Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new murine monoclonal antibody (MAb VK-8), detecting the CA 125 ovarian cancer antigen, was used to purify this antigen from OVCAR-3 ovarian cancer cells by affinity chromatography. The biochemical properties of the purified antigen are characteristic of a mucin-type glycoprotein: (1) the molecule is highly glycosylated (77% w/w), mainly with galactose, N-acetylglucosamine, and N-acetylgalactosamine, (2) the protein moiety is rich in serine, threonine and proline, (3) many of the serine and threonine residues are glycosylated, (4) the glycan chains are almost entirely O-linked, with core 2 [Galbeta1 --> 3(GlcNAcbeta1 --> 6)GalNAc] structures predominating and (5) these chains carry fucosylated Type 2 (Le(y) and Le(x) and H type 2) blood group structures. The antigen exhibited a very high m.w. (> 10(3) kDa) in aqueous buffer as well as in urea, but was degraded by proteolytic enzymes to smaller fragments that no longer reacted with the antibody. Although this result, and other immunochemical data, indicate that OC125, the original MAb to CA125, and VK-8 antibodies detect epitopes on the protein portion of the molecule, the involvement of carbohydrate cannot be ruled out. Further insight into the structure and function of the CA125 antigen will come from cloning the gene coding for the peptide backbone, and from more detailed carbohydrate structural analysis.
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PMID:Isolation and characterization of ovarian cancer antigen CA 125 using a new monoclonal antibody (VK-8): identification as a mucin-type molecule. 918 Jan 55

The human tumour associated cancer antigen CA 125 is a glycoprotein with high molecular weight. The determination of this antigen has been proven to be useful in the monitoring of patients with ovarian cancer. OPUS OV, the tumour marker assay for the ovarian cancer antigen CA 125 is an ELISA that was developed for the family of fully automated random-access analyzers, OPUS, OPUS Plus and OPUS I Magnum. The assay uses a double monoclonal sandwich format (antibodies B27.1 and B43.13, Biomira/Canada). The first antibody is immobilized on the solid phase of the OPUS modules. Sample is automatically added and incubated for 5 minutes. The addition of a solution of the second antibody conjugated to the enzyme alkaline phosphatase leads to the formation of a sandwich complex within 5 minutes. The last step, the addition of the fluorogenic substrate 4-methylumbelliferyl phosphate, serves both as washing procedure and for the development of the fluorescence signal (kinetic measurement). OPUS OV has an assay range from 0-1000 kU/L with a detection limit of 5 kU/L. Within run cv's are 6-8%. A good correlation was found to commercially available kits for the determination of CA 125. We conclude that this new OPUS OV assay is a valid alternative for use in the routine determination of the cancer associated antigen CA 125 and allows more reliable determinations in terms of random access, speed, and ease of operation.
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PMID:A new tumour marker assay for ovarian cancer on the OPUS immunoassay system. 932 99

Monoclonal antibody (mAb) MX35 reacts with approximately 90% of ovarian epithelial cancers and has been studied in localization and biodistribution trials in ovarian cancer patients. This study shows that mAb MX35 recognizes a cell surface antigen of about 95,000 D on OVCAR-3 ovarian cancer cells. The antigen could be immunoprecipitated from lysates of cells metabolically labeled with [3H]glucosamine and it bound to concanavalin A and wheat germ agglutinin lectins, showing that it is a glycoprotein. MX35 antigen can also be detected in detergent lysates of OVCAR-3 cells by Western blotting. Using this technique the MX35 epitope(s) was shown to be heat stable but susceptible to reduction by 2-mercaptoethanol. Protease digestion of the antigen resulted in smaller fragments (42-52 kDa) that still reacted with antibody. We conclude that MX35 antigen is a 95 kDa glycoprotein, stabilized by disulfide bonds, with a large protease-resistant region that carries the MX35 epitopes.
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PMID:Initial immunochemical characterization of MX35 ovarian cancer antigen. 936 6

Amplification and overexpression of the HER-2/neu proto-oncogene frequently coincide with an aggressive clinical course of certain human adenocarcinomas. To assess whether HER-2/neu plays a rate-limiting role in ovarian cancer, we used human SK-OV-3 ovarian cancer cells as a model. We applied a conditional mRNA depletion strategy of HER-2/neu with anti-HER-2/neu-targeted hammerhead ribozymes expressed under the control of a tetracycline-regulated promoter system. In these ovarian cancer cells, we reduced HER-2/neu mRNA, protein expression, and tumor growth in nude mice by transfection with HER-2/neu-targeted ribozymes and generated cell lines expressing different levels of HER-2/neu. Expression of the most effective ribozyme (Rz3) quenched HER-2/neu mRNA levels by >90%. Concomitantly, fluorescence-activated cell sorting analysis revealed that expression of the HER-2/neu-encoded surface glycoprotein was almost completely abrogated. In nude mice, tumor growth was dramatically inhibited in the HER-2/neu-depleted Rz3-expressing SK-OV-3 cells. Furthermore, already established tumors started to regress when Rz3 expression was activated midstream by withdrawal of the tetracycline treatment. This study supports the thesis that HER-2/neu can be rate-limiting for the malignant phenotype of ovarian cancer in a gene dose-dependent manner.
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PMID:HER-2/neu is rate-limiting for ovarian cancer growth. Conditional depletion of HER-2/neu by ribozyme targeting. 936 8

Little is known about the factors regulating epithelial ovarian cancer cell growth. This is due, in large part, to the difficulty in obtaining and culturing human ovarian cells for relevant in vitro studies. We recently developed a method for culturing epithelial carcinoma cells derived from fresh, untreated epithelial ovarian cancer specimens. The cell populations are free of fibroblasts and reflect the primary tumor as determined by chromosomal analysis. In this study we report on the cells' growth in serum-free medium and their secretion of CA-125, a glycoprotein marker for ovarian cancer. Furthermore we characterize the insulin-like growth factor (IGF) system in these primary ovarian carcinoma cell cultures. The cells secrete IGF peptides and IGF-binding proteins, possess specific type I IGF receptors, and respond to exogenous IGFs. The culture system reported here provides the basis for further study and manipulation of the IGF system as well as other regulators of epithelial ovarian cancer. Greater understanding of the cellular and molecular mediators of primary human ovarian cancer cell growth may translate into relevant clinical interventions.
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PMID:Biological characterization of human epithelial ovarian carcinoma cells in primary culture: the insulin-like growth factor system. 947 53

Recent studies have described the generation of a mAb, designated DF3-P, which reacts with underglycosylated precursors of the DF3/MUC1 mucin-like glycoprotein. The present work demonstrates that the epitope recognized by mAb DF3-P is expressed by cell lines derived from human epithelial ovarian carcinomas and not a teratocarcinoma. Indirect immunofluorescence assays of single-cell suspensions support expression of the DF3-P epitope on the surface of ovarian carcinomas. Immunofluorescence studies on chamber slides further demonstrate that the mAb DF3-P-reactive cells are present in clusters. We also demonstrate that 125I-labeled mAb DF3-P selectively localizes to human ovarian carcinoma xenografts in athymic mice. The percentage of injected 125I dose/g tissue ranged between 10 and 17% for implanted CAOV-3 and OVCAR-3 tumors. Finally, the results of immunoperoxidase staining studies demonstrate that the DF3-P epitope is detectable in formalin-fixed sections of ovarian tumors and that mAb DF3-P exhibits little if any reactivity with normal surrounding tissues. Selective expression of the DF3-P epitope may be useful as a target for radioimaging or immunotherapeutic approaches to ovarian cancer.
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PMID:Expression of the DF3-P epitope in human ovarian carcinomas. 981 17

The human cell-surface antigen epithelial glycoprotein-2 recognized by the monoclonal antibody MOC-31 is an epithelial tumour-associated glycoprotein expressed in non-squamous carcinomas. MOC-31 immunoreactivity was investigated in human breast, colon, ovarian and lung cancer cell lines, grown either in vitro or in severe combined immunodeficient (SCID) mice as solid tumours and/or metastases. Three of four small-cell lung cancer cell lines (NCI-H69, OH3 and SW2) and three of four ovarian cancer cell lines (SoTu 1, 3 and 4) expressed epithelial glycoprotein-2. In contrast, all three breast (MCF-7, BT20, T47D) and all three colon (HT29, CACO2, SW480) cancer cell lines strongly reacted with monoclonal antibody MOC-31. A notable difference in MOC-31 immunoreactivity was observed in spontaneously formed lung metastases of HT29 colon cancer cells. Whereas larger metastases (> 30 cells) reacted with a similar staining pattern to the primary tumour, smaller metastases did not. These findings indicate that differentiation processes during the epithelial-mesenchymal transition occur in metastases, which lead to a transient loss of epithelial glycoprotein-2 expression during the migratory and early post-migratory period. This loss of antigen expression indicates that the process of metastases formation is a regulatory event, and this transient loss of antigen expression might represent a potential obstacle to antibody-based therapy in the setting of minimal residual disease.
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PMID:Epithelial glycoprotein-2 expression is subject to regulatory processes in epithelial-mesenchymal transitions during metastases: an investigation of human cancers transplanted into severe combined immunodeficient mice. 987 99

Since the OC 125 monoclonal antibody (Mab) was generated, other Mabs to the CA 125 glycoprotein have been produced and classified into two families associated with two major epitope regions on the CA 125 molecule. New generation assays, combining Mabs to two distinct regions of the molecule, compare favorably with that of the original assays as demonstrated by ROC curves. The original CA 125 assay suffered from interference of HAMA, an important drawback considering the increasing use of murine antibodies for immunodiagnosis and treatment of ovarian cancer. This problem has been solved for the majority of currently available tests. The sensitivity of the assays for early ovarian cancer remains low, precluding its indiscriminate use for screening and diagnosis of ovarian cancer. Its use in screening for early cancer, combined with ultrasonography, is limited to high risk populations, such as women from families with mutations in the BRCA1 or 2 gene. Although CA 125 assessment may play a limited role in the (early) detection of ovarian cancer, its role in the follow-up during and after therapy is well established. The major contribution of CA 125 is in the monitoring of tumor response to chemotherapy, where it is valuable in detecting those patients with an inadequate response to the chosen treatment. The role of CA 125 in early detection of recurrences remains to be established and is currently the subject of two large clinical trials.
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PMID:CA 125: fundamental and clinical aspects. 1020 33

Over the last 15 years, substantial progress has been made in understanding the potential and the limitations of the CA 125 assay. More than 2000 papers have been published concerning laboratory and clinical studies of CA 125. The original CA 125 assay utilized the OC 125 antibody that recognizes the CA 125 epitope on a high molecular weight glycoprotein. Despite repeated attempts, the gene encoding the peptide component has not yet been cloned. Monoclonal antibodies have been raised against other epitopes expressed by this molecule, leading to the development of the CA 125-II assay that exhibits less day-to-day variation. Using either assay, elevated levels of CA 125 are detected in a number of benign conditions, including endometriosis. CA 125 is most consistently elevated in epithelial ovarian cancer, but can be expressed in a number of gynecologic (endometrial, fallopian tube) and non-gynecologic (pancreatic, breast, colon and lung) cancers. The best established application of the CA 125 assay is in monitoring ovarian cancer. The rate of decline in CA 125 during primary chemotherapy has been an important independent prognostic factor in several multivariate analyses. Persistent elevation of CA 125 at the time of a second look surgical surveillance procedure predicts residual disease with > 95% specificity. Rising CA 125 values have preceded clinical detection of recurrent disease by at least 3 months in most, but not all studies. Given the modest activity of salvage chemotherapy, this information has not yet impacted on survival. Rising CA 125 during subsequent chemotherapy has been associated with progressive disease in more than 90% of cases. CA 125 may serve as an effective surrogate marker for clinical response in phase II trials of new drugs. CA 125 levels can aid in distinguishing malignant from benign pelvic masses, permitting effective triage of patients for primary surgery. Early detection of ovarian cancer remains the most promising application of CA 125. An algorithm has been developed that estimates the risk of ovarian cancer (ROC) based upon the level and trend of CA 125 values. A major trial has been initiated that uses the ROC algorithm to trigger transvaginal sonography and/or subsequent laparotomy. Such a trial could demonstrate improvement in survival through early detection. This strategy should provide adequate specificity, but sensitivity for early stage disease may not be optimal. In the future, improved sensitivity may be attained using multiple markers and neural network analysis. Most serum tumor markers have been proteins or carbohydrates, but lipid markers such as lysophosphatidic acid deserve evaluation. Genomic and proteonomic technologies should identify additional novel markers.
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PMID:CA 125: the past and the future. 1022 98

The antigenic determinant CA 125 is a high molecular weight glycoprotein which is elevated in more than 80% of patients with epithelial ovarian cancer. Despite its good performance as a human tumor marker, only little is known about its physiological function. According to recent publications, CA 125 production and release appear to be related to cellular growth. In order to investigate this putative relationship more closely, we analyzed the pattern of CA 125 production and release by ovarian cancer cells during exponential cell growth, during cell cycle arrest by colchicine and during inhibition of cellular protein synthesis by cycloheximide. The results were correlated with the cell cycle distribution. According to our results, the main determinant of CA 125 release into the culture supernatant is the total cell count. Although cell cycle arrest in the G2 + M phase by means of colchicine treatment resulted in the death of most cells, which was reflected by an increased release of CA 125, no differences in the intracellular production rate between colchicine treated and untreated cells were seen. In contrast, treatment of cells with cycloheximide not only resulted in decreasing cell numbers but also in a complete inhibition of CA 125 production by surviving cells.
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PMID:CA 125 production and release by ovarian cancer cells in vitro. 1022 1


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