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Sample records for cancer antigen ca

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

    Science.gov (United States)

    ... as a tumor marker : To help differentiate between cancer of the pancreas and other conditions, such as pancreatitis To monitor ... levels of CA 19-9 are seen in cancer of the exocrine pancreas. This cancer arises in the tissues that produce ...

  2. Independent prognostic value of preoperative serum markers CA 242, specific tissue polypeptide antigen and human chorionic gonadotrophin beta, but not of carcinoembryonic antigen or tissue polypeptide antigen in colorectal cancer.

    OpenAIRE

    Carpelan-Holmström, M; Haglund, C.; Lundin, J; Alfthan, H.; Stenman, U H; Roberts, P. J.

    1996-01-01

    The prognostic value of preoperative serum concentrations of carcinoembryonic antigen (CEA), CA 242, tissue polypeptide antigen (TPA), specific tissue polypeptide antigen (TPS) and human chorionic gonadotrophin beta (hCG beta) in 251 patients with colorectal cancer (39 Dukes' A, 98 Dukes' B, 56 Dukes' C and 58 Dukes' D) was investigated. When using the cut-off levels recommended for diagnostic purposes, there was a significantly longer overall survival in patients with low tumour marker level...

  3. 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

    1997-01-01

    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 le

  4. Monitoring the response of breast cancer to radiotherapy and adjuvant therapy using breast cancer antigen CA 15-3

    International Nuclear Information System (INIS)

    In this study 35 breast cancer patients were followed during their treatment in Radiation and Isotope Center of Khartoum (RICK) using breast cancer antigen CA 15-3 as an indicator of tumor marker. They were classified into three categories of CA 15-3 concentration level as stated by Colomer and Genolla (1989) as follows: normal level less than 40 UI/ml, moderate level more than 40 UI/ml and less than 60 UI/ml, and high level, more than 60 UI/ml to 3000 UI/ml. A 5 ml of venous blood samples' were collected using sterile syringes from patients with different stage of breast cancer. The sample size were thirty-five cases, one of the cases is rejected because the patient discontinued the treatment. The blood samples were collected as follows: before starting the treatment course, at the mid time of treatment course, after completion the treatment course, and after one month of completion of the treatment course. The patients classified into two groups according to their treatment protocol. The first group received only external radiation therapy treatment and those were 18 patients out of 35, while the second group received combined therapy and those were 16 patients out of 35. For those whom received external radiation radiation therapy only, the results showed that the mean value of CA 15-3 concentration level decreased at the mid of the treatment as follows: 26±3 UI/ml, 24±3 UI/ml, 22±3 UI/ml respectively, while the mean value of CA 15-3 concentration level before starting the treatment was found to be 46±14 UI/ml. The number of the patients in the normal concentration level of CA 15-3 increased by 11% at the mid of external radiotherapy treatment and by 13% at the mid combined therapy, while the moderate level decreased by 6% for both external radiotherapy and combined therapy, while the number of patients within the high level decreased by 5% for external radiotherapy and 7% for combined therapy. After completion and after one month of completion of external

  5. A novel antibody-like material for breast cancer antigen CA15-3, used to track breast cancer by potentiometric transduction

    OpenAIRE

    Santos, Alexandra R. T.; Moreira, Felismina T. C.; Sales, M. Goreti F.

    2012-01-01

    This work presents the development of a low cost sensor device for the diagnosis of breast cancer in point-of-care, made with new synthetic biomimetic materials inside plasticized poly(vinyl chloride), PVC, membranes, for subsequent potentiometric detection. This concept was applied to target a conventional biomarker in breast cancer: Breast Cancer Antigen (CA15-3). The new biomimetic material was obtained by molecularly-imprinted technology. In this, a plastic antibody was obtained by pol...

  6. Combination of cancer antigen 125 and carcinoembryonic antigen can improve ovarian cancer diagnosis

    DEFF Research Database (Denmark)

    Sørensen, Sofie Sølvsten; Mosgaard, Berit Jul

    2011-01-01

    The purpose of the present study was to evaluate the ability of the tumour marker carcinoembryonic antigen (CEA) in combination with cancer antigen 125 (CA-125) to differentiate between malignant ovarian and malignant non-ovarian disease.......The purpose of the present study was to evaluate the ability of the tumour marker carcinoembryonic antigen (CEA) in combination with cancer antigen 125 (CA-125) to differentiate between malignant ovarian and malignant non-ovarian disease....

  7. 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

  8. 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 of...

  9. 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...... 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...

  10. The immunoradiometric assay for carbohydrate antigen CA-242

    International Nuclear Information System (INIS)

    Using 125I-labelled monoclonal antibody (C242) against carbohydrate antigen CA-242, the sandwich immunoradiometric assay (IRMA) was developed. In preliminary clinical application of this method, the results of serum CA-242 measurements were 2.5 ± 4.5 U/ml for 77 normal individuals, 3.5 ± 7.0 U/ml for 128 cases of benign diseases, and 56.0 ± 91.3 U/ml for 210 cases of malignant tumors. The CA-242 values of patients with malignant tumors were significantly higher than that of patients with benign diseases. Taking 12 U/ml as normal upper limit, the positive detective rates of pancreatic and colorectal cancers were 86.6% and 62.0% respectively, while the false positive rate for normal individuals was 4%

  11. A prospective study of serum tumour markers carcinoembryonic antigen, carbohydrate antigens 50 and 242, tissue polypeptide antigen and tissue polypeptide specific antigen in the diagnosis of pancreatic cancer with special reference to multivariate diagnostic score.

    OpenAIRE

    Pasanen, P. A.; Eskelinen, M.; Partanen, K.; Pikkarainen, P; Penttilä, I.; Alhava, E

    1994-01-01

    The aim of this study was to assess by a stepwise multivariate discriminant analysis the value of four current serum tumour markers - carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 50 and CA 242 and tissue polypeptide antigen (TPA) - and a new serum tumour marker, tissue polypeptide specific antigen (TPS), in the diagnosis of pancreatic cancer. The serum values were measured in a prospective series of patients with jaundice, with unjaundiced cholestasis and with a suspicion of chro...

  12. Levels of estrogen, carcinoembryonic antigen and cancer antigen of breast in breast cancer patients

    International Nuclear Information System (INIS)

    This study was conducted during the period from february 2004 to July 2004; with the objective of measuring the levels of estrogen (E2), carcinoembryonic antigen (CEA) and cancer antigen of breast (CA-15.3) so as to facilitate the early diagnosis of breast cancer and determine the involvement of these parameters as risk factors for breast cancer. Ninety blood samples were collected from Sudanese females, divided into two groups; control group and patient groups. The patients group was sixty Sudanese females visiting the Radio Isotope Center, Khartoum (RICK) and they were confirmed as breast cancer patient by histopathology. The levels of the above mentioned parameters were determined by using radioimmunoassay technique. The results showed that, no significant (p=0.05) difference between the levels of the estrogen in patients compared to the control, on the other hand there was non significant (p>0.05) elevation in CEA levels in the patients with breast cancer compared to the control. The level of CA15.3 was significantly (p<0.0001) higher in the breast cancer patients compared to the control.(Author)

  13. Combined detection of preoperative serum CEA, CA19-9 and CA242 improve prognostic prediction of surgically treated colorectal cancer patients

    OpenAIRE

    Wang, Jingtao; Xiao WANG; Yu, Fudong; Chen, Jian; Zhao, Senlin; Zhang, Dongyuan; YU, Yang; Liu, Xisheng; Tang, Huamei; Peng, Zhihai

    2015-01-01

    We assessed the prognostic significance of preoperative serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 242 (CA242) levels in surgically treated colorectal cancer patients. The relationship of preoperative serum CEA, CA19-9 and CA242 levels with disease characteristics was investigated in 310 patients. Correlation between tumor markers was investigated using Pearson correlation test. Univariate and multivariate survival analyses were used to s...

  14. Activity profile of the CA125 antigen towards human red blood cells

    Directory of Open Access Journals (Sweden)

    Mitić N.

    2010-01-01

    Full Text Available Starting from the mucin nature of the CA125 antigen and conditions associated with high serum concentrations, this study is an attempt to gain insight into its activity profile towards human erythrocytes. Carcinomaassociated and pregnancy-associated CA125 antigens were tested in agglutination/aggregation, adhesion and hemolysis assays. The results obtained indicated that CA125 antigens increased agglutination/aggregation and inhibited erythrocyte adhesion, but differed in their effective concentrations. Galectin-1 slightly modulated the effects observed. CA125 antigens had no effect on hemolysis. The activity profile of the CA125 antigen towards erythrocytes may have biomedical consequences in different microenvironments in relevant physiological and pathophysiological conditions.

  15. 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 family. Seru

  16. Monoclonal antibodies recognizing epitopes of calretinins: dependence on Ca2+-binding status and differences in antigen accessibility in colon cancer cells.

    Science.gov (United States)

    Zimmermann, L; Schwaller, B

    2002-01-01

    Monoclonal antibodies are very helpful tools to investigate the localization and sometimes even the function of specific proteins in cells and tissues. By generating monoclonal antibodies against calretinin-22k (CR-22k), a C-terminally truncated isoform of calretinin (CR) as a result of alternative splicing of the CR mRNA, we envisaged that screening multiple monoclonal antibodies would allow the identification of CR-22k as well as CR. Both proteins share the first 178 amino acids, but have different C-termini. All three antibodies 10C10, 6B3 and 2H4 recognize recombinant CR-22k and the specificity to also recognize CR was demonstrated in brain extracts of different species and human tumour cells, which express CR. All monoclonal antibodies did not crossreact with the closely related protein calbindin D-28k. Antibody binding was depending on the Ca2+-binding status of both forms of calretinin. Generally, the Ca2+-bound form was better recognized than the Ca2+-free form. Carboxy- and amino-terminally truncated CR proteins were expressed in E. coli in order to characterize the epitopes recognized by the three antibodies. Additionally, tryptic and cyanogen bromide fragments were produced to further narrow down the sequences recognized by the three antibodies. 10C10 recognizes an epitope consisting of the linker region between EF-hand domains I and II and the N-terminal part of EF-hand II, while the others (6B3, 2H4) bind to a region including the linker between EF-hand domains III and IV. These antibodies are valuable tools to further investigate the distribution and eventually the specific function of these two proteins in the nervous tissue and under pathological conditions, e.g. in colon tumours and mesotheliomas. PMID:11990296

  17. Receiver operating characteristic (ROC) curve analysis of the tumour markers CEA, CA 50 and CA 242 in pancreatic cancer; results from a prospective study.

    OpenAIRE

    Pasanen, P. A.; Eskelinen, M.; Partanen, K.; Pikkarainen, P; Penttilä, I.; Alhava, E

    1993-01-01

    The serum values of the tumour markers carcinoembryonic antigen (CEA), cancer-associated carboanhydrate antigens CA 50 and CA 242 were evaluated in 193 patients with hepatopancreato-biliary diseases by receiver operating characteristic (ROC) curve analysis in order to compare their diagnostic accuracy in pancreatic cancer (n = 26), and to define optimal cut-off levels for the serum values of these tumour markers in the diagnosis of pancreatic cancer. The ROC analysis showed that all marker te...

  18. Tissue expression of the tumour associated antigen CA242 in benign and malignant pancreatic lesions. A comparison with CA 50 and CA 19-9.

    OpenAIRE

    Haglund, C.; Lindgren, J.; Roberts, P. J.; Kuusela, P.; Nordling, S.

    1989-01-01

    The expression of a novel tumour associated antigen CA 242, defined by the monoclonal antibody C 242, was studied by immunoperoxidase staining in formalin-fixed, paraffin-embedded tissue sections from normal pancreata, pancreata with pancreatitis and benign and malignant pancreatic neoplasms. The antigenic determinant of the C 242 antibody is a sialylated carbohydrate structure, related but chemically different from tumour marker antigens CA 19-9 and CA 50. Thirty-eight of 41 (93%) well to mo...

  19. New tumor-associated antigen SC6 in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Min-Pei Liu; Xiao-Zhong Guo; Jian-Hua Xu; Di Wang; Hong-Yu Li; Zhong-Min Cui; Jia-Jun Zhao; Li-Nan Ren

    2005-01-01

    AIM: To examine the concentration of a new antigen SC6 (SC6-Ag) recognized by monoclonal antibody (MAb)in patients with pancreatic cancer and other malignant or benign diseases and to understand whether SC6-Ag has any clinical significance in distinguishing pancreatic cancer from other gastrointestinal diseases.METHODS: Six hundred and ninety-five serum specimens obtained from 115 patients with pancreatic cancer, 154 patients with digestive cancer and 95patients with non-digestive cancer were used and classified in this study. Serum specimens obtained from 140 patients with benign digestive disease and 89 patients with non-benign digestive disease served as controls. Ascites was tapped from 16 pancreatic cancer patients, 19 hepatic cancer patients, 16 colonic cancer patients, 10 gastric cancer and 6 severe necrotic pancreatitis patients. The samples were quantitated by solid-phase radioimmunoassay. The cut-off values (CV)of 41, 80, and 118 U/mL were used.RESULTS: The average intra- and interassay CV detected by immunoradiometric assay of SC6-Ag was 5.4% and 8.7%, respectively. The sensitivity and specificity were 73.0% and 90.9% respectively. The levels in most malignant and benign cases were within the normal upper limit. Among the 16 pancreatic cancer cases, the concentration of SC6-Ag in ascites was over the normal range in 93.8% patients. There was no significant difference in the concentration of SC6-Ag.Decreased expression of SC6-Ag in sera was significantly related to tumor differentiation. The concentration of SC6-Ag was higher in patients before surgery than after surgery. The specificity of SC6-Ag and CA19-9 was significantly higher than that of ultrasound and computer tomography (CT) in pancreatic cancer patients. Higher positive predictive values were indicated in 92.3% SC6-Ag and 88.5% CA19-9, but lower in 73.8% ultrasound and 76.2% CT.CONCLUSION: The combined test of SC6-Ag and CA19-9 may improve the diagnostic rate of primary cancer. The detection of

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

    OpenAIRE

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

    1993-01-01

    CA 242, a novel tumour carbohydrate antigen present in serum (upper limit of normal values: 20.0 U ml-1), has been measured in a group of 102 pathologically confirmed non-small cell lung cancer patients. The aim of the present prospective study was to identify any relationship between pre-treatment serum CA 242 level and different features of lung cancer including prognosis. Serum CA 242 was measured using the delayed europium lanthanide fluoroimmunometric assay. Sensitivity and specificity w...

  1. Basophil response to antigen and anti-IgE 3. Ca(2+) influx and histamine release

    OpenAIRE

    Tanizaki,Yoshiro; Kitani,Hikaru; Okazaki, Morihiro; Mifune, Takashi; Mitsunobu, Fumihiro; Kimura,Ikuro

    1992-01-01

    The release mechanism of chemical mediators from basophils and mast cells was discussed when these cells were stimulated by different antigens and anti-IgE. 1. Ca(2+) influx into mast cells increased after stimulation by antigen. The increased Ca(2+) uptake by mast cells was inhibited by antiallergic agents, disodium cromoglycate (DSCG) and tranilast, and calcium antagonists, nifedipine and nicardipine. 2. The dose-response curve of histamine release by antigen was different from that by anti...

  2. 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.

  3. Characterization of Ewing sarcoma associated cancer/testis antigens

    OpenAIRE

    Mahlendorf, Dorothea E.; Staege, Martin Sebastian

    2013-01-01

    The prognosis of patients suffering from tumors of the Ewing family (EFT) is still poor. Immunotherapy strategies are pursued and EFT-specific antigens have to be identified as targets for cytotoxic T-lymphocytes (CTL). Due to the lack of expression of cancer/testis antigens (CTA) in normal tissues, these antigens are partially able to induce immune responses in cancer patients. Therefore, they are promising targets for immunotherapy. EFT are characterized by chromosomal rearrangements involv...

  4. 78 FR 11895 - Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer...

    Science.gov (United States)

    2013-02-20

    ...-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..., gastric cancer, kidney cancer, liver cancer, lung cancer, ovarian......

  5. CD133 antigen expression in ovarian cancer

    International Nuclear Information System (INIS)

    Much attention has been recently focused on the role of cancer stem cells (CSCs) in the initiation and progression of solid malignancies. Since CSCs are able to proliferate and self-renew extensively, thus sustaining tumor growth, the identification of CSCs through their antigenic profile might have relevant clinical implications. In this context, CD133 antigen has proved to be a marker of tumor cells with stemness features in several human malignancies. The aim of the study was to investigate the clinical role of the immunohistochemically assessed expression of CD133 in a large single Institution series of ovarian cancer patients. The study included 160 cases admitted to the Gynecologic Oncology Unit, Catholic University of Campobasso and Rome. CD133 antigen was identified by the monoclonal mouse anti-CD133-1 antibody (clone CD133 Miltenyi biotec). In the overall series CD133 positive tumor cells were observed in 50/160 (31.2%) cases. A diffuse cytoplasmic pattern was identified in 30/50 (60.0%), while an apical cytoplasmic pattern was found in 20/50 (40.0%) of CD133 positive tumors. As of September 2008, the median follow up was 37 months (range: 2–112). During the follow up period, progression and death of disease were observed in 123 (76.9%), and 88 (55.0%) cases, respectively. There was no difference in TTP between cases with negative (median TTP = 23 months) versus positive CD133 expression (median TTP = 24 months) (p value = 0.3). Similar results were obtained for OS. When considering the TTP and OS curves according to the pattern of CD133 expression, a trend to a worse prognosis for cases with diffuse cytoplasmic versus the apical cytoplasmic pattern was documented, although the statistical significance was not reached. The immunohistochemical assessment of CD133 expression seems not to provide additional prognostic information in ovarian cancer patients. The role of the different pattern of CD133 immunoreaction deserves further investigation in a larger

  6. Quantitative autoradiography measurement of CA-MoV18 antigen concentration in ovarian carcinomas

    International Nuclear Information System (INIS)

    Concentrations of CA-MoV18 antigen in ovarian tumor and normal ovarian tissue samples were measured. Quantitative autoradiography was performed in 33 ovarian tissue samples with radiolabeled MoV18 monoclonal antibodies. Among them 22 samples were ovarian carcinomas, 7 samples were benign ovarian tumors and 4 samples were normal ovarian tissues. Among 19 serous ovarian carcinomas, 17 had MoV 18 antigen expression, ranging from 1.30 to 59.28 pmol/g tissue, 3 mutinous ovarian carcinomas and 11 nonmalignant ovaries (7 benign tumors and 4 normal tissues) were not detectable MoV 18 antigen. CA-MoV18 antigen was expressed in serous ovarian carcinomas. The concentration of CA-MoV 18 antigen was correlated with labelled antibodies (%ID/g) in tumor tissue

  7. A meta-analysis of serum cancer antigen 125 array for diagnosis of ovarian cancer in Chinese

    OpenAIRE

    Xiao-Yan Liao; Guo-Jun Huang; Chao Gao; Guang-Hong Wang

    2014-01-01

    Objective: To further evaluation the diagnosis accuracy of serum cancer antigen 125 (CA125) in the diagnosis of ovarian cancer in Chinese patients. Materials and Methods: The PubMed, Wanfang and CNKI databases were electric searched and relevant diagnosis trials were reviewed and finally included in this meta-analysis. The diagnosis sensitivity, specificity, positive likely hood ratio (+LR), negative likely hood ratio (−LR), diagnostic odds ratio (DOR) and receiver operating characteristi...

  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...... synergistic effect of combining CG antigen immunotherapeutic strategies with epigenetic modifiers. WHAT THE READER WILL GAIN: The reader will gain an overview of the past, present and future role of CG antigens in cancer immunotherapy. TAKE HOME MESSAGE: Chemoimmunotherapy using epigenetic drugs and CG...

  9. Localisation of Ca and HMFG2 antigens in breast tissue by immunoperoxidase, immunofluorescence, and immunoelectron microscopy.

    OpenAIRE

    Beckford, U; Barbatis, C; Beesley, J E; Linsell, J C; Chantler, S. M.

    1985-01-01

    The reactivities of Ca1 and HMFG2 monoclonal antibodies were compared on paraffin wax embedded breast tissues using indirect immunoperoxidase. The expression of Ca antigen, like HMFG2, is not exclusive to malignancy: Ca was present in 41/53 (77%) and HMFG2 in 42/53 (79.2%) non-malignant conditions and both were present in 33/35 (94%) carcinomas. Similar results were obtained when cryostat sections were used. Both antigens showed striking similarities in their topographical distributions, alth...

  10. Cancer Antigen-125 as a Marker of Ascites in Patients with Liver Cirrhosis

    International Nuclear Information System (INIS)

    Objective: To evaluate the correlation between Cancer Antigen-25 (CA-125) levels with the amount of ascites in patients with liver cirrhosis. Study Design: Observational, analytical study. Place and Duration of Study: Shifa International Hospital, Islamabad, from March 2012 to February 2013. Methodology: A total of 130 patients with liver cirrhosis (with and without ascites) had serum CA-125 levels measured. The amount of ascites was classified according to physical examination and ultrasound (USG) findings. CA-125 levels were compared and correlated with amount of ascites. Results: Majority of patients (57%) had hepatitis C virus and 60% were in class Child Pugh C. There was moderate correlation between amount of ascites and CA-125 levels (r = 0.642, p < 0.001) with significant raised levels of CA-125 in patients with ascites (p < 0.001). Conclusion: There was a moderate correlation between CA-125 levels and presence and amount of ascites. (author)

  11. Distribution of the Ca (Oxford) antigen in lung neoplasms and non-neoplastic lung tissues.

    OpenAIRE

    Paradinas, F. J.; Boxer, G.; Bagshawe, K D

    1984-01-01

    The Ca (Oxford) antigen was originally isolated from a malignant neoplasm and with few exceptions was reported to discriminate between malignant and non-malignant neoplasms or normal tissues. Using the Ca 1 antibody we have studied the Ca distribution in 54 lung neoplasms and adjacent non-neoplastic lung tissue. Staining of tumours was very focal and the proportion of positive cells varied from about 50% for adenocarcinomas to less than 1% for oat cell carcinomas, which were often negative. F...

  12. The preparation and clinical use of a radioimmunoassay CA125 kit for the diagnosis of epithelial ovarian cancer

    International Nuclear Information System (INIS)

    A self-made radioimmunoassay CA125 kit (using OC125 monoclonal antibody ascites offered by Dr. Bast Laboratory which was purified, solidified and labelled with 125I) was used for serum determination in 80 patients with epithelial ovarian cancer and in 40 standard antigen samples. The results demonstrated a statistically significant correlation between our self-made CA125 kit and an imported CENTOCOR CA125 kit (P125 kit is very useful in monitoring epithelial ovarian cancer

  13. Tumour associated antigen CA-50, CA-242 immunoradiometric assay (IRMA) in genitourinary malignancy and gastrointestinal carcinoma early diagnosis

    International Nuclear Information System (INIS)

    Tumour markers CA-50 and CA-242 were measured by immunometric assay (IRMA) to investigate their usefulness in the diagnosis of cancer of the pancreas, biliary tract, liver, breast, lung, gastrointestinal and genitourinary systems. The cutoff points, derived from studies on normal subjects and those with proven benign disease, were 20 u/ml and 12 u/ml for CA-50 and CA-242 respectively. Both markers were found to be generally useful with significant differences between malignant and non malignant disease. The highest positive rates, were found in cancers of the pancreas and gall bladder. The overall rate of false positives was low. It is concluded that measurements of CA-50 and CA-242 are useful in the detection of malignancy, particularly of the pancreas and biliary tract. 2 figs, 2 tabs

  14. Carbohydrate Antigen Sialyl Lewis a – Its Pathophysiological ignificance and Induction Mechanism in Cancer Progression

    OpenAIRE

    Reiji Kannagi

    2007-01-01

    Carbohydrate antigen sialyl Lewis a (CA19-9) is the mostfrequently applied serum tumor marker for diagnosis of cancersin the digestive organs. Recent progress disclosed thepresence of a normal counterpart of the determinant, namelydisialyl Lewis a, which is predominantly expressed in nonmalignantepithelial cells of the digestive organs, while sialylLewis a is preferentially expressed in cancers. The disialylLewis a determinant carries one extra sialic residue attachedthrough a 2 6 linkage to ...

  15. New tumor-associated antigen SC6 in pancreatic cancer

    OpenAIRE

    Liu, Min-Pei; Guo, Xiao-Zhong; Xu, Jian-Hua; Wang, Di; Li, Hong-Yu; Cui, Zhong-Min; Zhao, Jia-Jun; Ren, Li-Nan

    2005-01-01

    AIM: To examine the concentration of a new antigen SC6 (SC6-Ag) recognized by monoclonal antibody (MAb) in patients with pancreatic cancer and other malignant or benign diseases and to understand whether SC6-Ag has any clinical significance in distinguishing pancreatic cancer from other gastrointestinal diseases.

  16. Abnormal antigens in breast cancer tissues and production of monoclonal antibodies against one of these antigens

    International Nuclear Information System (INIS)

    Breast cancer is associated with up regulation, down regulation of normal antigens or abnormal antigens. These antigens are very useful candidates as targets for the different breast cancer therapies and for vaccination trials. This study was done to characterize abnormal antigens, extract one of them and to produce monoclonal antibodies against the extracted antigen. One hundred and twenty Sudanese female patients were included in this study after informed consent. The mean age was 47. 2 years (16-80). Two tissue samples were obtained from each patient and they were confirmed as normal and cancerous breast tissues microscopically. 2D PAGE was used to analyze the protein content of samples. LC/MS and nr. fast a database search were used for separation and indentification of the abnormal proteins. Three different patterns of 2D Page results were obtained, the first pattern involved detection of four abnormal proteins in 26.7% of the patient cancerous tissues while they were undetected in the normal tissues of the same patients. In the second 2D PAGE result pattern the cancerous and the normal tissues of 67.5% patients were identical and they did not contain the four abnormal proteins while the third 2D PAGE pattern involved the presence of two abnormal antigens (from the four) in the cancerous tissues of 5.8% of the patients and they were absent from the normal tissues of the same patients. The four abnormal proteins were identified as, human Thioredoxin (D60nmutant), x-ray crystal structure of human galectin-1, retrocopy of tropomyosin 3(rc TPM3) and beta-tropomyosin (isoform 2). The primary and the secondary structures were obtained from the SWISSPROT and the PDB databases. Beta tropomyosin spot was extracted and used as antigen for monoclonal antibody production. Monoclonal antibody against beta- tropomyosin with a concentration of 0.35 mg/ml and a G11 anti beta-tropomyosin hybridoma cell line were produced. The monoclonal antibody was with single bad and

  17. Gastric Cancer with a Very High Serum CA 19-9 Level

    Directory of Open Access Journals (Sweden)

    Kazuya Kato

    2011-04-01

    Full Text Available Carbohydrate antigen 19-9 (CA 19-9 is a sensitive marker for pancreatic and hepatobiliary malignancies. The highest frequency of elevated serum CA 19-9 levels is found among patients with pancreatic cancer. CA 19-9 has recently been demonstrated to be a marker of digestive tract malignancies. We report the case of a patient with a gastric cancer and a very high serum CA 19-9 level. During laparotomy, a large mass was found in the antrum. A distal gastrectomy with D2 dissection of the lymph nodes was performed. Histological examination, including immunohistochemistry, revealed an adenocarcinoma of the stomach producing CA 19-9. To the best of our knowledge, no patient with an extremely high serum CA 19-9 level resulting from a gastric adenocarcinoma has been reported previously.

  18. Gastric Cancer with a Very High Serum CA 19-9 Level.

    Science.gov (United States)

    Kato, Kazuya; Taniguchi, Masahiko; Kawakami, Takako; Nagase, Atsushi; Matsuda, Minoru; Onodea, Kazuhiko; Yamaguchi, Hidenori; Higuchi, Mineko; Furukawa, Hiroyuki

    2011-01-01

    Carbohydrate antigen 19-9 (CA 19-9) is a sensitive marker for pancreatic and hepatobiliary malignancies. The highest frequency of elevated serum CA 19-9 levels is found among patients with pancreatic cancer. CA 19-9 has recently been demonstrated to be a marker of digestive tract malignancies. We report the case of a patient with a gastric cancer and a very high serum CA 19-9 level. During laparotomy, a large mass was found in the antrum. A distal gastrectomy with D2 dissection of the lymph nodes was performed. Histological examination, including immunohistochemistry, revealed an adenocarcinoma of the stomach producing CA 19-9. To the best of our knowledge, no patient with an extremely high serum CA 19-9 level resulting from a gastric adenocarcinoma has been reported previously. PMID:21577374

  19. Comparative study of CA242 and CA19-9 for the diagnosis of pancreatic cancer.

    OpenAIRE

    Kawa, S; Tokoo, M.; Hasebe, O.; Hayashi, K.; Imai, H; Oguchi, H.; Kiyosawa, K; Furuta, S; Homma, T

    1994-01-01

    A comparative study of a new tumour marker, CA242, and CA19-9 was conducted with special reference to their diagnostic usefulness in pancreatic cancer. CA242 showed sensitivity similar to that of CA19-9 for overall cases and early cases (stage I tumour) of pancreatic cancer. For other malignancies, the positive rates of CA242 were lower than those of CA19-9 except for colorectal cancer. An important characteristics of CA242 was that it was only slightly and infrequently elevated in the sera o...

  20. Generation of Monoclonal Antibodies (mAbs) Against Breast Cancer Antigen

    International Nuclear Information System (INIS)

    Breast cancer is the most common type of cancer seen in women worldwide. Early detection and monitoring progress of treatment of the disease improves the outcome and prognosis. This study is a report on work in generating specific mAbs against breast cancer antigen, CA 15-3, with a view for use in research. Hybridoma cells that produce monoclonal antibody (mAb) against breast cancer antigen were generated by the fusion of mouse splenocytes with P3X63.Ag8.653 myeloma cell line. Four stable hybridoma clones expressing mAbs against CA15-3; D2, F11, E12 and E3, were successfully developed and were scaled up in CELLine CL 350 bioreactors. The mAbs bound to breast cancer cells in vitro; however, they did not react significantly with normal cells. These locally generated mAbs can be used for future work especially in human breast cancerous tissues and therefore can be used for in vivo tumor targeting and imaging. (author)

  1. Evaluation of tumor markers carcinoembryonic antigen, cytokeratin 19 fragment and cancer-associated antigen 72-4 in neoplastic and non-neoplastic canine effusions differentiation

    OpenAIRE

    L.V Teixeira; T.A. Guerra; F.O. Conrado; S.R. Terra; D.G. Gerardi; González, F.H.D.

    2014-01-01

    The concentration of tumor markers in body fluids can be used for diagnosis and prognosis of patients. This study aimed to investigate the performance of tumor markers cytokeratin 19 fragment (CYFRA 21-1), cancer-associated antigen 72-4 (CA 72-4) and carcinoembryonic antigen (CEA) in the neoplastic and non-neoplastic canine effusions. In thirty-two neoplastic (n=16) and non-neoplastic (n=16) samples of canine thoracic or abdominal effusions, tumor markers were measured. Significant statistica...

  2. Comparison of a new tumour marker CA 242 with CA 19-9, CA 50 and carcinoembryonic antigen (CEA) in digestive tract diseases.

    OpenAIRE

    Kuusela, P.; Haglund, C.; Roberts, P. J.

    1991-01-01

    The levels of CA 242, a new tumour marker of carbohydrate nature, were measured in sera of 185 patients with malignancies of the digestive tract and of 123 patients with benign digestive tract diseases. High percentages of elevated CA 242 levels (greater than 20 U ml-1) were recorded in patients with pancreatic and biliary cancers (68%). The sensitivity was somewhat lower than that of CA 19-9 (76%) and CA 50 (73%). On the other hand, in benign pancreatic and biliary tract diseases the CA 242 ...

  3. ANTIGEN MG7 IN GASTRIC CANCER AND GASTRIC PRECANCEROUS LESIONS

    Institute of Scientific and Technical Information of China (English)

    郭冬丽; 宁佩芳; 袁媛

    2004-01-01

    Objective: To study the dynamic change and its diagnostic significance of MG7 expression in the process of gastric cancer development. Methods: The expression level of antigen MG7 was determined by immunohistochemistry method in 406 cases of gastric mucosa. The classification of intestinal metaplasia of gastric mucosa was determined by histochemistry method in 82 cases. Results: The positive rate of MG7 expression in normal gastric mucosa, intestinal metaplasia and dysplasia of gastric mucosa and gastric cancer were increased gradually (P<0.01). The positive rate of MG7 expression in superficial gastritis, atrophic gastritis and gastric cancer were increased on sequence (P<0.01). The positive rate of antigen MG7 expression in type Ⅲ intestinal metaplasia of gastric mucosa had significant difference,compared with that in type Ⅰ an Ⅱ intestinal metaplasia (P<0.05). Conclusion: MG7 antigen had close relationship with gastric cancer. Type Ⅲ intestinal metaplasia, atrophic gastritis and dysplasia should be followed up in order to improve the early detection of gastric cancer. MG7 antigen had great clinical value in the dynamic follow-up of gastric precursors.

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

    International Nuclear Information System (INIS)

    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

  5. The Clinical Relevance of Rising CA-125 Levels Within the Normal Range in Patients With Uterine Papillary Serous Cancer

    OpenAIRE

    Frimer, Marina; Hou, June Y.; McAndrew, Thomas C.; Gary L. Goldberg; Shahabi, Shohreh

    2013-01-01

    The utility of cancer antigen 125 (CA-125) levels as an adjunct method of monitoring patients with uterine papillary serous carcinoma (UPSC) or endometrial serous carcinoma after surgery and adjuvant treatment has been reported. Our goal was to determine the significance of rising CA-125 levels within the normal range in these patients in the posttreatment surveillance setting. All patients with UPSC who underwent surgical staging and had preoperative CA-125 measurement from...

  6. CA 242, a new tumour marker for pancreatic cancer: a comparison with CA 19-9, CA 50 and CEA.

    OpenAIRE

    Haglund, C.; Lundin, J; Kuusela, P.; Roberts, P. J.

    1994-01-01

    The serum expression of a novel tumour marker, CA 242, defined by monoclonal antibody C 242, was studied in 179 patients with pancreatic cancer. The results were compared with CA 19-9, CA 50 and CEA. CA 242 is a carbohydrate closely related, but not identical, to CA 19-9 and CA 50. The overall sensitivity of the CA 242 assay was 74%: 55% in stage I, 83% in stage II-III and 78% in stage IV disease. The specificity calculated from 112 patients with benign diseases was 91%. CA 19-9 had a higher ...

  7. RHAMM (CD168) Is Overexpressed at the Protein Level and May Constitute an Immunogenic Antigen in Advanced Prostate Cancer Disease

    OpenAIRE

    Kilian M. Gust; Hofer, Matthias D; Sven R. Perner; Robert Kim; Arul M. Chinnaiyan; Sooryanarayana Varambally; Peter Moller; Ludwig Rinnab; Rubin, Mark A; Jochen Greiner; Michael Schmitt; Rainer Kuefer; Mark Ringhoffer

    2009-01-01

    Localized prostate cancer (CaP) can be cured using several strategies. However, the need to identify active substances in advanced tumor stages is tremendous, as the outcome in such cases is still disappointing. One approach is to deliver human tumor antigen-targeted therapy, which is recognized by T cells or antibodies. We used data mining of the Cancer Immunome Database (CID), which comprises potential immunologic targets identified by serological screening of expression libraries. Candidat...

  8. 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...

  9. 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.

  10. Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

    Institute of Scientific and Technical Information of China (English)

    Anil; Suri; Nirmala; Jagadish; Shikha; Saini; Namita; Gupta

    2015-01-01

    Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.

  11. 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

    , Denmark. POPULATION: Eight hundred and one women with expected normal pregnancies were investigated. Of these, 640 delivered vaginally, 82 by emergency cesarean section, and 79 by elective cesarean section; 720 women had uncomplicated pregnancies. METHODS: Samples were collected at gestational weeks 13...... 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......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...

  12. Exosome targeting of tumor antigens expressed by cancer vaccines can improve antigen immunogenicity and therapeutic efficacy.

    Science.gov (United States)

    Rountree, Ryan B; Mandl, Stefanie J; Nachtwey, James M; Dalpozzo, Katie; Do, Lisa; Lombardo, John R; Schoonmaker, Peter L; Brinkmann, Kay; Dirmeier, Ulrike; Laus, Reiner; Delcayre, Alain

    2011-08-01

    MVA-BN-PRO (BN ImmunoTherapeutics) is a candidate immunotherapy product for the treatment of prostate cancer. It encodes 2 tumor-associated antigens, prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP), and is derived from the highly attenuated modified vaccinia Ankara (MVA) virus stock known as MVA-BN. Past work has shown that the immunogenicity of antigens can be improved by targeting their localization to exosomes, which are small, 50- to 100-nm diameter vesicles secreted by most cell types. Exosome targeting is achieved by fusing the antigen to the C1C2 domain of the lactadherin protein. To test whether exosome targeting would improve the immunogenicity of PSA and PAP, 2 additional versions of MVA-BN-PRO were produced, targeting either PSA (MVA-BN-PSA-C1C2) or PAP (MVA-BN-PAP-C1C2) to exosomes, while leaving the second transgene untargeted. Treatment of mice with MVA-BN-PAP-C1C2 led to a striking increase in the immune response against PAP. Anti-PAP antibody titers developed more rapidly and reached levels that were 10- to 100-fold higher than those for mice treated with MVA-BN-PRO. Furthermore, treatment with MVA-BN-PAP-C1C2 increased the frequency of PAP-specific T cells 5-fold compared with mice treated with MVA-BN-PRO. These improvements translated into a greater frequency of tumor rejection in a PAP-expressing solid tumor model. Likewise, treatment with MVA-BN-PSA-C1C2 increased the antigenicity of PSA compared with treatment with MVA-BN-PRO and resulted in a trend of improved antitumor efficacy in a PSA-expressing tumor model. These experiments confirm that targeting antigen localization to exosomes is a viable approach for improving the therapeutic potential of MVA-BN-PRO in humans. PMID:21670078

  13. A novel cancer testis antigen protein phosphates gamma 2

    International Nuclear Information System (INIS)

    A novel cancer-testis antigen PP1a2, which is a serine/threonine phosphatase and known to regulate sperm motility and sperm maturation during spermeogenesis. Here we have identified PP1a2 as a cancer biomarker in Cervical (C33, Hela), Prostate (PC3, DU145) and Ovarian (PA1) cancer cell lines. PP1a2 expression was also found in Human Embryonic Kidney (HEK 293) cell lines. As a result PP1a2 was found to be a marker of germ cells, cancerous cells as well as embryonic cells. This invention led to the theory that aberrant expression of germline genes in cancer reflects the activation of the silenced gametogenic programme in somatic cells, and that this programmatic acquisition is one of the driving forces of tumorigenesis. (author)

  14. 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.

  15. Difference in motility of basophilic, granulocytes from atopic subjects following antigen- and Ca inophore A23187-stimulation

    OpenAIRE

    Tanizaki,Yoshiro; Kitani,Hikaru; Mifune, Takashi; Mitsunobu, Fumihiro; Ochi, Koji; Harada, Hideo; Nakagawa, Saburo; Soda, Ryo; Takahashi,Kiyoshi; Kimura,Ikuro

    1993-01-01

    We examined histamine release and morphological changes in basophilic granulocytes from atopic subjects, in response to stimulation with antigen and Ca ionophore A23187. 1. Histamine release and a reduction in the rumber of basophils were more rapid and greater in extent at an early stage of antigen stimulation compared with Ca ionophore A23187 stimulation. 2. Morphological changes in basophils, represented by increased motility, in terms of an increased ratio of short to long axis diameter (...

  16. Chimeric Antigen Receptors Modified T-Cells for Cancer Therapy.

    Science.gov (United States)

    Dai, Hanren; Wang, Yao; Lu, Xuechun; Han, Weidong

    2016-07-01

    The genetic modification and characterization of T-cells with chimeric antigen receptors (CARs) allow functionally distinct T-cell subsets to recognize specific tumor cells. The incorporation of costimulatory molecules or cytokines can enable engineered T-cells to eliminate tumor cells. CARs are generated by fusing the antigen-binding region of a monoclonal antibody (mAb) or other ligand to membrane-spanning and intracellular-signaling domains. They have recently shown clinical benefit in patients treated with CD19-directed autologous T-cells. Recent successes suggest that the modification of T-cells with CARs could be a powerful approach for developing safe and effective cancer therapeutics. Here, we briefly review early studies, consider strategies to improve the therapeutic potential and safety, and discuss the challenges and future prospects for CAR T-cells in cancer therapy. PMID:26819347

  17. Antigen

    Science.gov (United States)

    An antigen is any substance that causes your immune system to produce antibodies against it. This means your immune ... and is trying to fight it off. An antigen may be a substance from the environment, such ...

  18. 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. Immuno

  19. Advances in identification and application of tumor antigen inducing anti-cancer responses

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ Tumor antigen is one of the important bases of tumor immunotherapy[1]. With the discovery of novel tumor antigens, interest in specific immunotherapy for treatment of malignancies has increased substantially. Nowadays more and more scientists paid close attention to various tumor antigens with their roles or/and applications in anti-cancer immune responses, immune tolerance, tumor markers, tumor immunotherapy and so on. Here we discussed the classification of tumor antigens and summarized the technologies of identification and application of tumor antigens.

  20. RHAMM (CD168 Is Overexpressed at the Protein Level and May Constitute an Immunogenic Antigen in Advanced Prostate Cancer Disease

    Directory of Open Access Journals (Sweden)

    Kilian M. Gust

    2009-09-01

    Full Text Available Localized prostate cancer (CaP can be cured using several strategies. However, the need to identify active substances in advanced tumor stages is tremendous, as the outcome in such cases is still disappointing. One approach is to deliver human tumor antigen-targeted therapy, which is recognized by T cells or antibodies. We used data mining of the Cancer Immunome Database (CID, which comprises potential immunologic targets identified by serological screening of expression libraries. Candidate antigens were screened by DNA microarrays. Genes were then validated at the protein level by tissue microarrays, representing various stages of CaP disease. Of 43 targets identified by CID, 10 showed an overexpression on the complementary DNA array in CaP metastases. The RHAMM (CD168 gene, earlier identified by our group as an immunogenic antigen in acute and chronic leukemia, also showed highly significant overexpression in CaP metastases compared with localized disease and benign prostatic hyperplasia. At the protein level, RHAMM was highest in metastatic tissue samples and significantly higher in neoplastic localized disease compared with benign tissue. High RHAMM expression was associated with clinical parameters known to be linked to better clinical outcome. Patients with high RHAMM expression in the primaries had a significantly lower risk of biochemical failure. The number of viable cells in cell cultures was reduced in blocking experiments using hormone-sensitive and hormone-insensitive metastatic CaP cell lines. Acknowledging the proven immunogenic effects of RHAMM in leukemia, this antigen is intriguing as a therapeutic target in far-advanced CaP.

  1. Breast cancer: could the CA 15-3 dosages guide the prescription of osseous scintigraphies?

    International Nuclear Information System (INIS)

    One admits that prostatic specific antigens (PSA) can help in guiding indications of osseous scintigraphies in the initial or followup examinations in prostatic cancers. The question is posed whether this will be the same as the CA 15-3 serumal dosage in breast cancers. A retrospective study has been carried out over 14 months, from December 1995 to April 1997. One hundred and thirty six osseous scintigraphies were effectuated simultaneously in 129 females and 2 males, in the frame of the initial (47 cases) or followup (89 cases) examinations of breast cancer. The interpretation of the scintigraphies has been systematically blindly remade (without knowledge of the labeller rate) by the same nuclear physician. Among the 47 initial examinations, the CA 15-3 was normal (< 25 U/ml) in 39 cases; none had a scintigraphy evoking secondary localization. The other eight, with increased CA 15-3 (26 to 152 U/ml), had 5 suspect and 3 normal scintigraphies. Among the 89 followup, the CA 15-3 was normal in 52 cases (12/52 scintigraphies were +/- metastases evoking) and increased in 37 cases (29/37 metastases evoking scintigraphies). Our results suggest that in absence of increased CA 15-3 the osseous scintigraphy is not justified in the initial examination; in absence of increased CA 15-3, its effectuation in the followup should not be systematic but must be based on clinic arguments. This strategy should be confirmed by a more thorough study

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  3. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    International Nuclear Information System (INIS)

    Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8+ cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4+ T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy

  4. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, Andrea [Biologics Safety and Disposition, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstraße 141, Basel CH-4057 (Switzerland); Wehner, Rebekka [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Füssel, Susanne [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Bachmann, Michael [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Wirth, Manfred P. [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Schmitz, Marc, E-mail: marc.schmitz@tu-dresden.de [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany)

    2012-02-22

    Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8{sup +} cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4{sup +} T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.

  5. 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; Gjerstorff, Morten F

    2015-01-01

    Immunotherapy is emerging as a supplement to conventional cancer treatment, and identifying antigen targets for specific types of cancer is critical to optimizing therapeutic efficacy. Cancer/testis antigens are highly promising targets for immunotherapy due to their cancer-specific expression and...... other CT antigens, such as MAGE-A proteins. Surprisingly, we detected no ADAM2, CALR3 and SAGE1 in the 67 lung cancers (mainly non-small lung cancer) and 189 breast cancers, while MAGE-A proteins were present in 15% and 7-16% of these tumor types, respectively. Treatment with DNA methyltransferase...... and SAGE1 cancer/testis antigens are not promising targets for immunotherapy of breast and lung cancer....

  6. Characterization of crystals of an antibody-recognition fragment of the cancer differentiation antigen mesothelin in complex with the therapeutic antibody MORAb-009

    OpenAIRE

    Ma, Jichun; Tang, Wai Kwan; Esser, Lothar; Pastan, Ira; Xia, Di

    2012-01-01

    The therapeutic antibody MORAb-009 disrupts the interaction of mesothelin and the ovarian cancer antigen CA-125. Crystals have been grown of the Fab fragment derived from MORAb-009 and of its complex with an N-terminal fragment of mesothelin.

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

    International Nuclear Information System (INIS)

    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. 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. 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. 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. Challenges to the development of antigen-specific breast cancer vaccines

    International Nuclear Information System (INIS)

    Continued progress in the development of antigen-specific breast cancer vaccines depends on the identification of appropriate target antigens, the establishment of effective immunization strategies, and the ability to circumvent immune escape mechanisms. Methods such as T cell epitope cloning and serological expression cloning (SEREX) have led to the identification of a number target antigens expressed in breast cancer. Improved immunization strategies, such as using dendritic cells to present tumor-associated antigens to T lymphocytes, have been shown to induce antigen-specific T cell responses in vivo and, in some cases, objective clinical responses. An outcome of successful tumor immunity is the evolution of antigen-loss tumor variants. The development of a polyvalent breast cancer vaccine, directed against a panel of tumor-associated antigens, may counteract this form of immune escape

  9. Expression of an antigen homologous to the human CO17-1A/GA733 colon cancer antigen in animal tissues.

    OpenAIRE

    Zaloudik, J; Basak, S.; Nesbit, M.; Speicher, D W; Wunner, W H; Miller, E.; Ernst-Grotkowski, C.; Kennedy, R; Bergsagel, L. P.; Koido, T.; Herlyn, D

    1997-01-01

    The CO17-1A/GA733 antigen is associated with human carcinomas and some normal epithelial tissues. This antigen has shown promise as a target in approaches to passive and active immunotherapy of colorectal cancer. The relevance of animal models for studies of immunotherapy targeting this antigen in patients is dependent on the expression of the antigen on normal animal tissues. Immunohistoperoxidase staining with polyclonal rabbit antibodies to the human antigen revealed the human homologue on...

  10. A meta-analysis of serum cancer antigen 125 array for diagnosis of ovarian cancer in Chinese

    Directory of Open Access Journals (Sweden)

    Xiao-Yan Liao

    2014-01-01

    Full Text Available Objective: To further evaluation the diagnosis accuracy of serum cancer antigen 125 (CA125 in the diagnosis of ovarian cancer in Chinese patients. Materials and Methods: The PubMed, Wanfang and CNKI databases were electric searched and relevant diagnosis trials were reviewed and finally included in this meta-analysis. The diagnosis sensitivity, specificity, positive likely hood ratio (+LR, negative likely hood ratio (−LR, diagnostic odds ratio (DOR and receiver operating characteristic curve were pooled by Meta DiSc 1.4 software. Results: Nineteen studies with a total of 2426 subjects were included in this meta-analysis. The pooled sensitivity, specificity, +LR, −LR and DOR were 0.75 (95% confidence interval = 0.73-0.78, 0.80 (0.77-0.82, 4.52 (3.27-6.26, 0.31 (0.28-0.35 and 15.76 (10.45-23.75 respectively. The area under the summary receiver operating characteristic curve was 0.84. Conclusion: Serum CA125 was potential biomarker for diagnosis of ovarian cancer with acceptable diagnosis value.

  11. Serum levels of vascular endothelial growth factor and cancer antigen 125 are related to the prognosis of adenomyosis patients after interventional therapy

    OpenAIRE

    MU, YONGXU; Hu, Xiaoyan; He, Junfeng; Liu, Haiyan; Zhang, Lei; Liu, Heming; Hao, Zhiming

    2015-01-01

    Aims: This study is to investigate the expression levels of vascular endothelial growth factor (VEGF) and cancer antigen 125 (CA125) in serum of adenomyosis patients before and after interventional therapy. The role of serum levels of VEGF and CA125 for the prognosis of adenomyosis is further studied. Methods: A total of 80 adenomyosis patients treated with interventional therapy and 40 healthy individuals were enrolled in this study. Enzyme-linked immunosorbent assay was performed to detect ...

  12. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

    Directory of Open Access Journals (Sweden)

    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”.

  13. RHAMM (CD168) Is Overexpressed at the Protein Level and May Constitute an Immunogenic Antigen in Advanced Prostate Cancer Disease1

    OpenAIRE

    Kilian M. Gust; Hofer, Matthias D; Sven R. Perner; Kim, Robert; Arul M. Chinnaiyan; Varambally, Sooryanarayana; Moller, Peter; Rinnab, Ludwig; Rubin, Mark A; Greiner, Jochen; Schmitt, Michael; Kuefer, Rainer; Ringhoffer, Mark

    2009-01-01

    Localized prostate cancer (CaP) can be cured using several strategies. However, the need to identify active substances in advanced tumor stages is tremendous, as the outcome in such cases is still disappointing. One approach is to deliver human tumor antigen-targeted therapy, which is recognized by T cells or antibodies. We used data mining of the Cancer Immunome Database (CID), which comprises potential immunologic targets identified by serological screening of expression libraries. Candidat...

  14. Carcinoembryonic antigen (CEA) dynamics in stomach cancer patients receiving cryotherapy

    International Nuclear Information System (INIS)

    Radioimmunologic assays of blood serum carcinoembryonic antigen (CEA) level were conducted at major stages of treatment of gastric cancer by subtotal stomach resection and gastrectomy with preliminary cryotreatment and thawing of tumor. A short-term rise in CEA level occurred in 53.9 % of cases 3-4 days after combined therapy. A decrease in CEA concentration at discharge from hospital as compared with preoperative level and that registered 3-4 days after operation was observed in 50 and 75 % of cases of combined therapy, respectively, and 47.5 and 37.5 % of controls (surgery without cryotreatment). There was nocorrelation between cryotreatment and changes in CEA level in gastric ulcer patients

  15. Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens

    Science.gov (United States)

    Casalà, Carla; Briansó, Ferran; Castrejón, Nerea; Rodríguez, Eva; Suñol, Mariona; Carcaboso, Angel M.; Lavarino, Cinzia; Mora, Jaume; de Torres, Carmen

    2016-01-01

    The calcium–sensing receptor is a G protein-coupled receptor that exerts cell-type specific functions in numerous tissues and some cancers. We have previously reported that this receptor exhibits tumor suppressor properties in neuroblastoma. We have now assessed cinacalcet, an allosteric activator of the CaSR approved for clinical use, as targeted therapy for this developmental tumor using neuroblastoma cell lines and patient-derived xenografts (PDX) with different MYCN and TP53 status. In vitro, acute exposure to cinacalcet induced endoplasmic reticulum stress coupled to apoptosis via ATF4-CHOP-TRB3 in CaSR-positive, MYCN-amplified cells. Both phenotypes were partially abrogated by phospholipase C inhibitor U73122. Prolonged in vitro treatment also promoted dose- and time-dependent apoptosis in CaSR-positive, MYCN-amplified cells and, irrespective of MYCN status, differentiation in surviving cells. Cinacalcet significantly inhibited tumor growth in MYCN-amplified xenografts and reduced that of MYCN-non amplified PDX. Morphology assessment showed fibrosis in MYCN-amplified xenografts exposed to the drug. Microarrays analyses revealed up-regulation of cancer-testis antigens (CTAs) in cinacalcet-treated MYCN-amplified tumors. These were predominantly CTAs encoded by genes mapping on chromosome X, which are the most immunogenic. Other modulated genes upon prolonged exposure to cinacalcet were involved in differentiation, cell cycle exit, microenvironment remodeling and calcium signaling pathways. CTAs were up-regulated in PDX and in vitro models as well. Moreover, progressive increase of CaSR expression upon cinacalcet treatment was seen both in vitro and in vivo. In summary, cinacalcet reduces neuroblastoma tumor growth and up-regulates CTAs. This effect represents a therapeutic opportunity and provides surrogate circulating markers of neuroblastoma response to this treatment. PMID:26893368

  16. Diagnostic value of combined determinations of serum CA19-9, CA242 and CA50 levels in patients with pancreatic cancer

    International Nuclear Information System (INIS)

    Objective: To explore the diagnostic value of combined determinations of serum CA19-9, CA242 and CA50 levels in patients with pancreatic cancer. Methods: Serum CA19-9, CA242 and CA50 levels were determined with RIA in 120 patients with pancreatic cancer, 50 patients with chronic pancreatitis and 80 controls. Results: The serum levels of CA19-9, CA242 and CA50 in patients with pancreatic cancer were significantly higher than those in patients with pancreatitis and controls. With CA19-9, the diagnostic sensitivity and specificity for pancreatic cnrcinoma was 82.0% and 78.6% respectively. With CA242, the diagnostic sensitivity and specificity for pancreatic carcinoma was 78.5% and 81.6% respectively. With CA50, the diagnostic sensitivity and specificity for pancreatic carcinoma was 52.7% and 74.6% respectively. With combined determinations of CA19-9, CA242 and CA50, the sensitivity and specificity was enhanced to 96.82% and 98.75% respectively. Conclusion: Combined detection of CA19-9, CA242 and CA50 is clinically useful for early diagnosis of pancreatic cancer. (authors)

  17. Carbohydrate Antigen Sialyl Lewis a – Its Pathophysiological ignificance and Induction Mechanism in Cancer Progression

    Directory of Open Access Journals (Sweden)

    Reiji Kannagi

    2007-06-01

    Full Text Available Carbohydrate antigen sialyl Lewis a (CA19-9 is the mostfrequently applied serum tumor marker for diagnosis of cancersin the digestive organs. Recent progress disclosed thepresence of a normal counterpart of the determinant, namelydisialyl Lewis a, which is predominantly expressed in nonmalignantepithelial cells of the digestive organs, while sialylLewis a is preferentially expressed in cancers. The disialylLewis a determinant carries one extra sialic residue attachedthrough a 2 6 linkage to the GlcNAc moiety compared tocancer-associated sialyl Lewis a, which carries only one 2 3linked sialic acid residue (monosialyl Lewis a. Disialyl Lewisa in normal epithelial cells serves as a ligand for immunosuppressivereceptors such as sialic acid binding immunoglobulin(Ig-like lectins (siglec-7 and -9 expressed on resident monocytes/macrophages and maintains immunological homeostasisof mucosal membranes in digestive organs. Epigenetic silencing of a gene for a 2 6 sialyltransferasein the early stages of carcinogenesis results in an impairment of 2 6 sialylation,leading to incomplete synthesis and accumulation of sialyl Lewis a, which lacks the 2 6linked sialic acid residue, in cancer cells. Simultaneous determination of serum levels of sialyl-and disialyl Lewis a, and calculation of the monosialyl/disialyl Lewis a ratio provideinformation useful for excluding a false-positive serum diagnosis, and also for averting theundesired influence of the Lewis blood group of patients on serum antigen levels. During thecourse of cancer progression in locally advanced cancers, tumor hypoxia induces transcriptionof several glycogenes involved in sialyl Lewis a synthesis. Expression of the determinant,consequently, is further accelerated in more malignant hypoxia-resistant cancer cellclones, which become predominant clones in advanced stage cancers and frequently develophematogenous metastasis. Sialyl Lewis a, as well as its positional isomer sialyl Lewis x,serves as a

  18. Cancer/testis antigens: novel tools for discerning aggressive and non-aggressive prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Takumi Shiraishi; Robert H Getzenberg; Prakash Kulkarni

    2012-01-01

    The introduction of serum prostate-specific antigen (PSA) in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer.However,the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease.Thus,a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal.Although several serum and tissue biomarkers have been evaluated during the past decade,improved markers are still needed to enhance the accuracy,with which patients at risk can be discerned and treated more aggressively.The cancer/testis antigens (CTAs) are a group of proteins that are restricted to the testis in the normal adult,but are aberrantly expressed in several types of cancers.Because of their restricted expression pattern,the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis.Furthermore,several studies to date have reported the differential expression of CTAs in prostate cancer.Here,we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the aggressive phenotype of prostate cancer.

  19. Testis expressed 19 is a novel cancer-testis antigen expressed in bladder cancer.

    Science.gov (United States)

    Zhong, Jianhua; Chen, Yan; Liao, Xinhui; Li, Jiaqiang; Wang, Han; Wu, Chenglong; Zou, Xiaowen; Yang, Gang; Shi, Jing; Luo, Liya; Liu, Litao; Deng, Jianping; Tang, Aifa

    2016-06-01

    Bladder cancer exhibits high mortality as a result of limited therapeutic options and a high recurrence rate. Accordingly, novel treatments such as immunotherapy have emerged as promising therapeutic modalities to prolong overall patient survival and effect a disease cure, which has renewed enthusiasm for the identification of tumor-specific target antigens. Cancer-testis (CT) antigens are recognized as ideal targets for immunotherapy because of their expression features and high immunogenicity profiles. Here, we investigate the expression pattern of a novel CT antigen, testis-expressed 19 (TEX19), in patients with bladder carcinoma and among multiple human tissues. Six bladder cancer cell lines (T24, UM-UC-3, J82, 5637, SW780, and RT4) were also analyzed for TEX19 expression. Our results reveal that TEX19 expression in normal tissue is restricted to human testis. In addition, TEX19 mRNA expression was detected in 60 % (24/40) bladder cancer samples, whereas 58.20 % (110/189) were positive for TEXT19 protein expression. Compared to low-grade tumors, TEX19 exhibited increased expression in high-grade tumors, from 53.69 to 77.14 %, respectively (P = 0.011). TEX19 was also expressed in all six bladder cancer cell lines. Together, our findings suggest that TEX19 represents a novel CT gene and might play a role in the progression of bladder cancer and that this gene therefore provides a potential target for immunotherapy treatment strategies against bladder cancer. PMID:26695143

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

    Science.gov (United States)

    Mattes, Malcolm D.; Cardinal, Jon S.; Jacobson, Geraldine M.

    2016-01-01

    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. PMID:27306770

  1. Evaluation of tumor markers carcinoembryonic antigen, cytokeratin 19 fragment and cancer-associated antigen 72-4 in neoplastic and non-neoplastic canine effusions differentiation

    Directory of Open Access Journals (Sweden)

    L.V. Teixeira

    2014-10-01

    Full Text Available The concentration of tumor markers in body fluids can be used for diagnosis and prognosis of patients. This study aimed to investigate the performance of tumor markers cytokeratin 19 fragment (CYFRA 21-1, cancer-associated antigen 72-4 (CA 72-4 and carcinoembryonic antigen (CEA in the neoplastic and non-neoplastic canine effusions. In thirty-two neoplastic (n=16 and non-neoplastic (n=16 samples of canine thoracic or abdominal effusions, tumor markers were measured. Significant statistical difference was found only for the CYFRA 21-1 marker. The levels were significantly higher for the neoplastic group. The lack of significance between groups for markers CA 72-4 and CEA can be explained by the presence of other diseases in the non-neoplastic group, causing elevated levels of these markers. This study concludes that CYFRA 21-1 performed well, showing good sensitivity, specificity and accuracy in the diagnosis of neoplastic effusions in dogs. However, further investigations are necessary in patients with malignancy as those with benign effusions.

  2. Sensitivity and specificity of CA242 in gastro-intestinal cancer. A comparison with CEA, CA50 and CA 19-9.

    OpenAIRE

    Nilsson, O; Johansson, C.; Glimelius, B.; Persson, B.; Nørgaard-Pedersen, B.; Andrén-Sandberg, A.; Lindholm, L.

    1992-01-01

    A serological assay for the quantitative determination of the novel tumour-associated epitope CA242 was developed and used for determination of sensitivity and specificity of CA242 in gastrointestinal cancer. The CA242 assay showed a better tumour specificity than CA50 (and CA 19-9). This was most noticeable in benign hepatobiliary disease. The sensitivity at 90% specificity cut-off level was approximately three times higher for CA242 compared to CA50 in colo-rectal cancer Dukes A, B and C, w...

  3. Cancer-testis antigens and immunotherapy in the light of cancer complexity.

    Science.gov (United States)

    Grizzi, F; Mirandola, L; Qehajaj, D; Cobos, E; Figueroa, J A; Chiriva-Internati, M

    2015-03-01

    The ability of immunotherapy to evoke successful antitumor immune responses has been well documented over the past decade. Despite abundant preclinical data, it is only with the recent approval by the Food and Drug Administration (FDA) of the drugs such as sipuleucel-T and ipilimumab that immunotherapy is finally being recognized as a viable alternative to traditional therapies for treatment of various cancers. Despite the ability of immunotherapy to elicit successful antitumor immune responses, its efficacy is hindered by several factors. Among these are the paucity of tumor-associated antigens (TAA) that can be used as effective targets and the systemic toxicities that often lead to treatment interruption. Indeed, such adverse effects, which can be immunological and/or parenchymal, can be particularly severe and even fatal to some patients. A family of TAA called cancer-testis antigens (CTA) has been identified and their encoding genes have been extensively investigated. CTA expression has been demonstrated in a variety of human cancer tissues, and at least 19 CTA have been found to elicit humoral and/or cellular immune responses in cancer patients. Here we discuss how CTA and immunotherapy will most likely play a major role in the cure of cancer in the light of cancer complexity. PMID:25901859

  4. The Cancer Biomedical Informatics Grid (caBIG™) Security Infrastructure

    OpenAIRE

    Langella, Stephen; Oster, Scott; Hastings, Shannon; Siebenlist, Frank; Phillips, Joshua; Ervin, David; Permar, Justin; Kurc, Tahsin; Saltz, Joel

    2007-01-01

    Security is a high priority issue in medical domain, because many institutions performing biomedical research work with sensitive medical data regularly. This issue becomes more complicated, when it is desirable or needed to access and analyze data in a multi-institutional setting. In the NCI cancer Biomedical Informatics Grid (caBIG™) program, several security issues were raised that existing security technologies could not address. Considering caBIG is envisioned to span a large number of c...

  5. Derepression of Cancer/Testis Antigens in cancer is associated with distinct patterns of DNA Hypomethylation

    International Nuclear Information System (INIS)

    The Cancer/Testis Antigens (CTAs) are a heterogeneous group of proteins whose expression is typically restricted to the testis. However, they are aberrantly expressed in most cancers that have been examined to date. Broadly speaking, the CTAs can be divided into two groups: the CTX antigens that are encoded by the X-linked genes and the non-X CT antigens that are encoded by the autosomes. Unlike the non-X CTAs, the CTX antigens form clusters of closely related gene families and their expression is frequently associated with advanced disease with poorer prognosis. Regardless however, the mechanism(s) underlying their selective derepression and stage-specific expression in cancer remain poorly understood, although promoter DNA demethylation is believed to be the major driver. Here, we report a systematic analysis of DNA methylation profiling data from various tissue types to elucidate the mechanism underlying the derepression of the CTAs in cancer. We analyzed the methylation profiles of 501 samples including sperm, several cancer types, and their corresponding normal somatic tissue types. We found strong evidence for specific DNA hypomethylation of CTA promoters in the testis and cancer cells but not in their normal somatic counterparts. We also found that hypomethylation was clustered on the genome into domains that coincided with nuclear lamina-associated domains (LADs) and that these regions appeared to be insulated by CTCF sites. Interestingly, we did not observe any significant differences in the hypomethylation pattern between the CTAs without CpG islands and the CTAs with CpG islands in the proximal promoter. Our results corroborate that widespread DNA hypomethylation appears to be the driver in the derepression of CTA expression in cancer and furthermore, demonstrate that these hypomethylated domains are associated with the nuclear lamina-associated domains (LADS). Taken together, our results suggest that wide-spread methylation changes in cancer are linked

  6. Multifaceted plasma membrane Ca(2+) pumps: From structure to intracellular Ca(2+) handling and cancer.

    Science.gov (United States)

    Padányi, Rita; Pászty, Katalin; Hegedűs, Luca; Varga, Karolina; Papp, Béla; Penniston, John T; Enyedi, Ágnes

    2016-06-01

    Plasma membrane Ca(2+) ATPases (PMCAs) are intimately involved in the control of intracellular Ca(2+) concentration. They reduce Ca(2+) in the cytosol not only by direct ejection, but also by controlling the formation of inositol-1,4,5-trisphosphate and decreasing Ca(2+) release from the endoplasmic reticulum Ca(2+) pool. In mammals four genes (PMCA1-4) are expressed, and alternative RNA splicing generates more than twenty variants. The variants differ in their regulatory characteristics. They localize into highly specialized membrane compartments and respond to the incoming Ca(2+) with distinct temporal resolution. The expression pattern of variants depends on cell type; a change in this pattern can result in perturbed Ca(2+) homeostasis and thus altered cell function. Indeed, PMCAs undergo remarkable changes in their expression pattern during tumorigenesis that might significantly contribute to the unbalanced Ca(2+) homeostasis of cancer cells. This article is part of a Special Issue entitled: Calcium and Cell Fate . Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. PMID:26707182

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

    OpenAIRE

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

    2016-01-01

    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 an...

  8. Relationship between the downregulation of HLA class I antigen and clinicopathological significance in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yu-Qing Shen; Jian-Qiong Zhang; Feng-Qing Miao; Jian-Min Zhang; Qin Jiang; Hao Chen; Xiang-Nian Shan; Wei Xie

    2005-01-01

    AIM: To discuss the expression of human leukocyte antigen (HLA) class I antigens in gastric cancer and correlate these with pathologic type and TNM stage.METHODS: The expression of HLA class I antigen was detected by immunohistochemistry in 185 specimens of gastric cancer, 20 gastric cancer specimens with lymphatic metastasis and 22 controls of normal gastric mucosa using four monoclonal antibodies.RESULTS: The expression of HLA class I antigen (B/C locus) was significantly downregulated in gastric cancer and in lymphatic metastasis than that in normal gastricmucosa (x2 = 7.712, P<0.05). The expression of other HLA class I antigens was also downregulated, but the change was slight. There was no relationship betweenthe downregulation of HLA class I antigen and that ofβ2m and LMP2. The expression of HLA class I (B/C locus) was statistically correlated with pathologic stage in gastric adenocarcinoma (x2= 4.164, P<0.05).CONCLUSION: The expression of HLA class I antigen (B/Clocus) was obviously downregulated in gastric cancer andin lymphatic metastasis. This abnormal expression wouldprovide the tumor cells with a way to avoid immunologicalrecognition.

  9. Cancer-testis antigen expression and immunogenicity in AL amyloidosis

    International Nuclear Information System (INIS)

    Light-chain amyloidosis (AL) is a plasma cell dyscrasia closely related to multiple myeloma. In multiple myeloma, the cancer-testis antigens (CTAs) CT7 (MAGE-C1), CT10 (MAGE-C2) and MAGE-A CTAs are expressed in up to 80% of cases. In this study, we investigated the expression and immunogenicity of several CTAs in patients with AL amyloidosis in a total of 38 bone marrow specimens by employing standard immunohistochemistry techniques on paraffin-embedded archival tissues. Plasma samples from 35 patients (27 with matched bone marrow samples) were also analyzed by ELISA for sero reactivity to a group of full-length CTA proteins. CT7 was present in 25/38 (66%) while CT10 was demonstrated in 3/38 and GAGE in 1/38 AL amyloid cases. The expression pattern was mostly focal. There were no significant differences with regard to organ involvement, response to treatment, or prognosis in CTA positive compared to negative cases. None of the specimens showed spontaneous humoral immunity to CT7, but sero reactivity was observed in individual patients to other CTAs. This study identifies CT7 as the prevalent CTA in plasma cells of patients with AL amyloidosis. Further analyses determining the biology of CTAs in AL amyloidosis and their value as potential targets for immunotherapy are warranted

  10. CA-125 and Ceruloplasmin Levels in Ovarian Cancer Patients

    Directory of Open Access Journals (Sweden)

    Mangala Hegde

    2015-09-01

    Conclusion: Serum ceruloplasmin as well CA-125 level decline after treatment, and have been associated with efficacy and safety of novel therapeutic strategy to improve diagnosis and treatment for cancer. [Cukurova Med J 2015; 40(3.000: 510-516

  11. Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression.

    Science.gov (United States)

    Scanlan, M J; Gout, I; Gordon, C M; Williamson, B; Stockert, E; Gure, A O; Jäger, D; Chen, Y T; Mackay, A; O'Hare, M J; Old, L J

    2001-03-30

    The ability of the immune system to recognize structurally altered, amplified or aberrantly expressed proteins can be used to identify molecules of etiologic relevance to cancer and to define targets for cancer immunotherapy. In the current study, ninety-four distinct antigens reactive with serum IgG from breast cancer patients were identified by immunoscreening breast cancer-derived cDNA expression libraries (SEREX). A serological profile was generated for each antigen on the basis of reactivity with allogeneic sera from normal individuals and cancer patients, and mRNA expression profiles for coding sequences were assembled based upon the tissue distribution of expressed sequence tags, Northern blots and real-time RT-PCR. Forty antigens reacted exclusively with sera from cancer patients. These included well-characterized tumor antigens, e.g. MAGE-3, MAGE-6, NY-ESO-1, Her2neu and p53, as well as newly-defined breast cancer antigens, e.g. kinesin 2, TATA element modulatory factor 1, tumor protein D52 and MAGE D, and novel gene products, e.g. NY-BR-62, NY-BR-75, NY-BR-85, and NY-BR-96. With regard to expression profiles, two of the novel gene products, NY-BR-62 and NY-BR-85, were characterized by a high level of testicular mRNA expression, and were overexpressed in 60% and 90% of breast cancers, respectively. In addition, mRNA encoding tumor protein D52 was overexpressed in 60% of breast cancer specimens, while transcripts encoding SNT-1 signal adaptor protein were downregulated in 70% of these cases. This study adds to the growing list of breast cancer antigens defined by SEREX and to the ultimate objective of identifying the complete repertoire of immunogenic gene products in human cancer (the cancer immunome). PMID:12747765

  12. 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.

  13. The possible role of tumor antigen CA 15-3, CEA and ferritin in malignant and benign disease

    Directory of Open Access Journals (Sweden)

    Nafija Serdarević

    2012-09-01

    Full Text Available Introduction: Serum CA15-3 has been one of the most reliable tumor markers used in monitoring of breast cancer patients. To increase its sensitivity, the combined measurement of other tumor markers (CEA and ferritin with CA15-3 was investigated. The aim of this study was determination of CA 15-3, CEA and ferritin in female patients with breast cancer, lung cancer and mastitisMethods: 300 patients with carcinoma, hospitalized at Department of Gynecologic Oncology and Department for Oncology at the University Clinics Center of Sarajevo and 200 healthy subjects were compared.Results: In patients with breast cancer the mean value of tumor markers were CEA 155.61 ng/mL, CA 15-3 106.38 U/mL and ferritin 197.03 ng/mL. In patients with lung cancer CEA was 58.97 ng/ml, CA 15-3 40.62 U/mL and ferritin 544.16 ng/mL. Patients with mastitis had CEA 5.17 ng/mL, CA 15-3 112.67 U/mL and ferritin 174.92 ng/mL. The control group had values of tumor markers CEA 1.62 ng/mL, CA 15-3 11.72 U/mL and ferritin 85.35 ng/mL. We found good correlation between CA 15-3 and CEA correlation coeffi cient was r = 0.750. There was a low correlation between CA 15-3 and ferritin with correlation coeffi cient r = 0.274.Conclusions: The CA 15-3 and CEA are useful markers in patients with confi rmed diagnosis of breast and lung cancers. The ferritin concentration has not increased in patients with breast cancer but it increased inlung patients. The future study has to make investigations of tumor markers and ferritin in different stage of breast cancer.

  14. Epigenetic modulation of cancer-germline antigen gene expression in tumorigenic human mesenchymal stem cells: implications for cancer therapy

    DEFF Research Database (Denmark)

    Gjerstorff, Morten; Burns, Jorge S; Nielsen, Ole;

    2009-01-01

    Cancer-germline antigens are promising targets for cancer immunotherapy, but whether such therapies will also eliminate the primary tumor stem cell population remains undetermined. We previously showed that long-term cultures of telomerized adult human bone marrow mesenchymal stem cells can...... modulators, makes them promising targets for immunotherapeutic approaches to cancer treatment....... spontaneously evolve into tumor-initiating, mesenchymal stem cells (hMSC-TERT20), which have characteristics of clinical sarcoma cells. In this study, we used the hMSC-TERT20 tumor stem cell model to investigate the potential of cancer-germline antigens to serve as tumor stem cell targets. We found that...

  15. A Peptide mimicking a region in proliferating cell nuclear antigen specific to key protein interactions is cytotoxic to breast cancer.

    Science.gov (United States)

    Smith, Shanna J; Gu, Long; Phipps, Elizabeth A; Dobrolecki, Lacey E; Mabrey, Karla S; Gulley, Pattie; Dillehay, Kelsey L; Dong, Zhongyun; Fields, Gregg B; Chen, Yun-Ru; Ann, David; Hickey, Robert J; Malkas, Linda H

    2015-02-01

    Proliferating cell nuclear antigen (PCNA) is a highly conserved protein necessary for proper component loading during the DNA replication and repair process. Proteins make a connection within the interdomain connector loop of PCNA, and much of the regulation is a result of the inherent competition for this docking site. If this target region of PCNA is modified, the DNA replication and repair process in cancer cells is potentially altered. Exploitation of this cancer-associated region has implications for targeted breast cancer therapy. In the present communication, we characterize a novel peptide (caPeptide) that has been synthesized to mimic the sequence identified as critical to the cancer-associated isoform of PCNA. This peptide is delivered into cells using a nine-arginine linking mechanism, and the resulting peptide (R9-cc-caPeptide) exhibits cytotoxicity in a triple-negative breast cancer cell line, MDA-MB-436, while having less of an effect on the normal counterparts (MCF10A and primary breast epithelial cells). The novel peptide was then evaluated for cytotoxicity using various in vivo techniques, including ATP activity assays, flow cytometry, and clonogenetic assays. This cytotoxicity has been observed in other breast cancer cell lines (MCF7 and HCC1937) and other forms of cancer (pancreatic and lymphoma). R9-cc-caPeptide has also been shown to block the association of PCNA with chromatin. Alanine scanning of the peptide sequence, combined with preliminary in silico modeling, gives insight to the disruptive ability and the molecular mechanism of action of the therapeutic peptide in vivo. PMID:25480843

  16. Release of carcinoembryonic antigen from human colon cancer cells by phosphatidylinositol-specific phospholipase C.

    OpenAIRE

    Sack, T L; Gum, J R; Low, M G; Y. S. Kim

    1988-01-01

    Carcinoembryonic antigen (CEA) is released from colon cancer cells into the circulation where it is monitored clinically as an indicator of the recurrence or progression of cancer. We have studied the mechanism of CEA membrane attachment and release using the human colonic adenocarcinoma cell line LS-174T, specimens of human colon cancers, and serum from colon cancer patients. CEA release by cells in vitro and in vivo is associated with the conversion of CEA from a membrane-bound, hydrophobic...

  17. Prostate-specific antigen in the early detection of prostate cancer

    OpenAIRE

    Thompson, Ian M; Ankerst, Donna P.

    2007-01-01

    Throughout Canada, the United States and much of Europe, prostate-specific antigen (PSA) screening for prostate cancer has proliferated over the past 2 decades, leading to dramatic increases in detection rates of prostate cancer. Although it has unquestionably led to increased detection of cancer and a migration to lower-stage and -volume tumours, it is still unknown whether PSA screening significantly reduces mortality from prostate cancer. Often thought to be dichotomous (i.e., either norma...

  18. 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 of...

  19. Human antibodies targeting cell surface antigens overexpressed by the hormone refractory metastatic prostate cancer cells: ICAM-1 is a tumor antigen that mediates prostate cancer cell invasion

    OpenAIRE

    Conrad, Fraser; Zhu, Xiaodong; Zhang, Xin; Chalkley, Robert J.; Burlingame, Alma L; Marks, James D.; Liu, Bin

    2009-01-01

    Transition from hormone-sensitive to hormone-refractory metastatic tumor types poses a major challenge for prostate cancer treatment. Tumor antigens that are differentially expressed during this transition are likely to play important roles in imparting prostate cancer cells with the ability to grow in a hormone-deprived environment and to metastasize to distal sites such as the bone and thus, are likely targets for therapeutic intervention. To identify those molecules and particularly cell s...

  20. Identification of tumor-associated antigens as diagnostic and predictive biomarkers in cancer.

    Science.gov (United States)

    Zhang, Jian-Ying; Looi, Kok Sun; Tan, Eng M

    2009-01-01

    Many studies demonstrated that cancer sera contain antibodies which react with autologous cellular antigens generally known as tumor-associated antigens (TAAs). In our laboratories, the approach used in the identification of TAAs has involved initially examining the sera of cancer patients using extracts of tissue culture cells as source of antigens in Western blotting and by indirect immunofluorescence on whole cells. With these two techniques, we identify sera which have high-titer fluorescent staining or strong signals to cell extracts on Western blotting and subsequently use these sera as probes in immunoscreening cDNA expression libraries, and also in proteomic approaches to isolate and identify targeted antigens which might potentially be involved in malignant transformation. In this manner, several novel TAAs including HCC1, p62, p90, and others have been identified. In extension of these studies, we evaluate the sensitivity and specificity of different antigen-antibody systems as markers in cancer in order to develop "tumor-associated antigen array" systems for cancer diagnosis, cancer prediction, and for following the response of patients to treatment. PMID:19381943

  1. Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Despite recent advances in surgery, irradiation, and chemotherapy, the prognosis of patients with lung cancer is still poor. Therefore, the development and application of new therapeutic strategies are essential for improving the prognosis of this disease. Significant progress in our understanding of tumor immunology and molecular biology has allowed us to identify the tumor-associated antigens recognized by cytotoxic T lymphocytes. Immune responses and tumor-associated antigens against not only malignant melanoma but also lung cancer have been elucidated at the molecular level. In a theoretical sense, tumor eradication is considered possible through antigen-based immunotherapy against such diseases. However, many clinical trials of cancer vaccination with defined tumor antigens have resulted in objective clinical responses in only a small number of patients. Tumor escape mechanisms from host immune surveillance remain a major obstacle for cancer immunotherapy. A better understanding of the immune escape mechanisms employed by tumor cells is necessary before we can develop a more effective immunotherapeutic approach to lung cancer. We review recent studies regarding the identification of tumor antigens in lung cancer, tumor immune escape mechanisms, and clinical vaccine trials in lung cancer. (author)

  2. Epigenetic modulation of cancer-germline antigen gene expression in tumorigenic human mesenchymal stem cells: implications for cancer therapy.

    Science.gov (United States)

    Gjerstorff, Morten; Burns, Jorge S; Nielsen, Ole; Kassem, Moustapha; Ditzel, Henrik

    2009-07-01

    Cancer-germline antigens are promising targets for cancer immunotherapy, but whether such therapies will also eliminate the primary tumor stem cell population remains undetermined. We previously showed that long-term cultures of telomerized adult human bone marrow mesenchymal stem cells can spontaneously evolve into tumor-initiating, mesenchymal stem cells (hMSC-TERT20), which have characteristics of clinical sarcoma cells. In this study, we used the hMSC-TERT20 tumor stem cell model to investigate the potential of cancer-germline antigens to serve as tumor stem cell targets. We found that tumorigenic transformation of hMSC-TERT20 cells induced the expression of members of several cancer-germline antigen gene families (ie, GAGE, MAGE-A, and XAGE-1), with promoter hypomethylation and histone acetylation of the corresponding genes. Both in vitro cultures and tumor xenografts derived from tumorigenic hMSC-TERT20 single cell subclones exhibited heterogeneous expression of both GAGE and MAGE-A proteins, and similar patterns of expression were observed in clinical sarcomas. Importantly, histone deacetylase and DNA methyltransferase inhibitors were able to induce more ubiquitous expression levels of cancer-germline antigens in hMSC-TERT20 cells, while their expression levels in primary human mesenchymal stem cells remained unaffected. The expression pattern of cancer-germline antigens in tumorigenic mesenchymal stem cells and sarcomas, plus their susceptibility to enhancement by epigenetic modulators, makes them promising targets for immunotherapeutic approaches to cancer treatment. PMID:19498007

  3. Screening a Novel Human Breast Cancer-Associated Antigen from a cDNA Expression Library of Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Shuhua Yang; Lin Zhang; Ruifang Niu; Defa Wang; Yurong Shi; Xiyin Wei; Yi Yang

    2005-01-01

    OBJECTIVE The aim of this research was to clone and express the antigen of the previously prepared monoclonal antibody named M4G3.METHODS Western blots were used to screen a breast cancer cell line that overexpresses the M4G3-associated antigen. A λ zap cDNA expression library of breast cancer cells was constructed and screened using M4G3 as a probe to clone the antigen. The positive clones were subcloned and identified by homologous comparison using BLAST.RESULTS The λ zap cDNA expression library had 1.0x106 independent clones. Fifteen positive clones were isolated following 3 rounds of immunoscreening and identified as being from Mycoplasma pulmonis.CONCLUSION The specific antigen that matched the monoclonal M4G3 antibody is an unknown protein of M. pulmonis. This work is helpful for the further study of the association of M. pulmonis infection with breast cancer.

  4. Clinical analysis of the value of combined detection of serum CA199 and CA50 levels in patients with pancreatic cancer

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical value of combined test of serum CA199 and CA50 levels in the diagnosis and prognosis of patients with pancreatic cancer. Methods: Serum levels of CA199 and CA50 in 40 cases of pancreatic cancer, 20 cases of chronic pancreatitis and 30 normal controls were detected by radioimmunoassay. Results: Serum CA199 and CA50 levels in pancreatic cancer patients were significantly higher than those in normal controls and chronic pancreatitis patients (P 199 and CA50 were detected simultaneously, the sensitivity, specificity and accuracy of diagnosis of pancreatic cancer could be improved. Serum CA199 and CA50 levels in cancer patients with lymph node metastasis were much higher than those without lymph node metastasis (P 199 and CA50 detected simultaneously could improve the sensitivity and accuracy in diagnosis of pancreatic cancer. The changes of serum CA199 and CA50 level were helpful to predict whether metastasis or recurrence had occurred

  5. Tumor marker CA 15-3 in breast cancer patients

    OpenAIRE

    Hanifa Fejzić; Svjetlana Mujagić; Sanida Azabagić; Mensura Burina

    2015-01-01

    Objective. The aim of this study was to determine whether there is a correlation between the serum concentration of the tumor marker CA 15-3 and breast cancer, which has not been proven by the existence of regional and distant metastases, and breast cancer with the presence of regional and distant metastases. Patients and methods. The study was a retrospective-prospective study, and was conducted on 100 women aged 40-70 years of age in the period of January 2007 until June 2011, in whom, afte...

  6. Rapid detection and quantification of tumor marker carbohydrate antigen 72-4 (CA72-4) using a superparamagnetic immunochromatographic strip.

    Science.gov (United States)

    Chen, Yanrong; Wang, Kan; Liu, Zongrui; Sun, Rongjin; Cui, Daxiang; He, Jinghua

    2016-03-01

    Rapid and quantitative detection of biomarkers with high sensitivity and specificity has become a common practice in the clinical diagnosis and treatment of cancer. Herein, a quantitative lateral flow immunoassay (LFIA) based on superparamagnetic nanoparticles (SPMNPs) was developed for detection of carbohydrate antigen 72-4 (CA72-4) in human serum. This direct and rapid method did not involve any sample preparation and was accomplished using a test strip in which a sandwich reaction was performed. Probes on the conjugate pad were prepared by coupling monoclonal antibody CC49 specific to CA72-4 onto SPMNPs. Coupled monoclonal antibody B72.3 and goat anti-mouse IgG were loaded onto a nitrocellulose (NC) membrane, serving as the test and control lines, respectively. Initially, results were evaluated by macroscopic observation. Afterwards, the magnetic signal strength of the reaction area was quantified using a magnetic assay reader (MAR). Several parameters that may influence the detection sensitivity were studied and optimized. Under optimal conditions, the proposed method was capable of detecting as low as 0.38 IU/mL of CA72-4 in 20 min and had a wide detection linearity range (0-100 IU/mL). We evaluated 100 clinical samples (70 positive and 30 negative) to assess the validity of these test strips, which exhibited high sensitivity (99 %) and specificity (97 %). The results indicated a high rate of accuracy (98.4-102 %) and a low relative standard deviation according to the average recovery test. In conclusion, the test strips based on SPMNP probes are a rapid, sensitive, and quantitative method for the detection of CA72-4 and possess great potential in point-of-care testing (POCT). Graphical Abstract Schematic illustration of the strategy for CA72-4 detection and quantification using a superparamagnetic immunochromatographic strip. PMID:26825343

  7. An ultra-sensitive impedimetric immunosensor for detection of the serum oncomarker CA-125 in ovarian cancer patients

    Science.gov (United States)

    Johari-Ahar, M.; Rashidi, M. R.; Barar, J.; Aghaie, M.; Mohammadnejad, D.; Ramazani, A.; Karami, P.; Coukos, G.; Omidi, Y.

    2015-02-01

    Effective treatment of ovarian cancer depends upon the early detection of the malignancy. Here, we report on the development of a new nanostructured immunosensor for early detection of cancer antigen 125 (CA-125). A gold electrode was modified with mercaptopropionic acid (MPA), and then consecutively conjugated with silica coated gold nanoparticles (AuNP@SiO2), CdSe quantum dots (QDs) and anti-CA-125 monoclonal antibody (mAb). The engineered MPA|AuNP@SiO2|QD|mAb immunosensor was characterised using transmission electron microscopy (TEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Successive conjugation of AuNP@SiO2, CdSe QD and anti-CA-125 mAb onto the gold electrode resulted in sensitive detection of CA-125 with a limit of detection (LOD) of 0.0016 U mL-1 and a linear detection range (LDR) of 0-0.1 U mL-1. Based on the high sensitivity and specificity of the immunosensor, we propose this highly stable and reproducible biosensor for the early detection of CA-125.Effective treatment of ovarian cancer depends upon the early detection of the malignancy. Here, we report on the development of a new nanostructured immunosensor for early detection of cancer antigen 125 (CA-125). A gold electrode was modified with mercaptopropionic acid (MPA), and then consecutively conjugated with silica coated gold nanoparticles (AuNP@SiO2), CdSe quantum dots (QDs) and anti-CA-125 monoclonal antibody (mAb). The engineered MPA|AuNP@SiO2|QD|mAb immunosensor was characterised using transmission electron microscopy (TEM), atomic force microscopy (AFM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Successive conjugation of AuNP@SiO2, CdSe QD and anti-CA-125 mAb onto the gold electrode resulted in sensitive detection of CA-125 with a limit of detection (LOD) of 0.0016 U mL-1 and a linear detection range (LDR) of 0-0.1 U mL-1. Based on the high sensitivity and specificity of the immunosensor, we propose

  8. 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...... 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...

  9. 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.

  10. The clinical relevance of rising CA-125 levels within the normal range in patients with uterine papillary serous cancer.

    Science.gov (United States)

    Frimer, Marina; Hou, June Y; McAndrew, Thomas C; Goldberg, Gary L; Shahabi, Shohreh

    2013-04-01

    The utility of cancer antigen 125 (CA-125) levels as an adjunct method of monitoring patients with uterine papillary serous carcinoma (UPSC) or endometrial serous carcinoma after surgery and adjuvant treatment has been reported. Our goal was to determine the significance of rising CA-125 levels within the normal range in these patients in the posttreatment surveillance setting. All patients with UPSC who underwent surgical staging and had preoperative CA-125 measurement from 1999 to 2008 were included in this analysis. Information was extracted from records to assess the changes in CA-125 values with clinical and/or radiographic detection of recurrence. Of the 56 evaluable patients, 23 (41%) recurred. Of the 23 patients that recurred, 11 had serial CA-125 levels measured in remission. Elevated CA-125 levels at diagnosis were significantly associated with disease recurrence and advanced stage (P = .01, P = .001, respectively). The rise in CA-125 by 10 U/mL in the normal range and ≥ 15 U/mL were associated with disease recurrence (P UPSC after remission, surveillance of CA-125 levels may have a role in disease surveillance and management. PMID:22995987

  11. 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.

  12. Preliminary research on dendritic cells loaded with resistant breast cancer antigens in breast cancer-bearing nude mice

    Institute of Scientific and Technical Information of China (English)

    Wei Zhuang; Limin Lun

    2015-01-01

    Objective The aim of the study was to investigate the inhibitory ef ects of dendritic cel s (DCs) loaded with resistant breast cancer antigens on breast cancer in nude mice. Methods A single-cel suspension was prepared from a primary breast cancer and chemotherapeutic drugs were screened using the ATP-PCA susceptibility testing system. Cancer cel s were treated with 1/10 × IC50, 1/5 × IC50, 1/2 × IC50, 1 × IC50, and 2 × IC50 medium until their growth became steady in the 2 × IC50 medium. Peripheral blood mononuclear cel s (PBMCs) were obtained from the peripheral blood of patients with leukapheresis. The obtained adherent cel s were induced by granulocyte-macrophage colony-stimu-lating factor (GM-CSF) and interleukin-4 (IL-4) to generate DCs, which carried resistant strain cel lysis compounds or non-treated cancer cel lysis compounds. The former mature DCs carried resistant breast tumor antigens. A breast tumor-bearing nude mouse model was established with these resistant strains and the mice were randomly divided in three groups. The mice in the treatment group were injected with DCs loaded with resistant breast cancer antigens. The control group consisted of mice injected with DCs loaded with primary tumor cel antigens and the blank group consisted of mice injected with the same volume of normal saline. Changes in the cancers were observed. Results After treatment with the ef ector cel s, the cancer volume and weight were significantly dif erent to those before treatment in every group of mice (P Conclusion DCs loaded with resistant breast cancer antigens demonstrated a significant inhibition ef ect on the cancers of breast tumor-bearing nude mice.

  13. Benign Hydronephrosis and Elevated of Serum Levels of Carbohydrate Antigen CA 19-9: A Case Report.

    Science.gov (United States)

    Filipovic, Branka; Milinić, Nikola; Gacic, Jasna; Markovic, Olivera; Djokovic, Aleksandra; Filipovic, Branislav

    2016-01-01

    BACKGROUND Carbohydrate tumor-associated antigen (CA 19-9) has been shown to be upregulated in other malignant tumors including gastric, ovarian, hepatocellular, and colorectal carcinoma as well as benign diseases of the biliary track such as pancreatitis, cholangitis, and choledocholithiasis. According to the available literature, in several cases of benign hydronephrosis and in a few cases of benign renal diseases, elevated CA 19-9 has been noted. CASE REPORT A 58-year-old Caucasian male patient was admitted in our clinic with complaints about blunt abdominal pain in the past two-month period localized in the right lumbar region and irradiating into the right inguinal area, constipation, abdominal bloating, and intermittent hematuria. The concentration of serum CA 19-9 was 3500 U/mL. Urine cytology provided no signs of abnormality. Intravenous urography visualized right-sided pyelon and ureter duplex with the defect in contrast shade of the pyelon, caused by a stag horn calculus. Contrast added computerized axial tomography of the abdomen and pelvis visualized the pyelon casted concretion spreading throughout the right pyelon, with ureterohydronephrosis with the distal block for passage of the contrast to the distal part of the ureter. CONCLUSIONS There is no doubt that CA 19-9 level is occasionally elevated in patients with obstructive urolithiasis as it was in our case. In the routine medical praxis, urolithiasis should not be neglected in the differential diagnosis of elevated concentrations of CA 19-9 marker. PMID:27287959

  14. EVALUATION OF FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN RATIO IN THE DIAGNOSIS OF PROSTATE CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ It's reported that free to total prostate specific antigen ration (f/tPSA) can provide more benefit than the single use of prostate specific antigen (PSA) in the diagnosis of prostate cancer (PCa). We measured serum PSA and fPSA levels in 62 cases of benign prostatic hyperplasia (BPH) and 40 cases of PCa using radioimmunoassay, with patients' age range 59y~ 89y.

  15. Tumor markers CA19-9, CA242 and CEA in the diagnosis of pancreatic cancer: a meta-analysis

    OpenAIRE

    Zhang, Yimin; Yang, Jun; Li, Hongjuan; WU, YIHUA; Zhang, Honghe; Chen, Wenhu

    2015-01-01

    Background: Pancreatic cancer has the worst prognosis and early detection is crucial for improving patient prognosis. Therefore, we performed a meta-analysis to evaluate and compare the sensitivity and specificity of single test of CA19-9, CA242, and CEA, as well as combination test in pancreatic cancer detection. Methods: We searched PubMed, Embase, Medline, and Wanfang databases for studies that evaluated the diagnostic validity of CA19-9, CA242, and CEA between January 1990 and September 2...

  16. Distinct roles for histone methyltransferases G9a and GLP in cancer germline antigen gene regulation in human cancer cells and murine ES cells

    OpenAIRE

    Link, Petra A.; Gangisetty, Omkaram; James, Smitha R.; Woloszynska-Read, Anna; Tachibana, Makoto; Shinkai, Yoichi; Karpf, Adam R.

    2009-01-01

    The H3K9me2 histone methyltransferases G9a and GLP repress Mage-a class cancer germline (CG) antigen gene expression in murine ES cells but the role of these enzymes in CG antigen gene regulation in human cancer cells is unknown. Here we show that while independent or dual knockdown of G9a and GLP in human cancer cells leads to reduced global and CG antigen promoter-associated H3K9me2 levels it does not activate CG antigen gene expression. Moreover, CG antigen gene repression is maintained fo...

  17. 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

    response to a cancer related tumor antigen, Balb/c or B6.Cg(CB)-Tg(HLA-A/H2-D)2Enge/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-¿ release, and antibody induction. Gal...... 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....

  18. 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.

    2012-01-01

    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 mut

  19. 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...... confirmed in all three validation cohorts. CONCLUSIONS: CA19-9 response is a robust predictor of survival in patients with inoperable bile duct cancer in four independent data sets....... if a decline in CA19-9 (CA19-9 response) during chemotherapy is predictive of survival in patients with inoperable bile duct cancer. METHODS: 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...

  20. Lineage-specific T cell responses to cancer mucosa antigen oppose systemic metastases without mucosal inflammatory disease

    OpenAIRE

    Snook, Adam E.; Li, Peng; Stafford, Benjamin J.; Elizabeth J. Faul; Huang, Lan; Birbe, Ruth C; Bombonati, Alessandro; Schulz, Stephanie; Schnell, Matthias J.; Eisenlohr, Laurence C.; Waldman, Scott A.

    2009-01-01

    Cancer mucosa antigens comprise an emerging category of self-antigens expressed normally in immunologically privileged mucosal compartments and universally by their derivative tumors (1, 2). These antigens leverage the established immunological partitioning of systemic and mucosal compartments (3, 4), limiting tolerance opposing systemic antitumor efficacy (5). An unresolved issue surrounding self-antigens as immunotherapeutic targets is autoimmunity following systemic immunization (6-8). In ...

  1. Serum squamous cell carcinoma antigen and CYFRA 21-1 in cervical cancer treatment

    International Nuclear Information System (INIS)

    Purpose: To analyze whether serum squamous cell carcinoma (SCC) antigen and cytokeratin-19 fragments (CYFRA) levels can assist in selecting patients with locally advanced cervical cancer who will benefit from combined treatment or additive surgery. Methods and Materials: Of 114 patients with cervical cancer Stage IB-IV, the first 39 patients received radiotherapy, the following 75 patients received identical radiotherapy plus concomitant chemotherapy (3 cycles of carboplatin and 5-fluorouracil). SCC antigen and CYFRA 21-1 serum levels were measured before treatment, after therapy, and during follow-up. Baseline tumor markers were related to tumor stage and size and clinical outcome. Results: Before treatment, SCC antigen was elevated (>1.9 μg/L) in 60% and CYFRA 21-1 (>2.2 μg/L) in 46% of patients. For all patients, disease-free survival (DFS) was better after combined treatment (67% vs. 43%, p<0.0005). For patients with elevated baseline SCC antigen, DFS was better after combination therapy (67% vs. 27%, p=0.001) which resulted more frequently in a normal SCC antigen (93% vs. 65%, p=0.004). In contrast, in those with a normal baseline CYFRA 21-1, combined therapy resulted in a better DFS (p=0.04). Patients who achieved a normal SCC antigen or CYFRA 21-1 after treatment had a better DFS (respectively 63 vs. 17% and 64 vs. 30%). Elevated SCC antigen posttreatment indicated residual tumor in 11/12 patients (92%), elevated CYFRA 21-1 in 7/10 patients (70%). Forty-seven patients had a tumor recurrence. At recurrence, SCC antigen was raised in 70% and CYFRA 21-1 in 69%. Conclusions: In patients with an elevated pretreatment SCC antigen, SCC antigen normalized more frequently with combined treatment and those patients had a better DFS. Elevated SCC antigen or CYFRA 21-1 levels after treatment completion indicated residual tumor in respectively 92% and 70%. The presence of elevated posttreatment levels of SCC antigen or CYFRA 21-1 indicates the need for additional

  2. 检测胃癌血清和腹水中CA72-4抗原水平的临床意义%Clinical significance of CA72-4 antigen levels In serum and peritoneal washing for gastric carcinoma

    Institute of Scientific and Technical Information of China (English)

    孙萍; 盛家和; 王征帆

    2012-01-01

    目的:对胃癌患者进行CA72-4含量的检测,分析血清和腹水中的CA72-4水平与胃癌的相关性,预期判定腹膜复发的可能性.方法:研究了48例胃癌患者血清和腹水中的CA72-4水平、损伤部位及根除和淋巴结转移的数量.结果:淋巴结转移的胃癌患者与血清和腹水中的高水平CA72-4含量显著相关.浆膜浸润胃癌与血清中的CA72-4水平含量无显著统计学相关性,然而,与腹水中的CA72-4水平含量显著相关.尽管血清中的CA72-4水平含量与晚期胃癌无显著相关性,但腹水中的CA72-4水平含量与晚期胃癌呈显著相关.结论:腹水中的CA72-4高水平含量与淋巴结转移和浆膜浸润胃癌显著相关.血清中的CA72-4水平含量仅与淋巴结转移相关,与浆膜浸润胃癌无显著相关.%Objective To detect the content of CA72-4 antigen in ascites of gastric carcinoma patients, CA72-4 levels in serum and ascitic fluid were detected, the relationship between gastric cancer and CA72-4 levels was determined, the possibility of of recurrence in peritoneum was evaluated. Method CA72-4 levels in serum and ascites in 48 cases with gastric cancer were detected, injury site and the number of eradicated metastatic lymph node were documented. Result High content of CA72-4 in serum and ascites of patients was associated with lymph node metastasis of gastric cancer. No significance statistically was found between serum CA72-4 level and serosal invasion of gastric cancer, however, the level of CA72-4 in ascites was associated with serosal invasion of gastric cancer. Although serum CA72-4 level in serum was not correlated with advanced gastric cancer, CA72-4 level of in ascites of patients was not correlated with advanced gastric cancer. Conclusions CA72-4 high level in ascites were correlated with serosal invasion and lymph node metastasis of gastric cancer. Serum CA72-4 level was only associated with lymph node metastasis, but was not associated with serosal

  3. Lewis (y) Antigen Overexpression Increases the Expression of MMP-2 and MMP-9 and Invasion of Human Ovarian Cancer Cells

    OpenAIRE

    Shulan Zhang; Masao Iwamori; Changzhi Wang; Yifei Wang; Chuan Liu; Song Gao; Lili Gao; Bei Lin; Limei Yan

    2010-01-01

    Lewis (y) antigen is a difucosylated oligosaccharide present on the plasma membrane, and its overexpression is frequently found in human cancers and has been shown to be associated with poor prognosis. Our previous studies have shown that Lewis (y) antigen plays a positive role in the process of invasion and metastasis of ovarian cancer cells. However, the mechanisms by which Lewis (y) antigen enhances the invasion and tumor metastasis are still unknown. In this study, we established a stable...

  4. 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...

  5. Potential Target Antigens for a Universal Vaccine in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Renee Vermeij

    2010-01-01

    Full Text Available The prognosis of epithelial ovarian cancer (EOC, the primary cause of death from gynaecological malignancies, has only modestly improved over the last decades. Immunotherapeutic treatment using a cocktail of antigens has been proposed as a “universal” vaccine strategy. We determined the expression of tumor antigens in the context of MHC class I expression in 270 primary tumor samples using tissue microarray. Expression of tumor antigens p53, SP17, survivin, WT1, and NY-ESO-1 was observed in 120 (48.0%, 173 (68.9%, 208 (90.0%, 129 (56.3%, and 27 (11.0% of 270 tumor specimens, respectively. In 93.2% of EOC, at least one of the investigated tumor antigens was (overexpressed. Expression of MHC class I was observed in 78.1% of EOC. In 3 out 4 primary tumors, (overexpression of a tumor antigen combined with MHC class I was observed. These results indicate that a multiepitope vaccine, comprising these antigens, could serve as a universal therapeutic vaccine for the vast majority of ovarian cancer patients.

  6. CaV channels and cancer: canonical functions indicate benefits of repurposed drugs as cancer therapeutics

    OpenAIRE

    Buchanan, Paul J.; McCloskey, Karen D.

    2016-01-01

    The importance of ion channels in the hallmarks of many cancers is increasingly recognised. This article reviews current knowledge of the expression of members of the voltage-gated calcium channel family (CaV) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the CaV channel family are classified according to expression of their pore-forming α-subunit; moreover, co-expression of accessory α2δ, β and γ confers a spectrum of biophysical c...

  7. Genotyping of human leukocyte antigen (HLA) ancestral haplotypes as prognostic marker in cancer using PCR analysis.

    Science.gov (United States)

    Villabona, Lisa; Andersson, Emilia; Marchesi, Maddalena; Masucci, Giuseppe V

    2014-01-01

    The major histocompatibility complex (MHC) comprises a set of genes that are essential to immunity and surveillance against neoplastic transformation. MHC antigens not only regulate antitumor immune responses in experimental animal models but also directly correlate with survival and prognosis of patients with various types of cancers. Effective recognition of tumor cells by effector T cells may be affected by the genotype and the extent of expression of human leukocyte antigen (HLA)-peptide complexes. Therefore, MHC antigens may serve as potential biomarkers for prognosis and allow selection of cancer patients for specific therapy. We describe PCR-based method to determine the HLA genotype in healthy individuals and patients using blood and tumor tissue as DNA source. PMID:24258987

  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. 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...... 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...... relevant for the present study. Four of these included both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) patients, and 31 dealt solely with NSCLC patients. Regarding SCLC no studies showed that serum level of CEA was a prognostic marker for overall survival (OS). The use of CEA...

  10. 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 pros...

  11. Prostate-Specific Antigen Nadir and Time to Prostate-Specific Antigen Nadir Following Maximal Androgen Blockade Independently Predict Prognosis in Patients with Metastatic Prostate Cancer

    OpenAIRE

    Hong, Seok Young; Cho, Dae Sung; Kim, Sun Il; Ahn, Hyun Soo; Kim, Se Joong

    2012-01-01

    Purpose To evaluate the influence of prostate-specific antigen (PSA) kinetics following maximal androgen blockade (MAB) on disease progression and cancer-specific survival in patients with metastatic, hormone-sensitive prostate cancer. Materials and Methods One hundred thirty-one patients with metastatic, hormone-sensitive prostate cancer treated with MAB at our institution were included in this study. Patients' characteristics, PSA at MAB initiation, PSA nadir, time to PSA nadir (TTN), and P...

  12. Usefulness of cancer-testis antigens as biomarkers for the diagnosis and treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Frezza Eldo E

    2007-01-01

    Full Text Available Abstract Despite advances in our cellular and molecular knowledge, hepatocellular carcinoma (HCC remains one of the major public health problems throughout the world. It is now known to be highly heterogeneous: it encompasses various pathological entities and a wide range of clinical behaviors, and is underpinned by a complex array of gene alterations that affect supra-molecular processes. Four families of HCC tumour markers have been recently proposed: a onco-fetal and glycoprotein antigens; b enzymes and iso-enzymes; c cytokines and d genes. A category of tumour-associated antigens called cancer-testis (CT antigens has been identified and their encoding genes have been extensively investigated. CT antigens are expressed in a limited number of normal tissues as well as in malignant tumors of unrelated histological origin, including the liver. Given that cancers are being recognized as increasingly complex, we here review the role of CT antigens as liver tumour biomarkers and their validation process, and discuss why they may improve the effectiveness of screening HCC patients and help in determining the risk of developing HCC.

  13. Primary epithelial splenic cyst with micro-rupture and raised carbohydrate antigen CA 19-9: a proposal for management

    Science.gov (United States)

    Papadopoulos, Iordanis N; Davatzikos, Anastasios; Kasabalis, Georgios; Manti, Christina; Konstantoudakis, Georgios

    2010-01-01

    Background Epithelial splenic cysts are rare entities which surgeons may not have previously encountered. Their management is based on historical studies. Case presentation A 21-year-old woman presented with a cyst of the spleen that produced a high serum concentration of carbohydrate antigen CA 19-9. A partial splenectomy with removal of the entire cyst and preservation of the splenic parenchyma by laparotomy was performed and the patient made an uneventful recovery. A microscopic rupture of the wall of the cyst and blood degradation products in the fluid of the cyst were confirmed. A functional splenic parenchyma was documented 18 months after surgery. There was no infection during follow-up. Conclusion Partial surgical splenectomy with resection of the entire cyst prevents recurrence and preserves splenic function. PMID:22791783

  14. Primary epithelial splenic cyst with micro-rupture and raised carbohydrate antigen CA 19-9: a paradigm of management

    Science.gov (United States)

    Papadopoulos, Iordanis N; Davatzikos, Anastasios; Kasabalis, Georgios; Manti, Christina; Konstantoudakis, Georgios

    2010-01-01

    Epithelial splenic cysts are rare entities that surgeons might not have previously encountered and their management is based on historical studies. A 21-year-old female presented with a cyst of the spleen that produced a high serum concentration of carbohydrate antigen CA 19-9. A partial splenectomy with the removal of the entire cyst and preservation of splenic parenchyma by laparotomy was performed and the patient made an uneventful recovery. A microscopic rupture of the wall of the cyst and degradation of blood in the fluid of the cyst were confirmed. Eighteen months following surgery a functional splenic parenchyma was documented. There was no episode of infection during this follow-up time. Partial surgical splenectomy with resection of the entire cyst prevents recurrence and preserves splenic function. PMID:22767471

  15. The assessment of CA125 determination for ovarian cancer diagnosis and prognosis

    International Nuclear Information System (INIS)

    To study the clinical significance of serum CA125 in patients with ovarian cancer, the serum CA125 levels in 100 patients with gynecologic disease before and after treatment were examined by the method of enzyme linked immunosorbent assay (ELISA). With the positive standard of serum CA125 level > 35 kU/L, the positive rates of ovarian cancer, hysteromyoma, benign teratoma and other benign gynecologic disease were 95%(19/20), 16.7%(6/36), 20%(3/15) and 13.8%(4/29) respectively. But serum CA125 level > 65 kU/L, there was no positive rates except ovarian cancer group. Of the 20 ovarian cancer patients studied, serum CA125 level in 16 cases decreased significantly (< 35 kU/L) after chemical and surgical therapy. Serum CA125 is useful in the diagnosis and evaluation of treatment and prognosis for ovarian cancer

  16. Utility of endoscopic ultrasound, cytology and fluid carcinoembryonic antigen and CA 19-9 levels in pancreatic cystic lesions

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To assess the diagnostic accuracy of endoscopic ultrasound (EUS), fluid tumor markers and cytology in distinguishing benign from (pre)malignant pancreatic cystic lesions.METHODS: 46 consecutive patients, referred to a gastroenterologist and surgeon for a symptomatic or incidental pancreatic cyst, were reviewed. EUS, cytology,and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) levels were compared with the final diagnosis, based on surgical pathology and/or imaging follow-up of at least 12 mo. Cysts were classified as benign (pseudocyst, serous cystadenoma) or malignant/pre-malignant (mucinous cystic neoplasm). Receiveroperator characteristics (ROC) curve analysis was performed.RESULTS: The mean age was 56 years; 29% were male and median cyst diameter was 3 cm. Final outcome was obtained in 41 (89%) patients. Twenty-three (56%) of these 41 had surgical pathology. Twenty-three (56%)had benign lesions and 18 (44%) had malignant/premalignant lesions. Sensitivity, specificity and positive and negative predictive value of EUS alone to distinguish benign from malignant/premalignant pancreatic cystic lesions were 50%, 56%, 36% and 54% and for cytology were 71%, 96%, 92% and 85%, respectively. The corresponding values for the ROC-derived ideal cutoffs were 75%, 90%, 75%, 90% for CA 19-9 (> 37 U/mL)and 70%, 85%, 79% and 78% for CEA (> 3.1 ng/mL).Subgroup analysis of those with surgical pathology yielded almost identical performance and cutoffs.CONCLUSION: Cytology and cyst fluid tumor marker analysis is a very useful tool in distinguishing benign from (pre)malignant pancreatic cystic lesions.

  17. Diagnostic value of combined determination of serum tumor markers (NSE, CA-242, TPA, CEA) levels in patients with lung cancer

    International Nuclear Information System (INIS)

    Objective: To investigate the diagnostic value of combined determination of serum NSE, CA242, tissue polypeptide antigen (TPA) and CEA levels in patients with primary lung cancer. Methods: Serum NSE, CA242, TPA and CEA levels were determined with ELISA in (1) 102 patients with various types of primary lung carcinoma (adenocarcinoma 38, squamous cell carcinoma 32, small cell lung carcinoma 32) (2) 33 patients with open lung T. B. and (3) 30 controls. Results: (1) In patients with lung cancer, serum levels of all the four markers were increased and significantly higher than their respective values in patients with open lung T.B. and controls. (2) Positive rate of combined any two markers were 75% for adenocarcinoma, 50% for squamous cell carcinoma and 65% for small cell lung carcinoma, while false positive rate was only 9% for T.B patients and none for the controls. (3) The most appropriate single marker for each specific type of lung cancer was: NSE for SCLC (sensitivity 72%, specificity 97%, CA242 for adenocarcinoma sensitivity 62%, specificity 90%). Conclusion: Combined determination of these tumor markers would improve the sensitivity and specificity for diagnosis of primary lung carcinoma. (authors)

  18. 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

    increase in the number of gamma-H2AX ‘DNA damage foci’, indicating replicative stress, which may lead to genomic instability. As the p53 tumor suppressor is an inducer of G1 arrest after DNA damage and often deregulated in cancer cells, we investigated if the growth reduction due to SSX2 expression was p53...... 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......The SSX family of cancer and germline antigens is mainly expressed in the germ cells of healthy individuals as well as wide range of cancers and is therefore potential targets for immunotherapy. However, little is known about the role of SSX proteins in tumorigenesis and normal cell function. Here...

  19. Significance of determination of serum CA125 in patients with ovarian cancer

    International Nuclear Information System (INIS)

    Objective: To study the clinical values of determining plasma CA125 in diagnosing and evaluating therapeutic effects in patients with ovarian cancer. Methods: RIA was used to measure serum CA125 in 108 patients with ovarian tumor (malignant: 56 cases, benign: 52 cases) and 38 controls. Results: Serum CA125 levels in 56 ovarian cancer patients were significantly higher than those in controls and patients with ovarian benign tumors; serum CA125 levels in 36 epithelial cancer patients were significantly higher than those in 20 non-epithelial cancer patients. There was no significant difference between patients with benign tumor and controls in serum CA125 possesses greater value in diagnosing ovarian cancer, specially in epithelial cancer and is a useful marker for evaluation of therapeutic effect and prognosis

  20. Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

    OpenAIRE

    Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

    2016-01-01

    Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included ...

  1. Case report: diffuse splenic metastasis of occult breast cancer with incompatible blood group antigenic determinants.

    Science.gov (United States)

    Baranyay, Ferenc

    2009-01-01

    Cancer cells with immunogenic properties having altered protein glycosilation, modified blood group substances have been widely studied [Kannagi R, Miyake M, Zenita KM, Itai S, Hiraiwa N, Shigeta K, et al. Cancer-associated carbohydrate antigens: modified blood group substances and oncodevelopmental antigens on tumor cells. Gann Monogr Cancer Res 1988; 34: p. 15-28; Hakomori S. Antigen structure and genetic basis of histo-blood groups A, B and O their changes associated with human cancer. Biochem Biophys Acta 1999; 1473: p. 247-266; Brooks SA, Carter TM, Royle L, Harvey DJ, Fry SA, Kinch C, et al. Altered glycosilation of proteins in cancer: what is the potential for new anti-tumour strategies. Anticancer Agents Med Chem 2008; 8: p. 2-21]. In the study reported here, a 78-year-old female patient was admitted to the hospital with circulatory failure. At autopsy, the spleen (weight: 420 g) was extremely firm with a diffusely blackberry-colored cut surface. There were no signs of carcinomatous process at autopsy. By histology, the spleen showed diffuse metastatic carcinomatous infiltration. Using immunohistochemistry, an antibody to breast carcinoma antigen (BioGenex) labelled metastatic cells of the spleen and bone marrow. The patient was blood group O. Labelling for binding of lectins with and without blood group antigen specificity and monoclonal antibodies was carried out. The B blood group specific Banderiaea simplicifolia agglutinin I and an anti-B blood group monoclonal antibody labelled all the metastatic cells of spleen and bone marrow intensely. There was no detection of blood group A antigen by either binding of Dolichos biflorus agglutinin or anti-blood group A monoclonal antibodies. These observations raise the possibility that the detected incompatible B blood group antigen determinants on the metastatic cells were immunogenic. The surviving carcinoma cells may have found a place of refuge from immune surveillance in the spleen and in the bone marrow

  2. 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

    2007-01-01

    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. PMID:18693901

  3. Total internal reflection plasmonic scattering-based fluorescence-free nanoimmunosensor probe for ultra-sensitive detection of cancer antigen 125.

    Science.gov (United States)

    Chakkarapani, Suresh Kumar; Zhang, Peng; Ahn, Sujin; Kang, Seong Ho

    2016-07-15

    Highly sensitive detection of cancer antigen 125 (CA125) on nanoarray chips was carried out by means of total internal reflection (TIR) microscopy based on fluorescent labeling (i.e., TIR fluorescence microscopy; TIRFM) and fluorescent-free labeling (TIR scattering microscopy; TIRSM). TIR plasmonic scattering of nanoparticles (NPs) as a fluorescence-free immunosensor probe potentially superior to fluorescent probes was applied to quantify CA125 on a nanoarray chip. NP-labeled CA125 (NP-CA125) was immunoreacted on chips, and the TIR scattering illumination of NP-CA125 allowed quantitative TIRSM measurement of wavelength-dependent plasmonic scattering detection of CA125. In addition, Alexafluor 488-labeled CA125 was immunoreacted on the same chips for comparison of detection sensitivity. TIRSM showed less photobleaching and higher photostability and detection sensitivity than TIRFM, as well as a lower limit of detection (LOD), 0.0018U/mL. This LOD was ~144 times lower than that of previously reported detection methods. These results demonstrated that the wavelength-dependent TIR plasmon NPs can be used as an enhanced nanoimmunosensor probe, providing ultra-sensitive fluorescence-free biomolecule detection to enable earliest-stage disease diagnosis. PMID:26913504

  4. 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. PMID:26969591

  5. 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.

  6. Mitochondrial Ca2+ uniporter is critical for store-operated Ca2+ entry-dependent breast cancer cell migration

    International Nuclear Information System (INIS)

    Metastasis of cancer cells is a complicated multistep process requiring extensive and continuous cytosolic calcium modulation. Mitochondrial Ca2+ uniporter (MCU), a regulator of mitochondrial Ca2+ 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

  7. The novel prostate cancer antigen 3 (PCA3 biomarker

    Directory of Open Access Journals (Sweden)

    Andreas Bourdoumis

    2010-12-01

    Full Text Available PCA3 is a prostate specific, nonprotein coding RNA that is significantly over expressed in prostate cancer, without any correlation to prostatic volume and/or other prostatic diseases (e.g. prostatitis. It can now easily be measured in urine with a novel transcription-mediated amplification based test. Quantification of PCA3 mRNA levels can predict the outcome of prostatic biopsies with a higher specificity rate in comparison to PSA. Several studies have demonstrated that PCA3 can be used as a prognostic marker of prostate cancer, especially in conjunction with other predictive markers. Novel PCA3-based nomograms have already been introduced into clinical practice. PCA3 test may be of valuable help in several PSA quandary situations such as negative prostatic biopsies, concomitant prostatic diseases, and active surveillance. Results from relevant clinical studies, comparative with PSA, are warranted in order to confirm the perspective of PCA3 to substitute PSA.

  8. Loss of antigenicity with tissue age in breast cancer.

    Science.gov (United States)

    Combs, Susan E; Han, Gang; Mani, Nikita; Beruti, Susan; Nerenberg, Michael; Rimm, David L

    2016-03-01

    Archived tumor specimens, particularly those collected by large cooperative groups and trials, provide a wealth of material for post hoc clinical investigation. As these tissues are rigorously collected and preserved for many decades, subsequent use of the specimens to answer clinical questions must rely on the assumption that expression and detection of target biomarkers are not degraded with time. To test this assumption, we measured the expression of estrogen receptor (ER), human epidermal growth receptor 2 (HER2), and Ki67 in human breast carcinoma using quantitative immunofluorescence (QIF) in a series of formalin-fixed paraffin-embedded (FFPE) tissues from 1295 individual patients preserved for 7 to 53 years in four cohorts on tissue microarrays. Protein expression was measured using the automated quantitative analysis method for QIF. Change in quantitative protein expression over time was estimated in positive cases using both Pearson's correlation and a polynomial regression analysis with a random effects model. The average signal decreased with preservation time for all biomarkers measured. For ER and HER2, there was an average of 10% signal loss after 9.9 years and 8.5 years, respectively, compared with the most recent tissue. Detection of Ki67 expression was lost more rapidly, with 10% signal loss in just 4.5 years. Overall, these results demonstrate the need for adjustment of tissue age when studying FFPE biospecimens. The rate of antigenicity loss is biomarker specific and should be considered as an important variable for studies using archived tissues. PMID:26568292

  9. Evolutionary origin and human-specific expansion of a cancer/testis antigen gene family.

    Science.gov (United States)

    Zhang, Qu; Su, Bing

    2014-09-01

    Cancer/testis (CT) antigens are encoded by germline genes and are aberrantly expressed in a number of human cancers. Interestingly, CT antigens are frequently involved in gene families that are highly expressed in germ cells. Here, we presented an evolutionary analysis of the CTAGE (cutaneous T-cell-lymphoma-associated antigen) gene family to delineate its molecular history and functional significance during primate evolution. Comparisons among human, chimpanzee, gorilla, orangutan, macaque, marmoset, and other mammals show a rapid and primate specific expansion of CTAGE family, which starts with an ancestral retroposition in the haplorhini ancestor. Subsequent DNA-based duplications lead to the prosperity of single-exon CTAGE copies in catarrhines, especially in humans. Positive selection was identified on the single-exon copies in comparison with functional constraint on the multiexon copies. Further sequence analysis suggests that the newly derived CTAGE genes may obtain regulatory elements from long terminal repeats. Our result indicates the dynamic evolution of primate genomes, and the recent expansion of this CT antigen family in humans may confer advantageous phenotypic traits during early human evolution. PMID:24916032

  10. CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens.

    Science.gov (United States)

    Almeida, Luiz Gonzaga; Sakabe, Noboru J; deOliveira, Alice R; Silva, Maria Cristina C; Mundstein, Alex S; Cohen, Tzeela; Chen, Yao-Tseng; Chua, Ramon; Gurung, Sita; Gnjatic, Sacha; Jungbluth, Achim A; Caballero, Otávia L; Bairoch, Amos; Kiesler, Eva; White, Sarah L; Simpson, Andrew J G; Old, Lloyd J; Camargo, Anamaria A; Vasconcelos, Ana Tereza R

    2009-01-01

    The potency of the immune response has still to be harnessed effectively to combat human cancers. However, the discovery of T-cell targets in melanomas and other tumors has raised the possibility that cancer vaccines can be used to induce a therapeutically effective immune response against cancer. The targets, cancer-testis (CT) antigens, are immunogenic proteins preferentially expressed in normal gametogenic tissues and different histological types of tumors. Therapeutic cancer vaccines directed against CT antigens are currently in late-stage clinical trials testing whether they can delay or prevent recurrence of lung cancer and melanoma following surgical removal of primary tumors. CT antigens constitute a large, but ill-defined, family of proteins that exhibit a remarkably restricted expression. Currently, there is a considerable amount of information about these proteins, but the data are scattered through the literature and in several bioinformatic databases. The database presented here, CTdatabase (http://www.cta.lncc.br), unifies this knowledge to facilitate both the mining of the existing deluge of data, and the identification of proteins alleged to be CT antigens, but that do not have their characteristic restricted expression pattern. CTdatabase is more than a repository of CT antigen data, since all the available information was carefully curated and annotated with most data being specifically processed for CT antigens and stored locally. Starting from a compilation of known CT antigens, CTdatabase provides basic information including gene names and aliases, RefSeq accession numbers, genomic location, known splicing variants, gene duplications and additional family members. Gene expression at the mRNA level in normal and tumor tissues has been collated from publicly available data obtained by several different technologies. Manually curated data related to mRNA and protein expression, and antigen-specific immune responses in cancer patients are also

  11. 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; Ditzel, Henrik J

    2013-01-01

    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....

  12. A Novel Chimeric Antigen Receptor Against Prostate Stem Cell Antigen Mediates Tumor Destruction in a Humanized Mouse Model of Pancreatic Cancer

    Science.gov (United States)

    Lagisetty, Kiran H.; Tran, Eric; Zheng, Zhili; Gattinoni, Luca; Yu, Zhiya; Burns, William R.; Miermont, Anne M.; Teper, Yaroslav; Rudloff, Udo; Restifo, Nicholas P.; Feldman, Steven A.; Rosenberg, Steven A.; Morgan, Richard A.

    2014-01-01

    Abstract Despite advances in the understanding of its molecular pathophysiology, pancreatic cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate stem cell antigen (PSCA), a glycoprotein that is overexpressed in pancreatic cancer starting at early stages of malignant transformation. To optimize the CAR design, we used antigen-recognition domains derived from mouse or human antibodies, and intracellular signaling domains containing one or two T cell costimulatory elements, in addition to CD3zeta. Comparing multiple constructs established that the CAR based on human monoclonal antibody Ha1-4.117 had the greatest reactivity in vitro. To further analyze this CAR, we developed a human pancreatic cancer xenograft model and adoptively transferred CAR-engineered T cells into animals with established tumors. CAR-engineered human lymphocytes induced significant antitumor activity, and unlike what has been described for other CARs, a second-generation CAR (containing CD28 cosignaling domain) induced a more potent antitumor effect than a third-generation CAR (containing CD28 and 41BB cosignaling domains). While our results provide evidence to support PSCA as a target antigen for CAR-based immunotherapy of pancreatic cancer, the expression of PSCA on selected normal tissues could be a source of limiting toxicity. PMID:24694017

  13. Enzyme immunoassay of pancreatic oncofetal antigen (POA) as a marker of pancreatic cancer.

    OpenAIRE

    Nishida, K; Sugiura, M; Yoshikawa, T; Kondo, M

    1985-01-01

    For the quantitative measurement of pancreatic oncofetal antigen (POA), an enzyme immunoassay for POA has been developed, and is based on the sandwich method using antibody-coupled glass beads and enzyme (peroxidase)-labelled antibody. Serum POA concentrations were increased significantly in patients with pancreatic cancer, but not in those with chronic pancreatitis or other miscellaneous diseases, or in normal subjects. It is concluded that the enzyme immunoassay could be used for the assay ...

  14. Design and cancer-targeting potential of antibody-based molecules directed against carcinoembryonic antigen.

    OpenAIRE

    Huhalov, A.

    2004-01-01

    This thesis examines the use of protein engineering to create antibody-based molecules for cancer treatment. The targeting unit used for these molecules was the single chain Fv antibody fragment MFE-23, which is directed against the tumour-associated marker carcinoembryonic antigen (CEA). It was hypothesised that implementation of molecular design features such as humanisation, high affinity, multivalency and mannose glycosylation to accelerate systemic clearance would result in the favourabl...

  15. 肺癌抗原标志物联合检测的临床应用%Clinical application of joint detection with lung cancer antigen markers

    Institute of Scientific and Technical Information of China (English)

    温仁祝; 戴磊; 张亚男

    2015-01-01

    Objective To explore the best combination of joint detection with lung cancer antigen markers . Methods A random sample of 200 patients diagnosed with primary lung cancer patients ,measuring the level of a wide variety of tumor antigen markers in the blood and statistical analysis . Results In the detection of multiple tumor markers CEA ,NSE ,CYFRA21‐1 and CA125 positive rate is relatively high;serum markers in the expression of related to clinical stage . Conclusion The combined detection of CEA and CA125 ,NSE ,CYFRA21‐1 can im‐prove the accuracy of clinical diagnosis of lung cancer patients .%目的:探讨肺癌抗原标志物联合检测的最佳组合。方法随机抽取200例确诊为原发性肺癌的患者,测定患者血液中多种肿瘤抗原标志物的水平,并进行统计学分析。结果检测的多项肿瘤标志物中CEA、NSE、CYFRA21‐1和CA125的阳性率相对较高;血清各标志物的表达与临床分期有关。结论联合检测CEA、NSE、CYFRA21‐1和CA125能提高肺癌患者的临床诊断准确率。

  16. The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer

    DEFF Research Database (Denmark)

    You, Benoit; Colomban, Olivier; Heywood, Mark; Lee, Chee; Davy, Margaret; Reed, Nicholas; Pignata, Sandro; Varsellona, Nenzi; Emons, Günter; Rehman, Khalid; Steffensen, Karina Dahl; Reinthaller, Alexander; Pujade-Lauraine, Eric; Oza, Amit

    2013-01-01

    Unexpected results were recently reported about the poor surrogacy of Gynecologic Cancer Intergroup (GCIG) defined CA-125 response in recurrent ovarian cancer (ROC) patients. Mathematical modeling may help describe CA-125 decline dynamically and discriminate prognostic kinetic parameters....

  17. Humoral Immune Response against Neural Antigens and Its Effects on Cognition in Lung Cancer Patients.

    Science.gov (United States)

    Rybacka-Mossakowska, J; Ramlau, R; Gazdulska, J; Gołda-Gocka, I; Kozubski, W; Michalak, S

    2016-01-01

    Cognitive impairment develops as a clinical manifestation of immune-mediated indirect effects of malignancy in lung cancer patients. This study aimed to evaluate the effects of humoral immune response on cognition in lung cancer patients. Fifty-one lung cancer patients were subjected to neurological examination: Mini Mental State Examination (MMSE), Trail Making Test (TMT), and Hamilton scale. The Psychology Experiment Building Language software was used for the evaluation of digit span, simple reaction time (SRT), and choice reaction time (CRT) tests. Serum samples were tested for the presence of onconeuronal antibodies and antineural antibodies. The results demonstrate that autoantibodies were found in 31 % patients. MMSE scores were lower (26.7 ± 2.7) in seropositive patients than in seronegative subjects (28.7 ± 1.2; p = 0.013). Executive functions were also influenced by the presence of autoantibodies. The humoral immune response in lung cancer patients affected both SRT and CRT. We conclude that the humoral immune response in lung cancer patients is associated with cognitive impairment. Cognitive impairment is associated with both specific reactions against onconeuronal or antineural antigens and non-organ specific reactions against nucleosome antigens. PMID:26987335

  18. CA 19-9 Level as Indicator of Early Distant Metastasis and Therapeutic Selection in Resected Pancreatic Cancer

    International Nuclear Information System (INIS)

    Purpose: In patients with pancreatic cancer treated with curative resection, we evaluated the effect of clinicopathologic parameters on early distant metastasis within 6 months (DM6m) to identify patients who might benefit from surgery. Methods and Materials: The study involved 84 patients with pancreatic cancer who had undergone curative resection between August 2001 and April 2009. The parameters of gender, age, tumor size, histologic differentiation, T classification, N classification, pre- and postoperative carbohydrate antigen (CA) 19-9 level, resection margin, and adjuvant chemoradiotherapy were analyzed to identify the risk factors associated with DM6m. Results: Of the 84 patients, locoregional recurrence developed in 35 (41.7%) and distant metastasis in 58 (69%). Of the 58 patients with distant metastasis, DM6m had developed in 27 (46.6%). Multivariate analysis showed that preoperative CA 19-9 level was significantly associated with DM6m (p 6m was observed in 9.1%, 50%, and 80% of those with a preoperative CA 19-9 level of ≤100 U/mL, 101–400 U/mL, and >400 U/mL, respectively (p 6m and to identify those who would benefit from surgical resection.

  19. Significance of carbohydrate antigen 50 expression in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To evaluate the significance of carbohydrate antigen 50(CA50)expression in colorectal carcinoma.Methods Immunohistochemical staining was used to detect CA50 expression in 10 cases of normal colorectal mucosa and 40 cases of cancer mucosa.Results The expression of CA50 increased in normal colorectal mucosa,cancer distant mucosa,cancer adjacent mucosa and cancer mucosa,and there were significant differences among them(P<0.05).The expression of CA50 in colorectal carcinoma was correlated with the deg...

  20. Antigen dose escalation study of a VEGF-based therapeutic cancer vaccine in non human primates.

    Science.gov (United States)

    Morera, Yanelys; Bequet-Romero, Mónica; Ayala, Marta; Pérez, Pedro Puente; Castro, Jorge; Sánchez, Javier; Alba, José Suárez; Ancízar, Julio; Cosme, Karelia; Gavilondo, Jorge V

    2012-01-01

    CIGB-247 is a cancer therapeutic, based on recombinant modified human vascular endothelial growth factor (VEGF) as antigen, in combination with the oil free adjuvant VSSP (very small sized proteoliposomes of Neisseria meningitidis outer membrane). Our previous experimental studies in mice with CIGB-247 have shown that the vaccine has both anti-tumoral and anti-metastatic activity, and produces both antibodies that block VEGF-VEGF receptor interaction, and a specific T-cell cytotoxic response against tumor cells. CIGB-247, with an antigen dose of 100 μg, has been characterized by an excellent safety profile in mice, rats, rabbits, and non human primates. In this article we extend the immunogenicity and safety studies of CIGB-247 in non human primates, scaling the antigen dose from 100 μg to 200 and 400 μg/vaccination. Our results indicate that such dose escalation did not affect animal behavior, clinical status, and blood parameters and biochemistry. Also, vaccination did not interfere with skin deep skin wound healing. Anti-VEGF IgG antibodies and specific T-cell mediated responses were documented at all three studied doses. Antigen dose apparently did not determine differences in maximum antibody titer during the 8 weekly immunization induction phase, or the subsequent increase in antibodies seen for monthly boosters delivered afterwards. Higher antigen doses had a positive influence in antibody titer maintenance, after cessation of immunizations. Boosters were important to achieve maximum antibody VEGF blocking activity, and specific T-cell responses in all individuals. Purified IgG from CIGB-247 immunized monkey sera was able to impair proliferation and formation of capillary-like structures in Matrigel, for HMEC cells in culture. Altogether, these results support the further clinical development of the CIGB-247 therapeutic cancer vaccine, and inform on the potential mechanisms involved in its effect. PMID:22075086

  1. TUMOR MARKER CA125、 CA153、 CA199 AND CEA IN LUNG CANCER%肿瘤标记物CA125、CA153、CA199与CEA 在肺癌诊断中的意义

    Institute of Scientific and Technical Information of China (English)

    谢汉华

    2001-01-01

    目的:研究四种肿瘤标记物CA125、CA153、CA199与CEA在肺癌诊断中的意义,并以常见的几种呼吸道炎症性疾病(RIDs)作为对照。结果:肺癌患者CA125、CA153、CA199及CEA水平均显著高于RIDs患者(P<0.001),而CA125、CA153、CA199及CEA水平在肺癌的三种组织学类型和各期肺癌中并显著性差异(P>0.05)。采有四项指标的平均值作为标准,虽然并不能显著提高诊断的灵敏度(P>0.05),但可显著提高诊断的特异性(P<0.05或0.01)。结论:CA125、CA153、CA199及CEA可作为肺癌的标记物,检测这四项标记物在临床上具有一定的辅助意义。%Four tumor markers,CA125,CA153,CA199 and CEA are studied for their relations with lung cancer,using Respiratory Inflammatory Diseases,RIDs (bronchitis,bronchiectasis and pneumonia)as control.The result shows that the serum levels of CA125,CA153,CA199 and CEA are significantly higher in the patients with lung cancer than in those with RIDs(P<0.001).There are not significant differences of the serum level of CA125,CA153,CA199 and in different tissular types of lung cancer and at different phases of lung cancer (P>0.05).The mean value of the four markers is used for a new standard for judging lung cancer.The sensitivity is not significantly higher,but the specificity is significantly lifted(P<0.05 or 0.01).It seems that CA125,CA153,CA199 and CEA can be useful markers for lung cancer,and that the detection of the four markers can play assistant role in the judgement of lung cancer.

  2. AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer.

    Science.gov (United States)

    Vasudevan, Krishna M; Barbie, David A; Davies, Michael A; Rabinovsky, Rosalia; McNear, Chontelle J; Kim, Jessica J; Hennessy, Bryan T; Tseng, Hsiuyi; Pochanard, Panisa; Kim, So Young; Dunn, Ian F; Schinzel, Anna C; Sandy, Peter; Hoersch, Sebastian; Sheng, Qing; Gupta, Piyush B; Boehm, Jesse S; Reiling, Jan H; Silver, Serena; Lu, Yiling; Stemke-Hale, Katherine; Dutta, Bhaskar; Joy, Corwin; Sahin, Aysegul A; Gonzalez-Angulo, Ana Maria; Lluch, Ana; Rameh, Lucia E; Jacks, Tyler; Root, David E; Lander, Eric S; Mills, Gordon B; Hahn, William C; Sellers, William R; Garraway, Levi A

    2009-07-01

    Dysregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway occurs frequently in human cancer. PTEN tumor suppressor or PIK3CA oncogene mutations both direct PI3K-dependent tumorigenesis largely through activation of the AKT/PKB kinase. However, here we show through phosphoprotein profiling and functional genomic studies that many PIK3CA mutant cancer cell lines and human breast tumors exhibit only minimal AKT activation and a diminished reliance on AKT for anchorage-independent growth. Instead, these cells retain robust PDK1 activation and membrane localization and exhibit dependency on the PDK1 substrate SGK3. SGK3 undergoes PI3K- and PDK1-dependent activation in PIK3CA mutant cancer cells. Thus, PI3K may promote cancer through both AKT-dependent and AKT-independent mechanisms. Knowledge of differential PI3K/PDK1 signaling could inform rational therapeutics in cancers harboring PIK3CA mutations. PMID:19573809

  3. Preoperative serum levels of CEA and CA 242 in colorectal cancer.

    OpenAIRE

    Carpelan-Holmström, M; Haglund, C.; Kuusela, P.; Järvinen, H; Roberts, P. J.

    1995-01-01

    Preoperative serum levels of CEA and CA 242 were determined in 260 patients with colorectal cancer and in 92 patients with benign colorectal diseases. The overall sensitivity of the CEA test was 43% and of the CA 242 test 39%. The corresponding specificities were 90% and 87% respectively, using 5 ng ml-1 as cut-off level for CEA and 20 U ml-1 for CA 242. The sensitivity of CEA was 26%, 32%, 38% and 77% for Dukes A, B, C and D colorectal cancer, and the sensitivity of CA 242 was 26%, 26%, 40% ...

  4. Pretreatment prostate-specific antigen doubling times: clinical utility of this predictor of prostate cancer behavior

    International Nuclear Information System (INIS)

    Purpose: The distribution of pretreatment and posttreatment prostate specific antigen (PSA) doubling times (PSADT) varies widely. This report examines the pretreatment PSADT as an independent predictor of biochemical freedom from disease (bNED) and describes the clinical utility of PSADT. Methods and Materials: Ninety-nine patients with T1-3 NX, M-0 prostate cancer treated between February 1989 and November 1993 have pretreatment PSADTs calculated from three or more PSA levels. Biochemical disease-free (bNED) survival (failure is PSA ≥ 1.5 ngm/ml and rising) is evaluated by multivariate analysis of common prognostic indicators and PSADT. Results: Prostate-specific antigen doubling time (PSADT) is a significant predictor of survival along with radiation dose. Patients with a pretreatment PSADT of < 12 months show 50% failure by 18 months, while those with a PSADT that is not increasing show only 3% failure at 3 years. Conclusions: Prostate-specific antigen doubling time (PSADT) is a predictor of bNED outcome in prostate cancer. Patients with PSADT < 12 months have aggressive disease and should be considered for multimodal therapy. Slow PSADT (≥ 5 years) is observed in 57% of patients, and this end point may be considered in the decision to observe rather than to treat. After treatment failure, the PSADT may be used to determine which patients do not need immediate androgen deprivation

  5. Changes in tumor-antigen expression profile as human small-cell lung cancers progress

    International Nuclear Information System (INIS)

    Our group has previously observed that in patients with small-cell lung cancers (SCLCs), the expression of a tumor antigen, glioma big potassium (gBK) ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein (TAPP). We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production. SCLC samples (eight surgical resections and three autopsy samples) and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets. Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of P53-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody. Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages

  6. Expression of gastric cancer-associated MG7 antigen in gastric cancer, precancerous lesions and H. pylori-associated gastric diseases

    Institute of Scientific and Technical Information of China (English)

    Dong-Li Guo; Ming Dong; Lan Wang; Li-Ping Sun; Yuan Yuan

    2002-01-01

    AIM: To investigate the relationship between the antigen MG7 antigen expression and gastric cancer as well as precancerous condition; to study the relationship between the MG7 antigen expression and H. pyloriinfection in benign gastric lesions in order to find out the effect of H. pylori infection on the process of gastric cancer development.METHODS: The level of MG7 antigen expression was determined by immunohistochemical method in 383 gastric biopsied materials. The intestinal metaplasia was determined by histochemistry method. The H. pyloriinfection was determined by HE stain, PCR and ELISA in 291 specimens, among which only 34 cases of H. pylori-associated gastric lesions were followed up.RESULTS: The positive rate of MG7 expression in normal gastric mucosa, intestinal metaplasia, dysplasia and gastric cancer increased gradually in ascending order (P<0.01). The positive rate of MG7 antigen expression in type Ⅲ intestinal metaplasia of gastric mucosa was higher than that of type Ⅰand Ⅱ intestinal metaplasia, being highly significant (P<0.05).The positive rate of MG7 antigen expression in superficial gastritis, atrophic gastritis and gastric cancer increased gradually (11.9 %, 64.8 %, 91.2 %, P<0.01). There was no significant difference between H.pylori-negative and H. pyloripositive intestinal metaplasia, atrophic gastritis and dysplasia of gastric epithelium in the positive rate of MG7 antigen expression. There was no expression of MG7 antigen in H. pylori-negative superficial gastritis. The positive rate of MG7 expression in H. pylori-positive superficial gastritis was 20.5 %, and the difference between them was significant (P<0.05). During following up, one of the three H. pylori negative cases turned positive again, and its MG7 antigen expression turned to be stronger correspondingly. 3 of 31 H. pyloripositive cases were detected as early gastric cancer, among which one with "+++" MG7 antigen expression was diminished after H. pylori

  7. Targeting Tumor Initiating Cells through Inhibition of Cancer Testis Antigens and Notch Signaling: A Hypothesis.

    Science.gov (United States)

    Colombo, Michela; Mirandola, Leonardo; Reidy, Adair; Suvorava, Natallia; Konala, Venu; Chiaramonte, Raffaella; Grizzi, Fabio; Rahman, Rakhshanda Layeequr; Jenkins, Marjorie R; Nugyen, Diane D; Dalhbeck, Scott; Cobos, Everardo; Figueroa, Jose A; Chiriva-Internati, Maurizio

    2015-03-01

    Tumor initiating cells (TICs) differ from normal stem cells (SCs) in their ability to initiate tumorigenesis, invasive growth, metastasis and the acquisition of chemo and/or radio-resistance. Over the past years, several studies have indicated the potential role of the Notch system as a key regulator of cellular stemness and tumor development. Furthermore, the expression of cancer testis antigens (CTA) in TICs, and their role in SC differentiation and biology, has become an important area of investigation. Here, we propose a model in which CTA expression and Notch signaling interacts to maintain the sustainability of self-replicating tumor populations, ultimately leading to the development of metastasis, drug resistance and cancer progression. We hypothesize that Notch-CTA interactions in TICs offer a novel opportunity for meaningful therapeutic interventions in cancer. PMID:25901861

  8. 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...

  9. Ca²⁺ Movement Induced by Deltamethrin in PC3 Human Prostate Cancer Cells.

    Science.gov (United States)

    Lee, Hai-Hsiang; Chou, Chiang-Ting; Liang, Wei-Zhe; Chen, Wei-Chuan; Wang, Jue-Long; Yeh, Jeng-Hsien; Kuo, Chun-Chi; Shieh, Pochuen; Kuo, Daih-Huang; Chen, Fu-An; Jan, Chung-Ren

    2016-06-30

    This study explored the effect of deltamethrin, a pesticide, on intracellular free Ca²⁺ concentration ([Ca²⁺]i) in PC3 human prostate cancer cells. Deltamethrin at concentrations between 5 μM and 20 μM evoked [Ca²⁺]i rises in a concentration-dependent manner. This Ca²⁺ signal was inhibited by 22% by removal of extracellular Ca²⁺. Nifedipine, econazole, and SKF96365 also inhibited the Ca²⁺ signal. Treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) in Ca²⁺-free medium nearly abolished deltamethrin-induced [Ca²⁺]i rises. Treatment with deltamethrin also inhibited most of BHQ-induced [Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122 failed to alter deltamethrin-evoked [Ca²⁺]i rises. Deltamethrin killed cells at concentrations of 20-100 μM in a concentration-dependent fashion. Chelation of cytosolic Ca²⁺ with 1,2-bis (2-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid/acetoxymethyl ester (BAPTA/AM) did not prevent deltamethrin's cytotoxicity. Together, in PC3 human prostate cancer cells, deltamethrin induced [Ca²⁺]i rises that involved Ca²⁺ entry through store-operated Ca²⁺ channels and PLC-independent Ca²⁺ release from the endoplasmic reticulum. Deltamethrin induced cytotoxicity in a Ca²⁺-independent manner. PMID:27188467

  10. Chimeric Antigen Receptor-Engineered T Cells for Immunotherapy of Cancer

    Directory of Open Access Journals (Sweden)

    Marc Cartellieri

    2010-01-01

    Full Text Available CD4+ and CD8+ T lymphocytes are powerful components of adaptive immunity, which essentially contribute to the elimination of tumors. Due to their cytotoxic capacity, T cells emerged as attractive candidates for specific immunotherapy of cancer. A promising approach is the genetic modification of T cells with chimeric antigen receptors (CARs. First generation CARs consist of a binding moiety specifically recognizing a tumor cell surface antigen and a lymphocyte activating signaling chain. The CAR-mediated recognition induces cytokine production and tumor-directed cytotoxicity of T cells. Second and third generation CARs include signal sequences from various costimulatory molecules resulting in enhanced T-cell persistence and sustained antitumor reaction. Clinical trials revealed that the adoptive transfer of T cells engineered with first generation CARs represents a feasible concept for the induction of clinical responses in some tumor patients. However, further improvement is required, which may be achieved by second or third generation CAR-engrafted T cells.

  11. Serum CA125 is a novel predictive marker for pancreatic cancer metastasis and correlates with the metastasis-associated burden

    OpenAIRE

    Liu, Liang; Xu, Hua-Xiang; Wang, Wen-Quan; Wu, Chun-tao; Xiang, Jin-Feng; Liu, Chen; Long, Jiang; Xu, Jin; Fu, De-Liang; Ni, Quan-Xing; Houchen, Courtney W.; Postier, Russell G.; Li, Min; Yu, Xian-Jun

    2016-01-01

    This study evaluated potential of serum tumor markers to predict the incidence and intensity of pancreatic cancer metastasis as well as patient survival. Retrospective records from 905 patients and prospective data from 142 patients were collected from two high-volume institutions. The levels of eight serum tumor markers (CA19-9, CEA, CA242, CA72-4, CA50, CA125, CA153, and AFP) commonly used in gastroenterological cancer were analyzed in all stages of pancreatic cancer. Serum CA125 levels wer...

  12. 血清CEA、CA125、CA199、CA153联检在肺癌中的诊断价值%The value of joint detection of serum CEA, CA125, CA199 and CA153 in diagnosis of lung cancer

    Institute of Scientific and Technical Information of China (English)

    王露; 徐红珍

    2009-01-01

    目的 评价血清CEA、CA125、CA199、CA153联合检测对肺癌的诊断价值.方法 用化学发光法测定45例肺癌患者,50例肺良性疾病患者及30例健康体检者血清CEA、CA125、CA199、CA153水平的变化,评价4项指标联合应用的诊断价值.结果 肺癌组血清CEA、CA125、CA199、CA153含量明显高于对照组(P<0.01),单项肿瘤指标CEA、CA125、CA199、CA153的检测敏感性分别为53.3%、48.9%、35.6%、37.8%.联合检测可提高检测的敏感性达87.6%.结论 肿瘤标志物CEA、CA125、CA199、CA153的联合检测可提高肺癌的诊断率,可为肺癌的早期诊断提供有价值的资料.%Objective To evaluate the clinical value of measuring the four tumor makers(CEA,CA125,CA199,CA153)for diagnosis of lung cancer. Methods These tumor markers in serum were measured with chemiluminescence immunoassay in 45 patients with lung cancer, 50 benign lung diseases and 30 healthy subjects. Results The level of the markers in lung cancer group were all higher than those of benign lung diseases and healthy subjects. The sensitivity of single tumor marker (CEA,CA125,CA199,CA153)was 53.3%,48.9%,35.6%,37.8% respectively. The sensitivity of combined measurement was 87.6%. Conclusion The combined measurement of serum CEA,CA125,CA199,CA153 significantly increase the sensitivity for lung cancer, and provide useful information for early diagnosis of disease in patients with lung cancer.

  13. Detection of PIK3CA Mutations in Breast Cancer Bone Metastases

    OpenAIRE

    Manijeh Daneshmand; Hanson, Jennifer E. L.; Mitra Nabavi; Hilton, John F.; Lisa Vandermeer; Femina Kanji; Dent, Susan F; Mark Clemons; Ian A. J. Lorimer

    2012-01-01

    Background. An important goal of personalized cancer therapy is to tailor specific therapies to the mutational profile of individual patients. However, whole genome sequencing studies have shown that the mutational profiles of cancers evolve over time and often differ between primary and metastatic sites. Activating point mutations in the PIK3CA gene are common in primary breast cancer tumors, but their presence in breast cancer bone metastases has not been assessed previously. Results. Fourt...

  14. Grant R01CA138800 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  15. Grant R01CA107408 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  16. Grant R21CA184788 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  17. Grant R01CA161534 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  18. Grant R21CA182111 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  19. Grant R03CA121827 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  20. Grant R21CA185460 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  1. Up-regulation of HLA class-I antigen expression and antigen-specific CTL response in cervical cancer cells by the demethylating agent hydralazine and the histone deacetylase inhibitor valproic acid

    Directory of Open Access Journals (Sweden)

    Lizano-Soberón Marcela

    2006-12-01

    Full Text Available Abstract Background DNA hypermethylation and histone deacetylation are epigenetic events that contribute to the absence or downregulated expression of different components of the tumor recognition complex. These events affect the processing and presentation of antigenic peptides to CTLs by HLA class-I molecules. In this work evaluated the effect of the DNA hypomethylating agent hydralazine and the histone deacetylase inhibitor valproic acid, on the expression of HLA class-I molecules and on the antigen-specific immune recognition of cervical cancer cells. Methods Cell lines C33A (HPV-, CaSki (HPV-16+ and MS751 (HPV-18+ were treated with hydralazine and valproic acid to assess the expression of HLA class-I molecules by flow cytometry and RT-PCR. Promoter methylation of HLA class-I -A, -B and C, was also evaluated by Methylation-Specific PCR. Primary cervical tumors of four HLA-A*0201 allele patients were typed for HPV and their CTL's stimulated in vitro with the T2 cell line previously loaded with 50 μM of the HPV peptides. Cytotoxicity of stimulated CTL's was assayed against Caski and MS751 cells pre-treated with hydralazine and valproic acid. Results Valproic acid and hydralazine/valproic acid up-regulated the constitutive HLA class-I expression as evaluated by flow cytometry and RT-PCR despite constitutive promoter demethylation at these loci. Hydralazine and valproic acid in combination but no IFN-gamma hyperacetylated histone H4 as evaluated by ChiP assay. The antigenic immune recognition of CaSki and MS751 cells by CTLs specific to HPV-16/18 E6 and E7-derived epitopes, was increased by VA and H/VA and the combination of H/VA/IFN-gamma. Conclusion These results support the potential use of hydralazine and valproic acid as an adjuvant for immune intervention in cervical cancer patients whenever clinical protocols based on tumor antigen recognition is desirable, like in those cases where the application of E6 and E7 based therapeutic vaccines

  2. Comparative study of CA242 and CA19-9 in chronic pancreatitis.

    OpenAIRE

    Furuya, N; Kawa, S; Hasebe, O.; Tokoo, M.; Mukawa, K.; Maejima, S.; Oguchi, H.

    1996-01-01

    CA242 has been proved to be useful in the diagnosis of pancreatic cancer. The aim of the present study was to clarify the mechanisms contributing to the high specificity of CA242 as compared with CA19-9 resulting from scarce serum elevation of this antigen in patients with chronic pancreatitis by correlating serum levels and endoscopic retrograde choledocho-pancreatography (ERCP) findings and by immunohistochemical analysis. Serum CA19-9 levels were significantly elevated in patients with cal...

  3. Prostate cancer antigen 3 as a biomarker in the urine for prostate cancer diagnosis: A meta-analysis

    Directory of Open Access Journals (Sweden)

    Wu-Jin Xue

    2014-01-01

    Full Text Available Objective: The aim of this study was to investigate the clinical value of urine Prostate cancer antigen 3 (PCA3 test in the diagnosis of prostate cancer by pooling the published data. Methods: The clinical trials about urine PCA3 test in the diagnosis of prostate cancer were searched in the PubMed (January, 1966-July, 2014. Cochrane library (Section 3, 2013, CNKI (March, 1994-July, 2014. All relevant prospective studies of urine PCA3 test in the diagnosis of prostate cancer were screened. The aggregated sensitivity, specificity, positive likely hood ratio (+LR, negative likely hood ratio (−LR, diagnosis odds ratio (DOR and area under the area under curve (AUC were calculated by using Meta-disc 1.4 and STATA 11.0 statistic software. Results: Finally, a total of 13 trials including 3245 subjects were included in this meta-analysis. The pooled sensitivity, specificity, +LR, −LR, DOR and AUC were 0.62 (95% confidence interval [CI]: 0.59-0.65, 0.75 (95% CI: 0.73-0.76, 6.16 (95% CI: 3.39-11.21, 0.50 (95% CI: 0.43-0.59, 5.49 (95% CI: 3.76-8.019 and 0.75 (95% CI: 0.71-0.78, respectively. Conclusion: Urine PCA3 test has acceptable sensitivity and specificity in the diagnosis of prostate cancer, which can be used as non-invasive method for diagnosis of prostate cancer.

  4. 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

  5. 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

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

    International Nuclear Information System (INIS)

    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

  7. Molecular Pathways: Breaking the Epithelial Cancer Barrier for Chimeric Antigen Receptor and T-cell Receptor Gene Therapy.

    Science.gov (United States)

    Hinrichs, Christian S

    2016-04-01

    Adoptive transfer of T cells genetically engineered to express a tumor-targeting chimeric antigen receptor (CAR) or T-cell receptor (TCR) can mediate cancer regression in some patients. CARs are synthetic single-chain proteins that use antibody domains to target cell surface antigens. TCRs are natural heterodimeric proteins that can target intracellular antigens through recognition of peptides bound to human leukocyte antigens. CARs have shown promise in B-cell malignancies and TCRs in melanoma, but neither approach has achieved clear success in an epithelial cancer. Treatment of epithelial cancers may be particularly challenging because of a paucity of target antigens expressed by carcinomas and not by important healthy tissues. In addition, epithelial cancers may be protected by inhibitory ligands and soluble factors in the tumor microenvironment. One strategy to overcome these negative regulators is to modulate expression of T-cell genes to enhance intrinsic T-cell function. Programmable nucleases, which can suppress inhibitory genes, and inducible gene expression systems, which can enhance stimulatory genes, are entering clinical testing. Other work is delineating whether control of genes for immune checkpoint receptors (e.g.,PDCD1, CTLA4) and cytokine and TCR signaling regulators (e.g.,CBLB, CISH, IL12, IL15) can increase the antitumor activity of therapeutic T cells.Clin Cancer Res; 22(7); 1559-64. ©2016 AACR. PMID:27037253

  8. CA19-9-related tumor kinetics after first-line chemotherapy of patients with advanced pancreatic cancer: a monoinstitutional experience.

    Science.gov (United States)

    Colloca, Giuseppe; Venturino, Antonella; Guarneri, Domenico

    2016-09-01

    The absolute value of carbohydrate antigen 19-9 (CA19-9) pretreatment and its reduction after chemotherapy are established prognostic variables for patients with advanced pancreatic cancer. The present study is a retrospective monoinstitutional evaluation of the prognostic role of the CA19-9 reduction and some CA19-9-related tumor kinetics parameters, such as tumor growth rate constant (G), kinetic tumor response and log ratio. Forty-one cases met the selection criteria. After 8 weeks only G reported an inverse relationship with OS (r = -0.494) that was confirmed by regression analysis (R (2) = 0.192). G after 8 weeks of chemotherapy appears as a possible surrogate end point of overall survival. PMID:27522503

  9. Genetic Variant as a Selection Marker for Anti–Prostate Stem Cell Antigen Immunotherapy of Bladder Cancer

    OpenAIRE

    Kohaar, Indu; Porter-Gill, Patricia; Lenz, Petra; Fu, Yi-Ping; Mumy, Adam; Tang, Wei; Apolo, Andrea B.; Rothman, Nathaniel; Baris, Dalsu; Schned, Alan R.; Ylaya, Kris; Schwenn, Molly; Johnson, Alison; Jones, Michael; Kida, Masatoshi

    2012-01-01

    A monoclonal antibody against prostate stem cell antigen (PSCA) has emerged as a novel cancer therapy currently being tested in clinical trials for prostate and pancreatic cancers, but this treatment is likely to be efficient only in patients with PSCA-expressing tumors. The present study demonstrates that a genetic variant (rs2294008) discovered by bladder cancer genome-wide association studies is a strong predictor of PSCA protein expression in bladder tumors, as measured by two-sided multi...

  10. 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; Fuchs, Andreas; Linz, Christian; Kübler, Alexander C; Müller-Richter, Urs D A

    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 recep...... between MAGE-A5 and -A11 and lower efficacy of EGFR TKIs. Pretreatment analysis of MAGE-A status may therefore aid improvement of chemoprevention using erlotinib and gefitinib in head and neck cancer....

  11. Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications

    International Nuclear Information System (INIS)

    Cancer–testis antigens (CTA) comprise a family of proteins, which are physiologically expressed in adult human tissues solely in testicular germ cells and occasionally placenta. However, CTA expression has been reported in various malignancies. CTAs have been identified by their ability to elicit autologous cellular and or serological immune responses, and are considered potential targets for cancer immunotherapy. The breast differentiation antigen NY-BR-1, expressed specifically in normal and malignant breast tissue, has also immunogenic properties. Here we evaluated the expression patterns of CTAs and NY-BR-1 in breast cancer in correlation to clinico-pathological parameters in order to determine their possible impact as prognostic factors. The reactivity pattern of various mAbs (6C1, MA454, M3H67, 57B, E978, GAGE #26 and NY-BR-1 #5) were assessed by immunohistochemistry in a tissue micro array series of 210 randomly selected primary invasive breast cancers in order to study the diversity of different CTAs (e.g. MAGE-A, NY-ESO-1, GAGE) and NY-BR-1. These expression data were correlated to clinico-pathological parameters and outcome data including disease-free and overall survival. Expression of at least one CTA was detectable in the cytoplasm of tumor cells in 37.2% of the cases. NY-BR-1 expression was found in 46.6% of tumors, respectively. Overall, CTA expression seemed to be linked to adverse prognosis and M3H67 immunoreactivity specifically was significantly correlated to shorter overall and disease-free survival (p=0.000 and 0.024, respectively). Our findings suggest that M3H67 immunoreactivity could serve as potential prognostic marker in primary breast cancer patients. The exclusive expression of CTAs in tumor tissues as well as the frequent expression of NY-BR-1 could define new targets for specific breast cancer therapies

  12. 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.; Jarle, Christensen,I; Gayther, S.; Jacobs, I.J.; Hogdall, C.K.; Kjær, Susanne Krüger

    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......AIMS: To determine the variation in expression of carcinoembryonic antigen (CEA) in 760 epithelial ovarian tumours from Denmark, and to correlate expression with clinicopathological parameters and prognosis for the disease. METHODS: Using tissue arrays (TA), we analysed CEA expression in tissues...

  13. Body mass index in relation to serum prostate-specific antigen levels and prostate cancer risk.

    Science.gov (United States)

    Bonn, Stephanie E; Sjölander, Arvid; Tillander, Annika; Wiklund, Fredrik; Grönberg, Henrik; Bälter, Katarina

    2016-07-01

    High Body mass index (BMI) has been directly associated with risk of aggressive or fatal prostate cancer. One possible explanation may be an effect of BMI on serum levels of prostate-specific antigen (PSA). To study the association between BMI and serum PSA as well as prostate cancer risk, a large cohort of men without prostate cancer at baseline was followed prospectively for prostate cancer diagnoses until 2015. Serum PSA and BMI were assessed among 15,827 men at baseline in 2010-2012. During follow-up, 735 men were diagnosed with prostate cancer with 282 (38.4%) classified as high-grade cancers. Multivariable linear regression models and natural cubic linear regression splines were fitted for analyses of BMI and log-PSA. For risk analysis, Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) and natural cubic Cox regression splines producing standardized cancer-free probabilities were fitted. Results showed that baseline Serum PSA decreased by 1.6% (95% CI: -2.1 to -1.1) with every one unit increase in BMI. Statistically significant decreases of 3.7, 11.7 and 32.3% were seen for increasing BMI-categories of 25 prostate cancer risk although results were indicative of a positive association to incidence rates of high-grade disease and an inverse association to incidence of low-grade disease. However, findings regarding risk are limited by the short follow-up time. In conclusion, BMI was inversely associated to PSA-levels. BMI should be taken into consideration when referring men to a prostate biopsy based on serum PSA-levels. PMID:26914149

  14. Prostate-specific membrane antigen targeted protein contrast agents for molecular imaging of prostate cancer by MRI

    Science.gov (United States)

    Pu, Fan; Salarian, Mani; Xue, Shenghui; Qiao, Jingjuan; Feng, Jie; Tan, Shanshan; Patel, Anvi; Li, Xin; Mamouni, Kenza; Hekmatyar, Khan; Zou, Juan; Wu, Daqing; Yang, Jenny J.

    2016-06-01

    Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high resolution has yet to be achieved due to the lack of contrast agents with significantly improved relaxivity for sensitivity, targeting capabilities and metal selectivity. We have previously reported our creation of a novel class of protein Gd3+ contrast agents, ProCA32, which displayed significantly improved relaxivity while exhibiting strong Gd3+ binding selectivity over physiological metal ions. In this study, we report our effort in further developing biomarker-targeted protein MRI contrast agents for molecular imaging of PSMA. Among three PSMA targeted contrast agents engineered with addition of different molecular recognition sequences, ProCA32.PSMA exhibits a binding affinity of 1.1 +/- 0.1 μM for PSMA while the metal binding affinity is maintained at 0.9 +/- 0.1 × 10-22 M. In addition, ProCA32.PSMA exhibits r1 of 27.6 mM-1 s-1 and r2 of 37.9 mM-1 s-1 per Gd (55.2 and 75.8 mM-1 s-1 per molecule r1 and r2, respectively) at 1.4 T. At 7 T, ProCA32.PSMA also has r2 of 94.0 mM-1 s-1 per Gd (188.0 mM-1 s-1 per molecule) and r1 of 18.6 mM-1 s-1 per Gd (37.2 mM-1 s-1 per molecule). This contrast capability enables the first MRI enhancement dependent on PSMA expression levels in tumor bearing mice using both T1 and T2-weighted MRI at 7 T. Further development of these PSMA-targeted contrast agents are expected to be used for the precision imaging of prostate cancer at an early stage and to monitor disease progression and staging, as well as determine the effect of therapeutic treatment by non-invasive evaluation of the PSMA level using MRI.Prostate-specific membrane antigen (PSMA) is one of the most specific cell surface markers for prostate cancer diagnosis and targeted treatment. However, achieving molecular imaging using non-invasive MRI with high

  15. PIK3CA mutation detection in metastatic biliary cancer using cell-free DNA

    OpenAIRE

    Kim, Seung Tae; Lira, Maruja; Deng, Shibing; Lee, Sujin; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Mao, Mao; Heo, Jin Seok; Kwon, Wooil; Jang, Kee-Taek; Lee, Jeeyun; Park, Joon Oh

    2015-01-01

    PIK3CA mutation is considered a good candidate for targeted therapies in cancers, especially biliary tract cancer (BTC). We evaluated the utility of cell free DNA (cfDNA) from serum by using droplet digital PCR (ddPCR) as an alternative source for PIK3CA mutation analysis. To identify matching archival tumour specimens from serum samples of advanced BTC patients, mutation detection using ddPCR with Bio-Rad's PrimePCR mutation and wild type assays were performed for PIK3CA p.E542K, p.E545K, an...

  16. Pretreatment Carbohydrate Antigen 19-9 Level Indicates Tumor Response, Early Distant Metastasis, Overall Survival, and Therapeutic Selection in Localized and Unresectable Pancreatic Cancer

    International Nuclear Information System (INIS)

    Purpose: The use of chemoradiotherapy (CRT) for localized and unresectable pancreatic cancer has been disputed because of high probability of distant metastasis. Thus, we analyzed the effect of clinical parameters on tumor response, early distant metastasis within 3 months (DM3m), and overall survival to identify an indicator for selecting patients who would benefit from CRT. Methods and Materials: This study retrospectively analyzed the data from 84 patients with localized and unresectable pancreatic cancer who underwent CRT between August 2002 and October 2009. Sex, age, tumor size, histological differentiation, N classification, pre- and post-treatment carbohydrate antigen (CA) 19-9 level, and CA 19-9 percent decrease were analyzed to identify risk factors associated with tumor response, DM3m, and overall survival. Results: For all 84 patients, the median survival time was 12.5 months (range, 2–31.9 months), objective response (complete response or partial response) to CRT was observed in 28 patients (33.3%), and DM3m occurred in 24 patients (28.6%). Multivariate analysis showed that pretreatment CA 19-9 level (≤400 vs. >400 U/ml) was significantly associated with tumor response (45.1% vs. 15.2%), DM3m (19.6% vs. 42.4%), and median overall survival time (15.1 vs. 9.7 months) (p 3m, and overall survival and identifying patients who will benefit from CRT.

  17. Design of a bifunctional fusion protein for ovarian cancer drug delivery: single-chain anti-CA125 core-streptavidin fusion protein.

    Science.gov (United States)

    Wang, Welson Wen-Shang; Das, Dipankar; McQuarrie, Stephen A; Suresh, Mavanur R

    2007-03-01

    We have developed a universal ovarian cancer cell targeting vehicle that can deliver biotinylated therapeutic drugs. A single-chain antibody variable domain (scFv) that recognizes the CA125 antigen of ovarian cancer cells was fused with a core-streptavidin domain (core-streptavidin-VL-VH and VL-VH-core-streptavidin orientations) using recombinant DNA technology and then expressed in Escherichia coli using the T7 expression system. The bifunctional fusion protein (bfFp) was expressed in a shaker flask culture, extracted from the periplasmic soluble protein, and affinity purified using an IMAC column. The two distinct activities (biotin binding and anti-CA125) of the bfFp were demonstrated using ELISA, Western blot and confocal laser-scanning microscopy (CLSM). The ELISA method utilized human NIH OVCAR-3 cells along with biotinylated bovine serum albumin (B-BSA) or biotinylated liposomes, whereas, the Western blot involved probing with B-BSA. The CLSM study has shown specificity in binding to the OVCAR-3 cell-line. ELISA and Western blot studies have confirmed the bifunctional activity and specificity. In the presence of bfFp, there was enhanced binding of biotinylated antigen and liposome to OVCAR-3 cells. In contrast, the control EMT6 cells, which do not express the CA125 antigen, showed minimal binding of the bfFp. Consequently, bfFp based targeting of biotinylated therapeutic drugs, proteins, liposomes, or nanoparticles could be an alternative, convenient method to deliver effective therapy to ovarian cancer patients. Peritoneal infusion of the bfFp-therapeutic complex could also be effective in locally targeting the most common site of metastatic spread. PMID:17257818

  18. 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.

  19. CA-125 and Ceruloplasmin Levels in Ovarian Cancer Patients

    OpenAIRE

    Mangala Hegde; Yousef Rezaei Chianeh; Jeevan Shetty; Donald J. Fernandes; Pragna Rao

    2015-01-01

    Purpose: The initial stage of proliferation of epithelial ovarian carcinoma (EOCa) is usually asymptomatic. Due to the lack of sensitive and reliable markers in majority of patients the disease is widespread at the time of diagnosis. The reliable serum biomarkers currently accepted is CA125 but there is limitation in case of sensitivity of CA125 as it is detectable only in 50% of patients in stage I and 80% of patients with advanced stage. We have investigated a correlation between serum CA12...

  20. 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

  1. Prostate-Specific Antigen fluctuation: what does it mean in diagnosis of prostate cancer?

    Directory of Open Access Journals (Sweden)

    Jun Seok Kim

    2015-04-01

    Full Text Available Objective To investigate whether prostate-specific antigen (PSA fluctuation correlates with a prostate cancer and to assess whether PSA fluctuation could be used for diagnosis of prostate cancer. Materials and Methods Our study included 229 patients who were performed a prostate biopsy (non-cancer group, 177; prostate cancer group, 52. Enrolled patients were provided twice PSA tests within 6 months. PSA fluctuation (%/month was defined as a change rate of PSA per a month. Independent t test was used to compare between two groups. Receiver operator characteristic curve was used to assess the availability as a differential diagnostic tool and the correlation. Simple linear regression was performed to analyze a correlation between PSA fluctuation and other factors such as age, PSA, PSA density, and prostate volume. Results There were significant differences in PSA, PSA density, percentage of free PSA, and PSA fluctuation between two groups. PSA fluctuation was significantly greater in non-cancer group than prostate cancer group (19.95±23.34%/month vs 9.63±8.57%/month, P=0.004. The most optimal cut-off value of PSA fluctuation was defined as 8.48%/month (sensitivity, 61.6%; specificity, 59.6%; AUC, 0.633; P=0.004. In a simple linear regression model, only PSA level was significantly correlated with PSA fluctuation. Conclusion Patients with wide PSA fluctuations, although baseline PSA levels are high, might have a low risk of diagnosis with prostate cancer. Thus, serial PSA measurements could be an option in patients with an elevated PSA level.

  2. Expression of a plant-associated human cancer antigen in normal,premalignant and malignant esophageal tissues

    Institute of Scientific and Technical Information of China (English)

    Jun Fu; Ping Qu; Mo Li; Hai-Mei Tian; Zhen-Hai Zheng; Xin-Wen Zheng; Wei Zhang

    2003-01-01

    AIM: To study the relationship between the expression profiles of a plant-associated human cancer antigen and carcinogenesis of esophagus and its significance. METHODS: We analyzed expression of a plant-associated human cancer antigen in biopsy specimens of normal (n=29),mildly hyperplastic (n=29), mildly (n=30), moderately (n=27)and severely dysplastic (n=29) and malignant esophageal (n=30) tissues by immunohistochemistry. RESULTS: The plant-associated human cancer antigen was mainly confined to the cytoplasm and showed diffuse type of staining. Positive staining was absent or weak in normal (0/30) and mildly hyperplastic tissue samples (2/29), while strong staining was observed in severe dysplasia (23/29) and carcinoma in situ (24/30). There was significant difference of its expression between normal mucosa and severely dysplastic tissues (P<0.001) or carcinoma in situ (P<0.001). Significant difference was also observed between mild dysplasia and severe dysplasia (P<0.001) or carcinomain situ (P<0.001). An overall trend toward increased staining intensity with increasing grade of dysplasia was found. There was a linear correlation between grade of lesions and staining intensity (r=0.794,P<0.001). Samples from esophageal cancer showed no higher levels of expression than those in severely dysplastic lesions (P>0.05). CONCLUSION: The abnormal expression of this plantassociated human cancer antigen in esophageal lesions is a frequent and early finding in the normal-dysplasiacarcinoma sequence in esophageal carcinogenesis. It might contribute to the carcinogenesis of esophageal cancer. The abnormal expression of this plant-associated human cancer antigen in esophageal lesion tissues may serve as a potential new biomarker for early identification of esophageal cancer.

  3. The Expression Leuel of CA15-3 and TPS of Patient with Mamumary Cancer and its Clinical Value%乳腺癌患者血清CA15~3和TPS表达水平及其临床价值

    Institute of Scientific and Technical Information of China (English)

    王玉珍; 李军; 苗爱莲; 魏曙亚; 候蓉; 原荣; 张俊

    2002-01-01

    Objective To study the clinical value for breast cancer by combining testing the serumexpression levels of CA15-3and Tissue polypeptide specific antigen(TPS).Methods CA15-3 and TPS inserum sample of 92 cases of patients with breast cancer were analysed by using ELISA in two weeks beforeand after treatment of operation and drugs. Results The values of CA15 ~ 3 and TPS in serum were highersignificanec in patients with breast cancer than those in the control group of healthy subjects and breastbenign diseases goup(P < 0.01). Expression levels of CA15~3 in serum were significance increased with TNM staging and TPS with clinical one to two stage. The serum levels of CA15- 3 and TPS in the breastcancer patients with treatment of surgery were markly decreased in two weeks after operation(P < 0.01 )and no changed in the patients without operation whose condition was stable and it was significantly in-creased the patients with progressive and relapse especially TPS. Conelusion CA15 ~ 3 and TPS can beused as useful tumor markers of breast cancer in diagnosis of early stage, evaluating of therapeutic effect,assessing the prognosis of the disease, and it is highly usefulin monitoring recurrences of breast cancer, es-pecially dynamic detection.

  4. Evaluation of the potential role of the new Cancer-Testis Antigen BORIS for the development of novel strategies of immunotherapy of cancer

    International Nuclear Information System (INIS)

    BORIS/CTCFL (for brother of the regulator of imprinted sites), a paralogue of the transcription factor CTCF, is a recently described novel member of the cancer-testis (CT) antigen family (Loukinov D, et al. Proc Natl Acad Sci USA 2002;99:6806). BORIS expression appears to be restricted to testicular germ cells and to a vast majority of neoplastic cells including both cancer cell lines and primary tumors (Klenova EM, et al. Semin Cancer Biol 2002;12:399)

  5. 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.

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

    International Nuclear Information System (INIS)

    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

  7. Evaluation of prostate cancer antigen 3 for detecting prostate cancer: a systematic review and meta-analysis

    Science.gov (United States)

    Cui, Yong; Cao, Wenzhou; Li, Quan; Shen, Hua; Liu, Chao; Deng, Junpeng; Xu, Jiangfeng; Shao, Qiang

    2016-05-01

    Previous studies indicate that prostate cancer antigen 3 (PCA3) is highly expressed in prostatic tumors. However, its clinical value has not been characterized. The aim of this study was to investigate the clinical value of the urine PCA3 test in the diagnosis of prostate cancer by pooling the published data. Clinical trials utilizing the urine PCA3 test for diagnosing prostate cancer were retrieved from PubMed and Embase. A total of 46 clinical trials including 12,295 subjects were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (‑LR), diagnostic odds ratio (DOR) and area under the curve (AUC) were 0.65 (95% confidence interval [CI]: 0.63–0.66), 0.73 (95% CI: 0.72–0.74), 2.23 (95% CI: 1.91–2.62), 0.48 (95% CI: 0.44–0.52), 5.31 (95% CI: 4.19–6.73) and 0.75 (95% CI: 0.74–0.77), respectively. In conclusion, the urine PCA3 test has acceptable sensitivity and specificity for the diagnosis of prostate cancer and can be used as a non-invasive method for that purpose.

  8. 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.

  9. PIK3CA mutation detection in metastatic biliary cancer using cell-free DNA

    Science.gov (United States)

    Deng, Shibing; Lee, Sujin; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Mao, Mao; Heo, Jin Seok; Kwon, Wooil; Jang, Kee-Taek; Lee, Jeeyun; Park, Joon Oh

    2015-01-01

    PIK3CA mutation is considered a good candidate for targeted therapies in cancers, especially biliary tract cancer (BTC). We evaluated the utility of cell free DNA (cfDNA) from serum by using droplet digital PCR (ddPCR) as an alternative source for PIK3CA mutation analysis. To identify matching archival tumour specimens from serum samples of advanced BTC patients, mutation detection using ddPCR with Bio-Rad's PrimePCR mutation and wild type assays were performed for PIK3CA p.E542K, p.E545K, and p.H1047R. Thirty-eight patients with metastatic BTC were enrolled. Only one (BTC 29T) sample (n = 38) was positive for PIK3CA p.E542K and another (BTC 27T) for p.H1047R mutation; none was positive for PIK3CA p.E545K. Matched serum sample (BTC 29P) was positive for PIK3CA p.E542K with 28 mutant copies detected, corresponding to 48 copies/ml of serum and an allelic prevalence of 0.3%. Another matched serum sample (BTC 27P) was positive for PIK3CA p.H1047R with 10 mutant copies detected, i.e. 18 copies/ml and an allelic frequency of 0.2%. High correlation was noted in the PIK3CA mutation status between tumour gDNA and serum cfDNA. Low-level PIK3CA mutations were detectable in the serum indicating the utility of cfDNA as a DNA source to detect cancer-derived mutations in metastatic biliary cancers. PMID:26498688

  10. A novel strategy to improve antigen presentation for active immunotherapy in cancer. Fusion of the human papillomavirus type 16 E7 antigen to a cell penetrating peptide

    International Nuclear Information System (INIS)

    Facilitating the delivery of exogenous antigens to antigen-presenting cells, ensuing processing and presentation via the major histocompatibility complex class I and induction of an effective immune response are fundamental for an effective therapeutic cancer vaccine. In this regard, we propose the use of cell-penetrating peptides fused to a tumor antigen. To demonstrate this concept we designed a fusion protein comprising a novel cell-penetrating and immunostimulatory peptide corresponding to residues 32 to 51 of the Limulus anti-lipopolysaccharide factor protein (LALF32-51) linked to human papillomavirus 16 E7 antigen (LALF32-51-E7). In this work, we demonstrated that the immunization with LALF32-51-E7 using the TC-1 mouse model induces a potent and long-lasting anti-tumor response supported on an effective E7-specific CD8+T-cell response. The finding that therapeutic immunization with LALF32-51 or E7 alone, or an admixture of LALF32-51 and E7, does not induce significant tumor reduction indicates that covalent linkage between LALF32-51 and E7 is required for the anti-tumor effect. These results support the use of this novel cell-penetrating peptide as an efficient means for delivering therapeutic targets into cellular compartments with the induction of a cytotoxic CD8+T lymphocyte immune response. This approach is promissory for the treatment of tumors associated with the human papillomavirus 16, which is responsible for the 50% of cervical cancer cases worldwide and other malignancies. Furthermore, protein-based vaccines can circumvent the major histocompatibility complex specificity limitation associated with peptide vaccines providing a greater extent in their application

  11. CA 15-3 and lipid profile in preoperative breast cancer patients

    International Nuclear Information System (INIS)

    The transmembrane glycoprotein CA 15-3 is the most widely used serum tumor marker in breast cancer. At present the main uses of CA 15-3 are in pre-clinically detecting recurrent breast cancer and monitoring the treatment of patients with advanced breast cancer. The aim of this study was to define the role of preoperative concentrations of serum CA 15-3a sp rognostic factor and to determine its sensitivity. Serum and plasma samples from breast cancer patients and normal individuals under fasting condition were used to estimate CAlS-3 and lipid profile. The lipid profile was done in order to assess the impact of plasma lipid on the progression of breast cancer. The serum concentration of the tumor marker CAlS-3 in preoperative breast cancer patients was found to be significantly higher (p<0.001) as compared to the normal individuals. The plasma cholesterol (TC), triglyceride (TRG) and total lipid (TL) levels in breast cancer patients were found to be significantly higher (p< O.OI) for TC, TRG and TL as compared to the normal individuals. Moreover, plasma LDL-C levels in breast cancer patients were found to be significantly higher (p< O.OI) compared to the normal individuals. (author)

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

    Science.gov (United States)

    Tokudome, Shinkan; Ando, Ryosuke; Koda, Yoshiro

    2016-01-01

    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 in biopsy specimens; 2) independent quantification of Gleason grading; 3) developing ethnicity-specific staging nomograms based on tumor stage, PSA value, and Gleason score; 4) delineation of the natural history; 5) revisiting the significance of the androgen/testosterone hypothesis; and 6) devoting special attention to individuals with a certain genetic predisposition. Finally

  13. 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

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

    Science.gov (United States)

    Tokudome, Shinkan; Ando, Ryosuke; Koda, Yoshiro

    2016-01-01

    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 in biopsy specimens; 2) independent quantification of Gleason grading; 3) developing ethnicity-specific staging nomograms based on tumor stage, PSA value, and Gleason score; 4) delineation of the natural history; 5) revisiting the significance of the androgen/testosterone hypothesis; and 6) devoting special attention to individuals with a certain genetic predisposition. Finally

  15. Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning

    International Nuclear Information System (INIS)

    To determine whether tumors containing carcinoembryonic antigen could be detected by administration of a radiolabeled, affinity-purified, goat IgG having 70% immunoreactivity against carcinoembryonic antigen, 18 patients with a history of cancer of diverse histopathology received an average total dose of 1.0 mCi of 131I-labeled IgG. Total-body photoscans were performed with a gamma scintillation camera at various intervals after administration of the radioactive antibody. Ordinary photoscans proved difficult to interpret because of blood-pool background radioactivity, thus necessitating the computer subtraction of radioactive blood-pool agents from the antibody's 131I activity. Tumor location could be demonstrated at 48 hours after injection in almost all cases studied. The scans were negative in patients without demonstrable tumors or with tumors apparently devoid of carcinoembryonic antigen. Circulating antigen levels of up to 350 ng per milliliter did not prevent successful tumor imaging after injection of the radioantibody

  16. Invasive breast cancer in Argentine women: association between risk and prognostic factors with antigens of a peptidic and carbohydrate nature

    Directory of Open Access Journals (Sweden)

    Croce MV

    2011-12-01

    Full Text Available Sandra O Demichelis, Marina T Isla-Larrain, Luciano Cermignani, Cecilio G Alberdi, Amada Segal-Eiras, María Virginia CroceCentre of Basic and Applied Immunological Research, Faculty of Medical Sciences, National University of La Plata, La Plata, ArgentinaObjective: In breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis.Results: All the antigens showed an increased expression according to tumor size increment; moreover, sialyl Lewis x expression showed a significant increase in relation to disease stage, whereas Tn and TF presented a positive tendency. Vascular invasion was related to sialyl Lewis x expression and number of metastatic lymph nodes. Taking into account risk factors, when a patient had at least one child, Lewis antigens diminished their expression. In relation to breastfeeding, sialyl Lewis x expression diminished, although its apical expression increased.Conclusion: Associations between MUC1 and carbohydrate antigens and risk and prognostic factors show the complexity of the cellular biological behavior that these antigens modulate in breast cancer.Keywords: breast cancer, Argentine women, risk factors, prognostic factors, antigenic expression

  17. Antigen-receptor interaction requirement for conjugate formation and lethal-hit triggering by cytotoxic T lymphocytes can be bypassed by protein kinase C activators and Ca2+ ionophores

    International Nuclear Information System (INIS)

    The authors show that phorbol esters and Ca2+ ionophores can trigger the lysis of nonantigen-bearing target cells by cytotoxic T lymphocytes. This effect obviates the requirement for antigen-receptor-mediated recognition of the antigen; the intensity of lysis is dose and Ca2+ dependent and requires contact between cytotoxic T lymphocytes and target cells. Using a fluorescence-activated cell sorter to enumerate cytotoxic T lymphocyte-target cell conjugates, they show that phorbol esters at concentrations that triggered lysis of non-antigen-bearing target cells also increased the number of stable conjugates with these target cells. The results point to the importance of the antigen-nonspecific engagements of cytotoxic T lymphocytes in immunologic surveillance. The data also show that the linkage between the T-cell receptor and antigen is not mandatory for conjugate formation, for the strengthening of conjugates, and for lysis

  18. Expression Patterns of Cancer-Testis Antigens in Human Embryonic Stem Cells and Their Cell Derivatives Indicate Lineage Tracks

    OpenAIRE

    Olga Gordeeva; Tatyana Yakovleva; Galina Poljanskaya; Tatyana Krylova; Anna Koltsova; Nadya Lifantseva

    2011-01-01

    Pluripotent stem cells can differentiate into various lineages but undergo genetic and epigenetic changes during long-term cultivation and, therefore, require regular monitoring. The expression patterns of cancer-testis antigens (CTAs) MAGE-A2, -A3, -A4, -A6, -A8, -B2, and GAGE were examined in undifferentiated human embryonic stem (hES) cells, their differentiated derivatives, teratocarcinoma (hEC) cells, and cancer cell lines of neuroectodermal and mesodermal origin. Undifferentiated hES ce...

  19. A Peptide Mimicking a Region in Proliferating Cell Nuclear Antigen Specific to Key Protein Interactions Is Cytotoxic to Breast Cancer

    OpenAIRE

    Smith, Shanna J.; Gu, Long; Phipps, Elizabeth A.; Lacey E Dobrolecki; Mabrey, Karla S.; Gulley, Pattie; Dillehay, Kelsey L; Dong, Zhongyun; Fields, Gregg B.; Chen, Yun-Ru; Ann, David; Hickey, Robert J.; Malkas, Linda H.

    2015-01-01

    Proliferating cell nuclear antigen (PCNA) is a highly conserved protein necessary for proper component loading during the DNA replication and repair process. Proteins make a connection within the interdomain connector loop of PCNA, and much of the regulation is a result of the inherent competition for this docking site. If this target region of PCNA is modified, the DNA replication and repair process in cancer cells is potentially altered. Exploitation of this cancer-associated region has imp...

  20. 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. PMID:26869189

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

    Directory of Open Access Journals (Sweden)

    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.

  2. 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...

  3. 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.

    2011-01-01

    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 tr

  4. Expression and prognostic significance of cancer-testis antigens (CTA in intrahepatic cholagiocarcinoma

    Directory of Open Access Journals (Sweden)

    Chen Sun-xiao

    2011-01-01

    Full Text Available Abstract Background Cancer-testis antigens (CTAs are suitable targets for cancer-specific immunotherapy. The aim of the study is to investigate the expression of CTAs in intrahepatic cholagiocarcinoma (IHCC and evaluate their potential therapeutic values. Methods Eighty-nine IHCC patients were retrospectively assessed for their expression of CTAs and HLA Class I by immunohistochemistry using the following antibodies: MA454 recognizing MAGE-A1, 57B recognizing multiple MAGE-A (MAGE-A3/A4, E978 recognizing NY-ESO-1, and EMR8-5 recognizing HLA class I. The clinicopathological and prognostic significance of individual CTA markers and their combination were further evaluated. Results The expression rates of MAGE-A1, MAGE-A3/4 and NY-ESO-1 were 29.2%, 27.0% and 22.5%, respectively. The concomitant expression of CTAs and HLA class I antigen was observed in 33.7% of the IHCC tumors. We found that positive MAGE-3/4 expression correlated with larger tumor size (≥ 5 cm, tumor recurrence and poor prognosis. Moreover, we identified 52 cases (58.4% of IHCC patients with at least one CTA marker expression, and this subgroup displayed a higher frequency of larger tumor size and a shorter survival than the other cases. Furthermore, expression of at least one CTA marker was also an independent prognostic factor in patients with IHCC. Conclusion Our data suggest that specific immunotherapy targeted CTAs might be a novel treatment option for IHCC patients.

  5. 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.

  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. PMID:26921096

  7. Prevalence of PIK3CA mutations and the SNP rs17849079 in Arab breast cancer patients

    OpenAIRE

    Karakas, Bedri; Colak, Dilek; Kaya, Namik; Ghebeh, Hazem; Al-Qasem, Abeer; Hendrayani, Fawziah; Toulimat, Mohamed; Al-Tweigeri, Taher; Park, Ben Ho; ABOUSSEKHRA, ABDELILAH

    2013-01-01

    Carcinomas initiate and progress due to genetic and epigenetic alterations in epithelial cells. However, recently, these alterations have also been reported in stromal fibroblasts. The gain-of-function mutations in the PI3K p110 catalytic subunit (PIK3CA) have been identified in many cancers with a current global incidence of 26% (18–40%) in breast carcinomas. We analyzed the mutational frequency of PIK3CA of three hotspots (exons 1, 9, and 20) in 81 primary invasive breast cancers (BC) and 2...

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

    International Nuclear Information System (INIS)

    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

  9. 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.

  10. Epstein–Barr virus latent antigens EBNA3C and EBNA1 modulate epithelial to mesenchymal transition of cancer cells associated with tumor metastasis

    OpenAIRE

    Gaur, Nivedita; Gandhi, Jaya; Erle S Robertson; Verma, Subhash C.; Kaul, Rajeev

    2014-01-01

    Epithelial–mesenchymal transition is an important mechanism in cancer invasiveness and metastasis. We had previously reported that cancer cells expressing Epstein–Barr virus (EBV) latent viral antigens EBV nuclear antigen EBNA3C and/ or EBNA1 showed higher motility and migration potential and had a propensity for increased metastases when tested in nude mice model. We now show that both EBNA3C and EBNA1 can modulate cellular pathways critical for epithelial to mesenchymal transition of cancer...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Prevalence of PIK3CA mutations and the SNP rs17849079 in Arab breast cancer patients

    Science.gov (United States)

    Karakas, Bedri; Colak, Dilek; Kaya, Namik; Ghebeh, Hazem; Al-Qasem, Abeer; Hendrayani, Fawziah; Toulimat, Mohamed; Al-Tweigeri, Taher; Park, Ben Ho; Aboussekhra, Abdelilah

    2013-01-01

    Carcinomas initiate and progress due to genetic and epigenetic alterations in epithelial cells. However, recently, these alterations have also been reported in stromal fibroblasts. The gain-of-function mutations in the PI3K p110 catalytic subunit (PIK3CA) have been identified in many cancers with a current global incidence of 26% (18–40%) in breast carcinomas. We analyzed the mutational frequency of PIK3CA of three hotspots (exons 1, 9, and 20) in 81 primary invasive breast cancers (BC) and 25 cultured breast cancer-associated fibroblast (CAF) samples by Sanger sequencing in Arab breast cancer patients. Associations between the incidence of any PIK3CA mutation and several clinicopathologic characteristics were assessed using chi-square tests for categorical or t test for continuous variables. Furthermore, survival curves were estimated using the Kaplan–Meier method with the log rank test to evaluate the significance of their differences. We identified a total of 21 PIK3CA missense mutations with a frequency of 25.9%. The majority of the mutations, 17 out of 21 (81%), were in exon 20 (p.His1047Arg, p.His1047Lys, p.Thr1025Ala, p.Gly1049Arg, p.Asp1056Asn) while the remainder, 4 out of 21 (19%) were in exon 9 (p.Glu545Lys). PIK3CA mutations were significantly associated with lower grade and hormone receptor positivity. Although there was a favorable trend in overall survival for patients whose tumor harbored PIK3CA mutations, the difference was not statistically significant (P = 0.10). However, we did not detect any somatic mutations in CAFs. Furthermore, we have shown a high prevalence (8.2-fold) of a silent variant (SNP, rs17849079) in the Arab breast cancer population compared with disease-free individuals. PMID:23982433

  13. Prevalence of PIK3CA mutations and the SNP rs17849079 in Arab breast cancer patients.

    Science.gov (United States)

    Karakas, Bedri; Colak, Dilek; Kaya, Namik; Ghebeh, Hazem; Al-Qasem, Abeer; Hendrayani, Fawziah; Toulimat, Mohamed; Al-Tweigeri, Taher; Park, Ben Ho; Aboussekhra, Abdelilah

    2013-10-01

    Carcinomas initiate and progress due to genetic and epigenetic alterations in epithelial cells. However, recently, these alterations have also been reported in stromal fibroblasts. The gain-of-function mutations in the PI3K p110 catalytic subunit (PIK3CA) have been identified in many cancers with a current global incidence of 26% (18-40%) in breast carcinomas. We analyzed the mutational frequency of PIK3CA of three hotspots (exons 1, 9, and 20) in 81 primary invasive breast cancers (BC) and 25 cultured breast cancer-associated fibroblast (CAF) samples by Sanger sequencing in Arab breast cancer patients. Associations between the incidence of any PIK3CA mutation and several clinicopathologic characteristics were assessed using chi-square tests for categorical or t test for continuous variables. Furthermore, survival curves were estimated using the Kaplan-Meier method with the log rank test to evaluate the significance of their differences. We identified a total of 21 PIK3CA missense mutations with a frequency of 25.9%. The majority of the mutations, 17 out of 21 (81%), were in exon 20 (p.His1047Arg, p.His1047Lys, p.Thr1025Ala, p.Gly1049Arg, p.Asp1056Asn) while the remainder, 4 out of 21 (19%) were in exon 9 (p.Glu545Lys). PIK3CA mutations were significantly associated with lower grade and hormone receptor positivity. Although there was a favorable trend in overall survival for patients whose tumor harbored PIK3CA mutations, the difference was not statistically significant (P = 0.10). However, we did not detect any somatic mutations in CAFs. Furthermore, we have shown a high prevalence (8.2-fold) of a silent variant (SNP, rs17849079) in the Arab breast cancer population compared with disease-free individuals. PMID:23982433

  14. 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.

  15. Towards antibody-mediated targeting of dendritic cells for cancer immunotherapy with multivalent polymer-antigen conjugates

    OpenAIRE

    Reuter, Anika

    2013-01-01

    Der Fokus dieser Arbeit lag auf der definierten Synthese multifunktioneller Polymer-Konjugate zur Anwendung in der Krebs-Immunotherapie. Durch gezielte Variation der Kon-jugationsbedingungen wurde Zusammensetzung, Größe und Aggregationsverhalten in Zell-medium sowie in humanem Serum untersucht. Nach definierter physikalisch-chemischer Charakterisierung wurde dann die induzierte Antigen-Präsentation zur Aktivierung der T-Zellproliferation analysiert.rnDafür wurden zwei verschiedene polymere Ca...

  16. Human leukocyte antigen (HLA)-G gene polymorphism in patients with non-small cell lung cancer

    OpenAIRE

    Kowal, Aneta; Wiśniewski, Andrzej; Kuśnierczyk, Piotr; Jankowska, Renata

    2015-01-01

    Background Lung cancer represents the highest morbidity and mortality caused by neoplasms in the world; therefore researchers continue to search for new tools to diagnose and treat the disease. The aim of the study was to establish the role of single nucleotide polymorphisms (SNP) in the promoter region of the human leukocyte antigen (HLA)-G gene in patients with non-small cell lung cancer. Methods We enrolled 143 patients with a mean age of 63 years, diagnosed with non-small cell lung cancer...

  17. Elevated 68Ga Prostate-Specific Membrane Antigen Activity in Metastatic Non-Small Cell Lung Cancer.

    Science.gov (United States)

    Shetty, Deepa; Loh, Han; Bui, Chuong; Mansberg, Robert; Stevanovic, Amanda

    2016-05-01

    A 71-year-old man with a background of treated stage IIIB non-small cell lung cancer was referred for Ga prostate-specific membrane antigen (PSMA) PET/CT for staging of prostate cancer. In addition to the PSMA uptake in the known prostate malignancy, the study also demonstrated increased PSMA uptake in an enlarging left lower lobe lung mass with diffusely increased PSMA uptake in an enlarged thyroid gland and bilateral enlarged supraclavicular lymph nodes. Fine-needle aspiration biopsy of the thyroid gland and a left supraclavicular lymph node demonstrated metastatic adenocarcinoma from a primary lung cancer. PMID:26828144

  18. 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.

  19. 10-year biochemical (prostate-specific antigen) control of prostate cancer with 125I brachytherapy

    International Nuclear Information System (INIS)

    Purpose: To report 10-year biochemical (prostate-specific antigen [PSA]) outcomes for patients treated with 125I brachytherapy as monotherapy for early-stage prostate cancer. Methods and Materials: One hundred and twenty-five consecutively treated patients, with clinical Stage T1-T2b prostate cancer were treated with 125I brachytherapy as monotherapy, and followed with PSA determinations. Kaplan-Meier estimates of PSA progression-free survival (PFS), on the basis of a two consecutive elevations of PSA, were calculated. Aggregate PSA response by time interval was assessed. Comparisons were made to an earlier-treated cohort. Results: The overall PSA PFS rate achieved at 10 years was 87% for low-risk patients (PSA125I achieves a high rate (87%) of biochemical and clinical control in patients with low-risk disease at 10 years. The decline of PSA following brachytherapy with low-dose-rate isotopes can be protracted. Absolute PSA and PFS curves merge, and are comparable at 10 years

  20. A human monoclonal autoantibody to breast cancer identifies the PDZ domain containing protein GIPC1 as a novel breast cancer-associated antigen

    International Nuclear Information System (INIS)

    We have been studying the native autoimmune response to cancer through the isolation of human monoclonal antibodies that are cancer specific from cancer patients. To facilitate this work we previously developed a fusion partner cell line for human lymphocytes, MFP-2, that fuses efficiently with both human lymph node lymphocytes and peripheral blood lymphocytes. Using this unique trioma fusion partner cell line we isolated a panel of autologous human monoclonal antibodies, from both peripheral blood and lymph node lymphocytes, which are representative of the native repertoire of anti-cancer specific antibodies from breast cancer patients. The current study employs immunocytochemistry, immunohistochemistry, Western blot analysis as well as Northern blots, Scatchard binding studies and finally SEREX analysis for target antigen identification. By application of an expression cloning technique known as SEREX, we determined that the target antigen for two monoclonal antibodies, 27.B1 and 27.F7, derived from lymph node B-cells of a breast cancer patient, is the PDZ domain-containing protein known as GIPC1. This protein is highly expressed not only in cultured human breast cancer cells, but also in primary and metastatic tumor tissues and its overexpression appears to be cancer cell specific. Confocal microscopy revealed cell membrane and cytoplasmic localization of the target protein, which is consistent with previous studies of this protein. We have determined that GIPC1 is a novel breast cancer-associated immunogenic antigen that is overexpressed in breast cancer. Its role, however, in the initiation and/or progression of breast cancer remains unclear and needs further clarification

  1. Predictive and prognostic effect of CD133 and cancer-testis antigens in stage Ib-IIIA non-small cell lung cancer

    OpenAIRE

    SU, CHUNXIA; Xu, Ying; Xuefei LI; Ren, Shengxiang; Zhao, Chao; Hou, Likun; Ye, Zhiwei; Zhou, Caicun

    2015-01-01

    CD133 and cancer-testis antigens (CTAs) may be potential predicted markers of adjuvant chemotherapy or immune therapy, and they may be the independent prognostic factor of NSCLC. Nowadays, there is still no predictive biomarker identified for the use of adjuvant chemotherapy in non-small cell lung cancer (NSCLC) patients. To clarify the role of CD133 and CTAs as a predictive marker for adjuvant chemotherapy or prognostic factors of overall survival, we performed a retrospective study in 159 s...

  2. 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:: The...

  3. Value of Prostate-Specific Antigen and Prostate-Specific Antigen Density in Detection of Prostate Cancer in an Iranian Population of Men

    Directory of Open Access Journals (Sweden)

    Mahyar Ghafoori

    2009-08-01

    Full Text Available

    Introduction: The objective of this study was to evaluate the value of serum prostate-specific antigen (PSA and prostate-specific antigen density (PSAD in the diagnosis of prostate cancer.

    Materials and Methods: A total of 330 consecutive patients suspected of having prostate cancer due to either abnormal digital rectal examination or elevated serum PSA levels underwent transrectal ultrasonography-guided sextant biopsy of the prostate. The PSA and PSAD values were assessed based on the biopsy results.

    Results: One hundred and twenty-one patients (36.7% had prostate cancer. In this group, the mean PSA was 31.60 ± 30.85 ng/mL (range, 1.9 ng/mL to 166.0 ng/mL and the mean PSAD was 0.83 ± 1.01 (range, 0.04 ng/mL/cm3 to 6.38 ng/mL/cm3. In those without prostate cancer the mean PSA and PSAD levels were 13.80 ± 18.72 ng/mL (range, 0.4 ng/mL to 130.0 ng/mL; P < .001 and 0.24 ± 0.32 (range of 0.01 ng/mL/cm3 to 2.29 ng/mL/cm3; P < .001. The receiver operating characteristic curve analysis revealed that the discriminating power of serum PSA for detecting prostate cancer, as estimated by the area under the curve, was 0.74 while that for PSAD was 0.81 (P < .001. For the PSA range of 3.5 ng/mL to 41 ng/mL (gray zone the areas under the curve was 0.68 for PSA, while it was 0.78 for PSAD (P < .001.

    Conclusion: The use of PSAD instead of PSA in the diagnosis of prostatic cancer improves the diagnostic accuracy.

  4. Utility of squamous cell carcinoma antigen, carcinoembryonic antigen, Cyfra 21-1 and neuron specific enolase in lung cancer diagnosis: a prospective study from China

    Institute of Scientific and Technical Information of China (English)

    SONG Wei-an; LIU Xi; TIAN Xiao-dong; WANG Wei; LIANG Chao-yang; ZHANG Tao; GUO Jun-tang; PENG Yang-hong; ZHOU Nai-kang

    2011-01-01

    Background Early detection and diagnosis is urgent for the sake of effective treatment strategy for lung cancer.However,a convenient,economical and relatively precise method is not available.We here report a prospective study to find the possible value of the combined use of four popular tumor markers in the early diagnosis of lung cancer among patients with suspicious nodules in the lung.Methods Six hundred and sixty inpatients with suspicious nodules in the lung were divided into a lung cancer group and a benign pulmonary tumor group according to post-operative histological examinations.Serum levels of four tumor markers including squamous cell carcinoma antigen (SCC),carcinoembryonic antigen (CEA),Cyfra 21-1 and neuron specific enolase (NSE) were assayed for each patient.Receiver operating characteristic (ROC) curves were constructed for each tumor marker.The power of lung cancer diagnosis of each tumor marker,as well as a combination of them were analyzed and compared.Results The serum levels (median,range) of SCC,CEA,Cyfra 21-1 and NSE were 0.44 (0.01-35.70) ng/ml,2.49(0.30-26.78) ng/ml,2.30 (0.82-73.33) ng/ml and 10.54 (0.10-56.41) ng/ml respectively in lung cancer group,and were 0.32 (0.01-0.90) ng/ml,1.60 (0.20-8.93) ng/ml,1.41 (0.72-4.82) ng/ml and 9.36 (6.56-24.24) ng/ml respectively in the benign pulmonary tumor group.The difference in each tumor marker between the two groups was significant (P <0.05).The ROCs of SCC,CEA,Cyfra 21-1 and NSE were 0.702 (95% CI,0.654-0.751),0.611 (95% CI,0.563-0.659),0.650(95% CI,0.601-0.700) and 0.598 (95% CI,0.542-0.654) respectively,indicating very low power of these four tumor markers.When a combination of SCC,CEA,Cyfra 21-1 and NSE were employed,the diagnosis power was strengthened.Conclusion SCC,CEA,Cyfra 21-1 and NSE are valuable in the early diagnosis of lung cancer among suspicious nodules in the lung,especially when they were assayed together for one patient.

  5. Evaluation of Urinary Nuclear Matrix Protein-22 as Tumor Marker Versus Tissue Polypeptide Specific Antigen in Bilharzial and Bladder Cancer

    International Nuclear Information System (INIS)

    Urinary nuclear matrix protein-22 (NMP-22) and tissue polypeptide specific antigen (TPS) were determined as potential marker for early detection of bladder tumors in patients with high risk (Bilharzial-patients), monitoring and follow up bladder cancer patients. The objective was to determine sensitivity and specificity of markers for bilharzial and cancer lesions. The levels of two parameters were determined pre and post operation. A total of 110 individuals, 20 healthy, 20 bilharzial patients and 70 bladder cancer patients with confirmed diagnosis were investigated. Urine samples were assayed for NMP-22 and TPS test kits. Some bladder cancer patients were selected to follow up. NMP-22 showed highly significant increase (P,0.001) more than TPS (P<0.01) in bladder cancer patients when compared with bilharzial and control group. Overall sensitivity is 7.8% for TPS and 98.5% for NMP-22

  6. Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines

    Directory of Open Access Journals (Sweden)

    Yu Hao

    2010-04-01

    Full Text Available Abstract Background To observe mRNA expression of tumor-specific antigen MAGE, BAGE and GAGE in epithelial ovarian cancer tissues and cell lines, to explore the relationship between gene expression and diagnosis, treatment and prognosis of ovarian cancer, and to evaluate the feasibility of their gene products as markers, and an immunotherapy target for ovarian cancer. Methods mRNA expression of MAGE-1, MAGE-3, GAGE-1/2 and BAGE were determined by reverse transcription polymerase chain reaction (RT-PCR in 14 cases of normal ovarian tissue, 20 cases of ovarian benign tumor specimens, 41 cases of ovarian cancer specimens, and ovarian cancer cell lines SKOV3, A2780, and COC1. Results MAGE, GAGE and BAGE genes were not expressed in normal ovarian tissue. In benign tumors, only the MAGE gene was expressed; the expression rate of this gene in benign tumors was 15% (3/20. In ovarian cancer tissues, MAGE-1 and MAGE-3 was highly expressed, with expression rates of 53.7% (22/41 and 36.6% (15/41, while GAGE-1/2 and BAGE had relatively low expression, with rates of 26.8% (11/41 and 14.6% (6/41. In metastatic lesions of ovarian cancer, only MAGE-1 and BAGE were expressed, with expression rates of 28.6% (2/7 and 14.3% (1/7. The positive expression rates of MAGE-1 and MAGE-3 in serous cystadenocarcinoma were significantly higher than that in other types of ovarian cancer (P P Conclusion Tumor-specific antigen MAGE, BAGE and GAGE may play a role in the occurrence and development of ovarian cancer. These genes can be used as one of the important indicators for early diagnosis, efficacy evaluation and prognostic determination of ovarian cancer.

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

    Science.gov (United States)

    Akaza, Hideyuki; Kim, Choung Soo; Carroll, Peter; Choi, In Young; Chung, Byung Ha; Cooperberg, Matthew R.; Hirao, Yoshihiko; Hinotsu, Shiro; Horie, Shigeo; Lee, Ji Youl; Namiki, Mikio; Ng, Chi-Fai; Onozawa, Mizuki; Ozono, Seiichiro; Ueno, Satoru; Umbas, Rainy; Ye, Dingwei; Zhu, Gang

    2014-01-01

    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 and improving

  8. Tumor marker utility and prognostic relevance of cathepsin B, cathepsin L, urokinase-type plasminogen activator, plasminogen activator inhibitor type-1, CEA and CA 19-9 in colorectal cancer

    International Nuclear Information System (INIS)

    Cathepsin B and L (CATB, CATL), urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 play an important role in colorectal cancer invasion. The tumor marker utility and prognostic relevance of these proteases have not been evaluated in the same experimental setting and compared with that of CEA and CA-19-9. Protease, CEA and CA 19-9 serum or plasma levels were determined in 56 patients with colorectal cancer, 25 patients with ulcerative colitis, 26 patients with colorectal adenomas and 35 tumor-free control patients. Protease, CEA, CA 19-9 levels have been determined by ELISA and electrochemiluminescence immunoassay, respectively; their sensitivity, specificity, diagnostic accuracy have been calculated and correlated with clinicopathological staging. The protease antigen levels were significantly higher in colorectal cancer compared with other groups. Sensitivity of PAI-1 (94%), CATB (82%), uPA (69%), CATL (41%) were higher than those of CEA or CA 19-9 (30% and 18%, respectively). PAI-1, CATB and uPA demonstrated a better accuracy than CEA or CA 19-9. A combination of PAI-1 with CATB or uPA exhibited the highest sensitivity value (98%). High CATB, PAI-1, CEA and CA 19-9 levels correlated with advanced Dukes stages. CATB (P = 0.0004), CATL (P = 0.02), PAI-1 (P = 0.01) and CA 19-9 (P = 0.004) had a significant prognostic impact. PAI-1 (P = 0.001), CATB (P = 0.04) and CA 19-9 (P = 0.02) proved as independent prognostic variables. At the time of clinical detection proteases are more sensitive indicators for colorectal cancer than the commonly used tumor markers. Determinations of CATB, CATL and PAI-1 have a major prognostic impact in patients with colorectal cancer

  9. Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers: A Meta-Analysis.

    Science.gov (United States)

    Xu, Feng; Liu, Fuquan; Zhao, Hongwei; An, Guangyu; Feng, Guosheng

    2015-12-01

    Accumulating evidence indicates that mucin antigen MUC1 plays a fundamental role in the initiation and progression of several types of epithelial carcinomas. However, whether the expression of MUC1 on tumor cells is associated with patients' survival remains controversial. Medline/PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) databases, and Grey literature were searched up to 15 August 2015 for eligible studies of the association between the MUC1 expression and overall survival (OS) in various epithelial cancers. The hazard ratio (HR) and its 95% confidence interval (CI) were calculated from the included studies. Moreover, the odds ratio (OR) was also extracted to evaluate the association between the clinicopathological parameters of participants and MUC1 expression. A total of 3425 patients covering 23 studies were included in the analysis. The pooled results showed that positive MUC1 staining was a negative predictor of OS (HRFEM = 1.98,95% CIFEM: 1.76-2.22, PFEM = 0.479; HRREM = 2.16,95% CIREM: 1.58-2.94, PREM = 0.355) in various epithelial carcinomas. Subgroup analysis revealed that the increased MUC1 expression was significantly associated with poor OS in patients with gastric cancer (HRFEM = 2.12, 95%CIFEM: 1.75-2.57, PFEM = 0.359; HRREM = 1.89, 95% CIREM: 1.05-3.41, PREM = 0.238), colorectal cancer (HRFEM = 1.73, 95%CIFEM: 1.41-2.13, PFEM = 0.048; HRREM = 2.00,95% CIREM: 1.46-2.73, PREM = 0.019), cholangiocarcinoma (HRFEM = 2.52, 95% CIFEM: 1.42-4.49, PFEM = 0.252; HRREM = 2.34, 95% CIREM: 1.30-4.22, PREM = 0.244), and nonsmall cell lung cancer (NSCLC) (HRFEM = 2.14, 95% CIFEM: 1.46-3.14, PFEM = 0.591; HRREM = 2.81, 95% CIREM: 1.40-5.64, PREM = 0.280). In addition, MUC1 overexpression was more likely to be found in colorectal cancer patients with an advanced tumor node metastasis stage (ORREM = 1.55, 95% CIREM: 1.06-2.27; PREM = 0

  10. 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.

  11. Local prostate cancer radiotherapy after prostate-specific antigen progression during primary hormonal therapy

    International Nuclear Information System (INIS)

    The outcome of patients after radiotherapy (RT) for localized prostate cancer in case of prostate-specific antigen (PSA) progression during primary hormonal therapy (HT) is not well known. A group of 27 patients presenting with PSA progression during primary HT for local prostate cancer RT was identified among patients who were treated in the years 2000–2004 either using external-beam RT (EBRT; 70.2Gy; n=261) or Ir-192 brachytherapy as a boost to EBRT (HDR-BT; 18Gy + 50.4Gy; n=71). The median follow-up period after RT was 68 months. Median biochemical recurrence free (BRFS), disease specific (DSS) and overall survival (OS) for patients with PSA progression during primary HT was found to be only 21, 54 and 53 months, respectively, with a 6-year BRFS, DSS and OS of 19%, 41% and 26%. There were no significant differences between different RT concepts (6-year OS of 27% after EBRT and 20% after EBRT with HDR-BT). Considering all 332 patients in multivariate Cox regression analysis, PSA progression during initial HT, Gleason score>6 and patient age were found to be predictive for lower OS (p<0.001). The highest hazard ratio resulted for PSA progression during initial HT (7.2 in comparison to patients without PSA progression during primary HT). PSA progression and a nadir >0.5 ng/ml during initial HT were both significant risk factors for biochemical recurrence. An unfavourable prognosis after PSA progression during initial HT needs to be considered in the decision process before local prostate radiotherapy. Results from other centres are needed to validate our findings

  12. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma

    OpenAIRE

    Phan, Giao Q.; Yang, James C.; Sherry, Richard M.; Hwu, Patrick; Topalian, Suzanne L.; Schwartzentruber, Douglas J.; Restifo, Nicholas P; Haworth, Leah R.; Seipp, Claudia A.; Freezer, Linda J.; Morton, Kathleen E.; Mavroukakis, Sharon A.; Duray, Paul H.; Steinberg, Seth M.; Allison, James P.

    2003-01-01

    Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell activation. Blockade of CTLA-4 has been shown in animal models to improve the effectiveness of cancer immunotherapy. We thus treated 14 patients with metastatic melanoma by using serial i.v. administration of a fully human anti-CTLA-4 antibody (MDX-010) in conjunction with s.c....

  13. The store-operated Ca(2+) entry-mediated signaling is important for cancer spread.

    Science.gov (United States)

    Chen, Yih-Fung; Hsu, Keng-Fu; Shen, Meng-Ru

    2016-06-01

    Tumor cell migration and invasion are essential steps in the metastatic cascade that has great impact on patient outcomes. Spatial and temporal organization of Ca(2+) signaling regulates the multiple aspects of migration machinery, including cytoskeletal reorganization, traction force generation, and focal adhesion dynamics. Stromal interaction molecules (STIM) and Orai proteins, recently identified as critical constituents of store-operated Ca(2+) entry (SOCE), have been implicated in cancer cell migration and tumor metastasis. The clinical significance of STIM proteins and Orai Ca(2+) channels in tumor progression and their diagnostic and prognostic potentials have also been demonstrated in different types of cancers. Here we review the recent advances in understanding the important roles and regulatory mechanisms of STIM/Orai-mediated SOCE in cancer spread. The clinical implications and the emergence as a selective target for cancer therapeutics are also discussed. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen. PMID:26643254

  14. Construction, Expression and Characterization of a Chimeric Protein Targeting Carcinoembryonic Antigen in Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    LI Yang; HUA Shu-cheng; MA Cheng-yuan; YU Zhen-xiang; XU Li-jun; LI Dan; SUN Li-li; LI Xiao; PENG Li-ping

    2011-01-01

    The carcinoembryonic antigen(CEA) is an oncofetal glycoprotein known as an important clinical tumor marker and is overexpressed in several types of tumors, including colorectal and lung carcinomas. We constructed a chimeric protein that exhibits both specific binding and immune stimulating activities, by fusing staphylococcal enterotoxin A(SEA) to the C-terminus of an anti-CEA single-chain disulfide-stabilized Fv(scdsFv) antibody (single-chain-C-terminus/SEA, SC-C/SEA). The SC-C/SEA protein was expressed in Escherichia coli(E. coli), refolded, and purified on an immobilized Ni2+ affinity chromatography column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) and Western blot analysis reveal that the target protein was expressed sufficiently. We used immunofluorescence assays to demonstrate that SC-C/SEA could bind specifically to human lung carcinoma cells(A549), but almost human uterine cervix cells(HeLa). We also used the L-lactate dehydrogenase(LDH) release assay to show that SC-C/SEA elicits a strong A549 tumor-specific cytotoxic T lymphocyte(CTL) response in vitro. The results suggest that SC-C/SEA shows specific activity against CEA-positive cells and has potential application in CEA-targeted cancer immunotherapy.

  15. Design of Switchable Chimeric Antigen Receptor T Cells Targeting Breast Cancer.

    Science.gov (United States)

    Cao, Yu; Rodgers, David T; Du, Juanjuan; Ahmad, Insha; Hampton, Eric N; Ma, Jennifer S Y; Mazagova, Magdalena; Choi, Sei-Hyun; Yun, Hwa Young; Xiao, Han; Yang, Pengyu; Luo, Xiaozhou; Lim, Reyna K V; Pugh, Holly M; Wang, Feng; Kazane, Stephanie A; Wright, Timothy M; Kim, Chan Hyuk; Schultz, Peter G; Young, Travis S

    2016-06-20

    Chimeric antigen receptor T (CAR-T) cells have demonstrated promising results against hematological malignancies, but have encountered significant challenges in translation to solid tumors. To overcome these hurdles, we have developed a switchable CAR-T cell platform in which the activity of the engineered cell is controlled by dosage of an antibody-based switch. Herein, we apply this approach to Her2-expressing breast cancers by engineering switch molecules through site-specific incorporation of FITC or grafting of a peptide neo-epitope (PNE) into the anti-Her2 antibody trastuzumab (clone 4D5). We demonstrate that both switch formats can be readily optimized to redirect CAR-T cells (specific for the corresponding FITC or PNE) to Her2-expressing tumor cells, and afford dose-titratable activation of CAR-T cells ex vivo and complete clearance of the tumor in rodent xenograft models. This strategy may facilitate the application of immunotherapy to solid tumors by affording comparable efficacy with improved safety owing to switch-based control of the CAR-T response. PMID:27145250

  16. Proteogenomic-based discovery of minor histocompatibility antigens with suitable features for immunotherapy of hematologic cancers.

    Science.gov (United States)

    Granados, D P; Rodenbrock, A; Laverdure, J-P; Côté, C; Caron-Lizotte, O; Carli, C; Pearson, H; Janelle, V; Durette, C; Bonneil, E; Roy, D C; Delisle, J-S; Lemieux, S; Thibault, P; Perreault, C

    2016-06-01

    Pre-clinical studies have shown that injection of allogeneic T cells primed against a single minor histocompatibility antigen (MiHA) could cure hematologic cancers (HC) without causing any toxicity to the host. However, translation of this approach in humans has been hampered by the paucity of molecularly defined human MiHAs. Using a novel proteogenomic approach, we have analyzed cells from 13 volunteers and discovered a vast repertoire of MiHAs presented by the most common HLA haplotype in European Americans: HLA-A*02:01;B*44:03. Notably, out of >6000 MiHAs, we have identified a set of 39 MiHAs that share optimal features for immunotherapy of HCs. These 'optimal MiHAs' are coded by common alleles of genes that are preferentially expressed in hematopoietic cells. Bioinformatic modeling based on MiHA allelic frequencies showed that the 39 optimal MiHAs would enable MiHA-targeted immunotherapy of practically all HLA-A*02:01;B*44:03 patients. Further extension of this strategy to a few additional HLA haplotypes would allow treatment of almost all patients. PMID:26857467

  17. Targeted sonodynamic therapy of cancer using a photosensitizer conjugated with antibody against carcinoembryonic antigen.

    Science.gov (United States)

    Abe, Hironori; Kuroki, Motomu; Tachibana, Katsuro; Li, Tieli; Awasthi, Aradhana; Ueno, Aruto; Matsumoto, Hisanobu; Imakiire, Takayuki; Yamauchi, Yasushi; Yamada, Hiromi; Ariyoshi, Asami; Kuroki, Masahide

    2002-01-01

    The goal of this study was to develop a strategy for the selective destruction of cancer cells by ultrasonic irradiation in the presence of an antibody-conjugated photosensitizer. To this end, a photoimmunoconjugate (PIC) was prepared between ATX-70, a photosensitizer of a gallium-porphyrin analogue, and F11-39, a high affinity monoclonal antibody (MAb) against carcinoembryonic antigen (CEA), which is often overexpressed in various carcinoma cells. This conjugate, designated F39/ATX-70, retained immunoreactivity against purified CEA and CEA-expressing cells as determined by enzyme-linked immunosorbent assay, flow cytometry and immunofluorescence microscopic analysis. The cytotoxicity of F39/ATX-70 against CEA-expressing human gastric carcinoma cells in vitro was found to be greater than that of ATX-70 when applied in combination with ultrasound irradiation. When in vivo anti-tumor effects in a mouse xenograft model were assessed, intravenous administration of F39/ATX-70 followed by ultrasonic irradiation produced a marked growth inhibition of tumor compared with irradiation alone or irradiation after administration of ATX-70. These results suggest that the PIC between anti-CEA MAb and ATX-70 may have applications in sonodynamic therapy where destruction of CEA-expressing tumor is required. PMID:12168839

  18. Clinical value of combined detection of serum CEA, CA15-3 and SF in lung cancer

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical value of combined examination of serum CEA, CA15-3 and SF in lung cancer diagnosis. Methods: Serum concentrations of CEA, CA15-3 and SF were measured by chemiluminescent assay (CLA) in 99 patients with lung cancer and 25 patients with benign lung disease. Results: The positive rate of serum CEA, CA15-3 and SF in cases in lung cancer was 50.5%, 31.3% and 69.7%, respectively. Specificity of CEA, CA15-3 and SF measurements was 76%, 78% and 72%, respectively. In combined measurements, positive results of either two parameters revealed sensitivity and specificity of 82.8% and 92%, respectively. Conclusion: Combined measurements of CEA, CA15-3 and SF had evidently improved sensitivity and specificity in diagnosing lung cancer and thus were of good clinical value

  19. The role of CA-242 and CEA in surveillance following curative resection for colorectal cancer.

    OpenAIRE

    Hall, N. R.; Finan, P. J.; Stephenson, B M; Purves, D. A.; Cooper, E H

    1994-01-01

    This study was undertaken to evaluate the role of a new tumour marker, CA-242, alone or in combination with CEA in the practical management of colorectal cancer patients after potentially curative resection. A cohort of 149 patients who had undergone 'curative' surgery was followed up according to an intensive protocol in order to detect recurrent disease. Over a median tumour marker follow-up period of 24 months there were 25 recurrences in 24 patients. Both CEA and CA-242 alone detected hal...

  20. Detection of carcinoembryonic antigen mRNA in peritoneal washes from gastric cancer patients and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    Yan-Song Zhang; Jun Xu; Guang-Hua Luo; Rong-Chao Wang; Jiang Zhu; Xiao-Ying Zhang; Peter Nilsson-Ehle; Ning Xu

    2006-01-01

    AIM: To establish a more sensitive method for detection of free cancer cells in peritoneal washes from gastric cancer patients during surgery and to evaluate its clinical significance.METHODS: The carcinoembryonic antigen (CEA) mRNA levels in peritoneal washes from 65 cases of gastric cancer were detected by real-time RT-PCR. Peritoneal lavage cytology (PLC) was applied simultaneously to detection of free cancer cells. Negative controls included peritoneal washes from 5 cases of benign gastric disease and blood samples from 5 adult healthy volunteers.RESULTS: There was no CEA mRNA in peritoneal washes from benign gastric disease patients and in blood of adult healthy volunteers. The positive percentage of free cancer cells detected by real-time RT-PCR was 47.7% and only 12.3% by PLC. The positive rate of CEA mRNA was significantly related with serosa invasion between peritoneal metastasis and stage of gastric cancer.CONCLUSION: Real-time RT-PCR is a sensitive and rapid method for the detection of free cancer cells in peritoneal washes. The presence of free cancer cells in peritoneal washes is related to the pathologic stage of gastric cancer.

  1. Characterization of crystals of an antibody-recognition fragment of the cancer differentiation antigen mesothelin in complex with the therapeutic antibody MORAb-009

    International Nuclear Information System (INIS)

    The therapeutic antibody MORAb-009 disrupts the interaction of mesothelin and the ovarian cancer antigen CA-125. Crystals have been grown of the Fab fragment derived from MORAb-009 and of its complex with an N-terminal fragment of mesothelin. The mesothelin-specific monoclonal antibody MORAb-009 is capable of blocking the binding of mesothelin to CA-125 and displays promising anticancer potential. It is currently undergoing clinical trials. In order to understand the basis of the interaction between MORAb-009 and mesothelin at atomic resolution, both the Fab fragment of MORAb-009 and the complex between the Fab and an N-terminal fragment of mesothelin (residues 7–64) were crystallized. The crystals of the Fab diffracted X-rays to 1.75 Å resolution and had the symmetry of space group P41212, with unit-cell parameters a = b = 140.6, c = 282.0 Å. The crystals of the mesothelin–Fab complex diffracted to 2.6 Å resolution and belonged to the hexagonal space group P64, with unit-cell parameters a = b = 146.2, c = 80.9 Å. Structural analyses of these molecules are in progress

  2. 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...... 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 was...

  3. The use of tumour markers CEA, CA-195 and CA-242 in evaluating the response to chemotherapy in patients with advanced colorectal cancer.

    OpenAIRE

    Ward, U.; Primrose, J N; Finan, P. J.; Perren, T. J.; Selby, P.; Purves, D. A.; Cooper, E H

    1993-01-01

    Tumour markers CEA, CA-195 and CA-242 were measured in 33 patients undergoing chemotherapy for advanced colorectal cancer. The aim was to determine whether they could be used to accurately monitor the course of the disease, and reduce the need for imaging. Treatment with a 5-fluorouracil based regimen resulted in a partial response in nine patients (27%), whereas the remainder either had disease stabilisation or suffered from progression. Before treatment the CEA was elevated in 85% of patien...

  4. 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.

  5. CaCO3/CaIP6 composite nanoparticles effectively deliver AKT1 small interfering RNA to inhibit human breast cancer growth

    Directory of Open Access Journals (Sweden)

    Zhou H

    2015-07-01

    Full Text Available Hongyan Zhou,1,* Jinhuan Wei,2,* Qiangsheng Dai,3 Liping Wang,4 Junhang Luo,2 Tuckyun Cheang,4 Shenming Wang4 1Department of Neurological Intensive Care Unit, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Department of Urology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Breast Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Small interfering RNA (siRNA-mediated gene therapy is a promising strategy to temporarily inhibit the expression of genes involved in development of breast cancer. The lack of a safe and efficient gene delivery system has become a major hurdle for siRNA-mediated gene therapy in breast cancer. Our previous studies have demonstrated that inorganic amorphous calcium carbonate (ACC hybrid nanospheres functionalized with CaIP6 (ACC/CaIP6 nanoparticles are an efficient nucleic acid delivery tool. The present study aimed to evaluate the safety and efficiency of ACC/CaIP6 in delivering siRNA targeting AKT1 (siAKT1 for the treatment of breast cancer. Methods: The cytotoxicity of the ACC/CaIP6 nanoparticles was evaluated using a tetrazolium assay. The transfection efficiency and intracellular distribution of ACC/siAKT1 were analyzed by flow cytometry and confocal laser scanning microscopy, respectively. A series of in vitro and in vivo assays was performed to evaluate the effects of ACC/CaIP6/siAKT1 on growth of breast cancer cells. Results: ACC/CaIP6 nanoparticles effectively transfected cells with little or no toxicity. AKT1 knockdown by ACC/CaIP6/siAKT1 inhibited cell cycle progression and promoted apoptosis of MCF-7 cells. Intratumoral injection of ACC/CaIP6/siAKT1 significantly suppressed the

  6. Novel antigens in non-small cell lung cancer: SP17, AKAP4, and PTTG1 are potential immunotherapeutic targets.

    Science.gov (United States)

    Mirandola, Leonardo; Figueroa, Jose A; Phan, Tam T; Grizzi, Fabio; Kim, Minji; Rahman, Rakhshanda Layeequr; Jenkins, Marjorie R; Cobos, Everardo; Jumper, Cynthia; Alalawi, Raed; Chiriva-Internati, Maurizio

    2015-02-20

    Lung cancer is the leading cause of cancer deaths in both genders worldwide, with an incidence only second to prostate cancer in men and breast cancer in women. The lethality of the disease highlights the urgent need for innovative therapeutic options. Immunotherapy can afford efficient and specific targeting of tumor cells, improving efficacy and reducing the side effects of current therapies. We have previously reported the aberrant expression of cancer/testis antigens (CTAs) in tumors of unrelated histological origin. In this study we investigated the expression and immunogenicity of the CTAs, Sperm Protein 17 (SP17), A-kinase anchor protein 4 (AKAP4) and Pituitary Tumor Transforming Gene 1 (PTTG1) in human non-small cell lung cancer (NSCLC) cell lines and primary tumors. We found that SP17, AKAP4 and PTTG1 are aberrantly expressed in cancer samples, compared to normal lung cell lines and tissues. We established the immunogenicity of these CTAs by measuring CTA-specific autoantibodies in patients' sera and generating CTA-specific autologous cytotoxic lymphocytes from patients' peripheral blood mononuclear cells. Our results provide proof of principle that the CTAs SP17/AKAP4/PTTG1 are expressed in both human NSCLC cell lines and primary tumors and can elicit an immunogenic response in lung cancer patients. PMID:25739119

  7. Influence of radiotherapy on expression of the proliferating cell nuclear antigen (PCNA) and c-fos in human cervical cancer

    International Nuclear Information System (INIS)

    Objective: To investigate changes of proliferating cell nuclear antigen (PCNA) expression in human cervical cancer following irradiation. Methods: Immunohistochemical staining for PCNA was performed in frozen sections of formalin-fixed cervical cancer biopsy tissues. Results: The majority of the cancer cells showed PCNA-immunoreactivity before irradiation. Following irradiation (30-40 Gy/15-20 f) PCNA-immuno-positive staining was hardly detectable in most of the cancer cells. The PCNA-immunoreactivity, however, increased after radiotherapy, and moderate or heavy immuno-positive staining for PCNA was seen in irradiated mesenchymal tissue cells. On the other hand, after irradiation Fos-immunoreactivity decreased remarkably, and Fos-immuno-positive staining was hardly detectable in most of cancer cells. No obvious change in Fos-immuno-reactivity, however, was seen in mesenchymal connective tissue following irradiation. Conclusion: Irradiation inhibits PCNA and c-fos expression in cervical cancer cells whereas it induces the expression of PCNA in mesenchymal tissue cells. The present results suggest that expression of PCNA and c-fos may be regarded as a molecular marker for evaluating the cancer cell proliferation and mesenchymal tissue repair during radiotherapy of human cervical cancer

  8. Ovarian hemangioma with elevated CA125 and ascites mimicking ovarian cancer.

    Science.gov (United States)

    Erdemoglu, E; Kamaci, M; Ozen, S; Sahin, H G; Kolusari, A

    2006-01-01

    We report a case of a very rare tumor of the ovary with an unusual presentation; an ovarian hemangioma with massive ascites and elevated CA125. A 57-year-old woman presenting with elevated CA125, massive ascites and a left solid adnexal mass of 60 x 47 mm, with calcification and increased blood flow at Doppler examination, was submitted to laparotomy. Frozen section was inconclusive and a staging procedure which complicated the patient was performed. Pathologic examination revealed cavernous hemangioma which is an extremely rare tumor of the ovary. Although it is very unusual, an ovarian hemangioma may present with ascites and elevated CA125 and the differential diagnosis from ovarian cancer should be considered. PMID:16620071

  9. Comparison of ovarian cancer markers in endometriosis favours HE4 over CA125.

    Science.gov (United States)

    Mckinnon, Brett; Mueller, Michael D; Nirgianakis, Konstantinos; Bersinger, Nick A

    2015-10-01

    Endometriosis is a gynaecological condition with an associated chronic inflammatory response. The ectopic growth of 'lesions', consisting of endometrial cells outside the uterine cavity, stimulates an inflammatory response initiating the activation of macrophages, and resulting in increased cytokine and growth factor concentrations in the peritoneal fluid (PF). Endometriosis‑associated inflammation is chronic and long lasting. In patients with endometriosis, the risk of developing ovarian cancer within 10 years, particularly of the endometrioid or clear cell subtype, is increased 2.5‑4 times. Endometriosis creates a peritoneal environment that exposes the affected endometriotic and the normal ovarian surface epithelial cells to agents that have been suggested to be involved in the pathogenesis of cancer. Concentrations of several cytokines and growth factors were increased in the PF of patients with endometriosis. The ovarian cancer marker, CA125, was one such growth factor; however, this remains to be confirmed. Human epididymis protein 4 (HE4) was detected at high concentrations in patients with ovarian cancer and was identified as the best biomarker for the detection of ovarian cancer. The present study determined the levels of HE4 and CA125 in the peritoneal fluid of 258 patients with and 100 control individuals without endometriosis attending the Department of Obstetrics and Gynaecology, University of Berne (Berne, Switzerland) between 2007 and 2014. The cases were subdivided into groups without hormonal treatment (n=107), or treated with combined oral contraceptives (n=45), continuous gestagens (n=56) or GnRH agonists (n=50). Both of these markers were significantly increased in the non‑treated endometriosis samples compared with the control group. Hormone treatment with either of the three agents mentioned resulted in the concentration of CA125 returning to the control levels and the concentration of HE4 decreasing to below the control levels. CA125

  10. 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.

  11. Distribution of Ca, Fe, Cu and Zn in primary colorectal cancer and secondary colorectal liver metastases

    Energy Technology Data Exchange (ETDEWEB)

    Al-Ebraheem, A. [Department of Radiography, City Community and Health Sciences, City University, London, EC1V 0HB (United Kingdom); Mersov, A. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main St. West. Hamilton, Ontario, L8S 4L8 (Canada); Gurusamy, K. [HPB and Liver Transplant Surgery, Royal Free and University College School of Medicine, UCL and Royal Free NHS trust, London (United Kingdom); Farquharson, M.J., E-mail: farquhm@mcmaster.c [Department of Medical Physics and Applied Radiation Sciences, McMaster University, 1280 Main St. West. Hamilton, Ontario, L8S 4L8 (Canada)

    2010-07-21

    A microbeam synchrotron X-ray fluorescence ({mu}SRXRF) technique has been used to determine the localization and the relative concentrations of Zn, Cu, Fe and Ca in primary colorectal cancer and secondary colorectal liver metastases. 24 colon and 23 liver samples were examined, all of which were formalin fixed tissues arranged as microarrays of 1.0 mm diameter and 10 {mu}m thickness. The distribution of these metals was compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cells. Histological details were provided for each sample which enable concentrations of all elements in different tissue types to be compared. In the case of liver, significant differences have been found for all elements when comparing tumour, normal, necrotic, fibrotic, and blood vessel tissues (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have also been found to be significantly different among tumour, necrotic, fibrotic, and mucin tissues in the colon samples (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have been compared between primary colorectal samples and colorectal liver metastases. Concentration of Zn, Cu, Fe and Ca are higher in all types of liver tissues compared to those in the colon tissues. Comparing liver tumour and colon tumour samples, significant differences have been found for all elements (Mann Whitney, P<0.0001). For necrotic tissues, significant increase has been found for Zn, Ca, Cu and Fe (Mann Whitney, P<0.0001 for Fe and Zn, 0.014 for Ca, and 0.001 for Cu). The liver fibrotic levels of Zn, Ca, Cu and Fe were higher than the fibrotic colon areas (independent T test, P=0.007 for Zn and Mann Whitney test P<0.0001 for Cu, Fe and Ca). For the blood vessel tissue, the analysis revealed that the difference was only significant for Fe (P=0.009) from independent T test.

  12. Treating Cancer as an Infectious Disease—Viral Antigens as Novel Targets for Treatment and Potential Prevention of Tumors of Viral Etiology

    OpenAIRE

    Xing Guo Wang; Ekaterina Revskaya; Ruth A Bryan; Strickler, Howard D.; Robert D Burk; Arturo Casadevall; Ekaterina Dadachova

    2007-01-01

    BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: Viral antigens have not been previously considered as targets for treatment or prevention of virus-associated cancers. We hypothes...

  13. Expression of tumor-specific antigen MAGE, GAGE and BAGE in ovarian cancer tissues and cell lines

    International Nuclear Information System (INIS)

    To observe mRNA expression of tumor-specific antigen MAGE, BAGE and GAGE in epithelial ovarian cancer tissues and cell lines, to explore the relationship between gene expression and diagnosis, treatment and prognosis of ovarian cancer, and to evaluate the feasibility of their gene products as markers, and an immunotherapy target for ovarian cancer. mRNA expression of MAGE-1, MAGE-3, GAGE-1/2 and BAGE were determined by reverse transcription polymerase chain reaction (RT-PCR) in 14 cases of normal ovarian tissue, 20 cases of ovarian benign tumor specimens, 41 cases of ovarian cancer specimens, and ovarian cancer cell lines SKOV3, A2780, and COC1. MAGE, GAGE and BAGE genes were not expressed in normal ovarian tissue. In benign tumors, only the MAGE gene was expressed; the expression rate of this gene in benign tumors was 15% (3/20). In ovarian cancer tissues, MAGE-1 and MAGE-3 was highly expressed, with expression rates of 53.7% (22/41) and 36.6% (15/41), while GAGE-1/2 and BAGE had relatively low expression, with rates of 26.8% (11/41) and 14.6% (6/41). In metastatic lesions of ovarian cancer, only MAGE-1 and BAGE were expressed, with expression rates of 28.6% (2/7) and 14.3% (1/7). The positive expression rates of MAGE-1 and MAGE-3 in serous cystadenocarcinoma were significantly higher than that in other types of ovarian cancer (P < 0.05). Gene expression rate was not correlated with menopause or lymph node metastasis. Positive expression of MAGE-1 and MAGE-3 was positively correlated with tumor differentiation and the clinical stage of the ovarian cancer. In addition, the positive expression rate of BAGE was significantly higher in ovarian cancer patients with ascites (P < 0.05). The mRNA expression profiles of MAGE, GAGE and BAGE in ovarian carcinoma cell lines SKOV3, A2780 and COC1 varied, but there was at least one gene expressed in each cell line. Tumor-specific antigen MAGE, BAGE and GAGE may play a role in the occurrence and development of ovarian cancer

  14. Analysis of antigen TN and its relation to clinical profile, histology and bio marker in cancer patients with non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Full text: Background: The Tn antigen (GalNAc alpha-O-Ser/Thr), a product of incomplete O-glycosylation, is expressed in about 90% of human carcinomas, but not in normal human tissues, being related to poor prognosis in breast cancer. Objective: To study the Tn antigen expression in NSCLC, evaluating its relationship with the clinical profile and its usefulness as a prognostic factor. Methods: We studied 426 tumors from NSCLC patients, 359 without neoadjuvant (SNA)and 67 with neoadjuvant (CNA). Tn antigen expression was evaluated in tissue micro array by immunohistochemistry using monoclonal antibody antibody (mAb) 83D4. Degree of expression was analyzed by extension (0-3)and intensity (0-100). It was considered the score into two categories (Tn antigen expression high and low)according to the median overall results. Results: Tn antigen is significantly increased in adenocarcinomas (ADCA)compared with carcinomas squamous (MCS)(p < 0.004). The difference Tn antigen expression was not significant according to sex, race, age, grade, stage and completion of adjuvant treatment or not. Featuring a trend with more Tn antigen expression., In all groups for male Caucasian, under 70 years, adjuvant treatment and stage greater than I. In the group of ADCA -CNA, patients and former smokers have a significant difference in relation non-smokers with respect to the Tn antigen expression (p = 0.001). In this group, according to the histological pattern, There is a marked tendency for the solid subtype expression in subtypes unlike bronchioloalveolar papillary and acinar), being recognized in the literature as solid subtype with the worst prognosis, but with varying proportions depending on the level of expression of Tn (p = 0.06). The Tn antigen was significantly associated with different molecular alterations related to tumor biology for all groups together as being EPCAM - N (n = 393, r = 0.20, p = 0.001), EPCAM - C (n = 391, r = 0.12, p = 0.01), TTF- 1 (n = 250, r = -0.29 p = 0

  15. Production of monoclonal and polyclonal antibodies against prostate-specific antigen, a prostate cancer serum marker.

    Science.gov (United States)

    Chou, Shu-Fen; Chen, Chien-Yuan

    2004-02-01

    The aim of this study was to produce monoclonal and polyclonal antibodies against prostate-specific antigen (PSA), a prostate cancer serum marker. Hyperimmune ICR mice produced polyclonal antibodies (PoAbs) after injection with 0.5 mL of pristane, and were injected with NS-1 myeloma cells 2 weeks later. Hyperimmune Balb/c mice were used for the production of monoclonal antibodies (MAbs). Mice were immunized four times and given a final boost, and their spleen cells were collected and fused with NS-1 myeloma cells under the presence of PEG 1500. The fused cells were then selected in the HAT-RPMIX medium. Anti-PSA antibody-secreting hybridoma cell lines with high titer were cloned by enzyme-linked immunosorbent assay (ELISA) and then subcloned by limiting dilution in 15% fetal bovine serum (FBS) HT-RPMIX medium. Twelve murine hybridoma producing anti-PSA MAbs were obtained and designated C3m1G11, B3m1E5, C3m1E8, C3m1C5, C3m2F4, C3m1F8, C3m2B3, C3m2E6, B3m2B11, B3m2F2, C3m2C7, and C3m2D9. Isotypes of these MAbs were identified as IgG2a heavy chain and kappa light chain. Hitrap Protein A column was used for the purification of polyclonal and monoclonal antibodies. The purity analysis of MAb was performed by capillary electrophoresis. PMID:15000852

  16. Kinetics of serum prostate-specific antigen after external beam radiation for clinically localized prostate cancer

    International Nuclear Information System (INIS)

    Background and purpose: To determine the kinetics of serum prostate-specific antigen (PSA) after radiation therapy of localized prostate cancer and to evaluate whether such kinetics provide prognostic information. Materials and methods: Eight hundred forty-one men with serial PSA determinations who underwent external beam radiation without androgen ablation were analyzed to determine postradiation PSA kinetic parameters (half-life and doubling time) and to correlate these parameters with disease outcome. Non-linear regression techniques were used to determine half-lives and doubling times. Results: The postradiation serum PSA data fitted well to first order kinetic models. The median PSA half-life was 1.6 months (range 0.5-9.2 months). There was no correlation between half-life and T-stage or Gleason grade. A significant but quantitatively weak correlation was present between the pretreatment PSA level and half-life; lower pretreatment levels were associated with longer half-lives. Half-life did not correlate with disease outcome whether the endpoint was local recurrence, distant metastasis or rising PSA. In 263 men with a rising postradiation PSA profile the median PSA doubling time was 12.2 months (range 0.8-80.2 months). Faster doubling times were significantly associated with higher T-stage, higher Gleason grade and higher pretreatment PSA levels. Thus, patients with initially adverse disease developed faster rising PSA values after treatment than patients with less adverse disease. The most striking correlation was between rapid doubling time and the likelihood of metastatic relapse. Patients who developed metastases had a median PSA doubling time of 4.2 months compared to a median doubling time of 11.7 months in patients who developed local recurrence. Overall, patients with a PSA doubling time of less than 8 months had a 7-year actuarial metastatic rate of 54%, while patients with a PSA doubling time exceeding 8 months had only a 7% metastatic rate

  17. 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

  18. Prostate-specific antigen and radiation therapy for clinically localized prostate cancer

    International Nuclear Information System (INIS)

    Purpose: This study was undertaken to: (a) define the prognostic significance of pretreatment serum prostate-specific antigen (PSA) levels in localized prostate cancer treated with radiation; (b) define the prognostic usefulness of postradiation PSA levels; (c) evaluate the outcome of radiation using PSA as an endpoint. Methods and Materials: Disease outcome in 707 patients with Stages T1 (205 men), T2 (256 men), T3 (239 men), and T4 (7 men), receiving definitive external radiation as sole therapy, was evaluated using univariate and multivariate techniques. Results: At a mean follow-up of 31 months, 157 patients (22%) developed relapse or a rising PSA. Multivariate analysis revealed pretreatment PSA level to be the most significant prognostic factor, with lesser though significant contributions due to Gleason grade (2-6 vs. 7-10) and transurethral resection in (T3(T4)) disease. The following four prognostic groupings were defined: group I, PSA ≤ 4 ng/ml, any grade; group II, 4 20, any grade. Five-year actuarial relapse rates in these groups were: I, 12%; II, 34%; III, 40%; and IV, 81%. Posttreatment nadir PSA was an independent determinant of outcome and only patients with nadir values < 1 ng/ml fared well (5-year relapse rate 20%). Using rising PSA as an endpoint the 461 patients with (T1(T2)) disease had an actuarial freedom from disease rate of 70% at 5 years, which appeared to plateau, suggesting that many were cured. No plateau was evident for (T3(T4)) disease. Conclusion: Pretreatment serum PSA is the single most important predictor of disease outcome after radiation for local prostate cancer. Tumor grade has a lesser though significant prognostic role. Postirradiation nadir PSA value during the first year is a sensitive indicator of response to treatment. Only nadir values < 1 ng/ml are associated with a favorable outlook. A significant fraction of men with (T1(T2)) disease may be cured with radiation. There was no evidence for a cured fraction among

  19. 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.

  20. Teratoma during Pregnancy with Positive Estrogen and Progesterone Receptors and Elevated Ca19-9 Antigen Levels

    Directory of Open Access Journals (Sweden)

    Nilgun Kanlioglu Kuman

    2012-01-01

    Full Text Available We present a 27-year-old female patient admitted with an anterior mediastinal mass. She complained of chest discomfort and hemoptysis which began seven months prior. She had given birth five months prior. Thoracic X-ray showed an anterior mediastinal mass. Thorax computed tomography (CT confirmed a well-defined anterior mediastinal mass with  cm diameter, extending to the right hemithorax. It was composed of cystic spaces and discrete areas like soft tissue and fat. Serum Ca 19-9 level was elevated. CT features were consistent with a mature teratoma. During median sternotomy, the tumor revealed adhesions to the right lung and the right subclavian artery. Histologically, the tumor was diagnosed as a mature teratoma. Estrogen and progesterone receptors were detected to be positive in the resected tissue. We conclude that alterations in hormone levels during pregnancy might be the cause of rapid tumor growth which leads to hemoptysis.

  1. 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

    International Nuclear Information System (INIS)

    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

  2. 76 FR 24889 - Submission for OMB Review; Comment Request; Cancer Biomedical Informatics Grid® (caBIG®) Support...

    Science.gov (United States)

    2011-05-03

    ... information collection was previously published in the Federal Register on February 11, 2011 (76 FR 7867) and... Biomedical Informatics Grid (caBIG ) Support Service Provider (SSP) Program (NCI) Summary: Under the... control number. Proposed Collection: Title: cancer Biomedical Informatics Grid (caBIG ) Support...

  3. Physician Knowledge and Awareness of CA-125 As a Screen for Ovarian Cancer in the Asymptomatic, Average-Risk Population

    Science.gov (United States)

    Stewart, Sherri L.; Rim, Sun Hee; Gelb, Cynthia A.

    2012-01-01

    Effective early detection strategies for ovarian cancer do not exist. Current screening guidelines recommend against routine screening using CA-125 alone or in combination with transvaginal ultrasonography (TVS). In this study, the authors used the 2008 "DocStyles" survey to measure clinician beliefs about the effectiveness of CA-125 and TVS in…

  4. 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 nomo

  5. Elevated serum levels of fetal antigen 1,a member of the epidermal growth factor superfamily, in patients with small cell lung cancer

    DEFF Research Database (Denmark)

    Harken Jensen, C; Drivsholm, L; Laursen, I; Teisner, B

    1999-01-01

    Serum levels of fetal antigen 1 (FA1) were quantified pretherapeutically in 16 patients with pneumonia, 30 patients with small cell lung cancer (SCLC) and 10 patients with non-small cell lung cancer (NSCLC) and compared to the normal reference interval (n = 177). Serum FA1 levels were significantly...

  6. CA 19-9 is an index of the response to neoadjunctive chemoradiation therpay in pancreatic cancer

    International Nuclear Information System (INIS)

    Purpose: This study examines the changes of serum levels of CA 19-9 in patients with pancreatic cancer following neoadjuvant irradiation and chemotherapy to define the potential role of this tumor marker in preoperative management of these patients. Materials and Methods: Serum CA 19-9 levels were measured in 42 patients before receiving external beam irradiation with concurrent 5-fluorouracil in preparation for laparotomy and Whipple procedure or intraoperative irradiation (IORT). The CA 19-9 levels were determined again after irradiation, and changes were correlated with findings of restaging CT scan and laparatomy. Results: Following preoperative irradiation, 10 patients (24%) experienced an increase in CA 19-9 levels whereas 29 patients (69%) showed a decrease in CA 19-9. There was no change in the CA 19-9 levels of three patients (7%) after treatment. Of the 10 patients with increased CA 19-9 levels after irradiation, 9 patients (90%) had developed distant metastases or local tumor progression as determined by restaging CT scan or at laparotomy. In contrast, only 6 of 29 patients (21%) with declining CA 19-9 levels after irradiation demonstrated metastases or local tumor progression on restaging CT scan or at laparotomy. The correlation of CA 19-9 increase or decrease with disease progression or control, respectively, was statistically significant (p=0.009). Conclusions: Serum CA 19-9 levels may rise or fall during neoadjuvant therapy. A rising CA 19-9 reliably indicates cancer progression while a falling CA 19-9 connotes disease control in the majority of patients. In developing strategies for application of neoadjuvant therapy for pancreatic cancer, monitoring of CA 19-9 appears most useful for the identification of patients who manifest progressive tumor growth and metastasis in spite of this treatment

  7. Growth inhibiting effects of antisense eukaryotic expression vector of proliferating cell nuclear antigen gene on human bladder cancer cells

    Institute of Scientific and Technical Information of China (English)

    童强松; 曾甫清; 林晨; 赵军; 鲁功成

    2003-01-01

    Objective To explore the growth inhibiting effects on human bladder cancer by antisense RNA targeting the proliferating cell nuclear antigen (PCNA) gene. Methods The eukaryotic expression vector for antisense PCNA cDNA was constructed and transferred into a bladder cancer EJ cell line. The PCNA expression in the cancer cells was detected by RT-PCR and Western blotting assays. The in vitro proliferation activities of the transferred cells were observed by growth curve, tetrazolium bromide (MTT) colorimetry, tritiated thymidine (3H-TdR)incorporation, flow cytometry and clone formation testing, while its in vivo anti-tumor effects were detected on nude mice allograft models.Results After the antisense vector, pLAPSN, was transferred, cellular PCNA expression was inhibited at both protein and mRNA levels. The growth rates of EJ cells were reduced from 27.91% to 62.07% (P<0.01), with an inhibition of DNA synthesis rate by 52.31% (P<0.01). Transferred cells were blocked at G0/G1 phases in cell-cycle assay, with the clone formation ability decreased by 50.81% (P<0.01). The in vivo carcinogenic abilities of the transferred cancer cells were decreased by 54.23% (P<0.05). Conclusions Antisense PCNA gene transfer could inhibit the growth of bladder cancer cells in vitro and in vivo, which provided an ideal strategy for gene therapy of human cancers.

  8. 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.

  9. 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.

  10. PIK3CA genotype and a PIK3CA mutation-related gene signature and response to everolimus and letrozole in estrogen receptor positive breast cancer.

    Directory of Open Access Journals (Sweden)

    Sherene Loi

    Full Text Available The phosphatidylinositol 3' kinase (PI3K pathway is commonly activated in breast cancer and aberrations such as PI3K mutations are common. Recent exciting clinical trial results in advanced estrogen receptor-positive (ER breast cancer support mTOR activation is a major means of estrogen-independent tumor growth. Hence the means to identify a responsive breast cancer population that would most benefit from these compounds in the adjuvant or earlier stage setting is of high interest. Here we study PIK3CA genotype as well as a previously reported PI3K/mTOR-pathway gene signature (PIK3CA-GS and their ability to estimate the level of PI3K pathway activation in two clinical trials of newly diagnosed ER-positive breast cancer patients- a total of 81 patients- one of which was randomized between letrozole and placebo vs letrozole and everolimus. The main objectives were to correlate the baseline PIK3CA genotype and GS with the relative change from baseline to day 15 in Ki67 (which has been shown to be prognostic in breast cancer and phosphorylated S6 (S240 immunohistochemistry (a substrate of mTOR. In the randomized dataset, the PIK3CA-GS could identify those patients with the largest relative decreases in Ki67 to letrozole/everolimus (R = -0.43, p = 0.008 compared with letrozole/placebo (R = 0.07, p = 0.58; interaction test p = 0.02. In a second dataset of pre-surgical everolimus alone, the PIK3CA-GS was not significantly correlated with relative change in Ki67 (R = -0.11, p = 0.37 but with relative change in phosphorlyated S6 (S240 (R = -0.46, p = 0.028. PIK3CA genotype was not significantly associated with any endpoint in either datasets. Our results suggest that the PIK3CA-GS has potential to identify those ER-positive BCs who may benefit from the addition of everolimus to letrozole. Further evaluation of the PIK3CA-GS as a predictive biomarker is warranted as it may facilitate better selection of responsive patient populations for mTOR inhibition

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

    OpenAIRE

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

    2015-01-01

    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 impli...

  12. Synergistic effect of chimeric antigen receptors and cytokine-induced killer cells: An innovative combination for cancer therapy

    Directory of Open Access Journals (Sweden)

    Binh Thanh Vu

    2016-06-01

    Full Text Available In recent years, the combination of gene and immunotherapy for cancer treatment has been regarded as innovative and promising; together, both therapies can help overcome limitations associated with conventional treatments. In order to augment anti-cancer efficacy and to maintain the specificity of antibody therapy, chimeric antigen receptor (CAR-modified T cells, directed toward tumor-specific antigens, have emerged as a novel and promising therapeutic platform. CARs consist of a B cell receptor (BCR-derived extracellular domain and T cell receptor (TCR-associated signaling elements. Cytokine-induced killer (CIK cells are the effector immune cells that can be activated ex vivo and possess both the anti-tumor potency of T lymphocytes and the non-major histocompatibility complex-restricted elimination of natural killer cells. With their pre-eminent ability for robust proliferation, CIK cells may overcome the main limitations of adoptive immunotherapy strategies. CIK cells have strong tumor cell killing capacity; they are effective against a wide variety of malignant tumors and have been shown to be safe in cancer patients. This review summarizes the characteristics of CARs which make them attractive for in cancer treatment strategies. In addition, the role of CIK cells and the advantages of combining CIK cells with CAR-based therapy will be discussed. Scientific evidence to support their combined therapeutic application will be highlighted, with a focus on how their innovative combination may be translated into cancer clinical trials. [Biomed Res Ther 2016; 3(6.000: 653-665

  13. Stability of HE4 and CA125 in blood samples from patients diagnosed with ovarian cancer

    DEFF Research Database (Denmark)

    Sandhu, Noreen; Karlsen, Mona A; Høgdall, Claus; Laursen, Inga A; Christensen, Ib J; Høgdall, Estrid V S

    2014-01-01

    OBJECTIVE: To investigate the influence of handling and storage on HE4 and CA125 serum and EDTA plasma levels to clarify any important consequences for a clinical setting. METHODS: Blood samples from 13 ovarian cancer (OC) patients were collected and allowed to clot or sediment for up to 72 hours...... at 4 °C or 20 °C, then processed into serum and EDTA plasma. Furthermore, the effects of up to eight repetitive cycles of freeze/thaw were investigated. HE4 and CA125 were analyzed using a Chemiluminescent Microparticle Immunoassay on the Architect i2000sr System. RESULTS: No significant effect of...... processing time for HE4 could be shown. HE4 EDTA plasma levels were insignificantly lower (3%) than serum levels (p = 0.41). Similarly, no significant effect of processing time for CA125 could be demonstrated. CA125 levels at 4 °C were significantly reduced compared to levels at 20 °C (p = 0.024). No...

  14. Duodenal Duplication Cyst with Profound Elevation of Intracystic Carbohydrate Antigen (CA 19-9 and Carcinoembryonic Antigen (CEA: A Rare but Important Differential in the Diagnosis of Cystic Tumours of the Pancreas

    Directory of Open Access Journals (Sweden)

    Kant J Shah

    2006-03-01

    Full Text Available The diagnosis of cystic tumours of the pancreas can be difficult. The principal effort is directed towards distinguishing benign post-inflammatory pseudocysts from true cystic tumours [1, 2]. Pointers that may help to identify a cystic tumour include the presence of a thick or irregular lining with septae on cross-sectional imaging [2]. Further, endoscopic ultrasound (EUS with linear EUS-guided aspiration can aid this process of differentiation as cyst fluid can be analysed for tumour markers, amylase and cytology [3, 4]. Elevated levels of intra-cyst tumour markers favour the diagnosis of a true cystic lesion [5]. It is important to make the distinction between post-inflammatory pseudocysts and cystic tumours as the natural history of these conditions is different and this is reflected in their different optimal management. Cystic lesions carry a varying risk of malignant transformation and most require resection [2]. Further, mistaking a cystic tumour for a pseudocyst can have disastrous consequences and lead to inappropriate drainage surgery [6]. In practice, cystic tumours and pseudocysts are the principal differential diagnoses to be assessed in a patient with a pancreatic cystic lesion; however a third rare possible differential is that of duplication cyst. These are rare congenital abnormalities of the gut characterized by the presence of smooth muscle in the wall and can be lined with gastrointestinal mucosa [7]. Little is known of the natural history and malignant potential of these lesions and as a result of their rarity, knowledge of their presentation accrues principally through single case studies. This paper reports a patient presenting with a pancreatic cystic lesion who underwent resection on the grounds of having a complex cyst with a profoundly elevated intra-cystic carbohydrate antigen (CA 19-9 level together with carcinoembryonic antigen (CEA. Final histology revealed a duodenal duplication cyst without malignancy. To the

  15. A phase II trial of personalized peptide vaccination in castration-resistant prostate cancer patients: prolongation of prostate-specific antigen doubling time

    OpenAIRE

    Noguchi, Masanori; MORIYA, FUKUKO; SUEKANE, SHIGETAKA; Ohnishi, Rei; Matsueda, Satoko; Sasada, Tetsuro; Yamada, Akira; Itoh, Kyogo

    2013-01-01

    Background Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are curren...

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

    International Nuclear Information System (INIS)

    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

  17. Molecular and immuno-characteristics of immunoglobulin-like glycoproteins in cancer cell-expressed biomarker, CA215.

    Science.gov (United States)

    Lee, Gregory; Cheung, Anthony P; Li, Bo; Ge, Bixia; Chow, Po-Ming

    2012-01-01

    RP215 monoclonal antibody (Mab) was shown to recognize a specific carbohydrate-associated epitope found in cancer cell-expressed glycoproteins, known as CA215. The membrane-bound and soluble forms of CA215 were detected in almost all of the cancer cells in humans, but rarely found in normal tissues. Through MALDI-TOF MS analysis, it has been reported previously that as much as 40% of the detected tryptic peptides of CA215 showed high degrees of sequence homology to those found in immunoglobulin heavy chains. The cancer cell-derived immunoglobulins were further purified from CA215 by affinity column-linked with goat anti-human IgG for molecular characterizations. Semi-quantitative RT-PCR was used to determine the mRNA levels of various immunoglobulin genes expressed by cancer cells of single or multi-cell origins and compared with those found in normal human serum. The stability of CA215 was investigated under different experimental conditions. It was observed that the RP215-specific epitope in CA215 is stable at neutral pH, in human serum or in mice (half life of 5-18 days), but unstable at extreme pH's (pH ≤ 2.0; pH ≥ 12.0) or high temperatures. Enzyme immunoassays were performed with several secondary antibody probes related to human IgG. It was demonstrated that cancer cell-expressed immunoglobulins with RP215-specific epitope have much lower immunoactivity than that of normal human IgG (≤ 5%), despite the fact that both showed almost identical amino acid sequence in the respective Fc region reported previously. This could be the result of aberrant glycosylation of CA215 in cancer cells. Aberrant glycosylation of glycoproteins may have important biological implications on the proliferation of cancer cells in vitro or in vivo. PMID:22417288

  18. Methylanthraquinone from Hedyotis diffusa WILLD induces Ca(2+)-mediated apoptosis in human breast cancer cells.

    Science.gov (United States)

    Liu, Zheng; Liu, Ming; Liu, Miao; Li, Jianchun

    2010-02-01

    Methylanthraquinone from Hedyotis diffusa WILLD exhibited potent anticancer activity in many kinds of cancer cells. However, the exact mechanism and signaling pathway involved in methylanthraquinone-induced apoptosis have not been fully elucidated. Therefore, we explored the mechanisms of methylanthraquinone-mediated apoptosis in MCF-7 human breast cancer cells. When MCF-7 cells were co-incubated with methylanthraquinone, the percentage of apoptotic cell and S phase of cell cycle was markedly increased. In addition, a rise in intracellular calcium levels, phosphorylation of JNK and activation of calpain were found in MCF-7 cells after exposure to methylanthraquinone. With the methylanthraquinone-mediated reduction of mitochondrial membrane potential, cytochrome c was released from mitochondria to cytosol. Moreover, methylanthraquinone strongly induced cleavage of caspase-4, caspase-9 and caspase-7 in MCF-7 cells. These results suggested that methylanthraquinone from Hedyotis diffusa WILLD induced MCF-7 cells apoptosis via Ca(2+)/calpain/caspase-4 pathway. PMID:19686834

  19. Radiolocalization of human small cell lung cancer and antigen-positive normal tissues using monoclonal antibody LS2D617

    International Nuclear Information System (INIS)

    The murine monoclonal antibody LS2D617, which reacts with an antigen associated with human small cell lung carcinoma (SCLC), was tested in preclinical models to assess its potential for specific targeting of tumors in human SCLC cancer patients. LS2D617 detects a cell antigen on the surface of cultured SCLC and neuroblastoma cell lines. Scatchard analysis of the binding of LS2D617 to NCIH69 SCLC cells indicates an affinity constant of about 1 x 10(8) M-1 and an epitope expression level of approximately 2 x 10(6) antigenic sites/cell. Molecular weight analysis of the target antigen and antibody competition experiments showed that LS2D617 should be classified as a SCLC Cluster 1 antibody. LS2D617 was labeled with 111In and tested for biodistribution (4, 24, 48, 72, and 96 h postinjection) in nude mice bearing the human SCLC NCIH69 tumor. Tumor values peaked at about 35% injected dose/g (Day 3) compared with about 8% injected dose/g for an irrelevant IgG1 antibody while normal tissue accumulation for both antibodies was about 2-8% injected dose/g. Immunohistochemical studies demonstrated that LS2D617 reacts with the central nervous system, peripheral nerves, endocrine tissues, and heart tissue of rabbits as it does in human tissues. The ability of LS2D617 to accumulate in vivo in normal tissues that express the specific target antigen was tested in rabbits. Rabbits given i.v. injections of 111In-LS2D617 or control labeled antibody were sacrificed at 48 h and tissues were examined by gamma well counting, autoradiography, and immunohistochemical staining for murine immunoglobulin. Specific uptake was seen in all sites defined as antigen positive by immunohistology (i.e., heart, liver bile duct, peripheral nerves, pituitary, adrenal), except the central nervous system (brain and spinal cord) which was inaccessible to antibody because of the blood brain barrier

  20. Prospective study of Helicobacter pylori antigens and gastric noncardia cancer risk in the nutrition intervention trial cohort.

    Science.gov (United States)

    Murphy, Gwen; Freedman, Neal D; Michel, Angelika; Fan, Jin-Hu; Taylor, Philip R; Pawlita, Michael; Qiao, You-Lin; Zhang, Han; Yu, Kai; Abnet, Christian C; Dawsey, Sanford M

    2015-10-15

    Helicobacter pylori (H. pylori) infection is the strongest known risk factor for gastric noncardia adenocarcinoma (GNCA). We used multiplex serology to determine whether seropositivity to 15 H. pylori proteins is associated with the subsequent development of noncardia gastric cancer in Linxian, China. We included 448 GNCA cases and 1242 controls from two time points within the Linxian General Population Nutrition Intervention Trial, Linxian. H. pylori multiplex seropositivity was defined as positivity to ≥4 of the 15 included antigens. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major GNCA risk factors. In addition, we undertook a meta-analysis combining H. pylori multiplex serology data from both time points. H. pylori multiplex seropositivity was associated with a significant increase in risk of GNCA at one time point (1985; OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56, 5.47). Combining data from both time points in a meta-analysis H. pylori multiplex seropositivity was associated with an increased risk of GNCA, as were six individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was inversely associated with risk of GNCA. We identified six individual antigens that confer an increase in risk of GNCA within this population of high H. pylori seroprevalence, as well as a single antigen that may be inversely associated with GNCA risk. We further determined that the H. pylori multiplex assay provides additional information to the conventional ELISA methods on risk of GNCA. PMID:25845708

  1. 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

  2. pp-GalNAc-T13 induces high metastatic potential of murine Lewis lung cancer by generating trimeric Tn antigen

    International Nuclear Information System (INIS)

    Highlights: ► ppGalNAc-T13 was up-regulated in high metastatic sublines of Lewis lung cancer. ► ppGalNAc-T13 expression enhanced cell invasion activity in low metastatic sublines. ► Trimeric Tn antigen was induced in the transfectant cells of ppGalNAc-T13 cDNA. ► A major protein carrying trimeric Tn structure was identified as Syndecan-1. ► 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 subcutaneous injection of T13-KD clones showed lower coalescence to fascia and peritoneum, and significantly reduced lung

  3. A novel IgE antibody targeting the prostate-specific antigen as a potential prostate cancer therapy

    International Nuclear Information System (INIS)

    Prostate cancer (PCa) is the second leading cause of cancer deaths in men in the United States. The prostate-specific antigen (PSA), often found at high levels in the serum of PCa patients, has been used as a marker for PCa detection and as a target of immunotherapy. The murine IgG1 monoclonal antibody AR47.47, specific for human PSA, has been shown to enhance antigen presentation by human dendritic cells and induce both CD4 and CD8 T-cell activation when complexed with PSA. In this study, we explored the properties of a novel mouse/human chimeric anti-PSA IgE containing the variable regions of AR47.47 as a potential therapy for PCa. Our goal was to take advantage of the unique properties of IgE in order to trigger immune activation against PCa. Binding characteristics of the antibody were determined by ELISA and flow cytometry. In vitro degranulation was determined by the release of β-hexosaminidase from effector cells. In vivo degranulation was monitored in human FcεRIα transgenic mice using the passive cutaneous anaphylaxis assay. These mice were also used for a vaccination study to determine the in vivo anti-cancer effects of this antibody. Significant differences in survival were determined using the Log Rank test. In vitro T-cell activation was studied using human dendritic cells and autologous T cells. The anti-PSA IgE, expressed in murine myeloma cells, is properly assembled and secreted, and binds the antigen and FcεRI. In addition, this antibody is capable of triggering effector cell degranulation in vitro and in vivo when artificially cross-linked, but not in the presence of the natural soluble antigen, suggesting that such an interaction will not trigger systemic anaphylaxis. Importantly, the anti-PSA IgE combined with PSA also triggers immune activation in vitro and in vivo and significantly prolongs the survival of human FcεRIα transgenic mice challenged with PSA-expressing tumors in a prophylactic vaccination setting. The anti-PSA IgE exhibits

  4. Changes and clinical significance of serum HE4, CA125 and plasma LPA in patients with ovarian cancer

    International Nuclear Information System (INIS)

    Objective: To explore the clinical significance of changes of serum HE4, CA125 and plasma LPA level in patients with ovarian cancer. Methods: The levels of serum HE4, CA125 and plasma LPA were detected by ELISA, RIA and chemical method respectively in 50 patients with ovarian cancer and 50 health control. Results: The levels of serum CA125 and plasma LPA in patients with ovarian cancer (phase III/IV) were significantly increased then those in in phase I/II (P0.05). The levels of serum HE4, CA125 and plasma LPA were prominently higher in the patients before operation than those in controls (P0.05) and the levels of CA125 was positive correlation with the levels of HE4 and LPA (r=0.628, r=0.597, all P<0.01). Conclusion: The over-expression of HE4, CA125 and LPA in ovarian cancer indicates that may be related to ovarian carcinogenesis and development, which can be important index for assessment of early diagnosis, therapeutic efficacy and prognosis. (authors)

  5. Study on the status of breast and prostate cancers in Gazira State using (CA-15-3 and PSA) technology

    International Nuclear Information System (INIS)

    This study was conducted in Algezira State in two environmentally and economically different areas. The people in these areas were divided into two groups in the study: group (A) people who live alongside the Blue Nile bank. Group people who live away how the Blue Nile, I e in midland between the Blue Nile and White Nile which is called (AI-Bajour). The aim of the study was to recognize the normal rate of breast cancer markers(Carbohydrate Antigen 15-3), which is one of the most common cancers, and the prostate cancer (Prostate Cancer Markers), as compared with the global normal rate, in order to early detect and treat these types of cancers. The study was conducted on 336 men and 304 women, who are different in ages, work and social status. The researcher used an experimental, descriptive and analytical method, and the SPSS program for analysis. The study showed that the results of normal rate as compared with previous studies are typical to the breast cancer markers (carbohydrate antigen 15-3, ranging between (0-40) ngm/ml, where as the normal rate of the prostate cancer markers (PSA) ranges between (0-4) ngm/ml, and according to the previous African and American studies. The studies also showed that the results are different according to the group are different according to the group involved. There is an increase in normal rates of group (A) in the PSA markers. From 177 men, 49 had rated of (4-10) ng/ml, 6 had very high rates (10-20)ng/ml and extremely high rates of 2 samples (>20)ng/ml. It was noticed that the abnormal increase rate is directly proportional to the age development. The study showed high results of breast cancer markers (Carbohydrate antigen 15-3), as compared with the global normal rate (0-40)ng/ml, 6 had very high rates (60-100)ng/ml and extremely high rates (>100)ng/ml. Two women of uterus cancer died. Again the abnormal increase in the rates is directly proportional to age development. The study showed that the results of group (B) is

  6. A risk evaluation model of cervical cancer based on etiology and human leukocyte antigen allele susceptibility

    OpenAIRE

    Bicheng Hu; Ning Tao; Fanyu Zeng; Min Zhao; Lixin Qiu; Wen Chen; Yun Tan; Yun Wei; Xufeng Wu; Xinxing Wu

    2014-01-01

    Background: There are no reliable risk factors to accurately predict progression to cervical cancer in patients with chronic cervicitis infected with human papillomavirus (HPV). The aim of this study was to create a validated predictive model based on the risk factors for cervical cancer. A model to estimate the risk of cervical cancer may help select patients for intervention therapy in order to reduce the occurrence of cervical cancer after HPV infection. Methods: This retrospective anal...

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

    NARCIS (Netherlands)

    Nijman, HW; Lambeck, A; van der Burg, SH; van der Zee, AGJ; Daemen, T

    2005-01-01

    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 signif

  8. Immunotherapy for prostate cancer: lessons from responses to tumor-associated antigens

    NARCIS (Netherlands)

    Westdorp, H.; Skold, A.; Snijer, B.A.; Franik, S.; Mulder, S.F.; Major, P.P.; Foley, R.; Gerritsen, W.R.; Vries, I.J.M. de

    2014-01-01

    Prostate cancer (PCa) is the most common cancer in men and the second most common cause of cancer-related death in men. In recent years, novel therapeutic options for PCa have been developed and studied extensively in clinical trials. Sipuleucel-T is the first cell-based immunotherapeutic vaccine fo

  9. 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...

  10. Variation in general practice prostate-specific antigen testing and prostate cancer outcomes

    DEFF Research Database (Denmark)

    Hjertholm, Peter; Fenger-Grøn, Morten; Vestergaard, Mogens;

    2015-01-01

    Brugen af prostata-specifikt antigen (PSA) er mangedoblet i dansk almen praksis siden introduktionen i 1990’erne. Dansk Urologisk Selskab anbefaler brug af testen ved relevante symptomer og arvelig disposition, men ikke til screening. Alligevel varierer brugen af PSA-tests i almen praksis. Dette ...

  11. Identification of ATP synthase beta subunit (ATPB) on the cell surface as a non-small cell lung cancer (NSCLC) associated antigen

    International Nuclear Information System (INIS)

    Antibody-based immuneotherapy has achieved some success for cancer. But the main problem is that only a few tumor-associated antigens or therapeutic targets have been known to us so far. It is essential to identify more immunogenic antigens (especially cellular membrane markers) for tumor diagnosis and therapy. The membrane proteins of lung adenocarcinoma cell line A549 were used to immunize the BALB/c mice. A monoclonal antibody 4E7 (McAb4E7) was produced with hybridoma technique. MTT cell proliferation assay was carried out to evaluate the inhibitory effect of McAb4E7 on A549 cells. Flow cytometric assay, immunohistochemistry, western blot and proteomic technologies based on 2-DE and mass spectrometry were employed to detect and identify the corresponding antigen of McAb4E7. The monoclonal antibody 4E7 (McAb4E7) specific against A549 cells was produced, which exhibited inhibitory effect on the proliferation of A549 cells. By the proteomic technologies, we identified that ATP synthase beta subunit (ATPB) was the corresponding antigen of McAb4E7. Then, flow cytometric analysis demonstrated the localization of the targeting antigen of McAb4E7 was on the A549 cells surface. Furthermore, immunohistochemstry showed that the antigen of McAb4E7 mainly aberrantly expressed in tumor cellular membrane in non-small cell lung cancer (NSCLC), but not in small cell lung cancer (SCLC). The rate of ectopic expressed ATPB in the cellular membrane in lung adenocarcinoma, squamous carcinoma and their adjacent nontumourous lung tissues was 71.88%, 66.67% and 25.81% respectively. In the present study, we identified that the ectopic ATPB in tumor cellular membrane was the non-small cell lung cancer (NSCLC) associated antigen. ATPB may be a potential biomarker and therapeutic target for the immunotherapy of NSCLC

  12. Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients.

    Science.gov (United States)

    Knights, Ashley J; Nuber, Natko; Thomson, Christopher W; de la Rosa, Olga; Jäger, Elke; Tiercy, Jean-Marie; van den Broek, Maries; Pascolo, Steve; Knuth, Alexander; Zippelius, Alfred

    2009-03-01

    The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions. PMID:18663444

  13. Development of a new Ca2+/calmodulin antagonist and its anti-proliferative activity against colorectal cancer cells

    International Nuclear Information System (INIS)

    We previously identified a cellular target of a cell cycle inhibitor HBC as Ca2+/calmodulin (Ca2+/CaM) through chemical genetics approach. Using the mechanism-based drug design, we developed a new Ca2+/CaM antagonists based on the structure of HBC. The compound, (4-{3,5-bis-[2-(4-hydroxy-3-methoxy-phenyl)-vinyl]-4,5-dihydro-pyrazol-1-yl }-phenyl)-(4-methyl-piperazin-1-yl)-methanone (referred as HBCP), binds to Ca2+/CaM in vitro and inhibits the proliferation of HCT15 colon cancer cells. HBCP induced sustained phosphorylation of ERK1/2 and subsequently activated p21WAF1 expression in HCT15 cells. Moreover, HBCP reversibly induced the G0/G1 cell cycle arrest in the cells. These data demonstrate that HBCP is a new potent Ca2+/CaM antagonist and can be applied for CaM related therapeutic uses

  14. Anvendelse af prostataspecifikt antigen. En oversigt

    DEFF Research Database (Denmark)

    Brasso, K; Skaarup, P; Roosen, Jens Ulrik; Iversen, Peter

    1998-01-01

    Since it was first introduced, measurement of prostate specific antigen has gained increasing interest, and prostate specific antigen is regarded as being the best tumour marker available. The antigen lacks cancer specificity, limiting the usefulness in early diagnosis, The use of prostate specific...... antigen in early diagnosis, staging, and in monitoring patients with prostate cancer is reviewed....

  15. Impacts of CA9 Gene Polymorphisms and Environmental Factors on Oral-Cancer Susceptibility and Clinicopathologic Characteristics in Taiwan

    OpenAIRE

    Chien, Ming-Hsien; Yang, Jia-Sin; Chu, Yin-Hung; Lin, Chien-huang; Wei, Lin-Hung; Yang, Shun-Fa; Lin, Chiao-Wen

    2012-01-01

    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 Pr...

  16. FDG PET/CT and CA 15-3 in the early diagnosis of recurrent breast cancer

    International Nuclear Information System (INIS)

    The most widely used tumour marker in the follow-up of breast cancer is CA 15-3. But its use is still in debate. There is general agreement that a progressive increase of CA 15-3 might be the early signal of tumour relapse, even when found in an asymptomatic patient. The aim of this study is to evaluate the diagnostic effectiveness of PET/CT with FDG in the detection of breast cancer recurrence in cases of isolated elevation of CA 15-3. Methods: Fourteen patients, previously treated for breast cancer, with no clinical evidence of recurrence, negative conventional radiological examination but with an increase of CA15-3 were studied. 18FDG-PET/CT was performed. Results were correlated with histology, other imaging methods and clinical follow-up. Results: PET/CT was positive for 7 patients. One patient presented a recurrence with negative PET/CT. With an overall sensitivity of 87,5%, this exam identified a recurrence for 50% of the patients with isolated CA 15-3 elevation. Conclusion: These results suggest that tumour marker-guided PET/CT with FDG is a useful technique for the early detection of breast cancer recurrence. Further studies, with a greater number of patients and a longer follow-up, are necessary to evaluate the red diagnostic and therapeutic impact of this association. (authors)

  17. Diagnostic role of fluorine-18 (18F fluorodeoxyglucose positron emission tomography computed tomography in detecting recurrent disease in patients with colorectal cancer and elevated carcinoembryonic antigen

    Directory of Open Access Journals (Sweden)

    Matovina Emil

    2015-01-01

    Full Text Available Introduction. Early detection of recurrence is an important factor for long term survival of patients with colorectal cancer. Measurement of serum levels of carcinoembryonic antigen has been commonly used in the postoperative surveillance of colorectal cancer. The purpose of this study was to evaluate the ability of positron emission tomography-computed tomography to detect pathological substrate of elevated serum carcinoembryonic antigen in patients with colorectal cancer. Material and Methods. The patients with colorectal cancer who underwent curative surgical resection and/ or chemotherapy, who were found in our database, were analyzed retrospectively. Forty-eight 18F- fluorodeoxyglucose positron emission tomography-computed tomography studies including 45 patients (14 women, 31 men; mean age: 62.93 years with elevated serum, carcinoembryonic antigen levels, which had been performed between January 2011 and January 2014, were evaluated. Serum levels of carcinoembryonic antigen were measured within 3 months after positron emission tomography-computed tomography examination. Final diagnosis of recurrence was made by histopathological findings, radiology studies or clinical follow-up. Results. Recurrences were diagnosed in 37 patients, the prevalence being 77.1%. Liver metastases were found in 18 patients, abdominal, pelvic and/or mediastinal lymph nodes were positive in 19 patients, 11 patients had loco regional recurrences and 4 patients had pulmonary metastasis, and bone metastases were found in one patient. One patient was diagnosed with metastasis in scar tissue. The overall sensitivity and specificity of positron emission tomography-computed tomography was 90.24% and 71.42%, respectively. The positive and negative predictive values were 94.87% and 55.56%, respectively. Conclusion. 18F- fluorodeoxyglucose positron emission tomography-computed tomography is a powerful tool that could be used in determining colorectal cancer recurrence in

  18. Evaluation of CA 15-3 tumor marker in the diagnosis of breast cancer. A pilot study

    International Nuclear Information System (INIS)

    Single determinations of serum CA 15-3 levels were performed by sandwich immunoassay in 160 women: 77 patients with nonmalignant breast tumors (64 had fibrocystic disease, 11 had fibroadenoma, 2 had intra-ductal papillomas) and 83 patients with primary breast cancer prior to any treatment: the cut-off limit was established at 30 U/ml. The overall diagnostic sensitivity and specificity of the CA 15-3 test was 19.3% and 94.8%, respectively. The positive and negative predictive values were 80.0% and 52.1%. The mean CA 15-3 value was significantly lower in patients with benign breast tumors as compared with the breast cancer group: 16.8+-8.2 vs. 23.9+-20.9 U/ml (p<0.01) as well as percentage of positive results of the test: 5.2% vs. 19.3% (p<0.02). Serum CA 15-3 level in breast cancer patients correlated with: (1) clinical stage: a higher percentage of positive results was observed in patients with more advanced cancer: Stage I - 0%, Stage II - 10.6%, Stage III - 29.6%, and Stage IV - 100% according to UICC classification the comparison of breast cancer patients with early stage of disease (I+II) and those with more advanced cancer (III+IV) revealed statistically significant (p<0.01) difference in the mean serum CA 15-3 value (19.7+-12.8 vs. 31.5+-29.2 U/ml) as well as in the percentage of positive results (9.4% vs. 36.7%, p<0.01): (2) the histological goading according to Bloom and Richardson; 5.41% of positively was observed in low and intermediate grade cancers (I+II) vs. 66.7% in grade III(p,0.001). In conclusion, our data confirmed that the diagnostic sensitivity of CA 15-3 assay was low thus not suitable for diagnosis in early breast cancer and for differentiation between benign and malignant breast diseases. The CA 15-3 was directly related to the stage of breast cancer and the degree of malignancy which are highly correlated to prognosis. (author)

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

    Directory of Open Access Journals (Sweden)

    Tengfei Zhang

    2015-01-01

    Full Text Available 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 cells have shown promising outcomes in cancers, especially in hematologic malignancies. CTLA-4 and PD-1 are two important immune checkpoints negatively regulating T cell activation. Clinical benefits of CTLA-4/PD-1 antibodies are significant in melanoma and other solid tumors. PD-1 is predicted to have fewer side effects and greater antitumor activity than CTLA-4. In this review, we will summarize current immunotherapies based on CAR T cells and PD-1.

  20. Prostate-specific antigen as a risk factor for skeletal metastasis in native ethnic African Men with prostate cancer : a case control study

    OpenAIRE

    Qureshi, Ayman; Makhdomi, Khalid; Stones, William

    2016-01-01

    Prostate cancer is the commonest non cutaneous cancer in males. Men of African origin are at significantly higher risk as reflected in higher incidence and mortality rates in this racial group. Metastases incidence increases in parallel with serum levels of Prostate Specific Antigen (PSA), contributing significantly to morbidity and mortality. Staging of disease involves bone scans, which are sensitive in detecting skeletal metastases. Suggestions they may be omitted in some situations in pat...

  1. Dominant B-cell epitopes from cancer/stem cell antigen SOX2 recognized by serum samples from cancer patients

    OpenAIRE

    Shih, Julia; Rahman, Munira; Luong, Quang T; Lomeli, Shirley H.; Riss, Joseph; Prins, Robert M.; Gure, Ali O.; Zeng, Gang

    2014-01-01

    Human sex determining region Y-box 2 (SOX2) is an important transcriptional factor involved in the pluripotency and stemness of human embryonic stem cells. SOX2 plays important roles in maintaining cancer stem cell activities of melanoma and cancers of the brain, prostate, breast, and lung. SOX2 is also a lineage survival oncogene for squamous cell carcinoma of the lung and esophagus. Spontaneous cellular and humoral immune responses against SOX2 present in cancer patients classify it as a tu...

  2. Is tissue CA125 expression in epithelial ovarian adenocarcinoma heterogenic?

    DEFF Research Database (Denmark)

    Sparholt, Morten H; Høgdall, Claus K; Nedergaard, Lotte;

    2013-01-01

    To evaluate if heterogeneity of tissue cancer antigen 125 (CA125) expression is present in epithelial serous adenocarcinomas. Furthermore, to investigate whether there is a correlation between levels of CA125 tissue expression, serum level of CA125, stage, and grade. A total of 10 patients...... diagnosed with serous ovarian adenocarcinomas were included. Preoperative blood samples were collected to determine serum CA125 levels. Tumor tissue from primary surgery was collected and processed for immunohistochemical analyses. CA125 was expressed in varying degrees in tumor tissues from all patients....... Mean tissue CA125 expression for each patient ranged from 36% to 98%. Intrapatient variations in tissue expression ranged from 10% to 90% point. No significant correlations between levels of CA125 tissue expression, serum level of CA125, stage, and grade were found. We found that the tissue expression...

  3. 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.

    2008-01-01

    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 autoantib

  4. 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.

    2013-01-01

    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

  5. L1 Cell Adhesion Molecule-Specific Chimeric Antigen Receptor-Redirected Human T Cells Exhibit Specific and Efficient Antitumor Activity against Human Ovarian Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Hao Hong

    Full Text Available 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.

  6. Collaboration Opportunities with the Cancer Human Biobank (caHUB) at NCI | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The Biorepositories and Biospecimen Research Branch (BBRB) at the National Cancer Institute has developed the Cancer Human Biobank (caHUB), which is a unique infrastructure for collecting biospecimens for the purpose of conducting biospecimen research. Biospecimens from the BPV program will be made available to collaborators with the capability to perform molecular analysis as part of a collaborative research agreement with the NCI-BBRB.

  7. 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. PMID:3411695

  8. Changing prostate-specific antigen outcome after surgery or radiotherapy for localized prostate cancer during the prostate-specific antigen era

    International Nuclear Information System (INIS)

    Purpose: To evaluate the change in prostate-specific antigen (PSA) outcome after radical prostatectomy (RP) or external beam radiotherapy (EBRT), controlling for follow-up during the PSA era. Methods and Materials: The study cohort consisted of 1440 patients with clinically localized prostate cancer managed with RP (n=1059) or EBRT (n=381) between 1989 and 2000. A single genitourinary pathologist reviewed all pathology specimens. For patients with a 2-year minimal follow-up, the 2-year actual PSA outcome stratified by risk group (low vs. high) was calculated for three periods (January 1, 1989 to December 31, 1992; January 1, 1993 to December 31, 1996; and January 1, 1997 to December 31, 2000) and compared for each treatment modality. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition for all patients, and comparisons were made using a chi-square metric. Results: During the study period, the proportion of patients treated with RP and EBRT with low-risk disease increased significantly (p <0.0001) from 60% to 89% and from 26% to 76%, respectively. In addition, the 2-year actual PSA outcome also improved from 60% to 82% (RP: p<0.0001) and from 67% to 91% (RT: p=0.0008). The 2-year actual PSA outcome was not significantly different in the low-risk patients but improved during the three periods in the high-risk patients treated with RP (from 20% to 39% to 75%, p=0.0004) or EBRT (from 50% to 59% to 83%, p=0.01). This improvement in PSA outcome could be explained by a shift toward a more favorable PSA level (RP: p=0.0002; RT: p=0.006) and clinical T stage (RP: p=0.0008, RT: p<0.0001) distribution for patients with biopsy Gleason score ≥7 disease. Conclusion: Improved PSA outcome during the PSA era after RP or EBRT has resulted from a shift in presentation toward low-risk disease and earlier detection of high-grade disease

  9. The prostate cancer risk stratification (ProCaRS) project: Recursive partitioning risk stratification analysis

    International Nuclear Information System (INIS)

    Background: The Genitourinary Radiation Oncologists of Canada (GUROC) published a three-group risk stratification (RS) system to assist prostate cancer decision-making in 2001. The objective of this project is to use the ProCaRS database to statistically model the predictive accuracy and clinical utility of a proposed new multi-group RS schema. Methods: The RS analyses utilized the ProCaRS database that consists of 7974 patients from four Canadian institutions. Recursive partitioning analysis (RPA) was utilized to explore the sub-stratification of groups defined by the existing three-group GUROC scheme. 10-fold cross-validated C-indices and the Net Reclassification Index were both used to assess multivariable models and compare the predictive accuracy of existing and proposed RS systems, respectively. Results: The recursive partitioning analysis has suggested that the existing GUROC classification system could be altered to accommodate as many as six separate and statistical unique groups based on differences in BFFS (C-index 0.67 and AUC 0.70). GUROC low-risk patients would be divided into new favorable-low and low-risk groups based on PSA ⩽6 and PSA >6. GUROC intermediate-risk patients can be subclassified into low-intermediate and high-intermediate groups. GUROC high-intermediate-risk is defined as existing GUROC intermediate-risk with PSA >=10 AND either T2b/c disease or T1T2a disease with Gleason 7. GUROC high-risk patients would be subclassified into an additional extreme-risk group (GUROC high-risk AND (positive cores ⩾87.5% OR PSA >30). Conclusions: Proposed RS subcategories have been identified by a RPA of the ProCaRS database

  10. Synthesis and expression of CDw75 antigen in human colorectal cancer

    International Nuclear Information System (INIS)

    Increased ST6Gal I activity has been associated with the α(2,6)sialylation enhancement of membrane glycoconjugates observed in metastatic colorectal carcinomas (CRC). Siaα(2,6)Galβ(1,4)GlcNAc sequence, known as CDw75, is a sialylated carbohydrate determinant generated by the ST6Gal I. This epitope has been reported to be associated with the progression of gastric and colorectal tumours, hence there are only a few conclusive studies to date. By radioisotopic techniques we evaluated the ST6Gal I activity in healthy, transitional and tumour tissues from 43 patients with CRC. By immunohistochemistry we assessed the CDw75 expression in 25 colorectal adenomas, 43 tumours, 13 transitional and 28 healthy tissues of CRC patients. ST6Gal I activity was likewise found to be statistically higher in tumour tissue respect to healthy tissue from CRC patients. CDw75 expression was positive in 20% of colorectal adenomas. Furthermore, 70% of tumour specimens and 8.3% of transitional specimens were positive for CDw75 expression, whereas none of the healthy ones showed the presence of the epitope. The major contribution of this study is the inclusion of data from transitional tissue and the analysis of CDw75 antigen expression in CRC and in colorectal adenomas, little known so far. ST6Gal I activity and CDw75 antigen expression were increased in CRC. Although their comparison did not reach the statistical significance, a great extent of patients showed both, an enhanced tumour ST6Gal I activity and an increased CDw75 expression in the tumour tissue. So, these two variables may play a role in malignant transformation. The expression of CDw75 in colorectal adenomas suggests that this antigen may be a tumour marker in CRC

  11. Validation of the Kattan preoperative nomogram for prostate cancer recurrence using a community based cohort: Results from cancer of the prostate strategic urological research endeavor (CaPSURE)

    OpenAIRE

    Greene, KL; Meng, MV; Elkin, EP; Cooperberg, MR; Pasta, DJ; Kattan, MW; Wallace, K.; Carroll, PR

    2004-01-01

    Purpose: The Kattan preoperative nomogram combines preoperative prostate specific antigen (PSA), biopsy Gleason grade and clinical stage to estimate disease recurrence after radical prostatectomy. Several studies using patient data from academic centers have validated the nomogram. We assessed the performance of the Kattan nomogram using the Cancer of the Prostate Strategic Urological Research Endeavor database, a national, largely community based observational disease registry. Materials and...

  12. Engineering a prostate-specific membrane antigen-activated tumor endothelial cell prodrug for cancer therapy

    DEFF Research Database (Denmark)

    Denmeade, Samuel R; Mhaka, Annastasiah M; Rosen, D Marc;

    2012-01-01

    Heterogeneous expression of drug target proteins within tumor sites is a major mechanism of resistance to anticancer therapies. We describe a strategy to selectively inhibit, within tumor sites, the function of a critical intracellular protein, the sarcoplasmic/endoplasmic reticulum calcium...... adenosine triphosphatase (SERCA) pump, whose proper function is required by all cell types for viability. To achieve targeted inhibition, we took advantage of the unique expression of the carboxypeptidase prostate-specific membrane antigen (PSMA) by tumor endothelial cells within the microenvironment of...

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

    Aim: 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). Methods: A total of 12 027 Chinese men in Changchun were screened for prostate cancer by means of the serum total prostate specific antigen (tPSA) test (oy 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). Results: Of the 12 027 cases, 158 (including 137 patients whose serum tPSA values were >4.0 ng/mL and 21 patients [serum tPSA <4.0 ng/mL] who had obstructive symptoms) undertook prostate biopsy. Of the 158 biopsies, 41 cases of prostatic carcinoma were found (25.9 %, 41/158). The moderately differentiated carcinoma and poorly differentiated carcinoma accounted for 61% and 34%, respectively. A significant linear positive correlation between the serum tPSA and the Gleason scores in the 41 cases of prostatic carcinoma (r = 0.312, P < 0.01) was established. A significant linear positive correlation between the serum tPSA value of the 41 prostatic carcinoma and the positive counts of carcinoma in sextant biopsies was established (r = 0.406, P < 0.01), indicating a significant linear relationship between serum tPSA and the size of tumor.Conclusion: This study was the 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.

  14. In vitro cytotoxic effects of CTL activated by dendritic cells loaded with esophageal cancer antigen peptide by 51Cr release assay

    International Nuclear Information System (INIS)

    Objective: RIT plays an important role in the targeted therapy for tumors. The aim of the paper was to study cytotoxic effects of the cytotoxic T lymphocytes (CTL) to human esophageal cancer cell line TE-1, activated by dendritic cells (DC) loaded with esophageal cancer antigen peptide. Methods: Esophageal cancer TE-1 cell antigen peptide was obtained by citrate phosphate buffer elution. DC were induced and proliferated in vitro and were loaded with the esophageal cancer antigen peptide. The tumor antigen specific CTL were generated from the DC. And the cytotoxicity of CTL to TE-1 was assessed by 51Cr release assay. Results: The killing rate of CTL activated by loaded DC[(81.12±2.93)%] was higher than that of CTL activated by DC unloaded [(11.16±3.07)%]. The killing rate of CTL activated by loaded DC in TE-1 pretreated with interferon (IFN)-γ [(89.15±3.62)%] was higher than that in cells without IFN-γ [(61.19±5.17)%]. The killing rate of CTL was higher than that in TE-1 with acid elution [(9.18±2.52)%]. The killing rate of CTL activated by loaded DC diminished in order in Eta-109, human adenocarcinoma cell line K59 and human suprarenal epithelioma cell line 786-0. Conclusions: Acid elution could get effective esophageal cancer antigen peptide from TE-1 cell membrane. The CTL activated by DC loaded with that peptide had specific cytotoxic effects to TE-1 cells. (authors)

  15. The Mechanism of Safrole-Induced [Ca²⁺]i Rises and Non-Ca²⁺-Triggered Cell Death in SCM1 Human Gastric Cancer Cells.

    Science.gov (United States)

    Hung, Tzu-Yi; Chou, Chiang-Ting; Sun, Te-Kung; Liang, Wei-Zhe; Cheng, Jin-Shiung; Fang, Yi-Chien; Li, Yih-Do; Shieh, Pochuen; Ho, Chin-Man; Kuo, Chun-Chi; Lin, Jia-Rong; Kuo, Daih-Huang; Jan, Chung-Ren

    2015-10-31

    Safrole is a carcinogen found in plants. The effect of safrole on cytosolic free Ca²⁺ concentrations ([Ca²⁺](i)) and viability in SCM1 human gastric cancer cells was explored. The Ca²⁺-sensitive fluorescent dye fura-2 was applied to measure [Ca²⁺](i). Safrole at concentrations of 150-450 μM induced a [Ca²⁺](i) rise in a concentration-dependent manner. The response was reduced by 60% by removing extracellular Ca²⁺. Safrole-evoked Ca²⁺ entry was not altered by nifedipine, econazole, SKF96365, and protein kinase C activator or inhibitor. In Ca²⁺-free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) abolished safrole-evoked [Ca²⁺](i) rises. Conversely, treatment with safrole abolished thapsigargin or BHQ-evoked [Ca²⁺](i) rises. Inhibition of phospholipase C (PLC) with U73122 abolished safrole-induced [Ca²⁺](i) rises. At 250-550 μM, safrole decreased cell viability concentration-dependently, which was not reversed by chelating cytosolic Ca²⁺ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl (BAPTA/AM). Annexin V/propidium iodide staining data suggest that safrole (350-550 μM) induced apoptosis concentration-dependently. These studies suggest that in SCM1 human gastric cancer cells, safrole induced [Ca²⁺](i) rises by inducing PLC-dependent Ca²⁺ release from the endoplasmic reticulum and Ca²⁺ influx via non-store-operated Ca²⁺ entry pathways. Safrole-induced cell death may involve apoptosis. PMID:26387654

  16. The role of TF- and Tn-antigens in breast cancer metastasis.

    Science.gov (United States)

    Kölbl, Alexandra C; Jeschke, Udo; Friese, Klaus; Andergassen, Ulrich

    2016-06-01

    Almost 40 years ago, researchers found out that the Thomsen-Friedenreich (TF) and the Thomsen nouvelle (Tn) antigens could be detected in carcinoma, but not in healthy tissue. A short time after that it became clear that TF and Tn are precursor molecules of the MN-blood group antigens. In normal tissue TF and Tn are coated by glycosyl structures, thereby forming the glycoproteins which are known to account for the MN-blood group, but in malignant tissue these molecules are uncovered.TF, which has an additional Galectin-residue compared to Tn, is correlated with a more favourable prognosis for patients. On the contrary, patients with Tn-bearing tissues have a worse prognosis for overall and progression-free survival. It is known that TF and Tn are involved in the adhesion of tumour cells to the endothelium via a mechanism recruiting Galectin-3 and MUC-1, which is the first step in metastasis formation. Furthermore, it became clear that this pathway can be blocked by a growing number of molecules, thereby creating ways of therapeutical intervention. PMID:26758176

  17. The favorable impact of PIK3CA mutations on survival: an analysis of 2587 patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    Amaury G.Dumont; Sarah N.Dumont; Jonathan C.Trent

    2012-01-01

    The phosphatidylinositol-3 kinase (PI3K) pathway regulates a number of cellular processes,including cell survival,cell growth,and cell cycle progression.Consequently,this pathway is commonly deregulated in cancer.In particular,mutations in the gene PIK3CA that encodes the p110α catalytic subunit of the PI3K enzymes result in cell proliferation and resistance to apoptosis in vitro and induce breast tumors in transgenic mice.These data underscore the role of this pathway during oncogenesis.Thus,an ongoing,large-scale effort is underway to develop clinically active drugs that target elements of the PI3K pathway.However,conflicting data suggest that gain-of-function PIK3CA mutations may be associated with either a favorable or a poor clinical outcome,compared with the wild-type PIK3CA gene.In the current study,we performed a systematic review of breast cancer clinical studies.Upon evaluation of 2587 breast cancer cases from 12 independent studies,we showed that patients with tumors harboring a PIK3CA mutation have a better clinical outcome than those with a wild-type PIK3CA gene.Importantly,this improved prognosis may pertain only to patients with mutations in the kinase domain of p110α and to postmenopausal women with estrogen receptor-positive breast cancer.We propose three potential explanations for this paradoxical observation.First,PIK3CA mutations may interfere with the metastasis process or may induce senescence,which results in a better outcome for patients with mutated tumors.Secondly,we speculate that PIK3CA mutations may increase early tumor diagnosis by modification of the actin cytoskeleton in tumor cells.Lastly,we propose that PIK3CA mutations may be a favorable predictive factor for response to hormonal therapy,giving a therapeutic advantage to these patients.Ultimately,an improved understanding of the clinical impact of PIK3CA mutations is critical for the development of optimally personalized therapeutics against breast cancer and other solid tumors

  18. The association of preoperative serum tumour markers with Dukes' stage and survival in colorectal cancer.

    OpenAIRE

    Lindmark, G.; Bergström, R.; Påhlman, L; Glimelius, B.

    1995-01-01

    The tumour markers carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), TPS, CA 19-9, CA 50 and CA 242 were analysed in serum from 203 potentially curable colorectal cancer patients. The levels of all markers increased with increasing tumour stage, and all markers correlated with survival. Multivariate analyses indicated that the Dukes stage had the best prognostic explanatory power, followed by TPA. In the subset of 166 potentially cured patients, the prognostic information by t...

  19. Posttreatment prostatic-specific antigen doubling time as a surrogate endpoint for prostate cancer-specific survival: An analysis of Radiation Therapy Oncology Group Protocol 92-02

    International Nuclear Information System (INIS)

    Purpose: We evaluated whether posttreatment prostatic-specific antigen doubling time (PSADT) was predictive of prostate cancer mortality by testing the Prentice requirements for a surrogate endpoint. Methods and Materials: We analyzed posttreatment PSA measurements in a cohort of 1,514 men with localized prostate cancer (T2c-4 and PSA level Cox = 0.002), PSADT Cox Cox Cox Cox = 0.4). The significant posttreatment PSADTs were also significant predictors of CSS (pCox< 0.001). After adjusting for T stage, Gleason score and PSA, all of Prentice's requirements were not met, indicating that the effect of PSADT on CSS was not independent of the randomized treatment. Conclusions: Prostatic specific antigen doubling time is significantly associated with CSS, but did not meet all of Prentice's requirements for a surrogate endpoint of CSS. Thus, the risk of dying of prostate cancer is not fully explained by PSADT

  20. Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    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. 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). 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. 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

  1. 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.

  2. Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

    OpenAIRE

    Tanaka, Kimitaka; Tsuchikawa, Takahiro; Miyamoto, Masaki; Maki, Takehiro; ICHINOKAWA, MASAOMI; KUBOTA, KANAKO C.; Shichinohe, Toshiaki; Hirano, Satoshi; Ferrone, Soldano; DOSAKA-AKITA, HIROTOSHI; Matsuno, Yoshihiro; Kondo, Satoshi

    2012-01-01

    The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP-1, TAP-2, LMP-7 and LMP-10. Immunohi...

  3. Down-regulation of Human Leukocyte Antigen class I heavy chain in tumors is associated with a poor prognosis in advanced esophageal cancer patients

    OpenAIRE

    Tanaka, Kimitaka; Tsuchikawa, Takahiro; Miyamoto, Masaki; Maki, Takehiro; ICHINOKAWA, MASAOMI; KUBOTA, KANAKO C.; Shichinohe, Toshiaki; Hirano, Satoshi; Ferrone, Soldano; DOSAKA-AKITA, HIROTOSHI; Matsuno, Yoshihiro; Kondo, Satoshi

    2011-01-01

    The HLA class I antigen processing machinery (APM) plays a crucial role in the anticancer immune response. The aim of this study was to assess the clinical significance of APM components in esophageal cancer. A total of 11 esophageal cancer cell lines were evaluated by Western blot analysis for 13 HLA class I APM components. There was a different expression pattern among cancer cell lines for HLA class I heavy chain (HLA-HC), β2 microglobulin, Tapasin, TAP-1, TAP-2, LMP-7 and LMP-10. Immunohi...

  4. 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

    group (>10% lifetime risk of developing ovarian cancer), 77 in a moderate risk group (4-10% lifetime risk of developing ovarian cancer) and 71 in a near population risk group (<4% lifetime risk). METHODS: Retrospective audit of case records, laboratory CA125 results, radiology reports, histology records......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...... and local cancer registry data. MAIN OUTCOME MEASURES: Ovarian cancers occurring in study population. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of TVU, and CA125 as a screening tool for ovarian cancer. RESULTS: Four ovarian cancers and one...

  5. Label-free electrical detection of ovarian cancer biomarker CA-125 with a novel nanoscale coaxial array

    Science.gov (United States)

    Archibald, Michelle; Rizal, Binod; Cai, Dong; Connolly, Timothy; Burns, Michael; Naughton, Michael; Chiles, Thomas

    2013-03-01

    Technologies to detect early stage cancer would provide significant benefit to cancer disease patients. Clinical measurement of biomarkers offers the promise of a noninvasive and cost effective screening for early stage detection. We have developed a novel 3-dimensional nanocavity array for the detection of human cancer biomarkers. This all-electronic diagnostic sensor is based on a nanoscale coaxial array architecture that enables molecular-level detection. Each individual sensor in the array is a vertically-oriented coaxial capacitor, whose capacitance is measurably changed when target molecules enter the coax annulus. The coaxial array facilitates electrical-based detection in response to antibody or molecular imprint based recognition of a specific cancer biomarker, thereby providing a label-free, non-optical measurement. Here, we describe this nanoscale 3D architecture and its application to the detection of the ovarian cancer biomarker CA-125. We report our efforts on the development of molecular detection of CA-125 based on antibody-functionalized nanocoax arrays as well as molecular imprints. The results demonstrate the feasibility of using these arrays as ultrasensitive devices to detect a wide range of molecular targets, including disease biomarkers. Supported by the NIH grants NCI CA137681 and NIAID AI100216.

  6. The calcium pump plasma membrane Ca(2+)-ATPase 2 (PMCA2) regulates breast cancer cell proliferation and sensitivity to doxorubicin.

    Science.gov (United States)

    Peters, Amelia A; Milevskiy, Michael J G; Lee, Wei C; Curry, Merril C; Smart, Chanel E; Saunus, Jodi M; Reid, Lynne; da Silva, Leonard; Marcial, Daneth L; Dray, Eloise; Brown, Melissa A; Lakhani, Sunil R; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2016-01-01

    Regulation of Ca(2+) transport is vital in physiological processes, including lactation, proliferation and apoptosis. The plasmalemmal Ca(2+) pump isoform 2 (PMCA2) a calcium ion efflux pump, was the first protein identified to be crucial in the transport of Ca(2+) ions into milk during lactation in mice. In these studies we show that PMCA2 is also expressed in human epithelia undergoing lactational remodeling and also report strong PMCA2 staining on apical membranes of luminal epithelia in approximately 9% of human breast cancers we assessed. Membrane protein expression was not significantly associated with grade or hormone receptor status. However, PMCA2 mRNA levels were enriched in Basal breast cancers where it was positively correlated with survival. Silencing of PMCA2 reduced MDA-MB-231 breast cancer cell proliferation, whereas silencing of the related isoforms PMCA1 and PMCA4 had no effect. PMCA2 silencing also sensitized MDA-MB-231 cells to the cytotoxic agent doxorubicin. Targeting PMCA2 alone or in combination with cytotoxic therapy may be worthy of investigation as a therapeutic strategy in breast cancer. PMCA2 mRNA levels are also a potential tool in identifying poor responders to therapy in women with Basal breast cancer. PMID:27148852

  7. Inhibition of Spontaneous Breast Cancer Metastasis by Anti—Thomsen-Friedenreich Antigen Monoclonal Antibody JAA-F11

    Directory of Open Access Journals (Sweden)

    Jamie Heimburg

    2006-11-01

    Full Text Available Thomsen-Friedenreich antigen (TF-Ag is expressed in many carcinomas, including those of the breast, colon, bladder, prostate. TF-Ag is important in adhesion and metastasis and as a potential immunotherapy target. We hypothesized that passive transfer of JAAF11, an anti -TF-Ag monoclonal antibody, may create a survival advantage for patients with TIF-Ag -expressing tumors by cytotoxicity, blocking of tumor cell adhesion, inhibition of metastasis. This was tested using in vitro models of tumor cell growth; cytotoxicity assays; in vitro, ex vivo, in vivo models of cancer metastasis; and, finally, in vivo effects in mice with metastatic breast cancer. Unlike some anti-TF-Ag antibodies, JAA-F11 did not enhance breast carcinoma cell growth. JAA-F11 did not induce the killing of 4T1 tumor cells through complement-dependent cytotoxicity or apoptotic mechanisms. However, JAA-F11 blocked the stages of metastasis that involve the adhesion of human breast carcinoma cells to human endothelial cells (human umbilical vein endothelial cells and human bone marrow endothelial cells 60 in in vitro static adhesion models, in a perfused ex vivo model, in murine lung vasculature in an in vivo metastatic deposit formation assay. JAA-F11 significantly extended the median survival time of animals bearing metastatic 4T1 breast tumors and caused a > 50% inhibition of lung metastasis.

  8. Localization of 131Ilabeled goat and primate anti-carcinoembryonic antigen(CEA) antibodies in patients with cancer

    International Nuclear Information System (INIS)

    Thirty patients with anti-carcinoembryonic antigen (CEA)-producing cancers of the colon, breast, or thyroid were intected with 1 to 2 mCi of Iodine-131 (131I)-labeled, affinity-purified, goat or baboon anti-CEA antibodies. Images were obtained daily for four days. Computerized background subtraction using technetium 99m (99mTC)-labeled compounds was used. Images obtained with and without background subtraction were correlated with other evidence of disease. Activity levels in plasma, urine, and thyroid gland were monitored. Significant deiodination of antibody occurred within the first 24 hours. The mean plasma half-disappearance-time of baboon antibody was significantly longer than the mean half-disappearance-time of goat antibody. With exogenous blockade, total thyroid uptake was less than 0.1% of the injected dose. Without background subtraction, scintigraphic localization of known tumor was possible in one of two patients with colon carcinoma, in three of 20 patients with breast cancer, and in one of five patients with medullary carcinoma of the thyroid. With background subtraction, potential false-positive results could be generated for every patients, depending on the normalization site chosen and the degree of subtraction used. In contrast to results of previous reports, CEA-producing tumor was found to be infrequently localized using highly purified goat or primate radiolabeled anti-CEA. Furthermore, the subtraction technique described by previous investigators may lead to a high false-positive rate

  9. Somatic Mutations in the Notch, NF-KB, PIK3CA, and Hedgehog Pathways in Human Breast Cancers

    Science.gov (United States)

    Jiao, Xiang; Wood, Laura; Lindman, Monica; Jones, Sian; Buckhaults, Phillip; Polyak, Kornelia; Sukumar, Saraswati; Carter, Hannah; Kim, Dewey; Karchin, Rachel; Sjöblom, Tobias

    2012-01-01

    Exome sequencing of human breast cancers has revealed a substantial number of candidate cancer genes with recurring but infrequent somatic mutations. To determine more accurately their mutation prevalence, we performed a mutation analysis of 36 novel candidate cancer genes in 96 human breast cancers. Somatic mutations with potential impact on protein function were observed in the genes ADAM12, CENTB1, CENTG1, DIP2C, GLI1, GRIN2D, HDLBP, IKBKB, KPNA5, NFKB1, NOTCH1, and OTOF. These findings strengthen the evidence for involvement of the Notch, Hedgehog, NF-KB, and PIK3CA pathways in breast cancer development, and point to novel processes that likely are involved. PMID:22302350

  10. Prostate-Specific Antigen Bounce After High-Dose-Rate Monotherapy for Prostate Cancer

    International Nuclear Information System (INIS)

    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. 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.

  12. Normalization of prostate specific antigen in patients treated with intensity modulated radiotherapy for clinically localized prostate cancer

    International Nuclear Information System (INIS)

    The purpose of this study was to determine the expected time to prostate specific antigen (PSA) normalization with or without neoadjuvant androgen deprivation (NAAD) therapy after treatment with intensity modulated radiotherapy (IMRT) for patients with clinically localized prostate cancer. A retrospective cohort research design was used. A total of 133 patients with clinical stage T1c to T3b prostate cancer (2002 AJCC staging) treated in a community setting between January 2002 and July 2005 were reviewed for time to PSA normalization using 1 ng/mL and 2 ng/mL as criteria. All patients received IMRT as part of their management. Times to PSA normalization were calculated using the Kaplan-Meier method. Significance was assessed at p < 0.05. Fifty-six of the 133 patients received NAAD (42.1%). Thirty-one patients (23.8%) received radiation to a limited pelvic field followed by an IMRT boost, while 99 patients received IMRT alone (76.2%). The times to serum PSA normalization < 2 ng/mL when treated with or without NAAD were 298 ± 24 and 302 ± 33 days (mean ± SEM), respectively (p > 0.05), and 303 ± 24 and 405 ± 46 days, respectively, for PSA < 1 ng/mL (p < 0.05). Stage T1 and T2 tumors had significantly increased time to PSA normalization < 1 ng/mL in comparison to Stage T3 tumors. Also, higher Gleason scores were significantly correlated with a faster time to PSA normalization < 1 ng/mL. Use of NAAD in conjunction with IMRT leads to a significantly shortened time to normalization of serum PSA < 1 ng/mL in patients with clinically localized prostate cancer

  13. Treatment Outcomes in Non-Metastatic Prostate Cancer Patients With Ultra-High Prostate-Specific Antigen

    International Nuclear Information System (INIS)

    Purpose: It is commonly believed that prostate cancer patients with very high prostate-specific antigen (PSA) levels are unlikely to benefit from definitive local treatment, and patients with very high PSA are often underrepresented in, or excluded from, randomized clinical trials. Consequently, little is known about their optimal treatment or prognosis. We performed a registry-based analysis of management and outcome in this population of patients. Methods and Materials: Our provincial Cancer Registry was used to identify all men who were diagnosed with prostate cancer from 1990 to 2001. A retrospective chart review provided information on stage, Gleason score, PSA at diagnosis, and treatment. In this study, ultra-high PSA was defined as PSA of ≥50 ng/ml. For a more complete perspective, treatment outcomes of patients with PSA of 20 to 49.9 ng/ml were also studied. Results: Of the 8378 men diagnosed with prostate cancer during this period, 6,449 had no known nodal or distant metastatic disease. The median follow-up of this group was 67.2 months (range, 0–192 months). A total of 1534 patients had PSA of ≥20 ng/ml. Among the 995 patients with PSA 20 to 49.9 ng/ml, 85 had radical prostatectomy (RP), and their 5- and 10-year cause-specific survivals (CSS) were 95% and 84%, respectively. The 497 patients treated with radiotherapy (RT) had 5- and 10-year CSS of 92% and 71%. For the 332 patients with PSA 50–99.9 ng/ml, RT was associated with 5- and 10-year CSS of 81% and 55%. For the 207 patients with PSA of ≥100 ng/ml, RT was associated with 5- and 10-year CSS of 80% and 54%. Conclusions: This is the largest series in the world on non metastatic cancer patients with ultra-high PSA at diagnosis. Even in the setting of a very high presenting PSA level, prostatectomy and radiotherapy are often associated with prolonged survival.

  14. Therapeutic Potential of T Cell Chimeric Antigen Receptors (CARs) in Cancer Treatment: Counteracting Off-Tumor Toxicities for Safe CAR T Cell Therapy.

    Science.gov (United States)

    Gross, Gideon; Eshhar, Zelig

    2016-01-01

    A chimeric antigen receptor (CAR) is a recombinant fusion protein combining an antibody-derived targeting fragment with signaling domains capable of activating T cells. Recent early-phase clinical trials have demonstrated the remarkable ability of CAR-modified T cells to eliminate B cell malignancies. This review describes the choice of target antigens and CAR manipulations to maximize antitumor specificity. Benefits and current limitations of CAR-modified T cells are discussed, with a special focus on the distribution of tumor antigens on normal tissues and the risk of on-target, off-tumor toxicities in the clinical setting. We present current methodologies for pre-evaluating these risks and review the strategies for counteracting potential off-tumor effects. Successful implementation of these approaches will improve the safety and efficacy of CAR T cell therapy and extend the range of cancer patients who may be treated. PMID:26738472

  15. Glioblastoma specific antigens, GD2 and CD90, are not involved in cancer stemness

    OpenAIRE

    Woo, Seon Rang; Oh, Young Taek; An, Jae Yeol; Kang, Bong Gu; Nam, Do-Hyun; Joo, Kyeung Min

    2015-01-01

    Glioblastoma multiforme (GBM) is the most malignant World Health Organization grade IV brain tumor. GBM patients have a poor prognosis because of its resistance to standard therapies, such as chemotherapy and radiation. Since stem-like cells have been associated with the treatment resistance of GBM, novel therapies targeting the cancer stem cell (CSC) population is critically required. However, GBM CSCs share molecular and functional characteristics with normal neural stem cells (NSCs). To el...

  16. Diagnostic value of combined determination of serum CA19-9 and TGF-β contents in patients with pancreatic cancer

    International Nuclear Information System (INIS)

    Objective: To study the clinical diagnostic value of combined determination of serum contents of CA19-9 and TGF-β in patients with pancreatic cancer. Methods: Serum CA19-9 (with RIA) and TGF-β (with ELISA) contents were deter- mined in 30 patients with pancreatic cancer and 35 controls. Results: The serum CA19-9 and TGF-β contents in patients with pancreatic cancer were significantly higher than those in controls (P<0.01). The diagnostic sensitivity of CA19-9 for pancreatic cancer was 70.8%, lower than that of TGF-β (80.2%, P<0.05). The diagnostic specificity of CA19-9 and TGF-β was 90.2% and 93.4% respectively. Conclusion: Both determinations of serum CA19-9 and TGF-β contents would yield high specificity for diagnosis of pancreatic cancer. Sensitity of TGF-β determination was higher than that of CA19-9 determination. Combined determination of CA19-9 and TGF-β would improve the diagnostic accuracy in patients with pancreatic cancer. (authors)

  17. Validation of Serological Antibody Profiles Against Human Papillomavirus Type 16 Antigens as Markers for Early Detection of Cervical Cancer.

    Science.gov (United States)

    Salazar-Piña, Dolores Azucena; Pedroza-Saavedra, Adolfo; Cruz-Valdez, Aurelio; Ortiz-Panozo, Eduardo; Maldonado-Gama, Minerva; Chihu-Amparan, Lilia; Rodriguez-Ocampo, Angelica Nallelhy; Orozco-Fararoni, Emilia; Esquivel-Guadarrama, Fernando; Gutierrez-Xicotencatl, Lourdes

    2016-02-01

    Cervical cancer (CC) is the second most frequent neoplasia among women worldwide. Cancer prevention programs around the world have used the Papanicolaou (Pap) smear as the primary diagnostic test to reduce the burden of CC. Nevertheless, such programs have not been effective in developing countries, thus leading to research on alternative tests for CC screening. During the virus life cycle and in the process toward malignancy, different human papillomavirus (HPV) proteins are expressed, and they induce a host humoral immune response that can be used as a potential marker for different stages of the disease. We present a new Slot blot assay to detect serum antibodies against HPV16 E4, E7, and VLPs-L1 antigens. The system was validated with sera from a female population (n = 485) aged 18 to 64 years referred to the dysplasia clinic at the General Hospital in Cuautla, Morelos, Mexico. To evaluate the clinical performance of the serological markers, the sensitivity, specificity, positive, and negative predictive values and receiver-operating characteristic curves (for antibodies alone or in combination) were calculated in groups of lesions of increasing severity. The results showed high prevalence of anti-E4 (73%) and anti-E7 (80%) antibodies in the CC group. Seropositivity to 1, 2, or 3 antigens showed associations of increasing magnitude with CC (odds ratio [OR] = 12.6, 19.9, and 58.5, respectively). The highest association with CC was observed when the analysis was restricted to only anti-E4+E7 antibodies (OR = 187.7). The best clinical performance to discriminate CC from cervical intraepithelial neoplasia 2 to 3 was the one for the combination of anti-E4 and/or anti-E7 antibodies, which displayed high sensitivity (93.3%) and moderate specificity (64.1%), followed by anti-E4 and anti-E7 antibodies (73.3% and 80%; 89.6% and 66%, respectively). In addition, the sensitivity of anti-E4 and/or anti-E7 antibodies is high at any time of sexual activity (TSA

  18. 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

    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...... [38.7%], P = .14) compared with CP patients. The PFS for CPLD patients did not change statistically significantly after adjustment for early decline (adjusted HR = 0.80, 95% CI = 0.68 to 0.94, P = .007). These findings are opposite to what would be expected if these markers were good surrogates for...

  19. Monoclonal antibodies to murine thrombospondin-1 and thrombospondin-2 reveal differential expression patterns in cancer and low antigen expression in normal tissues

    International Nuclear Information System (INIS)

    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

  20. 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

  1. The Role of Prostate-Specific Antigen in Prostate Cancer Screening

    OpenAIRE

    Constantin Traian Vasile; Mădan Victor Lucian; Constantin Maria-Magdalena; Morariu Silviu-Horia; Braticevici Bogdan

    2014-01-01

    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, i...

  2. 68Ga-Labeled Anti-Prostate-Specific Membrane Antigen Peptide as Marker for Androgen Deprivation Therapy Response in Prostate Cancer.

    Science.gov (United States)

    Schlenkhoff, Carl Diedrich; Gaertner, Florian; Essler, Markus; Hauser, Stefan; Ahmadzadehfar, Hojjat

    2016-05-01

    Prostate cancer was diagnosed in a 71-year-old man with an elevated prostate-specific antigen. The CT of the abdomen showed multiple para-aortal lymph nodes, and thus, a Ga anti-prostate-specific membrane antigen (PSMA-11) PET/CT was initiated, which showed, aside from the prostate cancer and multiple iliacal and para-aortal lymph node metastases, an increased tracer uptake in a lymph node left cervical. According to this advanced disease, a palliative therapy with GnRH agonist was initiated. A second PSMA-11 PET/CT was performed 4 months later, which showed a very good response; thus, additional radiation of the pelvis and the draining lymphatic system was performed. PMID:26859213

  3. Prostate-associated gene 4 (PAGE4), an intrinsically disordered cancer/testis antigen, is a novel therapeutic target for prostate cancer

    Science.gov (United States)

    Kulkarni, Prakash; Dunker, A Keith; Weninger, Keith; Orban, John

    2016-01-01

    Prostate-associated gene 4 (PAGE4) is a remarkably prostate-specific Cancer/Testis Antigen that is highly upregulated in the human fetal prostate and its diseased states but not in the adult normal gland. PAGE4 is an intrinsically disordered protein (IDP) that functions as a stress-response protein to suppress reactive oxygen species as well as prevent DNA damage. In addition, PAGE4 is also a transcriptional regulator that potentiates transactivation by the oncogene c-Jun. c-Jun forms the AP-1 complex by heterodimerizing with members of the Fos family and plays an important role in the development and pathology of the prostate gland, underscoring the importance of the PAGE4/c-Jun interaction. HIPK1, also a component of the stress-response pathway, phosphorylates PAGE4 at T51 which is critical for its transcriptional activity. Phosphorylation induces conformational and dynamic switching in the PAGE4 ensemble leading to a new cellular function. Finally, bioinformatics evidence suggests that the PAGE4 mRNA could be alternatively spliced resulting in four potential isoforms of the polypeptide alluding to the possibility of a range of conformational ensembles with latent functions. Considered together, the data suggest that PAGE4 may represent the first molecular link between stress and prostate cancer (PCa). Thus, pharmacologically targeting PAGE4 may be a novel opportunity for treating and managing patients with PCa, especially patients with low-risk disease. PMID:27270343

  4. Prostate stem cell antigen-targeted nanoparticles with dual functional properties: in vivo imaging and cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Gao X

    2012-07-01

    Full Text Available Xin Gao,1,* Yun Luo,1,* Yuanyuan Wang,1,* Jun Pang,1 Chengde Liao,2 Hanlun Lu,3 Youqiang Fang11Department of Urology, The Third Affiliated Hospital, 2Department of Radiology, The Second Affiliated Hospital, Sun Yat-Sen University, 3Materials Science Institute of Zhongshan University, Guangzhou, China*These authors contributed equally to this workBackground: We designed dual-functional nanoparticles for in vivo application using a modified electrostatic and covalent layer-by-layer assembly strategy to address the challenge of assessment and treatment of hormone-refractory prostate cancer.Methods: Core-shell nanoparticles were formulated by integrating three distinct functional components, ie, a core constituted by poly(D,L-lactic-co-glycolic acid, docetaxel, and hydrophobic superparamagnetic iron oxide nanocrystals (SPIONs, a multilayer shell formed by poly(allylamine hydrochloride and two different sized poly(ethylene glycol molecules, and a single-chain prostate stem cell antigen antibody conjugated to the nanoparticle surface for targeted delivery.Results: Drug release profiles indicated that the dual-function nanoparticles had a sustained release pattern over 764 hours, and SPIONs could facilitate the controlled release of the drug in vitro. The nanoparticles showed increased antitumor efficiency and enhanced magnetic resonance imaging in vitro through targeted delivery of docetaxel and SPIONs to PC3M cells. Moreover, in nude mice bearing PC3M xenografts, the nanoparticles provided MRI negative contrast enhancement, as well as halting and even reversing tumor growth during the 76-day study duration, and without significant systemic toxicity. The lifespan of the mice treated with these targeted dual-function nanoparticles was significantly increased (Chi-square = 22.514, P < 0.0001.Conclusion: This dual-function nanomedical platform may be a promising candidate for tumor imaging and targeted delivery of chemotherapeutic agents in vivo

  5. Personalized peptide vaccination for advanced biliary tract cancer: IL-6, nutritional status and pre-existing antigen-specific immunity as possible biomarkers for patient prognosis

    OpenAIRE

    Yoshitomi, Munehiro; Yutani, Shigeru; Matsueda, Satoko; IOJI, TETSUYA; Komatsu, Nobukazu; SHICHIJO, SHIGEKI; Yamada, Akira; ITOH, KYOGO; SASADA, TETSURO; Kinoshita, Hisafumi

    2011-01-01

    Considering that the prognosis of patients with advanced biliary tract cancer (BTC) remains very poor, with a median survival of less than 1 year, new therapeutic approaches need to be developed. In the present study, a phase II clinical trial of personalized peptide vaccination (PPV) was conducted in advanced BTC patients to evaluate the feasibility of this treatment and to identify potential biomarkers. A maximum of 4 human leukocyte antigen-matched peptides, which were selected based on th...

  6. Peripheral zone prostate-specific antigen density: an effective parameter for prostate cancer prediction in men receiving 5α-reductase inhibitors

    OpenAIRE

    Koo, Kyo Chul; Lee, Dong Hoon; Lee, Seung Hwan; Chung, Byung Ha

    2013-01-01

    Purpose: To evaluate the predictive performance of various parameters derived from volume-adjusted prostate-specific antigen (PSA) values in detecting prostate cancer (PCa) and high-grade (Gleason score≥7) PCa according to treatment with a 5α-reductase inhibitor (5ARI). Methods: The results of 3,520 prostate biopsies performed between May 2006 and January 2013 were retrospectively assessed. With adjustment for age, 291 patients who had received 5ARI treatment for more than 6 months were ident...

  7. The serum carbohydrate antigen 125 and carcinoembryonic antigen comparsion for the han and uyghur patients of terminal gallbladder cancer in xinjiang uygur autonomous region%新疆地区汉族与维吾尔族晚期胆囊癌患者血清糖类抗原125、癌胚抗原水平比较

    Institute of Scientific and Technical Information of China (English)

    毛拉艾沙·买买提; 薛峰; 依马木买买提江·阿不拉

    2013-01-01

    目的 比较新疆地区汉族与维吾尔族晚期胆囊癌患者血清糖类抗原125(CA125)、癌胚抗原(CEA)水平是否存在差异.方法 原发性晚期胆囊癌患者80例,其中维吾尔族40例,汉族40例;随机选取同期住院的胆囊炎患者60例作为对照组,其中维吾尔族34例,汉族26例;均进行血清CA125、CEA检测.结果 胆囊癌组的汉族、维吾尔族患者与对照组同民族患者CA125、CEA水平差异均有统计学意义(t=27.01、28.06、10.68、11.25,均P<0.05);而两组内汉族、维吾尔族患者间的CA125、CEA水平差异均无统计学意义(t=0.47、0.34、0.11、1.23,均P>0.05);胆囊癌Ⅳ期汉族、维吾尔族患者与Ⅴ期同民族患者CA125、CEA水平差异均有统计学意义(t=26.92、25.01、16.58、14.54,均P<0.05);汉族、维吾尔族的胆囊癌Ⅳ期患者之间、Ⅴ期患者之间的CA125、CEA水平差异均无统计学意义(t=1.13、0.11、0.38、0.07,均P>0.05).结论 新疆地区汉族与维吾尔族晚期胆囊癌患者血清CA125、CEA水平无差异,晚期胆囊癌患者进行CA125、CEA检测有助于病情诊断.%Objective To compare the differences on the serum carbohydrate antigen 125 and carcinoembryonic antigen for the Han and Uyghur patients of terminal gallbladder cancer in Xinjiang Uygur Autonomous Region.Methods 80 cases of patients with primary advanced gallbladder,including 40 cases of Uighur,Han 40 cases,The cholecystitis patients randomly selected from the same period of hospitalization of 60 cases as the control group.Including 34 cases of Uighur and Han 26 cases,Levels of serum CA125,CEA were detected.Results The gallbladder group of Han,Uygur patients and the control group with ethnic patients CA125,CEA level differences were statistically significant(t =27.01,28.06,10.68,11.25,all P < 0.05) ; CA125,CEA level differences between the two groups within the Han,Uygur patients were not statistically significant(t =0.47,0.34,0.1 l,1.23,all P > 0

  8. New serum biomarkers for prostate cancer diagnosis

    OpenAIRE

    Chadha, Kailash C.; Austin Miller; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Willie Underwood

    2014-01-01

    Background: Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective: The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods: Concurrent meas...

  9. Prospects for chimeric antigen receptor (CAR) γδ T cells: A potential game changer for adoptive T cell cancer immunotherapy.

    Science.gov (United States)

    Mirzaei, Hamid Reza; Mirzaei, Hamed; Lee, Sang Yun; Hadjati, Jamshid; Till, Brian G

    2016-10-01

    Excitement is growing for therapies that harness the power of patients' immune systems to combat their diseases. One approach to immunotherapy involves engineering patients' own T cells to express a chimeric antigen receptor (CAR) to treat advanced cancers, particularly those refractory to conventional therapeutic agents. Although these engineered immune cells have made remarkable strides in the treatment of patients with certain hematologic malignancies, success with solid tumors has been limited, probably due to immunosuppressive mechanisms in the tumor niche. In nearly all studies to date, T cells bearing αβ receptors have been used to generate CAR T cells. In this review, we highlight biological characteristics of γδ T cells that are distinct from those of αβ T cells, including homing to epithelial and mucosal tissues and unique functions such as direct antigen recognition, lack of alloreactivity, and ability to present antigens. We offer our perspective that these features make γδ T cells promising for use in cellular therapy against several types of solid tumors, including melanoma and gastrointestinal cancers. Engineered γδ T cells should be considered as a new platform for adoptive T cell cancer therapy for mucosal tumors. PMID:27392648

  10. 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

    2016-03-16

    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. PMID:26932233

  11. Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models

    OpenAIRE

    Maawy, Ali A.; Hiroshima, Yukihiko; Kaushal, Sharmeela; Luiken, George A.; Robert M Hoffman; Bouvet, Michael

    2013-01-01

    Abstract. The aim of this study was to evaluate a set of visible and near-infrared dyes conjugated to a tumor-specific chimeric antibody for high-resolution tumor imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer was orthotopically implanted into pancreata of nude mice. Mice received a single intravenous injection of a chimeric anti-carcinoembryonic antigen antibody conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or DyLight 488); ...

  12. Is CA72-4 a Useful Biomarker in Differential Diagnosis between Ovarian Endometrioma and Epithelial Ovarian Cancer?

    OpenAIRE

    Emanuela Anastasi; Lucia Manganaro; Teresa Granato; Pierluigi Benedetti Panici; Luigi Frati; Maria Grazia Porpora

    2013-01-01

    Background. Surgical excision of ovarian endometriomas in patients desiring pregnancy has recently been criticized because of the risk of damage to healthy ovarian tissue and consequent reduction of ovarian reserve. A correct diagnosis in cases not scheduled for surgery is therefore mandatory in order to avoid unexpected ovarian cancer misdiagnosis. Endometriosis is often associated with high levels of CA125. This marker is therefore not useful for discriminating ovarian endometrioma from ova...

  13. Prostate-specific antigen (PSA) rate of decline post external beam radiotherapy predicts prostate cancer death

    International Nuclear Information System (INIS)

    Background and purpose: To assess the association between PSA velocity (PSAV) in the first 24 months after external beam radiotherapy (EBRT) and prostate cancer-specific mortality (PCSM) and all cause mortality. Materials and methods: All eligible patients in the South Australian (SA) Prostate Cancer Clinical Outcomes registry were followed. 848 Patients treated by definitive EBRT with more than one PSA recorded in the two year post-treatment were included. We calculated PSAV by linear regression. Results: The mean number of PSA measurements in the 2 year period was 4.4 (SD1.9). The median PSAVs across quartiles (Q1–Q4) were −4.17, −1.29, −0.38 and 0.20 ng/ml/yr. In multivariable analysis, a U-shaped relationship was seen between PSAV and PCSM with Q1–Q4 hazard ratios (HR) being 3.82 (1.46–10.00), 3.07 (1.10–8.58), 1, 5.15 (1.99–13.30) respectively. HR for all cause mortality in a similar model were 1.79 (1.07–2.98), 1.55 (0.93–2.59), 1.00 and 1.74 (1.04–2.90) for Q1 to Q4 respectively. A rapid PSA decline in the first year was a strong predictor of PCSM. However, in the second year PSA increase was positively associated with PCSM. Conclusion: A rapid decline in PSA in the first year following EBRT is positively associated with PCSM. This may be a useful early indicator of the need for additional therapies

  14. Decreased levels of serum cytokeratin 19 fragment CYFRA 21-1 predict objective response to chemotherapy in patients with non-small cell lung cancer

    OpenAIRE

    Pang, Li; Jing WANG; Jiang, Yanwen; Chen, Liangan

    2013-01-01

    Diagnostic tools capable of predicting early responses to chemotherapy are required to improve the individual management of cancer patients. The present study aimed to evaluate the prognostic significance of the serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigen (CA) 125, and CA 19-9 for predicting responses to different chemotherapy regimens in patients with non-small cell lung cancer (NSCLC). A total of 276 patients with posto...

  15. Predictive value of serum prostate specific antigen in detecting bone metastasis in prostate cancer patients using bone scintigraphy

    International Nuclear Information System (INIS)

    Radionuclide bone scan (BS) used to be the investigation of choice for detecting osseous metastases in prostate cancer. Now, with the availability serum prostate specific antigen (PSA) testing, clinicians do have a timely, cost-effective method to determine those patients who are highly unlikely to have osseous metastases. We determine the utility of PSA for predicting the presence of skeletal metastasis on BSs in prostate cancer patients. Retrospective analysis of medical records of 322 consecutive prostate cancers patients subjected to BS during the last 3 years was done. 52 cases were excluded due to following reasons: Serum PSA not available, hormonal or other therapy given prior to serum PSA measurement, and/or BS, and symptomatic for bone metastasis. In remaining 270 cases, PSA value and BS were evaluated. BS was performed with Tc99m methylene diphosphonate (MDP) as per the standard protocol. BS was found to be positive in 153/270 (56%) and negative in 117 (46%) patients. Of the 153 positive cases, 108 (70%) had serum PSA > 100 ng/ml, 42 (28%) had PSA of 20-100 ng/ml and only 3 (2%) had PSA < 20 ng/ml. All the patients with PSA > 100 ng/ml had multiple skeletal metastasis. Of the 117 negative cases, 110 (94%) had a PSA < 20 ng/ml, 5 had between 20 and 100 ng/ml and only 2 (1.8%) had PSA > 100 ng/ml. Of the 113 patients with serum PSA < 20 ng/ml, 110 (97.4%) did not show any bony metastasis. 150/157 (95.5%) patients with PSA > 20 ng/ml had bone metastasis. Using this criterion, 110 (40.7%) scans would have been omitted. Serum PSA < 20 ng/ml have high predictive value in ruling out skeletal metastasis. Our data are in corroboration with results from previous studies that BS should be performed only if PSA > 20 ng/ml. Using this cut-off, unnecessary investigation can be avoided. Avoiding BS in this group of patients would translate into a significant cost-saving and reduction in their psychological and physical burden

  16. Isolation and Evaluation of Specific Human Recombinant Antibodies from a Phage Display Library against HER3 Cancer Signaling Antigen

    Directory of Open Access Journals (Sweden)

    Foroogh Nejatollahi

    2014-07-01

    Full Text Available Background: The human epidermal growth factor receptor family comprises four homologous members: EGFR (ErbB1, ErbB2 (HER2, ErbB3 (HER3 and ErbB4 (HER4.This family plays an important role in the signaling pathway and cell proliferation. The heterodimerization of HER2 with HER3 leads to tumor cell proliferation. Monoclonal antibody to the human HER3 receptor blocks HER3 heterodimerization and inhibits the growth of breast cancer cells. Due to their human origin, small size, rapid penetration and high affinity properties, recombinant single chain antibodies (scFv have been introduced as the most desired agents for cancer immunotherapy. In this study, we use a phage display system to select specific scFvs against HER3 for their use in cancer targeted therapy. Methods: A phage antibody display library of scFv was panned against an immunodominant epitope of HER3. Phage rescue was performed on the library. The supernatant that contained the appropriate scFv (109 PFU/ml was added to an immunotube which was coated with the peptide. Elution was done using log phase E. coli TG1. The clones were amplified by PCR and DNA fingerprinted to select the specific clones against the epitope. The specificity of the selected antibodies was tested in ELISA. Results: The results represented two predominant patterns with the frequency of 25%. The other patterns showed the frequencies of 5%-10%. scFv1 and scFv2 demonstrated positive ELISA with absorbances of 0.63 and 0.46, respectively while the absorbances of wells without peptide were 0.19 and 0.11, respectively. Conclusion: In this study two specific scFvs were selected against HER3 antigen in a successful panning process. Phage ELISA represented the specific binding of scFvs against HER3.The selected scFvs reacted only with the corresponding peptides. However, no reaction with the other peptides was detected. The selected anti-HER3 scFvs have suggested that these human high affinity and small antibodies that bind

  17. Prostate cancer detection upon transrectal ultrasound-guided biopsy in relation to digital rectal examination and prostate-specific antigen level: what to expect in the Chinese population?

    Directory of Open Access Journals (Sweden)

    Jeremy YC Teoh

    2015-01-01

    Full Text Available We investigated the prostate cancer detection rates upon transrectal ultrasound (TRUS-guided biopsy in relation to digital rectal examination (DRE and prostate-specific antigen (PSA, and risk factors of prostate cancer detection in the Chinese population. Data from all consecutive Chinese men who underwent first TRUS-guided prostate biopsy from year 2000 to 2013 was retrieved from our database. The prostate cancer detection rates with reference to DRE finding and PSA level of 50 ng ml−1 were investigated. Multivariate logistic regression analyses were performed to investigate for potential risk factors of prostate cancer detection. A total of 2606 Chinese men were included. In patients with normal DRE, the cancer detection rates were 8.6%, 13.4%, 21.8%, 41.7% and 85.2% in patients with PSA 50 ng ml−1 respectively. In patients with abnormal DRE, the cancer detection rates were 12.4%, 30.2%, 52.7%, 80.6% and 96.4% in patients with PSA 50 ng ml−1 respectively. Older age, smaller prostate volume, larger number of biopsy cores, presence of abnormal DRE finding and higher PSA level were associated with increased risk of prostate cancer detection upon multivariate logistic regression analyses (P < 0.001. Chinese men appeared to have lower prostate cancer detection rates when compared to the Western population. Taking the different risk factors into account, an individualized approach to the decision of TRUS-guided biopsy can be adopted.

  18. Chemical proteomic and bioinformatic strategies for the identification and quantification of vascular antigens in cancer.

    Science.gov (United States)

    Strassberger, Verena; Fugmann, Tim; Neri, Dario; Roesli, Christoph

    2010-09-10

    One avenue towards the development of more selective anti-cancer drugs consists in the targeted delivery of bioactive molecules to the tumor environment by means of binding molecules specific to tumor-associated markers. In this context, the targeted delivery of therapeutic agents to newly-formed blood vessels ("vascular targeting") is particularly attractive, because of the dependence of tumors on new blood vessels to sustain growth and invasion, and because of the accessibility of neo-vascular structures for therapeutic agents injected intravenously. Ligand-based vascular targeting strategies crucially rely on good-quality vascular tumor markers. Here we describe a number of established technologies for the enrichment of accessible vascular proteins based on the isolation of glycoproteins, the in vivo coating of accessible cell surfaces with colloidal silica and the in vivo perfusion with reactive ester derivatives of biotin. Label-free as well as isotopic labeling based strategies for the subsequent MS-based protein quantification are outlined. Finally, bioinformatic workflows for protein quantification are depicted aiming at assisting in the evaluation of appropriate strategies for individual projects. This review gives an overview of current chemical proteomic strategies for the enrichment and quantification of the accessible vascular proteome and helps in selecting bioinformatic strategies for data analysis and validation. PMID:20538087

  19. Bone scans in conjunction with prostata-specific antigen levels in patients with prostate cancer

    International Nuclear Information System (INIS)

    The usefulness of the determination of PSA for primary diagnosis, follow-up, and therapy-monitoring of prostatic cancer is undebatable. It has been shown that more than 50% of the patients with stage A and B and about 90% of the patients with stage D demonstrate PSA-levels above the cut-off-level (4.0 ng/ml). Detection of bone metastases by bonescans is regarded as a marker for an extensive disease. In this stage, numerous groups have reported on PSA-levels >20 ng/ml in more than 98% of the patients. For PSA-levels 10 ng/ml or in cases of locally advanced stages with highly undifferentiated tumors. For follow-up purposes, the use of bonescans should be restrictes to patients with PSA-levels >20 ng/ml. Nevertheless, a bone-scan is mandatory for the evaluation of bone-pain, before surgery for local recurrence and before local radiation therapy. (orig.)

  20. The diagnostic value of monoclonal gastric cancer 7 antigen: a systematic review with meta-analysis.

    Science.gov (United States)

    Zeng, Zongyue; Fu, Sheng; Hu, Ping; Zhao, Liuyang; Zhang, Hailong; Tang, Xi; Yang, Xiaorong; Zeng, Zhaofang

    2014-08-01

    The aim of this study is to explore the clinical characteristic and the diagnostic role of MG7-Ag in detecting gastric cancer (GC) through a systematic review and meta-analysis. Relevant manuscripts aiming at the application of serum MG7-Ag level in GC diagnosis were searched in PubMed, Embase, Chinese National Knowledge Infrastructure, VIP, and Wan Fang Data independently,which were published between January 1, 1980 and February 28, 2013. The pooled sensitivity, specificity,positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), diagnostic odds ratio,and the area under the summary receiver operating characteristic(AUC) were used to evaluate the value of serum MG7-Ag in diagnosis of GC by using the Meta-DiSc and STATA 11.0 statistical software. 410 manuscripts were retrieved, and 7 manuscripts of high quality including 652 patients were of high quality in this meta-analysis. Overall,the pooled sensitivity, specificity, DLR+, DLR-, and AUC were 0.73 (95 % CI 0.63-0.82), 0.91 (95 % CI 0.84-0.94), 8.59 (95 % CI 5.62-13.11), 0.29 (95 % CI 0.21-0.42), and 0.92 (95 % CI 0.89-0.94), respectively. MG7-Ag is a potential biomarker for the diagnosis of GC.However, more studies are needed to confirm the standard criteria. PMID:23797567

  1. Evaluation of the Ca 1 antibody in the diagnosis of invasive breast cancer.

    OpenAIRE

    Clough, D G; Coghill, G R; Holley, M. P.

    1984-01-01

    An evaluation of Ca 1 antibody staining was performed on paraffin sections from 136 breast lesions (64 benign and 72 malignant). Although cytoplasmic staining was encountered significantly more often in malignant lesions, the false negative rate was 6.9% and the false positive rate 56.2%. Benign lesions which showed positive staining included gynaecomastia, cystic mastopathy and fibroadenomata. Various other monoclonal antibodies showed staining similar to Ca 1 antibody. Ca 1 antibody was obs...

  2. Effect of paclitaxel liposome combined with nedaplatin on serum HE4, CA125, CA19-9, AFP, CEA and T lymphocyte subsets in patients with advanced ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    Su-Yu Zhu; Jie Tan; Chen-Lu Zhang; Qun-Ying Wu; Xue-Xin Xie; Hua-Fang Yin

    2016-01-01

    Objective:To study the effect of paclitaxel liposome combined with nedaplatin on serum HE4, CA125, CA19-9, AFP, CEA and T lymphocyte subsets in patients with advanced ovarian cancer.Methods:A total of 80 patients with advanced ovarian cancer in our hospital from December 2012 to December 2015 were enrolled in this study. The subjects were divided into control group (n=40) and experiment group (n=40) randomly. The control group were treated with paclitaxel and cisplatin, the experiment group were treated with paclitaxel liposome combined with nedaplatin. 21 days for a period of treatment and the two groups were treated for 3 periods. The serum HE4, CA125, CA19-9, AFP, CEA levels and peripheral blood CD3+, CD4+, CD8+ and NK cells of the two groups before and after treatment were compared. Results:There were no significantly differences of the serum HE4, CA125, CA19-9, AFP, CEA level and peripheral blood CD3+, CD4+, CD8+ and NK cells of the two groups before treatment (P>0.05). The serum HE4, CA125, CA19-9, AFP and CEA level of the two groups after treatment were significantly lower than before treatment (P<0.05), and that of experiment were significantly lower than control group (P<0.05). The peripheral blood CD3+, CD4+, CD8+and NK cells of the two groups after treatment were significantly lower than before treatment (P<0.05), and that of experiment were significantly higher than control group (P<0.05). Conclusions:Paclitaxel liposome combined with nedaplatin can significantly reduce the serum HE4, CA125, CA19-9, AFP and CEA levels, improve peripheral blood CD3+, CD4+, CD8+ and NK levels of patients with advanced ovarian cancer, and it was worthy clinical application.

  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

    PIK3CA mutations. We wished to discern whether selective pressures occur and the influence of PIK3CA mutation on time to recurrence.EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded tumor blocks were obtained from 104 patients with paired samples from primary tumors and corresponding asynchronous...... 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. Determination of CA-125 levels in the serum, cervical and vaginal secretions, and endometrium in Chinese women with precancerous disease or endometrial cancer

    OpenAIRE

    Shu-ming HE; Xing, Fuqi; Sui, Hong; Wu, Youming; Wang, Yongli; Wang, Dong; Chen, Guanghui; Kong, Zijing; ZHOU, SHU-FENG

    2011-01-01

    Summary Background Serum CA-125 has been used as a biomarker of gynecological tumors. In this study, we investigated the CA-125 levels in cervical and vaginal secretions from Chinese patients with endometrial polyps, hyperplasia and carcinoma in comparison with those in endometrium and serum. Material/Methods An electro-chemiluminescent immunoassay was utilized to determine the levels of CA-125 in 51 healthy Chinese women and 97 patients with polyps, hyperplasia or endometrial cancer. An immu...

  5. Identification of IGFBP2 and IGFBP3 As Compensatory Biomarkers for CA19-9 in Early-Stage Pancreatic Cancer Using a Combination of Antibody-Based and LC-MS/MS-Based Proteomics.

    Science.gov (United States)

    Yoneyama, Toshihiro; Ohtsuki, Sumio; Honda, Kazufumi; Kobayashi, Makoto; Iwasaki, Motoki; Uchida, Yasuo; Okusaka, Takuji; Nakamori, Shoji; Shimahara, Masashi; Ueno, Takaaki; Tsuchida, Akihiko; Sata, Naohiro; Ioka, Tatsuya; Yasunami, Yohichi; Kosuge, Tomoo; Kaneda, Takashi; Kato, Takao; Yagihara, Kazuhiro; Fujita, Shigeyuki; Huang, Wilber; Yamada, Tesshi; Tachikawa, Masanori; Terasaki, Tetsuya

    2016-01-01

    Pancreatic cancer is one of the most lethal tumors, and reliable detection of early-stage pancreatic cancer and risk diseases for pancreatic cancer is essential to improve the prognosis. As 260 genes were previously reported to be upregulated in invasive ductal adenocarcinoma of pancreas (IDACP) cells, quantification of the corresponding proteins in plasma might be useful for IDACP diagnosis. Therefore, the purpose of the present study was to identify plasma biomarkers for early detection of IDACP by using two proteomics strategies: antibody-based proteomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics. Among the 260 genes, we focused on 130 encoded proteins with known function for which antibodies were available. Twenty-three proteins showed values of the area under the curve (AUC) of more than 0.8 in receiver operating characteristic (ROC) analysis of reverse-phase protein array (RPPA) data of IDACP patients compared with healthy controls, and these proteins were selected as biomarker candidates. We then used our high-throughput selected reaction monitoring or multiple reaction monitoring (SRM/MRM) methodology, together with an automated sample preparation system, micro LC and auto analysis system, to quantify these candidate proteins in plasma from healthy controls and IDACP patients on a large scale. The results revealed that insulin-like growth factor-binding protein (IGFBP)2 and IGFBP3 have the ability to discriminate IDACP patients at an early stage from healthy controls, and IGFBP2 appeared to be increased in risk diseases of pancreatic malignancy, such as intraductal papillary mucinous neoplasms (IPMNs). Furthermore, diagnosis of IDACP using the combination of carbohydrate antigen 19-9 (CA19-9), IGFBP2 and IGFBP3 is significantly more effective than CA19-9 alone. This suggests that IGFBP2 and IGFBP3 may serve as compensatory biomarkers for CA19-9. Early diagnosis with this marker combination may improve the prognosis of

  6. RESPONSE OF MONONUCLEAR CELLS TO CANCER-ASSOCIATED ANTIGENS, HUMORAL FACTORS OF IMMUNITY, AND PATHOHISTOLOGICAL FINDINGS IN WOMEN WITH GENITAL MALIGNANCIES CERVICAL EPITHELIAL DYSPLASIA

    Directory of Open Access Journals (Sweden)

    A. I. Autenshlus

    2014-07-01

    Full Text Available Abstract. In vitro response of blood mononuclear cells to cancer-associated antigens was studied in women with genital pathology, and these results were compared with serum levels of pro- and anti-inflammatory factors of immunity, like as with histological features of genital cancer and cervical epithelial dysplasia. In vitro cellular response was regarded as positive, if relative amounts of CD8-positive lymphocytes increased by > 15% following incubation of blood mononuclears with cancer-associated antigens. Positive reaction and elevated serum levels of anti-TNFα and anti-IFNγ antibodies were associated with lesser malignancy of tumor, as proven by histological findings in the women with genital cancer. A positive cellular reaction was associated with increased serum levels of IFNγ and anti-TNFα in women with grade II–III cervical epithelial dysplasia. It is concluded about potential applicability of testing mononuclears with fetal proteins, to determine a grade of malignancy for the female genital tumors, as well as a degree of regenerative disturbances of cervical epithelium.

  7. A method for determining a prostate-specific antigen cure after radiation therapy for clinically localized prostate cancer

    International Nuclear Information System (INIS)

    Purpose: A method that allows the determination of a prostate-specific antigen (PSA) cure after definitive management for prostate carcinoma with radiation therapy is presented and tested. Methods and Materials: The method involves a calculation of the patient's theoretical baseline PSA prior to the development of prostate cancer by using three serial rising PSA determinations obtained prior to the institution of therapy. The rate of rise of the PSA prior to therapy and the rate of decline of the PSA posttherapy are calculated, using an exponential model. Two criteria must be satisfied to define a PSA cure. First, the PSA nadir after treatment should be less than the calculated theoretical baseline PSA. Second, the rate of decline of PSA posttreatment should be greater than the rate of rise of the PSA prior to treatment. Results: Applying these two criteria to the patient data base (n 16) at a median follow-up of 19 months enabled the accurate prediction of 6 out of 6 (100%) of patients with documented PSA failure and 7 out of 10 (70%) of patients without PSA failure. Therefore, despite short follow-up, all six patients with PSA failure were predicted. Further follow-up is needed to ascertain if the seven patients predicted to be cured will remain PSA failure free and if the three patients currently without PSA failure in whom the model predicts failure, will subsequently fail. Conclusion: Therefore, using each patient's PSA history as the natural control may eliminate the error that is introduced with defining a PSA cure by using a single value for the PSA nadir at a specified time after radiation therapy

  8. Prostate-specific membrane antigen can promote in vivo osseous metastasis of prostate cancer cells in mice

    International Nuclear Information System (INIS)

    Reports remain insufficient on whether and how prostate-specific membrane antigen (PSMA) can influence in vivo osseous metastasis of prostate cancer (PCa). In the present study, the authors induced stable expression of PSMA in mouse PCa cell line RM-1. In vivo osseous metastasis was induced in 37 6-week-old female C57BL/6 mice weighing 22.45 ± 0.456 g. RM-1 cells were actively injected into the femoral bone cavity, leading to bilateral dissymmetry of bone density in the femoral bone. Tumor cells were also detected in bone tissue by pathological examination. The impact on bone density was demonstrated by the significant difference between animals injected with RM-PSMA cells (0.0738 ± 0.0185 g/cm2) and animals injected with RM-empty plasmid cells (0.0895 ± 0.0241 g/cm2). The lytic bone lesion of the RM-PSMA group (68.4%) was higher than that of the control group (27.8%). Immunohistochemistry showed that the expression of both vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) was distinctly higher in the RM-PSMA group than in the control group, while ELISA and Western blot assay indicated that VEGF and MMP-9 were higher in the RM-PSMA group compared to the control group (in vitro). Thus, the present study proposed and then confirmed for the first time that PSMA can promote in vivo osseous metastasis of PCa by increasing sclerotic destruction of PCa cells. Further analyses also suggested that PSMA functions positively on the invasive ability of RM-1 by increasing the expression of MMP-9 and VEGF by osseous metastases in vivo

  9. Pretreatment prostate-specific antigen values in patients with prostate cancer: 1989 patterns of care study process survey

    International Nuclear Information System (INIS)

    Purpose: A Patterns of Care Study (PCS) national survey was conducted to show the national averages for processes of radiation therapy care for prostate cancer patients in 1989. In the current study we report an analysis of pretreatment prostate-specific antigen (PSA) by stage, grade, and ethnic origin. Methods and Materials: Process data were collected from 672 patients treated in 1989 at 71 separate institutions. Four hundred and twenty-seven (64%) of these patients had a pretreatment PSA value recorded. Three hundred and forty-three of the 427 patients were treated with external beam irradiation alone and were selected for the current analysis. The 1992 AJCC staging system was used. Results: There was a significant increase in pretreatment PSA with increasing stage. The median values of PSA were 8.3 ngm/ml in the T1 group (n = 65), 11.2 ngm/ml in the T2 group (n = 178), and 20.9 ngm/ml in the T3 group (n = 90) (p < 0.001). Ten patients were not staged. There was a significant increase in pretreatment PSA with decreasing differentiation. The median pretreatment PSA was 9.7 ngm/ml in well-differentiated tumors (n = 109), 13.0 ngm/ml in moderately differentiated tumors (n = 163), and 22.0 ngm/ml in poorly differentiated tumors. (n = 61) (p < 0.001). Ten patients had no differentiation recorded. African Americans (24) showed a significant increase in pretreatment PSA compared to Caucasians (304). The respective medians were 23.2 ng/ml and 11.9 ng/ml (p = 0.04). They also show more poorly differentiated tumors (33% vs. 17%) and more T3 tumors (46% vs. 25%). Other minorities, although small in number (n = 9) were similar to African Americans. Conclusion: Pretreatment PSA levels were established for patients treated with external beam irradiation in 1989 in the United States. They increase with stage and decreasing differentiation. African Americans and other minorities show a doubling of median values compared to Caucasians' pretreatment PSA with an increase in stage

  10. Carcinoembryonic antigen (CEA) level, CEA ratio, and treatment outcome of rectal cancer patients receiving pre-operative chemoradiation and surgery

    International Nuclear Information System (INIS)

    To investigate serum carcinoembryonic antigen (CEA) as a prognostic factor for rectal cancer patients receiving pre-operative chemoradiotherapy (CRT). Between 2000 and 2009, 138 patients with advanced rectal cancer receiving CRT before surgery at our hospital were retrospectively classified into 3 groups: pre-CRT CEA <6 ng/ml (group L; n = 87); pre-CRT CEA ≥ 6 ng/ml and post-CRT CEA <6 ng/ml (group H-L; n = 32); and both pre- and post-CRT CEA ≥ 6 ng/ml (group H-H; n = 19). CEA ratio (defined as post-CRT CEA divided by pre-CRT CEA), post-CRT CEA level and other factors were reviewed for prediction of pathologic complete response (pCR). Five-year disease-free survival (DFS) was better in groups L (69.0%) and H-L (74.5%) than in group H-H (44.9%) (p = 0.024). Pathologic complete response was observed in 19.5%, 21.9% and 5.3% of groups L, H-L and H-H respectively (p = 0.281). Multivariate analysis showed that ypN stage and pCR were independent prognostic factors for DFS and that post-CRT CEA level was independently predictive of pCR. As a whole, post-CRT CEA <2.61 ng/ml predicted pCR (sensitivity 76.0%; specificity 58.4%). For those with pre-CRT CEA ≥6 ng/ml, post-CRT CEA and CEA ratio both predicted pCR (sensitivity 87.5%, specificity 76.7%). In patients with pre-CRT serum CEA ≥6 ng/ml, those with “normalized” CEA levels after CRT may have similar DFS to those with “normal” (<6 ng/ml) pre-CRT values. Post-CRT CEA level is a predictor for pCR, especially in those with pre-CRT CEA ≥6 ng/ml

  11. The source of pretreatment serum prostate-specific antigen in clinically localized prostate cancer--T, N, or M?

    International Nuclear Information System (INIS)

    Purpose: Prostate-specific antigen (PSA) is an important marker for prostate cancer and has been shown to be secreted from the primary tumor and from metastases. However, the relative contribution of the primary and micrometastatic disease to the serum level of PSA in patients with clinically localized disease has not been delineated. This study addresses the source of pretreatment serum PSA in patients with clinically localized disease. Methods and Materials: The fall in serum PSA level following radical prostatectomy (280 patients; 105 T1, 165 T2, 10 T3) or definitive radiotherapy (427 patients; 122 T1, 147 T2, 158 T3/T4) was analyzed with the assumption that any fall in PSA following local treatment reflects the fraction of PSA produced in the prostate and its primary tumor. Results: Serum PSA level became undetectable in 277 of the 280 (99%) patients within 6 months of radical prostatectomy. The three patients who did not achieve undetectable levels had postsurgical values ≤ 0.9 ng/ml. Following definitive radiotherapy, nadir serum PSA values were between ≤ 0.3 and 20.3 ng/ml, with mean and median values of 1.9 and 1.2 ng/ml, respectively. Nadir PSA was undetectable in 52 patients (12%). Four patients' PSA did not fall, but rose from the start, and each developed metastatic disease within 9 months, and in each metastases appeared to contribute to pretreatment serum PSA. In the remaining patients, the maximal factor by which PSA fell to its nadir was higher the higher the pretreatment PSA level. We present arguments that this is most consistent with the hypothesis that virtually all detectable pretreatment serum PSA derives from the primary tumor. Confirmatory evidence that little of the pretreatment serum PSA came from metastases was obtained by extrapolating the rising PSA profile in 97 patients back to pretreatment time. Back-extrapolated PSA contributed a mean of 7% and a median of 5% to the pretreatment serum value. Because such back-extrapolated values

  12. Human Leukocyte Antigens and Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: Old Associations Offer New Clues into the Role of Immunity in Infection-Associated Cancers

    Directory of Open Access Journals (Sweden)

    Wen-HuiSu

    2013-12-01

    Full Text Available Nasopharyngeal carcinoma (NPC is an Epstein-Barr virus (EBV associated tumor. In addition to EBV, host genetic factors are believed to be important determinants of NPC risk. Of all genes studies to date, human leukocyte antigen (HLA genes have shown the most consistent evidence for association with NPC, both from candidate-gene studies and genome-wide association studies (GWAS. In this report we summarize results from recent studies that evaluated the association between HLA and NPC, and discuss whether findings reflect direct causal associations for HLA genes and/or indirect associations that mark causal associations with other genes in the gene-dense major histocompatibility (MHC region where HLA resides. We also compare GWAS results across cancer sites for which strong hits in the MHC region were observed to generate new hypotheses regarding the role of HLA genes in the development of EBV-associated cancers such as NPC. Of note, we report that MHC associations for EBV-associated cancers (NPC, EBV+ Hodgkin lymphoma are driven by HLA class I genes. In contrast, MHC associations for other viral-associated cancers (cervical cancer, hepatocellular carcinoma or other hematopoetic cancers (EBV- Hodgkin lymphoma, leukemia, non-Hodgkin lymphomas are driven by HLA class II genes, and those for other solid tumors with less clear links to infections (lung, testicular, prostate cancers are driven by non-HLA genes in the MHC region. Future studies should aim to better understand these patterns.

  13. Silencing B7-H1 enhances the anti-tumor effect of bladder cancer antigen-loaded dendritic cell vaccine in vitro

    Directory of Open Access Journals (Sweden)

    Wang S

    2014-08-01

    Full Text Available Shuo Wang,1 Yonghua Wang,1 Jing Liu,2 Shixiu Shao,1 Xianjun Li,1 Jiannan Gao,1 Haitao Niu,1 Xinsheng Wang1 1Department of Urology, 2Department of Pediatrics, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China Objective: The aim of this study was to examine whether short hairpin RNA (shRNA expressing lentiviral particles targeting B7-H1 infection could result in B7-H1 knockdown on dendritic cells (DCs and to investigate whether B7-H1 silencing could augment the immune function of DCs and further elicit a more potent anti-tumor immune effect against bladder cancer cells in vitro. Methods: Monocyte-derived DCs, which were generated from peripheral blood mononuclear cells, were infected by a recombinant lentivirus containing shRNA sequence aimed at B7-H1. After that, the infected DCs were pulsed by tumor antigens and used to stimulate cytotoxic T lymphocytes-based anti-tumor effect in vitro. Results: The lentivirus-mediated shRNA delivery method efficiently and effectively silenced B7-H1 in DCs. Furthermore, the B7-H1 silencing enhanced the stimulatory capacity and the secretion of interleukin-12, but down-regulated interleukin-10 secretion. And more importantly, the anti-tumor effect of bladder cancer antigen-loaded DC vaccine in vitro was also potentially augmented. Conclusion: This study suggests that a combination of B7-H1 knockdown and target antigen delivery could augment anti-tumor effects in vitro, which potentially provides a novel strategy in the immunotherapy of bladder cancer. Keywords: B7-H1, bladder cancer, dendritic cell, vaccine, immunotherapy

  14. Preliminary Study on 41Ca-AMS Technology for Early Diagnosis and Monitoring of Bone Cancer

    Institute of Scientific and Technical Information of China (English)

    SHEN; Hong-tao; PANG; Fang-fang; HE; Ming; DONG; Ke-jun; DOU; Liang; SHI; Yan-jun; ZHANG; Shuang; WU; Shao-yong; WANG; Xiao-ming; ZHAO; Qin-zhang; YANG; Xu-ran; XU; Yong-ning; LAN; Xiao-xi; CAI; Li; JIANG; Shan

    2013-01-01

    The annual incidence of new cancer patients in China is about 2 million,50%-60%of which will end up with bone metastasis.The bone metastasis of cancer and bone cancer usually causes a variety of bone-related events,such as the pathological fracture,malignant hypercalcemia and bone marrow

  15. Clinical Use of Cancer Biomarkers in Epithelial Ovarian Cancer

    DEFF Research Database (Denmark)

    Söletormos, Georg; Duffy, Michael J; Othman Abu Hassan, Suher; Verheijen, René H M; Tholander, Bengt; Bast, Robert C; Gaarenstroom, Katja N; Sturgeon, Catharine M; Bonfrer, Johannes M; Petersen, Per Hyltoft; Troonen, Hugo; CarloTorre, Gian; Kanty Kulpa, Jan; Tuxen, Malgorzata K; Molina, Raphael

    2016-01-01

    OBJECTIVE: To present an update of the European Group on Tumor Markers guidelines for serum markers in epithelial ovarian cancer. METHODS: Systematic literature survey from 2008 to 2013. The articles were evaluated by level of evidence and strength of recommendation. RESULTS: Because of its low...... sensitivity (50-62% for early stage epithelial ovarian cancer) and limited specificity (94-98.5%), cancer antigen (CA) 125 (CA125) is not recommended as a screening test in asymptomatic women. The Risk of Malignancy Index, which includes CA125, transvaginal ultrasound, and menopausal status, is recommended...... candidate for secondary cytoreductive surgery. CONCLUSIONS: At present, CA125 remains the most important biomarker for epithelial ovarian cancer, excluding tumors of mucinous origin.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives...

  16. An adenoviral cancer vaccine co-encoding a tumor associated antigen together with secreted 4-1BBL leads to delayed tumor progression.

    Science.gov (United States)

    Ragonnaud, Emeline; Andersson, Anne-Marie C; Pedersen, Anders Elm; Laursen, Henriette; Holst, Peter J

    2016-04-19

    Previous studies have shown promising results when using an agonistic anti-4-1BB antibody treatment against established tumors. While this is promising, this type of treatment can induce severe side effects. Therefore, we decided to incorporate the membrane form of 4-1BB ligand (4-1BBL) 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 antibody administration. Furthermore, adenovirus encoded 4-1BBL expression has previously been successfully used to enhance responses toward Plasmodium falciparum and Influenza A antigens. We showed that the incorporation of 4-1BBL in the adenovirus vector led to surface expression of 4-1BBL on antigen 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 survival compared to the vaccine expressing the membrane form of 4-1BBL. Accordingly, secreted 4-1BBL co-encoded with the Ii linked antigen may offer a simplification compared to administration of drug and vaccine separately. PMID:27004934

  17. Auranofin, an Anti-Rheumatic Gold Compound, Modulates Apoptosis by Elevating the Intracellular Calcium Concentration ([Ca2+]i) in MCF-7 Breast Cancer Cells

    International Nuclear Information System (INIS)

    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

  18. 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.

  19. Diagnostic value of combined measurement of serum CEA, AFP, CA19-9 and SA levels in patients with primary hepatic cancer

    International Nuclear Information System (INIS)

    Objective: To study the diagnostic value of combined measurement of serum CEA, AFP, CA19-9 and SA levels for primary hepatic cancer. Methods: Serum CEA, AFP, CA19-9 (with RIA) SA (with biochemistry) levels were measured in 36 patients with primary hepatic cancer and 35 controls. Results: As a single tumor marker for diagnosis, the sensitivity of CEA, AFP, CA19-9, SA was 33.3%, 69.4%, 58.5% and 61.1% respectively, the specificity was 60.4%, 81.3% 68.8%, 64.4% respectively. With combined detection of the four markers and assuming two or more markers positive as positive, the sensitivity would be 94.4% and specificity would be 95.8%. Conclusion: Combined measurement of serum CEA, AFP, CA19-9 and SA levels is of clinical usefulness for diagnosis of primary hepatic cancer. (authors)

  20. The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate Cancer

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    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.

  1. Expression of the macrophage antigen CD163 in rectal cancer cells is associated with early local recurrence and reduced survival time.

    Science.gov (United States)

    Shabo, Ivan; Olsson, Hans; Sun, Xiao-Feng; Svanvik, Joar

    2009-10-15

    Expression of the macrophage antigen CD163 in breast cancer cells is recently shown to be related to early distant recurrence and shortened survival. In this study, 163 patients with rectal cancer, included in the Swedish rectal cancer trial and followed up for a median of 71 months, were examined for the expression of CD163 in the primary tumors. The cancer cells expressed CD163 in the primary tumors in 23% (n = 32) of the patients. In pretreatment biopsies from 101 patients, 10 had CD163-positive cancers and these patients had earlier local recurrence (p CD163-negative tumors. When studying surgical specimens from 61 patients randomized to preoperative irradiation (5 x 5 Gy delivered in 1 week), it was found that 31% were CD163 positive whereas the corresponding figure was only 17% for 78 patients who were nonirradiated (p CD163-positive tumors there was a reduced apoptotic activity as measured with the Termina deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique (p = 0.018). There tended also to be an increased proliferation activity measured as an expression of Ki-67 non significant (NS). It is concluded that primary rectal cancers may express CD-163, and this phenotypic macrophage trait is related to early local recurrence, shorter survival time and reduced apoptosis. Furthermore, the expression of CD163 is more common after irradiation. PMID:19582880

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

    OpenAIRE

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

    2015-01-01

    Aim: To investigate the prognostic value of carcinoembryonic antigen (CEA), CA199, CA724 and CA242 in peripheral blood and local draining venous blood in colon cancer patients after curative resection. Methods: 92 colon cancer patients who received curative resection were retrospectively analyzed. The CEA, CA199, CA724 and CA242 were detected in peripheral blood and local draining venous blood. Results: Metastasis or local recurrence was found in 29 (29/92, 31.5%) patients during follow-up pe...

  3. 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

    DEFF Research Database (Denmark)

    Martínez-Piñeiro, Luis; Schalken, Jack A; Cabri, Patrick;

    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...... change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse...... metastasis or unknown metastasis status. TMPRSS2-ERG scores ≥35 were considered positive (n = 149 [51.6%]). Age, presence of metastasis, PSA level and Gleason score at baseline were not associated with a significant difference in the proportion of TMPRSS2-ERG-positive scores. The median serum PSA levels...

  4. The Relationship between Tumour Marker CA15.3 and Some Trace Elements levels In Cancerous Patients

    International Nuclear Information System (INIS)

    In the current study, the plans focused on evaluation of some trace elements (Fe, Cu and Zn) concentration with traditional tumour marker CA15.3 and correlate their concentration changes in both serum and tissue with clinical stages may give early and precise diagnosis and pathological grading of tumours. The study was carried out on twenty-one female patients with different grades of breast cancer. Their mean age were 48.095± 9.675 years compared to thirteen female with mean age of 36.20± 9.035 years served as a healthy control group. This study was undertaken to evaluate the clinical value of assaying serum and tissue trace element levels (Fe, Cu and Zn) by using atomic absorption spectrophotometer (AAS) versus serum CA 15.3 by using IRMA in diagnosing and follow up the patients with cancerous breast. Significant gradual elevations (P< 0.01) in serum level of tumour marker CA15.3 among different grades of breast cancerous patients when compared to healthy control. Also, significant elevation (P < 0.05 and P < 0.01) were noticed in serum levels of Fe and Cu among different grades of tumour whereas Zn level revealed significant decreases (P < 0.05) particularly in grades II, III and IV when compared to that of control. Tissue biopsies showed significant increases (P< 0.01) in Fe level of all grades of tumour but increases were significant (P< 0.01) in Cu level of grades II, III and IV. On the contrary, Zn level recorded significant decreases (P< 0.01) in grades II, III and IV when compared with tumour free breast tissue. Gradual significant decreases (P< 0.01) in serum Cu/Fe ratios were observed in grades II, III and IV, but the decrease in grade I were non-significant, when compared with normal control. Decreases and increases were observed in Cu/Fe ratios between grades of malignancies

  5. The importance of preoperative elevated serum levels of CEA and CA15-3 in patients with breast cancer in predicting its histological type.

    Directory of Open Access Journals (Sweden)

    J Słonina

    2010-06-01

    Full Text Available It is not known whether in patients with breast cancer the occurrence of elevated serum tumour markers depends on its histological type. The aim of the study was to assess relationship between breast cancer histological type and the presence of increased serum levels of CEA and CA 15-3. The study population was 428 patients (all women, mean age 52.5 years, treated at The Department of Surgery of Wroclaw Medical University from 2005 to 2008 due to breast cancer. All of them had their preoperative CA 15-3 and CEA serum concentrations measured. According to the TNM system, 21% of patients were in stage I, 32.5% in stage II, 46.5% in stage III of the disease. In patients with ductal type of the cancer the elevated serum levels of CEA and CA 15-3 were observed in 48.7% and 42.2%, in lobular type in 42.4% and 52.5%, and in non-ductal/tubular types in 48.1% and 40.4% (p=N/S. Stepwise logistic regression analyses showed that ductal breast cancer is related to elevated CEA and normal CA 15-3 serum levels. The histological types of breast cancer are not significantly related to elevated serum levels of CEA and/or CA 15-3.

  6. 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)

    OpenAIRE

    Schröder, Fritz; Bangma, Chris; Angulo, A F; Alcaraz, Antonio; Colombel, Jean Frédéric; McNicholas, Tom; Tammela, Teuvo; Nandy, Indrani; 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 recurrence is controversial. Objective: To assess the effect of dutasteride on progression of PCa in patients with biochemical failure after radical therapy. Design, setting, and participants: Ran...

  7. The values of the expression of CA125 in serum, ascites and tissue in patients with ovarian cancer%卵巢癌患者血清、腹水、组织中CA125检测意义

    Institute of Scientific and Technical Information of China (English)

    刘超; 马晓艳; 李海霞; 廖琪

    2008-01-01

    Objective To find the source of CA 125 in serum and the values of the expression of CA125 in serum, ascites and tissue in patients with epithelial ovarian cancer. Methods Detected the expression of CA125 in the primary lesions of epithelial ovarian cancer and the metastasis in abdominopelvic cavity (peritoneal and omental metastatic lesions) by S-P immunohistochemical methods. Compared the expression of CA 125 in tuberculose focus and acute inflammation focus in abdominopelvic cavity and detected CA125 in serum and ascites by ELISA. Results The levels of CA125 in serum of the patients with epithelial ovarian cancer [(523.66±158.02)kU/L],benign epithelial ovarian tumor [(138.11±26.52)kU/L] and tuberculosis of abdominopelvie cavity [(486.56±147.10)kU/L] were higher than that with the normal ovary [(17.48±3.37)kU/L], and there were significant differences (P<0.05).The levels of CA125 in serum of the patients with epithelial ovarian cancer and tuberculosis of abdominopelvic cavity were significantly higher than that with benign epithelial ovarian tumor, and there were significant differenees (P<0.01). The levels of CA125 in ascites of the patients with epithelial ovarian cancer [(996.85±337.87)kU/L] and tuberculosis of abdominopelvic cavity [(596.78±197.10)kU/L] were higher than that with benign epithelial ovarian tumor [(179.48±63.08)kU/L] and normal ovary [(177.70±51.72)kU/L], and there were significant differences (P<0.01).The level of CA125 in ascites of the patients with epithelial ovarian cancer was higher than that with tuberculosis of abdominopelvic cavity, and there was significant difference (P<0.01). By correlation analysis, the relationship of the level of CA 125 in serum and in ascites of the patients with epithelial ovarian cancer was positive correlation(r=0.687). Conclusion Besides the original and metastatie lesions (greater omenta and peritoneum) of epithelial ovarian cancer can express CA 125, the second Maller canal, for example the

  8. 血清肿瘤标志物CA125、CA199、CEA、NSE联合检测在肺癌诊断中的应用%Serum tumor marker CA125, CA199, CEA, NSE combined detection of lung cancer diagnosis

    Institute of Scientific and Technical Information of China (English)

    王峰

    2010-01-01

    目的 探讨血清肿瘤标志物CA125、CA199、CEA、NSE联合检测在肺癌诊断中的应用价值.方法 选择本院2009年1月至2010年2月住院的肺癌患者220例肺癌病例组,选取同期我院健康体检人员为正常对照组250例,进行肿瘤标志物CA125、CA199、CEA、NSE进行联合检测.结果 经统计学分析肺癌病例组CA125、CEA、NSE血清水平明显高于正常对照组,差异有显著性意义(P<0.01),CA199在两组的表达水平比较无显著性差异(P>0.05).经统计学分析CA125、CEA、NSE与联合检测三项肿瘤标志物之间的敏感性、特异性比较有显著型差异(P<0.01).结论 单项肿瘤标志物检测,可以对临床有一定的指导性,但在敏感性、特异性均方面各有欠缺,很多肿瘤标志物与其他相应的疾病有一定的交叉性,对单项肿瘤标志物检测指导临床诊断价值有限,同时选用多项肿瘤标志物进行检测,可以达到单项检测在敏感性和特异性上的不足,能够有效的为临床提供有价值的佐证资料,以能够达到初筛和早期诊断的目的 .%Objective To explore the serum tumor marker CA125, CA199,CEA,NSE combined detection in the diagnosis of lung cancer in the application. Methods The hospital in January 2009-2010 year in February hospitalized patients with lung cancer group of 220 cases of lung cancer cases, select the same period the health physical examination in our hospital staff to the normal control group of 250 patients for tumor markers CA125,CA199,CEA,NSE to conduct joint detection. Results After statistical analysis of lung cancer cases group of CA125, CEA, NSE serum levels were significantly higher than the normal control group, the difference was significant(P < 0. 01 ), CA199 expression levels in the two groups showed no significant difference (P >0. 05 ). The statistical analysis of CA125, CEA, NSE and the combined detection of three tumor markers between the sensitivity,specificity,and there

  9. 小胰腺癌血清CA19-9测定及其临床意义%Detection and Clinical Significance of Serum CA19-9 for Small Pancreas Cancer

    Institute of Scientific and Technical Information of China (English)

    徐慧琴

    2001-01-01

    Objective: To determine the significance of serum CA19-9 for small pancreas cancer.Methods: The serum CA19-9 of 86 patients of pancreas cancer was detected. 18 patients of small pancreas cancer whose tumor diameter were less than 2 cm were received B ultrasound, CT, MRI and ERCP. Results: The serum CA19-9 positive rate was 61.1% in the patients of small pancreas cancer with its average value 140.5u/ml. The CA19-9 positive was common in the patient of small pancreas cancer with the lesion focus metastasis. There was no correlation between the serum CA19-9 and stage and tumor site of small pancreas cancer. Conclusion: The detection of serum CA19-9 might be helpful for the assessment of operative effect and supervision of follow-up after operation. The diagnostic positive rate of MRI and ERCP for small pancreas cancer should be higher than that of B ultrasound and CT. The combination detections of the serum CA19-9, MRI and ERCP could reach the purpose of early diagnosis.Early operation could reduce the mortality and improve the prognosis.%目的:明确血清CA19-9测定对小胰腺癌诊断的意义.方法:通过对86例胰腺癌患者血清CA19-9的检测,并对其中18例肿瘤直径≤2cm小胰腺癌)患者进行B超、CT、MRI及ERCP检测.结果:结果表明小胰腺癌患者血清CA19-9的阳性率为61.1%,平均值为140.5u/ml,病理显示CA19-9阳性多见于病灶有转移的小胰腺癌病人.血清CA19-9的阳性与小胰腺癌的病程,部位无关.结论:CA19-9检测有助于对手术疗效的评价与术后随访的监测.MRI、ERCP对小胰腺癌诊断阳性率明显高于B超、CT.联合应用血清CA19-9、MRI、ERCP 可达到早期诊断小胰腺癌的目的,而早期手术可降低死亡率,改善预后.

  10. Urinary microRNA-based signature improves accuracy of detection of clinically relevant prostate cancer within the prostate-specific antigen grey zone

    OpenAIRE

    SALIDO-GUADARRAMA, ALBERTO IVAN; MORALES-MONTOR, JORGE GUSTAVO; Rangel-Escareño, Claudia; Langley, Elizabeth; Peralta-Zaragoza, Oscar; COLIN, JOSE LUIS CRUZ; Rodriguez-dorantes, Mauricio

    2016-01-01

    At present, prostate-specific antigen (PSA) is used as a clinical biomarker for prostate cancer (PCa) diagnosis; however, a large number of patients with benign prostate hyperplasia (BPH) with PSA levels in the ʻgray areaʼ (4–10 ng/ml) are currently subjected to unnecessary biopsy due to overdiagnosis. Certain microRNAs (miRs) have been proven to be useful biomarkers, several of which are detectable in bodily fluids. The present study identified and validated a urinary miR-based signature to ...

  11. Imaging of non-small cell lung cancers with a monoclonal antibody, KC-4G3, which recognizes a human milk fat globule antigen

    International Nuclear Information System (INIS)

    To determine the role of lung cancer tumor imaging with monoclonal antibodies directed against high molecular weight human milk fat globule antigens, we administered i.v. 111In-KC-4G3 to 24 patients with advanced non-small cell lung cancer. One mg of 111In-KC-4G3 was mixed with 0, 9, 49, 99, or 499 mg of unlabeled KC-4G3 and infused i.v. over 1 to 5 h. The mean 111In-KC-4G3 radiochemical purity was greater than 97% and the resultant immunoreactivity averaged 62%. Successful imaging of cancer sites was accomplished in 92% of 24 patients, and 57% of 91 total lesions were visualized. Successful localization of tumor sites related to size (P less than 0.001), with 81% of lesions greater than 3.0 cm in diameter, 50% of lesions 1.5 to 3 cm, and 6% of lesions less than 1.5 cm successfully imaging, and to location (P less than 0.05), with 69% of pulmonary lesions, 80% of soft tissue lesions, and only 32% of bone metastases being visualized. Nonspecific reticulo-endothelial uptake of radioactivity was a major problem. Approximately 35% of 111In was chelated to serum transferrin by 24 and 48 h after infusion. The mean t 1/2 beta for plasma radioisotope and immunoreactive KC-4G3 was 29 and 27 h, respectively. There was no correlation between total infused antibody dose and imaging success or between total dose and effect on 111In and KC-4G3 kinetics. Circulating free KC-4 antigen was measurable in all but one patient before study. Tumor biopsy following infusion could demonstrate antibody presence but not saturable antigen binding. We conclude that (a) 111In-KC-4G3 demonstrates successful tumor localization in non-small cell lung cancers bearing generally high expression of its antigen and (b) further investigations to diminish nonspecific radioactivity for imaging and utilization of high dose radiolabeled antibody for therapeutic intent are warranted

  12. Aberrant sialylation of a prostate-specific antigen: Electrochemical label-free glycoprofiling in prostate cancer serum samples.

    Science.gov (United States)

    Pihikova, Dominika; Kasak, Peter; Kubanikova, Petra; Sokol, Roman; Tkac, Jan

    2016-08-31

    Electrochemical detection method allowing to detect prostate-specific antigen (PSA), a biomarker of prostate cancer (PCa), with PSA glycoprofiling was applied in an analysis of PCa serum samples for the first time. Electrochemical impedance spectroscopy (EIS) as a label-free method with immobilized anti-PSA was applied for PSA detection and lectins to glycoprofile captured PSA on the same surface. A proper choice of blocking agent providing high selectivity of biosensor detection with the immobilized anti-PSA antibody was done. The biosensor could detect PSA down to 100 ag/mL with a linear concentration working range from 100 ag/mL up to 1 μg/mL, i.e. 10 orders of concentration magnitude and the sensitivity of (5.5 ± 0.2)%/decade. The results showed that a commercial carbo-free blocking solution was the best one, reducing non-specific binding 55-fold when compared to the immunosensor surface without any blocking agent applied, while allowing to detect PSA. The biosensor response obtained after addition of lectin (i.e. proportional to the amount of a particular glycan on PSA) divided by the biosensor response obtained after incubation with a sample (i.e. proportional to the PSA level in the sample) was applied to distinguish serum samples of PCa patients from those of healthy individuals. The results showed that Maackia amurensis agglutinin (MAA) recognizing α-2,3-terminal sialic acid can be applied to distinguish between these two sets of samples since the MAA/PSA response obtained from the analysis of the PCa samples was significantly higher (5.3-fold) compared to the MAA/PSA response obtained by the analysis of samples from healthy individuals. Thus, combined analysis of serological PSA levels together with PSA glycoprofiling of aberrant glycosylation of PSA (i.e. increase in the level of α-2,3-terminal sialic acid) has a potential to improve detection of PCa. PMID:27506346

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

    DEFF Research Database (Denmark)

    Chen, Kowa; Gentry-Maharaj, Aleksandra; Burnell, Matthew; Steentoft, Catharina; da Silva, Lara Patricia Marcos; Mandel, Ulla; Jacobs, Ian; Dawnay, Anne; Menon, Usha; Blixt, Klas Ola

    2013-01-01

    neoplasms and endometriosis. Aberrant O-glycosylation is an inherent and specific property of cancer cells and could potentially aid in differentiating cancer from these benign conditions, thereby improving specificity of the assay. We report on the development of a novel microarray-based platform for...

  14. Combined detection of serum CEA, CA199, CA724 application value in patients with colorectal cancer TNM staging%血清CA199、CA724、CEA联合检测在结直肠癌患者TNM分期中的应用

    Institute of Scientific and Technical Information of China (English)

    林评跃; 李夏鲁

    2015-01-01

    目的:探讨血清糖类抗原CA199糖类抗原CA724癌胚抗原CEA在结直肠癌的TNM分期中的临床应用价值。方法:观察组结直肠癌患者100例与对照组同期非消化道肿瘤的住院病人100例,空腹抽取静脉血,采用罗氏公司E601电化学发光全自动免疫分析仪和罗氏原装试剂盒检测血清中CEA、CA199、CA724值。应用SPSS 17.0软件进行统计学处理,计量资料以均数±标准差f ±s)表示,采用单因素方差分析进行统计,计数资料采用X-2检验,P<0.05为差异有统计学意义。结果:在单项检测中,CEA的敏感率最高,达37%,且CEA>CA199>CA724.在两项联合检测中CA199+CEA的敏感度最高达53%,三项联合检测敏感度达64%,在各种联合检测中最高。三项肿瘤标志物的阳性率和升高水平随肿瘤的TNM分期的增加而递增。结论:三项肿瘤标志物的单一检测敏感度较低,肿瘤标志的联合检测结直肠癌可以提高敏感性,以CEA+CA199+CA724的效果最好,CA199+CEA次之。CA199、CA724、CEA三项肿瘤标志物的阳性率及升高水平依肿瘤的TNM分期的增加呈递增趋势。%Objective: To investigate the combined detection of serum CEA, CA199, CA724 application value in patients with colorectal cancer TNM staging.Methods:Venous bloods were collected from 100 patients with colorectal cancer and 100 healthy control cases of hospitalized patients during the same period of the digestive tract tumor. The Serum levels of CEA, CA199 and CA724 lwere determined by chemiluminescence immunoassay. All data are shown as mean X ±SD for the indicated number of independently performed experiments. All data were analyzed using the SPSS package for Windows(Version 17.0). Differences with P<0.05 were considered statistically significant.Results:The sensitivity of single tumor maker in the diagnosis of CEA was 37%, higher than CA199 and CA724 was less than CA199. The sensitivity of combined

  15. The potential role of prebiopsy magnetic resonance imaging combined with prostate-specific antigen density in the detection of prostate cancer

    International Nuclear Information System (INIS)

    Two-thirds of patients with a gray-zone prostate-specific antigen (PSA) level undergo unnecessary biopsy. Sensitivity is not yet sufficient to permit the use of modified PSA parameters or magnetic resonance (MR) imaging alone for prostate cancer screening. Thus, we evaluated the combination of MR imaging and PSA density (PSAD) for specificity and sensitivity. During the period April 2004 through March 2006, 185 patients with a PSA level of 4.0-10.0 ng/mL underwent MR imaging and transrectal ultrasonography-guided 8-core biopsy (systemic sextant biopsy of the peripheral zone plus two cores of transition zone). All MR images were interpreted prospectively by two radiologists. An image was considered positive for prostate cancer if any feature indicated a cancerous lesion. Receiver operating characteristic (ROC) curves were used to compare the usefulness of the PSA level, PSAD and PSA transitional zone density (PSATZ) for the detection of prostate cancer. Of the 185 patients, 62 had prostate cancer. Sensitivity and specificity of the axial T2-weighted MR imaging findings for cancer detection were 79.0% and 59.4%, respectively. The area under the ROC curve was 0.590 for the PSA level, 0.718 for PSAD and 0.695 for PSATZ. MR imaging findings and PSAD were shown by multivariate analysis to be statistically significant independent predictors of prostate cancer (P<0.001). With a PSAD cut-off value of 0.111, sensitivity was 96.8%, but specificity was 19.5%. Combining MR imaging findings with PSAD increased the specificity to 40% and retained 95% sensitivity. MR imaging findings combined with PSAD provide high sensitivity and improve the specificity for the early detection of prostate cancer. (author)

  16. Formation of the tetraploid intermediate is associated with the development of cells with more than four centrioles in the elastase-simian virus 40 tumor antigen transgenic mouse model of pancreatic cancer.

    OpenAIRE

    1991-01-01

    The development of pancreatic cancer in transgenic mice expressing the simian virus 40 tumor antigen placed under controlling regions of the elastase I gene is characterized by the sequential appearance of tetraploid and then multiple aneuploid cell populations. Pancreatic tissues from such transgenic mice were studied between 8 and 32 days of age. Virtually 100% of acinar cell nuclei had immunohistochemically detectable tumor antigen by 18 days. Tetraploid cells were demonstrated by DNA cont...

  17. Selective expression and immunogenicity of the cancer/testis antigens SP17, AKAP4 and PTTG1 in non-small cell lung cancer: new candidates for active immunotherapy.

    Science.gov (United States)

    Chiriva-Internati, Maurizio; Mirandola, Leonardo; Figueroa, Jose A; Yu, Yuefei; Grizzi, Fabio; Kim, Minji; Jenkins, Marjorie; Cobos, Everardo; Jumper, Cynthia; Alalawi, Raed

    2014-05-01

    ABSTRACT BACKGROUND. Lung cancer is the leading cause of cancer deaths in both genders worldwide, with an incidence only second to prostate cancer in men and breast cancer in women. The lethality of the disease highlights the urgent need for innovative therapeutic options. Immunotherapy can afford efficient and specific targeting of tumor cells, improving efficacy and reducing the side effects of current therapies. We have previously reported the aberrant expression of cancer/testis antigens (CTAs) in tumors of unrelated histological origin. In this study we investigated the expression and immunogenicity of the cancer/testis antigens (CTAs) Sperm Protein 17 (SP17), A-kinase anchor protein 4 (AKAP4) and Pituitary Tumor Transforming Gene 1 (PTTG1) in human non-small cell lung cancer (NSCLC) cell lines and primary tumors. METHODS. We used RT-PCR, immunofluorescence, flow cytometry, ELISA and cytotoxicity assays to determine the expression levels and immunogenicity of SP17, AKAP4 and PTTG1 in human NSCLC cell lines and primary tumors. RESULTS. We found that SP17, AKAP4 and PTTG1 are aberrantly expressed in NSCLC cancer cell lines and primary tumor tissues from patients, compared to normal lung cell lines and tissues. We established the immunogenicity of these CTAs by measuring CTA-specific autoantibodies in patients' sera and generating CTA-specific autologous cytotoxic lymphocytes (CTLs) from patients' peripheral blood mononuclear cells (PBMCs). CONCLUSIONS. Our results provide proof of principle that the CTAs SP17/AKAP4/PTTG1 are expressed in both human NSCLC cell lines and primary tumors and can elicit an immunogenic response in NSCLC patients. Based on our findings, further studies are warranted to explore the feasibility of developing CTA-specific immunotherapeutic strategies for NSCLC patients. PMID:24811938

  18. Long-Term Follow-Up of HLA-A2+ Patients with High-Risk, Hormone-Sensitive Prostate Cancer Vaccinated with the Prostate Specific Antigen Peptide Homologue (PSA146-154

    Directory of Open Access Journals (Sweden)

    Supriya Perambakam

    2010-01-01

    Full Text Available Twenty-eight HLA-A2+ patients with high-risk, locally advanced or metastatic, hormone-sensitive prostate cancer were immunized with a peptide homologue of prostate-specific antigen, PSA146-154, between July 2002 and September 2004 and monitored for clinical and immune responses. Fifty percent of the patients developed strong PSA146-154-peptide-specific delayed-type hypersensitivity skin responses, tetramer and/or IFN-γ responses within one year. Thirteen patients had stable or declining serum levels of PSA one year post-vaccination. A decreased risk of biochemical progression was observed in patients who developed augmented tetramer responses at six months compared to pre-vaccination levels (P=.02. Thirteen patients have died while 15 patients remain alive with a mean overall survival of 60 months (95% CI, 51 to 68 months per Kaplan-Meier analysis. A trend towards greater overall survival was detected in men with high-risk, hormone-sensitive CaP who developed specific T-cell immunity following vaccination with PSA146-154 peptide.

  19. Identification of new tumor associated antigens and their usage for new therapeutic strategies based on the combination of chemotherapy and immunotherapy for colorectal cancer patients

    International Nuclear Information System (INIS)

    The main general objective of this project was to characterize a new colorectal carcinoma (CRC) tumor-associated antigen (TAA) and validate a new therapeutic strategy combining chemotherapy and tumor vaccination for the treatment of cancer patients. To this purpose a strategic interaction between Drs. Proietti/Maccali at the ISS and the group of Drs. Rosenberg/Robbins at the NIH was established. A stage of Dr. Maccalli at the NIH allowed to carry out the first steps for the identification and the initial characterization of the CRC TAA named COA-1. A laboratory meeting with Dr. Robbins has been planned on May 24-25 2006 at the ISS, during the International Meeting on Immunotherapy of Cancer: Challenges and Needs, for discussing results and perspectives of this research project

  20. The analysis of PIK3CA mutations in gastric carcinoma and metanalysis of literature suggest that exon-selectivity is a signature of cancer type

    Directory of Open Access Journals (Sweden)

    Mattuzzi Silvia

    2010-04-01

    Full Text Available Abstract Background PIK3CA is one of the genes most frequently mutated in human cancers and it is a potential target for personalized therapy. The aim of this study was to assess the frequency and type of PIK3CA mutations in gastric carcinoma and compare them with their clinical pathological correlates. Methods We analysed 264 gastric cancers, including 39 with microsatellite instability (MSI, for mutations in the two PIK3CA hotspots in exons 9 and 20 by direct sequencing of DNA obtained from microdissected cancer cells. Results The cases harbouring mutations were 42 (16%. All were heterozygous missense single base substitutions; the most common was H1047R (26/42; 62% in exon 20 and the second was Q546K (4/42; 9.5% in exon 9. All the mutated MSI cases (8/39 carried the H1047R mutation. No other association between PI3KCA mutations and their clinical pathological covariates was found. A metanalysis of the mutations occurring in the same regions presented in 27 publications showed that ratio between exon 20 and exon 9 prevalences was 0.6 (95% CI: 0.5 -0.8 for colon, 1.6 (95% CI: 1.1 -2.3 for breast, 2.7 (95% CI: 1.6 -4.9 for gastric and 4.1 (95% CI: 1.9 -10.3 for endometrial cancer. Conclusions The overall prevalence of PIK3CA mutations implies an important role for PIK3CA in gastric cancer. The lack of association with any clinical-pathological condition suggests that mutations in PIK3CA occur early in the development of cancer. The metanalysis showed that exon-selectivity is an important signature of cancer type reflecting different contexts in which tumours arise.

  1. Post-transcriptional and epigenetic regulation of antigen processing machinery (APM components and HLA-I in cervical cancers from Uighur women.

    Directory of Open Access Journals (Sweden)

    Ayshamgul Hasim

    Full Text Available Normal function of human leukocyte antigen class I (HLA-I and antigen processing machinery (APM proteins is required for T cell-mediated anti-tumor or antiviral immunity, whereas the tumor survival indicates a failure of the host in immune surveillance associated with the dysfunction in antigen presentation, mainly due to the deregulation in HLA-I and APM expression or function. The posttranscriptional regulation of HLA-I and APM expression may associate with epigenetic modifications in cancer development which was not described so far. Here we showed that the development of cervical intraepithelial neoplasia (CIN and cervical squamous cell carcinoma (CSCC in Uighur women was accompanied with the partial or total loss of protein expression of HLA-I, ß2-m and APM components, including the transporter associated with antigen processing (TAP1/2, low molecular mass protein (LMP2, LMP7, endoplasmic reticulum aminopeptidase 1(ERAP1, chaperone molecules include calreticulin (CLR, calnexin (CNX and ERp57, and this was proved again by analysis of transcription of the same genes in addition to three genes HLA-A, B and C coding for HLA-I. By bisulfite sequencing approach, we identified target CpG islands methylated at the gene promoter region of TAP1, TAP2, LMP7, tapasin and ERp57 in cervical carcinoma cells. Further analysis of CpG site specific methylation of these genes in cases of CSCC and CIN demonstrated an inverse correlation of altered CpG island methylation of TAP1, LMP7, and ERp57 with changes in protein expression. Moreover, promoter methylation of these genes was significantly higher in cases positive for human papillomavirus 16 (HPV 16 than negative ones. Our results suggested that epigenetic modifications are responsible for the aberrant expression of certain HLA-I and APM genes, and may help to understand unrevealed mechanisms of tumor escape from immune surveillance in cervical carcinogenesis.

  2. Predicting Response of Ovarian Cancer to Paclitaxel Treatment Based on Trend Analysis of Serum CA125

    Czech Academy of Sciences Publication Activity Database

    Nekulová, M.; Pecen, Ladislav; Kalábová, R.; Šimíčková, M.; Topolčan, O.; Pikner, R.; Vondráček, J.; Valík, D.

    2002-01-01

    Roč. 48, č. 8 (2002), s. 1364-1367. ISSN 0009-9147 R&D Projects: GA MZd NC6405 Institutional research plan: AV0Z1030915 Keywords : tumor-markers * CA-125 * chemotherapy * regression * standard * criteria * therapy * TPS Subject RIV: BA - General Mathematics Impact factor: 4.788, year: 2002

  3. Notice of Changes to RFA-CA-15-022 and Pre-Application Webinar - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute will hold a public pre-application webinar on Wednesday, January 13, 2016 at 12:00 p.m. (EST) for the Funding Opportunity Announcement (FOA) RFA-CA-15-022 entitled “Proteogenomic Translational Research Centers for Clinical Proteomic Tumor Analysis Consortium (U01).” A major change for RFA-CA-15-022 is the new application due date (now May 11, 2016).

  4. CA-125 cut-off value as a predictor for complete interval debulking surgery after neoadjuvant chemotherapy in patients with advanced ovarian cancer

    OpenAIRE

    Furukawa, Naoto; Sasaki, Yoshikazu; Shigemitsu, Aiko; AKASAKA, JURIA; Kanayama, Seiji; Kawaguchi, Ryuji; Kobayashi, Hiroshi

    2013-01-01

    Objective In the present study, we evaluated changes in CA-125 cut-off values predictive of complete interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) using receiver operating characteristic (ROC) analysis. Methods This retrospective single-institution study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage III epithelial ovarian cancer and a pre-NAC serum CA-125 level of greater than 40 U/mL who were treated with neoadjuvant platinu...

  5. Generation of human monoclonal antibodies against ganglioside antigens and their applications in the diagnosis and therapy of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Alfonso, M. [Dept. of Tumor Cell Biology, Div. of Cancer Biology, Danish Cancer Society, Copenhagen (Denmark)]|[Dept. of Research and Development, Center of Molecular Immunology, Havana (Cuba); Zeuthen, J. [Dept. of Tumor Cell Biology, Div. of Cancer Biology, Danish Cancer Society, Copenhagen (Denmark)

    1996-10-01

    Different approaches to generating human monoclonal antibodies (MAbs) against tumor-associated ganglioside antigens have been carried out in several laboratories. A specific goal addressed by our laboratory is to produce human MAbs to several ganglioside antigens of relevance as therapeutic targets, such as the GM2, GD2, GD3 and GM3 gangliosides in melanoma. In vitro immunization of human B lymphocytes from normal donors was performed using liposomes containing gangliosides as the immunizing antigen combined with either complete tetanus toxoid or a synthetic peptide corresponding to a T helper epitope to stimulate in vitro immunization. Specific human anti-ganglioside antibodies were obtained, indicating that the antibdoy response found in vitro was antigen-driven. To overcome the widely reported problems concerning stability of immunoglobulin production by the antibody-secreting cell lines, a method of positive selection using GM3-coated magnetic beads has been developed in order to rescue unstable clones. Development of new methods to reproducibly generate ganglioside-specific human MAbs will amplify the possibilities for diagnostic and therapeutic applications. (orig.).

  6. Generation of human monoclonal antibodies against ganglioside antigens and their applications in the diagnosis and therapy of cancer

    International Nuclear Information System (INIS)

    Different approaches to generating human monoclonal antibodies (MAbs) against tumor-associated ganglioside antigens have been carried out in several laboratories. A specific goal addressed by our laboratory is to produce human MAbs to several ganglioside antigens of relevance as therapeutic targets, such as the GM2, GD2, GD3 and GM3 gangliosides in melanoma. In vitro immunization of human B lymphocytes from normal donors was performed using liposomes containing gangliosides as the immunizing antigen combined with either complete tetanus toxoid or a synthetic peptide corresponding to a T helper epitope to stimulate in vitro immunization. Specific human anti-ganglioside antibodies were obtained, indicating that the antibdoy response found in vitro was antigen-driven. To overcome the widely reported problems concerning stability of immunoglobulin production by the antibody-secreting cell lines, a method of positive selection using GM3-coated magnetic beads has been developed in order to rescue unstable clones. Development of new methods to reproducibly generate ganglioside-specific human MAbs will amplify the possibilities for diagnostic and therapeutic applications. (orig.)

  7. Use of serum squamous cell carcinoma antigen for follow-up monitoring of cervical cancer patients who were treated by concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    To investigate the significance of monitoring the levels of the serum squamous cell carcinoma antigen (SCC-Ag) for the detection of recurrent disease in patients with cervical cancer treated by concurrent chemoradiotherapy. The records of 112 patients with cervical cancer were reviewed. Serum SCC-Ag levels were measured at regular follow-up visits. A SCC-Ag level of 2 ng/mL was considered the upper limit of normal. Biochemical failure was defined as two consecutively increasing SCC-Ag values above normal. Recurrent disease was confirmed by histologic and radiographic studies. Eighteen patients (16%) developed recurrent disease. Sixteen patients had initially elevated SCC-Ag, post-treatment normalization of SCC-Ag, and tumor recurrence. The SCC-Ag difference (ΔSCC-Ag), defined as the difference between the last value after two consecutively increases above normal and the value immediately before the elevation, had good clinical performance in predicting cancer recurrence. The cutoff value of ΔSCC-Ag was 0.95 ng/mL. SCC-Ag is a relatively good method for the detection of disease recurrence in patients with cervical cancer who were treated by concurrent chemoradiotherapy

  8. Effect of ultrasound combined with determination of CA19-9 and hs-CRP on the accuracy of early diagnosis of gallbladder cancer

    Directory of Open Access Journals (Sweden)

    Hang-yu ZHANG

    2014-03-01

    Full Text Available Objective  To investigate the value of ultrasound combined with tumor marker CA19-9 and high sensitivity C reactive protein (hs-CRP on the accuracy of early diagnosis of gallbladder cancer. Methods  Ninety-five patients with pathologically confirmed primary gallbladder cancer who received cholecystectomy from Jan. 2008 to Jan. 2013 in our hospital were included in the study. The study also included 51 patients with benign cystic lesions and 51 healthy adults. In all patients, results of pathological examination, B-ultrasound, serum CA19-9 and hs-CRP detection were obtained. In all the healthy adults gallbladder diseases were ruled out, but all of them received serum CA19-9 and hs-CRP determination. Results  Of 95 patients with primary gallbladder cancer, B-ultrasound showed nodules in the gallbladder lumen in 31, tumor mass in 40, and thickened wall in 24. Histological examination showed adenocarcinoma in 87 cases, adenosquamous carcinoma in 6, and squamous carcinoma in 2. There was a statistical difference in hs-CRP and CA19-9 levels between the groups (P<0.05, and the highest level appeared in gallbladder cancer group. There was a high sensitivity but low specificity of CA19-9 or hs-CRP in the diagnosis of primary gallbladder cancer. The sensitivity and specificity were 74.7% and 75.0% when primary gallbladder cancer was diagnosed with B-ultrasound. The positive values of CA19-9 and hs-CRP were ≥100U/ml and ≥6mg/L respectively, when they were combined with B-ultrasound as a single serology factor. When both B-ultrasound and serum levels of CA19-9 and hs-CRP were positive, the diagnostic sensitivity and specificity were 71.6% and 84.4% respectively. When B-ultrasound or serum CA19-9 and hs-CRP were positive, the diagnostic sensitivity and specificity were 98.9% and 66.7% respectively. Conclusions  Combination of B-ultrasound and determination of serum of CA19-9 and hs-CRP can improve the accuracy of the diagnosis of gallbladder

  9. Molecular evaluation of PIK3CA gene mutation in breast cancer: determination of frequency, distribution pattern and its association with clinicopathological findings in Indian patients.

    Science.gov (United States)

    Ahmad, Firoz; Badwe, Anuya; Verma, Geeta; Bhatia, Simi; Das, Bibhu Ranjan

    2016-07-01

    Somatic mutations in the PIK3CA gene are common in breast cancer and represent a clinically useful marker for prognosis and therapeutic target. Activating mutations in the PI3K p110 catalytic subunit (PIK3CA) have been identified in 18-40 % of breast carcinomas. In this study, we evaluated PIK3CA mutation in 185 Indian breast cancer patients by direct DNA sequencing. PIK3CA mutations were observed in 23.2 % (43/185) of breast tumor samples. PIK3CA mutations were more frequent exon 30 (76.8 %) than in exon 9 (23.2 %). Mutations were mostly clustered within two hotspot region between nucleotides 1624 and 1636 or between 3129 and 3140. Sequencing analysis revealed four different missense mutations at codon 542 and 545 (E542K, E545K, E545A and E545G) in the helical domain and two different amino acid substitutions at codon 1047 (H1047R and H1047L) in the kinase domain. None of the cases harbored concomitant mutations at multiple codons. PIK3CA mutations were more frequent in older patients, smaller size tumors, ductal carcinomas, grade II tumors, lymph node-positive tumors and non-DCIS tumors; however, none of the differences were significant. In addition, PIK3CA mutations were common in ER+, PR+ and HER2+ cases (30 %), and a comparatively low frequency were noted in triple-negative tumors (13.6 %). In conclusion, to our knowledge, this is the largest study to evaluate the PIK3CA mutation in Indian breast cancer patients. The frequency and distribution pattern of PIK3CA mutations is similar to global reports. Furthermore, identification of molecular markers has unique strengths and can provide insights into the pathogenic process of breast carcinomas. PMID:27282497

  10. Multicenter, phase II clinical trial of cancer vaccination for advanced esophageal cancer with three peptides derived from novel cancer-testis antigens

    Directory of Open Access Journals (Sweden)

    Kono Koji

    2012-07-01

    Full Text Available Abstract Background Since a phase I clinical trial using three HLA-A24-binding peptides from TTK protein kinase (TTK, lymphocyte antigen-6 complex locus K (LY6K, and insulin-like growth factor-II mRNA binding protein-3 (IMP3 had been shown to be promising for esophageal squamous cell carcinoma (ESCC, we further performed a multicenter, non-randomized phase II clinical trial. Patients and methods Sixty ESCC patients were enrolled to evaluate OS, PFS, immunological response employing ELISPOT and pentamer assays. Each of the three peptides was administered with IFA weekly. All patients received the vaccination without knowing an HLA-A type, and the HLA types were key-opened at the analysis point. Hence, the endpoints were set to evaluate differences between HLA-A*2402-positive (24(+ and -negative (24(− groups. Results The OS in the 24 (+ group (n = 35 tended to be better than that in the 24(− group (n = 25 (MST 4.6 vs. 2.6 month, respectively, p = 0.121, although the difference was not statistically significant. However, the PFS in the 24(+ group was significantly better than that in the 24(− group (p = 0.032. In the 24(+ group, ELISPOT assay indicated that the LY6K-, TTK-, and IMP3-specific CTL responses were observed after the vaccination in 63%, 45%, and 60% of the 24(+ group, respectively. The patients having LY6K-, TTK-, and IMP3-specific CTL responses revealed the better OS than those not having CTL induction, respectively. The patients showing the CTL induction for multiple peptides have better clinical responses. Conclusions The immune response induced by the vaccination could make the prognosis better for advanced ESCC patients. Trial registration ClinicalTrials.gov, number NCT00995358

  11. Immunodominant PstS1 antigen of mycobacterium tuberculosis is a potent biological response modifier for the treatment of bladder cancer

    International Nuclear Information System (INIS)

    Bacillus Calmette Guérin (BCG)-immunotherapy has a well-documented and successful clinical history in the treatment of bladder cancer. However, regularly observed side effects, a certain degree of nonresponders and restriction to superficial cancers remain a major obstacle. Therefore, alternative treatment strategies are intensively being explored. We report a novel approach of using a well defined immunostimulatory component of Mycobacterium tuberculosis for the treatment of bladder cancer. The phosphate transport protein PstS1 which represents the phosphate binding component of a mycobacterial phosphate uptake system is known to be a potent immunostimulatory antigen of M. tuberculosis. This preclinical study was designed to test the potential of recombinant PstS1 to serve as a non-viable and defined immunotherapeutic agent for intravesical bladder cancer therapy. Mononuclear cells (PBMCs) were isolated from human peripheral blood and stimulated with PstS1 for seven days. The activation of PBMCs was determined by chromium release assay, IFN-γ ELISA and measurement of lymphocyte proliferation. The potential of PstS1 to activate monocyte-derived human dendritic cells (DC) was determined by flow cytometric analysis of the marker molecules CD83 and CD86 as well as the release of the cytokines TNF-α and IL-12. Survival of presensitized and intravesically treated, tumor-bearing mice was analyzed by Kaplan-Meier curve and log rank test. Local and systemic immune response in PstS1-immunotherapy was investigated by anti-PstS1-specific ELISA, splenocyte proliferation assay and immunohistochemistry. Our in vitro experiments showed that PstS1 is able to stimulate cytotoxicity, IFN-γ release and proliferation of PBMCs. Further investigations showed the potential of PstS1 to activate monocyte-derived human dendritic cells (DC). In vivo studies in an orthotopic murine bladder cancer model demonstrated the therapeutic potential of intravesically applied PstS1

  12. 基于IgY的ELISA用于囊尾蚴循环抗原的检测%Detecting the circulating antigen(CA) of Taenia solium cysticercosis with specific egg yolk antibody (IgY) by sandwich ELISA

    Institute of Scientific and Technical Information of China (English)

    刘玉; 王元伦; 唐雨德

    2013-01-01

    Objective To develop a sensitive and specific double antibody sandwich enzyme-linked immunosorbent assay (ELISA) to detect circulating antigen (CA) of Taeniasoliumcysticercosis with chicken egg yolk immunoglobulin antibodies (IgY).Methods Hens were subcutaneously immunized with CA and the crude IgY was extracted from egg yolk by water dilution method.A sandwich ELISA had been developed by purified IgY antibodies as capture antibody and monoclonal antibodies labeled with peroxidase as detecting antibody.The detection limits of CA were analyzed.The sera and cerebrospinal fluid of patients,the sera of healthy people,sick pigs and healthy pigs were detected in parallel by the established ELISA methods.It's sensitivity and specificity were evaluated by comparison with ELISA based monoclonal antibodies.Results The minimal detectable concentration of CA was 8.3 and 13.9 μg/ml by sandwich ELISA based IgY and monoclonal antibodies,respectively.The positive rates of samples from 139 patients,19 cerebrospinal fluid of patients and 222 sick pigs were 100% (139/139),89.5% (17/19) and 100% (222/222) by sandwich ELISA based IgY respectively.The negative rates of samples from 50 healthy people and 20 healthy pigs were 100%.Conclusion The novel double-antibody sandwich ELISA using anti-CA IgY appears to be sensitive and specific for detection the CA of Taenia solium cysticercosis.It is the promising assay for immunodiagnosis of Taenia solium cysticercosis.%目的 建立基于IgY的双抗体夹心ELISA用于囊尾蚴病的诊断.方法 制备并纯化抗囊尾蚴循环抗原(CA)卵黄抗体(IgY),建立以抗CA的IgY为捕获抗体,酶标记抗CA的单克隆抗体1A5为检测抗体的双抗体夹心ELISA法,共检测样品450份,并与捕获抗体和检测抗体均为单克隆抗体的ELISA法比较,验证方法的敏感性、特异性与实用性.结果 成功制备并鉴定了特异性IgY抗体,建立了基于Igy的双抗体夹心ELISA检测体系.IgY-ELISA和双单

  13. COLONOSCOPY AND CARCINOEMBRYONIC ANTIGEN VARIATIONS

    Directory of Open Access Journals (Sweden)

    Rita G SOUSA

    2014-03-01

    Full Text Available Context Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy. Objective To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels. Methods We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1 before bowel cleaning, (2 before colonoscopy and (3 immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by “Sandwich” immunoassay. The statistical methods used were the paired t-test and ANOVA. Results Thirty-seven patients (22M/15F were included; age range 28-84 (mean 56 years. Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1, (2 and (3, respectively. An increase in value (2 compared with (1 was observed in 20/37 patients (P = 0.018, mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2 to (3 (P = 1.3x10-7. Conclusions A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.

  14. The initial development of the 'Cancer Caregiving Tasks, Consequences and Needs Questionnaire' (CaTCoN)

    DEFF Research Database (Denmark)

    Lund, Line; Ross, Lone; Grønvold, Mogens

    2012-01-01

    To develop a questionnaire for cancer patients' informal caregivers, measuring the caregiving tasks and consequences, and the caregivers' needs with a main focus on the interaction with the health care professionals. Such an instrument is needed to evaluate the efforts directed towards caregivers...

  15. Auranofin, an Anti-Rheumatic Gold Compound, Modulates Apoptosis by Elevating the Intracellular Calcium Concentration ([Ca2+]i) in MCF-7 Breast Cancer Cells

    OpenAIRE

    Elizabeth Varghese; Dietrich Büsselberg

    2014-01-01

    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 a...

  16. Auranofin, an Anti-Rheumatic Gold Compound, Modulates Apoptosis by Elevating the Intracellular Calcium Concentration ([Ca{sup 2+}]{sub i}) in MCF-7 Breast Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Varghese, Elizabeth; Büsselberg, Dietrich, E-mail: dib2015@qatar-med.cornell.edu [Weil Cornell Medical College in Qatar, Qatar Foundation-Education City, P.O. Box 24144 Doha (Qatar)

    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 ([Ca{sup 2+}]{sub 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 ([Ca{sup 2+}]{sub 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 [Ca{sup 2+}]{sub 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 [Ca{sup 2+}]{sub i}. Overall, elevation of [Ca{sup 2+}]{sub i} by Auranofin might be crucial for triggering Ca{sup 2+}-dependent apoptotic pathways. Therefore, in anti-cancer therapy, modulating [Ca{sup 2+}]{sub i} should be considered as a crucial factor for the induction of cell death in cancer cells.

  17. Antigen-induced and non-antigen-induced histamine release from rat mast cells sensitized with mouse antiserum.

    Directory of Open Access Journals (Sweden)

    Kurose,Masao

    1981-10-01

    Full Text Available Marked IgE-mediated histamine release from rat mast cells sensitized in vitro with mouse antiserum occurs in the presence of added Ca++ and phosphatidylserine (PS, although a considerable degree of antigen-induced histamine release which may utilize intracellular or cell-bound calcium is also observed. The decay in the responsiveness to Ca++ of the sensitized cells stimulated by antigen in Ca++-free medium in the presence of PS is relatively slow, and maximum release is produced by Ca++ added 1 min after antigen. Histamine release also occurs when Ca++ is added after PS in the absence of antigen to the sensitized cells suspended in Ca++-free medium. Unlike the antigen-induced release, the intensity of this non-antigen-induced release varies depending on both mast-cell and antiserum pools. A heat-labile factor(s, which is different from antigen-specific IgE antibody and is also contained in normal mouse serum, is involved in this reaction. In the antigen-nondependent (PS + Ca++-induced release, no decay in the responsiveness to Ca++ is observed after PS addition. Both the antigen-induced and non-antigen-induced release are completed fairly rapidly and are dependent of temperature, pH and energy.

  18. Prolonged androgen deprivation leads to downregulation of androgen receptor and prostate-specific membrane antigen in prostate cancer cells

    OpenAIRE

    Liu, Tiancheng; Wu, Lisa Y.; Fulton, Melody D.; JOHNSON, JACQUELINE M.; Berkman, Clifford E.

    2012-01-01

    Emergence of androgen-independent cancer cells during androgen deprivation therapy presents a significant challenge to successful treatment outcomes in prostate cancer. Elucidating the role of androgen deprivation in the transition from an androgen-dependent to an androgen-independent state may enable the development of more effective therapeutic strategies against prostate cancer. Herein, we describe an in vitro model for assessing the effects of continuous androgen-deprivation on prostate c...

  19. Combination of Circulating Tumor Cells with Serum Carcinoembryonic Antigen Enhances Clinical Prediction of Non-Small Cell Lung Cancer

    OpenAIRE

    Xi Chen; Xu Wang; Hua He; Ziling Liu; Ji-Fan Hu; Wei Li

    2015-01-01

    Circulating tumor cells (CTCs) have emerged as a potential biomarker in the diagnosis, prognosis, treatment, and surveillance of lung cancer. However, CTC detection is not only costly, but its sensitivity is also low, thus limiting its usage and the collection of robust data regarding the significance of CTCs in lung cancer. We aimed to seek clinical variables that enhance the prediction of CTCs in patients with non-small cell lung cancer (NSCLC). Clinical samples and pathological data were c...

  20. Significance of PIK3CA Mutations in Patients with Early Breast Cancer Treated with Adjuvant Chemotherapy: A Hellenic Cooperative Oncology Group (HeCOG Study.

    Directory of Open Access Journals (Sweden)

    George Papaxoinis

    Full Text Available The PI3K-AKT pathway is frequently activated in breast cancer. PIK3CA mutations are most frequently found in the helical (exon 9 and kinase (exon 20 domains of this protein. The aim of the present study was to examine the role of different types of PIK3CA mutations in combination with molecular biomarkers related to PI3K-AKT signaling in patients with early breast cancer.Tumor tissue samples from 1008 early breast cancer patients treated with adjuvant chemotherapy in two similar randomized trials of HeCOG were examined. Tumors were subtyped with immunohistochemistry (IHC and FISH for ER, PgR, Ki67, HER2 and androgen receptor (AR. PIK3CA mutations were analyzed by Sanger sequencing (exon 20 and qPCR (exon 9 (Sanger/qPCR mutations. In 610 cases, next generation sequencing (NGS PIK3CA mutation data were also available. PIK3CA mutations and PTEN protein expression (IHC were analyzed in luminal tumors (ER and/or PgR positive, molecular apocrine carcinomas (MAC; ER/PgR negative / AR positive and hormone receptor (ER/PgR/AR negative tumors.PIK3CA mutations were detected in 235/1008 tumors (23% with Sanger/qPCR and in 149/610 tumors (24% with NGS. Concordance between the two methods was good with a Kappa coefficient of 0.76 (95% CI 0.69-0.82. Lobular histology, low tumor grade and luminal A tumors were associated with helical domain mutations (PIK3CAhel, while luminal B with kinase domain mutations (PIK3CAkin. The overall incidence of PIK3CA mutations was higher in luminal as compared to MAC and hormone receptor negative tumors (p = 0.004. Disease-free and overall survival did not significantly differ with respect to PIK3CA mutation presence and type. However, a statistically significant interaction between PIK3CA mutation status and PTEN low protein expression with regard to prognosis was identified.The present study did not show any prognostic significance of specific PIK3CA mutations in a large group of predominantly lymph-node positive breast cancer

  1. Prostate-specific antigen (PSA/hK3): a further player in the field of breast cancer diagnostics?

    OpenAIRE

    Mannello, Ferdinando; Gazzanelli, Giancarlo

    2001-01-01

    Since its identification, much information has been obtained about prostate-specific antigen (PSA, or human glandular kallikrein 3 [hK3]), a kallikrein-like serine protease that is the most valuable tumour marker for the screening, diagnosis and management of human prostate carcinoma. Recently, it has become widely accepted that PSA is also present in many nonprostatic sources, casting doubts about the specificity of its tissue expression. Here we summarize the findings on the biomolecular ex...

  2. Highlights from the prostate cancer genome report

    Institute of Scientific and Technical Information of China (English)

    Shyh-Han Tan; Gyorgy Petrovics; Shiv Srivastava

    2011-01-01

    @@ Prostate cancer (Cap) is the second most frequently diagnosed cancer of men worldwide (899 000 new cases,13.6% of the total),with nearly 75% of the registered cases occurring in developed countries (644000 cases).1 Blood prostate-specific antigen test has revolutionized the early detection of Cap and organ-confined Cap is effectively managed by state-of-the-art treatments including radical prostatectomy or radiation therapy.2 In the past decade,tremendous progress has also been made in our understanding of the biology and common genomicalterations in Cap 3.4 New molecular marker assays have promise in improving CaP diagnosis.Despite these advances,major challenges remain with our ability to distinguish indolent cancers from the more aggressive cancers detected early due to widely used prostate-specific antigen test.Furthermore,development of molecular stratification of CaP for targeted and more effective therapies is critically needed.

  3. The C-terminal fragment of prostate-specific antigen, a 2331 Da peptide, as a new urinary pathognomonic biomarker candidate for diagnosing prostate cancer.

    Directory of Open Access Journals (Sweden)

    Kenji Nakayama

    Full Text Available BACKGROUND AND OBJECTIVES: Prostate cancer (PCa is one of the most common cancers and leading cause of cancer-related deaths in men. Mass screening has been carried out since the 1990s using prostate-specific antigen (PSA levels in the serum as a PCa biomarker. However, although PSA is an excellent organ-specific marker, it is not a cancer-specific marker. Therefore, the aim of this study was to discover new biomarkers for the diagnosis of PCa. MATERIALS AND METHODS: We focused on urine samples voided following prostate massage (digital rectal examination [DRE] and conducted a peptidomic analysis of these samples using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS(n. Urinary biomaterials were concentrated and desalted using CM-Sepharose prior to the following analyses being performed by MALDI-TOF/MS(n: 1 differential analyses of mass spectra; 2 determination of amino acid sequences; and 3 quantitative analyses using a stable isotope-labeled internal standard. RESULTS: Multivariate analysis of the MALDI-TOF/MS mass spectra of urinary extracts revealed a 2331 Da peptide in urine samples following DRE. This peptide was identified as a C-terminal PSA fragment composed of 19 amino acid residues. Moreover, quantitative analysis of the relationship between isotope-labeled synthetic and intact peptides using MALDI-TOF/MS revealed that this peptide may be a new pathognomonic biomarker candidate that can differentiate PCa patients from non-cancer subjects. CONCLUSION: The results of the present study indicate that the 2331 Da peptide fragment of PSA may become a new pathognomonic biomarker for the diagnosis of PCa. A further large-scale investigation is currently underway to assess the possibility of using this peptide in the early detection of PCa.

  4. A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer.

    Science.gov (United States)

    Pavlenko, M; Roos, A-K; Lundqvist, A; Palmborg, A; Miller, A M; Ozenci, V; Bergman, B; Egevad, L; Hellström, M; Kiessling, R; Masucci, G; Wersäll, P; Nilsson, S; Pisa, P

    2004-08-16

    Prostate-specific antigen (PSA) is a serine protease secreted at low levels by normal luminal epithelial cells of the prostate and in significantly higher levels by prostate cancer cells. Therefore, PSA is a potential target for various immunotherapeutical approaches against prostate cancer. DNA vaccination has been investigated as immunotherapy for infectious diseases in patients and for specific treatment of cancer in certain animal models. In animal studies, we have demonstrated that vaccination with plasmid vector pVAX/PSA results in PSA-specific cellular response and protection against tumour challenge. The purpose of the trial was to evaluate the safety, feasibility and biological efficacy of pVAX/PSA vaccine in the clinic. A phase I trial of pVAX/PSA, together with cytokine granulocyte/macrophage-colony stimulating factor (GM-CSF) (Molgramostim) and IL-2 (Aldesleukin) as vaccine adjuvants, was carried out in patients with hormone-refractory prostate cancer. To evaluate the biologically active dose, the vaccine was administered during five cycles in doses of 100, 300 and 900 microg, with three patients in each cohort. Eight patients were evaluable. A PSA-specific cellular immune response, measured by IFN-gamma production against recombinant PSA protein, and a rise in anti-PSA IgG were detected in two of three patients after vaccination in the highest dose cohort. A decrease in the slope of PSA was observed in the two patients exhibiting IFN-gamma production to PSA. No adverse effects (WHO grade >2) were observed in any dose cohort. We demonstrate that DNA vaccination with a PSA-coding plasmid vector, given with GM-CSF and IL-2 to patients with prostate cancer, is safe and in doses of 900 microg the vaccine can induce cellular and humoral immune responses against PSA protein. PMID:15280930

  5. Are PIK3CA Mutation and Amplification Associated with Clinicopathological Characteristics of Gastric Cancer?

    Science.gov (United States)

    Lee, Hyunsu; Hwang, Il-Seon; Choi, In-Jang; Kang, Yu-Na; Park, Keon-Uk; Lee, Jae-Ho

    2015-01-01

    Alterations in mitochondrial DNA (mtDNA) have been studied in various cancers. However, the clinical value of mtDNA copy number (mtCN) alterations in gastric cancer (GC) is poorly understood. In the present study, we investigated whether alterations in mtCNs might be associated with clinicopathological parameters in GC cases. mtCN was measured in 109 patients with GC by real-time PCR. Then, correlations with clinicopathological characteristics were analyzed. mtCN was elevated in 64.2% of GC tissues compared with paired, adjacent, non- cancerous tissue. However, the observed alterations in mtCN were not associated with any clinicopathological characteristics, including age, gender, TN stage, Lauren classification, lymph node metastasis, and depth of invasion. Moreover, Kaplan-Meier survival curves revealed that mtCN was not significantly associated with the survival of GC patients. In this study, we demonstrated that mtCN was not a significant marker for predicting clinical characteristics or prognosis in GC. PMID:26107192

  6. Combined effects of 5-Fluorouracil, Folinic acid and Oxaliplatin on the expression of carcinoembryonic antigen in human colon cancer cells: pharmacological basis to develop an active antitumor immunochemotherapy

    Directory of Open Access Journals (Sweden)

    De Vecchis Liana

    2008-05-01

    Full Text Available Abstract Background Five-fluorouracil (FU, mainly associated with leucovorin (L, plays an essential role in chemotherapy of colorectal carcinoma. Moreover, FU ± L has been found to increase the expression of tumor-associated carcinoembryonic antigen (CEA, that may be an important target in therapeutic protocols of active specific immunotherapy. FU + L (FUL are frequently combined with oxaliplatin (OXA in advanced colon cancer patients. Thus, we investigated whether FUL in combination with OXA according to 2 different schedules may influence CEA expression in human colon cancer cells in vitro. Methods CEA protein expression was evaluated by cytofluorimetric and western blot analysis. Relative quantification of CEA mRNA was assessed by real time RT-PCR analysis. Results Levels of CEA protein and transcript were found to be higher in FUL-treated cells than in controls. However, when target cells were exposed to OXA before but not after FUL treatment, the up-regulation of CEA was partially inhibited. Conclusion These results suggest that target cells must be exposed to OXA after but not before treatment with the fluoropyrimidine in order to exploit drug-induced up-regulation of CEA. This finding appears to provide useful information to design chemo-immunotherapy protocols based on FUL + OXA, combined with host's immunity against CEA directed cancer vaccines.

  7. Incidental detection of prostate-specific antigen-negative metastatic prostate cancer initially presented with solitary pulmonary nodule on fluorodeoxyglucose positron emission tomography/computed tomography

    International Nuclear Information System (INIS)

    A 71-year-old male patient with solitary pulmonary nodule underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) showing slightly increased FDG uptake in this nodule. In addition, PET/CT detected hypermetabolic sclerotic bone lesions in the right second rib and 7th thoracic vertebrae, which were interpreted as possible metastases, and mildly increased FDG uptake in the prostate gland highly suspicious of malignancy. The patient's prostate-specific antigen (PSA) level was within normal range (3.8 ng/dL). The histopathological examination of the lung nodule and right second rib lesion proved metastases from prostate cancer, then the prostate biopsy-confirmed prostate adenocarcinoma. The unique feature of this case is to emphasize the importance of performing PET/CT for solitary pulmonary nodule in detecting PSA-negative metastatic prostate cancer. This case indicated that it should be kept in mind that, even if the PSA is negative, a lung metastasis of prostate cancer may be an underlying cause in patients evaluated for solitary pulmonary nodule by FDG PET/CT

  8. Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models

    Science.gov (United States)

    Maawy, Ali A.; Hiroshima, Yukihiko; Kaushal, Sharmeela; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

    2013-12-01

    The aim of this study was to evaluate a set of visible and near-infrared dyes conjugated to a tumor-specific chimeric antibody for high-resolution tumor imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer was orthotopically implanted into pancreata of nude mice. Mice received a single intravenous injection of a chimeric anti-carcinoembryonic antigen antibody conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or DyLight 488); 550-nm group (Alexa Fluor 555 or DyLight 550); 650-nm group (Alexa Fluor 660 or DyLight 650), or the 750-nm group (Alexa Fluor 750 or DyLight 755). After 24 h, the Olympus OV100 small-animal imaging system was used for noninvasive and intravital fluorescence imaging of mice. Dyes were compared with respect to depth of imaging, resolution, tumor-to-background ratio (TBR), photobleaching, and hemoglobin quenching. The longer wavelength dyes had increased depth of penetration and ability to detect the smallest tumor deposits and provided the highest TBRs, resistance to hemoglobin quenching, and specificity. The shorter wavelength dyes were more photostable. This study showed unique advantages of each dye for specific cancer imaging in a clinically relevant orthotopic model.

  9. Demethylation of Cancer/Testis Antigens and CpG ODN Stimulation Enhance Dendritic Cell and Cytotoxic T Lymphocyte Function in a Mouse Mammary Model

    Directory of Open Access Journals (Sweden)

    Jun-Zhong Sun

    2013-01-01

    Full Text Available Background. Cancer/testis antigens (CTAs are ideal targets for cancer immunotherapy in virtue of their restricted expression profile in normal tissues. However, CTA-targeted immunotherapy has been rather disappointing clinical setting for CTAs are downregulated by cytosine-phosphate-guanosine (CpG methylation in their promoter regions, so that tumor cells have low immunogenicity. Methods. We reinduced mouse CTA P1A through demethylation process and generated P1A-specific cytotoxic lymphocytes (CTLs by immunizing BALB/c (H-2d mice with dendritic cells pulsed with a P1A-specific peptide and CpG oligodeoxynucleotide (ODN immune adjuvant. Results. We found that demethylation and CpG ODN immune adjuvant stimulation facilitated DC maturation and enhanced the allogenic capacity of P1A-specific CTLs against target cells both in vitro and in vivo. Conclusions. Our results suggested that CTA induction and immune adjuvant stimulation is a feasible strategy in cancer immunotherapy.

  10. PIK3CA mutations are associated with decreased benefit to neoadjuvant human epidermal growth factor receptor 2-targeted therapies in breast cancer

    NARCIS (Netherlands)

    Majewski, Ian J; Nuciforo, Paolo; Mittempergher, Lorenza; Bosma, Astrid J; Eidtmann, Holger; Holmes, Eileen; Sotiriou, Christos; Fumagalli, Debora; Jimenez, Jose; Aura, Claudia; Prudkin, Ludmila; Díaz-Delgado, Maria Carmen; de la Peña, Lorena; Loi, Sherene; Ellis, Catherine; Schultz, Nikolaus; de Azambuja, Evandro; Harbeck, Nadia; Piccart-Gebhart, Martine; Bernards, René; Baselga, José

    2015-01-01

    PURPOSE: We investigated whether mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with response to neoadjuvant human epidermal growth factor receptor 2 (HER2) -targeted therapies in patients with breast cancer. PATIENTS AND METHODS: Baseli

  11. Melanoma-associated cancer-testis antigen 16 (CT16 regulates the expression of apoptotic and antiapoptotic genes and promotes cell survival.

    Directory of Open Access Journals (Sweden)

    Camilla Nylund

    Full Text Available Cancer-testis (CT antigens are predominantly expressed in testis or placenta, but absent in most adult tissues. During malignant transformation CT genes are often activated. CT antigen 16 (CT16, PAGE5 is frequently expressed in advanced melanoma but its biological function has been unknown. To examine the role of CT16 in cell survival we knocked it down in A2058 melanoma cells using specific siRNAs and exposed the cells to cancer drug cisplatin known to induce apoptosis. As a result, cell survival was markedly decreased. To study the effects of CT16 on cell survival in more detail, the cellular gene expression profiles were investigated after CT16 silencing in CT16 positive A2058 melanoma cells, as well as after CT16 overexpression in CT16 negative WM-266-4 melanoma cells. Among the 11 genes both upregulated by CT16 silencing and downregulated by CT16 overexpression or vice versa, 4 genes were potentially apoptotic or antiapoptotic genes. CT16 was recognized as a positive regulator of antiapoptotic metallothionein 2A and interleukin 8 genes, whereas it inhibited the expression of apoptosis inducing dickkopf 1 (DKK1 gene. In addition CT16 enhanced the expression of fatty acid binding protein 7, a known promoter of melanoma progression. The effect of CT16 on DKK1 expression was p53 independent. Furthermore, CT16 did not regulate apoptotic genes via DNA methylation. In twenty melanoma metastasis tissue samples average DKK1 mRNA level was shown to be significantly (p<0.05 lower in high CT16 expressing tumors (n = 3 when compared to the tumors with low CT16 expression (n = 17. Thus, our results indicate that CT16 promotes the survival of melanoma cells and is therefore a potential target for future drug development.

  12. Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors

    Directory of Open Access Journals (Sweden)

    Mitrou Panagiota N

    2011-04-01

    Full Text Available Abstract Background The PTEN tumour suppressor gene and PIK3CA proto-oncogene encode proteins which contribute to regulation and propagation of signal transduction through the PI3K/AKT signalling pathway. This study investigates the prevalence of loss of PTEN expression and mutations in both PTEN and PIK3CA in colorectal cancers (CRC and their associations with tumour clinicopathological features, lifestyle factors and dietary consumptions. Methods 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for PTEN and PIK3CA mutations by DNA sequencing and PTEN expression changes by immunohistochemistry. Dietary and lifestyle data were collected prospectively using seven day food diaries and lifestyle questionnaires. Results Mutations in exons 7 and 8 of PTEN were observed in 2.2% of CRC and PTEN loss of expression was identified in 34.9% CRC. Negative PTEN expression was associated with lower blood low-density lipoprotein concentrations (p = 0.05. PIK3CA mutations were observed in 7% of cancers and were more frequent in CRCs in females (p = 0.04. Analysis of dietary intakes demonstrated no link between PTEN expression status and any specific dietary factor. PTEN expression negative, proximal CRC were of more advanced Dukes' stage (p = 0.02 and poor differentiation (p PIK3CA mutations and loss of PTEN expression demonstrated that these two events were independent (p = 0.55. Conclusion These data demonstrated the frequent occurrence (34.9% of PTEN loss of expression in colorectal cancers, for which gene mutations do not appear to be the main cause. Furthermore, dietary factors are not associated with loss of PTEN expression. PTEN expression negative CRC were not homogenous, as proximal cancers were associated with a more advanced Dukes' stage and poor differentiation, whereas distal cancers were associated with earlier Dukes' stage.

  13. Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors

    International Nuclear Information System (INIS)

    The PTEN tumour suppressor gene and PIK3CA proto-oncogene encode proteins which contribute to regulation and propagation of signal transduction through the PI3K/AKT signalling pathway. This study investigates the prevalence of loss of PTEN expression and mutations in both PTEN and PIK3CA in colorectal cancers (CRC) and their associations with tumour clinicopathological features, lifestyle factors and dietary consumptions. 186 adenocarcinomas and 16 adenomas from the EPIC Norfolk study were tested for PTEN and PIK3CA mutations by DNA sequencing and PTEN expression changes by immunohistochemistry. Dietary and lifestyle data were collected prospectively using seven day food diaries and lifestyle questionnaires. Mutations in exons 7 and 8 of PTEN were observed in 2.2% of CRC and PTEN loss of expression was identified in 34.9% CRC. Negative PTEN expression was associated with lower blood low-density lipoprotein concentrations (p = 0.05). PIK3CA mutations were observed in 7% of cancers and were more frequent in CRCs in females (p = 0.04). Analysis of dietary intakes demonstrated no link between PTEN expression status and any specific dietary factor. PTEN expression negative, proximal CRC were of more advanced Dukes' stage (p = 0.02) and poor differentiation (p < 0.01). Testing of the prevalence of PIK3CA mutations and loss of PTEN expression demonstrated that these two events were independent (p = 0.55). These data demonstrated the frequent occurrence (34.9%) of PTEN loss of expression in colorectal cancers, for which gene mutations do not appear to be the main cause. Furthermore, dietary factors are not associated with loss of PTEN expression. PTEN expression negative CRC were not homogenous, as proximal cancers were associated with a more advanced Dukes' stage and poor differentiation, whereas distal cancers were associated with earlier Dukes' stage

  14. Stage-specific embryonic antigen-4 as a potential therapeutic target in glioblastoma multiforme and other cancers

    OpenAIRE

    Lou, Yi-Wei; Wang, Pao-Yuan; Yeh, Shih-Chi; Chuang, Po-Kai; Li, Shiou-Ting; wu, Chung-Yi; Khoo, Kay-Hooi; Hsiao, Michael; Hsu, Tsui-Ling; Wong, Chi-Huey

    2014-01-01

    Glioblastoma multiforme (GBM) is a deadly brain tumor. More than 50% of patients who suffer from GBM die within 15 mo even received all possible medical treatment. In this study we report that the glycolipid stage-specific embryonic antigen-4 (SSEA-4) is highly expressed on the surface of both GBM cells and GBM specimens. We further demonstrate that the growth of GBM tumor is inhibited when anti–SSEA-4 antibody is administered to experimental mice, suggesting a research proof of concept for t...

  15. Comparison patterns of 4 T1 antigens recognized by humoral immune response mediated by IgG and IgM antibodies in female and male mice with breast cancer using 2D-immnunoblots.

    Science.gov (United States)

    Díaz-Zaragoza, Mariana; Hernández-Ávila, Ricardo; Govezensky, Tzipe; Mendoza, Luis; Meneses-Ruíz, Dulce María; Ostoa-Saloma, Pedro

    2015-09-01

    The early detection of cancer is one of the most promising approaches to reduce its growing burden and develop a curative treatment before the tumor is established. The early diagnosis of breast cancer is the most demanding of all tumors, because it is the most common cancer in women worldwide. We have described a new approach to analyze humoral immune reactions against 4 T1 cell antigens in female mice, reporting that the IgG and IgM responses differed and varied over time and between individuals. In this study, we compared and analyzed the detection of tumor antigens with IgG and IgM from the sera of male mice that were injected with 4 T1 cells into the mammary gland nipple in 2D immunoblot images. The variability in IgM and IgG responses in female and male mice with breast cancer at various stages of disease was characterized, and the properties with regard to antigen recognition were correlated statistically with variables that were associated with the individuals and tumors. The ensuing IgG and IgM responses differed. Only the IgG response decreased over time in female mice--not in male mice. The IgM response was maintained during tumor development in both sexes. Each mouse had a specific pattern of antigen recognition--ie, an immunological signature--represented by a unique set of antigen spots that were recognized by IgM or IgG. These data would support that rationale IgM is a better tool for early diagnosis, because it is not subject to immunosuppression like IgG in female mice with breast cancer. PMID:26026196

  16. 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...... interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each...... treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed...

  17. Using the MCF10A/MCF10CA1a Breast Cancer Progression Cell Line Model to Investigate the Effect of Active, Mutant Forms of EGFR in Breast Cancer Development and Treatment Using Gefitinib.

    Directory of Open Access Journals (Sweden)

    Darrell C Bessette

    Full Text Available Basal-like and triple negative breast cancer (TNBC share common molecular features, poor prognosis and a propensity for metastasis to the brain. Amplification of epidermal growth factor receptor (EGFR occurs in ~50% of basal-like breast cancer, and mutations in the epidermal growth factor receptor (EGFR have been reported in up to ~ 10% of Asian TNBC patients. In non-small cell lung cancer several different mutations in the EGFR tyrosine kinase domain confer sensitivity to receptor tyrosine kinase inhibitors, but the tumourigenic potential of EGFR mutations in breast cells and their potential for targeted therapy is unknown.Constructs containing wild type, G719S or E746-A750 deletion mutant forms of EGFR were transfected into the MCF10A breast cells and their tumorigenic derivative, MCF10CA1a. The effects of EGFR over-expression and mutation on proliferation, migration, invasion, response to gefitinib, and tumour formation in vivo was investigated. Copy number analysis and whole exome sequencing of the MCF10A and MCF10CA1a cell lines were also performed.Mutant EGFR increased MCF10A and MCF10CA1a proliferation and MCF10A gefitinib sensitivity. The EGFR-E746-A750 deletion increased MCF10CA1a cell migration and invasion, and greatly increased MCF10CA1a xenograft tumour formation and growth. Compared to MCF10A cells, MCF10CA1a cells exhibited large regions of gain on chromosomes 3 and 9, deletion on chromosome 7, and mutations in many genes implicated in cancer.Mutant EGFR enhances the oncogenic properties of MCF10A cell line, and increases sensitivity to gefitinib. Although the addition of EGFR E746-A750 renders the MCF10CA1a cells more tumourigenic in vivo it is not accompanied by increased gefitinib sensitivity, perhaps due to additional mutations, including the PIK3CA H1047R mutation, that the MCF10CA1a cell line has acquired. Screening TNBC/basal-like breast cancer for EGFR mutations may prove useful for directing therapy but, as in non

  18. Expression of cell cycle regulator p57kip2, cyclinE protein and proliferating cell nuclear antigen in human pancreatic cancer: An immunohistochemical study

    Institute of Scientific and Technical Information of China (English)

    Hui Yue; Hui-Yong Jiang

    2005-01-01

    AIM: To investigate the effects of p57kip2, cyclinE protein and proliferating cell nuclear antigen (PCNA) on occurrence and progression of human pancreatic cancer.METHODS: The expression of p57kip2, cyclinE protein and PCNA in tumor tissues and adjacent tissues from 32patients with pancreatic cancer was detected by SP immunohistochemical technique.RESULTS: The positive expression rate of p57kip2 protein in tumor tissues was 46.9%, which was lower than that in adjacent pancreatic tissues (x2 = 5.317, P<0.05). P57kip2protein positive expression remarkably correlated with tumor cell differentiation (P<0.05), but not with lymph node metastasis (P>0.05). The positive expression rate of cyclinE protein in tumor tissues was 68.8%, which was higher than that in adjacent pancreatic tissues (x2 = 4.063,P<0.05). CyclinE protein positive expression significantly correlated with tumor cell differentiation and lymph node metastasis (P<0.05). The positive expression rate of PCNA in the tumor tissues was 71.9%, which was higher than that in adjacent pancreatic tissues (x2 = 5.189, P<0.05).PCNA positive expression remarkably correlated with tumor cell differentiation and lymph node metastasis (P<0.05).CONCLUSION: The decreased expression of p57kip2 and/or overexpression of cyclinE protein and PCNA may contribute to the occurrence and progression of pancreatic cancer.p57kip2, cyclinE protein, and PCNA play an important role in occurrence and progression of pancreatic cancer.

  19. Radiolabeling of anti-human prostatic specific membrane antigen antibody with 99Tcm and its biodistribution in nude mice bearing human prostate cancer

    International Nuclear Information System (INIS)

    Objective: To study the binding affinity of 99Tcm labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody (McAb) J591 to prostate cancer cells and the biodistribution of 99Tcm-J591 in nude mice bearing human prostate cancer. Methods: The McAb J591 was labeled with vTcm by improved Schwarz method and the labeled McAb was purified by Sephadex G-50. The binding affinity of J591 with prostate cancer cells was measured by Flow Cytometry. The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts were served as experiment groups, mice with PSMA-negative pc3 tumors served as controls. The biodistribution of 99Tcm-J591 were carried out in both model nude mice. Results: The radiolabeling efficiency of 99Tcm-J591 was 78.9±6.2%, and radiochemical purity was more than 90% after purification. The 99Tcm-J591 showed a good combination with PSMA-positive C4-2 cells and no combination with PSMA-negative PC3 cells in vitro. The biodistribution results showed that 99Tcm-J591 was accumulated in tumor tissue during the 2-24 hours after injection in experiment groups, and no significant uptake in control group. The uptake of 99Tcm-J591 in tumor tissue reached a maximum 15.91±5.16 % ID/g in experimental group at 12h post-injection. There was a significant difference compared with controls (P0.05). Conclusion: The monoclonal antibody J591 exhibits an excellent immuno-reactivity and tumor targeting property, and it may be used in diagnosis and target therapy of prostate cancer. (authors)

  20. Using stool antigen to screen for Helicobacter pylori in immigrants and refugees from high prevalence countries is relatively cost effective in reducing the burden of gastric cancer and peptic ulceration.

    Directory of Open Access Journals (Sweden)

    Thomas R Schulz

    Full Text Available OBJECTIVES: Refugees and immigrants from developing countries settling in industrialised countries have a high prevalence of Helicobacter pylori (H. pylori. Screening these groups for H. pylori and use of eradication therapy to reduce the future burden of gastric cancer and peptic ulcer disease is not currently recommended in most countries. We investigated whether a screening and eradication approach would be cost effective in high prevalence populations. METHODS: Nine different screening and follow-up strategies for asymptomatic immigrants from high H. pylori prevalence areas were compared with the current approach of no screening. Cost effectiveness comparisons assumed population prevalence's of H. pylori of 25%, 50% or 75%. The main outcome measure was the net cost for each cancer prevented for each strategy. Total costs of each strategy and net costs including savings from reductions in ulcers and gastric cancer were also calculated. RESULTS: Stool antigen testing with repeat testing after treatment was the most cost effective approach relative to others, for each prevalence value. The net cost per cancer prevented with this strategy was US$111,800 (assuming 75% prevalence, $132,300 (50% and $193,900 (25%. A test and treat strategy using stool antigen remained relatively cost effective, even when the prevalence was 25%. CONCLUSIONS: H. pylori screening and eradication can be an effective strategy for reducing rates of gastric cancer and peptic ulcers in high prevalence populations and our data suggest that use of stool antigen testing is the most cost effective approach.

  1. Does risk for ovarian malignancy algorithm excel human epididymis protein 4 and ca125 in predicting epithelial ovarian cancer: A meta-analysis

    International Nuclear Information System (INIS)

    Risk for Ovarian Malignancy Algorithm (ROMA) and Human epididymis protein 4 (HE4) appear to be promising predictors for epithelial ovarian cancer (EOC), however, conflicting results exist in the diagnostic performance comparison among ROMA, HE4 and CA125. Remote databases (MEDLINE/PUBMED, EMBASE, Web of Science, Google Scholar, the Cochrane Library and ClinicalTrials.gov) and full texts bibliography were searched for relevant abstracts. All studies included were closely assessed with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2). EOC predictive value of ROMA was systematically evaluated, and comparison among the predictive performances of ROMA, HE4 and CA125 were conducted within the same population. Sensitivity, specificity, DOR (diagnostic odds ratio), LR ± (positive and negative likelihood ratio) and AUC (area under receiver operating characteristic-curve) were summarized with a bivariate model. Subgroup analysis and sensitivity analysis were used to explore the heterogeneity. Data of 7792 tests were retrieved from 11 studies. The overall estimates of ROMA for EOC predicting were: sensitivity (0.89, 95% CI 0.84-0.93), specificity (0.83, 95% CI 0.77-0.88), and AUC (0.93, 95% CI 0.90-0.95). Comparison of EOC predictive value between HE4 and CA125 found, specificity: HE4 (0.93, 95% CI 0.87-0.96) > CA125 (0.84, 95% CI 0.76-0.90); AUC: CA125 (0.88, 95% CI 0.85-0.91) > HE4 (0.82, 95% CI 0.78-0.85). Comparison of OC predictive value between HE4 and CA125 found, AUC: CA125 (0.89, 95% CI 0.85-0.91) > HE4 (0.79, 95% CI 0.76-0.83). Comparison among the three tests for EOC prediction found, sensitivity: ROMA (0.86, 95%CI 0.81-0.91) > HE4 (0.80, 95% CI 0.73-0.85); specificity: HE4 (0.94, 95% CI 0.90-0.96) > ROMA (0.84, 95% CI 0.79-0.88) > CA125 (0.78, 95%CI 0.73-0.83). ROMA is helpful for distinguishing epithelial ovarian cancer from benign pelvic mass. HE4 is not better than CA125 either for EOC or OC prediction. ROMA is promising predictors of

  2. Growth delay of human bladder cancer cells by Prostate Stem Cell Antigen downregulation is associated with activation of immune signaling pathways

    International Nuclear Information System (INIS)

    Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI) anchored protein expressed not only in prostate but also in pancreas and bladder cancer as shown by immunohistochemistry and mRNA analysis. It has been targeted by monoclonal antibodies in preclinical animal models and more recently in a clinical trial in prostate cancer patients. The biological role played in tumor growth is presently unknown. In this report we have characterized the contribution of PSCA expression to tumor growth. A bladder cell line was engineered to express a doxycycline (dox) regulated shRNA against PSCA. To shed light on the PSCA biological role in tumor growth, microarray analysis was carried out as a function of PSCA expression. Expression of gene set of interest was further analyzed by qPCR Down regulation of the PSCA expression was associated with reduced cell proliferation in vitro and in vivo. Mice bearing subcutaneous tumors showed a reduced tumor growth upon treatment with dox, which effectively induced shRNA against PSCA as revealed by GFP expression. Pathway analysis of deregulated genes suggests a statistical significant association between PSCA downregulation and activation of genes downstream of the IFNα/β receptor. These experiments established for the first time a correlation between the level of PSCA expression and tumor growth and suggest a role of PSCA in counteracting the natural immune response

  3. Relationship between serum carcinoembryonic antigen level and epidermal growth factor receptor mutations with the influence on the prognosis of non-small-cell lung cancer patients

    Directory of Open Access Journals (Sweden)

    Cai ZX

    2016-06-01

    Full Text Available Zuxun Cai Department of Thoracic Surgery, Henan Provincial Chest Hospital, Zhengzhou City, People’s Republic of China Objective: To investigate the relationship between serum carcinoembryonic antigen (CEA level and epidermal growth factor receptor (EGFR gene mutations in non-small-cell lung cancer (NSCLC patients and to analyze the influence of CEA level on postoperative survival time in lung cancer patients. Methods: A total of 296 patients who were treated in Thoracic Surgery Department of Henan Provincial Chest Hospital from September 2011 to September 2013 were recruited. The level of tumor markers, such as CEA, was determined before the surgery, and EGFR gene mutations were detected after surgery. Thereby, the relationship between tumor makers, including CEA, and EGFR mutation and its influence on prognosis could be investigated. Results: Among 296 patients, the positive rate of EGFR gene mutation was 37.84% (112/296; the mutation occurred more frequently in nonsmokers, adenocarcinoma patients, women, and patients aged <60 years (P<0.05. Both tumor markers and chemosensitivity indicators were related to the profile of EGFR mutations. Elevated squamous cell carcinoma and Cyfra21-1 as well as positively expressed ERCC1 were more common in patients with wild-type EGFR (P<0.05, whereas increased CEA level was observed more frequently in patients with EGFR gene mutation (P=0.012. The positive rate of EGFR gene mutations was higher as the serum CEA level increased, that is, the positive rate in patients with serum CEA level <5, 5–20, and >20 µg/L was 39.81%, 45.32%, and 65.47%, respectively (P=0.004. Logistic regression analysis showed that CEA level was an independent factor in predicting EGFR gene mutations, and serum CEA level was also an independent factor in affecting the prognosis of NSCLC patients, as the overall 2-year survival rate was 73.86% in elevated CEA group and 86.43% in normal group (P<0.01. Conclusion: The prognosis of

  4. Prostate-specific antigen nadir after high-dose-rate brachytherapy predicts long-term survival outcomes in high-risk prostate cancer

    Science.gov (United States)

    Satoh, Takefumi; Ishiyama, Hiromichi; Tabata, Ken-ichi; Komori, Shouko; Sekiguchi, Akane; Ikeda, Masaomi; Kurosaka, Shinji; Fujita, Tetsuo; Kitano, Masashi; Hayakawa, Kazushige; Iwamura, Masatsugu

    2016-01-01

    Purpose To evaluate the prognostic value of prostate-specific antigen nadir (nPSA) after high-dose-rate (HDR) brachytherapy in clinically non-metastatic high-risk prostate cancer patients. Material and methods Data from 216 patients with high-risk or locally advanced prostate cancer who underwent HDR brachytherapy and external beam radiation therapy with long-term androgen deprivation therapy (ADT) between 2003 and 2008 were analyzed. The median prostate-specific antigen (PSA) level at diagnosis was 24 ng/ml (range: 3-338 ng/ml). The clinical stage was T1c-2a in 55 cases (26%), T2b-2c in 48 (22%), T3a in 75 (35%), and T3b-4 in 38 (17%). The mean dose to 90% of the planning target volume was 6.3 Gy/fraction of HDR brachytherapy. After 5 fractions, external beam radiation therapy with 10 fractions of 3 Gy was administered. All patients initially underwent neoadjuvant ADT for at least 6 months, and adjuvant ADT was continued for 36 months. The median follow-up was 7 years from the start of radiotherapy. Results The 7-year PSA relapse-free rate among patients with a post-radiotherapy nPSA level of ≤ 0.02 ng/ml was 94%, compared with 23% for patients with higher nPSA values (HR = 28.57; 95% CI: 12.04-66.66; p < 0.001). Multivariate analysis revealed that the nPSA value after radiotherapy was a significant independent predictor of biochemical failure, whereas pretreatment predictive values for worse biochemical control including higher level of initial PSA, Gleason score ≥ 8, positive biopsy core rate ≥ 67%, and T3b-T4, failed to reach independent predictor status. The 7-year cancer-specific survival rate among patients with a post-radiotherapy nPSA level of ≤ 0.02 ng/ml was 99%, compared with 82% for patients with higher nPSA values (HR = 32.25; 95% CI: 3.401-333.3; p = 0.002). Conclusions A post-radiotherapy nPSA value of ≤ 0.02 ng/ml was associated with better long-term biochemical tumor control even if patients had pretreatment predictive values for worse

  5. Breast Cancer Heterogeneity Examined by High-Sensitivity Quantification of PIK3CA, KRAS, HRAS, and BRAF Mutations in Normal Breast and Ductal Carcinomas.

    Science.gov (United States)

    Myers, Meagan B; Banda, Malathi; McKim, Karen L; Wang, Yiying; Powell, Michael J; Parsons, Barbara L

    2016-04-01

    Mutant cancer subpopulations have the potential to derail durable patient responses to molecularly targeted cancer therapeutics, yet the prevalence and size of such subpopulations are largely unexplored. We employed the sensitive and quantitative Allele-specific Competitive Blocker PCR approach to characterize mutant cancer subpopulations in ductal carcinomas (DCs), examining five specific hotspot point mutations (PIK3CA H1047R, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E). As an approach to aid interpretation of the DC results, the mutations were also quantified in normal breast tissue. Overall, the mutations were prevalent in normal breast and DCs, with 9/9 DCs having measureable levels of at least three of the five mutations. HRAS G12D was significantly increased in DCs as compared to normal breast. The most frequent point mutation reported in DC by DNA sequencing, PIK3CA H1047R, was detected in all normal breast tissue and DC samples and was present at remarkably high levels (mutant fractions of 1.1 × 10(-3) to 4.6 × 10(-2)) in 4/10 normal breast samples. In normal breast tissue samples, PIK3CA mutation levels were positively correlated with age. However, the PIK3CA H1047R mutant fraction distributions for normal breast tissues and DCs were similar. The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells. PMID:27108388

  6. Breast Cancer Heterogeneity Examined by High-Sensitivity Quantification of PIK3CA, KRAS, HRAS, and BRAF Mutations in Normal Breast and Ductal Carcinomas12

    Science.gov (United States)

    Myers, Meagan B.; Banda, Malathi; McKim, Karen L.; Wang, Yiying; Powell, Michael J.; Parsons, Barbara L.

    2016-01-01

    Mutant cancer subpopulations have the potential to derail durable patient responses to molecularly targeted cancer therapeutics, yet the prevalence and size of such subpopulations are largely unexplored. We employed the sensitive and quantitative Allele-specific Competitive Blocker PCR approach to characterize mutant cancer subpopulations in ductal carcinomas (DCs), examining five specific hotspot point mutations (PIK3CA H1047R, KRAS G12D, KRAS G12V, HRAS G12D, and BRAF V600E). As an approach to aid interpretation of the DC results, the mutations were also quantified in normal breast tissue. Overall, the mutations were prevalent in normal breast and DCs, with 9/9 DCs having measureable levels of at least three of the five mutations. HRAS G12D was significantly increased in DCs as compared to normal breast. The most frequent point mutation reported in DC by DNA sequencing, PIK3CA H1047R, was detected in all normal breast tissue and DC samples and was present at remarkably high levels (mutant fractions of 1.1 × 10− 3 to 4.6 × 10− 2) in 4/10 normal breast samples. In normal breast tissue samples, PIK3CA mutation levels were positively correlated with age. However, the PIK3CA H1047R mutant fraction distributions for normal breast tissues and DCs were similar. The results suggest PIK3CA H1047R mutant cells have a selective advantage in breast, contribute to breast cancer susceptibility, and drive tumor progression during breast carcinogenesis, even when present as only a subpopulation of tumor cells. PMID:27108388

  7. Interaction of serologically defined colon cancer antigen-3 with Arf6 and its predominant expression in the mouse testis.

    Science.gov (United States)

    Sakagami, Hiroyuki; Hara, Yoshinobu; Fukaya, Masahiro

    2016-09-01

    ADP ribosylation factor 6 (Arf6) is a small GTPase that regulates endosomal trafficking and actin cytoskeleton remodeling. Here, we identified the serologically defined colon antigen-3 (SDCCAG3) as an Arf6-interacting protein by yeast two-hybrid screening with a constitutively active Arf6 mutant. SDCCAG3 interacts specifically with Arf6 among the Arf family members through its 101  C-terminal amino acids. SDCCAG3 is expressed most intensely in the testis at the mRNA and protein levels. In the testis, SDCCAG3 is expressed in spermatocytes and spermatids. We also show that full-length SDCCAG3, but not a mutant lacking the ability to interact with Arf6, is recruited to the midbody during cytokinesis when expressed exogenously in HeLa cells. These findings suggest that SDCCAG3 might function in endosomal trafficking downstream of Arf6. PMID:27373827

  8. Analysis of DNA-chip and antigen-chip data: studies of cancer, stem cells and autoimmune diseases

    Science.gov (United States)

    Domany, Eytan

    2005-07-01

    Biology has undergone a revolution during the past decade. Deciphering the human genome has opened new horizons, among which the advent of DNA microarrays has been perhaps the most significant. These miniature measuring devices report the levels at which tens of thousands of genes are expressed in a collection of cells of interest (such as tissue from a tumor). I describe here briefly this technology and present an example of how analysis of data obtained from such high throughput experiments provides insights of possible clinical and therapeutic relevance for Acute Lymphoblastic Leukemia. Next, I describe how gene expression data is used to deduce a new design principle, " Just In Case", used by stem cells. Finally I briefly review a different novel technology, of antigen chips, which provide a fingerprint of a subject's immune system and may become a predictive clinical tool. The work reviewed here was done in collaboration with numerous colleagues and students.

  9. A nomogram based on age,prostate-specific antigen level,prostate volume and digital rectal examination for predicting risk of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Ping Tang; Hui Chen; Matthew Uhlman; Yu-Rong Lin; Xiang-Rong Deng; Bin Wang; Wen-Jun Yang; Ke-Ji Xie

    2013-01-01

    Nomograms for predicting the risk of prostate cancer developed using other populations may introduce sizable bias when applied to a Chinese cohort.In the present study,we sought to develop a nomogram for predicting the probability of a positive initial prostate biopsy in a Chinese population.A total of 535 Chinese men who underwent a prostatic biopsy for the detection of prostate cancer in the past decade with complete biopsy data were included.Stepwise logistic regression was used to determine the independent predictors of a positive initial biopsy.Age,prostate-specific antigen (PSA),prostate volume (PV),digital rectal examination (DRE) status,% free PSA and transrectal ultrasound (TRUS) findings were included in the analysis.A nomogram model was developed that was based on these independent predictors to calculate the probability of a positive initial prostate biopsy.A receiver-operating characteristic curve was used to assess the accuracy of using the nomogram and PSA levels alone for predicting positive prostate biopsy.The rate for positive initial prostate biopsy was 41.7% (223/535).The independent variables used to predict a positive initial prostate biopsy were age,PSA,PV and DRE status.The areas under the receiver-operating characteristic curve for a positive initial prostate biopsy for PSA alone and the nomogram were 79.7% and 84.8%,respectively.Our results indicate that the risk of a positive initial prostate biopsy can be predicted to a satisfactory level in a Chinese population using our nomogram.The nomogram can be used to identify and Counsel patients who should consider a prostate biopsy,ultimately enhancing accuracy in diagnosing prostate cancer.

  10. Dose-response association between hepatitis B surface antigen levels and liver cancer risk in Chinese men and women.

    Science.gov (United States)

    Yang, Yang; Gao, Jing; Li, Hong-Lan; Zheng, Wei; Yang, Gong; Zhang, Wei; Ma, Xiao; Tan, Yu-Ting; Rothman, Nathaniel; Gao, Yu-Tang; Chow, Wong-Ho; Shu, Xiao-Ou; Xiang, Yong-Bing

    2016-07-15

    We aimed at evaluating the risk of liver cancer in different levels of HBsAg among Chinese men and women. We carried out a nested case-control study including 363 cases and 3,511 controls in two population-based cohorts in Shanghai. Plasma samples collected at enrollment were quantified for HBsAg levels using the Architect QT assay. Conditional logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for liver cancer, with adjustment for potential confounders. HBsAg was detected in 6.29% of control subjects overall (7.02% in men and 4.98% in women). HBsAg levels were positively associated with liver cancer risk in a dose-response manner (ptrend  < 0.001). Such association showed a significant gender disparity. With increasing levels of HBsAg, liver cancer risks rose more steeply in men than in women. In men, the adjusted ORs increased from 7.27 (95% CI: 3.49-15.15) at the lowest detectable level of HBsAg (5-9 IU/ml) to 7.16 (95% CI: 3.21-15.96), 34.30 (95% CI: 16.94-69.44), and 47.33 (95% CI: 23.50-95.34) at the highest level of HBsAg (≥1,000 IU/ml) compared to those negative for HBsAg. The corresponding ORs were much lower for women, from 1.37 (95% CI: 0.25-7.47), 3.81 (95% CI: 1.09-13.28), 7.36 (95% CI: 2.41-22.46) and 16.86 (95% CI: 7.24-39.27), respectively. HBsAg quantification has potential to distinguish individuals at different risks of liver cancer. Men with the lowest detectable level of HBsAg should still pay attention to their liver cancer risks, but those with a higher level may be given a higher priority in future liver cancer surveillance program. PMID:26990915

  11. High resolution human leukocyte antigen (HLA class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

    Directory of Open Access Journals (Sweden)

    Barquera Rodrigo

    2009-02-01

    Full Text Available Abstract Background The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA alleles play an important role in immunity (cellular immunity and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. Methods We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. Results HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031. HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670. DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, p = 0.00001. Conclusion Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the

  12. High resolution human leukocyte antigen (HLA) class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

    International Nuclear Information System (INIS)

    The development of breast cancer is multifactorial. Hormonal, environmental factors and genetic predisposition, among others, could interact in the presentation of breast carcinoma. Human leukocyte antigen (HLA) alleles play an important role in immunity (cellular immunity) and may be important genetic traits. HLAAllele-specific interaction has not been well established. Recently, several studies had been conducted in order to do so, but the results are controversial and in some instances contradictory. We designed a case-control study to quantify the association of HLA class I and II genes and breast cancer. HLA typing was performed by high resolution sequence-specific oligotyping after DNA amplification (PCR-SSOP) of 100 breast cancer Mexican mestizo patients and 99 matched healthy controls. HLA-A frequencies that we were able to observe that there was no difference between both groups from the statistical viewpoint. HLA-B*1501 was found three times more common in the case group (OR, 3.714; p = 0.031). HLA-Cw is not a marker neither for risk, nor protection for the disease, because we did not find significant statistical differences between the two groups. DRB1*1301, which is expressed in seven cases and in only one control, observing an risk increase of up to seven times and DRB1*1602, which behaves similarly in being present solely in the cases (OR, 16.701; 95% CI, 0.947 – 294.670). DQ*0301-allele expression, which is much more common in the control group and could be protective for the presentation of the disease (OR, 0.078; 95% CI, 0.027–0.223, p = 0.00001). Our results reveal the role of the MHC genes in the pathophysiology of breast cancer, suggesting that in the development of breast cancer exists a disorder of immune regulation. The triggering factor seems to be restricted to certain ethnic groups and certain geographical regions since the relevant MHC alleles are highly diverse. This is the first study in Mexican population where high resolutions HLA

  13. Early diagnosis of prostate cancer using free/total prostate specific antigen ratio: a population based screening data

    Institute of Scientific and Technical Information of China (English)

    LingZhang; Guo-YIJi; Xiao-MengLi; Wei-HuaWang; Hong-WenGao; Yu-ZhuoPan; Hong-JunWang; KuwaharaMasaaki; Xue-JianZhao

    2004-01-01

    Aim: To evaluate the use of free/total prostate specific antig enratio (fPSA/tPSA ratio) in improving the early diagnosis of prostate cancer. Methods: The fPSA/tPSA ratio in the serum was analyzed in 187 men with tPSA ranging between 4.0 and 20.0μg/L. Allof them underwent ultrasound guided sextant prostatic biopsy.The results were calculated by SPSS 10.0 software.

  14. Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy

    Directory of Open Access Journals (Sweden)

    Hou Wei

    2008-05-01

    Full Text Available Abstract Background- Data exist that demonstrate isoflavones' potent antiproliferative effects on prostate cancer cells. We evaluated the efficacy of isoflavone in patients with PSA recurrent prostate cancer after prior therapy. We postulated that isoflavone therapy would slow the rate of rise of serum PSA. Methods- Twenty patients with rising PSA after prior local therapy were enrolled in this open-labeled, Phase II, nonrandomized trial (Trial registration # NCT00596895. Patients were treated with soy milk containing 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months. Serum PSA, testosterone, lipids, isoflavone levels (genistein, daidzein, and equol, and quality of life (QOL were measured at various time points from 0 to 12 months. PSA outcome was evaluated. Results- Within the mixed regression model, it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period (p = 0.05. Specifically, the slope of PSA after study entry was significantly lower than that before study entry in 6 patients and the slope of PSA after study entry was significantly higher than before study entry in 2 patients. For the remaining 12 patients, the change in slope was statistically insignificant. Nearly two thirds of the patients were noted to have significant levels of free equol in their serum while on therapy. Conclusion- Dietary intervention with isoflavone supplementation may have biologic activity in men with biochemical recurrent prostate cancer as shown by a decline in the slope of PSA. This study may lend support to the literature that nutritional supplements have biologic activity in prostate cancer and therefore, further studies with these agents in randomized clinical trials should be encouraged.

  15. Correlation between Tc-99m HMDP bone scintigrams and prostate-specific antigen in prostatic cancer patients

    International Nuclear Information System (INIS)

    To evaluate the clinical utility of prostate-specific antigen (PSA), 32 patients with prostatic carcinoma (PCA) and 13 patients without PCA underwent PSA measurement (normal, 0-4 ng/mL) at the time of bone scintigraphy. All patients without PCA had normal PSA values. The results in the 32 patients with PCA were divided into two groups of 16 each: (1) abnormal PSA levels and (2) normal PSA levels. Twelve patients in group 2 had no skeletal metastasis, one had regression of skeletal metastases, and three had unchanged bone lesions in a 6-12-month period. In group 1, 14 patients' bone images showed positive metastases; two patients with negative bone scans had had recent digital rectal or TUR. The authors conclude that PSA measurement may enhance bone imaging interpretation and provide valuable clinical monitoring of PCA. In a patient with a positive bone scan and an unknown primary, PSA measurement may determine definitely whether the metastasis originated from PCA

  16. 甘氨双唑钠(CMNa)联合紫杉醇卡铂化疗对中晚期卵巢癌术后CA125升高的影响%Effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in post-operation advanced ovarian cancer patients

    Institute of Scientific and Technical Information of China (English)

    Kaijian Lei; Yuming Jia; Jing Wang; Yiping Du

    2008-01-01

    Objective: To investigate the effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in post-operation advanced ovarian cancer patients. Methods: The effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in 25 post-operation advanced ovarian cancer patients were retrospectively analyzed and compared with those in 20 control cases. Results: After 1 cycle of chemotherapy, CA125 levels had decreasing trend compared with control, but had no statistical significance. While after two cycles of chemotherapy, CA125 levels decreased more rapidly compared with those in control. Side effects in two groups were alike. Conclusion: CMNa combined with paclitaxel and carboplatine has a stronger effect on the decrease of elevated CA125 levels than paclitaxel and carboplatin have in the treatment of post-operation advanced ovarian cancer, which indicates that CMNa has chemo-sensitizing effects on chemotherapy of paclitaxel and carboplatin.

  17. Clusterin silencing sensitizes pancreatic cancer MIA-PaCa-2 cells to gmcitabine via regulation of NF-kB/Bcl-2 signaling.

    Science.gov (United States)

    Xu, Miao; Chen, Xiumei; Han, Yanling; Ma, Chunqing; Ma, Lin; Li, Shirong

    2015-01-01

    Clusterin (CLU) is known as a multifunctional protein involved in a variety of physiological processes including lipid transport, epithelial cell differentiation, tumorigenesis, and apoptosis. Our recent study has demonstrated that knockdown of clusterin sensitizes pancreatic cancer cell lines to gmcitabine treatment. However the details of this survival mechanism remain undefined. Of the various downstream targets of CLU, we examined activation of the NF-kB transcription factor and subsequent transcriptional regulation of BCL-2 gene in pancreatic cancer cell MIA-PaCa-2. The MIA-PaCa-2 cells were transfected with an antisense oligonucleotide (ASO) against clusterin, which led to a decreased protein level of the antiapoptotic gene BCL-2. Furthermore, inhibition of CLU decreased the function of NF-kB, which is capable of transcriptional regulation of the BCL-2 gene. Inhibiting this pathway increased the apoptotic effect of gmcitabine chemotherapy. Re-activated NF-kB resulted in attenuation of ASO-induced effects, followed by the bcl-2 upregulation, and bcl-2 re-inhibition resulted in attenuation of Re-activated NF-kB -induced effects. Animals injected with ASO CLU in MIA-PaCa-2 cells combined with gmcitabine treatment had fewer tumors than gmcitabine or ASO CLU alone. These findings suggest that knockdown of CLU sensitized MIA-PaCa-2 cells to gmcitabine chemotherapy through modulating NF-Kb/bcl-2 pathway. PMID:26550158

  18. Induction of an antitumor response using dendritic cells transfected with DNA constructs encoding the HLA-A*02:01-restricted epitopes of tumor-associated antigens in culture of mononuclear cells of breast cancer patients.

    Science.gov (United States)

    Sennikov, Sergey Vital'evich; Shevchenko, Julia Alexandrovna; Kurilin, Vasilii Vasil'evich; Khantakova, Julia Nikolaevna; Lopatnikova, Julia Anatol'evna; Gavrilova, Elena Vasil'evna; Maksyutov, Rinat Amirovich; Bakulina, Anastasiya Yur'evna; Sidorov, Sergey Vasil'evich; Khristin, Alexander Alexandrovich; Maksyutov, Amir Zakievich

    2016-02-01

    Advances in oncoimmunology related to the definition of the basic mechanisms of the formation of antitumor immune response, as well as the opening of tumor-associated antigens recognized by immune cells, allowed to start developing ways to influence the effector cells of the immune system to generate effective antitumor cytotoxic response. We investigated the possibility to stimulate an antitumor response in a culture of mononuclear cells of breast cancer patients by dendritic cells transfected with HLA-A*02:01-restricted DNA constructs. We isolated dendritic cells from peripheral blood monocytes and delivered our constructs to these cells by magnetic transfection. Additionally, a series of experiments with loading of dendritic cells with autologous tumor cell lysate antigens was conducted. We have shown that dendritic cells transfected with the HLA-A*02:01-restricted DNA constructs are effective in inducing an antitumor response in a culture of mononuclear cells of breast cancer patients. Dendritic cells transfected with DNA constructor dendritic cells loaded with lysate antigens revealed a comparable stimulated cytotoxic response of mononuclear cells to these two ways of antigen delivery. We conclude that using DNA constructs in conjunction with patient stratification by HLA type allows the application of transfected DCs as an effective method to stimulate antitumor immunity in vitro. PMID:26590947

  19. Carcino-Embryonic Antigen

    International Nuclear Information System (INIS)

    Tumour marker analysis has increased our understanding of the presence of tumours in the body. Carcino-embryonic antigen, CEA, is one of the best studied tumour markers and has proved an ideal diagnostic adjuvant. It has helped in quantifying the amount of disease present in a patient and thence to make accurate prognosis on the various diagnosed ailments. At UCH, it is observed that there is an increase in cancer related ailments and therefore the need for early diagnosis is more compelling in our environment to mitigate future cost of managing advanced manifestation

  20. CaPTC Biennial Meetings

    Science.gov (United States)

    CaPTC hosts the 'Biennial Science of Global Prostate Cancer Disparities in Black Men' conference to address the growing global public health problem of prostate cancer among Black men in industrialized and developing countries.

  1. Investigating the Effects of Regular Resistance Training and Prostatic Massage on Proinflammatory Markers and Serum Prostate-Specific Antigen Levels in Males with Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Fathollahi Shoorabeh

    2016-01-01

    Full Text Available Background Prostate cancer (PC is one of the most common cancers worldwide. Some studies support that chronic inflammation of prostate tissue plays a role in the development of PC. A variety of growth factors and cytokines may lead to proinflammatory processes within the prostate. Objectives The aim of the present study was to investigate the effects of eight weeks of regular resistance training and prostatic massage on proinflammatory markers CRP, IL-6, TNF-α, and IL-10 and serum prostate-specific antigen (PSA levels in males with PC. Patients and Methods Forty-five patients with PC were selected for this study. They were randomized into either the resistance training intervention group (n = 15, the massage intervention group (n = 15, or the control group (n = 15. Resistance-training patients participated in resistance training for eight weeks, and massage was performed for six weeks on the massage group. Repeated measures analysis of variance (ANOVA was used to analyze the data (P ≤ 0.05. Results In the resistance training group, IL-10 levels significantly increased after four (P = 0.055 and eight weeks (P = 0.000. Four and eight weeks of resistance training showed a significant reduction in PSA, CRP, IL-6, and TNF-α levels (P < 0.05. Patients of massage intervention showed an increase in IL-10 after four (P = 0.045 and six weeks (P = 0.005. In addition, four and six weeks of massage intervention showed a significant reduction in PSA, CRP, IL-6, and TNF-α levels (P < 0.05. Conclusions Regular resistance training and prostatic massage can improve proinflammatory markers and PSA levels in men with PC.

  2. Immunohistochemical expression of carcinoembryonic antigen-related cell adhesion molecules 5, CEACAM6, and SLC7A5: Do they aid in predicting the response to neo-adjuvant chemotherapy in locally advanced breast cancer?

    OpenAIRE

    Anju Bansal; Mukesh Garg; Chintamani Chintamani; Sunita Saxena

    2014-01-01

    Context: Neo-adjuvant chemotherapy (NACT) has become an integral part of multimodality treatment for locally advanced breast cancer (LABC) worldwide. Predictors of therapeutic response to NACT are lacking. Whether carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) like CEACAM5 and CEACAM6 can act as a predictor of response to therapy is unclear. SLC7A5 gene in humans encodes a large neutral amino acid transporter protein, which has an essential role in tumor cell growth and su...

  3. Expression of Vicia villosa agglutinin (VVA)-binding glycoprotein in primary breast cancer cells in relation to lymphatic metastasis: is atypical MUC1 bearing Tn antigen a receptor of VVA?

    Science.gov (United States)

    Kawaguchi, Takanori; Takazawa, Hiroshi; Imai, Shunsuke; Morimoto, Junji; Watanabe, Takanori; Kanno, Masahiko; Igarashi, Seiji

    2006-07-01

    Aberrant carbohydrate expression frequently occurs in breast cancer and may endow cells with metastatic potential. Here we first studied the relationship between expression of Vicia villosa agglutinin (lectin) (VVA)-binding carbohydrates and aggressive breast cancer. We then investigated the molecular characteristics of these glycoproteins and compared them with those of glycoproteins recognized by the mouse anti-Tn monoclonal antibody (MAb) HB-Tn1. Histochemical studies of samples from 322 cases of invasive ductal carcinoma demonstrated that VVA-binding carbohydrate expression correlated with tumor stage, lymphatic invasion, and lymph node metastasis (p=0.0385, p=0.0019, and p=0.0430. respectively). Western blotting analysis of frozen materials from 39 cases, under denaturing and reducing conditions, revealed that the major cancer cell-specific VVA-binding proteins were molecules of about 30, 33, and >200 kDa. Cases expressing the approximately 33 kDa molecule had significant lymphatic invasion more frequently than did cases not expressing this molecule (p=0.0076). Binding of VVA to the approximately 30 and approximately 33 kDa molecules was completely lost by preincubation of VVA with 1 mM Tn antigen (N-acetylgalactosamine alpha1-O-serine). The VVA-binding molecules appeared to react with VU-3C6 anti-MUC1 MAb. Expression of HB-Tn1 in breast cancer cells showed significant correlation with expression of VVA-binding carbohydrate(s) (p<0.0001) but HB-Tn1 reactivity was not clearly related to breast cancer aggressiveness. Because anti-Tn MAbs bound to Tn antigen clusters, we concluded that atypical MUC1 bearing the noncluster form of Tn antigen is implicated in aggressive growth of primary breast cancer cells, particularly in lymphatic metastasis. PMID:16752227

  4. The possible role of the tumour necrosis factor polymorphisms and human leucocyte antigens in the development of prostate cancer.

    Science.gov (United States)

    Stingl Jankovic, K; Hudolin, T; Kastelan, Z; Zunec, R; Grubic, Z

    2016-06-01

    The cause of prostate cancer (PC), one of the most common cancers found among ageing men, remains unclear, but genetic predisposition is believed to play a major role in its aetiology. The aim of the study was to examine HLA genes polymorphism and TNF polymorphisms in PC development. Patients diagnosed with PC (N = 113) and 150 healthy individuals were tested for HLA-A, HLA-B and HLA-DRB1 genes and for TNFa, TNFb and TNFd microsatellites. The comparison of patients and controls revealed a positive association of HLA-DRB1*12, TNFa2 and TNFb5, and a negative association of HLA-DRB1*13 and TNFb4 with PC. A division of patients into groups according to age, pre-operative PSA level, Gleason score (GS) and involvement of prostatic capsule, seminal vesicles or bladder neck and perineural invasion of PC demonstrated the following: a positive correlation of HLA-DRB1*12 and a negative correlation of HLA-DRB1*13 with younger patients ( 7 and the positive association of prostatic capsule, seminal vesicles, bladder neck and perineural invasion of PC; TNFb4 allele's negative association with older patients displaying higher PSA levels, higher GS and positive surrounding tissue involvement; positive association of TNFb5 allele for both older and younger patients. Investigation of HLA genes and TNF microsatellites demonstrated a possible role of HLA-DRB1 and TNF regions in PC aetiology. PMID:27102235

  5. TCRs Used in Cancer Gene Therapy Cross-React with MART-1/Melan-A Tumor Antigens via Distinct Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Borbulevych, Oleg Y.; Santhanagopolan, Sujatha M.; Hossain, Moushumi; Baker, Brian M. (Notre)

    2013-09-18

    T cells engineered to express TCRs specific for tumor Ags can drive cancer regression. The first TCRs used in cancer gene therapy, DMF4 and DMF5, recognize two structurally distinct peptide epitopes of the melanoma-associated MART-1/Melan-A protein, both presented by the class I MHC protein HLA-A*0201. To help understand the mechanisms of TCR cross-reactivity and provide a foundation for the further development of immunotherapy, we determined the crystallographic structures of DMF4 and DMF5 in complex with both of the MART-1/Melan-A epitopes. The two TCRs use different mechanisms to accommodate the two ligands. Although DMF4 binds the two with a different orientation, altering its position over the peptide/MHC, DMF5 binds them both identically. The simpler mode of cross-reactivity by DMF5 is associated with higher affinity toward both ligands, consistent with the superior functional avidity of DMF5. More generally, the observation of two diverging mechanisms of cross-reactivity with the same Ags and the finding that TCR-binding orientation can be determined by peptide alone extend our understanding of the mechanisms underlying TCR cross-reactivity.

  6. Tales of Antigen Evasion from CAR Therapy.

    Science.gov (United States)

    Sadelain, Michel

    2016-06-01

    Both T cells bearing chimeric antigen receptors and tumor-specific antibodies can successfully target some malignancies, but antigen escape can lead to relapse. Two articles in this issue of Cancer Immunology Research explore what effective countermeasures may prevent it. Cancer Immunol Res; 4(6); 473-473. ©2016 AACRSee articles by Zah et al., p. 498, and Rufener et al., p. 509. PMID:27252092

  7. Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens.

    Science.gov (United States)

    Shigeta, Mika; Saiki, Minoru; Tsuruta, Daisuke; Ohata, Chika; Ishii, Norito; Ono, Fumitake; Hamada, Takahiro; Dainichi, Teruki; Furumura, Minao; Zone, John J; Karpati, Sarolta; Sitaru, Cassian; Hashimoto, Takashi

    2012-12-01

    Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten-sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme-linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti-endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten-sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten-sensitive enteropathy and no DH-specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH. PMID:22963165

  8. Complete Biochemical (Prostate-specific Antigen) Response to Sipuleucel-T With Enzalutamide in Castration-resistant Prostate Cancer: A Case Report With Implications for Future Research

    Science.gov (United States)

    Graff, Julie N.; Drake, Charles G.; Beer, Tomasz M.

    2016-01-01

    OBJECTIVE To describe the case of a patient with castration-resistant, metastatic prostate cancer who achieved a complete and durable biochemical response after treatment with sipuleucel-T while continuing with enzalutamide and to explore the immunologic basis for such a response. MATERIALS AND METHODS We obtained serial prostate-specific antigen (PSA) measurements and bone scans to assess the patient’s response to enzalutamide followed by the addition of sipuleucel-T. Using preclinical and clinical data, we describe his response through known immunobiologic mechanisms. RESULTS This patient’s PSA level became undetectable during treatment with enzalutamide and began to increase again after 14 months. He opted for treatment with sipuleucel-T, while continuing with the enzalutamide. This resulted in another complete PSA response 6 months after exposure to sipuleucel-T. CONCLUSION Sipuleucel-T typically does not produce significant PSA reductions, and, to the best of our knowledge, only 1 previous report of a durable complete PSA response in a patient with metastatic disease has been published. The timing of this response supports an immune mechanism. The biologic rationale for the combination, coupled with the clinical result observed in our patient, provides a basis for studies of the combination of sipuleucel-T and enzalutamide. PMID:23374810

  9. Evaluation of the use of decision-support software in carcino-embryonic antigen (CEA-based follow-up of patients with colorectal cancer

    Directory of Open Access Journals (Sweden)

    Verberne Charlotte J

    2012-03-01

    Full Text Available Abstract Background The present paper is a first evaluation of the use of "CEAwatch", a clinical support software system for surgeons for the follow-up of colorectal cancer (CRC patients. This system gathers Carcino-Embryonic Antigen (CEA values and automatically returns a recommendation based on the latest values. Methods Consecutive patients receiving follow-up care for CRC fulfilling our in- and exclusion criteria were identified to participate in this study. From August 2008, when the software was introduced, patients were asked to undergo the software-supported follow-up. Safety of the follow-up, experiences of working with the software, and technical issues were analyzed. Results 245 patients were identified. The software-supported group contained 184 patients; the control group contained 61 patients. The software was safe in finding the same amount of recurrent disease with fewer outpatient visits, and revealed few technical problems. Clinicians experienced a decrease in follow-up workload of up to 50% with high adherence to the follow-up scheme. Conclusion CEAwatch is an efficient software tool helping clinicians working with large numbers of follow-up patients. The number of outpatient visits can safely be reduced, thus significantly decreasing workload for clinicians.

  10. The predictive value of serum squamous cell carcinoma antigen in patients with cervical cancer who receive neoadjuvant chemotherapy followed by radical surgery: a single-institute study.

    Directory of Open Access Journals (Sweden)

    Xiong Li

    Full Text Available Neoadjuvant chemotherapy (NACT could affect the levels of squamous cell carcinoma antigen (SCC-Ag. This study evaluates the predictive value of pre- and posttreatment SCC-Ag levels in patients with cervical cancer who were treated with NACT followed by radical surgery.A total of 286 patients with Stage IB1-IIIB squamous cell carcinoma of the uterine cervix who were treated with NACT followed by radical hysterectomy were analyzed retrospectively. The relationship between SCC-Ag levels, the clinicopathologic parameters, the response to NACT and the three-year survival rate was investigated.The levels of SCC-Ag were elevated (>3.5 ng/mL in 43.8% of patients before NACT, and 13.0% of patients after NACT. Pre- and posttreatment levels of SCC-Ag correlated with the response to NACT (P = 0.010, and P3.5 ng/mL (P3.5 ng/mL indicated a poor response to NACT and a higher risk of lymph node metastases. Elevated posttreatment levels of SCC-Ag were correlated with poor DFS and OS.

  11. 78 FR 50425 - Prospective Grant of Exclusive License: Development of Brachyury Tumor Associated Antigens as...

    Science.gov (United States)

    2013-08-19

    ... Brachyury Tumor Associated Antigens as Cancer Vaccines for Colorectal Cancer AGENCY: National Institutes of... INFORMATION: Cancer immunotherapy is a recent approach where tumor associated antigens (TAAs), which are... employed to generate a tumor-specific immune response. Specifically, these antigens serve as targets...