical activity, geographical zone, race, such carcinogenic substances as: cadmium, materials used in rubber, painting, printing, ship industry etc., contagious factors and also older age and a positive family history of the disease. To diagnose prostate cancer in its early stage such screening procedures as physical examination--digital rectal exam (DRE) and determination of prostate-specific antigen (PSA) level in blood serum are used. The aim of the study was to assess prostate cancer risk factors occurrence in the examined 193 men, aged 50-70 years, who reported to urology outpatient department at Clinical Hospital in Lublin, measure the PSA level in blood serum and examine the correlation between them. Respondents filled in a questionnaire about the presence of prostate cancer risk factors and urogenital symptoms. The questionnaire was completed with DRE and PSA measurement. The results led us to the following conclusions: 1/ in the studied population elevated PSA level is determined in 3.1% of 193 examined men, 2/ increased PSA occurs mainly in men from rural areas, with elementary education, divorced, older (>60 years), using fat-rich diet, smokers, black coffee drinkers, with overweight or obesity and non diabetic, 3/ a combination of PSA test with DRE seems to be useful and rather cheap for the detection of prostate cancer in the early stage of its development.

  1. Trends in prostate cancer incidence and mortality in Canada during the era of prostate-specific antigen screening.

    Science.gov (United States)

    Dickinson, James; Shane, Amanda; Tonelli, Marcello; Connor Gorber, Sarah; Joffres, Michel; Singh, Harminder; Bell, Neil

    2016-01-01

    Widespread use of prostate-specific antigen (PSA) to screen for prostate cancer began in the early 1990s. Advocates for screening assert that this has caused a decrease in prostate cancer mortality. We sought to describe secular changes in prostate cancer incidence and mortality in Canada in relation to the onset of PSA screening. Age-standardized and age-specific prostate cancer incidence (1969-2007) and mortality (1969-2009) from Public Health Agency of Canada databases were analyzed by joinpoint regression. Changes in incidence and mortality were related to introduction of PSA screening. Prior to PSA screening, prostate cancer incidence increased from 54.2 to 99.8 per 100 000 between 1969 and 1990. Thereafter, incidence increased sharply (12.8% per year) to peak at 140.8/100 000 in 1993. After decreasing in all age groups between 1993 and 1996, incidence continued to increase for men aged less than 70 years, but decreased for older men. Age-standardized mortality was stable from 1969 to 1977, increased 1.4% per year to peak in 1995 and subsequently decreased at 3.3% per year; the decline started from 1987 in younger men (age prostate cancer mortality began before PSA screening was widely used and were larger than could be anticipated from screening alone. These findings suggest that screening caused artifactual increase in incidence, but no more than a part of reductions in prostate cancer mortality. The reduction may be due to changing treatment or certification of death.

  2. Role of Antigen Spread and Distinctive Characteristics of Immunotherapy in Cancer Treatment

    NARCIS (Netherlands)

    Gulley, J.L.; Madan, R.A.; Pachynski, R.; Mulders, P.; Sheikh, N.A.; Trager, J.; Drake, C.G.

    2017-01-01

    Immunotherapy is an important breakthrough in cancer. US Food and Drug Administration-approved immunotherapies for cancer treatment (including, but not limited to, sipuleucel-T, ipilimumab, nivolumab, pembrolizumab, and atezolizumab) substantially improve overall survival across multiple

  3. Increased intracellular Ca2+ decreases cisplatin resistance by regulating iNOS expression in human ovarian cancer cells.

    Science.gov (United States)

    Yu, Yang; Xie, Qi; Liu, Weimin; Guo, Yuting; Xu, Na; Xu, Lu; Liu, Shibing; Li, Songyan; Xu, Ye; Sun, Liankun

    2017-02-01

    Previous studies have reported that intracellular Ca2+ signals and inducible nitric oxide synthase (iNOS) are involved in cell apoptosis. However, the role of iNOS in cisplatin resistance in ovarian cancer remains unclear. Here, we demonstrate that SKOV3/DDP ovarian cancer cells were more resistant to cisplatin than were SKOV3 ovarian cancer cells. The expression of intracellular Ca2+ and iNOS was more strongly induced by cisplatin in SKOV3 cells than in SKOV3/DDP cells. TAT-conjugated IP3R-derived peptide (TAT-IDPS) increased cisplatin-induced iNOS expression and apoptosis in SKOV3/DDP cells. 2-Aminoethoxydiphenyl borate (2-APB) decreased cisplatin-induced iNOS expression and apoptosis in SKOV3 cells. Thus, iNOS induction may be a valuable strategy for improving the anti-tumor efficacy of cisplatin in ovarian cancer. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca²⁺/calmodulin-dependent protein kinase II.

    Science.gov (United States)

    Meng, Zhipeng; Li, Tao; Ma, Xiaoxiao; Wang, Xiaoqiong; Van Ness, Carl; Gan, Yichao; Zhou, Hong; Tang, Jinfen; Lou, Guiyu; Wang, Yafan; Wu, Jun; Yen, Yun; Xu, Rongzhen; Huang, Wendong

    2013-10-01

    Liver cancer is the third leading cause of cancer deaths worldwide but no effective treatment toward liver cancer is available so far. Therefore, there is an unmet medical need to identify novel therapies to efficiently treat liver cancer and improve the prognosis of this disease. Here, we report that berbamine and one of its derivatives, bbd24, potently suppressed liver cancer cell proliferation and induced cancer cell death by targeting Ca(2+)/calmodulin-dependent protein kinase II (CAMKII). Furthermore, berbamine inhibited the in vivo tumorigenicity of liver cancer cells in NOD/SCID mice and downregulated the self-renewal abilities of liver cancer-initiating cells. Chemical inhibition or short hairpin RNA-mediated knockdown of CAMKII recapitulated the effects of berbamine, whereas overexpression of CAMKII promoted cancer cell proliferation and increased the resistance of liver cancer cells to berbamine treatments. Western blot analyses of human liver cancer specimens showed that CAMKII was hyperphosphorylated in liver tumors compared with the paired peritumor tissues, which supports a role of CAMKII in promoting human liver cancer progression and the potential clinical use of berbamine for liver cancer therapies. Our data suggest that berbamine and its derivatives are promising agents to suppress liver cancer growth by targeting CAMKII. Mol Cancer Ther; 12(10); 2067-77. ©2013 AACR.

  5. Identification of Threshold Prostate Specific Antigen Levels to Optimize the Detection of Clinically Significant Prostate Cancer by Magnetic Resonance Imaging/Ultrasound Fusion Guided Biopsy

    Science.gov (United States)

    Shakir, Nabeel A.; George, Arvin K.; Siddiqui, M. Minhaj; Rothwax, Jason T.; Rais-Bahrami, Soroush; Stamatakis, Lambros; Su, Daniel; Okoro, Chinonyerem; Raskolnikov, Dima; Walton-Diaz, Annerleim; Simon, Richard; Turkbey, Baris; Choyke, Peter L.; Merino, Maria J.; Wood, Bradford J.; Pinto, Peter A.

    2015-01-01

    Purpose Prostate specific antigen sensitivity increases with lower threshold values but with a corresponding decrease in specificity. Magnetic resonance imaging/ultrasound targeted biopsy detects prostate cancer more efficiently and of higher grade than standard 12-core transrectal ultrasound biopsy but the optimal population for its use is not well defined. We evaluated the performance of magnetic resonance imaging/ultrasound targeted biopsy vs 12-core biopsy across a prostate specific antigen continuum. Materials and Methods We reviewed the records of all patients enrolled in a prospective trial who underwent 12-core transrectal ultrasound and magnetic resonance imaging/ultrasound targeted biopsies from August 2007 through February 2014. Patients were stratified by each of 4 prostate specific antigen cutoffs. The greatest Gleason score using either biopsy method was compared in and across groups as well as across the population prostate specific antigen range. Clinically significant prostate cancer was defined as Gleason 7 (4 + 3) or greater. Univariate and multivariate analyses were performed. Results A total of 1,003 targeted and 12-core transrectal ultrasound biopsies were performed, of which 564 diagnosed prostate cancer for a 56.2% detection rate. Targeted biopsy led to significantly more upgrading to clinically significant disease compared to 12-core biopsy. This trend increased more with increasing prostate specific antigen, specifically in patients with prostate specific antigen 4 to 10 and greater than 10 ng/ml. Prostate specific antigen 5.2 ng/ml or greater captured 90% of upgrading by targeted biopsy, corresponding to 64% of patients who underwent multiparametric magnetic resonance imaging and subsequent fusion biopsy. Conversely a greater proportion of clinically insignificant disease was detected by 12-core vs targeted biopsy overall. These differences persisted when controlling for potential confounders on multivariate analysis. Conclusions Prostate

  6. Shp2 confers cisplatin resistance in small cell lung cancer via an AKT-mediated increase in CA916798.

    Science.gov (United States)

    Yang, Xuemei; Tang, Chunlan; Luo, Hu; Wang, Haijing; Zhou, Xiangdong

    2017-04-04

    The tyrosine phosphatase Shp2 is associated with tumorigenesis in small cell lung cancer (SCLC). However, the relationship between Shp2 and resistance to chemotherapy remains unclear. Here, we show that Shp2 plays an important role in inducing resistance to cisplatin-based chemotherapy via the SHP2-AKT-CA916798 pathway. In an SCLC cell line, overexpression of Shp2 induced cisplatin resistance and the increased expression of AKT, pAKT, pmTOR, and CA916798. Conversely, depletion of Shp2 in a cisplatin-resistant cell line via RNA interference increased cisplatin sensitivity and decreased AKT, pAKT, pmTOR, and CA916798 expression levels. Activation of AKT stimulated CA916798 expression and altered the level of Shp2. A mouse xenograft model verified the results obtained from the in vitro experiments. In addition, we collected and analyzed clinical SCLC specimens and found that Shp2 levels correlated with CA916798 expression in tumor tissues. Importantly, higher levels of Shp2 or CA916798 were associated with a poorer prognosis in SCLC patients who received chemotherapy. Together, our findings indicate that Shp2 induces cisplatin resistance in SCLC patients via the SHP2-AKT-CA916798 pathway. Therefore, Shp2 and CA916798 may be promising biomarkers for predicting resistance to chemotherapy and may function as targets for enhancing treatments.

  7. Crosstalk of carcinoembryonic antigen and transforming growth factor-β via their receptors: comparing human and canine cancer.

    Science.gov (United States)

    Jensen-Jarolim, Erika; Fazekas, Judit; Singer, Josef; Hofstetter, Gerlinde; Oida, Kumiko; Matsuda, Hiroshi; Tanaka, Akane

    2015-05-01

    There is accumulating evidence that the transforming growth factor beta (TGF-β) and nuclear factor kappa-B (NFκB) pathways are tightly connected and play a key role in malignant transformation in cancer. Immune infiltration by regulatory T- and B-lymphocytes (Tregs, Bregs) has recently gained increased attention for being an important source of TGF-β. There is a plethora of studies examining the pro-tumorigenic functions of carcinoembryonic antigen (CEA), but its receptor CEAR is far less studied. So far, there is a single connecting report that TGF-β also may signal through CEAR. The crosstalk between cancer tissues is further complicated by the expression of CEAR and TGF-β receptors in stromal cells, and implications of TGF-β in epithelial-mesenchymal transition. Furthermore, tumor-infiltrating Tregs and Bregs may directly instruct cancer cells by secreting TGF-β binding to their CEAR. Therefore, both TGF-β and CEA may act synergistically in breast cancer and cause disease progression, and NFκB could be a common crossing point between their signaling. CEAR, TGF-β1-3, TGF-β-R types I-III and NFκB class I and II molecules have an outstanding human-canine sequence identity, and only a canine CEA homolog has not yet been identified. For these reasons, the dog may be a valid translational model patient for investigating the crosstalk of the interconnected CEA and TGF-β networks.

  8. Breast cancer 1 (BrCa1 may be behind decreased lipogenesis in adipose tissue from obese subjects.

    Directory of Open Access Journals (Sweden)

    Francisco J Ortega

    Full Text Available CONTEXT: Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1 interacts with acetyl-CoA carboxylase (ACC reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. RESEARCH DESIGN AND METHODS: BrCa1 gene expression, total and phosphorylated (P- BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. RESULTS: BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002 and subcutaneous (SC; 1.49-fold, p = 0.001 adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007 as well as in OM (p = 0.010 fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001 and protein (1.2-fold, p = 0.001 were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005 allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium, whereas lipogenic genes significantly decreased. CONCLUSIONS: The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.

  9. Aptamer and 5-fluorouracil dual-loading Ag2S quantum dots used as a sensitive label-free probe for near-infrared photoluminescence turn-on detection of CA125 antigen.

    Science.gov (United States)

    Jin, Hui; Gui, Rijun; Gong, Jun; Huang, Wenxue

    2017-06-15

    In this article, Ag 2 S quantum dots (QDs) were prepared by a facile aqueous synthesis method, using thiourea as a new sulfur precursor. Based on electrostatic interactions, 5-fluorouracil (5-Fu) was combined with the aptamer of CA125 antigen to fabricate aptamer/5-Fu complex. The surface of as-prepared Ag 2 S QDs was modified with polyethylenimine, followed by combination with the aptamer/5-Fu complex to form Ag 2 S QDs/aptamer/5-Fu hybrids. During the combination of Ag 2 S QDs with aptamer/5-Fu complex, near-infrared (NIR) photoluminescence (PL) of QDs (peaked at 850nm) was markedly reduced under excitation at 625nm, attributed to photo-induced electron transfer from QDs to 5-Fu. However, the addition of CA125 induced obvious NIR PL recovery, which was ascribed to the strong binding affinity of CA125 with its aptamer, and the separation of aptamer/5-Fu complex from the surface of QDs. Hence, the Ag 2 S QDs/aptamer/5-Fu hybrids were developed as a novel NIR PL turn-on probe of CA125. In the concentration range of [CA125] from 0.1 to 10 6 ngmL -1 , there were a good linear relationship between NIR PL intensities of Ag 2 S QDs and Log[CA125], and a low limit of detection of 0.07ngmL -1 . Experimental results revealed the highly selective and sensitive NIR PL responses of this probe to CA125, over other potential interferences. In real human body fluids, this probe also exhibited superior analytical performance, together with high detection recoveries. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. NY-ESO-1/LAGE-1 coexpression with MAGE-A cancer/testis antigens: a tissue microarray study.

    Science.gov (United States)

    Bolli, Martin; Schultz-Thater, Elke; Zajac, Paul; Guller, Ulrich; Feder, Chantal; Sanguedolce, Francesca; Carafa, Vincenza; Terracciano, Luigi; Hudolin, Tvrtko; Spagnoli, Giulio C; Tornillo, Luigi

    2005-07-20

    The characterization of the expression pattern of different families of cancer/testis (C/T) antigens in different tumors, at the protein level, might be of relevance in the development of multiantigen vaccine preparations for active specific immunotherapy. We have used tissue microarray (TMA) technology to explore in large numbers of tumor specimens the expression of NY-ESO-1/LAGE-1 C/T antigens and its correlation with MAGE-A expression by using D8.38 and 57B monoclonal antibodies (MAb). The epitopes recognized by these reagents in C/T antigens were identified by molecular mapping by using a bacterial expression system. Out of 2,052 samples, 119 (5.8%) scored positive upon staining with D8.38 NY-ESO-1/LAGE-1-specific MAb. Expression in >10% of cases was detectable in melanoma and basalioma (31.6 and 18.2%, respectively), large cell carcinomas and adenocarcinomas of the lung (17.8 and 10.5%, respectively), stomach adenocarcinomas of the intestinal type (13.2%), pT2-4 bladder TCC (18.2%), nonseminomatous carcinomas of the testis (10.4%) and liposarcomas (15.4%). Simultaneous expression of NY-ESO-1/LAGE-1 and MAGE-A C/T antigens was then addressed in a TMA where 101/845 and 73/845 samples (12 and 8.6%, respectively) showed evidence of MAGE-A or NY-ESO-1/LAGE-1 specific staining, respectively. In 35/845 specimens (4.1%) concomitant expression of MAGE-A and NY-ESO-1/LAGE-1 was observed (p = 0.0002). Discrepancies in the expression of NY-ESO-1/LAGE-1 and MAGE-A were conspicuously detectable in squamous cell carcinomas of the skin (MAGE-A positive but NY-ESO-1/LAGE-1 negative) and in liposarcomas (NY-ESO-1/LAGE-1 positive, but MAGE-A negative). Taken together, these data suggest novel areas of application of C/T antigens targeted active specific immunotherapy possibly based on multiantigen vaccine preparations. Copyright 2005 Wiley-Liss, Inc.

  11. Carbohydrate structure and differential binding of prostate specific antigen to Maackia amurensis lectin between prostate cancer and benign prostate hypertrophy.

    Science.gov (United States)

    Ohyama, Chikara; Hosono, Masahiro; Nitta, Kazuo; Oh-eda, Masayoshi; Yoshikawa, Kazuyuki; Habuchi, Tomonori; Arai, Yoichi; Fukuda, Minoru

    2004-08-01

    Serum prostate-specific antigen (PSA) assay is widely used for detection of prostate cancer. Because PSA is also synthesized from normal prostate, false positive diagnosis cannot be avoided by the conventional serum PSA test. To apply the cancer-associated carbohydrate alteration to the improvement of PSA assay, we first elucidated the structures of PSA purified from human seminal fluid. The predominant core structure of N-glycans of seminal fluid PSA was a complex type biantennary oligosaccharide and was consistent with the structure reported previously. However, we found the sialic acid alpha2-3 galactose linkage as an additional terminal carbohydrate structure on seminal fluid PSA. We then analyzed the carbohydrate moiety of serum PSA from the patients with prostate cancer and benign prostate hypertrophy using lectin affinity chromatography. Lectin binding was assessed by lectin affinity column chromatography followed by determining the amount of total and free PSA. Concanavalin A, Lens culinaris, Aleuria aurantia, Sambucus nigra, and Maackia amurensis lectins were tested for their binding to the carbohydrates on PSA. Among the lectins examined, the M. amurensis agglutinin-bound fraction of free serum PSA is increased in prostate cancer patients compared to benign prostate hypertrophy patients. The binding of PSA to M. amurensis agglutinin, which recognizes alpha2,3-linked sialic acid, was also confirmed by surface plasmon resonance analysis. These results suggest that the differential binding of free serum PSA to M. amurensis agglutinin lectin between prostate cancer and benign prostate hypertrophy could be a potential measure for diagnosis of prostate cancer.

  12. Enhancive effects of Lewis y antigen on CD44-mediated adhesion and spreading of human ovarian cancer cell line RMG-I

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    Liu Juanjuan

    2011-02-01

    Full Text Available Abstract Background This study aimed to investigate the molecular structural relationship between cell adhesive molecule CD44 and Lewis y antigen, and determine the effects of Lewis y antigen on CD44-mediated adhesion and spreading of ovarian cancer cell line RMG-I and the Lewis y antigen-overexpressed cell line RMG-I-H. Methods The expression of CD44 in RMG-I and RMG-I-H cells before and after treatment of Lewis y monoclonal antibody was detected by immunocytochemistry; the expression of Lewis y antigen and CD44 was detected by Western Blot. The structural relationship between Lewis y antigen and CD44 was determined by immunoprecipitation and confocal laser scanning microscopy. The adhesion and spreading of RMG-I and RMG-I-H cells on hyaluronic acid (HA were observed. The expression of CD44 mRNA in RMG-I and RMG-I-H cells was detected by real-time RT-PCR. Results Immunocytochemistry revealed that the expression of CD44 was significantly higher in RMG-I-H cells than in RMG-I cells (P P P P P > 0.05. Conclusion Lewis y antigen strengthens CD44-mediated adhesion and spreading of ovarian cancer cells.

  13. Rising cancer antigen 125 level and the type and timing of treatment for recurrent ovarian cancer: a clinical dilemma, but what would women do?

    Science.gov (United States)

    Harrison, James D; Juraskova, Ilona; Anderson, Caroline; Nattress, Kathryn; Beale, Philip; Lopez, Anna-Lena; Carter, Jonathan

    2009-08-01

    Clinical uncertainty currently exists for the timing of treatment for women with epithelial ovarian cancer who are under surveillance for their first recurrence and have rising cancer antigen 125 levels. This study ascertained women's preferences for this clinical scenario and the impact of regular surveillance on psychosocial well-being. Women with a diagnosis of epithelial ovarian cancer who had completed primary treatment and were in surveillance for their first recurrence were eligible to participate. Treatment preferences were ascertained using the Prospective Measure of Preference, and psychological well-being was ascertained using a series of psychological scales. Women (n = 21) had highly variable preferences for the type and timing of second-line treatment when basing their decision on rising cancer antigen 125 levels. Around half indicated a preference against treatment and were willing to trade life expectancy (WTT) to avoid chemotherapy (WTT = 0.45) or tamoxifen (WTT = 0.50). For these women, strong preferences against treatment were reflected in high Prospective Measure of Preference utility scores (0.15 for chemotherapy and 0.19 for tamoxifen). The negative experience of chemotherapy, the uncertainty about tamoxifen's effectiveness, and remaining symptom-free influenced these decisions. The remaining women indicated they would begin chemotherapy or tamoxifen immediately. These women believed taking early steps to treatment was positive and a coping mechanism; however, some revealed unrealistic expectations of treatment. Most women reported good levels of psychological well-being and were coping with ongoing surveillance. Women in surveillance for recurrent ovarian cancer have highly variable preferences, and their reasons for their treatment choices are diverse. Therefore, although uncertainty exists for this clinical scenario, treatment preference should be ascertained on an individual basis.

  14. Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer.

    Directory of Open Access Journals (Sweden)

    Nicolai A Schultz

    Full Text Available We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448 and Germany (n = 111 were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.Odds ratios (ORs for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87. Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22-5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021. Multivariate Cox analysis of non-operable patients (Stage IIB-IV showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022. Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005 compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months.Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.

  15. Cancer associated aberrant protein o-glycosylation can modify antigen processing and immune response

    DEFF Research Database (Denmark)

    Madsen, Caroline B; Petersen, Cecilie; Lavrsen, Kirstine

    2012-01-01

    NAc-glycosylation promoted presentation of OVA-MUC1 fusion peptides by MHC class II molecules and the MUC1 antigen elicited specific Ab production and T cell proliferation in both Balb/c and HLA-A2 transgenic mice. In contrast, GalNAc-glycosylation inhibited the presentation of OVA-MUC1 fusion peptides by MHC class I...... and abolished MUC1 specific CD8+ T cell responses in HLA-A2 transgenic mice. GalNAc glycosylation of MUC1 antigen therefore facilitates uptake, MHC class II presentation, and antibody response but might block the antigen presentation to CD8+ T cells......., and presentation on MHC class I and II molecules. The effect of GalNAc O-glycosylation was monitored with a model system based on ovalbumin (OVA)-MUC1 fusion peptides (+/- glycosylation) loaded onto dendritic cells co-cultured with IL-2 secreting OVA peptide-specific T cell hybridomas. To evaluate the in vivo...

  16. Effect of low-dose oral etoposide on serum CA-125 in patients with advanced epithelial ovarian cancer

    NARCIS (Netherlands)

    deJong, RS; Hofstra, LS; Willemse, PHB; deBruijn, HWA; deVries, EGE; Mulder, NH; Boonstra, J.

    The effect of oral etoposide on CA-125 serum levels was evaluated in 17 patients with epithelial ovarian cancer and progressive disease during, or relapsing after, prior chemotherapy. Only three patients had measurable lesions at extraperitoneal sites. Five had no measurable lesions. The oral

  17. Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma.

    Science.gov (United States)

    Iura, Kunio; Kohashi, Kenichi; Hotokebuchi, Yuka; Ishii, Takeaki; Maekawa, Akira; Yamada, Yuichi; Yamamoto, Hidetaka; Iwamoto, Yukihide; Oda, Yoshinao

    2015-07-01

    Myxoid liposarcoma is the second most common liposarcoma. Although myxoid liposarcoma is relatively chemosensitive and thus a good candidate for chemotherapy, cases with relapsed or metastatic disease still have poor outcome. Here, we performed a gene microarray analysis to compare the gene expression profiles in six clinical myxoid liposarcoma samples and three normal adipose tissue samples, and to identify molecular biomarkers that would be useful as diagnostic markers or treatment targets in myxoid liposarcoma. This showed that the cancer-testis antigen PRAME was up-regulated in myxoid liposarcoma. We then performed immunohistochemical, western blotting and real-time polymerase chain reaction analyses to quantify the expression of PRAME and another cancer-testis antigen, NY-ESO-1, in clinical samples of myxoid liposarcoma (n = 93), dedifferentiated (n = 46), well-differentiated (n = 32) and pleomorphic liposarcomas (n = 14). Immunohistochemically, positivity for PRAME and NY-ESO-1 was observed in 84/93 (90%) and 83/93 (89%) of the myxoid liposarcomas, and in 20/46 (43%) and 3/46 (7%) of the dedifferentiated, 3/32 (9%) and 1/32 (3%) of the well-differentiated and 7/14 (50%) and 3/21 (21%) of the pleomorphic liposarcomas, respectively. High immunohistochemical expression of PRAME and/or NY-ESO-1 was significantly correlated with tumour diameter, the existence of tumour necrosis, a round-cell component of >5%, higher histological grade and advanced clinical stage. High PRAME and NY-ESO-1 expression correlated significantly with poor prognosis in a univariate analysis. The myxoid liposarcomas showed significantly higher protein and mRNA expression levels of PRAME and NY-ESO-1 (CTAG1B) than the other liposarcomas. In conclusion, PRAME and NY-ESO-1 (CTAG1B) were expressed in the vast majority of myxoid liposarcomas, and their high-level expression correlated with tumour grade and poor prognosis. Our results support the potential use of PRAME and NY

  18. Analysis of serum level of HE4 and CA125 considering selected risk factors among patients with endometrioid endometrial cancer

    Directory of Open Access Journals (Sweden)

    Nabil Abdalla

    2017-01-01

    Full Text Available The aim of the study : To assess the difference of serum level of HE4 and CA125 among patients with endometrioid endometrial cancer, considering the presence or absence of selected risk factors. Material and methods: A retrospective study of 46 patients, whose serum level of HE4 and CA125 level was documented, admitted to our Clinic because of endometrioid endometrial cancer. The statistical difference of both markers was analyzed considering certain risk factors. Results : In the examined group of patients there was no significant statistical difference of HE4 and CA125 levels among patients with and without the following risk factors: older age, menopausal status, overweight and obesity, hypertension, diabetes, early menarche, and family history of certain cancers. Similar results were obtained within the subgroup of patients with stage I endometrial cancer. Both HE4 and CA125 were significantly higher in premenopausal patients than in those after menopause in the more advanced stages of the disease. The same results were obtained within group of patients with advanced histological grading G2 and G3. In this group, higher levels of CA125 were observed among patients without hypertension. Among patients with histological grade G1 the serum level of HE4 was higher in the group of patients older than 60 years than it was in younger patients. Conclusions : In the examined group of patients serum levels of tumour markers may not be affected by the selected risk factors. Higher HE4 and CA125 levels among premenopausal patients may be an alarming sign of advanced stages and classes of histological grading.

  19. Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC

    Directory of Open Access Journals (Sweden)

    Shi Bingyin

    2011-04-01

    Full Text Available Abstract Background Lung cancer is the leading cause of cancer-related death worldwide. Genetic and epigenetic alterations have been identified frequently in lung cancer, such as promoter methylation, gene mutations and genomic amplification. However, the interaction between genetic and epigenetic events and their significance in lung tumorigenesis remains poorly understood. Methods We determined the promoter methylation of 6 genes and PIK3CA amplification using quantitative methylation-specific PCR (Q-MSP and real-time quantitative PCR, respectively, and explore the association of promoter methylation with PIK3CA amplification in a large cohort of clinically well-characterized non-small cell lung cancer (NSCLC. Results Highly frequent promoter methylation was observed in NSCLC. With 100% diagnostic specificity, excellent sensitivity, ranging from 45.8 to 84.1%, was found for each of the 6 genes. The promoter methylation was associated with histologic type. Methylation of CALCA, CDH1, DAPK1, and EVX2 was more common in squamous cell carcinomas (SCC compared to adenocarcinomas (ADC. Conversely, there was a trend toward a higher frequency of RASSF1A methylation in ADC than SCC. In addition, PIK3CA amplification was frequently found in NSCLC, and was associated with certain clinicopathologic features, such as smoking history, histologic type and pleural indentation. Importantly, aberrant promoter methylation of certain genes was significantly associated with PIK3CA amplification. Conclusions Our data showed highly frequent promoter methylation and PIK3CA amplification in Chinese NSCLC population, and first demonstrated the associations of gene methylation with PIK3CA amplification, suggesting that these epigenetic events may be a consequence of overactivation of PI3K/Akt pathway.

  20. Simultaneous cytoplasmic and nuclear protein expression of melanoma antigen-A family and NY-ESO-1 cancer-testis antigens represents an independent marker for poor survival in head and neck cancer.

    Science.gov (United States)

    Laban, Simon; Atanackovic, Djordje; Luetkens, Tim; Knecht, Rainald; Busch, Chia-Jung; Freytag, Marcus; Spagnoli, Giulio; Ritter, Gerd; Hoffmann, Thomas K; Knuth, Alexander; Sauter, Guido; Wilczak, Waldemar; Blessmann, Marco; Borgmann, Kerstin; Muenscher, Adrian; Clauditz, Till S

    2014-09-01

    The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. The identification of high-risk subgroups is needed for the development of custom-tailored therapies. The expression of cancer-testis antigens (CTAs) has been linked to a worse prognosis in other cancer types; however, their prognostic value in HNSCC is unclear because only few patients have been examined and data on CTA protein expression are sparse. A tissue microarray consisting of tumor samples from 453 HNSCC patients was evaluated for the expression of CTA proteins using immunohistochemistry. Frequency of expression and the subcellular expression pattern (nuclear, cytoplasmic, or both) was recorded. Protein expression of melanoma antigen (MAGE)-A family CTA, MAGE-C family CTA and NY-ESO-1 was found in approximately 30, 7 and 4% of tumors, respectively. The subcellular expression pattern in particular had a marked impact on the patients' prognosis. Median overall survival (OS) of patients with (i) simultaneous cytoplasmic and nuclear expression compared to (ii) either cytoplasmic or nuclear expression and (iii) negative patients was 23.0 versus 109.0 versus 102.5 months, for pan-MAGE (p < 0.0001), 46.6 versus 50.0 versus 109.0 for MAGE-A3/A4 (p = 0.0074) and 13.3 versus 50.0 versus 100.2 months for NY-ESO-1 (p = 0.0019). By multivariate analysis, these factors were confirmed as independent markers for poor survival. HNSCC patients showing protein expression of MAGE-A family members or NY-ESO-1 represent a subgroup with an extraordinarily poor survival. The development of immunotherapeutic strategies targeting these CTA may, therefore, be a promising approach to improve the outcome of HNSCC patients. © 2014 UICC.

  1. Increased Avidity of the Sambucus nigra Lectin-Reactive Antibodies to the Thomsen-Friedenreich Antigen as a Potential Biomarker for Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Oleg Kurtenkov

    2015-01-01

    Full Text Available Aim. To determine whether the naturally occurring Thomsen-Friedenreich (TF antigen-specific antibodies differ in avidity between cancer patients and controls to find a novel biomarker for stomach cancer. Methods. Serum samples were taken from patients with cancer and controls. The level of TF-specific antibodies and their sialylation were determined using ELISA with synthetic TF-polyacrylamide conjugate as antigen and sialic acid-specific Sambucus nigra agglutinin (SNA. The avidity was determined using ammonium thiocyanate as a chaotrope. Results. A significantly higher SNA lectin binding to anti-TF antibodies was found in cancer patients irrespective of disease stage. The avidity of only IgM TF-specific antibodies was significantly higher in cancer patients compared to controls. The SNA-positive anti-TF antibodies of cancer patients showed a significantly higher avidity, P<0.001. The sensitivity and specificity of this increase for gastric cancer were 73.53% and 73.08%, respectively, with a 73.2% diagnostic accuracy. The higher avidity of SNA-reactive anti-TF antibodies was associated with a benefit in survival of stage 3 cancer patients. Conclusion. The SNA-reactive TF-specific antibodies display a significantly higher avidity in gastric cancer patients compared to controls, which can be used as a potential serologic biomarker for gastric cancer. It appears that IgM is the main target responsible for the above changes.

  2. Transient human anti-mouse antibody generated with immune enhancement in a carbohydrate antigen 19-9 immunoassay after surgical resection of recurrent cancer.

    Science.gov (United States)

    Nakano, Keiichi; Yasuda, Keiko; Shibuya, Hitoshi; Moriyama, Takanori; Kahata, Kaoru; Shimizu, Chikara

    2016-07-01

    We report a case of transient human anti-mouse antibody from a 64-year-old man in a carbohydrate antigen 19-9 immunoassay using an AIA 1800 analyser that generated immune enhancement after surgical resection of recurrent cancer. The carbohydrate antigen 19-9 concentration was measured using an AIA 1800 analyser and a UniCel Dxl 800. Size-exclusion high-performance liquid chromatography was carried out on a Superose 12 column to estimate the carbohydrate antigen 19-9 elution profile using an AIA 1800 analyser. To determine whether IgM in the patient contributed to the carbohydrate antigen 19-9 immunoassay, immunoprecipitation was performed. Furthermore, mouse immunoglobulins were added to the patient's serum to verify that the patient's IgM reacted with it. The carbohydrate antigen 19-9 concentration was >400 and 9.5 kU/L using an AIA 1800 analyser and using a UniCel Dxl 800, respectively. In the single carbohydrate antigen 19-9 peak, the molecular weight corresponded to IgM by size-exclusion high-performance liquid chromatography on a Superose 12 column. In the immunoprecipitation reaction and addition of mouse immunoglobulins, there was interference for anti-human IgM and mouse immunoglobulins whose recoveries were 3.2 and 14.2%, respectively. These results indicated that IgM in the patient's serum interfered with the carbohydrate antigen 19-9 immunoassay using an AIA 1800 analyser. A novel transient human anti-mouse antibody generated with immune activation in a carbohydrate antigen 19-9 immunoassay using an AIA 1800 analyser was identified in a patient with rectal cancer after surgical resection. These findings demonstrate the importance of monitoring tumour markers in patients after treatment with mouse monoclonal antibody. © The Author(s) 2016.

  3. Relationship between apoptosis and immunohistochemical staining for proliferating cell nuclear antigen and Ki-67 in non-small cell lung cancer.

    Science.gov (United States)

    Ishiwata, N; Jinn, Y; Tsukada, Y; Inase, N; Ichioka, M; Yoshizawa, Y

    2000-01-01

    The relationship between apoptosis and cellular proliferative activity in human non-small cell lung cancer (25 cases) was investigated using the in situ DNA nick-end labeling method and immunohistochemistry for both proliferating cell nuclear antigen (PCNA) and Ki-67 antigen. Comparison of the distribution of Ki-67-positive cells to that of apoptotic cells shows an inverse correlation in semi-serial sections. The PCNA labeling rates were closely correlated with Ki-67 labeling rates in non-small cell lung cancer. It was concluded that the immunostainings of PCNA and Ki-67 were almost equally valuable for assessing the proliferative activity in paraffin-embedded tissue from non-small cell lung cancer and that apoptosis may be related with the cell cycle in this cancer.

  4. Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer

    NARCIS (Netherlands)

    Martinez-Pineiro, L.; Schalken, J.A.; Cabri, P.; Maisonobe, P.; Taille, A. De La; Study, G.

    2014-01-01

    OBJECTIVE: To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics.

  5. Selection of DNA Aptamers for Ovarian Cancer Biomarker CA125 Using One-Pot SELEX and High-Throughput Sequencing

    Directory of Open Access Journals (Sweden)

    Delia J. Scoville

    2017-01-01

    Full Text Available CA125 is a mucin glycoprotein whose concentration in serum correlates with a woman’s risk of developing ovarian cancer and also indicates response to therapy in diagnosed patients. Accurate detection of this large, complex protein in patient samples is of great clinical relevance. We suggest that powerful new diagnostic tools may be enabled by the development of nucleic acid aptamers with affinity for CA125. Here, we report on our use of One-Pot SELEX to isolate single-stranded DNA aptamers with affinity for CA125, followed by high-throughput sequencing of the selected oligonucleotides. This data-rich approach, combined with bioinformatics tools, enabled the entire selection process to be characterized. Using fluorescence anisotropy and affinity probe capillary electrophoresis, the binding affinities of four aptamer candidates were evaluated. Two aptamers, CA125_1 and CA125_12, both without primers, were found to bind to clinically relevant concentrations of the protein target. Binding was differently influenced by the presence of Mg2+ ions, being required for binding of CA125_1 and abrogating binding of CA125_12. In conclusion, One-Pot SELEX was found to be a promising selection method that yielded DNA aptamers to a clinically important protein target.

  6. Does Obesity-Related Hemodilution of Carcinoembryonic Antigen Exist in Non-Small Cell Lung Cancer Patients?

    Science.gov (United States)

    Tomita, Masaki; Ayabe, Takanori; Nakamura, Kunihide

    2017-04-01

    Previous investigations reported inverse relationship between prostate-specific antigen concentration and body mass index (BMI). These results have been explained by a hemodilution effect among obese men. However, the hemodilution of serum carcinoembryonic antigen (CEA) concentration in obese patients with non-small cell lung cancer (NSCLC) has not been ever reported. Consecutive 381 NSCLC patients were enrolled. A body surface area (BSA)-based and a hematocrit (HCT)-based equations were applied for plasma volume (PV) estimation. The relationship between BMI and PV, serum CEA concentration and CEA amount, representing the total amount of CEA protein within the circulation, were examined. Higher BMI was significantly associated with higher PV (P < 0.001). However, serum CEA concentration was not significantly associated with increasing BMI. Furthermore, there was no significant association between BMI and CEA amount. The 5-year survival rate of patients with a high serum CEA concentration was significantly lower than that of patients with a normal CEA. There was no difference in the prognostic significance of serum CEA concentration and CEA amount. We failed to find the association between BMI and CEA, suggesting no or small hemodilution effect of CEA in NSCLC patients. Furthermore, the measurement of the CEA amount could not provide any additional information.

  7. Identification of Anti-tumor Cells Carrying Natural Killer (NK Cell Antigens in Patients With Hematological Cancers

    Directory of Open Access Journals (Sweden)

    Ewelina Krzywinska

    2015-10-01

    Full Text Available Natural killer (NK cells, a cytotoxic lymphocyte lineage, are able to kill tumor cells in vitro and in mouse models. However, whether these cells display an anti-tumor activity in cancer patients has not been demonstrated. Here we have addressed this issue in patients with several hematological cancers. We found a population of highly activated CD56dimCD16+ NK cells that have recently degranulated, evidence of killing activity, and it is absent in healthy donors. A high percentage of these cells expressed natural killer cell p46-related protein (NKp46, natural-killer group 2, member D (NKG2D and killer inhibitory receptors (KIRs and a low percentage expressed NKG2A and CD94. They are also characterized by a high metabolic activity and active proliferation. Notably, we found that activated NK cells from hematological cancer patients have non-NK tumor cell antigens on their surface, evidence of trogocytosis during tumor cell killing. Finally, we found that these activated NK cells are distinguished by their CD45RA+RO+ phenotype, as opposed to non-activated cells in patients or in healthy donors displaying a CD45RA+RO− phenotype similar to naïve T cells. In summary, we show that CD45RA+RO+ cells, which resemble a unique NK population, have recognized tumor cells and degranulate in patients with hematological neoplasias.

  8. Prostate specific antigen only androgen independent prostate cancer: natural history, challenges in management and clinical trial design.

    Science.gov (United States)

    Ryan, Charles J; Beer, Tomasz M

    2007-09-01

    There is no current standard of care for patients with nonmetastatic androgen independent prostate cancer, a condition defined by increasing serum prostate specific antigen despite anorchid testosterone levels and no radiographic evidence of metastases. A consensus panel was convened to review data and propose a strategy for trial design and prioritization. Published literature on the natural history of nonmetastatic androgen independent prostate cancer was reviewed. A panel discussion was held, focusing on reviewing current and past trials, and the development of research priorities for patients in this disease state. Based on 1 report the natural history of nonmetastatic androgen independent prostate cancer is relatively long but heterogeneous. External validation of these published findings has not been performed. Clinical trial design in this setting is impeded by heterogeneity and lack of knowledge about the natural history, prolonged time to clinical end points, such as the development of metastases or death, and a lack of knowledge about how intermediate end points, eg the development of bone metastases, are related to the long-term outcome, eg survival. In clinical practice a reluctance to use therapies with substantial toxicity as well as a lack of outcome data on such patients leaves a vacuum in which there is no standard of care, although secondary hormonal manipulations are widely used. Further research is needed to define the natural history of this disease state, educate patients and clinicians about its distinct natural history and develop informative clinical trial designs suited to this patient population.

  9. Profiling the humoral immune response in colon cancer patients: diagnostic antigens from Streptococcus bovis.

    NARCIS (Netherlands)

    Tjalsma, H.; Scholler-Guinard, M.; Lasonder, E.; Ruers, T.J.M.; Willems, H.L.; Swinkels, D.W.

    2006-01-01

    The human bowel contains a large and dynamic bacterial population that is not only essential for intestinal health, but also critical for the development of diseases such as cancer. In this respect, the Gram-positive bacterium Streptococcus bovis has been associated with colon cancer for many years.

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

    Science.gov (United States)

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

    2015-01-01

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

  11. Penile Metastasis from Prostate Cancer Presenting as Malignant Priapism Detected Using Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography.

    Science.gov (United States)

    Kamaleshwaran, Koramadai Karuppusamy; Balasundararaj, Barani Kumar Pollachi; Jose, Raghi; Shinto, Ajit Sugunan

    2018-01-01

    Gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (Ga-68 PSMA PET/CT) is a promising diagnostic tool for patients with prostate cancer. Penile metastasis from prostate cancer is a rare phenomenon that infrequently manifests as malignant priapism. We present a case of 79-year-old patient diagnosed as a case of adenocarcinoma prostate presenting with penile metastases imaged using Ga-68 PSMA PET/CT.

  12. Long-term Prostate-specific Antigen Velocity in Improved Classification of Prostate Cancer Risk and Mortality

    DEFF Research Database (Denmark)

    Ørsted, David Dynnes; Bojesen, Stig E; Kamstrup, Pia R

    2013-01-01

    BACKGROUND: It remains unclear whether adding long-term prostate-specific antigen velocity (PSAV) to baseline PSA values improves classification of prostate cancer (PCa) risk and mortality in the general population. OBJECTIVE: To determine whether long-term PSAV improves classification of PCa risk...... classification was assessed using the net reclassification index (NRI). RESULTS: Age-adjusted hazard ratios for PCa risk and mortality were 2.7-5.3 and 2.3-3.4, respectively, for long-term PSAV when added to models already including baseline PSA values. For PCa risk and mortality, adding long-term PSAV to models....... Correspondingly, inappropriately reclassified were 49 of 10 000 men with PCa and 1658 of 10 000 men with no PCa. CONCLUSIONS: Long-term PSAV in addition to baseline PSA value improves classification of PCa risk and mortality. Applying long-term PSAV nationwide, the ratio of appropriately to inappropriately...

  13. Tumor-specific immunotherapy of murine bladder cancer with butanol-extracted antigens and ethylchlorformate polymerized tumor protein.

    Science.gov (United States)

    Rochester, M G; Sarosdy, M F; Pickett, S H; Stogdill, B J; Lamm, D L

    1988-09-01

    Successful treatment of superficial bladder cancer using nonspecific immunotherapy with Bacillus Calmette-Guerin (BCG) has been well documented. Investigation of two potential tumor-specific immunotherapeutic agents using a murine transitional-cell carcinoma model (MBT-2) is reported. The survival of mice immunized with tumor proteins obtained by treating tumor cells with either 1-butanol or ethylchlorformate was compared to the survival of animals immunized with BCG. Long-term immunity conferred by each of these agents was also assessed. Significant protection by both agents was noted in all treatment groups compared to controls. Long-term immunity was also found to result from treatment with both investigational agents as well as with BCG. Butanol-extracted antigens and ethylchlorformate polymerized tumor protein may be useful as immunotherapeutic alternatives to BCG.

  14. DNA hypomethylation-mediated activation of Cancer/Testis Antigen 45 (CT45) genes is associated with disease progression and reduced survival in epithelial ovarian cancer.

    Science.gov (United States)

    Zhang, Wa; Barger, Carter J; Link, Petra A; Mhawech-Fauceglia, Paulette; Miller, Austin; Akers, Stacey N; Odunsi, Kunle; Karpf, Adam R

    2015-01-01

    Epithelial ovarian cancer (EOC) is a highly lethal malignancy due to a lack of early detection approaches coupled with poor outcomes for patients with clinically advanced disease. Cancer-testis (CT) or cancer-germline genes encode antigens known to generate spontaneous anti-tumor immunity in cancer patients. CT45 genes are a recently discovered 6-member family of X-linked CT genes with oncogenic function. Here, we determined CT45 expression in EOC and fully defined its epigenetic regulation by DNA methylation. CT45 was silent and hypermethylated in normal control tissues, but a large subset of EOC samples showed increased CT45 expression in conjunction with promoter DNA hypomethylation. In contrast, copy number status did not correlate with CT45 expression in the TCGA database for EOC. CT45 promoter methylation inversely correlated with both CT45 mRNA and protein expression, the latter determined using IHC staining of an EOC TMA. CT45 expression was increased and CT45 promoter methylation was decreased in late-stage and high-grade EOC, and both measures were associated with poor survival. CT45 hypomethylation was directly associated with LINE-1 hypomethylation, and CT45 was frequently co-expressed with other CT antigen genes in EOC. Decitabine treatment induced CT45 mRNA and protein expression in EOC cells, and promoter transgene analyses indicated that DNA methylation directly represses CT45 promoter activity. These data verify CT45 expression and promoter hypomethylation as possible prognostic biomarkers, and suggest CT45 as an immunological or therapeutic target in EOC. Treatment with decitabine or other epigenetic modulators could provide a means for more effective immunological targeting of CT45.

  15. Clinical value of routine serum squamous cell carcinoma antigen in follow-up of patients with early-stage cervical cancer

    NARCIS (Netherlands)

    Esajas, MD; Duk, JM; de Bruijn, HWA; Aalders, JG; Willemse, PHB; Sluiter, W; Pras, B; ten Hoor, K; Hollema, H; van der Zee, AGJ

    2001-01-01

    Purpose: To investigate the contribution to recurrence detection and survival of serum squamous cell carcinoma antigen (SCC-ag) analysis in the follow-up of early-stage cervical cancer patients. Patients and Methods: Follow-up data were evaluated in patients with early-stage squamous cell cervical

  16. Towards personalized treatment of prostate cancer: PSMA I&T, a promising prostate-specific membrane antigen-targeted theranostic agent

    NARCIS (Netherlands)

    K.L.S. Chatalic (Kristell); S. Heskamp (S.); M. Konijnenberg (Mark); Molkenboer-Kuenen, J.D.M. (Janneke D.M.); G.M. Franssen (Gerben); M.C. Clahsen-van Groningen (Marian); Schottelius, M. (Margret); Wester, H.-J. (Hans-Jürgen); W.M. van Weerden (Wytske); O.C. Boerman (Otto); M. de Jong (Marcel)

    2016-01-01

    textabstractProstate-specific membrane antigen (PSMA) is a well-established target for nuclear imaging and therapy of prostate cancer (PCa). Radiolabeled small-molecule PSMA inhibitors are excellent candidates for PCa theranostics-they rapidly and efficiently localize in tumor lesions. However, high

  17. Towards Personalized Treatment of Prostate Cancer: PSMA I&T, a Promising Prostate-Specific Membrane Antigen-Targeted Theranostic Agent

    NARCIS (Netherlands)

    Chatalic, K.L.S.; Heskamp, S.; Konijnenberg, M.; Molkenboer-Kuenen, J.D.; Franssen, G.M.; Clahsen-van Groningen, M.C.; Schottelius, M.; Wester, H.J.; Weerden, W.M. van; Boerman, O.C.; Jong, M. de

    2016-01-01

    Prostate-specific membrane antigen (PSMA) is a well-established target for nuclear imaging and therapy of prostate cancer (PCa). Radiolabeled small-molecule PSMA inhibitors are excellent candidates for PCa theranostics-they rapidly and efficiently localize in tumor lesions. However, high tracer

  18. Impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) on prostate-specific antigen (PSA) testing by Dutch general practitioners

    NARCIS (Netherlands)

    Van der Meer, Saskia; Kollen, Boudewijn J.; Hirdes, Willem H.; Steffens, Martijn G.; Hoekstra-Weebers, Josette E. H. M.; Nijman, Rien M.; Blanker, Marco H.

    Objective To determine the impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) publication in 2009 on prostate-specific antigen (PSA) level testing by Dutch general practitioners (GPs) in men aged 40 years. Materials and Methods Retrospective study with a Dutch insurance

  19. Prostate-specific Antigen Decline After 4 Weeks of Treatment with Abiraterone Acetate and Overall Survival in Patients with Metastatic Castration-resistant Prostate Cancer

    NARCIS (Netherlands)

    Rescigno, P.; Lorente, D.; Bianchini, D.; Ferraldeschi, R.; Kolinsky, M.P.; Sideris, S.; Zafeiriou, Z.; Sumanasuriya, S.; Smith, A.D.; Mehra, N.; Jayaram, A.; Perez-Lopez, R.; Mateo, J.; Parker, C.; Dearnaley, D.P.; Tunariu, N.; Reid, A.; Attard, G.; Bono, J.S. de

    2016-01-01

    BACKGROUND: The availability of multiple new treatments for metastatic castration-resistant prostate cancer (mCRPC) mandates earlier treatment switches in the absence of a response. A decline in prostate-specific antigen (PSA) is widely used to monitor treatment response, but is not validated as an

  20. Survival of ovarian cancer patients overexpressing the tumour antigen p53 is diminished in case of MHC class I down-regulation

    NARCIS (Netherlands)

    Leffers, Ninke; Lambeck, Annechien J. A.; de Graeff, Pauline; Bijlsma, Astrid Y.; Daemen, Toos; van der Zee, Ate G. J.; Nijman, Hans W.

    Objectives. The adaptive immune system seems to play an essential role in the natural course of ovarian cancer. Aim of this study was to establish whether disease-specific survival for patients expressing the tumour antigen p53 is influenced by MHC class I expression or the presence of p53

  1. Prostate cancer screening by prostate-specific antigen (PSA); a relevant approach for the small population of the Cayman Islands.

    Science.gov (United States)

    Jyoti, Shravana Kumar; Blacke, Camille; Patil, Pallavi; Amblihalli, Vibha P; Nicholson, Amanda

    2018-01-01

    The common tool for diagnosing prostate cancer is prostate-specific antigen (PSA), but the high sensitivity and low specificity of PSA testing are the problems in clinical practice. There are no proper guidelines to investigate the suspected prostate cancer in the Cayman Islands. We correlated PSA levels with the incidence of prostate cancers by tissue diagnosis and proposed logical protocol for prostate screening by using PSA test in this small population. A total of 165 Afro Caribbean individuals who had prostate biopsy done after the investigations for PSA levels from year 2005 to 2015 were studied retrospectively. The patients were divided into subgroups by baseline PSA levels as follows: 100 ng/mL and were correlated to the age and presence of cancer. Benign lesions had lower PSA levels compared to cancer which generally had higher values. Only three cases that had less than 4 ng/mg were turned out to be malignant. When PSA value was more than 100 ng/mL, all the cases were malignant. Between PSA values of 4-100 ng/mL, the probability of cancer diagnosis was 56.71% (76 cancers out of 134 in this range). Limitation of PSA testing has the risk of over diagnosis and the resultant negative biopsies owing to poor specificity. Whereas the cutoff limit for cancer diagnosis still remains 4 ng/mL from our study, most of the patients can be assured of benign lesion below this level and thus morbidity associated with the biopsy can be prevented. When the PSA value is greater than 100 ng, biopsy procedure was mandatory as there were 100% cancers above this level. On the background of vast literature linking PSA to prostate cancer and its difficulty in implementing in clinical practice, we studied literature of this conflicting and complex topic and tried to bring relevant protocols to the small population of Cayman Islands for the screening of prostate cancer. In this study, a total of 165 Afro Caribbean individuals who had prostate biopsy done after the

  2. Danish General Practitioners' Use of Prostate-Specific Antigen in Opportunistic Screening for Prostate Cancer

    DEFF Research Database (Denmark)

    Jessen, Kasper; Søndergaard, Jens; Larsen, Pia Veldt

    2013-01-01

    Background. The use of prostate-specific antigen test has markedly increased in Danish general practice in the last decade. Despite the national guidelines advice against PSA screening, opportunistic screening is supposed to be the primary reason for this increased number of PSA tests performed...... be potential reasons for measuring PSA for asymptomatic patients. Almost all GPs stated that a PSA measurement is indicated for symptomatic 49- and 78-year-old men, respectively, 98.9% and 93.8%. Conclusion. Opportunistic PC screening is being performed in general practice to a high degree. Hence, current...

  3. Prostate-Specific Antigen (PSA) Test

    Science.gov (United States)

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Prostate-Specific Antigen (PSA) Test On This Page What ... the PSA test for prostate cancer screening? Detecting prostate cancer early may not reduce the chance of ...

  4. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

    Science.gov (United States)

    Hong, Hao; Brown, Christine E; Ostberg, Julie R; Priceman, Saul J; Chang, Wen-Chung; Weng, Lihong; Lin, Paul; Wakabayashi, Mark T; Jensen, Michael C; Forman, Stephen J

    2016-01-01

    New therapeutic modalities are needed for ovarian cancer, the most lethal gynecologic malignancy. Recent clinical trials have demonstrated the impressive therapeutic potential of adoptive therapy using chimeric antigen receptor (CAR)-redirected T cells to target hematological cancers, and emerging studies suggest a similar impact may be achieved for solid cancers. We sought determine whether genetically-modified T cells targeting the CE7-epitope of L1-CAM, a cell adhesion molecule aberrantly expressed in several cancers, have promise as an immunotherapy for ovarian cancer, first demonstrating that L1-CAM was highly over-expressed on a panel of ovarian cancer cell lines, primary ovarian tumor tissue specimens, and ascites-derived primary cancer cells. Human central memory derived T cells (TCM) were then genetically modified to express an anti-L1-CAM CAR (CE7R), which directed effector function upon tumor antigen stimulation as assessed by in vitro cytokine secretion and cytotoxicity assays. We also found that CE7R+ T cells were able to target primary ovarian cancer cells. Intraperitoneal (i.p.) administration of CE7R+ TCM induced a significant regression of i.p. established SK-OV-3 xenograft tumors in mice, inhibited ascites formation, and conferred a significant survival advantage compared with control-treated animals. Taken together, these studies indicate that adoptive transfer of L1-CAM-specific CE7R+ T cells may offer a novel and effective immunotherapy strategy for advanced ovarian cancer.

  5. The cancer-germline antigen SSX2 causes cell cycle arrest and DNA damage in cancer cells

    DEFF Research Database (Denmark)

    Greve, Katrine Buch Vidén; Lindgreen, Jonas; Terp, Mikkel Green

    2011-01-01

    , we show that SSX2 is involved in regulation of cancer cell growth. We found that ectopic expression of SSX2 in melanoma and colon cancer cells strongly reduced cell growth and induced apoptosis in vitro. Importantly, in a xenograft mouse model, the growth of tumors derived from SSX2 overexpressing...... dependent. The growth reduction was similar in isogenic colon cancer cells with and without p53, indicating that SSX2 is able to inhibit the growth of cancer cells, even in absence of functional p53. Our results show that SSX2 acts as an inhibitor of cancer cell proliferation, possibly through replicative...... stress, and therefore have important implications for the use of SSX2 as a target for cancer therapy....

  6. NY-BR-1 Antigen Expression and anti-NY-BR-1 IgG in Egyptian Breast Cancer Patients: Clinicopathological and Prognostic Significance.

    Science.gov (United States)

    Abu El-Nazar, Salma Y; Ghazy, Amany A; Ghoneim, Hossam E; Zoheir, Malak; Ahmed, Ahmed S; Sorour, Sally S; Abouelella, Amira M

    2015-01-01

    Breast cancer is the most common gynecological malignancy in the world. In Egypt, it ranks the first among female malignancies with incidence of 37.7%. Over the last decades, the integration of prognostic and predictive markers in treatment decisions has led to more individualized and optimized therapy. NY-BR-1 antigen has been shown to be frequently expressed in breast cancers. The study aimed to assess the tissue expression of NY-BR-1 antigen and serum IgG antibody to this antigen in Egyptian breast cancer females. The study was conducted on 60 females (10 healthy, 10 having benign breast lesions, 40 with malignant breast cancer). NY-BR-1 Ag expression was evaluated by immunohistochemistry and anti-NY-BR-1 IgG was assessed by ELISA. Results revealed a significant difference in NY-BR-1 Ag expression between benign and malignant breast cancer patients. There was a significant correlation between NY-BR-1 antigen expression and estrogen receptor's status (P = 0.019), stage of the disease (P = 0.008), menopausal status (P = 0.008), lymph node involvement (P = 0.022) and anti-NY-BR-1 IgG (P = 0.032) among the studied individuals. In addition, there was a statistically significant increase in anti-NY-BR-1 IgG O.D. results among malignant breast cancer group. It is correlated with tumor type (P 1) and progesterone receptor status (P = 0.038). In conclusion, our work may represent a step towards identification of a new prognostic marker specific for breast cancer.

  7. The role of serum testosterone to prostate-specific antigen ratio as a predictor of prostate cancer risk

    Directory of Open Access Journals (Sweden)

    Cenk Gurbuz

    2012-12-01

    Full Text Available We analyzed the ratio of serum total testosterone (sTT to prostate-specific antigen (PSA as a predictor of prostate cancer risk. One-hundred-four consecutive men with a normal digital rectal examination and a serum PSA level of 2.5–10 ng/ml underwent transrectal ultrasonography-guided biopsy using a 10-core scheme. The sTT level was determined before the procedure using a chemiluminescent assay, and the ratio of sTT to PSA (sTT/PSA was calculated after transforming sTT measurements from ng/dL to ng/mL. The overall cancer detection rate was 17.3%. The median sTT level was 332 ng/dl in men with cancer and 413 ng/dL in those without (p = 0.032. The median sTT/PSA ratio in these groups was 0.55 and 0.74, respectively (p = 0.035. The receiver operator characteristic (ROC method was used to evaluate the properties of the sTT/PSA ratio, with testosterone and PSA as predictors of prostate cancer risk. The accuracy of the sTT/PSA ratio in prostate cancer diagnosis, represented by the area under the curve (AUC, was 0.739 (95% CI 0.640–0.823, p < 0.05. Optimizing the sensitivity and specificity of the sTT/PSA ratio using the ROC provided a cutoff point of 0.60, which corresponded to 82% sensitivity and 62% specificity. When the patients were divided into normal- and low-sTT level groups according to testosterone value (300 ng/dl, the probability of detecting prostate cancer was 3.3-fold higher in hypogonadal men as compared with eugonadal men. These results support the use of the sTT-to-PSA ratio for predicting the risk of prostate cancer and increasing the specificity of PSA measurement.

  8. Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens.

    Science.gov (United States)

    MacLachlan, Bruce J; Greenshields-Watson, Alexander; Mason, Georgina H; Schauenburg, Andrea J; Bianchi, Valentina; Rizkallah, Pierre J; Sewell, Andrew K; Fuller, Anna; Cole, David K

    2017-02-06

    Human CD8+ cytotoxic T lymphocytes (CTLs) are known to play an important role in tumor control. In order to carry out this function, the cell surface-expressed T-cell receptor (TCR) must functionally recognize human leukocyte antigen (HLA)-restricted tumor-derived peptides (pHLA). However, we and others have shown that most TCRs bind sub-optimally to tumor antigens. Uncovering the molecular mechanisms that define this poor recognition could aid in the development of new targeted therapies that circumnavigate these shortcomings. Indeed, present therapies that lack this molecular understanding have not been universally effective. Here, we describe methods that we commonly employ in the laboratory to determine how the nature of the interaction between TCRs and pHLA governs T-cell functionality. These methods include the generation of soluble TCRs and pHLA and the use of these reagents for X-ray crystallography, biophysical analysis, and antigen-specific T-cell staining with pHLA multimers. Using these approaches and guided by structural analysis, it is possible to modify the interaction between TCRs and pHLA and to then test how these modifications impact T-cell antigen recognition. These findings have already helped to clarify the mechanism of T-cell recognition of a number of cancer antigens and could direct the development of altered peptides and modified TCRs for new cancer therapies.

  9. Identification of novel helper epitope peptides of Survivin cancer-associated antigen applicable to developing helper/killer-hybrid epitope long peptide cancer vaccine.

    Science.gov (United States)

    Ohtake, Junya; Ohkuri, Takayuki; Togashi, Yuji; Kitamura, Hidemitsu; Okuno, Kiyotaka; Nishimura, Takashi

    2014-09-01

    We identified novel helper epitope peptides of Survivin cancer antigen, which are presented to both HLA-DRB1*01:01 and DQB1*06:01. The helper epitope also contained three distinct Survivin-killer epitopes presented to HLA-A*02:01 and A*24:02. This 19 amino-acids epitope peptide (SU18) induced weak responses of Survivin-specific CD4(+) and CD8(+) T cells though it contained both helper and killer epitopes. To enhance the vaccine efficacy, we synthesized a long peptide by conjugating SU18 peptide and another DR53-restricted helper epitope peptide (SU22; 12 amino-acids) using glycine-linker. We designated this artificial 40 amino-acids long peptide containing two helper and three killer epitopes as Survivin-helper/killer-hybrid epitope long peptide (Survivin-H/K-HELP). Survivin-H/K-HELP allowed superior activation of IFN-γ-producing CD4(+) Th1 cells and CD8(+) Tc1 cells compared with the mixture of its component peptides (SU18 and SU22) in the presence of OK-432-treated monocyte-derived DC (Mo-DC). Survivin-H/K-HELP-pulsed Mo-DC pretreated with OK-432 also exhibited sustained antigen-presentation capability of stimulating Survivin-specific Th1 cells compared with Mo-DC pulsed with a mixture of SU18 and SU22 short peptides. Moreover, we demonstrated that Survivin-H/K-HELP induced a complete response in a breast cancer patient with the induction of cellular and humoral immune responses. Thus, we believe that an artificially synthesized Survivin-H/K-HELP will become an innovative cancer vaccine. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Mehta, Niraj H., E-mail: nmehta@mednet.ucla.edu [University of California, Los Angeles, Los Angeles, California (United States); Kamrava, Mitchell; Wang, Pin-Chieh; Steinberg, Michael; Demanes, Jeffrey [University of California, Los Angeles, Los Angeles, California (United States)

    2013-07-15

    Purpose: To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce. Methods and Materials: Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL). Results: A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged <55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045). Conclusions: A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from <1 in 28% of cases to ≥1 in 15%. The median duration of bounce is <1 year. More bounces were identified in patients with lower Gleason score and age <55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way.

  11. DNA vaccine coding for the rhesus prostate specific antigen delivered by intradermal electroporation in patients with relapsed prostate cancer.

    Science.gov (United States)

    Eriksson, Fredrik; Tötterman, Thomas; Maltais, Anna-Karin; Pisa, Pavel; Yachnin, Jeffrey

    2013-08-20

    We tested safety, clinical efficacy and immunogenicity of a DNA vaccine coding for rhesus prostate specific antigen (PSA) delivered by intradermal injection and skin electroporation. Fifteen patients with biochemical relapse of prostate cancer without macroscopic disease participated in this phase I study. Patients were started on a 1 month course of androgen deprivation therapy (ADT) prior to treatment. Vaccine doses ranged from 50 to 1,600 μg. Study subjects received five vaccinations at four week intervals. All patients have had at least one year of follow-up. No systemic toxicity was observed. Discomfort from electroporation did not require analgesia or topical anesthetic. No clinically significant changes in PSA kinetics were observed as all patients required antiandrogen therapy shortly after completion of the 5 months of vaccination due to rising PSA. Immunogenicity, as measured by T-cell reactivity to the modified PSA peptide and to a mix of overlapping PSA peptides representing the full length protein, was observed in some patients. All but one patient had pre-study PSA specific T-cell reactivity. ADT alone resulted in increases in T-cell reactivity in most patients. Intradermal vaccination with skin electroporation is easily performed with only minor discomfort for the patient. Patients with biochemical relapse of prostate cancer are a good model for testing immune therapies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Study of Prostate Specific Antigen Gene Expression and Telomerase in Breast Cancer Patients: Relationship to Steroid Hormone Receptors

    Directory of Open Access Journals (Sweden)

    N. Zarghami

    2007-10-01

    Full Text Available Introduction & Objective: Breast cancer is the most common disease in women. In the expansion and progression of breast tumors combination of tumor markers including prostate specific antigen (PSA and telomerase are engaged. The aim of this study was to evaluate relationship between telomerase activity and prostate specific antigen gene expression with steroid hormone receptors in breast cancer patients. Materials & Methods: This study was a case-control and consisted of 50 women diagnosed with breast benign tumors as control and 50 women having malignant tumors as cases. Telomerase activity was measured in tumor cytosol of samples by telomeric repeat amplification protocol (TRAP assay. PSA protein was measured using ultra sensitive immunoflourometric assay and PSA mRNA expression was carried out using RT-PCR technique in all tumor tissues. Estrogen and progesterone receptors were stained using immunohistochemistry technique in tumor tissues. Data analysis was carried out by using SPSS software version 11.6 and paired t-student test. Results: Using TRAP assay, presence of the telomerase activity was positive in all of the breast cancer patients. The difference of relative telomerase activity (RTA values between stages and also all grades were more statistically significant (p<0.05. The mRNA of PSA was detected only in benign tumors and stage I and grade I malignant tumor cytosols. Difference of tumor cytosol PSA levels between the cases and control groups and also between all grades and stages of diseases were significant (p <0.05. In all, there was an inverse significant correlation between the RTA and PSA protein levels in the case groups. (r=-0.42, p<0.05.There was a statistically difference between steroid hormone receptors (ER and PR positive and negative on PSA and telomerase gene expression in breast tumor tissues (p<0.05. Conclusion: It is speculated that differential expression of PSA and telomerase genes in breast tumors are under

  13. Phenotype of dendritic cells generated in the presence of non-small cell lung cancer antigens - preliminary report.

    Directory of Open Access Journals (Sweden)

    Dariusz Sagan

    2009-01-01

    Full Text Available Therapeutic outcomes of definitively treated non-small-cell lung cancer (NSCLC are unacceptably poor. It has been proposed that the manipulation of dendritic cells (DCs as a "natural" vaccine adjuvant may prove to be a particularly effective way to stimulate antitumor immunity. Presently, there is no standardized methodology for preparing vaccines and many questions concerning the optimal source and type of antigens as well as maturation state and activity of DCs are still unsolved. The study population comprised of ten patients with histologically confirmed NSCLC (mean age: 67.63 +/- 6.15 years. Resected small tumor pieces were placed in tissue culture dishes containing different growth factors in order to obtain pure cancer cells. Seven days after the operation, the PBMC were collected and monocytes were purified by the adherence to culture dishes. Monocytes were cultured in RPMI 1640 medium supplemented with 10% of autologous plasma in the presence of rhIL-4 and rhGM-CSF to generate immature autologous (DCs. TNF-alpha with or without tumor cells' lysate were added to maturation of DCs. After 7 days of culture, DCs were harvested and the expression of CD1a, CD83, CD80, CD86 and HLA-DR antigens were analyzed by flow cytometry. We discovered higher (p=0.07 percentage of semimature DCs in tumor cell lysate culture in comparison with TNF-alpha culture (21.22 +/- 16.82% versus 11.27 +/- 11.64%. The expression of co-stimulatory and maturation markers (CD86, CD83 and HLA-DR was higher on DCs from the culture with tumor cell lysate compared with TNF-alpha culture as a control. Specimen of NSCLC's culture prepared in this way could generate differences in DCs phenotype, which may have an influence on the therapeutic and protective antitumor immunity of the vaccine. Our research seems to be the next step in the development of DC-based vaccine. We are going to continue the investigation to start the preparation of a pattern of immunological vaccine

  14. Soluble Human Leukocyte Antigen-G in the Bronchoalveolar Lavage of Lung Cancer Patients.

    Science.gov (United States)

    Montilla, Dayana; Pérez, Mario; Borges, Lérida; Bianchi, Guillermo; Cova, José-Angel

    2016-08-01

    The main function of the HLA-G molecule in its membrane-bound and soluble forms is to inhibit the immune response by acting on CD4+ T cells, cytotoxic T cells, NK cells and dendritic cells. Lung cancer is a leading cause of death worldwide, and annual incidence is high in both women and men. Some studies have reported an increase of HLA-G serum levels in lung cancer, probably generated by tumor cells escaping the antitumor immune response. In this study the concentration of soluble HLA-G in bronchoalveolar lavage (BAL) in patients with primary and metastatic lung cancer was measured to determine its relation with tumor histological type and overall patient status according to the Karnofsky scale. Thirty-one lung cancer patients were included. A tumor biopsy was obtained by bronchoscopy and the tumor type was determined by hematoxylin and eosin staining. BAL samples were obtained to measure soluble HLA-G concentrations in an ELISA sandwich assay. The average value of soluble HLA-G was 49.04ng/mL. No correlation between soluble HLA-G levels and age, gender or smoking was observed. A highly significant difference was observed in the levels of soluble HLA-G in BAL from patients with different histological types of lung cancer, especially in metastatic tumors. The Karnofsky index showed a significant and inverse correlation with soluble HLA-G levels in BAL. Soluble HLA-G protein is significantly associated with metastatic tumors and patients with lower Karnofsky index and may be useful as a prognostic marker in lung cancer. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Prophylactic Oophorectomy: Preventing Cancer by Surgically Removing Your Ovaries

    Science.gov (United States)

    ... much lower than the lifetime risk of ovarian cancer if the ovaries remain intact. Prophylactic oophorectomy might relieve much of ... cancer. Screening usually includes a blood test for cancer antigen CA 125 and an ultrasound exam of your ovaries. In theory, increased screening should be able to ...

  16. Expression of Lewisa, Sialyl Lewisa, Lewisx, Sialyl Lewisx, Antigens as Prognostic Factors in Patients with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Tohru Nakagoe

    2000-01-01

    Full Text Available BACKGROUND: Altered expression of blood group-related carbohydrate antigens such as sialyl Lewis (Lex antigen in tumours is associated with tumour progression behaviour and subsequent prognosis. However, the prognostic value of the expression of Le-related antigens in colorectal tumours remains unclear.

  17. Can Prostate Specific Antigen Be Used as New Biomarker for Early Diagnosis of Breast Cancer?

    Directory of Open Access Journals (Sweden)

    Seyed Mostafa Shiryazdi

    2015-09-01

    Conclusion: Plasma PSA level is not a reliable biomarker to diagnose breast cancer, though regarding existing scientific evidence, more comprehensive studies are required to consider other features of malignant samples so as to evaluate the role of PSA in differentiating breast neoplastic lesions in a more meticulous way based on the degree of tumor differentiation.

  18. Meanings of prostate-specific antigen testing as narrated by men with localized prostate cancer after primary treatment.

    Science.gov (United States)

    Hedestig, Oliver; Sandman, Per-Olof; Widmark, Anders; Rasmussen, Birgit H

    2008-01-01

    To illuminate the meanings of prostate-specific antigen (PSA) testing as narrated by men with localized prostate cancer (LPC) after primary treatment. Fifteen men were interviewed in their homes. The narrative interview text was analyzed using a phenomenological hermeneutic method inspired by the philosophy of Paul Ricoeur. Life after treatment for LPC means feeling unsafe because of being affected by a life-threatening and unpredictable disease, characterized by a lack of early signs of progression. In this situation, PSA testing is ascribed as providing a sense of control to enable one to achieve a feeling of safety. Thus one meaning of PSA testing is receiving a message about the status of the body; another is a tense waiting related to fear of the results. A low, stable PSA value is interpreted as a sense of being safe based on confidence in the PSA tests and a sense of having control over the LPC via regular PSA testing. A rising value of the PSA blood test is understood as an indication of progression of the disease, but confidence in PSA testing also means that when the PSA value rises there is a sense of catching the cancer in good time. The comprehensive understanding of the meaning of PSA testing can be understood in terms of a lifeline to cling to when wondering whether the cancer is still in progress in the body or whether the treatment has been curative. This lifeline creates a feeling of security in a post-treatment life situation which is experienced as being unsafe.

  19. Utility of free prostate specific antigen serum level and its related parameters in the diagnosis of prostate cancer

    Directory of Open Access Journals (Sweden)

    Azmi A Haroun

    2011-01-01

    Full Text Available We evaluated the role of free prostate specific antigen (f-PSA serum level and its related parameters in detecting prostate cancer. This retrospective study was conducted between January 2006 and March 2008. Trans-rectal ultrasound guided prostate biopsy was performed for 107 patients who had total PSA (t-PSA level of either >4 ng/mL with or without palpable nodule or ≤4 ng/mL with palpable nodule on digital rectal examination. The perfor-mance measurements for f-PSA, percent free PSA (%f-PSA and free PSA density (f-PSAD were determined and compared with those for t-PSA and total PSA density (t-PSAD. Descriptive statistics for all variables of interest were calculated, and receiver operating characteristic curves were generated. Nine patients (8.4% had normal histology, 69 patients (64.4% had benign disease and 29 patients (27.1% had prostate cancer. The performance of f-PSA in PCa detection was better than other evaluated parameters. The largest area under the curve for patients in the gray area (t-PSA range 4.1-10 ng/mL was for f-PSA, with a value of 0.64 and a sensitivity and specificity of 44% and 87%, respectively. For %f-PSA, these values were 0.59, 63% and 62%, respectively. For patients with a t-PSA level of 10.1-20 ng/mL, they were 0.68, 67%, and 81%, respectively, for f-PSA, and 0.64, 67%, and 76%, respectively, for %f-PSA. In conclusion, f-PSA serum levels performed better than free to total PSA ratio and t-PSA for prostate cancer screening. It is of clinical value which could affect the biopsy decision avoiding unnecessary interventions.

  20. Utility of free prostate specific antigen serum level and its related parameters in the diagnosis of prostate cancer.

    Science.gov (United States)

    Haroun, Azmi A; Hadidy, Azmy S; Awwad, Ziad M; Nimri, Caramella F; Mahafza, Waleed S; Tarawneh, Emad S

    2011-03-01

    We evaluated the role of free prostate specific antigen (f-PSA) serum level and its related parameters in detecting prostate cancer. This retrospective study was conducted between January 2006 and March 2008. Transrectal ultrasound guided prostate biopsy was performed for 107 patients who had total PSA (t-PSA) level of either >4 ng/mL with or without palpable nodule or ≤4 ng/mL with palpable nodule on digital rectal examination. The performance measurements for f-PSA, percent free PSA (%f-PSA) and free PSA density (f-PSAD) were determined and compared with those for t-PSA and total PSA density (t-PSAD). Descriptive statistics for all variables of interest were calculated, and receiver operating characteristic curves were generated. Nine patients (8.4%) had normal histology, 69 patients (64.4%) had benign disease and 29 patients (27.1%) had prostate cancer. The performance of f-PSA in PCa detection was better than other evaluated parameters. The largest area under the curve for patients in the gray area (t-PSA range 4.1-10 ng/mL) was for f-PSA, with a value of 0.64 and a sensitivity and specificity of 44% and 87%, respectively. For %f-PSA, these values were 0.59, 63% and 62%, respectively. For patients with a t-PSA level of 10.1-20 ng/mL, they were 0.68, 67%, and 81%, respectively, for f-PSA, and 0.64, 67%, and 76%, respectively, for %f-PSA. In conclusion, f-PSA serum levels performed better than free to total PSA ratio and t-PSA for prostate cancer screening. It is of clinical value which could affect the biopsy decision avoiding unnecessary interventions.

  1. Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV.

    Science.gov (United States)

    Liu, Dongfang; Tian, Shuo; Zhang, Kai; Xiong, Wei; Lubaki, Ndongala Michel; Chen, Zhiying; Han, Weidong

    2017-12-01

    Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body's immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use. To alleviate these disadvantages of CAR-modified T cell immunotherapy, additional cytotoxic cell-mediated immunotherapies are urgently needed. The unique biology of NK cells allows them to serve as a safe, effective, alternative immunotherapeutic strategy to CAR-modified T cells in the clinic. While the fundamental mechanisms underlying the cytotoxicity and side effects of CAR-modified T and NK cell immunotherapies remain poorly understood, the formation of the immunological synapse (IS) between CAR-modified T or NK cells and their susceptible target cells is known to be essential. The role of the IS in CAR T and NK cell immunotherapies will allow scientists to harness the power of CAR-modified T and NK cells to treat cancer and infectious diseases. In this review, we highlight the potential applications of CAR-modified NK cells to treat cancer and human immunodeficiency virus (HIV), and discuss the challenges and possible future directions of CAR-modified NK cell immunotherapy, as well as the importance of understanding the molecular mechanisms of CAR-modified T cell- or NK cell-mediated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.

  2. Differential percentage of serum prostate-specific antigen subforms suggests a new way to improve prostate cancer diagnosis.

    Science.gov (United States)

    Sarrats, Ariadna; Comet, Josep; Tabarés, Glòria; Ramírez, Manel; Aleixandre, R Núria; de Llorens, Rafael; Peracaula, Rosa

    2010-01-01

    Prostate-specific antigen (PSA) is the tumor marker currently used for prostate cancer (PCa) screening and diagnosis. However, its use is controversial as serum PSA levels are also increased in other non-malignant prostatic diseases such as benign prostatic hyperplasia (BPH). PSA sialic acid content is altered in tumor situation and modifies PSA's isoelectric point (pI). Our goal has been to evaluate serum PSA subforms from PCa and BPH patients by two-dimensional electrophoresis (2-DE) and to investigate whether they could be used to improve PCa diagnosis. PSA from 20 PCa and 20 BPH patients' sera was subjected to a four-step method to obtain serum PSA 2-DE subforms from free PSA (fPSA) plus PSA released from the complex with alpha-1-antichymotrypsin. Relative percentages of PSA spots were quantified and subjected to statistical analysis. Five PSA subforms (F1, F2, F3, F4, and F5) of different pI were obtained. Relative percentages of F3 (%F3) and F4 (%F4) were different between PCa and BPH groups. %F3 decreased in cancers and this decrease correlated with the cancer stage, while F4 behaved oppositely. These observations were also found when only focusing on the patients within the low total PSA (tPSA) range 2-20 ng/ml. %F3 showed a tendency of higher sensitivity and specificity than the currently used tPSA and %fPSA tests. Therefore, %F3 measurement should be investigated in a larger cohort of patients to study whether it could be introduced to improve PCa diagnosis. (c) 2009 Wiley-Liss, Inc.

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

    Science.gov (United States)

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

    2003-01-01

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

  4. Near-infrared-conjugated humanized anti-carcinoembryonic antigen antibody targets colon cancer in an orthotopic nude-mouse model.

    Science.gov (United States)

    DeLong, Jonathan C; Murakami, Takashi; Yazaki, Paul J; Hoffman, Robert M; Bouvet, Michael

    2017-10-01

    The success of a curative surgery for cancer is dependent on the complete removal of all cancer cells. Tumor visualization by the surgeon can be enhanced through fluorescent-antibody targeting. To further develop such technology, we selected humanized anti-carcinoembryonic antigen (CEA) conjugated to a near-infrared dye to target orthotopically-implanted human colon cancer in nude mice. The HT-29 human colon cancer cell line was grown in culture and subcutaneously injected in mice. After 3 wk of growth, tumors were resected and cut into 2 mm3 fragments that were sutured to the cecum of five additional nude mice for orthotopic implantation. The tumors were allowed to grow for 4 wk at which point 3 had successful orthotopic tumor growth and were selected for injection of the humanized anti-CEA antibody conjugated to the near-infrared dye IRDye800CW (anti-CEA-IRDye800CW). The antibody-dye conjugate (75 μg) was administered via tail vein injection. Images were obtained with the Pearl Trilogy Small Animal Imaging System with both 700 and 800 nm channels and evaluated using Image Studio. Laparotomy was performed 24 h after labeling the tumors. When imaged through the 800 nm channel, the tumors were observed to be strongly labeled with anti-CEA-IRDye800. At 48 h, laparotomy was repeated which again demonstrated strong labeling of the tumors through the 800 nm channel, but with a lower absolute intensity (in relative units), than at 24 h. Humanized anti-CEA-IRDye800CW can rapidly and effectively label CEA-expressing human colon cancer in an orthotopic nude mouse model. Given the ability of this technology to target and label tumors with great specificity, the anti-CEA-IRDye800CW is currently being developed for clinical use in fluorescence-guided surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Evaluation of serum prostate specific antigen in diagnosis of patients with prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Torizumi, Kazutami; Kumayama, Yoshitaka; Tuda, Tadaaki; Ota, Kiichiro; Morita, Teruo; Miyai, Masahiro; Hagino, Keizo; Hirano, Atuyuki; Uekado, Yasunari (Wakayama Medical Coll. (Japan))

    1991-07-01

    Serum PSA level in patients with urogenital disorders was measured by PSA kits using monoclonal antibody. Serum PSA values in 122 healthy men were 1.1 {+-} 0.3 ng/ml (mean {+-} S.D.) and upper limit of mean + 2 S.D. in healthy men was 1.7 ng/ml. Serum PSA levels in 15 male patients with prostate cancer were more increased than those in 11 male patients with prostate hypertrophy (556.9 {+-} 896.1 ng/ml vs. 8.4 {+-} 10.4 ng/ml, p < 0.001). It is our conclusion that the estimate of serum PSA level provided a useful diagnostic information of prostate cancer. (author).

  6. Immunohistochemical expression of tumor antigens MAGE-A1, MAGE-A3/4, and NY-ESO-1 in cancerous and benign prostatic tissue.

    Science.gov (United States)

    Hudolin, Tvrtko; Juretic, Antonio; Spagnoli, Giulio Cesare; Pasini, Josip; Bandic, Daniela; Heberer, Michael; Kosicek, Miljenko; Cacic, Mirjana

    2006-01-01

    To investigate immunohistochemical expression of MAGE-A and NY-ESO-1/LAGE-1, cancer testis antigens in prostate tissues showing evidence of malignant transformation or benign hyperplasia. 112 prostate samples from patients undergoing surgery at the Urology Clinic at the Zagreb Clinical Hospital Center from 1995 to 2003 were investigated in this study. Of these, 92 carcinoma samples were obtained by radical prostatectomy, and 20 benign prostatic hyperplasia samples by transvesical prostatectomy. Three monoclonal antibodies were used for immunohistochemical staining: 77B for MAGE-A1, 57B for multi-MAGE-A and D8.38 for NY-ESO-1 expression. Expression of MAGE-A1 was observed in 10.8% of carcinoma samples, whereas multi-MAGE-A and NY-ESO-1/LAGE-1 stained 85.9% and 84.8% of samples. Immunohistochemical staining was only detectable in the cytoplasm. A significant heterogeneity could be observed within a same tissue sample where areas with strong positivities coexisted with cancer testis antigens negative areas. Interestingly, a majority of 57B positive cases were also found to be D8.38 positive (correlation coefficient r=0.727 (P<0.01)). Cancer testis antigens expression was neither significantly correlated with PSA values nor with Gleason score. In benign prostatic hyperplasia tissues MAGE-A1 expression was detected in 5%, while 57B and D8.38 staining was observed in 15% samples, and in all cases percentages of positive cells were always <10%. Our data underline the peculiar relevance of cancer testis antigens expression in prostate cancers, with potential implications regarding both diagnosis and therapy. Copyright (c) 2005 Wiley-Liss, Inc.

  7. Tumor markers of breast cancer: New prospectives

    Directory of Open Access Journals (Sweden)

    Ahmed M. Kabel

    2017-04-01

    Full Text Available Tumor markers are substances produced by the tumors or by other cells of the body in response to cancer or certain benign conditions. Although most of these markers are made by the normal cells as well as by cancer cells, they are produced at much higher levels in cancerous conditions. These markers are used to evaluate the patient's response to treatment and to detect the presence of metastasis or recurrence. Breast cancer is one of the most common malignancies in females worldwide. The CA 27-29, CA 15-3, CA27.29, carcinoembryonic antigen, tissue polypeptide specific antigen, p53, cathepsin D, cyclin E, nestin and HER-2 are tumor markers that are often expressed in people with breast cancer. They play a crucial role in diagnosis, monitoring response to therapy, early detection of metastasis and determination of recurrence in patients with breast cancer.

  8. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    Energy Technology Data Exchange (ETDEWEB)

    Bujak, Emil [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland); Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah [Philochem AG, Libernstrasse 3, CH-8112 Otelfingen (Switzerland); Neri, Dario, E-mail: neri@pharma.ethz.ch [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland)

    2014-09-10

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  9. Expression, purification and characterization of the cancer-germline antigen GAGE12I: a candidate for cancer immunotherapy

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Besir, Hüseyin; Larsen, Martin R

    2010-01-01

    for immunotherapy and candidates for cancer vaccines. Recombinant proteins may be superior to peptides as immunogens, since they have the potential to prime both CD4(+) and CD8(+) T cells and are not dependent on patient HLA-type. We have developed a method for production of highly pure recombinant GAGE12I...

  10. Expression of MAGE-A and NY-ESO-1 cancer-testis antigens is enriched in triple-negative invasive breast cancers.

    Science.gov (United States)

    Raghavendra, Ashwini; Kalita-de Croft, Priyakshi; Vargas, Ana Cristina; Smart, Chanel E; Simpson, Peter T; Saunus, Jodi M; Lakhani, Sunil R

    2018-02-21

    A better understanding of the expression of cancer testis antigens (CTA) in breast cancer might identify new immunotherapy options, especially for triple-negative (TN) tumours, which lack expression of conventional therapeutic targets ER, PR and HER2 (receptors for Oestrogen, Progesterone and Human epidermal growth factor). The aim of this study was to quantify the expression of MAGE-A and NY-ESO-1 CTAs in breast cancer, and relate this to known clinicopathologic parameters. We surveyed MAGE-A and NY-ESO-1 protein expression in an unselected cohort of 367 breast tumours (out of which 65 tumours were TN), with accompanying clinical follow-up data, using immunohistochemistry (IHC) analysis of tissue microarrays. Relevant to their potential as vaccine targets in breast cancer, MAGE-A was expressed in 13% of cases, and NY-ESO-1 in 3.8%, with the majority of tumours exhibiting fairly homogeneous staining within individual tissue cores (~85% of cases with staining in >75% tumour cells). Most NY-ESO-1 positive cases also expressed MAGE-A (p=2.06x10 -9 ), and both were strongly associated with the TN phenotype (pESO-1 are frequently expressed in TNBC (~47% and 17% of TN cases, respectively), suggesting that targeting them could be feasible in this patient group. Expression is reasonably homogeneous in positive cases suggesting that IHC analysis of tissue biopsies would be a reliable companion biomarker. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  11. The trophoblast cell surface antigen 2 and miR-125b axis in urothelial bladder cancer.

    Science.gov (United States)

    Avellini, Chiara; Licini, Caterina; Lazzarini, Raffaella; Gesuita, Rosaria; Guerra, Emanuela; Tossetta, Giovanni; Castellucci, Clara; Giannubilo, Stefano Raffaele; Procopio, Antonio; Alberti, Saverio; Mazzucchelli, Roberta; Olivieri, Fabiola; Marzioni, Daniela

    2017-08-29

    Human trophoblast cell surface antigen 2 (Trop-2) is a 40-kDa transmembrane glycoprotein that was first identified as a marker of human trophoblast cells. Trop-2 acts on cell proliferation, adhesion, and migration by activating a number of intracellular signalling pathways. Elevated Trop-2 expression has been demonstrated in several types of cancer and correlated with aggressiveness and poor prognosis. Since no data are available on Trop-2 in bladder cancer (BC), the purpose of the study was to determine its levels in tissue specimens from normal individuals and patients with BC at different stages. Moreover, since according to recent evidence Trop-2 is a miR-125b target, miR-125b expression was also assessed in tissue specimens. Finally, the effect of the Trop-2/miR-125b axis on the proliferation and migration of BC cells was evaluated in vitro. The Trop-2/miR-125b axis was seen to be differentially expressed in normal urothelium, non-invasive BC and invasive BC tissue. Significant miR-125b down-regulation was associated with a significant increase in Trop-2 protein levels in BC tissue and correlated with disease severity. In vitro analysis confirmed the role of miR-125b in down-modulation of Trop-2 protein levels and showed that Trop-2/miR-125b axis affects cellular proliferation in bladder tissue. In conclusion, our findings highlight a role for the Trop-2/miR-125b axis in BC progression and suggest Trop-2 and miR-125b as diagnostic/prognostic marker candidates as well as druggable targets for innovative therapeutic approaches.

  12. Clinical significance and therapeutic potential of prostate cancer antigen-1/ALKBH3 in human renal cell carcinoma.

    Science.gov (United States)

    Hotta, Kiyohiko; Sho, Masayuki; Fujimoto, Kiyohide; Shimada, Keiji; Yamato, Ichiro; Anai, Satoshi; Harada, Hiroshi; Tsujikawa, Kazutake; Konishi, Noboru; Shinohara, Nobuo; Nakajima, Yoshiyuki

    2015-08-01

    Prostate cancer antigen-1 (PCA-1)/ALKBH3 has been recently identified in human prostate cancer and its expression is correlated with disease progression and prognosis. However, the precise role and function of PCA-1/ALKBH3 in human malignancies are largely unknown. In the present study, we investigated the clinical significance and therapeutic potential of PCA-1/ALKBH3 in renal cell carcinoma (RCC). PCA-1/ALKBH3 expression was examined by immunohistochemistry in 101 RCC patients who underwent radical or partial nephrectomy. Its expression was positively correlated with advanced pathological T- and M-factors and TNM stage (T, P<0.05; M, P<0.01; TNM, P<0.01, respectively). In the prognostic analysis, PCA-1/ALKBH3-negative patients with RCC had a significantly better prognosis than PCA-1/ALKBH3-positive patients (5-year survival rate, 92.9 vs. 75.9%, respectively; P<0.05). Next, the therapeutic potential of targeting PCA-1/ALKBH3 was further evaluated by small interfering RNA method using a human RCC cell line (CAKI-1). We found that PCA-1/ALKBH3 knockdown significantly inhibited the growth of CAKI-1 cells compared with the control (P<0.001). Furthermore, knockdown of PCA-1 induced apoptosis in CAKI-1 cells, as assessed by poly(ADP-ribose) polymerase-cleavage assays. We demonstrated for the first time that PCA-1/ALKBH3 expression has a significant prognostic impact on patient prognosis in RCC. Furthermore, its knockdown has a therapeutic efficacy on RCC. Taken together, both our clinical and experimental data strongly suggest that PCA-1/ALKBH3 may be functionally important and a novel molecular target for human RCC.

  13. Predictors of survival in prostate cancer patients with bone metastasis and extremely high prostate-specific antigen levels.

    Science.gov (United States)

    Koo, Kyo Chul; Park, Sang Un; Kim, Ki Hong; Rha, Koon Ho; Hong, Sung Joon; Yang, Seung Choul; Chung, Byung Ha

    2015-03-01

    Prostate-specific antigen (PSA) is a surrogate marker of disease progression; however, its predictive ability in the extreme ranges is unknown. We determined the predictors of survival in patients with bone metastatic prostate cancer (BMPCa) and with extremely high PSA levels. Treatment-naïve patients (n = 248) diagnosed with BMPCa between December 2002 and June 2012 were retrospectively analyzed. Clinicopathological features at diagnosis, namely age, body mass index, serum alkaline phosphatase (ALP) and PSA levels, PSA nadir, time to PSA nadir and its maintenance period, PSA declining velocity, Gleason grade, clinical T stage, pain score, Eastern Cooperative Oncology Group performance score (ECOG PS), and the number of bone metastases were assessed. The patients were stratified according to PSA ranges of bone lesions (P < 0.001). During the follow-up period (median, 39.9 months; interquartile range, 21.5-65.9 months), there were no differences between the groups in terms of the survival endpoints. High ALP levels, shorter time to PSA nadir, and pain were associated with an increased risk of progression to CRPC, and high ALP levels, ECOG PS ≥ 1, and higher PSA nadir independently predicted CSS. PSA response to androgen deprivation therapy and serum ALP are reliable predictors of survival in patients with BMPCa presenting with extremely high PSA levels. These patients should not be deterred from active treatment based on baseline PSA values.

  14. The Role of Prostate-Specific Antigen in Prostate Cancer Screening

    Directory of Open Access Journals (Sweden)

    Constantin Traian Vasile

    2014-06-01

    Full Text Available Cancerul de prostată reprezintă, după cancerul pulmonar, cea mai frecventă afecţiune malignă diagnosticată în cadrul populaţiei masculine. Introducerea în practica curentă în anii 80-90 a determinării Antigenului Specific al Prostatei (PSA seric, ca şi componentă a screeningului pentru cancerul de prostată, a reprezentat un moment de răscruce în practica medicală. Datorită acestei enzime produsă exclusiv de către glanda prostatică, rata detecţiei cancerului de prostată (în stadii curative, intracapsulare s-a îmbunătăţit semnificativ. PSA - ul seric reprezintă un factor predictiv pentru cancerul de prostată (CP mai bun decât tuşeul rectal sau ecografia prostatică transrectală

  15. Efficient in vivo priming by vaccination with recombinant NY-ESO-1 protein and CpG in antigen naive prostate cancer patients.

    Science.gov (United States)

    Karbach, Julia; Neumann, Antje; Atmaca, Akin; Wahle, Claudia; Brand, Kathrin; von Boehmer, Lotta; Knuth, Alexander; Bender, Armin; Ritter, Gerd; Old, Lloyd J; Jäger, Elke

    2011-02-15

    NY-ESO-1, one of the most immunogenic tumor antigens, is expressed in 15% to 25% of metastatic prostate cancers. The immunological and clinical effects of vaccination with recombinant NY-ESO-1 protein combined with CpG as adjuvant were evaluated. In a phase I clinical study, patients with advanced prostate cancer were vaccinated with recombinant NY-ESO-1 protein (100 μg) mixed with CpG 7909 (2.5 mg) every 3 weeks intradermally for 4 doses. Objectives of the study were the safety of the vaccine and changes of specific humoral and cellular immunological responses to NY-ESO-1 in relation to detectable NY-ESO-1 expression in the individual tumor. All 12 baseline sero-negative patients developed high-titer NY-ESO-1 antibody responses. B-cell epitope mapping identified NY-ESO-1 p91-110 to be recognized most frequently by vaccine-induced antibodies. Two patients developed significant antibody titers against the adjuvant CpG. NY-ESO-1-specific CD4+ and/or CD8+ T-cell responses were induced in 9 patients (69%). Five of these 9 patients did not express NY-ESO-1 in the autologous tumor. Postvaccine CD8+ T-cell clones recognized and lyzed HLA-matched tumor cell lines in an antigen-specific manner. Our data provide clear evidence for the capacity of NY-ESO-1 protein/CpG vaccine to induce integrated antigen-specific immune responses in vivo and to efficiently prime CD8+ T-cell responses in NY-ESO-1 antigen-negative patients. Our results may also support further clinical vaccination protocols with NY-ESO-1 protein not only focused on the treatment of existing cancer, but also to prevent further development of NY-ESO-1 positive cancers in vivo. ©2010 AACR.

  16. A Multiplex Cancer/Testis Antigen-Based Biomarker Panel to Predict the Aggressive Phenotype of Prostate Cancer

    Science.gov (United States)

    2016-09-01

    confined to germ cells in normal testis and placenta , but aberrantly expressed in several types of cancers (Scanlan et al, 2004). Unfortunately, their...qRT-PCR 4 3. OVERALL PROJECT SUMMARY Summary of Tasks in SOW Tasks Summarized aims Time Major Task 1 Subtasks 1 and 2 Year 1 CTA gene expression...cells, except by normal testis that is an immune -privileged organ. Also, they are capable of inducing an immune response and though are good targets

  17. A Multiplex Cancer/Testis Antigen-Based Biomarker Panel to Predict Aggressive Phenotype of Prostate Cancer

    Science.gov (United States)

    2015-10-01

    normally confined to germ cells in normal testis and placenta , but aberrantly expressed in several types of cancers (Scanlan et al, 2004...Nanostring 10. qRT-PCR 4 3. OVERALL PROJECT SUMMARY Summary of Tasks in SOW Tasks Summarized aims Time Major Task 1 Subtasks 1 and 2 Year 1 CTA...obtain new TMAs for validation of our biomarkers. In an attempt to determine if CTA expression by the PCa cells can induce cellular mediated immune

  18. Enhanced therapeutic effect using sequential administration of antigenically distinct oncolytic viruses expressing oncostatin M in a Syrian hamster orthotopic pancreatic cancer model.

    Science.gov (United States)

    Nistal-Villan, Estanislao; Bunuales, Maria; Poutou, Joanna; Gonzalez-Aparicio, Manuela; Bravo-Perez, Carlos; Quetglas, Jose I; Carte, Beatriz; Gonzalez-Aseguinolaza, Gloria; Prieto, Jesus; Larrea, Esther; Hernandez-Alcoceba, Ruben

    2015-12-16

    The limited efficacy of current treatments against pancreatic cancer has prompted the search of new alternatives such as virotherapy. Activation of the immune response against cancer cells is emerging as one of the main mechanisms of action of oncolytic viruses (OV). Direct oncolysis releases tumor antigens, and viral replication within the tumor microenvironment is a potent danger signal. Arming OV with immunostimulatory transgenes further enhances their therapeutic effect. However, standard virotherapy protocols do not take full advantage of OV as cancer vaccines because repeated viral administrations may polarize immune responses against strong viral antigens, and the rapid onset of neutralizing antibodies limits the efficacy of redosing. An alternative paradigm based on sequential combination of antigenically distinct OV has been recently proposed. We have developed a protocol consisting of sequential intratumor administrations of new Adenovirus (Ad) and Newcastle Disease Virus (NDV)-based OV encoding the immunostimulatory cytokine oncostatin M (OSM). Transgene expression, toxicity and antitumor effect were evaluated using an aggressive orthotopic pancreatic cancer model in Syrian hamsters, which are sensitive to OSM and permissive for replication of both OVs. NDV-OSM was more cytolytic, whereas Ad-OSM caused higher OSM expression in vivo. Both viruses achieved only a marginal antitumor effect in monotherapy. In addition, strong secretion of OSM in serum limited the maximal tolerated dose of Ad-OSM. In contrast, moderate doses of Ad-OSM followed one week later by NDV-OSM were safe, showed a significant antitumor effect and stimulated immune responses against cancer cells. Similar efficacy was observed when the order of virus administrations was reversed. Sequential administration of oncolytic Ad and NDV encoding OSM is a promising approach against pancreatic cancer.

  19. Diagnostic accuracy of serum antibodies to human papillomavirus type 16 early antigens in the detection of human papillomavirus-related oropharyngeal cancer.

    Science.gov (United States)

    Dahlstrom, Kristina R; Anderson, Karen S; Field, Matthew S; Chowell, Diego; Ning, Jing; Li, Nan; Wei, Qingyi; Li, Guojun; Sturgis, Erich M

    2017-12-15

    Because of the current epidemic of human papillomavirus (HPV)-related oropharyngeal cancer (OPC), a screening strategy is urgently needed. The presence of serum antibodies to HPV-16 early (E) antigens is associated with an increased risk for OPC. The purpose of this study was to evaluate the diagnostic accuracy of antibodies to a panel of HPV-16 E antigens in screening for OPC. This case-control study included 378 patients with OPC, 153 patients with nonoropharyngeal head and neck cancer (non-OPC), and 782 healthy control subjects. The tumor HPV status was determined with p16 immunohistochemistry and HPV in situ hybridization. HPV-16 E antibody levels in serum were identified with an enzyme-linked immunosorbent assay. A trained binary logistic regression model based on the combination of all E antigens was predefined and applied to the data set. The sensitivity and specificity of the assay for distinguishing HPV-related OPC from controls were calculated. Logistic regression analysis was used to calculate odds ratios with 95% confidence intervals for the association of head and neck cancer with the antibody status. Of the 378 patients with OPC, 348 had p16-positive OPC. HPV-16 E antibody levels were significantly higher among patients with p16-positive OPC but not among patients with non-OPC or among controls. Serology showed high sensitivity and specificity for HPV-related OPC (binary classifier: 83% sensitivity and 99% specificity for p16-positive OPC). A trained binary classification algorithm that incorporates information about multiple E antibodies has high sensitivity and specificity and may be advantageous for risk stratification in future screening trials. Cancer 2017;123:4886-94. © 2017 American Cancer Society. © 2017 American Cancer Society.

  20. Ectopic expression of cancer/testis antigen SSX2 induces DNA damage and promotes genomic instability

    DEFF Research Database (Denmark)

    Greve, Katrine Buch Vidén; Lindgreen, Jonas; Terp, Mikkel Green

    2015-01-01

    of senescence (i.e. an irregular and enlarged cell shape, enhanced β-galactosidase activity and DNA double-strand breaks). Since replication defects, DNA damage and senescence are interconnected and well-documented effects of oncogene expression, we tested the oncogenic potential of SSX2. Importantly, knockdown...... in an increased DNA content and enlargement of cell nuclei, suggestive of replication aberrations. The cells further displayed signs of DNA damage and genomic instability, associated with p53-mediated G1 cell cycle arrest and a late apoptotic response. These results suggest a model wherein SSX2-mediated...... replication stress translates into mitotic defects and genomic instability. Arrest of cell growth and induction of DNA double-strand breaks was also observed in MCF7 breast cancer cells in response to SSX2 expression. Additionally, MCF7 cells with ectopic SSX2 expression demonstrated typical signs...

  1. Adsorption according to the Langmuir-Freundlich model is the detection mechanism of the antigen p53 for early diagnosis of cancer.

    Science.gov (United States)

    Soares, Juliana Coatrini; Soares, Andrey Coatrini; Pereira, Paulo Augusto Raymundo; Rodrigues, Valquiria da Cruz; Shimizu, Flavio Makoto; Melendez, Matias Eliseo; Scapulatempo Neto, Cristovam; Carvalho, André Lopes; Leite, Fábio L; Machado, Sergio A S; Oliveira, Osvaldo N

    2016-03-28

    Biosensors for early detection of cancer biomarkers normally depend on specific interactions between such biomarkers and immobilized biomolecules in the sensing units. Though these interactions are expected to yield specific, irreversible adsorption, the underlying mechanism appears not to have been studied in detail. In this paper, we show that adsorption explained with the Langmuir-Freundlich model is responsible for detection of the antigen p53 associated with various types of cancers. Irreversible adsorption was proven between anti-p53 antibodies immobilized on the biosensors and the antigen p53, with the adequacy of the Langmuir-Freundlich model being confirmed with three independent experimental methods, viz. polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), nanogravimetry using a quartz crystal microbalance and electrochemical impedance spectroscopy. The method based on this irreversible adsorption was sufficiently sensitive (limit of detection of 1.4 pg mL(-1)) for early diagnosis of Hodgkin lymphoma, pancreatic and colon carcinomas, and bladder, ovarian and lung cancers, and could distinguish between MCF7 cells containing the antigen p53 from Saos-2 cells that do not contain it.

  2. Preoperative CA125 as a prognostic factor in stage I epithelial ovarian cancer

    DEFF Research Database (Denmark)

    Petri, Anette Lykke; Høgdall, Estrid; Christensen, Ib Jarle

    2006-01-01

    was evaluated and compared with other prognostic factors (age, grade, substages, histologic type). By the Kaplan-Meier estimate we demonstrated that patients with stage I EOC and preoperative serum CA125 levels U/mL had a significantly longer survival compared to stage I EOC patients with preoperative serum...... CA125 > or = 65 U/mL (p=0.01). The results from the present study may be useful for decision making respecting postoperative chemotherapy in stage I EOC patients. Serum CA125 levels might therefore be included as a prognostic factor in future clinical trials of stage I EOC....

  3. Protein expression levels of carcinoembryonic antigen (CEA) in Danish ovarian cancer patients: from the Danish 'MALOVA'ovarian cancer study

    DEFF Research Database (Denmark)

    Hogdall, E.V.; Christensen, L.; Blaakaer, J.

    2008-01-01

    from 189 women diagnosed with low malignant potential ovarian tumours (LMP, borderline ovarian tumours) and 571 women diagnosed with ovarian cancer (OC). RESULTS: Using 30% as the cut-off level for CEA over-expression, 18% of LMPs and 4% of OCs were positive. A higher proportion of mucinous tumours...... (I to IV), the highest CEA expression compared with no expression was found to be a prognostic factor (level 3 versus negative: HR = 2.12, 95%CI 1.11-4.05). FIGO stage, residual tumour after primary surgery, age at diagnosis, other histological types versus serous adenocarcinoma and low versus high...

  4. Ferromagnetic thermal ablation of locally recurrent prostate cancer: prostate specific antigen results and immediate/intermediate morbidities.

    Science.gov (United States)

    Master, Viraj A; Shinohara, Katsuto; Carroll, Peter R

    2004-12-01

    Curative options for locally recurrent prostate cancer following external beam radiotherapy are limited due to the significant morbidity associated with surgical therapy. ThermoRods (Ablation Technologies, San Diego, California) are permanently implantable, 14 mm cobalt-palladium alloy rods that produce heat through oscillation of a magnetic field. The rod is designed to self-regulate the temperature to 70C by a temperature dependent magnetic transition (Curie effect). We determined whether patients with prostate cancer and local failure could be treated with thermal ablation of the prostate using this novel technology. A total of 14 men with an average age of 72 years (range 62 to 81) were enrolled in the study. All had biopsy proven prostate cancer with increasing prostate specific antigen (PSA) (1.0 to 10.3 ng/ml). The seminal vesicles were not routinely biopsied. Metastatic disease was assayed in all men with bone scan and in later patients with abdominopelvic computerized tomography. Patients had ThermoRods placed under transrectal ultrasound guidance, similar to brachytherapy. The pre-plan was rigorously followed to produce a 3-dimensional array with rods separated by 1 cm across the short axis. Patients were treated in a magnetic field for 1 hour. Urethral and rectal temperatures were also monitored and cooled appropriately. Serial PSA measurements and 6 month posttreatment biopsies were obtained after the procedure. Average time since radiation was 4.5 years. PSA nadir values after radiation were between 0.3 and 2.2 ng/ml. Prostatic temperatures were homogeneously increased greater than 50C, while rectal and urethral temperatures did not exceed 44C at any point. The urethral catheter was removed 2 weeks postoperatively in all cases. Six months after the procedure 8 of the 14 men (57%) had a PSA decrease to less than 0.1 ng/ml. Complications included urinary retention as well as incontinence. Incontinence was generally temporary and only 1 patient (7%) had

  5. Development of an Effective Cancer Vaccine Using Attenuated Salmonella and Type III Secretion System to Deliver Recombinant Tumor-Associated Antigens

    Science.gov (United States)

    Xu, Xin; Hegazy, Wael Abdel Halim; Guo, Linjie; Gao, Xiuhua; Courtney, Amy N.; Kurbanov, Suhrab; Liu, Daofeng; Tian, Gengwen; Manuel, Edwin R.; Diamond, Don J.; Hensel, Michael; Metelitsa, Leonid S.

    2014-01-01

    One of the major limitations of modern cancer vaccine vectors is that, unlike infectious pathogens, to which the immune system has evolved to respond, they are not sufficiently effective in delivering tumor-associated antigens (TAAs) in an immunogenic form to intact professional antigen-presenting cells (APCs) at their anatomic location. To overcome this challenge, we exploited Salmonella Pathogenicity Island 2 (SPI2) and its type III secretion system (T3SS) to deliver a TAA of choice into the cytosol of APCs in situ. We have systematically compared candidate genes from the SPI2 locus of Salmonella typhimurium in the vaccine design, using model antigens and a codon-optimized human TAA, survivin (coSVN). In a screen of 20 SPI2 promoter/effector combinations, the PsifB::sseJ pair demonstrated the maximal potency for antigen translocation in the APC cytosol, presentation to CD8 T cells, and immunogenicity in mice. Therapeutic vaccination with the PsifB::sseJ-coSVN construct (p8032) resulted in CXCR3-dependent tumor infiltration with CD8 T cells, reversal of the CD8:Treg ratio at the tumor site, and potent anti-tumor activity in a CT26 colon carcinoma model. The vaccine’s immunogenicity and anti-tumor potency were further enhanced by co-administration of an NKT-cell ligand, 7WD8-5, which strongly enhanced production of IL-12 and IFNγ in vaccinated mice. Furthermore, therapeutic vaccination with p8032/7WD8-5 resulted in complete tumor regression in an A20 lymphoma model, with the generation of protective memory. Thus, oral antigen delivery via SPI2-encoded T3SS of Salmonella may be the foundation for an effective cancer vaccine platform. PMID:25213323

  6. The TF-antigen binding lectin from Sclerotium rolfsii inhibits growth of human colon cancer cells by inducing apoptosis in vitro and suppresses tumor growth in vivo.

    Science.gov (United States)

    Inamdar, Shashikala R; Savanur, Mohammed Azharuddin; Eligar, Sachin M; Chachadi, Vishwanath B; Nagre, Nagaraja N; Chen, Chen; Barclays, Monica; Ingle, Aravind; Mahajan, Praveen; Borges, Anita; Shastry, Padma; Kalraiya, Rajiv D; Swamy, Bale M; Rhodes, Jonathan M; Yu, Lu-Gang

    2012-09-01

    Glycan array analysis of Sclerotium rolfsii lectin (SRL) revealed its exquisite binding specificity to the oncofetal Thomsen-Friedenreich (Galβ1-3GalNAcα-O-Ser/Thr, T or TF) antigen and its derivatives. This study shows that SRL strongly inhibits the growth of human colon cancer HT29 and DLD-1 cells by binding to cell surface glycans and induction of apoptosis through both the caspase-8 and -9 mediated signaling. SRL showed no or very weak binding to normal human colon tissues but strong binding to cancerous and metastatic tissues. Intratumor injection of SRL at subtoxic concentrations in NOD-SCID mice bearing HT29 xenografts resulted in total tumor regression in 9 days and no subsequent tumor recurrence. As the increased expression of TF-associated glycans is commonly seen in human cancers, SRL has the potential to be developed as a therapeutic agent for cancer.

  7. Auranofin, an anti-rheumatic gold compound, modulates apoptosis by elevating the intracellular calcium concentration ([ca2+]I) in mcf-7 breast cancer cells.

    Science.gov (United States)

    Varghese, Elizabeth; Büsselberg, Dietrich

    2014-11-06

    Auranofin, a transition metal complex is used for the treatment of rheumatoid arthritis but is also an effective anti-cancer drug. We investigate the effects of Auranofin in inducing cell death by apoptosis and whether these changes are correlated to changes of intracellular calcium concentration ([Ca2+]i) in breast cancer cells (MCF-7). Cytotoxicity of Auranofin was evaluated using MTS assay and the Trypan blue dye exclusion method. With fluorescent dyes SR-FLICA and 7-AAD apoptotic death and necrotic death were differentiated by Flow cytometry. A concentration dependent decrease in the viability occurred and cells were shifted to the apoptotic phase. Intracellular calcium ([Ca2+]i) was recorded using florescence microscopy and a calcium sensitive dye (Fluo-4 AM) with a strong negative correlation (r = -0.713) to viability. Pharmacological modulators 2-APB (50 μM), Nimodipine (10 μM), Caffeine (10 mM), SKF 96365(20 μM) were used to modify calcium entry and release. Auranofin induced a sustained increase of [Ca2+]i in a concentration and time dependent manner. The use of different blockers of calcium channels did not reveal the source for the rise of [Ca2+]i. Overall, elevation of [Ca2+]i by Auranofin might be crucial for triggering Ca2+-dependent apoptotic pathways. Therefore, in anti-cancer therapy, modulating [Ca2+]i should be considered as a crucial factor for the induction of cell death in cancer cells.

  8. Auranofin, an Anti-Rheumatic Gold Compound, Modulates Apoptosis by Elevating the Intracellular Calcium Concentration ([Ca2+]i in MCF-7 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Elizabeth Varghese

    2014-11-01

    Full Text Available Auranofin, a transition metal complex is used for the treatment of rheumatoid arthritis but is also an effective anti-cancer drug. We investigate the effects of Auranofin in inducing cell death by apoptosis and whether these changes are correlated to changes of intracellular calcium concentration ([Ca2+]i in breast cancer cells (MCF-7. Cytotoxicity of Auranofin was evaluated using MTS assay and the Trypan blue dye exclusion method. With fluorescent dyes SR-FLICA and 7-AAD apoptotic death and necrotic death were differentiated by Flow cytometry. A concentration dependent decrease in the viability occurred and cells were shifted to the apoptotic phase. Intracellular calcium ([Ca2+]i was recorded using florescence microscopy and a calcium sensitive dye (Fluo-4 AM with a strong negative correlation (r = −0.713 to viability. Pharmacological modulators 2-APB (50 μM, Nimodipine (10 μM, Caffeine (10 mM, SKF 96365(20 μM were used to modify calcium entry and release. Auranofin induced a sustained increase of [Ca2+]i in a concentration and time dependent manner. The use of different blockers of calcium channels did not reveal the source for the rise of [Ca2+]i. Overall, elevation of [Ca2+]i by Auranofin might be crucial for triggering Ca2+-dependent apoptotic pathways. Therefore, in anti-cancer therapy, modulating [Ca2+]i should be considered as a crucial factor for the induction of cell death in cancer cells.

  9. EGFR gene copy number predicts response to anti-EGFR treatment in RAS wild type and RAS/BRAF/PIK3CA wild type metastatic colorectal cancer.

    Science.gov (United States)

    Ålgars, Annika; Sundström, Jari; Lintunen, Minnamaija; Jokilehto, Terhi; Kytölä, Soili; Kaare, Milja; Vainionpää, Reetta; Orpana, Arto; Österlund, Pia; Ristimäki, Ari; Carpen, Olli; Ristamäki, Raija

    2017-02-15

    Anti-EGFR antibodies are used for the treatment of RAS wild type metastatic colorectal cancer. We previously showed that EGFR gene copy number (GCN) predicts response to anti-EGFR therapy in KRAS exon 2 wild type metastatic colorectal cancer. The aim of our study was to analyse the predictive role of EGFR GCN in RAS/BRAF/PIK3CA wild type metastatic colorectal cancer. The material included 102 patients with KRAS exon 2 wild type metastatic colorectal cancer treated with anti-EGFR ± cytotoxic therapy. Next generation sequencing was used for KRAS, NRAS, BRAF and PIK3CA gene mutation analyses. EGFR GCN was analysed by EGFR immunohistochemistry guided automated silver in situ hybridisation. Increased EGFR GCN (≥4.0) predicted a better response and prolonged progression free survival in anti-EGFR treated RAS/BRAF/PIK3CA wild type patients (Log-rank test, p = 0.0004). In contrast, survival of RAS/BRAF/PIK3CA wild type, EGFR GCN below 4.0 patients did not differ from patients with mutant RAS, BRAF or PIK3CA. Our study indicates that EGFR GCN predicts anti-EGFR treatment efficacy in patients with RAS/BRAF/PIK3CA wt metastatic CRC. Tumours with EGFR GCN below 4.0 appear to be as refractory to anti-EGFR treatment as tumours with mutation in any of the RAS/RAF/PIK3CA pathway genes. © 2016 UICC.

  10. Performance of seven criteria to assess CA125 increments among ovarian cancer patients monitored during first-line chemotherapy and the post-therapy follow-up period

    DEFF Research Database (Denmark)

    Abu Hassan, Suher O; Nielsen, Dorte L; Tuxen, Malgorzata K

    2017-01-01

    AIM: To investigate seven CA125 criteria to monitor progressive ovarian cancer among patients with stage IC-IV disease. MATERIALS & METHODS: Four criteria were used to asses CA125 increments starting from concentrations ≥35 U/ml and three criteria to asses increments starting from concentrations...... U/ml. RESULTS: A total of 231 patients were allocated to CA125 monitoring. The performances of the CA125 criteria were similar with sensitivities of 30-55%, negative predictive values of 28-46%, positive predictive values of 90-100% and median lead times of 26-87 days. CONCLUSION: The criteria...

  11. MAGE-A10 cancer/testis antigen is highly expressed in high-grade non-muscle-invasive bladder carcinomas.

    Science.gov (United States)

    Mengus, Chantal; Schultz-Thater, Elke; Coulot, Julie; Kastelan, Zeljko; Goluza, Eleonora; Coric, Marijana; Spagnoli, Giulio C; Hudolin, Tvrtko

    2013-05-15

    Bladder cancer is a common urinary malignancy and a prevalent cause of cancer-related death. Current therapies of early stage non-muscle-invasive bladder cancer (NMIBC) are frequently associated with undesirable toxicities and recurrence. Active antigen-specific immunotherapy may provide a valid therapeutic option for patients with NMIBC. Cancer-testis antigens (CTA) expressed in various tumour types and in a limited range of healthy tissues may represent potential targets for specific immunotherapy. MAGE-A10 is probably the most immunogenic antigen of the MAGE-A family. We evaluated the expression of MAGE-A10 in NMIBC. Seventy-nine patients undergoing surgical treatment for NMIBC were enrolled in the study. MAGE-A10 gene expression was assessed by quantitative real-time polymerase chain reaction. Immunohistochemistry was performed on paraffin-embedded sections. MAGE-A10 gene was specifically expressed in one-third of NMIBC (n = 24: 32.43%). Gene expression was correlated with high tumour grade. MAGE-A10 protein was exclusively detectable in nuclei of tumour cells. More importantly, MAGE-A10 protein was also more frequently detectable in high-grade tumours (p = 0.0001) and in stage T1 tumours invading subepithelial tissue or lamina propria (p = 0.01). A strong correlation between MAGE-A10 staining score and tumour grade and stage could accordingly be observed. These data indicate that MAGE-A10 expression is a feature of aggressive NMIBC and might be used as a novel target for specific immunotherapy of these cancers. Copyright © 2012 UICC.

  12. The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Nader Al Nakouzi

    2012-05-01

    Full Text Available Bone metastases have a devastating impact on quality of life and bone pain in patients with prostate cancer and decrease survival. Animal models are important tools in investigating the pathogenesis of the disease and in developing treatment strategies for bone metastases, but few animal models recapitulate spontaneous clinical bone metastatic spread. In the present study, IGR-CaP1, a new cell line derived from primary prostate cancer, was stably transduced with a luciferase-expressing viral vector to monitor tumor growth in mice using bioluminescence imaging. The IGR-CaP1 tumors grew when subcutaneously injected or when orthotopically implanted, reconstituted the prostate adenocarcinoma with glandular acini-like structures, and could disseminate to the liver and lung. Bone lesions were detected using bioluminescence imaging after direct intratibial or intracardiac injections. Anatomic bone structure assessed using high-resolution computed tomographic scans showed both lytic and osteoblastic lesions. Technetium Tc 99m methylene diphosphonate micro single-photon emission computed tomography confirmed the mixed nature of the lesions and the intensive bone remodeling. We also identified an expression signature for responsiveness of IGR-CaP1 cells to the bone microenvironment, namely expression of CXCR4, MMP-9, Runx2, osteopontin, osteoprotegerin, ADAMTS14, FGFBP2, and HBB. The IGR-CaP1 cell line is a unique model derived from a primary tumor, which can reconstitute human prostate adenocarcinoma in animals and generate experimental bone metastases, providing a novel means for understanding the mechanisms of bone metastasis progression and allowing preclinical testing of new therapies.

  13. Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer

    DEFF Research Database (Denmark)

    Kristiansen, Søren; Jørgensen, Lars Mønster; Høgh Hansen, Morten

    2015-01-01

    The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the ...

  14. Annual surveillance by CA125 and transvaginal ultrasound for ovarian cancer in both high-risk and population risk women is ineffective

    DEFF Research Database (Denmark)

    Woodward, E R; Sleightholme, H V; Considine, A M

    2007-01-01

    OBJECTIVE: To assess the efficacy of annual CA125 and transvaginal ultrasound (TVU) scan as surveillance for ovarian cancer. DESIGN: Retrospective audit. SETTING: NHS Trust. POPULATION: Three hundred and forty-one asymptomatic women enrolled for ovarian cancer screening: 179 were in a high-risk g...

  15. Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer*

    Science.gov (United States)

    Young, Christian D.; Zimmerman, Lisa J.; Hoshino, Daisuke; Formisano, Luigi; Hanker, Ariella B.; Gatza, Michael L.; Morrison, Meghan M.; Moore, Preston D.; Whitwell, Corbin A.; Dave, Bhuvanesh; Stricker, Thomas; Bhola, Neil E.; Silva, Grace O.; Patel, Premal; Brantley-Sieders, Dana M.; Levin, Maren; Horiates, Marina; Palma, Norma A.; Wang, Kai; Stephens, Philip J.; Perou, Charles M.; Weaver, Alissa M.; O'Shaughnessy, Joyce A.; Chang, Jenny C.; Park, Ben Ho; Liebler, Daniel C.; Cook, Rebecca S.; Arteaga, Carlos L.

    2015-01-01

    Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K) have been shown to transform human mammary epithelial cells (MECs). These mutations are present in all breast cancer subtypes, including basal-like breast cancer (BLBC). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 72 protein expression changes in human basal-like MECs with knock-in E545K or H1047R PIK3CA mutations versus isogenic MECs with wild-type PIK3CA. Several of these were secreted proteins, cell surface receptors or ECM interacting molecules and were required for growth of PIK3CA mutant cells as well as adjacent cells with wild-type PIK3CA. The proteins identified by MS were enriched among human BLBC cell lines and pointed to a PI3K-dependent amphiregulin/EGFR/ERK signaling axis that is activated in BLBC. Proteins induced by PIK3CA mutations correlated with EGFR signaling and reduced relapse-free survival in BLBC. Treatment with EGFR inhibitors reduced growth of PIK3CA mutant BLBC cell lines and murine mammary tumors driven by a PIK3CA mutant transgene, all together suggesting that PIK3CA mutations promote tumor growth in part by inducing protein changes that activate EGFR. PMID:25953087

  16. Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer.

    Science.gov (United States)

    Young, Christian D; Zimmerman, Lisa J; Hoshino, Daisuke; Formisano, Luigi; Hanker, Ariella B; Gatza, Michael L; Morrison, Meghan M; Moore, Preston D; Whitwell, Corbin A; Dave, Bhuvanesh; Stricker, Thomas; Bhola, Neil E; Silva, Grace O; Patel, Premal; Brantley-Sieders, Dana M; Levin, Maren; Horiates, Marina; Palma, Norma A; Wang, Kai; Stephens, Philip J; Perou, Charles M; Weaver, Alissa M; O'Shaughnessy, Joyce A; Chang, Jenny C; Park, Ben Ho; Liebler, Daniel C; Cook, Rebecca S; Arteaga, Carlos L

    2015-07-01

    Mutations in PIK3CA, the gene encoding the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K) have been shown to transform human mammary epithelial cells (MECs). These mutations are present in all breast cancer subtypes, including basal-like breast cancer (BLBC). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we identified 72 protein expression changes in human basal-like MECs with knock-in E545K or H1047R PIK3CA mutations versus isogenic MECs with wild-type PIK3CA. Several of these were secreted proteins, cell surface receptors or ECM interacting molecules and were required for growth of PIK3CA mutant cells as well as adjacent cells with wild-type PIK3CA. The proteins identified by MS were enriched among human BLBC cell lines and pointed to a PI3K-dependent amphiregulin/EGFR/ERK signaling axis that is activated in BLBC. Proteins induced by PIK3CA mutations correlated with EGFR signaling and reduced relapse-free survival in BLBC. Treatment with EGFR inhibitors reduced growth of PIK3CA mutant BLBC cell lines and murine mammary tumors driven by a PIK3CA mutant transgene, all together suggesting that PIK3CA mutations promote tumor growth in part by inducing protein changes that activate EGFR. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Comparison of cancer stem cell antigen expression by tumor cell lines and by tumor biopsies from dogs with melanoma and osteosarcoma.

    Science.gov (United States)

    Guth, Amanda M; Deogracias, Mike; Dow, Steven W

    2014-10-15

    Cancer stem cells (CSCs) represent a small subpopulation of tumor cells that play a critical role in initiating and sustaining tumor growth. However, we currently have an incomplete understanding of the expression patterns of CSC antigens in tumors of dogs, nor do we understand how expression of these antigens vary between tumor cell lines and tumor biopsy specimens. Therefore, we used flow cytometry and commonly reported CSC surface and intracellular markers to evaluate the phenotype and overall frequency of CSC subpopulations in tumor cell lines and primary tumor biopsy samples from dogs with melanoma and osteosarcoma. We found that cells expressing common CSC antigens were rare in tumor cell lines, with the exception of tumor cells expressing CD44 and CD90. In contrast, tumor cells expressing conventional CSC antigens such as CD133, CD34, CD44, CD24 and Oct3/4 were much more common in tumor biopsy samples. Notably, the frequency and types of putative CSC subpopulations were very similar in biopsy samples from dogs with either melanoma or osteosarcoma. Our results suggest that the tumor microenvironment significantly influences CSC subpopulations within tumors and that tumor cell lines may not accurately reflect the actual frequency or types of CSC subpopulations present in tumor tissues in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. SKF-96365 activates cytoprotective autophagy to delay apoptosis in colorectal cancer cells through inhibition of the calcium/CaMKIIγ/AKT-mediated pathway.

    Science.gov (United States)

    Jing, Zhao; Sui, Xinbing; Yao, Junlin; Xie, Jiansheng; Jiang, Liming; Zhou, Yubin; Pan, Hongming; Han, Weidong

    2016-03-28

    Store-operated Ca(2+) entry (SOCE) inhibitors are emerging as an attractive new generation of anti-cancer drugs. Here, we report that SKF-96365, an SOCE inhibitor, exhibits potent anti-neoplastic activity by inducing cell-cycle arrest and apoptosis in colorectal cancer cells. In the meantime, SKF-96365 also induces cytoprotective autophagy to delay apoptosis by preventing the release of cytochrome c (cyt c) from the mitochondria into the cytoplasm. Mechanistically, SKF-96365 treatment inhibited the calcium/calmodulin-dependent protein kinase IIγ (CaMKIIγ)/AKT signaling cascade in vitro and in vivo. Overexpression of CaMKIIγ or AKT abolished the effects of SKF-96365 on cancer cells, suggesting a critical role of the CaMKIIγ/AKT signaling pathway in SFK-96365-induced biological effects. Moreover, Hydroxychloroquine (HCQ), an FDA-approved drug used to inhibit autophagy, could significantly augment the anti-cancer effect of SFK-96365 in a mouse xenograft model. To our best knowledge, this is the first report to demonstrate that calcium/CaMKIIγ/AKT signaling can regulate apoptosis and autophagy simultaneously in cancer cells, and the combination of the SOCE inhibitor SKF-96365 with autophagy inhibitors represents a promising strategy for treating patients with colorectal cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Association of pretreatment serum carcinoembryonic antigen levels with chemoradiation-induced downstaging and downsizing of rectal cancer.

    Science.gov (United States)

    Yeo, Seung-Gu

    2016-04-01

    The aim of this study was to identify pretreatment clinical parameters associated with preoperative chemoradiotherapy (CRT)-induced downstaging and downsizing of locally advanced rectal cancer (LARC T3-4 or N+). Data from 51 LARC patients, who received preoperative CRT and radical surgery between 2010 and 2013, were retrospectively analyzed. Rectal adenocarcinoma was histologically confirmed in all patients, who ranged in age between 41 and 81 years (median, 64 years). CRT consisted of 50.4 Gy pelvic radiotherapy with concurrent chemotherapy using 5-fluorouracil and leucovorin. After a median interval of 7 weeks post-CRT, the patients underwent total mesorectal excision. Downstaging was defined as the transition from cStage II-III to ypStage 0-I. The longest tumor diameter was measured pre- and post-CRT using computed tomography or magnetic resonance imaging, and based on the surgical specimen, respectively. Downstaging was observed in 16 (31.4%) patients, including 5 (9.8%) with a pathological complete response. The median downsizing rate was 60%. The serum carcinoembryonic antigen (CEA) levels were 0.8-153.9 ng/ml (median, 4.4 ng/ml). The maximum standardized uptake value was 4.7-33.9 (median, 10.8). On univariate analysis, cT stage, tumor size and CEA level were associated with downstaging. On multivariate analysis, only CEA level (≤5 ng/ml) was a significant predictor of downstaging (odds ratio = 16.0; 95% confidence interval: 1.8-146.7; P=0.014). CEA level was the only factor significantly associated with downsizing (>60%) in the univariate analysis. These results demonstrated that pretreatment serum CEA levels are significantly associated with downstaging as well as downsizing of LARC following preoperative CRT. Therefore, this parameter may be useful in personalizing the management of LARC patients.

  20. Prostate-specific antigen flare induced by cabazitaxel-based chemotherapy in patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Angelergues, Antoine; Maillet, Denis; Fléchon, Aude; Ozgüroglu, Mustafa; Mercier, Florence; Guillot, Aline; Le Moulec, Sylvestre; Gravis, Gwenaelle; Beuzeboc, Philippe; Massard, Christophe; Fizazi, Karim; de La Motte Rouge, Thibault; Delanoy, Nicolas; Elaidi, Reza-Thierry; Oudard, Stéphane

    2014-06-01

    A prostate-specific antigen (PSA) flare occurs in about 15% of metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel. This flare has no standard definition. Its impact on treatment efficacy is unclear. We sought to evaluate the incidence and characteristics of PSA flare on cabazitaxel, and its impact on survival. Multicentre retrospective review of consecutive patients treated with cabazitaxel second-line chemotherapy for mCRPC. Collection of baseline characteristics, disease history and PSA levels before and during cabazitaxel therapy. Overall survival (OS) and radiological/clinical progression-free survival (PFS) for patient groups corresponding to different definitions of PSA flare estimated by the Kaplan-Meier method and compared using the log-rank test. Overall, 125 patients were included. Median PFS and OS were 6.5 and 13.3 months, respectively. Depending upon the definition used, flare incidence ranged from 8.3% to 30.6%. The flare lasted <2.6 months. A PSA flare followed by a ⩾ 50% decrease was associated with a median PFS and OS of 11.2 and 25.2 months, respectively. Median PFS and OS for a ⩾ 30% rather than ⩾ 5 0% decrease were 10.4 and 16.5 months. These outcomes were not significantly different from those in patients with immediate PSA decreases of ⩾ 50% or ⩾ 30% from baseline, but were significantly better than in patients experiencing no PSA decrease (p = 0.006 and 0.015, respectively, for OS). The PSA response to cabazitaxel, with or without initial flare, was associated with a strong survival benefit. The taxane-induced flare during the first 12 weeks of therapy can be ignored when evaluating PSA response. Copyright © 2014. Published by Elsevier Ltd.

  1. Serological response to Epstein-Barr virus early antigen is associated with gastric cancer and human immunodeficiency virus infection in Zambian adults: a case-control study.

    Science.gov (United States)

    Kayamba, Violet; Monze, Mwaka; Asombang, Akwi Wasi; Zyambo, Kanekwa; Kelly, Paul

    2016-01-01

    Gastric cancer is one of the major causes of cancer related deaths, but data from sub-Saharan Africa are very scanty. The cancer genome atlas (TCGA) initiative confirmed Epstein-Barr virus (EBV) related cancer as a distinct subtype, and we set out to look for serological evidence of its role in a sub-Saharan African patient group. We used stored serum samples obtained from a gastric cancer case-control study conducted between 2010 and 2012 in Lusaka, Zambia. A total of 147 patients were included with 51 gastric adenocarcinoma cases and 96 age and sex matched controls. The presence of antibodies to EBV nuclear antigen-1 (EBNA-1) and early antigen (EA) was determined using commercially available ELISA kits. Data were analysed in STATA Stata Corp, College Station TX. Over 90% of all the samples analysed were positive for antibodies to EBNA-1. The presence of antibodies to EBV EA was significantly higher in gastric cancer cases than in controls, (OR 4.38; 95% CI 1.53-13.06, P = 0.0027), with an attributable risk of 23%. HIV infection was also associated with EBV EA seroprevalence (OR 10.97; 95% CI 2.26 -13.06, P = 0.001) but not EBNA-1 (OR 0.81; 95% CI 0.10 -38.75, P = 0.596). There was no association of EBV infection with age below 45 years, Helicobacter pylori infection, intestinal metaplasia, gastric atrophy or inflammation. We therefore conclude that EBV exposure is common among Zambian adults and that EBV EA seropositivity is associated with gastric cancer and HIV infection, but not premalignant lesions.

  2. The cancer-testis antigen NY-ESO-1 is highly expressed in myxoid and round cell subset of liposarcomas.

    Science.gov (United States)

    Hemminger, Jessica A; Ewart Toland, Amanda; Scharschmidt, Thomas J; Mayerson, Joel L; Kraybill, William G; Guttridge, Denis C; Iwenofu, O Hans

    2013-02-01

    Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n=15): myxoid and round cell (n=8); well-differentiated (n=4), and dedifferentiated (n=3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n=44): myxoid and round cell (n=18); well-differentiated (n=10); dedifferentiated (n=10); and pleomorphic (n=6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1-3+), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2-3+ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1+ intensity in 50% of cells; 2+ intensity in 5% of cells; and 3+ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3+ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this

  3. Screening for prostate cancer using prostate-specific antigen alone as a first-line checkup parameter: results of the health checkup system.

    Science.gov (United States)

    Uchida, K; Takeshima, H; Akaza, H; Ono, Y

    2000-02-01

    The incidence of prostate cancer in Japan is not very high but it is the most increasing malignant tumor form. To decrease the mortality from cancer, detection of early cancer and early treatment are most effective. As a primary screening for prostate cancer, measurement of serum prostate-specific antigen(PSA) added to the health checkup system has not been assessed. Among males who received a health checkup during a 30-month period, serum PSA levels were measured in males who desired prostate cancer screening. The cut-off value for PSA was 4.0 ng/ml. Males with serum PSA levels exceeding this value were referred for further screening by digital rectal examination (DRE) and transrectal ultrasonography (TRUS). In secondary screening, in all males with PSA levels of 10.0 ng/ml or more and in males in whom PSA levels were within the gray zone (4.0-10.0 ng/ml) and either DRE or TRUS showed abnormal findings, systematic prostate sextant needle biopsy was performed. Of 24528 males who received a health checkup, 1125 (4.6%) underwent prostate cancer screening. In 60 (5.3%) of these males, PSA levels exceeded the cut-off value. In 34 of 50 males who received further screening, prostate biopsy was performed. Seventeen males were diagnosed as having prostate cancer. Detection rates of prostate cancer were 1.53% (17/1125) in males overall and 2.1% (17/819) in males > or =50 years old. In 16 of 17 males, clinically localized cancer was suggested. In 12 of these patients, radical prostatectomy was performed. No lymph node metastasis was detected in any patient. These results suggest that prostate cancer screening using PSA as a primary screening parameter during general health checkups is very useful for efficiently detecting early-stage prostate cancer.

  4. Single-step antigen loading and maturation of dendritic cells through mRNA electroporation of a tumor-associated antigen and a TriMix of costimulatory molecules.

    Science.gov (United States)

    Benteyn, Daphné; Van Nuffel, An M T; Wilgenhof, Sofie; Bonehill, Aude

    2014-01-01

    Dendritic cells (DC) are key players in several types of cancer vaccines. Large numbers of DC can easily be generated in closed systems from the monocyte fraction of the peripheral blood. They are the professional antigen-presenting cells, and electroporation of mRNA-encoding tumor antigens is a very efficient and a relatively simple way to load the DC with antigen. The co-electroporation of a tumor antigen of choice and the combination of 3 costimulatory molecules, including CD70, caTLR4, and CD40L (TriMix-DC), leads to fully potent antigen-presenting DC able to generate a broad immune response.Here we describe the in vitro transcription of the mRNA and the subsequent generation and electroporation of autologous DC used for the treatment of melanoma patients.

  5. High expressions of BCL6 and Lewis y antigen are correlated with high tumor burden and poor prognosis in epithelial ovarian cancer.

    Science.gov (United States)

    Zhu, Liancheng; Feng, Huilin; Jin, Shan; Tan, Mingzi; Gao, Song; Zhuang, Huiyu; Hu, Zhenhua; Wang, Huimin; Song, Zuofei; Lin, Bei

    2017-07-01

    Aberrant regulation of BCL6 plays crucial oncogenic roles in various malignant tumors; howbeit, the function of BCL6 in tumorigenesis of ovarian cancer remains unclear. The aim of this study is to investigate the role of BCL6 in ovarian cancer. The methods of immunohistochemical staining, quantitative real-time polymerase chain reaction, immunocytochemical staining, and gene expression profile enrichment analysis were performed to identify the possible role of BCL6 in ovarian cancer. We observed that the expression of BCL6 was significantly higher in ovarian cancer tissues and correlated with higher tumor burden including advanced International Federation of Gynecology and Obstetrics stages, poor differentiation, Type II ovarian cancer, the presence of >1 cm residual tumor size, and appearance of recurrence or death (all p 1 cm, as well as high expressions of BCL6 and Lewis y antigen were independent factors of worse progression-free survival and overall survival (all p ovarian cancer and targeting BCL6 could be a novel therapeutic strategy for ovarian cancer treatment.

  6. Prostate Cancer in Patients With High Prostate-Specific Antigen Levels but Otherwise Very-Low-Risk Disease Behaves Like Prostate Cancer in High-Risk Patients.

    Science.gov (United States)

    Gestaut, Matthew M; Pruszynski, Jessica E; Swanson, Gregory P

    2017-08-01

    Rarely, patients with prostate cancer present with prostate-specific antigen (PSA) scores > 20 ng/mL but with otherwise very-low-risk disease. Oncologists have debated whether the malignancies in these patients behave more comparably to low-risk or high-risk disease. Our objective was to elucidate the behavior of these malignancies. A retrospective review was conducted of prostate cancer patients treated with radiation from 2000 to 2013. The inclusion criteria for very-low-risk disease included stage T1a-T1c, Gleason score ≤ 6, ≤ 3 positive cores, ≤ 50% involvement of any core, and PSA level high-grade, low-volume group consisted of patients with stage T1c-T2a, PSA level high-grade groups, respectively. Biochemical progression-free survival at 5 years was 71.3% for the divergent group, 68.8% for the high-grade group, and 98.3% for the low-risk group. The biochemical failure rate for the divergent group differed significantly from the low-risk group (P = .021), and that for the low-risk group was significantly different from that of the high-grade group (P = .025). However, the divergent group did not appear different from the high-grade group (P = .53). The results of our study have shown that the disease prognosis for the divergent-risk group is worse than that for the very-low-risk disease group and does not appear to be different from that for the low-volume, high-grade disease group. Oncologists should be aware that the outcomes for divergent patients are similarly poor to their low-volume, classically high-risk counterparts. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. An adenoviral cancer vaccine co-encoding a tumor associated antigen together with secreted 4-1BBL leads to delayed tumor progression

    DEFF Research Database (Denmark)

    Ragonnaud, Emeline; Andersson, Anne-Marie C; Pedersen, Anders Elm

    2016-01-01

    ) in a replicative deficient adenovirus vaccine expressing the invariant chain (Ii) adjuvant fused to a tumor associated antigen (TAA). The Ii adjuvant increases and prolongs TAA specific CD8+ T cells as previously shown and local expression of 4-1BBL was chosen to avoid the toxicity associated with systemic...... presenting cells, but it did not enhance T cell responses in mice towards the Ii linked antigen. In tumor-bearing mice, our vaccine was found to decrease the frequency of TAA specific CD8+ T cells, but this difference did not alter the therapeutic efficacy. In order to reconcile our findings...... with the previous reports of increased anti-cancer efficacy using systemically delivered 4-1BB agonists, we incorporated a secreted version of 4-1BBL (Fc-4-1BBL) in our vaccine and co-expressed it with the Ii linked to TAA. In tumor bearing mice, this vaccine initially delayed tumor growth and slightly increased...

  8. Interaction of proliferation cell nuclear antigen (PCNA with c-Abl in cell proliferation and response to DNA damages in breast cancer.

    Directory of Open Access Journals (Sweden)

    Huajun Zhao

    Full Text Available Cell proliferation in primary and metastatic tumors is a fundamental characteristic of advanced breast cancer. Further understanding of the mechanism underlying enhanced cell growth will be important in identifying novel prognostic markers and therapeutic targets. Here we demonstrated that tyrosine phosphorylation of the proliferating cell nuclear antigen (PCNA is a critical event in growth regulation of breast cancer cells. We found that phosphorylation of PCNA at tyrosine 211 (Y211 enhanced its association with the non-receptor tyrosine kinase c-Abl. We further demonstrated that c-Abl facilitates chromatin association of PCNA and is required for nuclear foci formation of PCNA in cells stressed by DNA damage as well as in unperturbed cells. Targeting Y211 phosphorylation of PCNA with a cell-permeable peptide inhibited the phosphorylation and reduced the PCNA-Abl interaction. These results show that PCNA signal transduction has an important impact on the growth regulation of breast cancer cells.

  9. All care, but whose responsibility? Community juries reason about expert and patient responsibilities in prostate-specific antigen screening for prostate cancer.

    Science.gov (United States)

    Degeling, Chris; Carter, Stacy M; Rychetnik, Lucie

    2016-09-01

    General practitioners have implicitly been given responsibility for guiding men's decisions about prostate-specific antigen-based screening for prostate cancer, but patients' expectations of the bounds of this responsibility remain unclear. We sought to explore how well-informed members of the public allocate responsibilities in prostate-specific antigen screening decision-making. In 2014, we convened two Community juries in Sydney, Australia, to address questions related to the content and timing of information provision and respective roles of patients and general practitioners in screening decisions. Participants in the first jury were of mixed gender and of all ages (n = 15); the participants in the second jury were all male and of screening age (n = 12). Both juries were presented with balanced factual evidence on the harms and benefits of prostate-specific antigen screening and expert perspectives on ethico-legal aspects of consent in medical practice. In their deliberations, jurors agreed that general practitioners should take responsibility for informing men of the options, risks and benefits of prostate-specific antigen testing, but arrived at different positions on whether or not general practitioners should also guide screening decisions. Jurors also disagreed on how much and when general practitioners should provide detailed information about biopsies and treatments. These responses suggest that for prostate-specific antigen testing, there is a public expectation that both the allocation of responsibility between general practitioners and their male patients, and the level of information provided will be tailored to individual men. In the presence of expert uncertainty, a well-informed public may have reason to embrace or resist shared decision-making processes. © The Author(s) 2016.

  10. PIK3CA gene alterations in bladder cancer are frequent and associate with reduced recurrence in non-muscle invasive tumors.

    Science.gov (United States)

    Dueñas, Marta; Martínez-Fernández, Mónica; García-Escudero, Ramón; Villacampa, Felipe; Marqués, Miriam; Saiz-Ladera, Cristina; Duarte, José; Martínez, Victor; Gómez, M José; Martín, M Luisa; Fernández, Manoli; Castellano, Daniel; Real, Francisco X; Rodriguez-Peralto, Jose L; De La Rosa, Federico; Paramio, Jesús M

    2015-07-01

    Bladder cancer (BC) is the fifth most common cancer in the world, being the non-muscle invasive tumors (NMIBC) the most frequent. NMIBC shows a very high frequency of recurrence and, in certain cases, tumor progression. The phosphatidylinositol 3-kinase (PI3K) pathway, which controls cell growth, tumorigenesis, cell invasion and drug response, is frequently activated in numerous human cancers, including BC, in part through alterations of PIK3CA gene. However, the significance of PIK3CA gene alterations with respect to clinicopathological characteristics, and in particular tumor recurrence and progression, remains elusive. Here, we analyzed the presence of mutations in FGFR3 and PIK3CA genes and copy number alterations of PIK3CA gene in bladder tumor and their correspondent paired normal samples from 87 patients. We observed an extremely high frequency of PIK3CA gene alterations (mutations, copy gains, or both) in tumor samples, affecting primarily T1 and T2 tumors. A significant number of normal tissues also showed mutations and copy gains, being coincident with those found in the corresponding tumor sample. In low-grade tumors PIK3CA mutations associated with FGFR3 mutations. Alterations in PIK3CA gene resulted in increased Akt activity in tumors. Interestingly, the presence of PIK3CA gene alterations, and in particular gene mutations, is significantly associated with reduced recurrence of NMIBC patients. Importantly, the presence of FGFR3 mutations may influence the clinical outcome of patients bearing alterations in PIK3CA gene, and increased recurrence was associated to FGFR3 mutated, PIK3CA wt tumors. These findings may have high relevance in terms of using PI3K-targeted therapies for BC treatment. © 2013 Wiley Periodicals, Inc.

  11. Performance of the prostate cancer antigen 3 (PCA3) gene and prostate-specific antigen in prescreened men: exploring the value of PCA3 for a first-line diagnostic test.

    Science.gov (United States)

    Roobol, Monique J; Schröder, Fritz H; van Leeuwen, Pim; Wolters, Tineke; van den Bergh, Roderick C N; van Leenders, Geert J L H; Hessels, Daphne

    2010-10-01

    The performance characteristics of serum prostate-specific antigen (PSA) as a diagnostic test for prostate cancer (PCa) are poor. The performance of the PCa antigen 3 (PCA3) gene as a primary diagnostic is unknown. Assess the value of PCA3 as a first-line diagnostic test. Participants included men aged 63-75 who were invited for rescreening in the period from September 2007 to February 2009 within the European Randomised Study of Screening for Prostate Cancer, Rotterdam section. Lateral sextant biopsies were performed if the serum PSA value was > or =3.0 ng/ml and/or the PCA3 score was > or =10. Measurements included distribution and correlation of PSA value and PCA3 score and their relation to the number of cases and the characteristics of PCa detected. Additional value of PCA3 was included in men with previous negative biopsy and/or PSA or =3.0 ng/ml misses 64.7% of the total PCa that can be detected with the sextant biopsy technique and 57.9% of serious PCa (T2a or higher and/or Gleason grade > or =4, n=19), and 68.2% of biopsies could have been avoided; the respective data for PCA3 > or =35 are 32%, 26.3%, and 51.7%. Performance of PCA3 in men with low PSA (area under the curve [AUC]: 0.63) and/or previous negative biopsy (AUC: 0.68) is unclear but has limited reliability due to small numbers. PCA3 as a first-line screening test shows improvement of the performance characteristics and identification of serious disease compared with PSA in this prescreened population. Copyright 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  12. Improvement of protein immobilization for the elaboration of tumor-associated antigen microarrays: application to the sensitive and specific detection of tumor markers from breast cancer sera.

    Science.gov (United States)

    Yang, Zhugen; Chevolot, Yann; Géhin, Thomas; Solassol, Jérôme; Mange, Alain; Souteyrand, Eliane; Laurenceau, Emmanuelle

    2013-02-15

    There is an urgent need to identify relevant tumor markers showing high sensitivity and specificity for early diagnosis and prognosis of breast cancer. Protein microarrays have demonstrated to be cost-effective, high through-put and powerful tools for screening and identifying tumor markers with only minute samples. Autoantibodies directed against tumor-associated antigens (TAAs) were shown to be relevant tumor markers. However, due to the variability of immune response from one individual to another and depending on the type of cancer, detection of only one type of anti-TAA autoantibody is not sufficient to give a reliable and precise diagnosis. It is necessary to use a set of several TAAs for determining specific autoimmune profiles. Therefore, combining various TAAs on different surfaces could improve sensitivity and specificity for anti-TAA autoantibody detection. Herein a panel of 10 proteins, including well-known tumor-associated antigens (TAAs) and potential new biomarkers of breast cancer, were immobilized onto microstructured microarray under optimized conditions (spotting pH buffer, surface chemistry, blocking procedure), in order to determine an autoimmune signature of breast cancer. Sera from 29 breast cancer patients and 28 healthy donors were screened in sandwich immunoassays on the miniaturized system to detect the eventual presence of anti-TAAs autoantibodies. Results indicated that the detection level of each anti-TAA autoantibody in a given serum sample was strongly dependant on the surface chemistry. Combining five TAAs (p53, Hsp60, Hsp70, Her2-Fc, NY-ESO-1) on two different surface chemistries (NHS and APDMES) allowed the significant detection of more than 82% breast cancer sera. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Alpha 2HS-glycoprotein, a tumor-associated antigen (TAA) detected in Mexican patients with early-stage breast cancer.

    Science.gov (United States)

    Fernández-Grijalva, A L; Aguilar-Lemarroy, A; Jave-Suarez, L F; Gutiérrez-Ortega, A; Godinez-Melgoza, P A; Herrera-Rodríguez, S E; Mariscal-Ramírez, I; Martínez-Velázquez, M; Gawinowicz, M A; Martínez-Silva, M G; Cruz-Ramos, J A; Hernández-Gutiérrez, R

    2015-01-01

    Several studies have demonstrated that the serum of patients with cancer contains antibodies that react with a group of autoantigens denominated tumor-associated antigens (TAA). TAA can be detected prior to clinical diagnosis; thus, they would be ideal biomarkers for early detection of cancer, using only a few microliters of a patient's serum. In the current study, we used an immune proteomic approach, combining two-dimensional (2D) electrophoresis, Western blot, and matrix-associated laser desorption/ionization-mass spectrometry (MALDI-MS) methods to identify TAA in the sera of patients diagnosed with breast cancer. Sera were obtained from 36 newly diagnosed patients with stage II breast cancer and those from 36 healthy volunteers were evaluated for the presence of the TAA. Alpha 2HS-glycoprotein (AHSG) antibodies were detected in 33 of 36 patients with breast cancer (91.7%) and in only 3 of 36 healthy patients (controls, 8.3%). Sensitivity of detection of autoantibodies against AHSG in patients with breast cancer was 91.7%. AHSG was detected in cancer tissue by immunohistochemistry. Our results strongly suggest that the presence of serum autoantibodies against AHSG protein may be useful as serum biomarkers for early-stage breast cancer screening and minimally invasive diagnosis in Mexican populations. In the present study, 2D immunoblot analysis was used to make a screening in samples of sera from patients with a diagnosis of early-stage breast cancer, in order to identify some autoantibodies that react against TAA. Proteins identified in the present study, particularly alpha 2HS-glycoprotein (AHSG), might be useful as potential biomarkers for breast cancer in early stages for Mexican populations. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Development of E-info gene(ca): a website providing computer-tailored information and question prompt prior to breast cancer genetic counseling.

    Science.gov (United States)

    Albada, Akke; van Dulmen, Sandra; Otten, Roel; Bensing, Jozien M; Ausems, Margreet G E M

    2009-08-01

    This article describes the stepwise development of the website 'E-info gene(ca)'. The website provides counselees in breast cancer genetic counseling with computer-tailored information and a question prompt prior to their first consultation. Counselees generally do not know what to expect from genetic counseling and they tend to have a passive role, receiving large amounts of relatively standard information. Using the "intervention mapping approach," we developed E-info gene(ca) aiming to enhance counselees' realistic expectations and participation during genetic counseling. The information on this website is tailored to counselees' individual situation (e.g., the counselee's age and cancer history). The website covers the topics of the genetic counseling process, breast cancer risk, meaning of being a carrier of a cancer gene mutation, emotional consequences and hereditary breast cancer. Finally, a question prompt encourages counselees to prepare questions for their genetic counseling visit.

  15. The histocompatibility antigen in asbestos related disease.

    Science.gov (United States)

    Al Jarad, N; Uthayakumar, S; Buckland, E J; Green, T S; Ord, J; Newland, A C; Rudd, R M

    1992-12-01

    Thirty nine phenotypes of human leucocyte antigens (HLA)-A-B-DR and DQ were obtained from 99 asbestos workers (one woman and 98 men). Presence or absence of antinuclear antibodies and rheumatoid factor was determined in 91 of them. Workers were divided into five groups: asbestos workers with no apparent disease (AW; n = 17), diffuse benign pleural disease (PD; n = 31), asbestosis (AS; n = 24), asbestosis with lung cancer (AS-CA; n = 14), and mesothelioma (M; n = 13). Compared with AW, several trends of differences of HLA antigen prevalence were found in patients with asbestos related disease, but these did not achieve statistical significance when p was corrected (pcorr) by number of analyses undertaken. Analysis of the results obtained in previous studies together with the results of this study showed that compared with AW, AS patients had decreased prevalence of HLA-DR5 (pcorr < 0.02). Reasons for the differences in results of previous studies and statistical methods commonly used to compare prevalences of HLA antigen are discussed.

  16. Accuracy of the prostate health index versus the urinary prostate cancer antigen 3 score to predict overall and significant prostate cancer at initial biopsy.

    Science.gov (United States)

    Seisen, Thomas; Rouprêt, Morgan; Brault, Didier; Léon, Priscilla; Cancel-Tassin, Géraldine; Compérat, Eva; Renard-Penna, Raphaële; Mozer, Pierre; Guechot, Jérome; Cussenot, Olivier

    2015-01-01

    It remains unclear whether the Prostate Health Index (PHI) or the urinary Prostate-Cancer Antigen 3 (PCA-3) score is more accurate at screening for prostate cancer (PCa). The aim of this study was to prospectively compare the accuracy of PHI and PCA-3 scores to predict overall and significant PCa in men undergoing an initial prostate biopsy. Double-blind assessments of PHI and PCA-3 were conducted by referent physicians in 138 patients who subsequently underwent trans-rectal ultrasound-guided prostate biopsy according to a 12-core scheme. Predictive accuracies of PHI and PCA-3 were assessed using AUC and compared according to the DeLong method. Diagnostic performances with usual cut-off values for positivity (i.e., PHI >40 and PCA-3 >35) were calculated, and odds ratios associated with predicting PCa overall and significant PCa as defined by pathological updated Epstein criteria (i.e., Gleason score ≥7, more than three positive cores, or >50% cancer involvement in any core) were estimated using logistic regression. Prevalences of overall and significant PCa were 44.9% and 28.3%, respectively. PCA-3 (AUC = 0.71) was the most accurate predictor of PCa overall, and significantly outperformed PHI (AUC = 0.65; P = 0.03). However, PHI (AUC = 0.80) remained the most accurate predictor when screening exclusively for significant PCa and significantly outperformed PCA-3 (AUC = 0.55; P = 0.03). Furthermore, PCA-3 >35 had the best accuracy, and positive or negative predictive values when screening for PCa overall whereas these diagnostic performances were greater for PHI >40 when exclusively screening for significant PCa. PHI > 40 combined with PCA-3 > 35 was more specific in both cases. In multivariate analyses, PCA-3 >35 (OR = 5.68; 95%CI = [2.21-14.59]; P 40 (OR = 9.60; 95%CI = [1.72-91.32]; P = 0.001) was the only independent predictor for detecting significant PCa. Although PCA-3 score is the best predictor for PCa

  17. Hidden IgG Antibodies to the Tumor-Associated Thomsen-Friedenreich Antigen in Gastric Cancer Patients: Lectin Reactivity, Avidity, and Clinical Relevance

    Science.gov (United States)

    Kurtenkov, Oleg

    2017-01-01

    Natural antibodies to the tumor-associated Thomsen-Friedenreich antigen (TF) are related to tumor immunosurveillance and cancer patients' survival. Hidden IgG antibodies (HAbs) to TF, their lectin reactivity, avidity, and clinical relevance were studied. HAbs were present in cancer patients and controls. A decreased level of IgG HAbs was detected in cancer. The HAbs level positively correlated with the sialospecific SNA lectin binding in purified total IgG (tIgG) in donors and cancer patients, indicating that HAbs are higher sialylated. The avidity of anti-TF IgG in tIgG samples was lower in cancer patients (P = 0.025) while no difference in the avidity of free anti-TF IgG was established. A negative correlation between the avidity of anti-TF IgG in tIgG and SNA binding in both groups was observed (P IgG avidity in tIgG only in donors (P = 0.003). Changes in the level of HAbs and Abs avidity showed a rather good stage- and gender-dependent diagnostic accuracy. Cancer patients with a lower anti-TF IgG avidity in tIgG showed a benefit in survival. Thus the TF-specific HAbs represent a particular subset of anti-TF IgG that differ from free serum anti-TF IgG in SNA reactivity, avidity, diagnostic potential, and relation to survival. PMID:28316982

  18. Increased Sialylation of Anti-Thomsen-Friedenreich Antigen (CD176 Antibodies in Patients with Gastric Cancer: A Diagnostic and Prognostic Potential

    Directory of Open Access Journals (Sweden)

    Oleg Kurtenkov

    2014-01-01

    Full Text Available Aim. To study whether alterations in the sialylation of antibodies (Ab specific to the Thomsen-Friedenreich (TF glycotope have a diagnostic and prognostic potential in gastric cancer. Methods. Serum samples were taken from patients with gastric carcinoma (n=142 and controls (n=61. The level of TF-specific antibodies and their sialylation was detected using ELISA with synthetic TF-polyacrylamide conjugate as antigen and sialic acid-specific Sambucus nigra agglutinin (SNA. Results. The level of TF-specific IgM was significantly decreased in cancer compared with controls (P≤0.001. Cancer patients showed a higher level of SNA binding to anti-TF IgM and IgA (P≤0.001 irrespective of disease stage, tumor morphology, and gender. Changes in the SNA/Ab index demonstrated moderate sensitivity (66–71% and specificity (60–73% for stomach cancer. The best diagnostic accuracy (100% was achieved in 29% patients with high SNA binding and low anti