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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. New mucin-like cancer-associated antigens (CA M 26, CA M 29 and CA 549) and a new proliferation marker (TPS) in patients with primary or advanced breast cancer.

    Science.gov (United States)

    Locker, G J; Mader, R M; Braun, J; Sieder, A E; Marosi, C; Rainer, H; Jakesz, R; Steger, G G

    1995-01-01

    In patients with breast cancer no tumor markers giving satisfactory results have been found yet. The aim of our investigation was to compare the usefulness of newly developed tumor markers with the most common used carcinoembryonic antigen and cancer antigen (CA) 15-3. We evaluated the concentrations of carcinoma-associated antigen (CA) 549, carcinoma-associated mucin antigen (CA M) 26 and CA M 29, and the proliferation markers tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS) in 84 breast cancer patients with disease progression and in 69 patients with no evidence of disease after surgery for breast cancer. Using receiver-operating characteristic curves (ROC curves) we were able to demonstrate increased sensitivity and specificity of all tested tumor markers in patients with metastatic disease compared with local disease. In our investigation TPA is superior to TPS in all disease states. In local disease, none of the tested markers shows satisfying results. In metastatic disease, the new mucin markers CA M 26 and CA M 29 show slightly better results than CA 15-3 although their ROC curves are nearly congruent. CA 549 is exceeded by the other mucin markers. The best results in this investigation were obtained with CA M 29. The overall results concerning the detection of small tumor masses (i.e. local disease) were unsatisfactory.

  3. 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...

  4. 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

  5. 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

  6. A comparative study of mucin-like carcinoma-associated antigen (MCA), CA 125, CA 19-9 and CEA in patients with ovarian cancer.

    Science.gov (United States)

    Koelbl, H; Schieder, K; Neunteufel, W; Bieglmayer, C

    1989-01-01

    A mucin-like carcinoma associated antigen (MCA), which is recognized by the monoclonal antibody b-12, was found to be elevated in sera of breast cancer patients. Since an immunohistochemical reaction of the monoclonal antibody b-12 was found in epithelial tumors of the ovary we investigated MCA serum levels in 50 patients with ovarian cancer (mean age 59 years, range 31-81 years). In addition, CA 125, CA 19-9 and CEA were determined to compare sensitivity, specificity and the predictive value of the positive test of each parameter used in this study. Blood samples were obtained in 20 patients with progressive disease and in 30 patients during disease free intervals. The MCA serum levels of patients with progressive ovarian cancer (mean +/- SD: 14.7 +/- 14.6 U/ml) did not differ significantly from those of patients in remission (mean +/- SD: 8.2 +/- 5.3 U/ml) or from values of a healthy control group (mean +/- SD: 7.7 +/- 3.8 U/ml, n = 70). Women with progressive disease displayed significantly higher CA 125 (p less than 0.0001) and CEA (p less than 0.0063) serum levels than patients in remission. No significant difference was found for CA 19-9 in patients with ovarian cancer, irrespective of the clinical status. Considering marker surge and tumor progression, the highest sensitivity was found for CA 125 (75%). Sensitivities of the other markers were significantly lower and reached only 25-35%. The predictive value of elevated marker levels as well as specificity of the marker substances were similar. Sensitivity could be extended to 90% if elevation of CA 125, CA 19-9, CEA and MCA were taken into consideration, however specificity was lowered by using this marker combination.

  7. 血清CA125、CEA水平与宫颈癌相关性分析%Association of serum carcinoembryonic antigen and carbohydrate antigen 125 with cervical cancer

    Institute of Scientific and Technical Information of China (English)

    胡跃华

    2012-01-01

    Objective To analyze the association of serum carcinoembryonic antigen ( CEA )and carbohydrate antigen 125 ( CA125 ) with cervical cancer.Methods 100 patients with cervical cancer who had been treated in our hospital during the period of February 2007 to March 2011 were enrolled into a study group.Serum levels of CEA and CA125 were detected and their assoication with cervical cancer was analyzed; and the levels of these markers were compared with those from 60 non-cervical cancer patients ( control group ).Results Serum levels of CEA and CA125 were higher in the study group than in the control group,with a significant difference between 2 groups ( P< 0.05 ) except for stage Ⅰ cervical cancer.The correlation between CA125 and stages of cervical cancer was greater than that between CEA and cervical cancer ( P< 0.05 ).Conclusions Serum levels of CEA and CA125 are associated with cervical cancer at some degree.CA125 has more diagnostic values than CEA.%目的 分析研究血清CA125(糖链抗原125)、CEA(癌胚抗原)水平与宫颈癌的相关性.方法 将我院从2007年2月至2011年3月收治的100例宫颈癌病患设为实验组,进行血清CA125、CEA水平检测,并与宫颈癌分期相分析,将同期收治的60例非宫颈癌病患设为对照组,对比两组血清CA125、CEA水平.结果 实验组血清CA125、CEA水平均高于对照组,除Ⅰ期宫颈癌数据外,差异有统计学意义(P<0.05);血清CA125与宫颈癌分期的相关性高于血清CEA,差异有统计学意义(P<0.05 ).结论 血清CA125、CEA水平与宫颈癌有一定相关性,检测简单方便,且血清CA125比血清CEA更具诊断价值.

  8. Optofluidic ring resonator sensor for sensitive label-free detection of breast cancer antigen CA15-3 in human serum

    Science.gov (United States)

    Zhu, Hongying; Dale, Paul S.; Fan, Xudong

    2009-05-01

    Breast cancer is the most frequently diagnosed malignancy in women worldwide. Because of its great impact on society, a lot of research funding has been used to develop novel detection tools for aiding breast cancer diagnosis and prognosis. In this work, we demonstrated a simple, fast, and sensitive detection of circulating breast cancer biomarker CA15-3 with opto-fluidic ring resonator (OFRR) sensors. The OFRR sensor employs a thin-walled capillary with wall thickness less than 4 μm. The circular cross section of the capillary forms the optical ring resonator, in which the light circulates in the form of whispering gallery modes (WGMs). The capillary wall is thin enough that the evanescent field of the WGM extends into the capillary core and responds to refractive index changes in the capillary core or close to its interior surface. The WGM spectral position will change when the biomolecules bind to the surface, yielding quantitative and kinetic information about the biomolecule interaction. Here, the direct immunoassay method was employed for the detection of CA15-3 antigen without any signal amplification steps. The sensor performance in both PBS buffer and human serum were investigated, respectively. The experimental detection limit was 5 units/mL in PBS buffer and 30 units/mL for CA15-3 spiked in serum, both of which satisfied clinical diagnosis requirements. The potential use of the OFRR as the point-of-care device for breast cancer detection was tested by measuring the CA15-3 level in blood samples collected from stage IV breast cancer patients and the results were compared with standard clinical test.

  9. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

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

    2015-01-01

    /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...

  10. Cancer testis antigen and immunotherapy

    Directory of Open Access Journals (Sweden)

    Krishnadas DK

    2013-04-01

    Full Text Available Deepa Kolaseri Krishnadas, Fanqi Bai, Kenneth G Lucas Department of Pediatrics, Division of Hematology/Oncology, University of Louisville, KY, USA Abstract: The identification of cancer testis (CT antigens has been an important advance in determining potential targets for cancer immunotherapy. Multiple previous studies have shown that CT antigen vaccines, using both peptides and dendritic cell vaccines, can elicit clinical and immunologic responses in several different tumors. This review details the expression of melanoma antigen family A, 1 (MAGE-A1, melanoma antigen family A, 3 (MAGE-A3, and New York esophageal squamous cell carcinoma-1 (NY-ESO-1 in various malignancies, and presents our current understanding of CT antigen based immunotherapy. Keywords: cancer testis antigens, immunotherapy, vaccine

  11. 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%

  12. 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...

  13. 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)

  14. 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...

  15. Comparison between tissue and serum content of CA 125, CA 19-9, and carcinoembryonic antigen in ovarian tumors.

    Science.gov (United States)

    Breitenecker, G; Neunteufel, W; Bieglmayer, C; Kölbl, H; Schieder, K

    1989-01-01

    Tumor markers CA 125, CA 19-9, and carcinoembryonic antigen (CEA) were detected by immunohistochemistry in paraffin embedded tissue samples obtained from two different locations in 35 ovarian tumors. In addition, serum concentrations of these tumor markers were measured before cytoreductive surgery. The staining reaction was heterogeneous in different parts of the tumor as well as within the parenchyma. Of the marker positive tumors, a staining reaction was observed in both tissue samples in only 10 of 22 cases for CA 125, in eight of 13 cases for CEA, and in three of eight cases for CA 19-9. Eighty-one percent of the patients whose tumor was positive for CA 125 also showed elevated serum levels of this marker. A poor correlation was found between tissue and circulating CA 19-9 levels. CEA was detected in 28% of the tumors and seemed to be valuable only for monitoring in rare cases of ovarian cancer. For purposes of selecting a marker for monitoring of patients with ovarian carcinoma, immunohistochemistry has a predictive value for CA 125 only. In order to better define the marker expressed in a tumor, it is necessary to examine at least two samples of different parts of the malignant tissue.

  16. 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

  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. Antigen-specific active immunotherapy for ovarian cancer

    NARCIS (Netherlands)

    Leffers, N.; Daemen, T.; Helfrich, W.; Boezen, H. M.; Cohlen, B. J.; Melief, Cornelis; Nijman, H. W.

    2010-01-01

    BACKGROUND: Despite advances in chemotherapy, prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce a tumour-antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer. OBJECTIVES: To assess feasibility of antigen-specific ac

  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. 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

  2. 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...

  3. 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.

  4. 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...

  5. 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......

  6. CA19-9 as a Potential Target for Radiolabeled Antibody-Based Positron Emission Tomography of Pancreas Cancer

    Directory of Open Access Journals (Sweden)

    Mark D. Girgis

    2011-01-01

    Full Text Available Introduction. Sensitive and specific imaging of pancreas cancer are necessary for accurate diagnosis, staging, and treatment. The vast majority of pancreas cancers express the carbohydrate tumor antigen CA19-9. The goal of this study was to determine the potential to target CA19-9 with a radiolabeled anti-CA19-9 antibody for imaging pancreas cancer. Methods. CA19-9 was quantified using flow cytometry on human pancreas cancer cell lines. An intact murine anti-CA19-9 monoclonal antibody was labeled with a positron emitting radionuclide (Iodine-124 and injected into mice harboring antigen positive and negative xenografts. MicroPET/CT were performed at successive time intervals (72 hours, 96 hours, 120 hours after injection. Radioactivity was measured in blood and tumor to provide objective confirmation of the images. Results. Antigen expression by flow cytometry revealed approximately 1.3×106 CA19-9 antigens for the positive cell line and no expression in the negative cell line. Pancreas xenograft imaging with Iodine-124-labeled anti-CA19-9 mAb demonstrated an average tumor to blood ratio of 5 and positive to negative tumor ratio of 20. Conclusion. We show in vivo targeting of our antigen positive xenograft with a radiolabeled anti-CA19-9 antibody. These data demonstrate the potential to achieve anti-CA19-9 antibody based positron emission tomography of pancreas cancer.

  7. PIK3CA in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Gieri eCathomas

    2014-03-01

    Full Text Available PIK3CA, the catalytic subunit of PI3K, is mutated in many different tumours, including colorectal cancer. Mutations of PIK3CA have been reported in 10 – 20% of colorectal cancer, about 80% of mutations found in two hot spots in exon 9 and exon 20. In RAS wild-type colorectal cancers, PIK3CA mutations have been associated with a worse clinical outcome and with a negative prediction of a response to targeted therapy by anti-EGFR monoclonal antibodies. However, these findings have not been confirmed in all studies and subsequent more detailed analysis has revealed that these effects may be restricted to mutations in Exon 20. Finally, mutations in PIK3CA may be the long sought biomarker for successful adjuvant therapy with aspirin in patients with colorectal cancer. Therefore, PIK3CA mutations appear to be a promising predictive biomarker; however, further data are needed to conclusively define the impact of somatic mutations in the PIK3CA gene for the management of patients with colorectal cancer.

  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. Tumor Antigen-Derived Peptides Delivery for Cancer Immunotherapy.

    Science.gov (United States)

    Wenxue, Ma

    2014-02-05

    Tumor antigenic peptides therapeutics is a promising field for cancer immunotherapy. Benefits include the ease and rapid synthesis of antigenic peptides and capacity for modifications. In the past years, many peptide-based cancer vaccines have been tested in clinical trials with a limited success because of the difficulties associated with peptide stability and delivery approaches, consequently, resulting in inefficient antigen presentation and low response rates in patients with cancer. The development of suitable and efficient vaccine carrier systems still remains a major challenge. This article aims to describe a new delivery approach for tumor antigenic peptides and rationales of dendritic cells (DCs)-based vaccination. In order to elicit enhanced immune responses, poly(DL-lactide-co-glycolide) (PLGA), which has been approved by the US Food and Drug Administration (FDA) for the use of drug delivery, diagnostics and other applications of clinical and basic science research were employed for the formulation of making nanoparticles (NPs) while delivering tumor antigenic peptides.

  10. 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...

  11. 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

  12. Monoclonal antibody-defined human pancreatic cancer-associated antigens.

    Science.gov (United States)

    Schmiegel, W H; Kalthoff, H; Arndt, R; Gieseking, J; Greten, H; Klöppel, G; Kreiker, C; Ladak, A; Lampe, V; Ulrich, S

    1985-03-01

    Three pancreatic cancer-associated antigens were characterized by use of monoclonal antibodies in immunobinding studies with various cellular and soluble target antigens, in immunoprecipitation, and in immunoperoxidase staining. C54-0 represents a tumor-associated Mr 122,000 antigen, which appears to be widely distributed on various epithelial tumors and to a lower extent on normal tissue. C1-N3 antigen exhibited a more restricted distribution, reacting with pancreatic and various gastrointestinal tract tumors as well as with chronically inflamed pancreatic tissue. The most specific antigen expression was observed for C1-P83 antigen, found on all exocrine tumors of the pancreas, but not on normal or chronically inflamed pancreatic tissue.

  13. 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 ...

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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...

  19. Trypanosoma cruzi as an effective cancer antigen delivery vector.

    Science.gov (United States)

    Junqueira, Caroline; Santos, Luara I; Galvão-Filho, Bruno; Teixeira, Santuza M; Rodrigues, Flávia G; DaRocha, Wanderson D; Chiari, Egler; Jungbluth, Achim A; Ritter, Gerd; Gnjatic, Sacha; Old, Lloyd J; Gazzinelli, Ricardo T

    2011-12-01

    One of the main challenges in cancer research is the development of vaccines that induce effective and long-lived protective immunity against tumors. Significant progress has been made in identifying members of the cancer testis antigen family as potential vaccine candidates. However, an ideal form for antigen delivery that induces robust and sustainable antigen-specific T-cell responses, and in particular of CD8(+) T lymphocytes, remains to be developed. Here we report the use of a recombinant nonpathogenic clone of Trypanosoma cruzi as a vaccine vector to induce vigorous and long-term T cell-mediated immunity. The rationale for using the highly attenuated T. cruzi clone was (i) the ability of the parasite to persist in host tissues and therefore to induce a long-term antigen-specific immune response; (ii) the existence of intrinsic parasite agonists for Toll-like receptors and consequent induction of highly polarized T helper cell type 1 responses; and (iii) the parasite replication in the host cell cytoplasm, leading to direct antigen presentation through the endogenous pathway and consequent induction of antigen-specific CD8(+) T cells. Importantly, we found that parasites expressing a cancer testis antigen (NY-ESO-1) were able to elicit human antigen-specific T-cell responses in vitro and solid protection against melanoma in a mouse model. Furthermore, in a therapeutic protocol, the parasites expressing NY-ESO-1 delayed the rate of tumor development in mice. We conclude that the T. cruzi vector is highly efficient in inducing T cell-mediated immunity and protection against cancer cells. More broadly, this strategy could be used to elicit a long-term T cell-mediated immunity and used for prophylaxis or therapy of chronic infectious diseases.

  20. 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 ...

  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. 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.

  3. 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 ...

  4. 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...

  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. Tissue Carcinoembryonic Antigen, Calcium, Copper and Iron Levels in Cancerous Lung Patients

    Directory of Open Access Journals (Sweden)

    Nasar Yousuf ALWAHAIBI

    2011-01-01

    Full Text Available Background and objective The expression of various trace elements and markers in lung cancer is controversial. The aim of this study is to evaluate the presence of calcium (Ca, copper (Cu, iron (Fe and carcinoembryonic antigen (CEA in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer. Methods Fourty-eight cancerous lung tissue blocks, from Sultan Qaboos University Hospital, Sultanate of Oman, were studied. Fe, Ca, Cu, and CEA were demonstrated in the tissue blocks using Perl's Prussian blue, Von Kossa's, modified rhodanine and immunohistochemical staining methods, respectively. Results Twenty-three of 48 specimens showed positive Fe staining, 2 showed positive Ca staining and Cu was absent in all specimens. 93.7% expressed CEA in varying degree of positivity. 81.25% of these sections showed high expression of CEA. Conclusion Tissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker. Despite the low sensitivity and specificity of CEA as previously reported, tissue CEA should be considered as a potential marker in the evaluation of lung cancer.

  7. Tissue Carcinoembryonic Antigen, Calcium, Copper and Iron Levels in Cancerous Lung Patients

    Institute of Scientific and Technical Information of China (English)

    Nasar Yousuf ALWAHAIBI; Jokha Sultan ALGHARIBI; Amna Salim ALSHUKAILI; Ahmed Khalifa ALSHUKAILI

    2011-01-01

    Background and objective The expression of various trace elements and markers in lung cancer is controversial. The aim of this study is to evaluate the presence of calcium (Ca), copper (Cu), iron (Fe) and carcinoembryonic antigen (CEA) in cancerous untreated lung tissues and to determine a possible association between these markers and lung cancer.Methods Fourty-eight cancerous lung tissue blocks, from Sultan Qaboos University Hospital, Sultanate of Oman, were studied. Fe, Ca, Cu, and CEA were demonstrated in the tissue blocks using Perl's Prussian blue, Von Kossa's, modified rhodanine and immunohistochemical staining methods, respectively.Results Twenty-three of 48 specimens showed positive Fe staining, 2 showed positive Ca staining and Cu was absent in all specimens. 93.7% expressed CEA in varying degree of positivity. 81.25% of these sections showed high expression of CEA. Conclusion Tissue concentrations of trace elements were not elevated in lung cancer and therefore cannot be considered as a potential marker. Despite the low sensitivity and specificity of CEA as previously reported, tissue CEA should be considered as a potential marker in the evaluation of lung cancer.

  8. Differential diagnosis of tuberculosis and lung cancer pleural effusion by CEA, CA125,CA50%CEA、CA125、CA50在结核及肺癌性胸水鉴别中的意义

    Institute of Scientific and Technical Information of China (English)

    冯金栋; 赵卫国; 保鹏涛

    2013-01-01

    Objective:To explore the significance of differential diagnosis of pleural effusion by detection of carci-noembryonic antigen (CEA) ,carbohydrate antigen (CA125) and carbohydrate antigen (CA50). Methods: A total of 126 specimens from pleural effusion diagnosed as TB in 70 cases and lung cancer in 56 cases were collected. CEA, CA125,CA50 in the pleural effusion were analyzed. ResuItS:The expression level and sensitivity of CEA and CA50 in pleural effusion of lung cancer was significantly higher than that in tuberculous (P 0.05). The specificity was only 5.71%. Combining CEA with CA125 to diagnose pleural effusion resulted fom lung cancer, the sensitivity was 92. 11% and combining CA125 with CA50 the sensitivity was 95. 24% . When the concetration of CEA was more than 10ng/ml or the concetration of CA125 was more than 2000U/ml,pleural effusion of lung cancer should be highly suspected. Conclusion;The use of CEA.CA125 and CA50 separately,or in combination is helpful to differential diagnosis of pleural effusion resulted from tuberculosis and lung cancer.%目的:探讨癌胚抗原(CEA)、糖类抗原(CA125)、糖类抗原(CA50)在胸水鉴别诊断中的意义.方法:收集已明确胸水性质的标本126例(结核性70例、癌性56例),检测胸水中CEA、CA125、CA50的数值,进行统计分析.结果:肺癌性胸水中CEA、CA50表达水平及敏感度明显高于结核性胸腔积液(P<0.05),特异性分别为95.71%和98.57%.同样CA125在肺癌性胸水中高表达(P<0.05),但两组敏感度无差异(P>0.05),特异性仅为5.71%;CEA和CA125联合诊断肺癌性胸水的敏感度为92.11%,CA125和CA50联合诊断敏感度为95.24%.CEA> 10ng/ml或CA125> 2000U/ml,可初步定为肺癌性胸水.结论:CEA、CA125、CA50单独或联合检测对鉴别诊断结核及肺癌性胸水有重要临床指导意义.

  9. 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...

  10. Serum level of TSGF,CA242 and CA19-9 in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Chang-Ping Wu; Hai-Feng Deng; Ming-Yang Lu; Jun Wu; Hong-Yu Zhang; Wen-Hui Sun; Mei Ji

    2004-01-01

    AIM: To establish a method to detect the expression of the tumor specific growth factor TSGF, CA242 and CA19-9 in serum and evaluate their value in diagnosis of pancreatic cancer.METHODS: ELISA and Biochemical colorimetric assay were used to detect the serum content of TSGF, CA242 and CA19-9 in 200 normal cases, 52 pancreatitis patients and 96 pancreatic cancer patients.RESULTS: The positive likelihood ratios of TSGF, CA242and CA19-9 were 5.4, 12.6 and 6.3, respectively, and their negative likelihood ratios were 0.10, 0.19 and 0.17,respectively. With single tumor marker diagnosed pancreatic cancer, the highest sensitivity and specificity of TSGF were 91.6% and 93.5%. In combined test with 3 markers, when all of them were positive, the sensitivity changed to 77.0%and the specificity and the positive predictive value were 100%. The levels of TSGF and CA242 were significantly higher in the patients with pancreatic cancer of head than those in the patients with pancreatic cancer of body, tail and whole pancreas, but the expression of CA19-9 had no correlation with the positions of the pancreatic cancer. The sensitivity of TSGF, CA242 and CA19-9 was increased with the progress in stages of pancreatic cancer. In stage I, the sensitivity of TSGF was markedly higher than CA242 and CA19-9.CONCLUSION: The combined use of TSGF, CA242 and CA19-9 expressions can elevate the specificity for pancreatic cancer diagnosis. And it shows that it plays an important role to differentiate positions and tissue typing. It is a forepart diagnosis for the pancreatic cancer by combination checking.There is very important correlation between the three markers and the pancreatic cancer.

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  12. 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.

  13. 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.

  14. 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...

  15. 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.

  16. 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 (...

  17. 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

  18. 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.

  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. 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

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

  2. Reactivity of Monoclonal Antibodies Directed against Lung Cancer Antigens with Human Lung, Breast and Colon Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Udo Schumacher

    1993-01-01

    Full Text Available A panel of monoclonal antibodies (n=72 including controls directed against lung cancer antigens was screened immunohistochemically against a panel of seven human lung cancer cell lines (including small cell carcinoma, squamous cell carcinoma, adenocarcinoma and mesothelioma, six human breast cancer cell lines and one human colon cancer cell line, The majority of the antibodies (n=42 reacted also with antigens present on breast and colon cancer cell lines, This cross reactivity especially between lung and breast cancer cell lines is not altogether unexpected since antigens common to breast and lung tissue including their neoplasms such as MUC1 antigen have been described, Our results indicate that epitopes shared by lung and breast cancers are probably more common than previously thought. The relevance for prognosis and therapy of these shared antigens, especially as disease markers in breast cancer, has to be investigated.

  3. 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.

  4. 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

  5. Integrative discovery of epigenetically derepressed cancer testis antigens in NSCLC.

    Directory of Open Access Journals (Sweden)

    Chad A Glazer

    Full Text Available BACKGROUND: Cancer/testis antigens (CTAs were first discovered as immunogenic targets normally expressed in germline cells, but differentially expressed in a variety of human cancers. In this study, we used an integrative epigenetic screening approach to identify coordinately expressed genes in human non-small cell lung cancer (NSCLC whose transcription is driven by promoter demethylation. METHODOLOGY/PRINCIPAL FINDINGS: Our screening approach found 290 significant genes from the over 47,000 transcripts incorporated in the Affymetrix Human Genome U133 Plus 2.0 expression array. Of the top 55 candidates, 10 showed both differential overexpression and promoter region hypomethylation in NSCLC. Surprisingly, 6 of the 10 genes discovered by this approach were CTAs. Using a separate cohort of primary tumor and normal tissue, we validated NSCLC promoter hypomethylation and increased expression by quantitative RT-PCR for all 10 genes. We noted significant, coordinated coexpression of multiple target genes, as well as coordinated promoter demethylation, in a large set of individual tumors that was associated with the SCC subtype of NSCLC. In addition, we identified 2 novel target genes that exhibited growth-promoting effects in multiple cell lines. CONCLUSIONS/SIGNIFICANCE: Coordinated promoter demethylation in NSCLC is associated with aberrant expression of CTAs and potential, novel candidate protooncogenes that can be identified using integrative discovery techniques. These findings have significant implications for discovery of novel CTAs and CT antigen directed immunotherapy.

  6. The effect of dwell time on dialysate cancer antigen 125 appearance rates in patients on continuous ambulatory peritoneal dialysis.

    Science.gov (United States)

    Akman, Sema; van Westrhenen, Roos; De Waart, Dirk R; Hiralall, Johan K; Zweers, Machteld M; Krediet, Raymond T

    2003-01-01

    The dialysate concentration of cancer antigen 125 (CA125) can be considered a reflection of mesothelial cell mass or turnover in stable continuous ambulatory peritoneal dialysis (CAPD) patients. The effect of dwell times exceeding 4 hours on CA125 appearance rate (CA125AR) is not known. Therefore, our objective in the present study was to analyze the effect of dwell time on CA125AR in stable CAPD patients. In 43 stable CAPD patients, we analyzed standard peritoneal permeability analyses (SPAs) performed with a 3.86% glucose dialysate, and night-dwell effluents from the night dwell prior to the SPA. Dialysate CA125 concentration was measured by radioimmunoassay (RIA II: Fujirebio Diagnostics, Malvern, PA, U.S.A.). Night-dwell CA125 correlated with the duration of the dwell (r = 0.32, p = 0.04) and with the CA125 concentration in the 4-hour dwell (r = 0.83, p < 0.001). The mean CA125AR in the SPA effluent was 97.8 +/- 46.3 U/min; in the overnight effluent, it was 108.8 +/- 73.7 U/min (nonsignificant). A good correlation was present between the CA125AR in the 4-hour dwells and in the overnight dwells (r = 0.82, p < 0.001). We conclude that using night dwells to regularly assess dialysate CA125--for instance, at every out-patient visit--is possible in CAPD patients, provided that appearance rate is calculated.

  7. 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.

  8. Comparative study of CEA and CA19-9 in esophageal, gastric and colon cancers individually and in combination (ROC curve analysis)

    Institute of Scientific and Technical Information of China (English)

    Bhawna Bagaria; Sadhna Sood; Rameshwaram Sharma; Soniya Lalwani

    2013-01-01

    Objective:To determine the clinical serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), individually and in combination, for the diagnosis of 50 healthy subjects and 150 cases of esophageal, gastric, and colon cancers. Methods:The sensitivities of the two markers were compared individually and in combination, with specificity set at 100%. Receiver operating characteristic (ROC) curves were plotted. Results:Serum CEA levels were significantly higher in cancer patients than in the control group. The sensitivity of CEA was determined:in esophageal cancer, sensitivity=28%, negative predictive value (NPV)=61.72%, and AUC=0.742 (SE=0.05), with a significance level of P Conclusion:CEA exhibited the highest sensitivity for colon cancer, and CA19-9 exhibited the highest sensitivity for gastric cancer. Combined analysis indicated an increase in diagnostic sensitivity in esophageal and gastric cancer compared with that in colon cancer.

  9. 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.

  10. 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...

  11. 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”.

  12. Use of CA 125 monoclonal antibody to monitor patients with ovarian cancer.

    Science.gov (United States)

    Kudlacek, S; Schieder, K; Kölbl, H; Neunteufel, W; Nowotny, C; Breitenecker, G; Biegelmayer, G; Vetterlein, M; Fürlinger, B; Micksche, M

    1989-12-01

    The monoclonal antibody (mAb) OC 125 reacts with an antigen on human ovarian carcinoma (OVCA) cells that is also shed into the body fluids and can be detected in patients' sera and/or ascites with a radioimmunometric assay. For the present study, serum CA 125 levels of patients (n = 36) with different stages of OVCA were investigated. Serum levels seem to correlate with tumor burden. In stages I and II (n = 12), 33% of patients were CA 125 positive, whereas 70% of stage III and IV patients (n = 24) were CA 125 positive. Mean serum levels were in 93 U/ml (stages I, II) and 279 U/ml (stages III, IV). CA 125 levels in ascites and in pleural effusions were manyfold higher than serum levels of the same patients (P less than 0.0001). Immunohistochemical investigations of CA 125 in different ovarian tumors (n = 91) revealed that 85% of malignant and 75% of borderline serous cystadenocarcinomas had detectable CA 125 surface expression. Furthermore, 71% of benign tumors showed the CA 125 epitope, whereas mucinous tumors were negative for this marker. One of six ovarian cancer cell lines was CA 125 positive, whereas in 6 of 11 patients, ascites-derived ovarian cancer cells (fresh and gradient isolated) were positive for this marker. The proportion of positive cells ranged from 10 to 90% in these samples. Intraperitoneal recombinant interferon-gamma (rIFN-gamma) therapy resulted in an increase in the number of cells reacting with CA 125. The results of monitoring in patients receiving different therapeutic regimens and/or agents demonstrate the usefulness of this marker.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    and antigenic properties, but the expression patterns of most of the more than 200 identified cancer/testis antigens in various cancers remain largely uncharacterized. In this study, we investigated the expression of the cancer/testis antigens ADAM2, CALR3 and SAGE1 in lung and breast cancer, the two most...... frequent human cancers, with the purpose of providing novel therapeutic targets for these diseases. We used a set of previously uncharacterized antibodies against the cancer/testis antigens ADAM2, CALR3 and SAGE1 to investigate their expression in a large panel of normal tissues as well as breast and lung...... cancers. Staining for the well-characterized MAGE-A proteins was included for comparison. Immunohistochemical staining confirmed previous mRNA analysis demonstrating that ADAM2, CALR3 and SAGE1 proteins are confined to testis in normal individuals. Negative tissues included plancenta, which express many...

  14. 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)

  15. 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...

  16. 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

  17. 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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  19. 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.

  20. 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...

  1. 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...

  2. 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

  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. 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.

  5. 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...

  6. 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

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

    NARCIS (Netherlands)

    Eggermont, L.J.; Paulis, L.E.M.; Tel, J.; Figdor, C.G.

    2014-01-01

    Active anti-cancer immune responses depend on efficient presentation of tumor antigens and co-stimulatory signals by antigen-presenting cells (APCs). Therapy with autologous natural APCs is costly and time-consuming and results in variable outcomes in clinical trials. Therefore, development of artif

  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. 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.

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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

  15. 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

  16. 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...

  17. 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.

  18. 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

  19. 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

    Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing...

  20. 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

  1. Expression of Cancer Testis Antigens in Colorectal Cancer: New Prognostic and Therapeutic Implications.

    Science.gov (United States)

    Tarnowski, Maciej; Czerewaty, Michał; Deskur, Anna; Safranow, Krzysztof; Marlicz, Wojciech; Urasińska, Elżbieta; Ratajczak, Mariusz Z; Starzyńska, Teresa

    2016-01-01

    Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study. We selected a panel of 18 CTAs that were previously detected in CRC as well as some new gene candidates, and their expression was detected at the mRNA level by employing RQ-PCR. Additionally, we evaluated CTA expression in three colon cancer cell lines (CL-188, HTB-39, and HTB-37) after exposure to the DNA methylation-modifying drug 5-azacytidine. Results. We report that 6 out of 18 (33%) CTAs tested (MAGEA3, OIP5, TTK, PLU1, DKKL1, and FBXO39) were significantly (p colon samples isolated from the same patients. Conclusions. Moreover, we found that MAGEA3, PLU-1, and DKKL expression positively correlated with disease progression, evaluated according to the Dukes staging system. Finally, 5-azacytidine exposure significantly upregulated expression of CTAs on CRC cells, which indicates that this demethylation agent could be employed therapeutically to enhance the immune response against tumor cells. PMID:27635108

  2. Expression, purification and characterization of the cancer-germline antigen GAGE12I: a candidate for cancer immunotherapy

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Besir, Hüseyin; Larsen, Martin R;

    2010-01-01

    GAGE cancer-germline antigens are frequently expressed in a broad range of different cancers, while their expression in normal tissues is limited to the germ cells of the immune privileged organs, testis and ovary. GAGE proteins are immunogenic in humans, which make them promising targets for imm...

  3. 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...

  4. Metal based nanoparticles as cancer antigen delivery vehicles for macrophage based antitumor vaccine.

    Science.gov (United States)

    Chattopadhyay, Sourav; Dash, Sandeep Kumar; Mandal, Debasis; Das, Balaram; Tripathy, Satyajit; Dey, Aditi; Pramanik, Panchanan; Roy, Somenath

    2016-02-10

    In the present study, we would like to evaluate the efficacy of modified metal oxide nanoparticles (NPs) as cancer antigen delivery vehicles for macrophage (MФs) based antitumor vaccine. The cobalt oxide nanoparticles (CoO NPs) were promising tools for delivery of antigens to antigen presenting cells and have induced an antitumor immune response. Synthesized CoO NPs were modified by N-phosphonomethyliminodiacetic acid (PMIDA), facilitated the conjugation of lysate antigen, i.e. cancer antigen derived from lysis of cancer cells. The cancer cell lysate antigen conjugated PMIDA-CoO NPs (Ag-PMIDA-CoO NPs) successfully activated macrophage (MФ) evident by the increasing the serum IFN-γ and TNF-α level. Immunization of mice with the Ag-PMIDA-CoO NPs constructed an efficient immunological adjuvant induced anticancer IgG responses, and increased the antibody dependent cellular cytotoxicity (ADCC) response than only lysate antigen treated group to combat the cancer cell. The nanocomplexes enhanced the anticancer CD4(+)T cell response in mice. The result showed that Ag-PMIDA-CoO NPs can stimulate the immune responses over only lysate antigens, which are the most important findings in this study. These NP-mediated Ag deliveries may significantly improve the anticancer immune response by activating MФs and may act as adjuvant and will balance the pro-inflammatory and anti-inflammatory immunoresponse. The crosstalk between the activated MФ with other immune competent cells will be monitored by measuring the cytokines which illustrate the total immunological network setups.

  5. 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

  6. 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...

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

    Directory of Open Access Journals (Sweden)

    van der Burg SH

    2005-09-01

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

  8. Cancer testis antigen 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.

  9. 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.

  10. 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.

  11. 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

  12. Comparison of CYFRA 21-1, CEA, CA 19-9 and CA 72-4 levels in gastric cancer

    Directory of Open Access Journals (Sweden)

    Gökhan Çakırca

    2013-01-01

    Full Text Available Objective: Gastric cancer is the fourth most common malignancy,and the second most common cause of cancermortality worldwide. The aim of this study was to investigatethe role of biomarkers CYFRA 21-1, CA 19-9, CEA,CA72.4 at diagnosis and throughout the follow-up in patientswith gastric cancer.Methods: 30 patients with gastric cancer diagnosed and31 healthy people as a control group were included in thisstudy. According to the TNM staging system, there were16 patients with stage II and 14 patients with stage III inthe group of patients with gastric cancer. CEA, CA 19-9,CA 72-4 and CYFRA 21-1 levels were studied by elektrochemiluminescenceimmunasay (ECLIA method in theCobas e 601 instrument.Results: Statistically the level of CA 72-4, CA 19-9, CEAand CYFRA 21-1 gastric cancer groups was found significanthigh accaording to healthy control group (p<0.01.Statistically compared with II stage patient group, the levelof CA 19-9, CEA and CYFRA 21-1 of III stage patientgroup was found significant high (p<0.01. The diagnosticcut-off, sensitivity and specificity for CEA were 4.15 ng/mL, 46 % and 96%, respectively; for CA 19-9 were 24.50U/mL, 17 % and 96 %; for CA 72-4 were 2.46 U/mL, 53% and 96% and for CYFRA 21-1 were 3.36 ng/mL, 46%and 100%.Conclusion: Our study demonstrates that the associationof biomarkers CYFRA 21-1, CEA, and CA72.4 providesa valuable contribution in the follow-up of gastriccancer patients.Key words: Gastric cancer, tumor markers, CYFRA 21-1

  13. CA153 in Breast Secretions as a Potential Molecular Marker for Diagnosing Breast Cancer: A Meta Analysis

    Science.gov (United States)

    Zhou, Fang; Zhu, Shengbo; Yang, Renqi; Huang, Yiyong; Zhang, Hongyu; Xu, Hong; Yang, Jianqing

    2016-01-01

    Purpose Many studies have reported that carbohydrate antigen 153 (CA153) in breast secretions (BS) can discriminate breast cancer (BC) patients from healthy individuals, indicating CA153 in BS as a potential index for BC. This meta-analysis aimed to evaluate the actual diagnostic value of CA153 in BS. Methods Related papers were obtained from Pubmed, Embase, Scopus, Ovid, Sciverse, the Cochrane library, Chinese Biomedical literature Database (CBM), Technology of Chongqing (VIP), Wan Fang Data, and Chinese National Knowledge Infrastructure (CNKI). Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) of CA153 in BS for BC diagnosis were analyzed with the random effect model. SROC and the area under the curve (AUC) were applied to assess overall diagnostic efficiency. Results This meta-analysis included five studies with a total of 329 BC patients and 381 healthy subjects. For CA153 in BS, the summary sensitivity, specificity, and DOR to diagnose BC were 0.63 (95% confidence interval (CI): 0.57∼0.68), 0.82 (95% CI: 0.78∼0.86), and 9.18 (95% CI: 4.22∼19.95), respectively. Furthermore, the AUC of BS CA153 in the diagnosis of BC was 0.8614. Conclusions CA153 in BS is a valuable molecular marker in diagnosing BC and should be applied in standard clinical practices of BC screening upon confirmation of our findings in a larger prospective study. PMID:27636552

  14. 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

  15. 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...

  16. 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

  17. 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...

  18. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    tissue samples of breast carcinoma and normal breast tissue were obtained from 175 breast cancer patients at the time of primary surgery, of these 105 patients were lymph node positive. Expression of PIK3CA and PTEN mRNA was quantified with Quantitative Real Time PCR. Somatic mutations in exon 9 and exon......PURPOSE: High activity of the intracellular phosphatidylinositol-3 kinase (PI3K) pathway is common in breast cancer. Here, we explore differences in expression of important PI3K pathway regulators: the activator, phosphatidylinositol-3-kinase catalytic subunit alpha (PIK3CA), and the tumour...... suppressor, phosphatase and tensin homolog (PTEN), in breast carcinoma tissue and normal breast tissue. Furthermore, we examine whether expression of PIK3CA and PTEN mRNA and occurrence of PIK3CA mutations are associated with lymph node metastases in patients with primary breast cancer. METHODS: Paired...

  20. 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

    Patient: Male, 58 Final Diagnosis: Hydronephrosis Symptoms: Blunt abdominal pain • constipation • constipation Medication: — Clinical Procedure: Extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy Specialty: Gastroenterology and Hepatology Objective: Rare co-existance of disease or pathology 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

  1. The Detection Value Analysis of Tumor Markers CEA,CA125 in Cervical Cancer%肿瘤标记物CEA、CA125在宫颈癌中的检测价值分析

    Institute of Scientific and Technical Information of China (English)

    戴伟萍

    2013-01-01

      目的:探讨肿瘤标记物 CEA、CA125在宫颈癌中的检测的临床价值.方法:选取笔者所在医院2011年1月-2012年8月经临床确诊的100例宫颈癌患者(宫颈癌组)及40例进行健康体检的妇女(对照组)为研究对象,测定两组的血清肿瘤标记物癌胚抗原(CEA)、糖抗原(CA125).结果:宫颈癌组的血清 CEA、CA125含量显著高于对照组(P<0.05).在宫颈癌组中,随着临床分期的增加 CEA、CA125的阳性率逐渐增加,Ⅲ、Ⅳ期较Ⅰ、Ⅱ期显著增加(P<0.05).结论:肿瘤标记物 CEA、CA125在宫颈癌中有较高的诊断价值,可辅助判断宫颈癌的临床分期.%Objective:To investigate the clinical value of tumor markers CEA,CA125 detection in cervical cancer and the significance.Methods:100 cases of cervical cancer (the cervical cancer group )that was clinical diagnosis from January 2011 to August 2012 in author’s hospital and 40 cases of healthy women (the control group) were chosen as the research object,two groups were measured in serum tumor marker carcinoembryonic antigen (CEA),carbohydrate antigens (CA125).Results:Serum CEA,CA125 in the cervical cancer group were significantly higher than those in the control group (P<0.05).In the cervical cancer group, CEA,CA125 positive rate increased gradually along with the clinical stagin,stage Ⅲ,Ⅳ were significantly than istage Ⅰ,Ⅱ (P<0.05).Conclusion:There is a high diagnostic value of the tumor markers CEA,CA125 in cervical carcinoma;they can help judge clinical cervical cancer staging.

  2. 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...

  3. 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.

  4. 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

  5. The clinical value of squamous cell carcinoma antigen in cancer of the uterine cervix

    NARCIS (Netherlands)

    de Bruijn, HWA; Duk, JM; van der Zee, AGJ; Pras, E; Willemse, PHB; Hollema, H; Mourits, MJE; de Vries, EGE; Aalders, JG; Boonstra, J.

    1998-01-01

    A review is given of the clinical use and interpretation of serum tumor marker levels during the treatment of patients with cancer of the uterine cervix, Pretreatment serum squamous cell carcinoma (SCC) antigen provides a new prognostic factor in early stage squamous cell carcinoma of the uterine ce

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

    NARCIS (Netherlands)

    Pras, E; Willemse, PHB; Canrinus, AA; de Bruijn, HWA; Sluiter, WJ; ten Hoor, KA; Aalders, JG; Szabo, BG; de Vries, EGE

    2002-01-01

    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 cervica

  7. 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...

  8. Ferrocenyl-doped silica nanoparticles as an immobilized affinity support for electrochemical immunoassay of cancer antigen 15-3

    Energy Technology Data Exchange (ETDEWEB)

    Hong Chenglin [Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); College of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832002 (China); Yuan Ruo [Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)], E-mail: yuanruo@swu.edu.cn; Chai Yaqin; Zhuo Ying [Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)

    2009-02-09

    The aim of this study is to elaborate a simple and sensitive electrochemical immunoassay using ferrocenecarboxylic (Fc-COOH)-doped silica nanoparticles (SNPs) as an immobilized affinity support for cancer antigen 15-3 (CA 15-3) detection. The Fc-COOH-doped SNPs with redox-active were prepared by using a water-in-oil microemulsion method. The use of colloidal silica could prevent the leakage of Fc-COOH and were easily modified with trialkoxysilane reagents for covalent conjugation of CA 15-3 antibodies (anti-CA 15-3). The Fc-COOH-doped SNPs were characterized by X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The fabrication process of the electrochemical immunosensor was demonstrated by using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. Under optimal conditions, the developed immunosensor showed good linearity at the studied concentration range of 2.0-240 U mL{sup -1} with a coefficient 0.9986 and a detection limit of 0.64 U mL{sup -1} at S/N = 3.

  9. 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.

  10. 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)

  11. 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.

  12. 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

    prostate cancer and benign prostatic conditions. In 105 patients with newly diagnosed prostate cancer, scintigraphic evidence of osseous metastases was found in thirty-seven. No patients with a serum PSA value less than three times the upper normal limit of the assay had a positive bone scan. Isotope bone......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...... scan can be omitted in these patients, if they are not considered candidates for curative treatment....

  13. 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...

  14. 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

  15. 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

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

    Science.gov (United States)

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

    2016-03-01

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

  17. 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

  18. 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.

  19. 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

  20. 糖类抗原检测在非小细胞肺癌诊疗中的应用%Application of the carbohydrate antigen detection for diagnosis and treatment in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    吴小进; 米燕燕; 胡安康; 王伟; 桑纯利; 冯苏梅; 殷咏梅; 鄂云祥

    2013-01-01

    目的 探讨糖类抗原检测用于非小细胞肺癌(NSCLC)诊疗的临床意义.方法 采用血清糖类抗原多肿瘤标志物蛋白芯片检测系统对已确诊的60例NSCLC患者的血清CA19-9、CA242、CA125和CA153水平进行检测,并与肺良性病变对照组和健康对照组进行比较.结果 肺癌组血清CA19-9、CA242、CA125和CA153的阳性检出率高于肺良性病变对照组和健康对照组,且3组血清CA19-9、CA125和CA153的差异尤为显著(P<0.05).肺腺癌患者血清CA19-9和CA125的阳性检出率高于肺鳞癌患者(P<0.05).NSCLC患者分期越晚,4种糖类抗原的阳性检出率越高,其中CA125和CA153在Ⅰ~Ⅱ期的阳性检出率分别为38.5%和30.8%,高于CA19-9和CA242的7.7%和7.7%(P<0.05).结论 糖类抗原检测在NSCLC诊疗方面具有较好的临床应用价值,可以作为诊断、分期及病程监测等方面常规检测方法的辅助手段.%Objective To explore the clinical significance of the carbohydrate antigen detection for diagnosis and treatment in non-small cell lung cancer(NSCLC). Methods The levels of serum CA19-9, CA242, CA125 and CA153 of 60 confirmed patients with NSCLC were measured by multiple tumor marker protein chip detection system and were compared with benign lung lesions control group and the healthy control group. Results The positive rate of serum CA19-9, CA242, CA125 and CA153 in the lung cancer group were higher than benign lung lesions control group and healthy control group, but there was particularly apparent difference in serum CA19-9, CA125 and CA153( P <0. 05). The positive rates of serum CA19-9 and CA125 in the patients with lung adenocarcinoma were significantly higher than those in patients with squamous cell carcinoma ( P <0. 05) . The positive rates of 4 carbohydrate antigens raised with clinical stages. The positive rates of CA125 and CA153 in stage I -II were 38. 5% and 30. 8% , which were higher than those of CA19-9 and CA242, with significant

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

    Directory of Open Access Journals (Sweden)

    Caroline B Madsen

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

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

    Directory of Open Access Journals (Sweden)

    Marcus M. Wilkes

    2014-07-01

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

  3. 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

  4. 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;

    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....

  5. 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 ...

  6. 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...

  7. 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

  8. 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...... against both proliferative and quiescent (i.e., G0-arrested) cells. However, thapsigargin's mechanism of action indicates that it is unlikely to be selective for cancer cells or prostate cells....

  9. 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.

  10. 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。

  11. 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-LiGuo; MingDong; LanWang; Li-PingSun; YuanYuan

    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.pyiori infection in benign gastric lesions in order to find out the effect of H.pylori infection on the process of gastric cancer development.

  12. 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...

  13. 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% ...

  14. Cancer-testis antigen expression in digestive tract carcinomas: frequent expression in esophageal squamous cell carcinoma and its precursor lesions.

    Science.gov (United States)

    Chen, Yao-Tseng; Panarelli, Nicole C; Piotti, Kathryn C; Yantiss, Rhonda K

    2014-05-01

    Cancer-testis (CT) antigens are attractive tumor antigens for cancer immunotherapy. They comprise a group of proteins normally expressed in germ cells and aberrantly activated in a variety of human cancers. The protein expression of eight cancer-testis antigens [MAGEA, NY-ESO-1, GAGE, MAGEC1 (CT7), MAGEC2 (CT10), CT45, SAGE1, and NXF2] was evaluated by immunohistochemistry in 61 esophageal carcinomas (40 adenocarcinoma and 21 squamous cell carcinoma), 50 gastric carcinomas (34 diffuse and 16 intestinal type), and 141 colorectal carcinomas. The highest frequency of expression was found in esophageal squamous cell carcinomas: Positive staining for MAGEA, CT45, CT7, SAGE1, GAGE, NXF2, NY-ESO-1, and CT10 was observed in 57%, 38%, 33%, 33%, 29%, 29%, 19%, and 14% of squamous cell carcinomas, respectively. Similar staining patterns were observed in squamous dysplasias. Expression frequencies of cancer-testis antigens were seen in 2% to 24% of gastroesophageal adenocarcinomas and were not significantly different between adenocarcinomas of the stomach versus the esophagus, or between diffuse and intestinal types of gastric adenocarcinomas. Colorectal cancers did not express NY-ESO-1, CT7, CT10, or GAGE, and only infrequently expressed SAGE1 (0.7%) MAGEA (1.4%), CT45 (3.5%), and NXF2 (8.5%). We conclude that cancer-testis antigens are frequently expressed in esophageal squamous neoplasms. Although cancer-testis antigens are generally considered to be expressed later in tumor progression, they are found in squamous dysplasias, suggesting a potential diagnostic role for cancer-testis antigens in the evaluation of premalignant squamous lesions.

  15. 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

  16. 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...

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Grant R01CA128134 | 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.

  6. Grant R01CA148817 | 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.

  7. Grant R21CA190028 | 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.

  8. Grant R01CA154489 | 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.

  9. Grant R01CA179511 | 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.

  10. Grant R01CA170549 | 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.

  11. Grant R01CA155297 | 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.

  12. Grant R21CA182861 | 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.

  13. Grant U01CA163056 | 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.

  14. Grant R21CA174541 | 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 R01CA164782 | 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 R01CA155301 | 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 R01CA098286 | 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 R21CA174594 | 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 U54CA163060 | 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. Grant R21CA190021 | 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.

  2. Grant R01CA132951 | 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.

  3. Grant R01CA134620 | 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.

  4. 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

  5. Cancer-testis antigens and lung cancer%肿瘤-睾丸抗原与肺癌

    Institute of Scientific and Technical Information of China (English)

    徐瑛

    2010-01-01

    肿瘤-睾丸抗原(CTA)在正常睾丸组织的生殖细胞及多种不同组织类型的癌细胞中特异表达.研究证明CTA表达与肺癌的分期、病理类型、复发、转移等密切相关,且在肺癌患者中有抗原性免疫反应.应用CTA对肺癌开展免疫治疗表现出良好的前景.%Cancer-testis antigens (CTAs) are protein antigens with normal expression restricted to adult testis and yet are aberrantly activated and expressed in a proportion of various types of tumor tissues. The expressions of CTA correlate with tumor staging, histopathological subtype, recurrence and metastasis in nonsmall cell lung cancer. CTAs are immunogenic in lung cancer patients and have a good prospect in lung cancer Immunotherapy.

  6. Glycoprotein screening in colorectal cancer based on differentially expressed Tn antigen.

    Science.gov (United States)

    Wei, Hongyun; Cheng, Zongyong; Ouyang, Chunhui; Zhang, Yu; Hu, Yanyan; Chen, Shuijiao; Wang, Chunlian; Lu, Fanggen; Zhang, Jie; Wang, Yongjun; Liu, Xiaowei

    2016-09-01

    Colorectal cancer (CRC) is one of the most common cancers worldwide, and the identification of new biomarkers for CRC is valuable for its diagnosis and treatment. We aimed to screen differentially expressed glycoproteins (especially O-glycoproteins) and to identify diagnostic or therapeutic candidates for colorectal cancer (CRC) based on different Tn antigen expression levels. Fresh cancer tissues and adjacent healthy tissues were obtained from CRC patients and classified into three groups based on their Tn antigen expression: CRC with negative Tn expression (CRC Tn‑), CRC with positive Tn expression (CRC Tn+) and normal control without Tn expression (NC). Protein extractions were separated and identified by iTRAQ technology. Glycoproteins and O-glycoproteins were selected using UniProt and DAVID. Deep bioinformatic analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KO), was used to annotate this O-glycoprotein interaction network. Subsequently, two O‑glycoproteins were verified by western blotting and immunohistochemistry in either LS174T cells or CRC tissues. We found that 330 differentially expressed proteins were identified by iTRAQ between CRC Tn‑ and NC tissues, 317 between CRC Tn+ and NC tissues, and 316 between CRC Tn‑ and Tn+ tissues. Of the 316 proteins, 55 glycoproteins and 19 O‑glycoproteins were identified and analyzed via deep informatics. Namely, different Tn antigen expression levels in CRC led to differential protein expression patterns, especially for glycoproteins and O‑glycoproteins. Decorin and SORBS1, two representative functional O-glycoproteins, were significantly downregulated in the CRC Tn+ tissues compared with the level in the CRC Tn‑ or NC tissues. Based on this deep bioinformatic analysis, Decorin and SORBS1 are hypothesized to be involved in the TGF‑β and PPAR‑γ signaling pathways, respectively. PMID:27432485

  7. Higher importance of interleukin 6 than classic tumor markers (carcinoembryonic antigen and squamous cell cancer antigen) in the diagnosis of esophageal cancer patients.

    Science.gov (United States)

    Łukaszewicz-Zając, M; Mroczko, B; Kozłowski, M; Nikliński, J; Laudański, J; Szmitkowski, M

    2012-04-01

    It has been suggested that interleukin 6 (IL-6) plays a potential role in the growth and progression of tumors, including esophageal cancer (EC). The aim of the study was to compare clinical significance of serum IL-6 with classic tumor markers - carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC-Ag) - in EC patients in relation to its histological types - squamous cell carcinoma of esophagus (ESCC) and adenocarcinoma (AD) of esophagus. The study included 53 EC patients and 90 healthy subjects. Serum IL-6 and CEA levels were determined using immunoenzyme assays, while SCC-Ag - chemiluminescent assay. The diagnostic criteria and prognostic values for markers were defined. The levels of all proteins tested in EC, ESCC, and AD were higher than in healthy subjects. The percentage of elevated results was substantially higher for IL-6 (86%) than for CEA (30%) and SCC-Ag (24%) in EC, similarly as in ESCC (87%, 23%, and 33%) and AD (87%, 39%, and 13%, respectively) patients. Concentrations of IL-6 depended on distant metastases and patients' survival in EC and were significantly higher in ESCC patients with more advanced tumor stage and nodal metastases. The IL-6 area under receiver operating characteristic curve (0.92) was larger than for CEA (0.84) and SCC-Ag (0.62) in EC, likewise in ESCC (0.92, 0.87, 0.77) and AD (0.91, 0.79, 0.57, respectively). Our findings indicate better usefulness of IL-6 than classic tumor markers in the diagnosis of EC, especially in patients with ESCC.

  8. 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

  9. 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...

  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. 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...

  12. Safrole-induced Ca2+ mobilization and cytotoxicity in human PC3 prostate cancer cells.

    Science.gov (United States)

    Chang, H C; Cheng, H H; Huang, C J; Chen, W C; Chen, I S; Liu, S I; Hsu, S S; Chang, H T; Wang, J K; Lu, Y C; Chou, C T; Jan, C R

    2006-01-01

    The effect of the carcinogen safrole on intracellular Ca2+ mobilization and on viability of human PC3 prostate cancer cells was examined. Cytosolic free Ca2+ levels ([Ca2+]i) were measured by using fura-2 as a probe. Safrole at concentrations above 10 microM increased [Ca2+]i in a concentration-dependent manner with an EC50 value of 350 microM. The Ca2+ signal was reduced by more than half after removing extracellular Ca2+ but was unaffected by nifedipine, nicardipine, nimodipine, diltiazem, or verapamil. In Ca2+-free medium, after treatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) failed to release Ca2+. Neither inhibition of phospholipase C with U73122 nor modulation of protein kinase C activity affected safrole-induced Ca2+ release. Overnight incubation with 0.65-65 microM safrole did not affect cell viability, but incubation with 325-625 microM safrole decreased viability. Collectively, the data suggest that in PC3 cells, safrole induced a [Ca2+]i increase by causing Ca2+ release from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion, and by inducing Ca2+ influx. Safrole can decrease cell viability in a concentration-dependent manner.

  13. Reduction of prostate cancer mortality in Tyrol, Austria, after introduction of prostate-specific antigen testing.

    Science.gov (United States)

    Oberaigner, Willi; Horninger, Wolfgang; Klocker, Helmut; Schönitzer, Dieter; Stühlinger, Wolf; Bartsch, Georg

    2006-08-15

    The objective of this study was to analyze in detail the time trend in prostate cancer mortality in the population of Tyrol, Austria. In Tyrol, prostate-specific antigen tests were introduced in 1988-1989 and, since 1993, have been offered to all men aged 45-74 years free of charge. More than three quarters of all men in this age group had at least one such test in the last decade. The authors applied the age-period-cohort model by Poisson regression to mortality data covering more than three decades, from 1970 to 2003. For Tyrol, the full model with age and period and cohort terms fit fairly well. Period terms showed a significant reduction in prostate cancer mortality in the last 5 years, with a risk ratio of 0.81 (95% confidence interval: 0.68, 0.98) for Tyrol; for Austria without Tyrol, no effect was seen, with a risk ratio of 1.00 (95% confidence interval: 0.95, 1.05). Each was compared with the mortality rate in the period 1989-1993. Although the results of randomized screening trials are not expected until 2008-2010, these findings support the evidence that prostate-specific antigen testing offered to a population free of charge can reduce prostate cancer mortality.

  14. The biology of cancer testis antigens: putative function, regulation and therapeutic potential.

    Science.gov (United States)

    Fratta, Elisabetta; Coral, Sandra; Covre, Alessia; Parisi, Giulia; Colizzi, Francesca; Danielli, Riccardo; Nicolay, Hugues Jean Marie; Sigalotti, Luca; Maio, Michele

    2011-04-01

    Cancer testis antigens (CTA) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches, and prompted the development of several clinical trials of CTA-based vaccine therapy. Driven by this practical clinical interest, a more detailed characterization of CTA biology has been recently undertaken. So far, at least 70 families of CTA, globally accounting for about 140 members, have been identified. Most of these CTA are expressed during spermatogenesis, but their function is still largely unknown. Epigenetic events, particularly DNA methylation, appear to be the primary mechanism regulating CTA expression in both normal and transformed cells, as well as in cancer stem cells. In view of the growing interest in CTA biology, the aim of this review is to provide the most recent information on their expression, regulation and function, together with a brief summary of the major clinical trials involving CTA as therapeutic agents. The pharmacologic modulation of CTA expression profiles on neoplastic cells by DNA hypomethylating drugs will also be discussed as a feasible approach to design new combination therapies potentially able to improve the clinical efficacy of currently adopted CTA-based immunotherapeutic regimens in cancer patients.

  15. 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

  16. Effects of distant metastasis and peripheral CA 15-3 on the induction of spontaneous T cell responses in breast cancer patients.

    Science.gov (United States)

    Domschke, Christoph; Schuetz, Florian; Sommerfeldt, Nora; Rom, Joachim; Scharf, Alexander; Sohn, Christof; Schneeweiss, Andreas; Beckhove, Philipp

    2010-03-01

    Tumor-specific memory T cells are detectable in the bone marrow (BM) of a majority of breast cancer patients. In vitro they can be reactivated to IFN-gamma producing, cytotoxic effector cells and reject autologous, xenotransplanted tumors in NOD/SCID mice after specific restimulation with autologous dendritic cells (DC). In this study, we demonstrate the presence of specific tumor-reactive BM memory T cells in altogether 56 out of 129 primarily operated breast cancer patients by short-term IFN-gamma EliSpot assays with unstimulated T cells and tumor antigen presenting, autologous DCs. We observed tumor-reactive BM memory T cells predominantly in patients with primarily metastatic disease (P = 0.011) or with increased concentrations of tumor marker CA 15-3 in the peripheral blood (P = 0.004), respectively. Memory T cell reactivity against HLA-A(*0201)-restricted peptides from the tumor-associated antigens MUC1, Hpa(16-24) and Hpa(183-191) was also detected particularly in patients with elevated peripheral CA 15-3 concentrations (P < 0.05). Altogether these data indicate that the systemic presence of tumor-derived antigens promotes an induction of tumor-specific cellular immune responses in the human BM. PMID:19957084

  17. 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

  18. 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

  19. 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

  20. 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...

  1. 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...

  2. 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...

  3. 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.

  4. Peritoneal lavage cytology and carcinoembryonic antigen determination in predicting peritoneal metastasis and prognosis of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ji-Kun Li; Miao Zheng; Chuan-Wen Miao; Jian-Hai Zhang; Guang-Han Ding; Wen-Shen Wu

    2005-01-01

    AIM: To evaluate the role of peritoneal lavage cytology (PLC) and carcinoembryonic antigen (CEA) determination of peritoneal washes (pCEA) in predicting the peritoneal metastasis and prognosis after curative resection of gastric cancer.METHODS: PLC and radioimmunoassay of CEA were performed in peritoneal washes from 64 patients with gastric cancer and 8 patients with benign diseases.RESULTS: The positive rate of pCEA (40.6%) was significantly higher than that of PLC (23.4%) (P<0.05).The positive rates of PLC and pCEA correlated with the depth of tumor invasion and lymph node metastasis (P<0.05). pCEA was found to have a higher sensitivity and a lower false-positive rate in predicting peritoneal metastasis after curative resection of gastric cancer as compared to PLC. The 1-, 3-, and 5-year survival rates of patients with positive cytologic findings or positive pCEA results were significantly lower than those of patients with negative cytologic findings or negative pCEA results (P<0.05). Multivariate analysis indicated that pCEA was an independent prognostic factor for the survival of patients with gastric cancer.CONCLUSION: Intraoperative pCEA is a more sensitive and reliable predictor of peritoneal metastasis as well as prognosis in patients with gastric cancer as compared to PLC method.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Effect of methoxychlor on Ca2+ handling and viability in OC2 human oral cancer cells.

    Science.gov (United States)

    Tseng, Li-Ling; Shu, Su-Shung; Kuo, Chun-Chi; Chou, Chiang-Ting; Hsieh, Yao-Dung; Chu, Sau-Tung; Chi, Chao-Chuan; Liang, Wei-Zhe; Ho, Chin-Man; Jan, Chung-Ren

    2011-05-01

    The effect of the insecticide methoxychlor on the physiology of oral cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) in human oral cancer cells (OC2) by using the Ca(2+)-sensitive fluorescent dye fura-2. Methoxychlor at 5-20 μM increased [Ca(2+)](i) in a concentration-dependent manner. The signal was reduced by 70% by removing extracellular Ca(2+). Methoxychlor-induced Ca(2+) entry was not affected by nifedipine, econazole, SK&F96365 and protein kinase C modulators but was inhibited by the phospholipase A2 inhibitor aristolochic acid. In Ca(2+)-free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) inhibited or abolished methoxychlor-induced [Ca(2+)](i) rise. Incubation with methoxychlor also inhibited thapsigargin- or BHQ-induced [Ca(2+)](i) rise. Inhibition of phospholipase C with U73122 did not alter methoxychlor-induced [Ca(2+)](i) rise. At 5-20 μM, methoxychlor killed cells in a concentration-dependent manner. The cytotoxic effect of methoxychlor was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/AM (BAPTA/AM). Annexin V-FITC data suggest that methoxychlor (10 and 20 μM) evoked apoptosis in a concentration-dependent manner. Together, in human OC2, methoxychlor induced a [Ca(2+)](i) rise probably by inducing phospholipase C-independent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via phospholipase A(2)-sensitive channels. Methoxychlor induced cell death that may involve apoptosis.

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

    Science.gov (United States)

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

    2015-10-01

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

  12. 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.

  13. Cancer T cell immunotherapy with bispecific antibodies and chimeric antigen receptors.

    Science.gov (United States)

    Lacher, Markus D; Provenzano, Maurizio

    2013-09-01

    Solid tumors contain several different types of malignant cells. This cellular heterogeneity complicates therapy for at least two reasons. First, each subpopulation may respond differently to a given treatment. Second, cancer cells are plastic, and thus may convert from a therapy-sensitive to a therapy-resistant cell type represented by another subpopulation. Therefore, successful therapies will have to target numerous malignant cell types, not just the rapidly proliferating cells as most standard treatments do. Immunotherapies with T cells engineered to recognize cancer cells via bispecific antibodies (bsAbs) or chimeric antigen receptors (CARs) are particularly promising approaches with potential to ablate both dividing and non/slow-dividing subpopulations of cancer cells. Here, we discuss several patents associated with exceptionally effective bsAbs of the tandem single-chain variable fragment (taFv) class and untangle a part of the complex network of patents directly or indirectly related to CARs. Furthermore, we speculate on the future of bsAbs and CARs for both treatment and prevention of solid tumors such as prostate cancer. PMID:23688207

  14. Diagnostic value of cancer-testis antigen mRNA in peripheral blood from hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To evaluate the diagnostic value of cancer-testis antigen(CTA) mRNA in peripheral blood samples from hepatocellular carcinoma(HCC) patients.METHODS:Peripheral blood samples were taken from 90 patients with HCC before operation.Expression of melanoma antigen-1(MAGE-1),synovial sarcoma X breakpoint-1(SSX-1),and cancer-testis-associated protein of 11 kDa(CTp11) mRNA in peripheral blood mononuclear cells(PBMC) was tested by nested reverse transcriptspolymerase chain reaction(RT-PCR).Serum α-fetoprotein(AFP)...

  15. 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

  16. 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.

  17. 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.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  19. Development of an antigen-capture ELISA for the detection of the p27-CA protein of HERV-K(HML-2).

    Science.gov (United States)

    Hohn, Oliver; Mostafa, Saeed; Norley, Stephen; Bannert, Norbert

    2016-08-01

    The detection or quantification of retroviruses is often achieved using an antigen-capture ELISA (AC-ELISA) that targets the Gag capsid (CA) protein. We report here the development of an AC-ELISA specific for the p27-CA protein of HERV-K(HML-2). A monoclonal p27-specific antibody is used for capture and a polyclonal anti-p27-CA immune serum generated in rabbits serves for detection. The assay was shown to be specific for HERV-K(HML-2), showing no evidence of cross reactivity with the human retroviruses HIV-1, HIV-2 and HTLV-1 or with XMRV (as a model non-human gammaretrovirus). Using purified recombinant antigen, the limit of detection was shown to be 130pg/ml. The AC-ELISA can be used to quantify HERV-K(HML-2) expression in teratocarcinoma cell lines and to normalize HERV particles generated by transfecting HEK 293T cells with full-length molecular clones. This novel AC-ELISA also proved useful in studies of virus regulation, for example in demonstrating that HERV-K(HML-2) expression is dramatically enhanced by overexpression of Staufen-1, a binding partner of the HERV-K(HML-2) Rec protein. This specific and sensitive HERV-K(HML-2) AC-ELISA will be a useful tool for investigating many aspects of endogenous retroviruses, from basic research to the role they may play in human diseases or as a surrogate marker for particular diseases.

  20. The role of E-cadherin - 160C/A polymorphism in breast cancer

    Directory of Open Access Journals (Sweden)

    Luo Gaojian

    2016-08-01

    Full Text Available Breast cancer is the most prevalent cancer in women worldwide. Numerous studies have suggested that the E-cadherin adhesion system is dysregulated in cancer cells. These impaired functions of E-cadherin contribute to releasing cancer cells from the primary lesion to cell dedifferentiation. Some studies have shown that polymorphism may affect E-cadherin expression, and then play a role in susceptibility to breast cancer. However, the results remained controversial. In this short review, we summarize the functions of E-cadherin and the signaling pathways it regulates, and assess the association between CDH1 polymorphisms and breast cancer susceptibility. This study suggests that genetic variation in CDH1 and -160C/A polymorphism may have an association with breast cancer risk. The assessment of CDH1 polymorphisms may be used for the identification of patients suitable for anti- CDH1 therapy.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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...

  7. Direct identification of an HPV-16 tumor antigen from cervical cancer biopsy specimens

    Directory of Open Access Journals (Sweden)

    Derin B Keskin

    2011-12-01

    Full Text Available Persistent infection with high-risk human papilloma viruses (HPV is the worldwide cause of many cancers, including cervical, anal, vulval, vaginal, penile and oropharyngeal. Since T cells naturally eliminate the majority of chronic HPV infections by recognizing epitopes displayed on virally altered epithelium, we exploited Poisson detection mass spectrometry (MS3 to identify those epitopes and inform future T cell-based vaccine design. Nine cervical cancer biopsies from HPV-16 positive HLA-A*02 patients were obtained, histopathology determined, and E7 oncogene PCR-amplified from tumor DNA and sequenced. Conservation of E7 oncogene coding segments was found in all tumors. MS3 analysis of HLA-A*02 immunoprecipitates detected E711-19 peptide (YMLDLQPET in seven of the nine tumor biopsies. The remaining two samples were E711-19 negative and lacked the HLA-A*02 binding GILT thioreductase peptide despite possessing binding-competent HLA-A*02 alleles. Thus, the conserved E711-19 peptide is a dominant HLA-A*02 binding tumor antigen in HPV-16 transformed cervical squamous and adenocarcinomas. Findings that a minority of HLA-A*02:01 tumors lack expression of both E711-19 and a peptide from a thioreductase important in processing of cysteine-rich proteins like E7 underscore the value of physical detection, define a potential additional tumor escape mechanism and have implications for therapeutic cancer vaccine development.

  8. Engineered Human Ferritin Nanoparticles for Direct Delivery of Tumor Antigens to Lymph Node and Cancer Immunotherapy

    Science.gov (United States)

    Lee, Bo-Ram; Ko, Ho Kyung; Ryu, Ju Hee; Ahn, Keum Young; Lee, Young-Ho; Oh, Se Jin; Na, Jin Hee; Kim, Tae Woo; Byun, Youngro; Kwon, Ick Chan; Kim, Kwangmeyung; Lee, Jeewon

    2016-01-01

    Efficient delivery of tumor-specific antigens (TSAs) to lymph nodes (LNs) is essential to eliciting robust immune response for cancer immunotherapy but still remains unsolved. Herein, we evaluated the direct LN-targeting performance of four different protein nanoparticles with different size, shape, and origin [Escherichia coli DNA binding protein (DPS), Thermoplasma acidophilum proteasome (PTS), hepatitis B virus capsid (HBVC), and human ferritin heavy chain (hFTN)] in live mice, using an optical fluorescence imaging system. Based on the imaging results, hFTN that shows rapid LN targeting and prolonged retention in LNs was chosen as a carrier of the model TSA [red fluorescence protein (RFP)], and the flexible surface architecture of hFTN was engineered to densely present RFPs on the hFTN surface through genetic modification of subunit protein of hFTN. The RFP-modified hFTN rapidly targeted LNs, sufficiently exposed RFPs to LN immune cells during prolonged period of retention in LNs, induced strong RFP-specific cytotoxic CD8+ T cell response, and notably inhibited RFP-expressing melanoma tumor growth in live mice. This suggests that the strategy using protein nanoparticles as both TSA-carrying scaffold and anti-cancer vaccine holds promise for clinically effective immunotherapy of cancer. PMID:27725782

  9. 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.

  10. 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...

  11. 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...

  12. 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.

  13. 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

  14. 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.

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

    Science.gov (United States)

    Tang, Shihao; Wang, Xubu; Shen, Qiang; Yang, Xinyi; Yu, Changhui; Cai, Chunqing; Cai, Guoshuai; Meng, Xiaojing; Zou, Fei

    2015-02-27

    Metastasis of cancer cells is a complicated multistep process requiring extensive and continuous cytosolic calcium modulation. Mitochondrial Ca(2+) uniporter (MCU), a regulator of mitochondrial Ca(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.

  16. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas.

    Science.gov (United States)

    Ishikawa, Nobuhisa; Takano, Atsushi; Yasui, Wataru; Inai, Kouki; Nishimura, Hitoshi; Ito, Hiroyuki; Miyagi, Yohei; Nakayama, Haruhiko; Fujita, Masahiro; Hosokawa, Masao; Tsuchiya, Eiju; Kohno, Nobuoki; Nakamura, Yusuke; Daigo, Yataro

    2007-12-15

    Gene expression profile analyses of non-small cell lung carcinomas (NSCLC) and esophageal squamous cell carcinomas (ESCC) revealed that lymphocyte antigen 6 complex locus K (LY6K) was specifically expressed in testis and transactivated in a majority of NSCLCs and ESCCs. Immunohistochemical staining using 406 NSCLC and 265 ESCC specimens confirmed that LY6K overexpression was associated with poor prognosis for patients with NSCLC (P = 0.0003), as well as ESCC (P = 0.0278), and multivariate analysis confirmed its independent prognostic value for NSCLC (P = 0.0035). We established an ELISA to measure serum LY6K and found that the proportion of the serum LY6K-positive cases was 38 of 112 (33.9%) NSCLC and 26 of 81 (32.1%) ESCC, whereas only 3 of 74 (4.1%) healthy volunteers were falsely diagnosed. In most cases, there was no correlation between serum LY6K and conventional tumor markers of carcinoembryonic antigen (CEA) and cytokeratin 19-fragment (CYFRA 21-1) values. A combined ELISA for both LY6K and CEA classified 64.7% of lung adenocarcinoma patients as positive, and the use of both LY6K and CYFRA 21-1 increased sensitivity in the detection of lung squamous cell carcinomas and ESCCs up to 70.4% and 52.5%, respectively, whereas the false positive rate was 6.8% to 9.5%. In addition, knocked down of LY6K expression with small interfering RNAs resulted in growth suppression of the lung and esophageal cancer cells. Our data imply that a cancer-testis antigen, LY6K, should be useful as a new type of tumor biomarker and probably as a target for the development of new molecular therapies for cancer treatment.

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

    Directory of Open Access Journals (Sweden)

    Angharad eLloyd

    2013-08-01

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

  18. Targeting dendritic cells in lymph node with an antigen peptide-based nanovaccine for cancer immunotherapy.

    Science.gov (United States)

    Qian, Yuan; Jin, Honglin; Qiao, Sha; Dai, Yanfeng; Huang, Chuan; Lu, Lisen; Luo, Qingming; Zhang, Zhihong

    2016-08-01

    The design of peptide-based subunit vaccine formulations for the direct delivery of tumor antigen peptides (Aps) to dendritic cells (DCs) localized within draining lymph nodes (DLNs) is challenging. Mature DCs (mDCs) are abundantly distributed within DLNs but have dramatically reduced endocytic uptake and antigen-processing abilities, so their role as potential vaccine targets has been largely overlooked. Here we report an ultra-small biocompatible nanovaccine (α-Ap-FNP) functionalized by avidly targeting delivery of Ap via the scavenger receptor class B1 (SR-B1) pathway to mDCs. The self-assembly, small size (∼30 nm), SR-B1-targeting and optical properties of α-Ap-FNP resulted in its efficient Ap loading, substantial LN accumulation, targeting of mDCs and enhanced Ap presentation, and fluorescence trafficking, respectively. We also demonstrate that the α-Ap-FNP can be either used alone or encapsulated with CpG oligodeoxynucleotide as a prophylactic and therapeutic vaccine. Thus, the excellent properties of α-Ap-FNP provide it potential for clinical applications as a potent nanovaccine for cancer immunotherapy.

  19. Preoperative serum squamous cell carcinoma antigen levels in clinical decision making for patients with early-stage cervical cancer

    NARCIS (Netherlands)

    Reesink-Peters, N; van der Velden, J; ten Hoor, KA; Boezen, HM; de Vries, EGE; Schilthuis, MS; Mourits, MJE; Nijman, HW; Aalders, JG; Hollema, H; Pras, E; Duk, JM; van der Zee, AGJ

    2005-01-01

    PURPOSE: To prevent morbidity associated with double modality treatment, early-stage cervical cancer patients should only be offered surgery when there is a low likelihood for adjuvant radiotherapy. We analyzed whether serum squamous cell carcinoma antigen (SCC-ag) analysis allows better preoperativ

  20. 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

  1. 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...

  2. Demethylating agent decitabine induces autologous cancer testis antigen specific cytotoxic T lymphocytes in vivo

    Institute of Scientific and Technical Information of China (English)

    ZHOU Ji-hao; YAO Yu-shi; WANG Li-xin; WANG Jia; LI Yong-hui; JIANG Meng-meng; ZHOU Min-hang

    2013-01-01

    Background Cancer testis antigens (CTAs) are a novel group of tumor associated antigens.Demethylating agent decitabine was reported to be able to up-regulate CTAs through its hypomethylation mechanism,thus enhance the immunogenicity of leukemia cells.However,few researches have ever focused on the questions that whether this immunostimulatory effect of decitabine could induce autologous CTA specific cytotoxic T lymphocytes (CTLs) in vivo,and if so,whether this effect contributes to disease control.In this study,we aimed to show that decitabine could induce specific autologous CTLs against some mouse CTAs in leukemia cells in vitro and in vivo.Methods Several mouse CTAs were screened by RT-PCR.CTL specific to one of the CTAs named P1A was detected and sorted by P1A specific dimer by flow cytometry.The activity of specific CTLs was measured by real time RT-PCR.Results We firstly screened expression of some CTAs in mouse leukemia cells before and after decitabine treatment and found that decitabine treatment did up-regulate expression of many CTAs.Then we measured the CTLs' activity specific to a mouse CTA P1A in vivo and showed that this activity increased after decitabine treatment.Finally,we sorted these in vivo induced P1A specific CTLs by flow cytometry and demonstrated their cytotoxicity against decitabine treated leukemia cells.Conclusions Our study showed the autologous immune response induced by decitabine in vivo.And more importantly,we firstly proved that this response may contribute to disease control.We believe that this immunostimulatory effect is another anti-cancer mechanism of decitabine,and this special effect would inspire new applications of decitabine in the field of leukemia treatment in the future.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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...

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  9. 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...

  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;

    2015-01-01

    receptor (EGFR). The efficacy of tyrosine kinase inhibitors (TKI) in the context of melanoma-associated antigens is discussed in the present study. Five human squamous cell carcinoma cell lines were treated with the EGFR TKIs, erlotinib and gefitinib. The efficacy of these agents was measured using......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...... correlation 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. 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.

  12. 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...

  13. 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

  14. Role of tumor-associated antigen expression in radioimmunoguided surgery for colorectal and breast cancer.

    Science.gov (United States)

    Bertoglio, S; Percivale, P; Schenone, F; Peressini, A; Murolo, C; Badellino, F

    1998-12-01

    One hundred thirty-six patients with colorectal and breast cancer were enrolled in a retrospective study using radioimmunoguided surgery (RIGS) with Iodine-125 (I125) radiolabeled B72.3 (Group A, 73 patients) and F023C5 (Group B, 63 patients) monoclonal antibodies (MAbs). The correlation between intraoperative tumor-to-normal tissue (T/NT) gamma-detecting probe (GDP) counts ratio and the expression of tumor-associated glycoprotein (TAG)-72 (GroupA patients) and carcinoembryonic antigen (CEA; Group B patients) tumor-associated antigens (TAA) expression of 209 resected or biopsy tumor specimens was assessed. Ex vivo radioimmunolocalization index (R.I.) was carried out on the same specimens as a control of intraoperative GDP ratio values. RIGS positive definition of tumor occurred in 80/113 (70.8%) tumor sites of Group A patients and in 84/96 (87.5%) tumor sites of Group B patients. Mean percent B72.3 TAA expression of 113 tumor sites of Group A patients was 62.74 +/- 28.79% vs. 73.00 +/- 26.28% of 96 tumor sites of Group B patients (P < 0.05). The higher incidence of positive RIGS results was observed in tumor sites with the higher expression of the relative TAA. A statistically significant correlation between RIGS ratios and B72.3 and CEA expression was observed in the 113 tumor sites of Group A (P < 0.05) and in the 96 tumor sites of Group B (P < 0.01), respectively. The role of a preoperative evaluation of TAA expression in patients undergoing RIGS is discussed. Its assessment, whenever possible, may help to select those patients who will benefit more from this immunodiagnostic technique.

  15. 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.

  16. Decreasing trend in prostate cancer with high serum prostate-specific antigen levels detected at first prostate-specific antigen-based population screening in Japan

    Directory of Open Access Journals (Sweden)

    Yasuhide Kitagawa

    2014-12-01

    Full Text Available To clarify the recent trends in prostate-specific antigen (PSA distribution in men in Japan, we analyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54-69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng ml−1 in 2000, and gradually decreased to approximately 1.30 ng ml−1 in 2006. That of participants excluding prostate cancer patients was 1.46 ng ml−1 in 2000, and there was no remarkable change during the study period. The 95 th percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54-59, 60-64, and 65-69 years old were 2.90, 3.60, and 4.50 ng ml−1 , respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.

  17. Independent [Ca2+]i increases and cell proliferation induced by the carcinogen safrole in human oral cancer cells.

    Science.gov (United States)

    Huang, Jong-Khing; Huang, Chun-Jen; Chen, Wei-Chuan; Liu, Shiuh-Inn; Hsu, Shu-Shong; Chang, Hong-Tai; Tseng, Li-Ling; Chou, Chiang-Ting; Chang, Chih-Hung; Jan, Chung-Ren

    2005-07-01

    The effect of the carcinogen safrole on intracellular Ca2+ movement and cell proliferation has not been explored previously. The present study examined whether safrole could alter Ca2+ handling and growth in human oral cancer OC2 cells. Cytosolic free Ca2+ levels ([Ca2+]i) in populations of cells were measured using fura-2 as a fluorescent Ca2+ probe. Safrole at a concentration of 325 microM started to increase [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 40% by removing extracellular Ca2+, and was decreased by 39% by nifedipine but not by verapamil or diltiazem. In Ca2+-free medium, after pretreatment with 650 microM safrole, 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) barely induced a [Ca2+]i rise; in contrast, addition of safrole after thapsigargin treatment induced a small [Ca2+]i rise. Neither inhibition of phospholipase C with 2 microM U73122 nor modulation of protein kinase C activity affected safrole-induced Ca2+ release. Overnight incubation with 1 microM safrole did not alter cell proliferation, but incubation with 10-1000 microM safrole increased cell proliferation by 60+/-10%. This increase was not reversed by pre-chelating Ca2+ with 10 microM of the Ca2+ chelator BAPTA. Collectively, the data suggest that in human oral cancer cells, safrole induced a [Ca2+]i rise by causing release of stored Ca2+ from the endoplasmic reticulum in a phospholipase C- and protein kinase C-independent fashion and by inducing Ca2+ influx via nifedipine-sensitive Ca2+ entry. Furthermore, safrole can enhance cell growth in a Ca2+-independent manner.

  18. IMMUNOTHERAPY OF SPONTANEOUS METASTATIC LUNG CANCER WITH TUMOR ANTIGEN-PULSED, INTERLEUKIN-12 GENE-MODIFIED DENDRITIC CELLS

    Institute of Scientific and Technical Information of China (English)

    陈吉泉; 修清玉; 颜泽敏; 罗文侗

    2003-01-01

    Objective: To investigate the treatment of spontaneous metastatic lung cancer by tumor antigen-pulsed, interleukin-12 (IL-12) gene-modified dendritic cells (DC). Methods:The spontaneous metastatic lung cancer model, prepared by injection of the 3LL Lewis lung cancer cells into the footpads of C57BL/6 mice, was treated by subcutaneous vaccination with tumor antigen peptide mut1-pulsed, IL-12 gene-modified dendritic cells (DC-IL-12/mut1) derived from the normal bone morrow. After treatment, the lung weight, the number of lung metastatic nodes and the survival time of the tumor-bearing mice were observed, and the NK and CTL activity were determined respectively. The mice were divided into 8 groups with 12 mice in each group. Results: Compared with mice treated with mut1-pulsed, control LacZ gene modified DC and untreated DC, tumor-bearing mice treated with DC-IL-12/mut1 had the lightest lung weights (P<0.01), the least lung metastatic node number (P<0.01), the longest survival time (P<0.01), also with the induction of potent CTL activity (P<0.01) and NK activity (P<0.01). Conclusion: Tumor antigen-pulsed, IL-12 gene-modified dendritic cells have significant therapeutic effects on the spontaneous metastatic lung cancer, providing a new approach to treatment of lung tumors.

  19. 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

  20. 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.

  1. 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

  2. Effect of NPC15199 on [Ca²⁺]i and viability in SCM1 human gastric cancer cells.

    Science.gov (United States)

    Cheng, He-Hsiung; Chou, Chiang-Ting; Liang, Wei-Zhe; Cheng, Jin-Shiung; Chang, Hong-Tai; Kuo, Chun-Chi; Chen, I-S; Lu, Ti; Yu, C-C; Chen, Fu-An; Kuo, Daih-Huang; Shieh, Pochuen; Jan, Chung-Ren

    2016-10-31

    NPC15199 is a synthesized compound that inhibits inflammation in some models. However, whether NPC15199 affects Ca²⁺ homeostasis in human gastric cancer is unclear. This study examined the effect of NPC15199 on cytosolic free Ca²⁺ concentrations ([Ca²⁺]i) and viability in SCM1 human gastric cancer cells. The Ca²⁺-sensitive fluorescent dye fura-2 was used to measure [Ca²⁺]i. NPC15199 evoked [Ca²⁺]i rises concentration-dependently. The response was reduced by removing extracellular Ca²⁺. NPC15199-evoked Ca²⁺ entry was not inhibited by store-operated channel inhibitors (nifedipine, econazole and SKF96365) and protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate, PMA), or PKC inhibitor (GF109203X). In Ca²⁺-free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) nearly abolished NPC15199-evoked [Ca²⁺]i rises. Conversely, treatment with NPC15199 also nearly abolished thapsigargin or BHQ-evoked [Ca²⁺]i rises. Inhibition of phospholipase C (PLC) with U73122 did not affect NPC15199-evoked [Ca²⁺]i rises. NPC15199 at concentrations of 100-900 μM induced concentration-dependent, Ca²⁺-independent decrease in viability. Together, in SCM1 cells, NPC15199 induced [Ca²⁺]i rises that involved Ca²⁺ entry through PKC-insensitive non-store-operated Ca²⁺ channels and PLC-independent Ca²⁺ release from the endoplasmic reticulum. NPC15199 also induced Ca²⁺-independent cell death.

  3. 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

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  5. 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...

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

    NARCIS (Netherlands)

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

    1996-01-01

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

  7. 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...

  8. 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.

  9. CA 125 in the follow-up of patients with ovarian cancer.

    Science.gov (United States)

    Koelbl, H; Schieder, K; Neunteufel, W; Bieglmayer, C

    1988-04-01

    Three hundred and ninety-five CA 125 serum values of 72 patients with ovarian cancer were correlated with the clinical status. With a threshold value of 35 U/ml we found true negative values in 85% and true positive values in 93%. No correlation between preoperative CA 125 values and tumor stage was noted at primary surgery. During follow-up, 17 women had marker values between 35 and 65 U/ml. Three out of 7 women in clinical remission showed a value greater than 65 U/ml at subsequent follow-up and developed recurrent disease. In 8 patients out of 20 re-laparotomies, tumors with a maximum diameter of greater than 2 cm were confirmed with a preoperative serum CA 125 concentration greater than 65 U/ml. Two out of 3 patients with a tumor diameter less than 2 cm at re-laparotomy revealed CA 125 serum concentrations less than 35 U/ml. A false positive CA 125 value was found in one patient without demonstrable active disease. The calculated doubling time of the CA 125 values ranged between 23 and 173 days; the median value was 67 +/- 47 days. After 6.2 +/- 1.3 doubling times death ensued.

  10. 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.

  11. Drug-resistant colon cancer cells produce high carcinoembryonic antigen and might not be cancer-initiating cells

    Directory of Open Access Journals (Sweden)

    Lee HC

    2013-06-01

    Full Text Available Hsin-chung Lee,1,2 Qing-Dong Ling,1,3 Wan-Chun Yu,4 Chunh-Ming Hung,4 Ta-Chun Kao,4 Yi-Wei Huang,4 Akon Higuchi3–51Graduate Institute of Systems Biology and Bioinformatics, National Central University, Jhongli, Taoyuan, 2Department of Surgery, Cathay General Hospital, Da'an District, Taipei, 3Cathay Medical Research Institute, Cathay General Hospital, Hsi-Chi City, Taipei, 4Department of Chemical and Materials Engineering, National Central University, Jhongli, Taoyuan, Taiwan; 5Department of Reproduction, National Research Institute for Child Health and Development, Okura, Tokyo, JapanPurpose: We evaluated the higher levels of carcinoembryonic antigen (CEA secreted by the LoVo human colon carcinoma cells in a medium containing anticancer drugs. Drug-resistant LoVo cells were analyzed by subcutaneously xenotransplanting them into mice. The aim of this study was to evaluate whether the drug-resistant cells isolated in this study were cancer-initiating cells, known also as cancer stem cells (CSCs.Methods: The production of CEA was investigated in LoVo cells that were cultured with 0–10 mM of anticancer drugs, and we evaluated the increase in CEA production by the LoVo cells that were stimulated by anticancer drug treatment. The expression of several CSC markers in LoVo cells treated with anticancer drugs was also evaluated. Following anticancer drug treatment, LoVo cells were injected subcutaneously into the flanks of severe combined immunodeficiency mice in order to evaluate the CSC fraction.Results: Production of CEA by LoVo cells was stimulated by the addition of anticancer drugs. Drug-resistant LoVo cells expressed lower levels of CSC markers, and LoVo cells treated with any of the anticancer drugs tested did not generate tumors within 8 weeks from when the cells were injected subcutaneously into severe combined immunodeficiency mice. These results suggest that the drug-resistant LoVo cells have a smaller population of CSCs than the

  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. Prospects for adoptive immunotherapy of pancreatic cancer using chimeric antigen receptor-engineered T-cells.

    Science.gov (United States)

    Alrifai, Doraid; Sarker, Debashis; Maher, John

    2016-01-01

    Adoptive immunotherapy using chimeric antigen receptor (CAR) engineered T-cells is emerging as a powerful new approach to cancer immunotherapy. CARs are fusion molecules that couple the antibody-like binding of a native cell surface target to the delivery of a bespoke T-cell activating signal. Recent studies undertaken by several centers have demonstrated highly compelling efficacy in patients with acute and chronic B-cell malignancies. However, comparable therapeutic activity has not been achieved in solid tumors. Modern management of pancreatic ductal adenocarcinoma (PDAC) remains ineffective, reflected in the virtual equivalence of annual incidence and mortality statistics for this tumor type. Increasing evidence indicates that these tumors are recognized by the immune system, but deploy powerful evasion strategies that limit natural immune surveillance and render efforts at immunotherapy challenging. Here, we review preclinical and clinical studies that have been initiated or completed in an effort to develop CAR-based immunotherapy for PDAC. We also consider the hurdles to the effective clinical development of this exciting new therapeutic modality.

  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. The serologically defined colon cancer antigen-3 (SDCCAG3) is involved in the regulation of ciliogenesis

    Science.gov (United States)

    Yu, Fangyan; Sharma, Shruti; Skowronek, Agnieszka; Erdmann, Kai Sven

    2016-01-01

    A primary cilium is present on most eukaryotic cells and represents a specialized organelle dedicated to signal transduction and mechanosensing. Defects in cilia function are the cause for several human diseases called ciliopathies. The serologically defined colon cancer antigen-3 (SDCCAG3) is a recently described novel endosomal protein mainly localized at early and recycling endosomes and interacting with several components of membrane trafficking pathways. Here we describe localization of SDCCAG3 to the basal body of primary cilia. Furthermore, we demonstrate that decreased expression levels of SDCCAG3 correlate with decreased ciliary length and a reduced percentage of ciliated cells. We show that SDCCAG3 interacts with the intraflagellar transport protein 88 (IFT88), a crucial component of ciliogenesis and intraciliary transport. Mapping experiments revealed that the N-terminus of SDCCAG3 mediates this interaction by binding to a region within IFT88 comprising several tetratricopeptide (TRP) repeats. Finally, we demonstrate that SDCCAG3 is important for ciliary localization of the membrane protein Polycystin-2, a protein playing an important role in the formation of polycystic kidney disease, but not for Rab8 another ciliary protein. Together these data suggest a novel role for SDCCAG3 in ciliogenesis and in localization of cargo to primary cilia. PMID:27767179

  16. 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.

  17. Antiproliferative effects of goniothalamin on Ca9-22 oral cancer cells through apoptosis, DNA damage and ROS induction.

    Science.gov (United States)

    Yen, Ching-Yu; Chiu, Chien-Chih; Haung, Rou-Wen; Yeh, Chi-Chen; Huang, Kuang-Jing; Chang, Kuo-Feng; Hseu, You-Cheng; Chang, Fang-Rong; Chang, Hsueh-Wei; Wu, Yang-Chang

    2012-09-18

    Goniothalamin (GTN), a plant bioactive styryl-lactone, is a natural product with potent anti-tumorigenesis effects for several types of cancer. Nonetheless, the anticancer effect of GTN has not been examined in oral cancer. The present study was designed to evaluate its potential anticancer effects in an oral squamous cell carcinoma (OSCC) model and to determine the possible mechanisms with respect to apoptosis, DNA damage, reactive oxygen species (ROS) induction, and mitochondrial membrane potential. Our data demonstrated that cell proliferation was significantly inhibited by GTN in Ca9-22 OSCC cancer cells in concentration- and time-dependent manners (pGTN-treated Ca9-22 cancer cells, the sub-G1 population and annexin V-intensity significantly increased in a concentration-dependent manner (pGTN-treated Ca9-22 cancer cells in concentration-response relationship (pGTN significantly induced intracellular ROS levels in Ca9-22 cancer cells in a concentration- and time-dependent manner (pGTN-treated Ca9-22 cancer cells was significantly decreased in concentration- and time-dependent relationships (pGTN against oral cancer cells is valid and GTN-induced growth inhibition and apoptosis influence the downstream cascade including ROS induction, DNA damage, and mitochondria membrane depolarization. Therefore, GTN has potential as a chemotherapeutic agent against oral cancer.

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Ian M Smith

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

  20. Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers.

    Science.gov (United States)

    Wernicke, Alla Gabriella; Varma, Sonal; Greenwood, Eleni A; Christos, Paul J; Chao, K S Clifford; Liu, He; Bander, Neil H; Shin, Sandra J

    2014-06-01

    Prostate-specific membrane antigen (PSMA) has been found to be expressed in the tumor-associated neovasculature of multiple solid tumor types including breast cancers. However, thus far, the number of cases studied from some tumor types has been limited. In this study, we set out to assess PSMA expression in the tumor-associated vasculature associated with invasive breast carcinomas in a sizable cohort of patients. One hundred and six patients with AJCC stage 0-IV breast cancer were identified. Ninety-two of these patients had primary breast cancer [invasive breast carcinoma with or without co-existing ductal carcinoma in situ (DCIS) (74) or DCIS alone (18)]. In addition, 14 patients with breast cancer metastases to the brain were identified. Immunohistochemical staining for PSMA and CD31 was performed on parallel representative tumor sections in each case. Tumor-associated vascular endothelial cell PSMA immunoreactivity was semi-quantitatively assessed based on two parameters: overall percent of endothelial positivity and staining intensity. PSMA expression for tumor-associated vascular endothelial cells was scored 0 if there was no detectable PSMA expression, 1 if PSMA staining was detectable in 5-50%, and 2 if PSMA expression was positive in >50% of microvessels. CD 31 staining was concurrently reviewed to confirm the presence of vasculature in each case. Tumor-associated vasculature was PSMA-positive in 68/92 (74%) of primary breast cancers and in 14/14 (100%) of breast cancers metastatic to brain. PSMA was not detected in normal breast tissue or carcinoma cells. All but 2 cases (98%) showed absence of PSMA expression in normal breast tissue-associated vasculature. The 10-year overall survival was 88.7% (95% CI = 80.0%, 93.8%) in patients without brain metastases. When overall survival (OS) was stratified based on PSMA score group, patients with PSMA scores of 0, 1, and 2 had 10-year OS of 95.8%, 96.0%, and 79.7%, respectively (p = 0.12). When PSMA scores

  1. 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

  2. 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.

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

    NARCIS (Netherlands)

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

    1991-01-01

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

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

    Directory of Open Access Journals (Sweden)

    N. Povolotskaya

    2014-01-01

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

  5. 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

  6. 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.

  7. 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...

  8. 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

  9. A combined approach of human leukocyte antigen ligandomics and immunogenicity analysis to improve peptide-based cancer immunotherapy.

    Science.gov (United States)

    Peper, Janet Kerstin; Stevanović, Stefan

    2015-10-01

    The breakthrough development of immune checkpoint inhibitors as clinically effective novel therapies demonstrates the potential of cancer immunotherapy. The identification of suitable targets for specific immunotherapy, however, remains a challenging task. Most peptides previously used for vaccination in clinical trials were able to elicit strong immunological responses but failed with regard to clinical benefit. This might, at least partly, be caused by an inadequate peptide selection, usually derived from established tumor-associated antigens which are not necessarily presented as human leukocyte antigen (HLA) ligands. Recently, HLA ligandome analysis revealed cancer-associated peptides, which have been used in clinical trials showing encouraging impact on survival. To improve peptide-based cancer immunotherapy, our group established a combined approach of HLA ligandomics and immunogenicity analysis for the identification of vaccine peptides. This approach is based on the identification of naturally presented HLA ligands on tumor samples, the selection of tumor-associated/tumor-specific HLA ligands and their subsequent testing for immunogenicity in vitro. In this review, we want to present our pipeline for the identification of vaccine peptides, focusing on ovarian cancer, and want to discuss differences to other approaches. Furthermore, we want to give a short outlook of a potential multi-peptide vaccination trial using the novel identified peptides.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2015-12-15

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

  12. 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

  13. 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.

  14. Prostate-specific antigen (PSA) velocity: a test of controversial benefit in the era of increased prostate cancer screening

    Institute of Scientific and Technical Information of China (English)

    Michael S Borofsky; Danil V Makarov

    2011-01-01

    @@ Determining the need for prostate biopsy remains one of the most controversial questions in urology.Over the past 10 years, practice guidelines have changed dramatically, especially among asymptomatic men with low prostate-specific antigen (PSA) and negative digital rectal exam.Thompson et al.Found that nearly 15% of men with PSA <4.0 had evidence of prostate cancer on biopsy;1 however, the clinical significance of these tumors is unclear.PSAvelocity (PSAV) has been suggested as a measurement to discriminate between aggressive and indolent cancers.Both the NCCN2 and AUA3 guidelines recommend considering prostate biopsy for men with PSA <4.0 and high PSAV (0.35 and 0.4 ng/ml/year, respectively); however, a recent article by Vickers et al.4 has called these recommendations into question, suggesting that PSAV adds little predictive accuracy to the standard risk factor assessment for prostate cancer.

  15. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-05-01

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

  17. 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

  18. 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.

  19. 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

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

    Directory of Open Access Journals (Sweden)

    Xing Guo Wang

    Full Text Available 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 hypothesized that it was possible to treat experimental HPV16-associated cervical cancer (CC and Hepatitis B-associated hepatocellular carcinoma (HCC by targeting viral antigens expressed on cancer cells with radiolabeled antibodies to viral antigens. Treatment of experimental CC and HCC tumors with (188Re-labeled mAbs to E6 and HBx viral proteins, respectively, resulted in significant and dose-dependent retardation of tumor growth in comparison with untreated mice or mice treated with unlabeled antibodies. CONCLUSIONS/SIGNIFICANCE: This strategy is fundamentally different from the prior uses of radioimmunotherapy in oncology, which targeted tumor-associated human antigens and promises increased specificity and minimal toxicity of treatment. It also raises an exciting possibility to prevent virus-associated cancers in chronically infected patients by eliminating cells infected with oncogenic viruses before they transform into cancer.

  1. 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...

  2. 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.

  3. 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.

  4. 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

  5. Cancer immunotherapy using novel tumor-associated antigenic peptides identified by genome-wide cDNA microarray analyses.

    Science.gov (United States)

    Nishimura, Yasuharu; Tomita, Yusuke; Yuno, Akira; Yoshitake, Yoshihiro; Shinohara, Masanori

    2015-05-01

    Recent genome-wide cDNA microarray analysis of gene expression profiles in comprehensive tumor types coupled with isolation of cancer tissues by laser-microbeam microdissection have revealed ideal tumor-associated antigens (TAAs) that are frequently overexpressed in various cancers including head and neck squamous cell cancer (HNSCC) and lung cancer, but not in most normal tissues except for testis, placenta, and fetal organs. Preclinical studies using HLA-transgenic mice and human T cells in vitro showed that TAA-derived CTL-epitope short peptides (SPs) are highly immunogenic and induce HLA-A2 or -A24-restricted CTLs. Based on the accumulated evidence, we carried out a phase II clinical trial of the TAA-SP vaccine in advanced 37 HNSCC patients. This study showed a significant induction of TAA-specific CTLs in the majority of patients without serious adverse effects. Importantly, clinical responses including a complete response were observed in this study. Another phase II clinical trial of therapeutic TAA-SP vaccine, designed to evaluate the ability of prevention of recurrence, is ongoing in HNSCC patients who have received curative operations. Further studies in human preclinical studies and in vivo studies using HLA class I transgenic mice showed TAA-derived long peptides (TAA-LPs) have the capacity to induce not only promiscuous HLA class II-restricted CD4(+) T helper type 1 cells but also tumor-specific CTLs through a cross-presentation mechanism. Moreover, we observed an augmentation of TAA-LP-specific T helper type 1 cell responses and tumor antigen-spreading in HNSCC patients vaccinated with TAA-SPs. This accumulated evidence suggests that therapeutic TAA-SPs and LPs vaccines may provide a promising cancer immunotherapy.

  6. 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

  7. 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

  8. 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...

  9. Anti-colorectal cancer effect of interleukin-2 and interferon-β fusion gene driven by carcinoembryonic antigen promoter

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-05-01

    Full Text Available Yan Wang, Mengchun Wang, Yan LiDepartment of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaAbstract: This study was designed to investigate the antitumor effects of combined interleukin-2/interferon-β-based gene therapy in colorectal cancer. Transfection of the fusion gene expression plasmid induced significant apoptosis of Lovo cells. Additionally, the fusion gene exhibited strong inhibitory activity against tumor growth and apoptosis when being injected into the nude mice implanted with human colon cancer cells. Furthermore, the tail-vein injection showed a more notable effect than direct injection into tumor. These results suggest that the combined interleukin-2/interferon-β-based gene therapy with the carcinoembryonic antigen promoter might be an effective antitumor strategy.Keywords: apoptosis, interferon-β, interleukin-2, antitumor, combined gene therapy

  10. MAGE-A1, GAGE and NY-ESO-1 cancer/testis antigen expression during human gonadal development

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Kock, Kirsten; Nielsen, Ole;

    2007-01-01

    BACKGROUND: Cancer/testis antigens (CTAs) are expressed in several cancers and during normal adult male germ cell differentiation. Little is known about their role in fetal development of human germ cells. METHODS: We examined expression of the CTAs MAGE-A1, GAGE and NY-ESO-1 in fetal gonads...... by single and double immunohistochemical staining. RESULTS: We found that GAGE was expressed in the primordial germ cells of the gonadal primordium, whereas MAGE-A1 and NY-ESO-1 were first detected in germ cells of both testis and ovary after sexual differentiation was initiated. The number of positive germ...... cells and the staining intensity of all three CTAs peaked during the second trimester and gradually decreased towards birth in both male and female germ cells. In oocytes, MAGE-A1 expression terminated around birth, whereas NY-ESO-1 expression persisted through the neonatal stage and GAGE expression...

  11. 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

  12. 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

  13. 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

  14. 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

  15. Recombinant Lactobacillus plantarum induces immune responses to cancer testis antigen NY-ESO-1 and maturation of dendritic cells.

    Science.gov (United States)

    Mobergslien, Anne; Vasovic, Vlada; Mathiesen, Geir; Fredriksen, Lasse; Westby, Phuong; Eijsink, Vincent G H; Peng, Qian; Sioud, Mouldy

    2015-01-01

    Given their safe use in humans and inherent adjuvanticity, Lactic Acid Bacteria may offer several advantages over other mucosal delivery strategies for cancer vaccines. The objective of this study is to evaluate the immune responses in mice after oral immunization with Lactobacillus (L) plantarum WCFS1 expressing a cell-wall anchored tumor antigen NY-ESO-1. And to investigate the immunostimulatory potency of this new candidate vaccine on human dendritic cells (DCs). L. plantarum displaying NY-ESO-1 induced NY-ESO-1 specific antibodies and T-cell responses in mice. By contrast, L. plantarum displaying conserved proteins such as heat shock protein-27 and galectin-1, did not induce immunity, suggesting that immune tolerance to self-proteins cannot be broken by oral administration of L. plantarum. With respect to immunomodulation, immature DCs incubated with wild type or L. plantarum-NY-ESO-1 upregulated the expression of co-stimulatory molecules and secreted a large amount of interleukin (IL)-12, TNF-α, but not IL-4. Moreover, they upregulated the expression of immunosuppressive factors such as IL-10 and indoleamine 2,3-dioxygenase. Although L. plantarum-matured DCs expressed inhibitory molecules, they stimulated allogeneic T cells in-vitro. Collectively, the data indicate that L. plantarum-NY-ESO-1 can evoke antigen-specific immunity upon oral administration and induce DC maturation, raising the potential of its use in cancer immunotherapies.

  16. Detection rate of prostate cancer using prostate specific antigen in patients presenting with lower urinary tract symptoms: A retrospective study

    Directory of Open Access Journals (Sweden)

    Chavan P

    2009-01-01

    Full Text Available Background: Need for undertaking prostate biopsies for detection of prostate cancer is often decided on the basis of serum levels of prostate specific antigen (PSA. Aim: To evaluate the case detection rate of prostate cancer among patients presenting with lower urinary tract symptoms (LUTS on the basis of PSA levels and to assess the scope of prostate biopsy in these patients. Setting and Design: A retrospective study from a tertiary care center. Materials and Methods: The clinical and histopathological data of 922 patients presenting with LUTS in the last five years was obtained from the medical record section. They had been screened for prostate cancer using PSA and /or digital rectal examination examination followed by confirmation with prostate biopsy. Statistical Analysis Used: Detection rate and receiver operating characteristic curve were performed using SPSS 16 and Medcalc softwares. Results: The detection rate of prostate cancer according to the PSA levels was 0.6%, 2.3%, 2.5%, 34.1% and 54.9% in the PSA range of 0-4, 4-10, 10-20, 20-50 and> 50 ng/ml, respectively. Maximum prostate cancer cases were detected beyond a PSA value of 20 ng/ml whereas no significant difference in the detection rate was observed in the PSA range of 0-4, 4-10 and 10-20 ng/ml. Conclusion: A low detection rate of prostate cancer observed in the PSA range of 4-20 ng/ml in LUTS patients indicates the need for use of higher cutoff values of PSA in such cases. Therefore we recommend a cutoff of 20 ng/ml of PSA for evaluation of detection rate of prostate cancer among patients presenting with LUTS.

  17. Expression of prostate-specific membrane antigen in lung cancer cells and tumor neovasculature endothelial cells and its clinical significance.

    Directory of Open Access Journals (Sweden)

    Hai-long Wang

    Full Text Available Prostate-specific membrane antigen (PSMA has been found in tumor neovasculature endothelial cells (NECs of non-prostate cancers and may become the most promising target for anti-tumor therapy. To study the value of PSMA as a potential new target for lung cancer treatment, PSMA expression in non-small cell lung cancer (NSCLC and small cell lung cancer (SCLC tissues and its relationship with clinicopathology were investigated in the current study.Immunohistochemistry was used to detect PSMA expression in a total of 150 lung specimens of patients with lung cancer. The data were analyzed using univariate and multivariate statistical analyses.The percentages of NSCLC patients who had PSMA (+ tumor cells and PSMA (+ NECs were 54.02% and 85.06%, respectively. The percentage of patients younger than 60 years old who had PSMA (+ tumor cells was 69.05%, which was significantly greater than the percentage of patients aged 60 years or older (40.00%, p<0.05. A significant difference was observed in the percentage of NSCLC patients with PMSA (+ NECs and stage I or II cancer (92.98% and those patients with stage III or IV cancer (76.77%. In the SCLC tissues, NEC PSMA expression (70.00% did not differ significantly from NSCLC. SCLC tumor cells and normal lung tissues cells were all negative. There was no significant correlation between the presence of PSMA (+ NECs in SCLC patients and the observed clinicopathological parameters.PSMA is expressed not only in NECs of NSCLC and SCLC but also in tumor cells of most NSCLC patients. The presence of PSMA (+ tumor cells and PSMA (+ NECs in NSCLC was negatively correlated with age and the clinicopathological stage of the patients, respectively.

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

    Science.gov (United States)

    Matsumoto, Yasuyuki; Zhang, Qing; Akita, Kaoru; Nakada, Hiroshi; Hamamura, Kazunori; Tokuda, Noriyo; Tsuchida, Akiko; Matsubara, Takeshi; Hori, Tomoko; Okajima, Tetsuya; Furukawa, Keiko; Urano, Takeshi; Furukawa, Koichi

    2012-03-01

    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 metastasis than control clones. These data suggested that high expression of pp-GalNAc-T13 gene generated trimeric Tn antigen on Syndecan-1, leading to the enhanced metastasis.

  19. 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...

  20. 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

  1. 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

  2. Danish General Practitioners' Use of Prostate-Specific Antigen in Opportunistic Screening for Prostate Cancer

    DEFF Research Database (Denmark)

    Jessen, Kasper; Søndergaard, Jens; Larsen, Pia Veldt;

    2013-01-01

    Background. The use of prostate-specific antigen test has markedly increased in Danish general practice in the last decade. Despite the national guidelines advice against PSA screening, opportunistic screening is supposed to be the primary reason for this increased number of PSA tests performed. ...

  3. Squamous cell carcinoma antigen isoforms in serum from cervical cancer patients

    NARCIS (Netherlands)

    Roijer, E; de Bruijn, HWA; Dahlen, U; ten Hoor, K; Lundin, M; Nilsson, K; Soderstrom, K; Nilsson, O

    2006-01-01

    Squamous cell carcinoma antigen (SCCA) is a serological marker of squamous cell carcinomas (SCC). To study whether any of the SCCA isoforms would provide additional and more specific/sensitive clinical information than total SCCA, immunoassays specific for the different forms of SCCA (free SCCA2, to

  4. 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

  5. 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)

  6. 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)

  7. Proliferating cell nuclear antigen immunohistochemistry using monoclonal antibody 19A2 and a new antigen retrieval technique has prognostic impact in archival paraffin-embedded node-negative breast cancer.

    Science.gov (United States)

    Siitonen, S M; Kallioniemi, O P; Isola, J J

    1993-04-01

    We evaluated whether proliferating cell nuclear antigen (PCNA) immunohistochemistry with antigen retrieval could be used as a measure of cell proliferation in archival, formalin-fixed, paraffin-embedded tissues and whether the staining results have long-term prognostic significance in axillary node-negative breast cancer. Primary tumor samples obtained from 109 axillary-node-negative breast cancer cases were used for the study. The best staining results were obtained with the 19A2 antibody after microwave heating in a solution of saturated lead thiocyanate. Using this method, there was a significant correlation (linear regression, r = 0.580, P treatment may offer a useful alternative to DNA flow cytometry for the analysis of cell proliferation activity from formalin-fixed, paraffin-embedded breast carcinomas.

  8. Cancer-testis antigens PRAME and NY-ESO-1 correlate with tumour grade and poor prognosis in myxoid liposarcoma.

    Science.gov (United States)

    Iura, Kunio; Kohashi, Kenichi; Hotokebuchi, Yuka; Ishii, Takeaki; Maekawa, Akira; Yamada, Yuichi; Yamamoto, Hidetaka; Iwamoto, Yukihide; Oda, Yoshinao

    2015-07-01

    Myxoid liposarcoma is the second most common liposarcoma. Although myxoid liposarcoma is relatively chemosensitive and thus a good candidate for chemotherapy, cases with relapsed or metastatic disease still have poor outcome. Here, we performed a gene microarray analysis to compare the gene expression profiles in six clinical myxoid liposarcoma samples and three normal adipose tissue samples, and to identify molecular biomarkers that would be useful as diagnostic markers or treatment targets in myxoid liposarcoma. This showed that the cancer-testis antigen PRAME was up-regulated in myxoid liposarcoma. We then performed immunohistochemical, western blotting and real-time polymerase chain reaction analyses to quantify the expression of PRAME and another cancer-testis antigen, NY-ESO-1, in clinical samples of myxoid liposarcoma (n = 93), dedifferentiated (n = 46), well-differentiated (n = 32) and pleomorphic liposarcomas (n = 14). Immunohistochemically, positivity for PRAME and NY-ESO-1 was observed in 84/93 (90%) and 83/93 (89%) of the myxoid liposarcomas, and in 20/46 (43%) and 3/46 (7%) of the dedifferentiated, 3/32 (9%) and 1/32 (3%) of the well-differentiated and 7/14 (50%) and 3/21 (21%) of the pleomorphic liposarcomas, respectively. High immunohistochemical expression of PRAME and/or NY-ESO-1 was significantly correlated with tumour diameter, the existence of tumour necrosis, a round-cell component of >5%, higher histological grade and advanced clinical stage. High PRAME and NY-ESO-1 expression correlated significantly with poor prognosis in a univariate analysis. The myxoid liposarcomas showed significantly higher protein and mRNA expression levels of PRAME and NY-ESO-1 (CTAG1B) than the other liposarcomas. In conclusion, PRAME and NY-ESO-1 (CTAG1B) were expressed in the vast majority of myxoid liposarcomas, and their high-level expression correlated with tumour grade and poor prognosis. Our results support the potential use of PRAME and NY

  9. 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.

  10. Detection CEA,CA125,CA153 in breast cancer patients and its correlation with quality of life%乳腺癌患者CEA、CA125、CA153检测及其与生活质量的相关性分析

    Institute of Scientific and Technical Information of China (English)

    潘中华

    2013-01-01

    Objective To study the level of CEA,CA125,CA153 in breast cancer patients and its correlation with quality of life. Methods the breast cancer patients were selected as observation group,benign breast disease patients as benign control group, and healthy people as healthy control group,the peripheral blood levels of CEA,CA125, CA153 were detected and quality of life were observed. Results The CEA,CA125,CA153 levels and physical function,psychological function,social function,cognitive function,overall quality of life scores of observation group were significantly higher than benign control group and healthy control group;physical function,psychological function,social function,cognitive function,overall quality of life score were negatively correlated with CEA,CA125,CA153 levels. Conclusion The clinical value of positive CEA,CA125,CA153 examination in the diagnosis of breast cancer,which is closely related with the quality of life.%  目的研究乳腺癌患者血清中CEA、CA125、CA153的水平及其与生活质量的相关性。方法选择乳腺癌患者作为观察组、乳腺良性疾病患者作为良性对照组、健康体检者作为健康对照组,检测外周血中CEA、CA125、CA153的含量并观察生活质量相关指标。结果观察组患者CEA、CA125、CA153水平以及躯体功能、心理功能、社会功能、认知功能、总体生活质量评分明显高于良性对照组和健康对照组;躯体功能、心理功能、社会功能、认知功能、总体生活质量评分与CEA、CA125、CA153水平呈负相关。结论CEA、CA125、CA153检查对乳腺癌的诊断具有积极的临床价值,且与生活质量密切相关。

  11. Simultaneous cytoplasmic and nuclear protein expression of melanoma antigen-A family and NY-ESO-1 cancer-testis antigens represents an independent marker for poor survival in head and neck cancer.

    Science.gov (United States)

    Laban, Simon; Atanackovic, Djordje; Luetkens, Tim; Knecht, Rainald; Busch, Chia-Jung; Freytag, Marcus; Spagnoli, Giulio; Ritter, Gerd; Hoffmann, Thomas K; Knuth, Alexander; Sauter, Guido; Wilczak, Waldemar; Blessmann, Marco; Borgmann, Kerstin; Muenscher, Adrian; Clauditz, Till S

    2014-09-01

    The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. The identification of high-risk subgroups is needed for the development of custom-tailored therapies. The expression of cancer-testis antigens (CTAs) has been linked to a worse prognosis in other cancer types; however, their prognostic value in HNSCC is unclear because only few patients have been examined and data on CTA protein expression are sparse. A tissue microarray consisting of tumor samples from 453 HNSCC patients was evaluated for the expression of CTA proteins using immunohistochemistry. Frequency of expression and the subcellular expression pattern (nuclear, cytoplasmic, or both) was recorded. Protein expression of melanoma antigen (MAGE)-A family CTA, MAGE-C family CTA and NY-ESO-1 was found in approximately 30, 7 and 4% of tumors, respectively. The subcellular expression pattern in particular had a marked impact on the patients' prognosis. Median overall survival (OS) of patients with (i) simultaneous cytoplasmic and nuclear expression compared to (ii) either cytoplasmic or nuclear expression and (iii) negative patients was 23.0 versus 109.0 versus 102.5 months, for pan-MAGE (p ESO-1 (p = 0.0019). By multivariate analysis, these factors were confirmed as independent markers for poor survival. HNSCC patients showing protein expression of MAGE-A family members or NY-ESO-1 represent a subgroup with an extraordinarily poor survival. The development of immunotherapeutic strategies targeting these CTA may, therefore, be a promising approach to improve the outcome of HNSCC patients.

  12. 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...

  13. 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...

  14. 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...

  15. 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.

  16. Evaluating the value of CEA and CA153 during follow-up in HER-2 overexpressing breast cancer u-sing ROC curves%利用 ROC 曲线评价 CEA、CA153在 HER -2阳性乳腺癌术后随访中的价值

    Institute of Scientific and Technical Information of China (English)

    侯军君; 任立瑾; 高媛媛; 刘潇莲; 蔡莉

    2014-01-01

    目的:用ROC曲线评价CEA及CA153监测HER-2阳性乳腺癌患者术后复发转移的价值,并确立诊断HER-2阳性乳腺癌患者术后复发转移的最佳临界值。方法收集127例HER-2阳性乳腺癌患者CEA及CA153数值,将其分为复发转移及未复发转移两组。绘制ROC曲线,找到最佳临界值,同时比较最佳临界值与常规诊断值诊断复发转移的优劣。结果复发转移组较未复发转移组CEA及CA153水平显著偏高(P<0.0001),CEA、CA153诊断复发转移ROC曲线下面积分别为0.752、0.820,对应的最佳临界值分别为3.5 ng/mL、17.89 U/mL。 CEA和CA153最佳临界值敏感性分别为46.15%、65.38%,CEA和CA153最佳临界值特异性分别为97.33%、89.33%。结论 CEA、CA153在HER-2阳性乳腺癌患者术后判断复发转移中具有中等价值,诊断术后复发转移的最佳临界值分别为3.5 ng/mL、17.89 U/mL。%Objective To explore the value of carcinoembryonic antigen ( CEA) and cancer antigen 153 ( CA153 ) in detecting tumor recurrences and to establish the optimal operating point of diagnosis of recurrences in HER-2 overexpressing breast cancer using ROC curves .Methods A total of 127 HER -2 overexpressing breast cancer patients was enrolled into this study and subdivided into two groups ,the recurrence group and the non-recurrence group .We created a ROC curve and found out the optimal operating point .Then we compared the advantage of detecting recurrences between optimal operating point in the ROC curve and the diagnostic point that we usually used .Results The recurrence groups showed significantly higher CEA and CA 153 levels than the non-recurrence groups(P<0.0001).The area under the curve(AUC)of the CEA and CA153 were 0.752 and 0.820 respectively and the optimal operating point were 3.5 ng/mL and 17.89 U/mL,respectively.The sensitivi-ties of the optimal operating point of CEA and CA 153 were 46.15%and 65.38%respectively

  17. Intensified follow-up in colorectal cancer patients using frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging : Results of the randomized "CEAwatch" trial

    NARCIS (Netherlands)

    Verberne, C. J.; Zhan, Z.; van den Heuvel, E.; Grossmann, I.; Doornbos, P. M.; Havenga, K.; Manusama, E.; Klaase, J.; van der Mijle, H. C. J.; Lamme, B.; Bosscha, K.; Baas, P.; van Ooijen, B.; Nieuwenhuijzen, G.; Marinelli, A.; van der Zaag, E.; Wasowicz, D.; de Bock, G. H.; Wiggers, T.

    2015-01-01

    Aim: The value of frequent Carcino-Embryonic Antigen (CEA) measurements and CEA-triggered imaging for detecting recurrent disease in colorectal cancer (CRC) patients was investigated in search for an evidence-based follow-up protocol. Methods: This is a randomized-controlled multicenter prospective

  18. Impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC) on prostate-specific antigen (PSA) testing by Dutch general practitioners

    NARCIS (Netherlands)

    Van der Meer, Saskia; Kollen, Boudewijn J.; Hirdes, Willem H.; Steffens, Martijn G.; Hoekstra-Weebers, Josette E. H. M.; Nijman, Rien M.; Blanker, Marco H.

    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

  19. 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

  20. Role of metabolic modulator Bet-CA in altering mitochondrial hyperpolarization to suppress cancer associated angiogenesis and metastasis

    Science.gov (United States)

    Saha, Suchandrima; Ghosh, Monisankar; Dutta, Samir Kumar

    2016-01-01

    Solid tumors characteristically reflect a metabolic switching from glucose oxidation to glycolysis that plays a fundamental role in angiogenesis and metastasis to facilitate aggressive tumor outcomes. Hyperpolarized mitochondrial membrane potential is a manifestation of malignant cells that compromise the intrinsic pathways of apoptosis and confer a suitable niche to promote the cancer associated hallmark traits. We have previously reported that co-drug Bet-CA selectively targets cancer cells by inducing metabolic catastrophe without a manifest in toxicity. Here we report that the same molecule at a relatively lower concentration deregulates the cardinal phenotypes associated with angiogenesis and metastasis. In mice syngeneic 4T1 breast cancer model, Bet-CA exhibited effective abrogation of angiogenesis and concomitantly obliterated lung metastasis consistent with altered mitochondrial bioenergetics. Furthermore, Bet-CA significantly lowered vascular endothelial growth factor (VEGF) levels and obviated matrix metalloproteases (MMP-2/9) production directly to the criterion where abrogation of autocrine VEGF/VEGFR2 signalling loop was documented. In vitro studies anticipatedly documented the role of Bet-CA in inhibiting actin remodeling, lamellipodia formation and cell membrane ruffling to constitutively suppress cell motility and invasion. Results comprehensively postulate that Bet-CA, a mitochondria targeting metabolic modulator may serve as an excellent candidate for combating angiogenesis and metastasis. PMID:27003027

  1. Characterization of a common antigen of colorectal and mucinous ovarian tumors, COTA.

    Science.gov (United States)

    Pant, K D; Zamora, P O; Rhodes, B A; Sachatello, C R; Hagihara, P F; Griffen, W O; van Nagell, J R; Fulks, R; Ram, M D

    1984-01-01

    A new colon cancer antigen is reported. It is designated as COTA, Colon-Ovarian Tumor Antigen, because it is found in mucins produced by both tissues during malignancy. The new antigen was identified by making antibodies against human colon cancer tissue in goats. The antisera were exhaustively absorbed with lyophilized extracts of normal colon, lung, liver, spleen, kidney, plasma, and the well-known colon tumor antigen, carcinoembryonic antigen (CEA). The new antigen was identified by immunodiffusion. Studies of 28 malignant tissue extracts, 10 ovarian adenocarcinoma cyst fluids, 43 normal tissues, and 5 plasma samples revealed that this antigen is found only in colon tumors and mucinous ovarian adenocarcinomas. The antigen was not detected in serous adenocarcinoma of the ovaries, extracts of adenocarcinoma of lung, breast, kidney or stomach nor in the extracts of normal tissues. Other tests show that this antigen is not CEA, Ca 19-9, or CSAp. It is stable to heating at 65 degrees for 5 minutes; it elutes from an ion exchange matrix (DEAE) with 0.3-0.5M NaCl; it migrates to the alpha-2 region on immunoelectrophoresis; and its size, by exclusion chromatography on Sepharose 4B, is 3-15 million daltons. Anti-COTA stains colon cancer tissue sections indicating that COTA is present in goblet-cell mucin.

  2. 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...

  3. 76 FR 24889 - Submission for OMB Review; Comment Request; Cancer Biomedical Informatics Grid® (caBIG®) Support...

    Science.gov (United States)

    2011-05-03

    ... Business or other for-profits and not- for-profit organizations and institutions. Type of Respondents... information collection was previously published in the Federal Register on February 11, 2011 (76 FR 7867) and... control number. Proposed Collection: Title: cancer Biomedical Informatics Grid (caBIG ) Support...

  4. Breast cancer 1 (BrCa1 may be behind decreased lipogenesis in adipose tissue from obese subjects.

    Directory of Open Access Journals (Sweden)

    Francisco J Ortega

    Full Text Available CONTEXT: Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1 interacts with acetyl-CoA carboxylase (ACC reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. RESEARCH DESIGN AND METHODS: BrCa1 gene expression, total and phosphorylated (P- BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. RESULTS: BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002 and subcutaneous (SC; 1.49-fold, p = 0.001 adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007 as well as in OM (p = 0.010 fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001 and protein (1.2-fold, p = 0.001 were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005 allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium, whereas lipogenic genes significantly decreased. CONCLUSIONS: The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.

  5. 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

  6. 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.

  7. 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.

  8. Primary breast cancer tumours contain high amounts of IgA1 immunoglobulin: an immunohistochemical analysis of a possible carrier of the tumour-associated Tn antigen.

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

    Full Text Available The Tn antigen (GalNAc alpha-O-Ser/Thr as defined by the binding of the lectin, helix pomatia agglutinin (HPA or anti-Tn monoclonal antibodies, is known to be exposed in a majority of cancers, and it has also been shown to correlate positively with the metastatic capacity in breast carcinoma. The short O-glycan that forms the antigen is carried by a number of different proteins. One potential carrier of the Tn antigen is immunoglobulin A1 (IgA1, which we surprisingly found in tumour cells of the invasive parts of primary breast carcinoma. Conventional immunohistochemical analysis of paraffin-embedded sections from primary breast cancers showed IgA1 to be present in the cytoplasm and plasma membrane of 35 out of 36 individual primary tumours. The immunohistochemical staining of HPA and anti-Tn antibody (GOD3-2C4 did to some extent overlap with the presence of IgA1 in the tumours, but differences were seen in the percentage of stained cells and in the staining pattern in the different breast cancers analysed. Anti-Tn antibody and HPA were also shown to specifically bind to a number of possible constellations of the Tn antigen in the hinge region of IgA1. Both reagents could also detect the presence of Tn positive IgA in serum. On average 51% of the tumour cells in the individual breast cancer tumour sections showed staining for IgA1. The overall amount of staining in the invasive part of the tumour with the anti Tn antibody was 67%, and 93% with HPA. The intra-expression or uptake of IgA1 in breast cancer makes it a new potential carrier of the tumour associated and immunogenic Tn antigen.

  9. 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.

  10. Tumor Destruction and In Situ Delivery of Antigen Presenting Cells Promote Anti-Neoplastic Immune Responses: Implications for the Immunotherapy of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Manfredi AA

    2004-07-01

    Full Text Available Antigen presenting cells (APCs activate helper and cytotoxic T cells specific for antigens expressed by tissue cells, including neoplastic cells. This event occurs after the antigen transfer from tissue cells to APC, and is referred to as "cross-presentation". The number and the state of activation of APC in the tumor control the outcome of cross-presentation, including the establishment of protective immune responses. Cell death favors cross-presentation. Cancer cells normally die, either spontaneously or as a consequence of targeted therapies. The transfer of tumor antigens from dying tumor cells to APCs in vivo, exploiting the cross-presentation pathway, has the potential of yielding novel immunotherapeutic strategies. Their success will depend on at least two factors: the induction of synchronized cell death in the tumor, and the recruitment of activated dendritic cells in the tumor. Under normal conditions, pancreatic cancer represents a privileged environment; its profound chemoresistance reflects limited apoptosis after chemotherapy. Moreover, it usually contains only a few cells endowed with APC function. Endoscopic ultrasonography offers attractive possibilities of circumventing this privilege, including the delivery of ultrasound, radiofrequency or radiation in order to destroy the tumor and the delivery in situ of autologous APC or appropriate chemotactic signals. In general, loco-regional approaches offer the possibility of using the tumor of each patient as a complex antigen source, thus limiting the risk of tumor escape and reducing the need for extensive ex vivo handling of the neoplasm and of the patient APCs.

  11. 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...

  12. 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...

  13. 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...

  14. Association of defective HLA-Ⅰ expression with antigen processing machinery and their association with clinicopathological characteristics in Kazak patients with esophageal cancer

    Institute of Scientific and Technical Information of China (English)

    Ayshamgul Hasim; MA Hong; Ilyar Sheyhidin; ZHANG Li-wei; Abulizi Abudula

    2011-01-01

    Background It has been confirmed that defective expression of human leukocyte antigen class Ⅰ (HLA-Ⅰ) molecules can contribute to the immune evasion of cancer cells in some types of cancer. The aim of this study was to examine the expression of HLA class Ⅰ antigen and the antigen-processing machinery (APM) components in esophageal squamous cell carcinoma (ESCC) and their role in high risk human papillomavirus (HPV) infection, and to analyze their association with histopathological characteristics in the Kazak ethnic group.Methods A total of 50 formalin-fixed, paraffin-embedded ESCC lesions were collected from the First Affiliated Hospital of Xinjiang Medical University, China. The expression levels of HLA-Ⅰ antigen and APM components were determined by immunohistochemistry; the HPV DNA were detected using polymerase chain reaction (PCR).Results A high frequency of down-regulation or loss of expression of HLA and APM components were found in esophageal cancer in Kazak people. HLA-Ⅰ, TAP1, CNX, LMP7, Erp57, Tapasin and ERAP1 were down-regulated in 68%,44%, 48%, 40%, 52%, 32% and 20% of ESCC lesions then, respectively. The loss of expression of HLA-Ⅰ antigen was significantly correlated with part of the APM components and positively correlated with high risk HPV16 infection. TAP1,CNX, LMP7, Erp57 and Tapasin loss were significantly associated with tumor grading, lymph node metastasis and depth of invasion (P<0.05).Conclusion Our results suggest that APM component defects are a mechanism underlying HLA-Ⅰ antigen down-regulation in ESCC lesions, and indicate that the loss expression of HLA-Ⅰ and APM components will become an important marker of ESCC and analysis of HLA-Ⅰ and APM component expression can provide useful prognostic information for patients with ESCC from the Kazak ethnic group.

  15. 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.

  16. 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

  17. CA125、CYFRA21-1、HPV 联合检测 TCT 诊断宫颈癌的临床价值%Clinical value of CA125,CYFRA21-1,HPV detection combined with TCT in diagnosis of cervical cancer

    Institute of Scientific and Technical Information of China (English)

    黄伟强; 杨艳梅

    2015-01-01

    Objective To investigate the value of cytokeratin fragment antigen 21‐1(CYFRA21‐1) ,carbohydrate antigen‐125 (CA125) ,human papillomavirus (HPV ) detection with Thinprep cytologic test (TCT ) in the diagnosis of cervical cancer . Methods 70 patients with cervical cancer ,60 patients with benign cervical diseases and 70 healthy people were selected .CYFRA21‐1 ,CA125 ,HPV detection and TCT results were analyzed .Results The positive rates of HPV ,TCT ,CA125 and CYFRA21‐1 in cervical cancer group were significantly higher than those in cervical benign lesion group and the healthy group ,the difference were statistically significant (P TSGF>CEA>SIL‐2R .The specificity was CYFRA21‐1> TCT>CA125> HPV .In HPV ,TCT ,CA125 and CYFRA21‐1parallel diagnostic test ,the sensitivity was up to 100 .00% ,and in series diagnostic test ,the specificity was up to 98 .3% .Conclu‐sion HPV ,CA125 ,CYFRA21‐1 detection combined with TCT in diagnosis of cervical cancer has strong reliability ,it is worth u‐sing w idely in clinic .%目的:探讨细胞角蛋白21‐1(CYFRA21‐1)、糖类抗原‐125(CA125)、人乳头瘤病毒(HPV)检测联合新柏氏液基细胞学检查(TCT)在宫颈癌诊断的临床价值。方法选取宫颈癌患者70例,宫颈良性疾病60例和同期检查的健康者70例作为健康组,对3组人群CYFRA21‐1、CA125、HPV检测与TCT结果进行分析。结果 HPV、TCT、CA125与CYFRA21‐1在宫颈癌患者中检出阳性率明显高于宫颈良性病变组和健康组,差异有统计学意义(P<0.01);HPV、TCT、CA125与CYFRA21‐1诊断宫颈癌的敏感度从大到小依次为 TCT、CYFRA21‐1、CA125、HPV ,特异度从高到低分别是 CYFRA21‐1、TCT、CA125、HPV。 HPV、TCT、CA125与CYFRA21‐1进行并联诊断试验中敏感度高达100.00%,在串联诊断试验中特异度高达98.3%。结论 HPV、CA125、CYFRA21‐1检测与TCT联合诊断宫颈癌具有较强的可靠性

  18. 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......-tests. Den mest testende fjerdedel af praksis brugte teksten 3,6 gange oftere end den mindst testende praksisgruppe. I den mest testende gruppe fik 76 % flere personer en biopsi af prostata og 37 % flere mænd blev diagnosticeret med prostatacancer sammenlignet med den mindst testende gruppe. Risikoen......,25 gange større i den mest testende gruppe sammenlignet med den mindst testende gruppe. Dødeligheden (mortaliteten) – både den over¬ordnede og den prostata-specifikke – var den samme i alle fire grupper. Resultaterne indikerer, at der er forskellig klinisk praksis for brugen af PSA-tests, og at forskellene...

  19. Elimination of progressive mammary cancer by repeated administrations of chimeric antigen receptor-modified T cells.

    Science.gov (United States)

    Globerson-Levin, Anat; Waks, Tova; Eshhar, Zelig

    2014-05-01

    Continuous oncogenic processes that generate cancer require an on-going treatment approach to eliminate the transformed cells, and prevent their further development. Here, we studied the ability of T cells expressing a chimeric antibody-based receptor (CAR) to offer a therapeutic benefit for breast cancer induced by erbB-2. We tested CAR-modified T cells (T-bodies) specific to erbB-2 for their antitumor potential in a mouse model overexpressing a human erbB-2 transgene that develops mammary tumors. Comparing the antitumor reactivity of CAR-modified T cells under various therapeutic settings, either prophylactic, prior to tumor development, or therapeutically. We found that repeated administration of CAR-modified T cells is required to eliminate spontaneously developing mammary cancer. Systemic, as well as intratumoral administered CAR-modified T cells accumulated at tumor sites and eventually eliminated the malignant cells. Interestingly, within a few weeks after a single CAR T cells' administration, and rejection of primary lesion, tumors usually relapsed both in treated mammary gland and at remote sites; however, repeated injections of CAR-modified T cells were able to control the secondary tumors. Since spontaneous tumors can arise repeatedly, especially in the case of syndromes characterized by specific susceptibility to cancer, multiple administrations of CAR-modified T cells can serve to control relapsing disease.

  20. 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)

  1. 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.

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

    Science.gov (United States)

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

    2003-01-01

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

  3. Expression of Lewisa, Sialyl Lewisa, Lewisx, Sialyl Lewisx, Antigens as Prognostic Factors in Patients with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Tohru Nakagoe

    2000-01-01

    Full Text Available BACKGROUND: Altered expression of blood group-related carbohydrate antigens such as sialyl Lewis (Lex antigen in tumours is associated with tumour progression behaviour and subsequent prognosis. However, the prognostic value of the expression of Le-related antigens in colorectal tumours remains unclear.

  4. 非小细胞肺癌患者血清中TSGF及CA125水平检测的意义%Significance of Serum TSGF and CA125 Detection for the Patients with Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    唐艳; 李娜; 刘翠兰

    2012-01-01

    目的 探讨恶性肿瘤特异性生长因子(TSGF)和糖类抗原-125 (CA125)血清水平检测对非小细胞肺癌(NSCLC)患者诊断的临床价值.方法 选取50例NSCLC患者,及50例良性肺部病变患者,检测血清TSGF和CA125水平,比较不同组别患者及肺癌患者不同病理类型、不同临床分期血清TSGF和CA125的表达水平.结果 血清TSGF和CA125水平在肺癌组明显高于肺良性病变组(P<0.001);肺癌患者CA125表达水平与组织类型有关,肺腺癌明显高于肺鳞癌(P<0.01);肺癌患者血清TSGF和CA125的阳性率与NSCLC临床分期有关,临床分期越晚,其阳性率越高.结论 CA125及TSGF均对肺癌的辅助诊断具有一定价值,临床上需要结合症状、影像学及病理学综合判断,为NSCLC提供更好的诊疗效果.%Objective To explore the clinical values of serum tumor specific growth factor (TSGF) and carbohydrate antigen (CA125) detection in the diagnosis of non?small cell lung cancer (NSCLC). Methods The serum TSGF and CA125 levels were measured in 50 patients with NSCLC and 50 cases with benign lung diseases. The detection results were compared between the two groups and among patients with lung cancers of different pathological types and clinical stages. Results The serum TSGF and CA125 levels in the lung cancer group were significantly higher than those in the control group (P<0.001). The serum CA125 level was related with the pathological types of the lung carcinoma, which was statistically higher in the patients with lung adenocarcinoma than in those with lung squamous cell carcinoma (P<0.01). The positive rates of serum TSGF and CA125 in patients with NSCLC were related with the clinical stage of the carcinoma. The later the clinical stage, the higher the positive rates. Conclusions Serum TSGF and CA125 detection is of clinical significance in the diagnosis of patients with non - small cell lung cancer.

  5. 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....... On the basis of these data, a phase 1 dose-escalation clinical trial has been initiated with G202 in patients with advanced cancer....

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

    Directory of Open Access Journals (Sweden)

    Qian Zhi

    2009-01-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

  7. PIK3CA rs7640662 (C/G) single nucleotide polymorphism lacks association with breast cancer cases in Persians.

    Science.gov (United States)

    Mir, Atefeh; Sadegh, Mahdiyeh Harati; Ahmadinia, Zahra; Kaboli, Parham Jabbarzadeh

    2015-03-01

    Phosphatidylinositol-3-kinase (PI3K) is a group of enzymes involved in cellular growth, proliferation, differentiation, cell motility, intracellular trafficking, and survival that play very important roles in developing breast cancer. PIK3CA is a gene that encodes α catalytic subunit of this enzyme. A common polymorphism of PIK3CA, rs7640662 (C/G), was analyzed, and its association to breast cancer cases was determined. In this study, DNA was extracted from peripheral blood samples of 278 women suffering from breast cancer and 128 healthy women. Tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method was performed to genotype rs7640662. P values and ODD ratios were measured using SPSS. P value less than 0.05 and ODD ratios more than 1 were considered as significant. All ODD ratios were less than 1, and P values were more than 0.05 showing that rs7640662 (C/G) and breast cancer are not significantly associated. However, the genotypes observed in the Persian population, as an ancient population living in the Middle East, was significantly different from the genotypes reported by HapMap for Asian populations. As a conclusion, rs7640662 was not associated with the risk of breast cancer in a Persian population; however, it was observed that heterozygote (GC) is the most common genotypes in both case and control samples. PMID:25838920

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

    Energy Technology Data Exchange (ETDEWEB)

    Bujak, Emil [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland); Pretto, Francesca; Ritz, Danilo; Gualandi, Laura; Wulhfard, Sarah [Philochem AG, Libernstrasse 3, CH-8112 Otelfingen (Switzerland); Neri, Dario, E-mail: neri@pharma.ethz.ch [Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich), Vladimir-Prelog-Weg 2, CH-8093 Zurich (Switzerland)

    2014-09-10

    There is a considerable interest for the discovery and characterization of tumor-associated antigens, which may facilitate antibody-based pharmacodelivery strategies. Thrombospondin-1 and thrombospondin-2 are homologous secreted proteins, which have previously been reported to be overexpressed during remodeling typical for wound healing and tumor progression and to possibly play a functional role in cell proliferation, migration and apoptosis. To our knowledge, a complete immunohistochemical characterization of thrombospondins levels in normal rodent tissues has not been reported so far. Using antibody phage technology, we have generated and characterized monoclonal antibodies specific to murine thrombospondin-1 and thrombospondin-2, two antigens which share 62% aminoacid identity. An immunofluorescence analysis revealed that both antigens are virtually undetectable in normal mouse tissues, except for a weak staining of heart tissue by antibodies specific to thrombospondin-1. The analysis also showed that thrombospondin-1 was strongly expressed in 5/7 human tumors xenografted in nude mice, while it was only barely detectable in 3/8 murine tumors grafted in immunocompetent mice. By contrast, a high-affinity antibody to thrombospondin-2 revealed a much lower level of expression of this antigen in cancer specimens. Our analysis resolves ambiguities related to conflicting reports on thrombosponding expression in health and disease. Based on our findings, thrombospondin-1 (and not thrombospondin-2) may be considered as a target for antibody-based pharmacodelivery strategies, in consideration of its low expression in normal tissues and its upregulation in cancer. - Highlights: • High affinity monoclonal antibodies to murine and human TSP1 and 2 were raised. • Both antigens are virtually undetectable in normal mouse tissues. • Strong positivity of human tumor xenografts for TSP1 was detected. • Study revealed much lower level of TSP2 expression in cancer specimens

  9. 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...

  10. The diagnostic accuracy of carcinoembryonic antigen to detect colorectal cancer recurrence

    DEFF Research Database (Denmark)

    Sørensen, Caspar G; Karlsson, William K; Pommergaard, Hans-Christian;

    2016-01-01

    was to assess the diagnostic accuracy of CEA in detecting recurrence after intended curative surgery for primary colorectal cancer. METHODS: Systematic literature searches were performed in PubMed, EMBASE and Cochrane databases, and articles were chosen based on predefined inclusion criteria. Reference lists...... from included articles were manually searched for additional publications of relevance. RESULTS: Forty-two original studies with generally representative populations and long follow-up were included. Data were reported on outcomes from 9,834 CEA tests during follow-up. Reporting on the reference...

  11. 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

  12. 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

    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 endometrial......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 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 (

  13. 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

  14. Identification of prostate-specific G-protein coupled receptor as a tumor antigen recognized by CD8(+ T cells for cancer immunotherapy.

    Directory of Open Access Journals (Sweden)

    Satoko Matsueda

    Full Text Available BACKGROUND: Prostate cancer is the most common cancer among elderly men in the US, and immunotherapy has been shown to be a promising strategy to treat patients with metastatic castration-resistant prostate cancer. Efforts to identify novel prostate specific tumor antigens will facilitate the development of effective cancer vaccines against prostate cancer. Prostate-specific G-protein coupled receptor (PSGR is a novel antigen that has been shown to be specifically over-expressed in human prostate cancer tissues. In this study, we describe the identification of PSGR-derived peptide epitopes recognized by CD8(+ T cells in an HLA-A2 dependent manner. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-one PSGR-derived peptides were predicted by an immuno-informatics approach based on the HLA-A2 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs obtained from either HLA-A2(+ healthy donors or HLA-A2(+ prostate cancer patients. The recognition of HLA-A2 positive and PSGR expressing LNCaP cells was also tested. Among the 21 PSGR-derived peptides, three peptides, PSGR3, PSGR4 and PSGR14 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and prostate cancer patients. Importantly, these peptide-specific T cells recognized and killed LNCaP prostate cancer cells in an HLA class I-restricted manner. CONCLUSIONS/SIGNIFICANCE: We have identified three novel HLA-A2-restricted PSGR-derived peptides recognized by CD8(+ T cells, which, in turn, recognize HLA-A2(+ and PSGR(+ tumor cells. The PSGR-derived peptides identified may be used as diagnostic markers as well as immune targets for development of anticancer vaccines.

  15. 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

  16. 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...

  17. 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;

    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...... of limited/extensive disease. Immunohistochemical analysis of a biopsy from 1 SCLC patient with an elevated serum FA1 also showed the presence of FA1 in tumor cells. FA1 in serum from SCLC patients was identical to that of FA1 in normal serum/amniotic fluid with respect to size distribution and also revealed...

  18. 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

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

    Directory of Open Access Journals (Sweden)

    Constantin Traian Vasile

    2014-06-01

    Full Text Available Cancerul de prostată reprezintă, după cancerul pulmonar, cea mai frecventă afecţiune malignă diagnosticată în cadrul populaţiei masculine. Introducerea în practica curentă în anii 80-90 a determinării Antigenului Specific al Prostatei (PSA seric, ca şi componentă a screeningului pentru cancerul de prostată, a reprezentat un moment de răscruce în practica medicală. Datorită acestei enzime produsă exclusiv de către glanda prostatică, rata detecţiei cancerului de prostată (în stadii curative, intracapsulare s-a îmbunătăţit semnificativ. PSA - ul seric reprezintă un factor predictiv pentru cancerul de prostată (CP mai bun decât tuşeul rectal sau ecografia prostatică transrectală

  20. 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

  1. 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

  2. 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...

  3. 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.

  4. 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

    in 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...

  5. The network of antigen-antibody reactions in adult women with breast cancer or benign breast pathology or without breast pathology.

    Directory of Open Access Journals (Sweden)

    Tania Romo-González

    Full Text Available The Immunoglobulin G (IgG antibody response to different protein antigens of the mammary ductal carcinoma by adult women affected by Breast Cancer (BC distinguishes at least 103 proteins that differ in their molecular weights (MW. The IgG producing cell clones (nodes coexist with each other in each individual organism and share energy resources among themselves, as well as factors that control the level of expression and Specificity of their IgG antibodies. So, it can be proposed that among them there is a Network of interconnections (links unveiled by the antigens, which specifically react with the IgG antibodies produced by the clones. This Network possibly regulates IgG antibodies' activity and effectiveness. We describe the Network of nodes and links that exists between the different antigens and their respective IgG producing cell clones against the extracted protein antigens from the cells of the T47D Cell-Line, in 50 women with BC, 50 women with Benign Breast Pathology (BBP and 50 women without breast pathology (H. We have found that women with BBP have the highest number of Links, followed by the H group and, lastly, the women with BC, a finding which suggests that cancer interferes with the Connectivity between the IgG producing cell clones and blocks the expression of 322 links in women with BBP and 32 links in women with H. It is also plausible that the largest number of links in the women with BBP indicates the Network's state of arousal that provides protection against BC. On the other hand, there were many missing links in the BC group of women; the clone which lost more links in the BC group was the hub 24, which point to some of the antigens of T47D as potentially useful as vaccines, as the immune system of women with BBP is well aware of them.

  6. 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...

  7. 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

  8. 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.)

  9. 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.

  10. 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...

  11. 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

  12. The prevalence of PIK3CA mutations in gastric and colon cancer

    NARCIS (Netherlands)

    Velho, S; Oliveira, C; Ferreira, A; Ferreira, AC; Suriano, G; Schwartz, S; Duval, A; Carneiro, F; Machado, JC; Hamelin, R; Seruca, R

    2005-01-01

    A wide variety of tumours show PIK3CA mutations leading to increased phosphatidylinositol-3 kinase (PI3K) activity. We have determined the frequency of PIK3CA mutations in exons 9 and 20 that has previously been reported as mutational hotspot regions in distinct tumour models. One hundred and fifty

  13. 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

  14. 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

    with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) to determine whether this treatment could improve the profile of tumor antigen genes expressed in these cells. In addition, the presence of MAGE-A tumor antigen protein was evaluated in the purified tumor cell lysate used...

  15. 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

    2007-01-01

    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.

  16. Antitumoral efficacy of the protease inhibitor gabexate mesilate in colon cancer cells harbouring KRAS, BRAF and PIK3CA mutations.

    Directory of Open Access Journals (Sweden)

    Giovanni Brandi

    Full Text Available The employment of anti-epidermal growth factor receptor (EGFR antibodies represents a backbone of the therapeutic options for the treatment of metastatic colorectal cancer (mCRC. However, this therapy is poorly effective or ineffective in unselected patients. Mutations in KRAS, BRAF and PIK3CA genes have recently emerged as the best predictive factors of low/absent response to EGFR-targeted therapy. Due to the need for efficacious treatment options for mCRC patients bearing these mutations, in this short report we examined the antitumoral activity of the protease inhibitor gabexate mesilate, alone and in combination with the anti-EGFR monoclonal antibody cetuximab, in a panel of human CRC cell lines harbouring a different expression pattern of wild-type/mutated KRAS, BRAF and PIK3CA genes. Results obtained showed that gabexate mesilate significantly inhibited the growth, invasive potential and tumour-induced angiogenesis in all the CRC cells employed in this study (including those ones harbouring dual KRAS/PIK3CA or BRAF/PIK3CA mutation, while cetuximab affected these parameters only in CRC cells with KRAS, BRAF and PIK3CA wild-type. Notably, the antitumoral efficacy of gabexate mesilate and cetuximab in combination was found to be not superior than that observed with gabexate mesilate as single agent. Overall, these preliminary findings suggest that gabexate mesilate could represent a promising therapeutic option for mCRC patients, particularly for those harbouring KRAS, BRAF and PIK3CA mutations, either as mono-therapy or in addition to standard chemotherapy regimens. Further studies to better elucidate gabexate mesilate mechanism of action in CRC cells are therefore warranted.

  17. KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in Chinese patients with colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Chen Mao

    Full Text Available BACKGROUND: To investigate the frequency and relationship of the KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression in Chinese patients with colorectal cancer (CRC. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA was extracted from the formalin-fixed paraffin-embedded (FFPE tissues of 69 patients with histologically confirmed CRC. Automated sequencing analysis was conducted to detect mutations in the KRAS (codons 12, 13, and 14, BRAF (codon 600 and PIK3CA (codons 542, 545 and 1047. PTEN protein expression was evaluated by immunohistochemistry on 3 mm FFPE tissue sections. Statistical analysis was carried out using SPSS 16.0 software. The frequency of KRAS, BRAF and PIK3CA mutations and loss of PTEN expression was 43.9% (25/57, 25.4% (15/59, 8.2% (5/61 and 47.8% (33/69, respectively. The most frequent mutation in KRAS, BRAF and PIK3CA was V14G (26.7% of all mutations, V600E (40.0% of all mutations and V600L (40.0% of all mutations, and H1047L (80.0% of all mutations, respectively. Six KRAS mutant patients (24.0% harbored BRAF mutations. BRAF and PIK3CA mutations were mutually exclusive. No significant correlation was observed between the four biomarkers and patients' characteristics. CONCLUSIONS/SIGNIFICANCE: BRAF mutation rate is much higher in this study than in other studies, and overlap a lot with KRAS mutations. Besides, the specific types of KRAS and PIK3CA mutations in Chinese patients could be quite different from that of patients in other countries. Further studies are warranted to examine their impact on prognosis and response to targeted treatment.

  18. 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

  19. PI3K expression and PIK3CA mutations are related to colorectal cancer metastases

    Institute of Scientific and Technical Information of China (English)

    Yu-Fen Zhu; Bao-Hua Yu; Da-Li Li; Hong-Lin Ke; Xian-Zhi Guo; Xiu-Ying Xiao

    2012-01-01

    AIM:To assess the significance of phosphatidylinositol 3-kinase (PI3K) in colorectal cancer (CRC) and toxicity of LY294002 in CRC cells with different metastatic abilities.METHODS:Sixty formalin-fixed and paraffin-embedded CRC tumor specimens were investigated.Adjacent normal colonic mucosa specimens from 10 of these cases were selected as controls.PI3K protein was detected by immunohistochemistry and PIK3CA mutations were investigated by gene sequencing analysis.A flowcytometry-based apoptosis detection kit was used to determine PI3K inhibitor-induced apoptosis in CRC cell lines SW480 and SW620.Expression of phosphorylated protein kinase B in CRC cell lines was detected by Western blotting.RESULTS:There was a significant difference in the proportion of primary lesions (30%,18/60) vs metastatic lesions (46.7%,28/60) that were positive for PI3K (P <0.05).Mutations were detected in exon 9 (13.3%) and exon 20 (8.3%).Out of 60 cases,seven mutations were identified:two hotspot mutations,C.1633G>A resulting in E545A,and C.3140A>G resulting in H1047R; two novel missense mutations C.1624G>A and C.3079G>A;and three synonymous mutations (C.1641G>A,C.1581C>T and C.3027T>A).Exposure of SW480 cells to PI3K inhibitor for 48 h resulted in a significant increase of apoptotic cells in a dose-dependent manner [3.2% apoptotic cells in 0 μmol/L,4.3% in 5 μmol/L,6.3% in 10 μ.mol/L (P < 0.05),and 6.7% in 20 μmol/L (P < 0.05)].Moreover,PI3K inhibitor induced a similar significant increase of apoptotic cells in the SW620 cell line for 48 h [3.3% apoptotic cells in 0 μmol/L,13.3%in 5 μmol/L (P < 0.01),19.2% in 10 μmol/L (P < 0.01),and 21.3% in 20 μmol/L (P < 0.01)J.CONCLUSION:High PI3K expression is associated with CRC metastasis.PI3K inhibitor induced apoptosis in CRC cells and displayed strong cytotoxicity for highly metastatic cells.PI3K inhibition may be an effective treatment for CRC.

  20. 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

  1. The cancer-testis antigen NY-ESO-1 is highly expressed in myxoid and round cell subset of liposarcomas.

    Science.gov (United States)

    Hemminger, Jessica A; Ewart Toland, Amanda; Scharschmidt, Thomas J; Mayerson, Joel L; Kraybill, William G; Guttridge, Denis C; Iwenofu, O Hans

    2013-02-01

    Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n=15): myxoid and round cell (n=8); well-differentiated (n=4), and dedifferentiated (n=3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n=44): myxoid and round cell (n=18); well-differentiated (n=10); dedifferentiated (n=10); and pleomorphic (n=6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1-3+), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2-3+ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1+ intensity in 50% of cells; 2+ intensity in 5% of cells; and 3+ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3+ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this

  2. 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 ...

  3. 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

  4. 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.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

    was evaluated and compared with other prognostic factors (age, grade, substages, histologic type). By the Kaplan-Meier estimate we demonstrated that patients with stage I EOC and preoperative serum CA125 levels U/mL had a significantly longer survival compared to stage I EOC patients with preoperative serum...... CA125 > or = 65 U/mL (p=0.01). The results from the present study may be useful for decision making respecting postoperative chemotherapy in stage I EOC patients. Serum CA125 levels might therefore be included as a prognostic factor in future clinical trials of stage I EOC....

  6. Interaction of proliferation cell nuclear antigen (PCNA with c-Abl in cell proliferation and response to DNA damages in breast cancer.

    Directory of Open Access Journals (Sweden)

    Huajun Zhao

    Full Text Available Cell proliferation in primary and metastatic tumors is a fundamental characteristic of advanced breast cancer. Further understanding of the mechanism underlying enhanced cell growth will be important in identifying novel prognostic markers and therapeutic targets. Here we demonstrated that tyrosine phosphorylation of the proliferating cell nuclear antigen (PCNA is a critical event in growth regulation of breast cancer cells. We found that phosphorylation of PCNA at tyrosine 211 (Y211 enhanced its association with the non-receptor tyrosine kinase c-Abl. We further demonstrated that c-Abl facilitates chromatin association of PCNA and is required for nuclear foci formation of PCNA in cells stressed by DNA damage as well as in unperturbed cells. Targeting Y211 phosphorylation of PCNA with a cell-permeable peptide inhibited the phosphorylation and reduced the PCNA-Abl interaction. These results show that PCNA signal transduction has an important impact on the growth regulation of breast cancer cells.

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

    Directory of Open Access Journals (Sweden)

    Nader Al Nakouzi

    2012-05-01

    Full Text Available Bone metastases have a devastating impact on quality of life and bone pain in patients with prostate cancer and decrease survival. Animal models are important tools in investigating the pathogenesis of the disease and in developing treatment strategies for bone metastases, but few animal models recapitulate spontaneous clinical bone metastatic spread. In the present study, IGR-CaP1, a new cell line derived from primary prostate cancer, was stably transduced with a luciferase-expressing viral vector to monitor tumor growth in mice using bioluminescence imaging. The IGR-CaP1 tumors grew when subcutaneously injected or when orthotopically implanted, reconstituted the prostate adenocarcinoma with glandular acini-like structures, and could disseminate to the liver and lung. Bone lesions were detected using bioluminescence imaging after direct intratibial or intracardiac injections. Anatomic bone structure assessed using high-resolution computed tomographic scans showed both lytic and osteoblastic lesions. Technetium Tc 99m methylene diphosphonate micro single-photon emission computed tomography confirmed the mixed nature of the lesions and the intensive bone remodeling. We also identified an expression signature for responsiveness of IGR-CaP1 cells to the bone microenvironment, namely expression of CXCR4, MMP-9, Runx2, osteopontin, osteoprotegerin, ADAMTS14, FGFBP2, and HBB. The IGR-CaP1 cell line is a unique model derived from a primary tumor, which can reconstitute human prostate adenocarcinoma in animals and generate experimental bone metastases, providing a novel means for understanding the mechanisms of bone metastasis progression and allowing preclinical testing of new therapies.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. Frequent mutations of the CA simple sequence repeat in intron 1 of EGFR in mismatch repair-deficient colorectal cancers

    Institute of Scientific and Technical Information of China (English)

    Marie-Pierre Buisine; Thècla Lesuffleur; Agnès Wacrenier; Christophe Mariette; Emmanuelle Leteurtre; Fabienne Escande; Sana Aissi; Amandine Ketele; Annette Leclercq; Nicole Porchet

    2008-01-01

    AIM:To investigate the polymorphic simple sequence repeat in intron 1 of the epidermal growth factor receptor gene(EGFR)(CA-SSR I),which is known to affect the efficiency of gene transcription as a putative target of the mismatch repair (MMR) machinery in colorectal tumors.METHODS:The CA-SSR I genotype was analyzed in a total of 86 primary colorectal tumors,selected upon their microsatellite instability (MSI) status [42 with high frequency MSI (MSI-H) and 44 microsatellite stable (MSS)]and their respective normal tissue.The effect of the CASSR I genotype on the expression of the EGFR gene was evaluated in 18 specimens using quantitative real-time reverse transcription PCR and immunohistochemistry.RESULTS:Mutations in CA-SSR I were detected in 86%(36 of 42) of MSI-H colorectal tumors and 0% (0 of 44) of MSS tumors,indicating the EGFR gene as a novel putative specific target of the defective MMR system (P<0.001).Impaired expression of EGFR was detected in most of the colorectal tumors analyzed [6/12 (50%) at the mRNA level and 15/18 (83%) at the peptide level].However,no association was apparent between EGFR expression and CA-SSR I status in tumors or normal tissues.CONCLUSION:Our results suggest that CA-SSR I sequence does not contribute to the regulation of EGFR transcription in colon,and should thus not be considered as a promising predictive marker for response to EGFR inhibitors in patients with colorectal cancer.

  13. 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

  14. 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...

  15. 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...

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

    DEFF Research Database (Denmark)

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

    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...

  17. 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...

  18. 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

  19. 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 ...

  20. Imaging of non-small cell lung cancers with a monoclonal antibody, KC-4G3, which recognizes a human milk fat globule antigen

    Energy Technology Data Exchange (ETDEWEB)

    Dienhart, D.G.; Schmelter, R.F.; Lear, J.L.; Miller, G.J.; Glenn, S.D.; Bloedow, D.C.; Kasliwal, R.; Moran, P.; Seligman, P.; Murphy, J.R. (Univ. of Colorado Cancer Center, Denver (USA))

    1990-11-01

    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.

  1. 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

  2. Lack of Association between the CDH1 -160C>A Polymorphism and Risk of Gastrointestinal Cancer - a Meta-Analysis.

    Science.gov (United States)

    Sahami-Fard, Mohammad Hossein; Yazd, Ehsan Farashahi; Khazaei, Zahra; Neamatzadeh, Hossein

    2016-01-01

    E-cadherin (CDH1) genetic variations alter gene transcriptional activity of epithelial cells in vitro and may cause susceptibility to various cancers. Associations of CDH1 -160C>A polymorphism with various cancers have been widely reported. However, the results are controversial and inconsistent. To derive a more accurate estimation of the relationship, a meta-analysis was performed with regard to gastrointestinal (GI) cancer risk. Eligible studies were identified through a search of PubMed database until December 2015. Associations between the CDH1 -160C>A polymorphism and GI cancer risk was considered by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 31 studies including 11,606 cases and 12,655 controls were involved in this meta-analysis. Overall, this meta-analysis showed no association between CDH1 -160C>A polymorphism and GI cancer risk (A vs. C: OR = 1.08, 95%CI = 0.98-1.18, P = 0.086;CA vs. CC: OR = 1.09, 95%CI = 0.97- 1.22, P = 0.118; AA vs. CC: OR = 1.10, 95%CI = 0.89-1.35, P = 0.356; AA vs. CC + CA: OR = 1.06, 95%CI = 0.96-1.18, P = 0.207; CA+AA vs. CC: OR = 1.01, 95%CI = 0.84-1.22, P = 0.89). In subgroup analysis, similar results were found. In conclusion, this meta-analysis has demonstrated that there is a lack of association of the CDH1-160C>A polymorphism with GI cancer susceptibility.

  3. 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

  4. Construction of the Antisense Eukaryotic Vector for Proliferating Cell Nuclear Antigen Gene and Its Expression in Bladder Cancer EJ Cell Line

    Institute of Scientific and Technical Information of China (English)

    童强松; 曾甫清; 齐义鹏; 朱朝晖; 鲁功成

    2002-01-01

    Summary: To explore a novel strategy for antisense gene therapy of cancer, the coding sequence ofhuman proliferating cell nuclear antigen (PCNA) cDNA was reversely inserted into the eukaryoticvector pLXSN by molecular cloning techniques and transferred into bladder cancer EJ cells with li-posome. The PCNA expression in transferred cells was dynamically detected by immunofluo-rescence and RT-PCR techniques. Changes of proliferation activities of cancer cells were assayedby MTT colorimetric and cloning formation methods. In the experiment, the antisense eukaryoticvector was successfully constructed and named as pLAPSN. After transfection with it for 1-7days, PCNA protein and mRNA levels in cancer cells were blocked by 16. 74 % - 84.21% (P<0. 05) and 23.27 % - 86.15 % (P<0. 05) respectively. The proliferation activities of transferredcells were inhibited by 27.91% - 62.07 % (P<0. 01), with cloning formation abilities being de-creased by 50. 81% (P<0. 01). It was concluded that the in vitro proliferation activities of cancercells could be effectively inhibited by blocking PCNA expression with antisense technique, whichcould serve as an ideal strategy for gene therapy of bladder cancer.

  5. The prognostic and predictive value of combined HE4 and CA-125 in ovarian cancer patients

    DEFF Research Database (Denmark)

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

    2012-01-01

    A risk-of-ovarian-malignancy algorithm (ROMA) based on human epididymis protein 4 (HE4) and CA-125 has been reported to categorize women with a pelvic mass into high or low risk of ovarian malignancy. Originally, the ROMA score was developed for diagnostic purposes and the clinical application of...

  6. A Bead-Based Multiplexed Immunoassay to Evaluate Breast Cancer Biomarkers for Early Detection in Pre-Diagnostic Serum

    Directory of Open Access Journals (Sweden)

    Carla H. van Gils

    2012-10-01

    Full Text Available This study investigates whether a set of ten potential breast cancer serum biomarkers and cancer antigens (osteopontin (OPN, haptoglobin, cancer antigen 15-3 (CA15-3, carcinoembryonic antigen (CEA, cancer antigen 125 (CA-125, prolactin, cancer antigen 19-9 (CA19-9, α-fetoprotein (AFP, leptin and migration inhibitory factor (MIF can predict early stage breast cancer in samples collected before clinical diagnosis (phase III samples. We performed a nested case-control study within the Prospect-EPIC (European Prospective Investigation into Cancer and nutrition cohort. We examined to what extent the biomarker panel could discriminate between 68 women diagnosed with breast cancer up to three years after enrollment and 68 matched healthy controls (all 56-64 years at baseline. Using a quantitative bead-based multiplexed assay, we determined protein concentrations in serum samples collected at enrollment. Principal Component Analysis (PCA and Random Forest (RF analysis revealed that on the basis of all ten proteins, early cases could not be separated from controls. When we combined serum protein concentrations and subject characteristics related to breast cancer risk in the RF analysis, this did not result in classification accuracy scores that could correctly classify the samples (sensitivity: 50%, specificity: 50%. Our findings indicate that this panel of selected tumor markers cannot be used for diagnosis of early breast cancer.

  7. Effects of Fresh Yellow Onion Consumption on CEA, CA125 and Hepatic Enzymes in Breast Cancer Patients: A Double- Blind Randomized Controlled Clinical Trial.

    Science.gov (United States)

    Jafarpour-Sadegh, Farnaz; Montazeri, Vahid; Adili, Ali; Esfehani, Ali; Rashidi, Mohammad-Reza; Mesgari, Mehran; Pirouzpanah, Saeed

    2015-01-01

    Onion (Allium cepa) consumption has been remarked in folk medicine which has not been noted to be administered so far as an adjunct to conventional doxorubicin-based chemotherapy in breast cancer patients. To our knowledge, this is the first study aimed to investigate the effects of consuming fresh yellow onions on hepatic enzymes and cancer specific antigens compared with a low-onion containing diet among breast cancer (BC) participants treated with doxorubicin. This parallel design randomized controlled clinical trial was conducted on 56 BC patients whose malignancy was confirmed with histopathological examination. Subjects were assigned in a stratified-random allocation into either group received body mass index dependent 100-160 g/d of onion as high onion group (HO; n=28) or 30-40 g/d small onion in low onion group (LO; n=28) for eight weeks intervention. Participants, care givers and laboratory assessor were blinded to the assignments (IRCT registry no: IRCT2012103111335N1). The compliance of participants in the analysis was appropriate (87.9%). Comparing changes throughout pre- and post-dose treatments indicated significant controls on carcinoembryonic antigen, cancer antigen-125 and alkaline phosphatase levels in the HO group (P<0.05). Our findings for the first time showed that regular onion administration could be effective for hepatic enzyme conveying adjuvant chemotherapy relevant toxicity and reducing the tumor markers in BC during doxorubicin-based chemotherapy. PMID:26625755

  8. 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...

  9. 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.

  10. 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

  11. A reusable localized surface plasmon resonance biosensor for quantitative detection of serum squamous cell carcinoma antigen in cervical cancer patients based on silver nanoparticles array

    Directory of Open Access Journals (Sweden)

    Zhao Q

    2014-02-01

    Full Text Available Qianying Zhao,1 Ruiqi Duan,1 Jialing Yuan,1 Yi Quan,1 Huan Yang,2 Mingrong Xi1 1Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, 2State Key Laboratory of Optical Technologies for Micro-fabrication, Institute of Optics and Electronics, Chinese Academy of Science, Chengdu, Sichuan, People's Republic of China Abstract: Squamous cell carcinoma antigen (SCCa, as a tumor biomarker, plays an important role in adjuvant diagnosis, treatment evaluation, and prognosis prediction for cervical cancer patients. Localized surface plasmon resonance (LSPR technique based on noble metal nanoparticles bypasses the disadvantages of traditional testing strategies, in terms of free-labeling, short assay time, good sensitivity, and selectivity. Herein, we develop a novel and reusable LSPR biosensor for the detection of SCCa. First, a triangle-shaped silver nanoparticle array was fabricated using the nanosphere lithography method. Next, we investigated and verified the feasibility of amino coupling method using 11-mercaptoundecanoic acid (MUA to form a functionalized chip surface with monoclonal anti-SCCa antibodies on the silver nanoparticles for distinct detection of SCCa. Different concentrations of SCCa were successfully tested in both buffer and human serum by the ultrasensitive and specific LSPR system, with a linear quantitative detection range of 0.1–1,000 pM under optimal conditions. With appropriate regeneration solution, for example 50 mM glycine-HCl (pH 2.0, the LSPR biosensor featured effective fabrication reproducibility, which reduced both production cost and testing time. Our study represents the first application of the LSPR biosensor in cervical cancer, and demonstrates that the rapid, simple, and reusable nanochip can serve as a potential alternative for clinical serological diagnosis of SCCa in cervical cancer patients. Keywords: localized surface plasmon resonance, nanotechnology, biosensor

  12. 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).

  13. Tumour markers in gastrointestinal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lamerz, R.

    1988-02-01

    For non-endocrine gastrointestinal tumours the following tumour markers are of clinical interest: For esophageal cancer CEA (sensitivity, s: 40-60%) and SCC (squamous cell carcinoma antigen, x: 20-50%); for gastric cancer CEA (s: 30-40%) as well as CA 19-9 (s: 30-40%) because of complementary results (additive s: 50-60); for hepatocellular cancer AFP (first choice, s: 70-90%; second choice CA 19-9, s: 50-70%); for cholangiocellular cancer CA 19-9 (s: 40-70%); for secondary liver cancer in general CEA; for biliary tract cancer CA 19-9 (s: 40-70%) as well as for excretory pancreatic cancer (s: 70-90%); for colorectal cancer CEA (s: 40-70%) as a first choice marker, and CA 19-9 (s: 20-60%) as a second choice marker, and for anal cancer SCC. The frequency of tumour marker determinations depends on follow-up care recommendations for different tumour diseases (e.g. 1-3 monthly during the 1st and 2nd postoperative year, following chemotherapy courses, on change of therapy, on restaging and at unclear alteration of the clinical state). Tumour markers are only valuable adjuncts to the medical care of tumour patients and therefore useless as solitary findings or on missing therapeutic consequence.

  14. 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.

  15. Clinical significance of lueasurement of changes of serum CA153、CA125、Hcy and IL-8 levels after operation in patients with Breast cancer%乳腺癌患者手术治疗前后血清CA153、CA125、Hcy和IL-8水平检测的临床意义

    Institute of Scientific and Technical Information of China (English)

    王永东; 丁贤

    2014-01-01

    目的:探讨了乳腺癌患者手术治疗前后血清C A153、C A125、H c y和I L-8水平的变化及临床意义。方法:应用放射免疫分析法和免疫化学法对38例乳腺癌患者进行了手术治疗前后血清C A153、C A125、H c y和I L-8水平检测,并与35个正常健康人做比较。结果:乳腺癌患者在手术治疗前血清C A153、C A125、H c y和I L-8水平均非常显著地高于正常人组(P<0.05),手术治疗3个月后则与正常人比较无显著性差异(P>0.05),血清C A153水平与C A125、IL-8水平呈显著正相关(r=0.6028、0.5722、0.4986,P<0.01)结论:检测乳腺癌患者手术治疗前后血清CA153、CA125、Hcy和IL-8水平的变化对观察病情和预后判定均具有重要的临床价值。%Objective: to explore the clinical significance of changes of serum CA153、CA125、Hcy and IL-8 levels after operation in patients with Breast cancer. Methods: serum CA153、CA125、IL-8 (with RIA) serum Hcy(with immune chemistry)levels were determined in 38 patients with Breast cancer and 35 controls . Result: Before operation serum CA153、CA125、Hcy and IL-8 levels were significantly higher than those in controls (P0.05). serum CA153 levels were positively correlated with serum CA125、Hcy、IL-8 levels(r=0.6028、0.5722、0.4986,P<0.01). Conclusions:Detection of serum CA153、CA125、Hcy and IL-8 levels after operation might be of prognostic importance in patients with Breast cancer.

  16. 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

  17. Prostate-specific antigen (PSA) blood test

    Science.gov (United States)

    Prostate-specific antigen; Prostate cancer screening test; PSA ... PSA testing is an important tool for detecting prostate cancer, but it is not foolproof. Other conditions can cause a rise in PSA, including: A larger prostate ...

  18. Predictive value of prostate-specific antigen for prostate cancer: a nested case-control study in EuroSIDA

    Directory of Open Access Journals (Sweden)

    Leah Shepherd

    2014-11-01

    Full Text Available 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 predictive value of PSA in HIV+ men. Methods: Men with PCa (n=21 and up to two matched controls (n=40 with prospectively stored plasma samples before PCa (or matched date in controls were selected. Cases and controls were matched on date of first and last sample, age, region of residence and CD4 count at first sample date. Total PSA (tPSA, free PSA (fPSA, testosterone and sex hormone binding globulin (SHBG were measured. Conditional logistic regression models investigated associations between markers and PCa. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. Mixed models were used to describe kinetics. Results: Sixty-one men were included with a median six (IQR 2–9 years follow-up. Time between last sample and PCa was seven (4–11 months. Cases and controls were well matched at first sample, with a median age of 51 (IQR 48–57 and CD4 of 437 (243–610 cells/mm3. Median tPSA [2.8 (IQR: 1.6–4.6 and 0.8 (0.5–1.2 µg/L] and fPSA [0.4 (0.2–0.8 and 0.3 (0.2–0.4 µg/L] levels were higher in cases than controls at first sample. Both tPSA and fPSA increased significantly over time in cases (Figure 1, to a median at last sample of 6.1 (4.7–9.5 and 0.9 (0.6–1.3 µg/L, respectively, but were stable in controls, with a median at last sample of 0.8 (0.5–1.4 and 0.2 (0.2–0.4 µg/L (Figure. Higher levels of tPSA and fPSA were associated with higher odds of PCa at first sample [OR for 2-fold higher 4.7 (CI: 1.7–12.9 and 5.4 (1.7–17.4]. Elevated tPSA values in cases were detectable ≥5 years before PCa (p0.7. The most informative predictor of PCa was tPSA (AUC=0.9, followed by fPSA (0.8. Testosterone (AUC = 0.5 and SHBG

  19. 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

  20. 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.

  1. 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

  2. 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

  3. 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...

  4. 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...

  5. 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.

  6. Antiproliferation and induction of apoptosis in Ca9-22 oral cancer cells by ethanolic extract of Gracilaria tenuistipitata.

    Science.gov (United States)

    Yeh, Chi-Chen; Tseng, Chao-Neng; Yang, Jing-Iong; Huang, Hurng-Wern; Fang, Yi; Tang, Jen-Yang; Chang, Fang-Rong; Chang, Hsueh-Wei

    2012-09-11

    The water extract of Gracilaria tenuistipitata have been found to be protective against oxidative stress-induced cellular DNA damage, but the biological function of the ethanolic extracts of G. tenuistipitata (EEGT) is still unknown. In this study, the effect of EEGT on oral squamous cell cancer (OSCC) Ca9-22 cell line was examined in terms of the cell proliferation and oxidative stress responses. The cell viability of EEGT-treated OSCC cells was significantly reduced in a dose-response manner (p < 0.0001). The annexin V intensity and pan-caspase activity of EEGT-treated OSCC cells were significantly increased in a dose-response manner (p < 0.05 to 0.0001). EEGT significantly increased the reactive oxygen species (ROS) level (p < 0.0001) and decreased the glutathione (GSH) level (p < 0.01) in a dose-response manner. The mitochondrial membrane potential (MMP) of EEGT-treated OSCC cells was significantly decreased in a dose-response manner (p < 0.005). In conclusion, we have demonstrated that EEGT induced the growth inhibition and apoptosis of OSCC cells, which was accompanied by ROS increase, GSH depletion, caspase activation, and mitochondrial depolarization. Therefore, EEGT may have potent antitumor effect against oral cancer cells.

  7. Antiproliferation and Induction of Apoptosis in Ca9-22 Oral Cancer Cells by Ethanolic Extract of Gracilaria tenuistipitata

    Directory of Open Access Journals (Sweden)

    Chi-Chen Yeh

    2012-09-01

    Full Text Available The water extract of Gracilaria tenuistipitata have been found to be protective against oxidative stress-induced cellular DNA damage, but the biological function of the ethanolic extracts of G. tenuistipitata (EEGT is still unknown. In this study, the effect of EEGT on oral squamous cell cancer (OSCC Ca9-22 cell line was examined in terms of the cell proliferation and oxidative stress responses. The cell viability of EEGT-treated OSCC cells was significantly reduced in a dose-response manner (p < 0.0001. The annexin V intensity and pan-caspase activity of EEGT-treated OSCC cells were significantly increased in a dose-response manner (p < 0.05 to 0.0001. EEGT significantly increased the reactive oxygen species (ROS level (p < 0.0001 and decreased the glutathione (GSH level (p < 0.01 in a dose-response manner. The mitochondrial membrane potential (MMP of EEGT-treated OSCC cells was significantly decreased in a dose-response manner (p < 0.005. In conclusion, we have demonstrated that EEGT induced the growth inhibition and apoptosis of OSCC cells, which was accompanied by ROS increase, GSH depletion, caspase activation, and mitochondrial depolarization. Therefore, EEGT may have potent antitumor effect against oral cancer cells.

  8. Combined detection of CEA, CA19-9 and CA125 in the differential diagnosis of benign and malignant ascites%联合检测CEA、CA19-9和CA125对鉴别良恶性腹水的价值

    Institute of Scientific and Technical Information of China (English)

    卢冰贤; 周云英

    2011-01-01

    目的 探讨检测CEA(癌胚抗原)、CA19-9(糖类抗原19-9)和CA125(糖类抗原125)对鉴别良、恶性腹水的临床价值. 方法 化学发光法检测120例患者腹水CEA、CA19-9和CA125的含量. 结果 化学发光法检测恶性腹水中的CEA、CA19-9和CA125分别为(37±16) ng/ml、(236±78) U/ml和(602士211)U/ml,良性腹水分别为(13±2)ng/ml、(34士3)U/ml和(32±3)U/ml,差异均有统计学意义(P<0.05).同时,3种抗原检测的敏感性和特异性各有特点,需要联合检测. 结论 联合检测良、恶性腹水中CEA、CA19-9和CA125水平对鉴别诊断有一定临床意义.%Objective To explore the clinical value of detecting CEA (cancer embryo antigen), CA19-9 (sugar 19-9 antigen), and CA125 (sugar antigen 125) to differentiate benign and malignant ascites. Methods CA19-9, CEA, and CA125 levels were determined by chemiluminescence detection in 120 patients with ascites. Results Chemiluminescence of patients with malignant ascites revealed a CEA level of (37± 16) ng/ml, a CA19-9 level of (236±78) U/ml, and a CA125 level of (602 + 211) U/ml while chemiluminescence of patients with benign ascites revealed a CEA level of (13± 2) ng/ml, a CA19-9 level of (34±3) U/ml and a CA125 level of (32 ± 3) U/ml. Differences were statistically significant (P<0. 05). Testing with 3 different antigens revealed a particular sensitivity and specificity, and combined testing was required. Conclusion Combined testing of CA19-9, CEA, and CA125 levels has some clinical significance in the differential diagnosis of benign and malignant ascites.

  9. 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

  10. The prognostic value of pre-operative serum tetranectin, CA-125 and a combined index in women with primary ovarian cancer

    DEFF Research Database (Denmark)

    Høgdall, Claus K; Nørgaard-Pedersen, Bent; Mogensen, Ole

    2002-01-01

    OBJECTIVE: To study the prognostic value of pre-operative serum tetranectin (TN), CA125 levels and a mathematical formula (Index1) in primary ovarian cancer. MATERIALS AND METHODS: The study group consisted of sixty-six patients with varying FIGO stages I-IV. The end-point was death from ovarian...

  11. 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.

  12. The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Therkildsen, Christina; Bergmann, Troels K; Henrichsen-Schnack, Tine;

    2014-01-01

    -RAF-MAPK and PI3K-AKT-mTOR pathways in colorectal cancer is uncertain, which led us to systematically review the impact of alterations in KRAS (outside of exon 2), NRAS, BRAF, PIK3CA and PTEN in relation to the clinical benefit from anti-EGFR treatment. METHODS: In total, 22 studies that include 2395 patients...... formed the basis for a meta-analysis on alterations in KRAS exons 3 and 4, NRAS, BRAF, and PIK3CA and PTEN and outcome of anti-EGFR treatment. Odds ratios for objective response rate (ORR) and hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) were calculated. RESULTS......, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti-EGFR therapies and demonstrates that biomarker analysis beyond KRAS exon 2 should be implemented for prediction of clinical benefit from anti-EGFR antibodies in metastatic colorectal cancer....

  13. Serum concentrations of the biomarkers CA125, CA15-3, CA72-4, tPSA and PAPP-A in natural and stimulated ovarian cycles

    Institute of Scientific and Technical Information of China (English)

    Melissa Stemp; Peter Roberts; Allison McClements; Vincent Chapple; Jay Natalwala; Michael Black; Phillip Matson

    2014-01-01

    Objective:Biomarkers associated with cancer screening (CA125, CA15‐3, CA72‐4, total prostate specific antigen [tPSA]) and the monitoring of pregnancy (pregnancy associated plasma protein‐A [PAPP‐A]) were measured during natural and stimulated ovarian cycles in disease‐free non-pregnant women to determine if they could reflect normal events relating to ovulation and/or endometrial changes. Methods: A total of 73 blood samples (10 women) collected throughout the natural menstrual cycle, and 64 blood samples (11 women) taken during stimulated ovarian cycles, were analysed on the Roche Cobas e411 automated analyser. Results:Detectable levels of tPSA were measured in at least one point in the cycle in 6/10 of women in the natural cycle and 10/11 of women in stimulated cycles, and CA72-4 was detected in only 12/21 women tested. Concentrations of CA125, tPSA, CA15‐3 and CA72‐4 showed no significant difference between the natural and stimulated ovarian cycle groups. On average the mean PAPP‐A of the natural group was (2.41±0.58) mIU/L higher than the stimulated group (t=4.10, P< 0.001). CA125 and CA15‐3 results were both significantly influenced by the stage of the cycle (P<0.0001), whereas tPSA and PAPP‐A concentrations revealed no significant changes (P≥0.65). CA72‐4 was not affected by the stage of the cycle nor ovarian stimulation. Conclusion:Ovarian stimulation reduced serum PAPP‐A levels, CA125 and CA15‐3 levels were generally unaffected by ovarian stimulation but displayed cyclical changes throughout both natural and stimulated cycles, whilst tPSA and CA72-4 were not affected by the stage of the cycle or ovarian stimulation.

  14. 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

  15. Comparison Study of Cyfra 21-1, Carcinoembryonic Antigen and Telomerase Activity between Non Small Cell and Small Cell Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    B. Alani

    2008-10-01

    Full Text Available Introduction & Objective: The roles of tumor markers in the prognosis and diagnosis of lung cancer is under investigation. The aim of this study was to examine correlation between serum levels of Carcinoembryonic Antigen (CEA and Cyfra 21-1 with telomerase activity on biopsy samples in patients with lung cancer and controls.Materials & Methods: We studied 50 malignant lung cancer patients (mean age 68.3±13.8 years and 20 normal individuals (mean age 64.9±11.4 years. Serum levels of Cyfra21-1 and CEA were measured with available enzyme immunoassay kits. Telomerase activity was measured by TRAP assay based on PCR-ELISA in lung tumor biopsy. To compare quantitative means of the two groups, t-independent and Man-Whitney analysis were applied.Results: The mean serum levels of CEA and Cyfra21-1 concentration together telomerase activity of biopsy samples in lung cancer patients were significantly higher than controls. There were a strong correlation between Cyfra21-1 and CEA, Telomerase and CEA and Telomerase and Cyfra21-1 in patient group. In patients with small cell carcinoma, the mean serum levels of Cyfra21-1 and CEA were significantly higher than non small cell carcinoma patients. Telomerase activities in biopsy samples of small cell carcinoma were significantly lower than non small cell carcinoma patients.Conclusion: It is speculated that based on this findings, telomerase activity in biopsy samples for small cell carcinoma patients and serum levels of Cyfra 21-1 and CEA are the most useful tumor markers for diagnosis of squamous and adenocarcinoma of non small cell cancers respectively.

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

    DEFF Research Database (Denmark)

    Gjerstorff, M F; Ditzel, H J

    2008-01-01

    cell biology. When expressed in tumor cells, GAGE proteins can elicit both cellular and humoral immune responses, indicating that they are appropriate targets for cancer immunotherapy. The potential use of GAGE proteins in cancer immunotherapy, including possible limitations, is also discussed....

  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. 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.

  19. 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.

  20. 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.

  1. Positive predictive value of CEA and Ca19-9 as tumor markers for recurrent colorectal cancer in cases where conventional work-up fail to localize disease.

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    Yana Bocheva

    2015-12-01

    Full Text Available Introduction: Routine surveillance of colorectal cancer includes serial measurements of CEA levels. Although not routinely indicated Ca 19-9 is also a tool for recurrence. When any of these serum markers is elevated during follow up, this could represent a recurrence. The management of elevated tumor marker levels include clinical exams, endoscopy and conventional imaging –ultrasound, CT, MRI.Objective: To evaluate the positive predictive value of CEA and Ca19-9 as tumor markers for recurrent colorectal cancer in cases where conventional imaging and endoscopic studies fail to localize disease.Materials and methods: A total of 75 patients with elevated CEA and/or Ca19-9 serum levels and negative endoscopic exam as well as negative abdominal CT and Chest X-ray were included in the study. CEA levels were tested in 50 patients. Ca 19-9 was tested in 65 patients. 34 of the patients had both markers tested. All patients underwent whole body 18F-FDG PET/CT. Patients with negative of equivocal PET scan were further followed up (10 to 24 months.Results: Based on the reference standard – the results from PET/CT, if positive and the results from follow-up in cases of negative or equivocal scans, the positive predictive value of Ca 19-9 was 84% and that of CEA -83%. There was no significant difference in the PPV of Ca19-9 and CEA.Conclusion: Elevated CEA and Ca 19-9 levels in patients under active surveillance after operation for colorectal cancer have high positive predictive value for recurrence, even in cases where conventional work-up – endoscopy and CT don’t localize disease.

  2. Prediction of the presence of ovarian cancer at surgery by an immunochemical panel: CA 125 and copper-to-zinc ratio.

    Science.gov (United States)

    Gal, D; Lischinsky, S; Friedman, M; Zinder, O

    1989-11-01

    Preoperative levels of the trace elements copper and zinc, in addition to the level of the known marker CA 125, were studied in sera of 32 patients undergoing exploratory laparotomy for suspicion of ovarian cancer and in sera of 49 patients with the diagnosis of ovarian cancer prior to second-look operation. Most patients (63/81) had stage III or IV disease. CA 125 levels greater than 35 U/ml, copper levels greater than 1.5 mg/liter, and zinc levels less than 0.9 mg/liter were considered pathologic. An immunochemical panel composed of CA 125 serum level and ratio of copper to zinc (Cu/Zn) (normal less than 1.65) was found to be most sensitive (98%) in predicting the existence of ovarian cancer before laparotomy, and its overall predictability was 89%. In 14 of 14 patients (100%) who had complete primary surgery for ovarian cancer, the panel was correct in predicting no tumor at second-look operation. In 13 of 14 patients (93%) who had incomplete primary surgery but had no clinical evidence of disease prior to second-look operation, the panel was correct in predicting ovarian cancer. In these two groups of patients, second-look operation could have been replaced by the results of the immunochemical panel.

  3. Alterations in PTEN and PIK3CA in colorectal cancers in the EPIC Norfolk study: associations with clinicopathological and dietary factors

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    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.

  4. Induction of Mitochondria-Mediated Apoptosis in Ca Ski Human Cervical Cancer Cells Triggered by Mollic Acid Arabinoside Isolated from Leea indica

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    Yau Hsiung Wong

    2012-01-01

    Full Text Available Leea indica is a medicinal plant traditionally used to treat cancer. Through bioassay-guided approach, we isolated mollic acid arabinoside (MAA, for the first time from Leea indica. Here, we present the apoptosis-inducing effect of MAA on Ca Ski cervical cancer cells. Based on DAPI staining, MAA-treated cells manifested nuclear shrinkage, condensation, and fragmentation. We further confirmed the fragmentation of DNA using TUNEL assay. During early apoptosis, MAA caused the perturbation of plasma membrane through externalization of PS, followed by the formation of apoptotic blebs. Prior to these events, MAA triggered rapid dissipation of the mitochondrial membrane potential. In the upstream, MAA increased the expression of Bax, decreased the expression of Bcl-2, and augmented the Bax/Bcl-2 ratio. These findings suggested that MAA induced mitochondrial-mediated apoptosis in Ca Ski cells and thus provide the scientific explanation for the traditional application of this herbal medicine in cancer treatment.

  5. 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

  6. KRAS, BRAF, PIK3CA, and PTEN mutations: implications for targeted therapies in metastatic colorectal cancer.

    Science.gov (United States)

    De Roock, Wendy; De Vriendt, Veerle; Normanno, Nicola; Ciardiello, Fortunato; Tejpar, Sabine

    2011-06-01

    The discovery of mutant KRAS as a predictor of resistance to epidermal growth-factor receptor (EGFR) monoclonal antibodies brought a major change in the treatment of metastatic colorectal cancer. This seminal finding also highlighted our sparse knowledge about key signalling pathways in colorectal tumours. Drugs that inhibit oncogenic alterations such as phospho-MAP2K (also called MEK), phospho-AKT, and mutant B-RAF seem promising as single treatment or when given with EGFR inhibitors. However, our understanding of the precise role these potential drug targets have in colorectal tumours, and the oncogenic dependence that tumours might have on these components, has not progressed at the same rate. As a result, patient selection and prediction of treatment effects remain problematic. We review the role of mutations in genes other than KRAS on the efficacy of anti-EGFR therapy, and discuss strategies to target these oncogenic alterations alone or in combination with receptor tyrosine-kinase inhibition.

  7. Diagnostic value of alpha fetoprotein (AFP),α-L-fucosidase(AFU) and carbohydrate antigen 199 (CA199)combined detection in early stage orimary hepatocellular carcinoma (PHC)%AFP、AFU、CA199联合检测对早期原发性肝癌的诊断价值

    Institute of Scientific and Technical Information of China (English)

    邓爱红; 彭燕华; 周少雄; 沈永坚; 肖海萍; 何彩云; 林经良

    2015-01-01

    目的:探讨肿瘤标志物甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)、糖类抗原199(CA199)对早期原发性肝癌(primary carcinoma of the liver,PHC)联合检测的诊断价值。方法:选取2013年1月到2014年5月佛山市第二人民医院肝科门诊初诊患者,通过病史、症状和查体拟诊为疑似PHC患者,再采用诊断金标准将疑似患者(研究对象)确诊分为PHC(48例)和非PHC(76例),所有研究对象均检测血清AFP、AFU和CA199,检测AFP和CA199采用化学发光法,检测AFU采用全自动生化仪器法,采用循证检验医学的方法统计各诊断价值性能指标。结果:PHC组患者AFP、AFU和CA199水平较非PHC组非常显著升高(P<0.01)。单一指标AFP、AFU和CA199检测PHC的诊断灵敏度分别为74.3%、51.4%、51.4%。单一指标AFP、AFU和CA199检测PHC的诊断特异性分别为82.4%、94.1%、94.1%。3指标并联灵敏度最高,为86.4%,其漏检率为13.6%。3指标串联和AFU/CA199串联特异性最高,约为96.5%,其误诊率为3.5%。结论:3指标并联是最佳PHC筛查联合指标,AFU和CA199串联是最佳PHC确诊联合指标。%Objective:To investigate the diagnostic value of the alpha fetoprotein (AFP), α-L- fucosidase(AFU), carbohydrate antigen 199 (CA199) and their combinations in Early Stage Primary Hepatocellular Carcinoma (PHC). Methods:Selected the Hepatological outpatients at their first visit to the second people’s hospital of Foshan from January,2013 to May,2014.Suspicious PHC patients were diagnosed by medical history, symptoms and physical check,and suspicious PHC patients were classified into PHC patients(n=48) and non-PHC patients(n=76) following the diagnosed gold criteria.The concentration of AFP and CA199 was determined by Chemiluminescence method.The concentration of AFU were determined by full automatic biochemical instrument.The assessed parameters of diagnostic value were measured using the evidence-based laboratory

  8. Type 2 diabetes mellitus and CA 19-9 levels

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To prospectively investigate serum CA 19-9 levels in type 2 diabetic patients in comparison with age- and gender-matched control subjects. METHODS: We recorded duration of diabetes and examined fasting glucose levels, HbA1c levels and serum CA 19-9 levels in 76 type 2 diabetic patients and 76 controls. Abdominal CT was performed in order to eliminate abdominal malignancy in the diabetic and control groups. RESULTS: The average CA 19-9 level was 46.0 ± 22.4 U/mL for diabetic patients whereas it was 9.97 ± 7.1 U/mL for the control group (P < 0.001 ). Regression analysis showed a positive correlation between diabetes and CA 19-9 independent from age, gender, glucose level and HbA1c level (t = 8.8, P < 001 ). Two of the diabetic patients were excluded from the study because of abdominal malignancy shown by CT at the initial evaluation. For all patients, abdominal CT showed no pancreatic abnormalities. CONCLUSION: CA 19-9 is a tumor-associated antigen, which is elevated in pancreatic, upper gastrointestinal tract, ovarian hepatocellular, and colorectal cancers, as well as in inflammatory conditions of the hepatobiliary system, biliary obstruction and in thyroid diseases. Diabetes has been claimed to be a risk factor for pancreatic cancer, which is increasing its incidence and has one of the lowest survival rates of all cancers. CA 19-9 is used in the diagnosis of pancreatic cancer but is also a marker of pancreatic tissue damage that might be caused by diabetes. We propose that a higher cutoff value of CA 19-9 should be used in diabetics to differentiate benign and malignant pancreatic disease, and subtle elevations of CA 19-9 in diabetics should be considered as the indication of exocrine pancreatic dysfunction.

  9. Construction of human liver cancer vascular endothelium cDNA expression library and screening of the endothelium-associated antigen genes

    Institute of Scientific and Technical Information of China (English)

    Xing Zhong; Yu-Liang Ran; Jin-Ning Lou; Dong Hu; Long Yu; Yu-Shan Zhang; Zhuan Zhou; Zhi-Hua Yang

    2004-01-01

    AIM: To gain tumor endothelium associated antigen genes from human liver cancer vascular endothelial cells (HLCVECs)cDNA expression library, so as to find some new possible targets for the diagnosis and therapy of liver tumor.METHODS: HLCVECs were isolated and purified from a fresh hepatocellular carcinoma tissue sample, and were cultured and proliferated in vitro. A cDNA expression library was constructed with the mRNA extracted from HLCVECs.Anti-sera were prepared from immunized BALB/c mice through subcutaneous injection with high dose of fixed HLCVECs, and were then tested for their specificity against HLCVECs and angiogenic effectsin vitro, such as inhibiting proliferation and inducing apoptosis of tumor endothelial cells, using immunocytochemistry, immunofiuorescence,cell cycle analysis and MTT assays, etc. The identified xenogeneic sera from immunized mice were employed to screen the library of HLCVECs by modified serological analyses of recombinant cDNA expression libraries (SEREX).The positive clones were sequenced and analyzed by bioinformatics.RESULTS: The primary cDNA library consisted of 2x106recombinants. Thirty-six positive clones were obtained from6×10s independent clones by immunoscreening. Bio-informatics analysis of cDNA sequences indicated that 36 positive clones represented 18 different genes. Among them, 3 were new genes previously unreported, 2 of which were hypothetical genes. The other L5 were already known ones. Series analysis of gene expression (SAGE) database showed that ERP70,GRP58, GAPDH, SSB, S100A6, BMP-6, DVS27, HSP70 and NAC alpha in these genes were associated with endothelium and angiogenesis, but their effects on HLCVECs were still unclear. GAPDH, S100A6, BMP-6 and hsp70 were identified by SEREX in other tumor cDNA expression libraries.CONCLUSION: By screening of HLCVECs cDNA expression library using sera from immunized mice with HLCVECs,the functional genes associated with tumor endothelium or angiogenesis were identified. The

  10. Human Leukocyte Antigen-Presented Macrophage Migration Inhibitory Factor Is a Surface Biomarker and Potential Therapeutic Target for Ovarian Cancer.

    Science.gov (United States)

    Patterson, Andrea M; Kaabinejadian, Saghar; McMurtrey, Curtis P; Bardet, Wilfried; Jackson, Ken W; Zuna, Rosemary E; Husain, Sanam; Adams, Gregory P; MacDonald, Glen; Dillon, Rachelle L; Ames, Harold; Buchli, Rico; Hawkins, Oriana E; Weidanz, Jon A; Hildebrand, William H

    2016-02-01

    T cells recognize cancer cells via HLA/peptide complexes, and when disease overtakes these immune mechanisms, immunotherapy can exogenously target these same HLA/peptide surface markers. We previously identified an HLA-A2-presented peptide derived from macrophage migration inhibitory factor (MIF) and generated antibody RL21A against this HLA-A2/MIF complex. The objective of the current study was to assess the potential for targeting the HLA-A2/MIF complex in ovarian cancer. First, MIF peptide FLSELTQQL was eluted from the HLA-A2 of the human cancerous ovarian cell lines SKOV3, A2780, OV90, and FHIOSE118hi and detected by mass spectrometry. By flow cytometry, RL21A was shown to specifically stain these four cell lines in the context of HLA-A2. Next, partially matched HLA-A*02:01+ ovarian cancer (n = 27) and normal fallopian tube (n = 24) tissues were stained with RL21A by immunohistochemistry to assess differential HLA-A2/MIF complex expression. Ovarian tumor tissues revealed significantly increased RL21A staining compared with normal fallopian tube epithelium (P < 0.0001), with minimal staining of normal stroma and blood vessels (P < 0.0001 and P < 0.001 compared with tumor cells) suggesting a therapeutic window. We then demonstrated the anticancer activity of toxin-bound RL21A via the dose-dependent killing of ovarian cancer cells. In summary, MIF-derived peptide FLSELTQQL is HLA-A2-presented and recognized by RL21A on ovarian cancer cell lines and patient tumor tissues, and targeting of this HLA-A2/MIF complex with toxin-bound RL21A can induce ovarian cancer cell death. These results suggest that the HLA-A2/MIF complex should be further explored as a cell-surface target for ovarian cancer immunotherapy.

  11. 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

  12. 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

  13. 化學發光法血清CEA、CA15-3和SF聯合測定對肺癌的診斷價值%Clinical value of combined detection of serum CEA, CA15 3 and SF in lung cancer

    Institute of Scientific and Technical Information of China (English)

    周愛清; 王雪芹; 吴建國

    2001-01-01

    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, CA153 and SF were measured by chemiluminescent assay (CLA) in 99 patients with lung cancer and 25 patients with benign lung diseases. Results The positive rate of serum CEA, CA15-3 and SF in cases of lung cancer was 50. 5%, 31. 3% and 69. 7%, respectively. Specificity of CEA, CA153 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.

  14. 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.

  15. 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)

  16. Contribution of allelic variability in prostate specific antigen (PSA & androgen receptor (AR genes to serum PSA levels in men with prostate cancer

    Directory of Open Access Journals (Sweden)

    Sushant V Chavan

    2014-01-01

    Full Text Available Background & objectives: Wide variability in serum prostate specific antigen (PSA levels exists in malignant conditions of the prostate. PSA is expressed in normal range in 20 to 25 per cent of prostate cancer cases even in presence of high grade Gleason score. This study was aimed to assess the influence of genetic variants exhibited by PSA and androgen receptor (AR genes towards the variable expression of PSA in prostate cancer. Methods: Pre-treatment serum PSA levels from 101 prostate cancer cases were retrieved from medical record. PSA genotype analysis in promoter region and AR gene microsatellite Cytosine/Adenine/Guanine (CAG repeat analysis in exon 1 region was performed using DNA sequencing and fragment analysis techniques. Results: A total of seven single nucleotide polymorphisms (SNPs in the PSA promoter region were noted. Only two SNPs viz., 158G/A (P<0.001 in the proximal promoter region and -3845G/A (P<0.001 in enhancer region showed significant association with serum PSA levels. The carriers of homozygous GG genotype (P<0.001 at both of these polymorphic sites showed higher expression of PSA whereas homozygous AA genotype (P<0.001 carriers demonstrated lower PSA levels. The combination effect of PSA genotypes along with stratified AR CAG repeats lengths (long, intermediate and short was also studied. The homozygous GG genotype along with AR long CAG repeats and homozygous AA genotype along with AR short CAG repeats at position -3845 and -158 showed strong interaction and thus influenced serum PSA levels. Interpretation & conclusions: The genetic variants exhibited by PSA gene at positions -3845G/A and -158G/A may be accountable towards wide variability of serum PSA levels in prostate cancer. Also the preferential binding of G and A alleles at these polymorphic sites along with AR long and short CAG repeats may contribute towards PSA expression.

  17. 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

  18. 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.

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    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.

  19. 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

  20. Carcinoembryonic antigen: assay following heat compared with perchloric acid extraction in patients with colon cancer, non-neoplastic gastrointestinal diseases, or chronic renal failure

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    Witherspoon, L.R.; Shuler, S.E.; Alyea, K.; Husserl, F.E.

    1983-10-01

    Heat inactivation has been proposed as an alternative to perchloric acid (PCA) precipitation for the extraction of carcinoembryonic antigen (CEA) from human plasma. A commercial RIA kit using heat inactivation was examined and results compared with those obtained with PCA precipitation. Adequate sensitivity (1.5 ..mu..g CEA/I plasma), satisfactory analytical recovery of CEA added to plasma, and dilutional linearity of samples found to have elevated CEA concentrations, were demonstrated for the heat-inactivation assay. Between-assay precision was better with the heat inactivation than with the PCA assay. Although the absolute concentration of CEA estimated after heat inactivation was consistently lower than that estimated after PCA extraction of plasma specimens, there was excellent correlation between results obtained with the two methods in colon cancer patients free of disease, colon cancer patients with residual or recurrent disease, patients with benign gastrointestinal disease, and in patients with chronic renal failure. The heat-inactivation assay is an excellent alternative to the PCA assay.

  1. Carcinoembryonic antigen: assay following heat compared with perchloric acid extraction in patients with colon cancer, non-neoplastic gastrointestinal diseases, or chronic renal failure.

    Science.gov (United States)

    Witherspoon, L R; Shuler, S E; Alyea, K; Husserl, F E

    1983-10-01

    Heat inactivation has been proposed as an alternative to perchloric acid (PCA) precipitation for the extraction of carcinoembryonic antigen (CEA) from human plasma. We examined a commercial RIA kit using heat inactivation, and compared results with those obtained with PCA precipitation. Adequate sensitivity (1.5 micrograms CEA/l plasma), satisfactory analytical recovery of CEA added to plasma, and dilutional linearity of samples found to have elevated CEA concentrations, were demonstrated for the heat-inactivation assay. Between-assay precision was better with the heat inactivation than with the PCA assay. Although the absolute concentration of CEA estimated after heat inactivation was consistently lower than that estimated after PCA extraction of plasma specimens, there was excellent correlation between results obtained with the two methods in colon cancer patients free of disease, colon cancer patients with residual or recurrent disease, patients with benign gastrointestinal disease, and in patients with chronic renal failure. We conclude that the heat-inactivation assay is an excellent alternative to the PCA assay.

  2. 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

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    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

  3. Interaction of serologically defined colon cancer antigen-3 with Arf6 and its predominant expression in the mouse testis.

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    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

  4. 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.

  5. 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, Nat; Gao, Yu-Tang; Chow, Wong-Ho; Shu, Xiao-Ou; Xiang, Yong-Bing

    2016-01-01

    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) to 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

  6. Bladder tumour antigen (BTA stat) test compared to the urine cytology in the diagnosis of bladder cancer: A meta-analysis

    Science.gov (United States)

    Guo, Aiye; Wang, Xiuhua; Gao, Lan; Shi, Juan; Sun, Changyi; Wan, Zhen

    2014-01-01

    Introduction: We evaluate the diagnostic value of bladder tumour antigen (BTA stat) tests compared with urine cytology test in detecting bladder cancer. Methods: We searched public databases including PubMed, MEDLINE Springer, Elsevier Science Direct, Cochrane Library and Google Scholar before December 2012. To collect relevant data of BTA stat tests and urine cytology tests in patients with bladder cancer, we studied meta-analyses of sensitivity, specificity, positive likelihood ratio (LR), negative LR and diagnostic odds ratios (DOR) of BTA stat tests and cytology tests from published studies. We applied the software of Rev. Man 5.1 and Stata 11.0 to the meta-analysis. Results: A total of 13 separate studies consisting of 3462 patients with bladder cancer were considered in the meta-analysis. We found that the BTA stat test had a higher sensitivity than the urine cytology test (0.67, 95% confidence interval [CI] 0.64 to 0.69 vs. 0.43, 95% CI 0.40 to 0.46), but the specificity, positive LR, negative LR, DOR, the area under the curve (AUC) and Q index of the BTA stat test were lower compared with the urine cytology test. The results of the Egger’s linear regression test showed no publication bias (p > 0.05). Conclusions: Specificity, positive LR, negative LR, DOR, the AUC and the Q index of the urine cytology test may be superior to the BTA stat test, but the BTA stat test has greater sensitivity than the urine cytology test. PMID:24940462

  7. 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.

  8. Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients.

    Science.gov (United States)

    Odunsi, Kunle; Matsuzaki, Junko; Karbach, Julia; Neumann, Antje; Mhawech-Fauceglia, Paulette; Miller, Austin; Beck, Amy; Morrison, Carl D; Ritter, Gerd; Godoy, Heidi; Lele, Shashikant; duPont, Nefertiti; Edwards, Robert; Shrikant, Protul; Old, Lloyd J; Gnjatic, Sacha; Jäger, Elke

    2012-04-10

    Recombinant poxviruses (vaccinia and fowlpox) expressing tumor-associated antigens are currently being evaluated in clinical trials as cancer vaccines to induce tumor-specific immune responses that will improve clinical outcome. To test whether a diversified prime and boost regimen targeting NY-ESO-1 will result in clinical benefit, we conducted two parallel phase II clinical trials of recombinant vaccinia-NY-ESO-1 (rV-NY-ESO-1), followed by booster vaccinations with recombinant fowlpox-NY-ESO-1 (rF-NY-ESO-1) in 25 melanoma and 22 epithelial ovarian cancer (EOC) patients with advanced disease who were at high risk for recurrence/progression. Integrated NY-ESO-1-specific antibody and CD4(+) and CD8(+) T cells were induced in a high proportion of melanoma and EOC patients. In melanoma patients, objective response rate [complete and partial response (CR+PR)] was 14%, mixed response was 5%, and disease stabilization was 52%, amounting to a clinical benefit rate (CBR) of 72% in melanoma patients. The median PFS in the melanoma patients was 9 mo (range, 0-84 mo) and the median OS was 48 mo (range, 3-106 mo). In EOC patients, the median PFS was 21 mo (95% CI, 16-29 mo), and median OS was 48 mo (CI, not estimable). CD8(+) T cells derived from vaccinated patients were shown to lyse NY-ESO-1-expressing tumor targets. These data provide preliminary evidence of clinically meaningful benefit for diversified prime and boost recombinant pox-viral-based vaccines in melanoma and ovarian cancer and support further evaluation of this approach in these patient populations.

  9. High resolution human leukocyte antigen (HLA class I and class II allele typing in Mexican mestizo women with sporadic breast cancer: case-control study

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    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

  10. 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

  11. 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 chemother