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)

Thirteen endometrioid carcinomas of the ovary with predominant patterns resembling those of sex cord-stromal tumors are reported. Eight of these neoplasms had been misinterpreted by the referring pathologists as sex cord-stromal tumors, almost always of the Sertoli-Leydig cell type. The latter diagnosis was suggested by a predominance of small tubular glands or winding, elongated solid tubular structures. In four cases, the presence of luteinized cells in the tumor stroma contributed to the misinterpretation. Each specimen, however, had one or more features establishing its endometrioid nature, including large tubular glands resembling those of the typical endometrioid adenocarcinoma, foci of squamous differentiation, luminal mucin accumulation, and adenofibromatous components. Two tumors were bilateral. The age range of the patients (from 58 to 86 years) differed markedly from that of patients with Sertoli-Leydig cell tumors, who are generally much younger, as did the associated clinical manifestations, which were those of ovarian cancer in general. No androgenic effects were observed and estrogenic manifestations were evident in only one of the cases.
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PMID:Ovarian endometrioid carcinomas resembling sex cord-stromal tumors. A clinicopathological analysis of 13 cases. 689 Jul 71

The MUC1 mucin produced by many adenocarcinomas has functions that may be of biological significance and is of importance clinically as a serum tumour marker and as a candidate target for immunotherapy. Previous studies of MUC1 production by ovarian cancers have been limited to immunohistochemical studies of tumour specimens and in vitro studies using cell lines. In this study the biosynthesis, secretion and glycosylation of MUC1 were studied in primary cultures of tumour cells obtained from 35 patients with stage 3 ovarian cancer. Although 34 of the 35 tumours produced MUC1 in vitro, the concentrations of intracellular and secreted MUC1, as measured by an ELISA using core protein-reactive antibodies, varied over a wide range. In addition, the amount of secreted MUC1 as a proportion of the intracellular concentration varied between tumours. Pulse/chase amino acid labelling studies of MUC1 biosynthesis also demonstrated variation in secretion rates. Multivariate regression analysis showed that of the variables tumour size, histological type, grade, ploidy status and intracellular and secreted MUC1 concentrations in vitro, only mucin secretion rate was significantly associated with serum mucin concentrations (p < 0.001). Culture of tumour cells for 4 days in the presence or absence of a competitive inhibitor of O-glycosylation, BAG, showed that the degree of glycosylation of MUC1 varied between tumours and that under-glycosylation was not correlated with production or secretion rates. Our study has shown heterogeneity in the production, secretion and glycosylation of MUC1 and a strong correlation between the secretion rate in vitro and the concentration in the serum of patients.
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PMID:Heterogeneity in production, secretion and glycosylation of MUC1 epithelial mucin by primary cultures of ovarian carcinoma. 759 Dec 41

A strategy for directing and enhancing B cell immune responses against synthetic peptide determinants has been developed in order to produce antibodies specifically against protein epitopes of clinical relevance. A peptide sequence based upon the MUC-1 mucin protein core was selected for this purpose since anti-MUC-1 antibodies have proven diagnostic application and therapeutic potential in human breast and ovarian cancer. Peptide constructs were synthesised co-linearly linking the immunodominant B cell determinant region, PDTRPAP, in the protein core of the MUC-1 mucin, to sequence 111-120 of influenza haemagglutinin A/X-31, a determinant recognised by T helper cells through association with MHC class II molecules. Induction of anti-MUC-1 antibodies to the B cell determinant region by immunisation with peptide was shown to be dependent upon both the presence and the position of the T cell determinant. In addition, haplotype mismatching with respect to the T cell determinant resulted in a significant lowering of the anti-MUC-1 antibody response in peptide construct immunised mice. These findings are relevant to the design of immunogens to produce antibodies against peptide epitopes of tumour associated proteins and glycoproteins.
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PMID:Induction of antibody responses to breast carcinoma associated mucins using synthetic peptide constructs as immunogens. 768 35

CTL isolated from tumor infiltrating lymphocytes/tumor associated lymphocytes (TAL) infiltrating ovarian tumors have been demonstrated to mediate lysis of tumor targets after in vitro culture. These effector cells are of particular interest as cellular probes to detect and define human tumor Ag and epitopes that stimulate cellular immunity to human tumors. Polymorphic epithelial mucin (PEM) core peptides are potential candidates as tumor specific Ag because of their preferential expression on epithelial tumors. We report here that ovarian CTL-TAL can recognize mucin (Muc-1) core peptide of PEM. Several ovarian CTL-TAL lines were developed that recognized in a non-MHC restricted fashion an Muc-1+ ovarian tumor, but not Muc-1-tumor. To define the specificity of these CTL-TAL and exclude cross-reactivity with other potential Ag, cytotoxicity experiments were performed using as targets EBV-transformed cell lines with an expression construct containing the Muc.1 cDNA. These ovarian CTL-TAL lysed mucin core-peptide transfected cells but not targets transfected with an expression construct containing a mucin frame-shift mutant cDNA as control. In addition, targets pulsed with short synthetic peptides composed of amino acids 1-14 of the Muc 1 core peptide repeat were also lysed by the same CTL-TAL. This lysis was inhibited by the mAb SM3 that recognize an epitope on the mucin core peptide. These results, which are a demonstration of a specific Ag recognized by ovarian CTL-TAL, may be of interest for specific immunotherapy of ovarian cancer.
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PMID:Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides. 769 Aug 10

Markers supplementing CA 125 are important for monitoring of the disease in patients with mucinous and non-epithelial ovarian cancers. Tumour-associated trypsin inhibitor (TATI) or one of the gastrointestinal mucin markers, CA 19-9 or CA 72.4 are good supplements to CA 125 in mucinous ovarian cancer. Chorionic gonadotrophin (hCG) and alpha fetoprotein (AFP) are the most useful markers for germ cell tumours, and hCG beta may provide additional information. In addition to hCG beta, M-CSF and inhibin show promise of becoming useful supplements to CA 125 in ovarian cancer in general. Markers other than CA 125 may also play a role as prognostic indicators. TATI and procollagen peptides appear useful for this purpose. If these markers prove to provide reliable prognostic information, they could be used to aid selection of optimal treatment regimens.
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PMID:Markers supplementing CA 125 in ovarian cancer. 774 89

Molecular modeling and two-dimensional NMR techniques enable us to identify structural features in the third variable region (V3) loop of the human immunodeficiency virus (HIV) surface glycoprotein gp120, in particular the principal neutralizing determinant (PND), that remain conserved despite the sequence variation. The conserved structure of the PND is a solvent-accessible protruding motif or a knob, structurally isomorphous with the immunodominant knobs in the tandem repeat protein of human mucin 1 (MUC1) (a tumor antigen for breast, pancreatic, and ovarian cancer). We have replaced the mucin antigenic knobs by the PND knobs of the HIV MN isolate in a set of chimeric human MUC1/HIV V3 antigens. This produced multivalent HIV antigens in which PNDs are located at regular intervals and separated by extended mucin spacers. In this article we show by two-dimensional NMR spectroscopy that the multivalent antigens preserve the PNDs in their native structure. We also demonstrate by ELISA that the antigens correctly present the PNDs for binding to monoclonal antibodies or polyclonal antisera from HIV-infected patients.
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PMID:Human immunodeficiency virus (HIV) antigens: structure and serology of multivalent human mucin MUC1-HIV V3 chimeric proteins. 781 40

To obtain monoclonal antibodies directed to mucin-type sugar chains, mice were immunized with bovine submaxillary mucin (BSM) that had been conjugated with ovalbumin. Conjugation of BSM with ovalbumin enhanced the antigenicity of BSM to about five to ten times that of intact BSM and resulted in the establishment of ten hybridomas, all of which secreted monoclonal antibodies toward BSM. Most of the antibodies secreted by these hybridomas did not react with glycolipids but did react with glycoproteins. Several antibodies lost their reactivity when sialic acid residues were removed from BSM, indicating that these antibodies recognize carbohydrate moieties of mucins. Immunohistochemical studies revealed that three of the antibodies recognized human ovarian cancer-associated carbohydrate antigens. In addition, one of these three antibodies reacted with a human cultured colonic cancer cell line. The protocol described in this paper was effective in producing monoclonal antibodies that recognize mucin-carbohydrates and some of the generated antibodies can be applied to the detection of cancers.
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PMID:Production of monoclonal antibodies recognizing cancer-associated antigens expressed on mucin-type sugar chains. 794 35

The serum MUC1 markers CASA and CA 15-3 were compared with CA 125 in the serum of patients with ovarian cancer and in pregnant women. Used individually, CASA and CA 15-3 gave sensitivities of 54 and 56% in pre-operative ovarian carcinoma (n = 50), though these were lower than with CA 125 (84%). CASA levels were elevated in 3 women with a negative CA 125, while CA 15-3 was elevated in 2 of these women. The combined use of CA 125 with CASA or CA 15-3 led to the preclinical detection of recurrence in 4/5 patients, with mean lead times of 3.6 and 4.3 months, respectively. Of particular interest was the marked difference in reactivity observed with CASA and CA 15-3 in some patients, despite both assays utilising monoclonal antibodies (MAbs) that react with the MUC1 mucin. CA 15-3 and CASA showed a lower than expected correlation in patients with ovarian cancer (r = 0.70), with some patients having high concentrations of one mucin marker and low concentrations of another. Furthermore, different marker profiles were observed when monitoring the progress of patients with these markers. Marked differences between CA 15-3 and CASA were also observed in the serum of pregnant women (n = 10), where CASA showed marked elevation (mean 33.6 times cutpoint) and CA 15-3 did not (mean 0.88 times cutpoint). These data suggest that the specificities of the MAbs used in these assays affect the glycoform of MUC1 detected, and that it should not be assumed that all MUC1 assays will behave in the same manner.
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PMID:Serum markers CASA and CA 15-3 in ovarian cancer: all MUC1 assays are not the same. 799 5

MUC1 epithelial mucins are produced by both normal and malignant epithelial cells. Serum proteins reactive with monoclonal antibodies against MUC1 mucins were studied using several techniques. Separation of proteins by native PAGE showed that anti-MUC1 core protein antibodies reacted with a high M(r) mucin but also with a 70-kD protein (p70) in normal women and women with ovarian cancer. After purification by gel filtration, p70 was not reactive in a double-determinant ELISA (CASA) and only weakly reactive in an inhibition assay. Serum CASA levels increased during pregnancy but p70 disappeared. Neuraminidase treatment of serum resulted in a greater increase in CASA in normal women and in ovarian cancer patients with low initial CASA than in ovarian cancer patients with high CASA and pregnant women (p < 0.05). These findings suggest that pregnancy and ovarian cancer-derived mucins are less heavily sialylated than mucin derived from normal tissues. An inhibition assay was developed which was more sensitive, but provided no diagnostic advantage over CASA. MUC1 is present in the serum of all women, reactivity in assays utilizing core protein antibodies is probably dependent not only on molar concentration but on the degree of exposure of peptide epitopes.
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PMID:Factors effecting the measurement of tumor-associated MUC1 mucins in serum. 814 28

Levels of carcinoembryonic antigen (CEA), CA-19-9, CA-125, and mucin-like associated tumor antigen (MAA) were measured in the blood sera of 108 patients with uterine cervix and body, and ovarian carcinomas before treatment, and in those with ovarian carcinoma over the course of treatment to monitor its efficacy. The findings indicate that neither CEA nor MAA were diagnostically informative in malignant tumors of female genitals, and in uterine cervix cancer none of the tumor markers was diagnostically valuable. In neglected cases of uterine body cancer blood levels of CA-19-9 and CA-125 were elevated. In ovarian carcinoma CA-125 levels varied statistically significantly (p < 0.05) in various stages of the disease. CA-125 measurements are recommended for monitoring the treatment efficacy in patients with ovarian cancer.
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PMID:[The use of tumor markers in the diagnosis and treatment monitoring of malignant tumors of the female genitalia]. 825 Jan 20


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