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1.
Experiments in CBA mice with transplanted CaO 1 ovarian carcinoma possessing common antigenic determinants with human ovarian carcinoma showed that specific immunotherapy with mucin containing CA 125 antigen inhibited tumor growth by 60% and prolonged antimal lifespan by 40–60% in comparison with the control. The correlation coefficient between the tumor size and antibody titer after injection of mucin was −0.4 for IgM and −0.6 for IgG. Titration of IgG may be used for monitoring of the efficiency of specific immunotherapy. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 4, pp. 456–458, April, 2000  相似文献   

2.
Protein blotting: a review   总被引:5,自引:0,他引:5  
The CA125 (carcinoma antigen 125)-specific antibody MAb-B43.13 (OvaRex MAb-B43.13) is in clinical trials for patients with ovarian carcinoma as an immunotherapeutic agent. To develop an assay for monitoring CA125-specific as well as tumor-specific T cells in the peripheral circulation of ovarian cancer patients treated with this antibody, the IFN (interferon)-gamma enzyme-linked immuno SPOT (ELISPOT) assay was optimized. Various assay formats and experimental conditions were evaluated, using peripheral blood mononuclear cells (PBMC) obtained from normal donors and patients with ovarian cancer. T cell proliferation assays were performed in parallel. Conditions tested included different types of antigen presenting cells (APC), the need for and length of in vitro sensitization to enrich in T cell precursors, titration of the antigen and comparison of pulsing dendritic cells (DC) with immune complexes (IC) of CA125 and monoclonal antibody (MAb)-B43.13 or CA125 antigen alone. Proliferation assays were found not to be sufficiently sensitive for detection of CA125-specific T cells in the peripheral circulation of normal donors. A more sensitive 24-h direct ELISPOT assay was also negative. However, ELISPOT assays preceded by a 7-day in vitro sensitization (IVS) step allowed the detection of CA125 antigen-specific T cells in the circulation of normal donors and patients with ovarian cancer. The use of DC as APC was compared to whole PBMC or immortalized B cells. Most donors and ovarian cancer patients responded best to DC pulsed with CA125 in the form of immune complexes. Optimal responses were seen using CA125 concentrations of 500 U/ml and 5 microg/ml of MAb-B43.13. The data indicate that precursor cells specific for CA125 antigen are present at low frequencies in the peripheral circulation of normal donors and patients with ovarian carcinoma and need to be expanded ex vivo for frequency determinations. The optimized assay is able to detect increases in T cell precursor frequencies to CA125 in ovarian cancer patients after immunization with MAb-B43.13.  相似文献   

3.
The interactions between tumor cells and autoantibodies to tumor-associated human ovarian cancer antigen isolated from the plasma of a non-cancer patient are demonstrated using an original model of pseudomucinous murine ovarian carcinoma CaO-1. The use of natural auto-antibodies for active immunotherapy of tumors may be more effective and safe than murine monoclonal antibodies to CA 125, because there will be no reaction to a foreign protein. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 2, pp. 227–229, February, 1999  相似文献   

4.
In a first clinical trial, 45 patients with advanced ovarian carcinoma and recurrences were treated with the murine monoclonal anti-idiotypic antibody (Ab2) designated ACA125 for active immunotherapy. The monoclonal antibody (MAb) ACA125 mimics a specific epitope of the tumor-associated antigen CA125 expressed by most malignant ovarian tumors. Patients with CA125-positive tumors are immunologically tolerant to CA125, which could be overcome by the use of an anti-idiotypic antibody as a surrogate for the tumor antigen CA125. An immunological response to the anti-idiotype ACA125 in these patients was associated with a statistically significant survival prolongation. Humoral immunity to ACA125 was assessed by induction of anti-anti-idiotypic antibodies (Ab3) directed against CA125. Using flow cytometric detection methods we observe alterations of the intracellular cytokines IFN-gamma, IL-2, and IL-4 at the single-cell level during the course of immunization. There was a strong increase of intracellular IFN-gamma and IL-2 characteristic for a Th1 cell type immune response after treatment with ACA125. A delayed induction of Th2 type response, which promotes antibody-mediated immunity by B cells, could also be detected. The understanding of the kinetics of Th1 and Th2 responses could be important to improve treatment schedules for effective immunotherapy with anti-idiotype vaccines.  相似文献   

5.
Metastatic papillary adenocarcinomas of the ovary are rare compared to primary ovarian papillary serous carcinomas. We report a case of pulmonary papillary adenocarcinoma metastatic to the ovary and show how this tumor can be differentiated immunohistochemically from an ovarian primary. Paraffin blocks of the ovarian tumor were analyzed for carcinoembryonic antigen, CA 125, surfactant, E-cadherin, N-cadherin, and vimentin. These markers are useful in differentiating epithelial tumors of lung versus ovarian origin. The papillary tumor showed expression of carcinoembryonic antigen, surfactant, and E-cadherin, but was negative for CA 125, N-cadherin, and vimentin. These findings support a lung carcinoma metastatic to the ovary.  相似文献   

6.
A case of primary seminal vesicle carcinoma is reported. The tumor was a CA125-producing adenocarcinoma consisting of fine papillary-tubular, intricate branching or anastomosing glandular structures and was composed of small cuboidal, but occasionally hobnailed, cells with mostly clear, but occasionally granular, cytoplasm. Some tumor cells showed evidence of secretion of seromucinous materials into the interpapillary and cystic space. lmmunohistochemically, almost half of the tumor cells expressed a positive reaction with anti-CAl25, a common serological marker for ovarian epithelial carcinomas; however, no tumor cells expressed any other serological tumor markers such as carcinoem-bryonic antigen, α-fetoprotein, human chorionic gonadotropin, prostatic specific acid phosphatase, or prostatic specific antigen. The patient showed a high level of serological CA125, which fluctuated parallel with the growth, removal and recurrence of the tumor. The morphological and immunohistochemical findings suggested a close relationship between the present tumor and clear cell carcinoma of the ovary, which is thought to be of a Müllerian-Wolfian duct origin.  相似文献   

7.
Immunohistochemical studies revealed a relationship between the expression of nm23 protein in gastric cancer cells and some parameters characterizing plasminogen activation system and clinical morphological factors. Expression of nm23 in the cytoplasm was detected almost 3-fold more often than in the nuclei; cytoplasmic expression more strictly correlated with patient’s age, tumor location, and its histological structure than nuclear expression. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 6, pp. 678–681, June, 2007  相似文献   

8.
CA125 is a tumor antigen used to monitor the progression and regression of epithelial ovarian cancer. Despite the widespread use of CA125, the biochemical and molecular nature of this antigen is poorly understood. Analysis of the structure of CA125 is essential for determining the physiological role of this very significant tumor marker. Accumulated experimental evidence has shown that CA125 epitopes reside on a molecule of very complex architecture in terms of both protein backbone and oligosaccharide structures. It is not clear whether the heterogeneity of CA125 molecular characteristics are due to the variability of biological sources from which the molecule was isolated or to the different biophysical methods used for the characterization of all the oligosaccharides linked to CA125 or to the presence of glycoisoforms for this protein. This review attempts to summarize emerging data related to molecular characteristics of CA125 and to compare approaches undertaken to reach a better understanding of molecular features of this tumor marker.  相似文献   

9.
《Immunobiology》2020,225(6):152010
The purpose of this study was to investigate the association of iNKT (human invariant natural killer T) cells with the key marker of ovarian cancer (OC) - CA125 (cancer antigen125) in serum. The study reports the assessment of iNKT cells in peripheral blood and tissue of benign and borderline ovarian tumors (BOTs) and in the advanced-stage ovarian cancer. The study groups were as follows: 25 women with benign ovarian tumors, 11 women with BOTs, and 24 women with primary advanced-stage ovarian cancers. The control group consisted of 20 patients without the ovarian pathology. The rates of iNKT lymphocytes in the peripheral blood and tissue specimens were evaluated by a flow cytometry. Significant differences in the percentage of iNKT+/CD3+ of CD3+ lymphocytes, iNKT+/CD3+/CD161+ among CD3+ and iNKT+/CD3+/CD161+ among CD3+/iNKT+ between the control group and patients with ovarian tumors in the peripheral blood and tumor tissue were identified. Significant correlations were noticed between the proportion of lymphocytes iNKT+/CD3+/CD161+ among CD3+/iNKT cells in blood and in cancer tissue of both benign and malignant tumors. In the OC group, neither the ratio of iNKT cells in the blood (P = 0.07), nor the intra-tumor NKT-cell infiltration (P = 0.5) were independent prognostic factors for the follow-up. An increased rate of iNKT cells was detected in benign ovarian tumors compared to OCs. In patients with ovarian cancer, a higher rate of iNKT cells in tumor tissue was present related to that noted in the patient’s blood. In addition, a correlation was discovered between the CA125 serum marker and NKT cells from the ovarian cancer tissue. This article has for the first time demonstrated a negative relationship between serum levels and NKT lymphocyte count from ovarian tissue. The inflammatory process in ovarian cancer tissue and the potential infiltration of endothelial immune cells, may result in a reduced number of NKT cells in the tumor microenvironment and increased circulation of the CA125 marker. Presented findings underscore new aspects of the iNKT cells involvement in the ovarian cancer development.  相似文献   

10.
目的 探讨卵巢癌患者、卵巢良性疾病及健康成人女性调节性T细胞(Tregs)和肿瘤标志物CA125、CA19-9水平的差异,并将其与临床病理因素及预后进行相关分析。 方法 选择2016年10月~2017年10月承德医学院附属医院妇科收治的经病理确诊的卵巢癌患者43例,设为恶性组,另选择同期医院收治的卵巢良性疾病患者55例作为良性组,健康体检妇女50例作为对照组。比较3组患者Tregs和肿瘤标志物CA125、CA19 9在卵巢癌患者中的表达水平,分析其与临床病理因素及预后的关系。 结果 恶性组和良性组Tregs比例、CA125和CA19-9水平均高于对照组,恶性组Tregs比例、CA125和CA19-9水平高于良性组(P<0.05)。CA125、CA19-9、Tregs水平与患者的年龄差异无显著性(P>0.05);CA125水平与卵巢癌患者的淋巴结是否转移、肿瘤分期和组织学类型均有关;Tregs表达水平与卵巢癌患者的淋巴结是否转移和肿瘤分期均相关,CA19-9水平只与肿瘤分期相关(P<0.05)。随访12个月后,Tregs-low组中位生存时间高于Tregs-high组(P<0.05)。卵巢癌中Tregs数与CA125存在显著正相关性(P<0.05),而与CA19-9不具有相关性(P>0.05)。 结论 Tregs、CA125和CA19-9均可有望成为卵巢癌临床诊断、治疗和预后的指标。  相似文献   

11.
We investigated plasma levels of selected hematopoietic cytokines: stem cell factor (SCF), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF) and the tumor marker cancer antigen (CA 125) in epithelial ovarian cancer patients as compared with control groups: benign ovarian tumor patients (cysts) and healthy subjects. Cytokine levels were determined by enzyme-linked immunosorbent assay, CA 125 – using the chemiluminescent microparticle immunoassay method. Our results have demonstrated significant differences in the concentrations of M-CSF, G-CSF, SCF (with the exception of GM-CSF), and CA 125 between the groups of ovarian cancer patients, cysts patients, and the healthy controls. When compared with CA 125, M-CSF has equal or higher values of diagnostic sensitivity and specificity. The M-CSF area under the receiver-operating characteristic curve (AUC) was the largest from all the cytokines tested and slightly lower than the AUC of CA 125. These findings suggest the usefulness of M-CSF in diagnosing ovarian cancer, especially when discriminating between cancer and non-carcinoma lesions.  相似文献   

12.
Proteomic approaches to tumor marker discovery   总被引:30,自引:0,他引:30  
CONTEXT: Current tumor markers for ovarian cancer still lack adequate sensitivity and specificity to be applicable in large populations. High-throughput proteomic profiling and bioinformatics tools allow for the rapid screening of a large number of potential biomarkers in serum, plasma, or other body fluids. OBJECTIVE: To determine whether protein profiles of plasma can be used to identify potential biomarkers that improve the detection of ovarian cancer. DESIGN: We analyzed plasma samples that had been collected between 1998 and 2001 from patients with sporadic ovarian serous neoplasms before tumor resection at various International Federation of Gynecology and Obstetrics stages (stage I [n = 11], stage II [n = 3], and stage III [n = 29]) and from women without known neoplastic disease (n = 38) using proteomic profiling and bioinformatics. We compared results between the patients with and without cancer and evaluated their discriminatory performance against that of the cancer antigen 125 (CA125) tumor marker. RESULTS: We selected 7 biomarkers based on their collective contribution to the separation of the 2 patient groups. Among them, we further purified and subsequently identified 3 biomarkers. Individually, the biomarkers did not perform better than CA125. However, a combination of 4 of the biomarkers significantly improved performance (P < or =.001). The new biomarkers were complementary to CA125. At a fixed specificity of 94%, an index combining 2 of the biomarkers and CA125 achieves a sensitivity of 94% (95% confidence interval, 85%-100.0%) in contrast to a sensitivity of 81% (95% confidence interval, 68%-95%) for CA125 alone. CONCLUSIONS: The combined use of bioinformatics tools and proteomic profiling provides an effective approach to screen for potential tumor markers. Comparison of plasma profiles from patients with and without known ovarian cancer uncovered a panel of potential biomarkers for detection of ovarian cancer with discriminatory power complementary to that of CA125. Additional studies are required to further validate these biomarkers.  相似文献   

13.
Experiments on male hybrid mice demonstrated that specific immunotherapy with preparations based on carcinoembryonal antigen and mucin containing CA 125 antigen was not associated with general toxicity, local irritating effect, and hepatorenal dysfunction. The absence of toxicity is apparently due to the fact that antigens injected intramuscularly or subcutaneously virtually do not enter the blood. Injections of preparations based on carcinoembryonal antigen and mucin containing CA 125 antigen to mice induced a standard immune response with predominance of class M immunoglobulins during the early terms and class G immunoglobulins at later terms. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 4, pp. 462–464, April, 2000  相似文献   

14.
Gene-based strategies for the immunotherapy of cancer   总被引:13,自引:0,他引:13  
 T lymphocytes play a crucial role in the host’s immune response to cancer. Although there is ample evidence for the presence of tumor-associated antigens on a variety of tumors, they are seemingly unable to elicit an adequate antitumor immune response. Modern cancer immunotherapies are therefore designed to induce or enhance T cell reactivity against tumor antigens. Vaccines consisting of tumor cells transduced with cytokine genes in order to enhance their immunogenicity have been intensely investigated in the past decade and are currently being tested in clinical trials. With the development of novel gene transfer technologies it has now become possible to transfer cytokine genes directly into tumors in vivo. The identification of genes encoding tumor-associated antigens and their peptide products which are recognized by cytotoxic T lymphocytes in the context of major histocompatibility complex class I molecules has allowed development of DNA-based vaccines against defined tumor antigens. Recombinant viral vectors expressing model tumor antigens have shown promising results in experimental models. This has led to clinical trials with replication-defective adenoviruses encoding melanoma-associated antigens for the treatment of patients with melanoma. An attractive alternative concept is the use of plasmid DNA, which can elicit both humoral and cellular immune responses following injection into muscle or skin. New insights into the molecular biology of antigen processing and presentation have revealed the importance of dendritic cells for the induction of primary antigen-specific T cell responses. Considerable clinical interest has arisen to employ dendritic cells as a vehicle to induce tumor antigen-specific immunity. Advances in culture techniques have allowed the generation of large numbers of immunostimulatory dendritic cells in vitro from precursor populations derived from blood or bone marrow. Experimental immunotherapies which now transfer genes encoding tumor-associated antigens or cytokines directly into professional antigen-presenting cells such as dendritic cells are under evaluation in preclinical studies at many centers. Gene therapy strategies such as in vivo cytokine gene transfer directly into tumors as well as the introduction of genes encoding tumor-associated antigens into antigen-presenting cells hold considerable promise for the treatment of patients with cancer. Received: 20 January 1997 / Accepted: 17 February 1997  相似文献   

15.
The monoclonal antibody (MAb) B43.13, binding to the ovarian cancer-associated antigen CA125, has been injected into more than 200 patients with ovarian cancer to detect recurrence of the disease. The follow-up of the patients revealed surprisingly long survival spans for several patients despite high CA125 levels. To investigate the therapeutic effectiveness of OvaRex MAb-B43.13 (AltaRex, Edmonton, Canada) under well-controlled conditions, the antibody was tested in a human-PBL-SCID/BG mouse model with CA125 positive human ovarian cancer cells. Mice were reconstituted with human peripheral blood lymphocytes (PBL, normal donors) by intraperitoneal (IP) injection of 2 to 3 x 10(7) PBL/mouse. OvaRex MAb-B43.13 was administered at 100 microg/mouse in phosphate buffered saline (PBS), in three different experimental set-ups. An isotype-matched control antibody (MOPC21 or MAb-170) and PBS injection served as controls. The ovarian cancer cell line NIH:OVCAR-NU-3 was injected IP at 1 x 10(6) cells/mouse or subcutaneously (SC) at 4 x 10(6) cells/mouse. Human-PBL-SCID/BG mice were either immunized before injection of tumor cells, along with tumor cells or after small tumors were established (2 weeks after transplantation). Antibody injections were repeated twice in 2-week intervals. Functional and cellular characterization of serum and PBL from these mice demonstrated the successful engraftment of a human immune system in those mice. All three experiments showed that OvaRex MAb-B43.13 treatment could (a) delay or prevent development of tumors; (b) reduce the size of small established tumors (SC tumor injection) or suppress ascites formation; (c) delay tumor growth when injected prior to tumor implantation; and (d) prolong the survival of the mice (i.p. tumor injection).  相似文献   

16.
The OC 125 monoclonal antibody was used to localize CA 125 antigen in routine paraffin sections of ovarian tumors with the use of a modified avidin-biotin-peroxidase complex (ABC) technic. Pretreatment of the paraffin sections with Pronase allowed subsequent detection of CA 125 antigen. OC 125 stained 4 (80%) of 5 benign and borderline serous ovarian tumors, 12 (86%) of 14 serous adenocarcinomas, and 3 (23%) of 13 benign and malignant mucinous ovarian tumors. The pattern of distribution of CA 125 antigen was mostly at the intraluminal and peripheral cell surfaces, while intracytoplasmic staining also was seen. Overall, CA 125 antigen detectability rate in paraffin sections was found to be compatible with those reported in frozen sections. The method allows retrospective immunohistochemical examination of a large number of cases with ovarian tumors.  相似文献   

17.
A prospective collection of serum samples and ovarian cyst fluidwas used to assess the use of different tumour markers and cystfluid cytology in combination with serum tumour markers forthe differential diagnosis of benign ovarian cysts. A consecutiveseries of 108 women of median age 30 years (range 15–75)undergoing laparotomy or operative laparoscopy for presumedlybenign ovarian cyst(s) were studied at a teaching hospital atthe University of Milan, Italy. The main outcome measures weretumour markers CA 125, CA 19.9 and carcino-embryonic antigen(CEA) in serum and ovarian cyst fluid, oestradiol and progesteroneconcentrations in cyst fluid, and cytology of the sediment.The studied cysts were endometriotic (55 subjects), dermoid(16), mucinous (12), serous (10) or of miscellaneous histotype(15, including four follicular and one luteal). Serum CA 125concentrations were significantly higher in the endometriomapatients than in the other groups. The sensitivity of CA 125in the differentiation of endometriomas from other adnexal tumourswas 61.8% and the specificity 94.3%; combining CA 125 and CA19.9 assays yielded a sensitivity of 83.6% and specificity of62.3%. Cyst fluid tumour markers values were extremely scatteredwith ample overlap between different cyst types. Oestradioland progesterone concentrations were similar in the histologicalsubgroups. Cyst fluid cytology was non-specific. We concludedthat the aspiration of fluid from presumedly benign ovariancysts appears to contribute little to the differential diagnosisof various tumours. The use of combining serum CA 125 and CA19.9 assays in the diagnosis of endometriomas needs furtherconfirmation.  相似文献   

18.
目的 探讨血清糖类抗原125(CA125)、人附睾蛋白4(HE4)及骨桥蛋白(OPN)联合检测在卵巢癌中的诊断意义.方法 收集2016年8月至2017年5月本院经病理确诊的卵巢良性囊肿患者血清58例,卵巢癌患者血清66例(按照FIGO临床分期标准,其中Ⅰ期17例,Ⅱ期21例,Ⅲ期13例,Ⅳ期15例)作为观察组,同时收集健康体检妇女(经B超检查排除卵巢及其它妇科疾病)的血清样本60例作为正常对照组.分别利用化学发光法检测各组中的血清CA125含量,酶联免疫法检测HE4及OPN含量,通过受试者工作曲线(receiver operator characteristic,ROC)计算曲线下面积(area under the curve,AUC)及各指标的灵敏度和特异性,评价标志物单独及联合检测对卵巢癌的诊断意义.结果 与正常对照组相比,CA125、HE4及OPN在卵巢癌中均有明显的升高,差异有统计学意义(P<0.05).在卵巢癌组中的Ⅱ、Ⅲ、Ⅳ期,其CA125、HE4及OPN的含量较卵巢囊肿组升高,有统计学差异.CA125、HF4、OPN及CA125+ HF4+ OPN在诊断卵巢癌时,其ROC曲线下AUC分别为0.74、0.89、0.81和0.95;各指标的诊断灵敏度分别为48.2%、76.8%、71.7%及94.5%;特异性为72.7%、87.4%、79.8%及92.6%.结论 卵巢癌患者的血清CA125、HE4及OPN含量明显高于卵巢囊肿患者(除卵巢癌Ⅰ期)及正常人群;相对于单一项目检测,血清CA125、HE4及OPN三者联合检测能大大提高卵巢癌诊断的特异性(除HE4)和灵敏度,为患者的早期诊断提供帮助.  相似文献   

19.
A case of ovarian serous adenocarcinoma presenting with ascitic fluid is reported. Cytology of the ascitic fluid showed the presence of cilia on most of malignant tumor cells. These tumor cells occurred singly; cilia usually appeared in unipolar locations. Immunocytochemical studies were performed on the ascitic fluid samples as well as tissue sections. CA19-9, CA125, CA50, and epithelial antigens were positive, while carcinoembryonic antigen was negative. The positive reactions were characteristic for cilia of the tumor cells. The findings also emphasize that positive reaction of these markers will usually exclude a noncommon epithelial tumor, but will not distinguish between benign and malignant ovarian tumors. Report of cilia-bearing tumor cells in ascitic fluid are few; no one, to the best of our knowledge, has previously documented the immunocytochemistry of these tumor cells.  相似文献   

20.
OBJECTIVE: Tumor-associated antigens may be expressed as surface glycoproteins. These molecules undergo qualitative and quantitative modifications during cell differentiation and malignant transformation. During malignant transformation, incomplete glycosylation is common, and certain glycosylation pathways are preferred. These antigens might help distinguish between ovarian and colonic adenocarcinomas in the primary and metastatic lesions. Different cytokeratins have been proposed as relatively organ-specific antigens. DESIGN: We used monoclonal antibodies against T1, Tn, sialosyl-Tn, B72.3, CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 to detect tumor-associated glycoproteins and keratin proteins in ovarian and colonic carcinomas. RESULTS: CA125, carcinoembryonic antigen, and cytokeratins 7 and 20 can distinguish between colonic and serous or endometrioid adenocarcinomas of the ovary in both primary and metastatic lesions. Mucinous ovarian adenocarcinomas differed in that they express carcinoembryonic antigen and cytokeratins 7 and 20 and weakly express CA125. The other glycoprotein antigens were equally expressed by ovarian and colonic adenocarcinomas and therefore were of no use in distinguishing between these 2 entities. CONCLUSION: A panel of monoclonal antibodies against cytokeratins 7 and 20 antigens, CA125, and carcinoembryonic antigen is useful in differentiating serous and endometrioid adenocarcinomas of the ovary from colonic adenocarcinomas. Mucinous ovarian adenocarcinomas cannot be distinguished from colonic adenocarcinomas using immunohistochemistry.  相似文献   

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