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

The circulating ovarian cancer associated antigen CA 125 was determined in serum of 63 patients with ovarian malignancies by radioimmunometric solid phase assay using the monoclonal antibody OC 125 as catcher and tracer. The results of 41 patients with 43 active tumour situations were compared with the CA 125 serum levels of 27 patients without recurrence after therapy of ovarian cancer and 49 benign ovarian tumours. Significant differences exist between these three groups (p less than 0.001) with elevated values (greater than 35 U/ml) in 84 per cent in ovarian carcinoma, 22 per cent in benign tumours and nought per cent in woman without recurrence in follow-up. The pre-operative sensitivity in ovarian cancer is 93 per cent (in epithelial carcinoma 96 per cent) with a distinct dependence of the CA 125 serum levels on the stage of the disease (stage III and IV versus stage I and II; p less than 0.01). A positive correlation of CA 125 values to clinical status was found in 82 per cent in follow-up. Increasing values of CA 125 can detect the recurrence any months earlier than the clinical examination. Decreasing serum levels in chemotherapy don't reflect the objective tumour remission in every case. Because of elevated values in benign and inflammatory adnexal tumours and the relative low sensitivity in borderline cases (three of seven patients greater than 35 U/ml) the CA 125 assay seems not be suitable for a screening method. However it is a substantial amplification in control of therapeutic success and an early detection of recurrence of ovarian cancer disease.
 ...
PMID:[The value of CA 125 determination in the serum of patients with ovarian cancer]. 272 73

A new method with a low pH step to dissociate serum complexes has been developed to measure serum levels of antigens associated with ovarian cancer. The antigens are detected by monoclonal antibodies HMFG1 and HMFG2 and have been compared to an existing ovarian cancer associated antigen detected by the antibody CA125. Elevated HMFG1 was found in 56%, and elevated HMFG2 in 65% of 924 sera from 85 patients with ovarian cancer. CA125 was elevated in 85% of these sera. When the three markers were used in conjunction, 95% of sera from patients with ovarian cancer were positive--compared with 7% in sera from healthy control subjects. Therefore, the combination of HMFG1, HMFG2 and CA125 increases the diagnostic accuracy. If all three markers are normal in a patient previously treated for ovarian cancer then no further positive information regarding disease status can be obtained by ultrasound and CT scanning.
 ...
PMID:A new immunoassay using monoclonal antibodies HMFG1 and HMFG2 together with an existing marker CA125 for the serological detection and management of epithelial ovarian cancer. 346 85

We have used in vivo and in vitro procedures to select a subpopulation of cells from the human ovarian carcinoma cell line, NIH:OVCAR-3, with the capacity to grow i.p. in female nude athymic mice. After i.p. injection of these cells, animals develop metastatic spread similar to that of clinical ovarian cancer. Disease progression is characterized by the development of massive ascites, extensive invasive i.p. tumors, and pulmonary metastases. The malignant ascites cells are transplantable, manifest cytoplasmic androgen and estrogen receptors, and express the ovarian cancer associated antigen CA125 (116,000 units/ml of ascites supernatant). The cells also have the same chromosome markers which were present in the original cell line, NIH:OVCAR-3. Survival following i.p. passage of ascites is dependent on tumor cell inoculum ranging from a median survival of 39 days with 40 million cells to 84 days for 11.5 million transplanted cells. The characteristics of this unique in vivo model make it well suited for the evaluation of new drugs and novel experimental therapies in ovarian cancer. In addition, this in vivo model, together with ovarian cancer cell lines, may prove particularly useful for the study of pharmacological ways to specifically increase the cytotoxicity of anticancer agents in tumor cells while not increasing toxicity in normal tissues. The presence of hormone receptors should facilitate the experimental evaluation of hormonal therapy in ovarian cancer.
 ...
PMID:Characterization of a xenograft model of human ovarian carcinoma which produces ascites and intraabdominal carcinomatosis in mice. 633 72

The 11q13 chromosomal region encodes oncogenes relevant to a variety of human cancers as well as a tumour suppressor gene implicated in multiple endocrine neoplasia type 1. In addition, high affinity folate receptor (FOLR1), which maps to 11q13.3-13.5, is expressed at an elevated level on the surface of over 80% of nonmucinous epithelial ovarian cancers. Further telomeric, 11q breakpoints are found in many cancers. We studied the involvement of 11q markers in ovarian cancer by looking for tumour-specific loss of heterozygosity (LOH), as well as amplification or rearrangements that might explain the overexpression of FOLR1. Twenty eight epithelial ovarian cancers, along with lymphocyte DNA from the same individual were used for Southern blotting with polymorphic probes from 11q. PCR primers from 11q23.3 were also used. The 11q13 band was amplified in four out of 28 cancers. The amplicon included the probe D11S146 as well as FGF3 (formerly INT2) and FOLR1 in one out of these four cases, thus crossing the bcl1 translocation breakpoint. LOH was seen in three out of 16 cases with FGF3 (11q13). A much higher frequency of LOH (8/12) was found at 11q23.3-qter, implying the presence of a tumour suppressor gene in this region.
 ...
PMID:Loss of heterozygosity and amplification on chromosome 11q in human ovarian cancer. 809 91

This study describes a simple method for long-term establishment of human ovarian tumor lines and prediction of T-cell epitopes that could be potentially useful in the generation of tumor-specific cytotoxic T lymphocytes (CTLs). Nine ovarian tumor lines (INT.Ov) were generated from solid primary or metastatic tumors as well as from ascitic fluid. Notably all lines expressed HLA class I, intercellular adhesion molecule-1 (ICAM-1), polymorphic epithelial mucin (PEM) and cytokeratin (CK), but not HLA class II, B7.1 (CD80) or BAGE. While of the 9 lines tested 4 (INT.Ov1, 2, 5 and 6) expressed the folate receptor (FR-alpha) and 6 (INT.Ov1, 2, 5, 6, 7 and 9) expressed the epidermal growth factor receptor (EGFR); MAGE-1 and p185HER-2/neu were only found in 2 lines (INT.Ov1 and 2) and GAGE-1 expression in 1 line (INT.Ov2). The identification of class I MHC ligands and T-cell epitopes within protein antigens was achieved by applying several theoretical methods including: 1) similarity or homology searches to MHCPEP; 2) BIMAS and 3) artificial neural network-based predictions of proteins MAGE, GAGE, EGFR, p185HER-2/neu and FR-alpha expressed in INT.Ov lines. Because of the high frequency of expression of some of these proteins in ovarian cancer and the ability to determine HLA binding peptides efficiently, it is expected that after appropriate screening, a large cohort of ovarian cancer patients may become candidates to receive peptide-based vaccines.
 ...
PMID:Generation and phenotypic characterization of new human ovarian cancer cell lines with the identification of antigens potentially recognizable by HLA-restricted cytotoxic T cells. 933 22

The folate receptor (FR) type alpha is known to be frequently overexpressed in ovarian cancer and is the target for a number of novel experimental cancer therapies. The relative levels of FR expression among specific cell types and its relationship to malignant transformation have not been adequately established because of several inherent limitations of the immunocytochemical approaches used previously. We used a quantitative in situ hybridization method to examine the expression of the mRNAs for the known isoforms of FR in paraffin-embedded tissue sections of multiple samples of the various subtypes of ovarian, uterine, and cervical cancers. Benign lesions, as well as the various normal cell types in the ovary, the uterus, and the cervix, were examined similarly. FR mRNA levels were quantitated relative to the transcript levels for beta-actin using NIH Image 1.57 computer software. The results show that the ovary, the uterus, and the cervix present different patterns of FR regulation in differentiation and in malignancy. In the ovary, benign differentiation of the germinal epithelium into mucinous or serous tumors or malignant transformation into mucinous tumors is associated with down-regulation of FR-alpha, whereas FR-alpha expression is retained in malignant lesions of serous and endometrioid differentiation. In contrast, malignant transformation of the glandular epithelial cells of the uterine endometrium is associated with de novo expression of FR-alpha. Heterogeneity in FR expression within malignant ovarian and uterine tumors is related to differentiation. In contrast to the uterus, malignant transformation of glandular epithelial cells in the cervix may frequently result in down-regulation of FR-alpha. These results shed new light for the identification of malignancies suitable for FR-mediated therapies and for prognostic/diagnostic applications of FR. They also provide a phenomenological basis for molecular studies of FR regulation in malignant cells.
 ...
PMID:Expression of folate receptor type alpha in relation to cell type, malignancy, and differentiation in ovary, uterus, and cervix. 1049 96

The detrimental effect of chronic administration of carbamazepine (CBZ) on serum and erythrocyte folates of patients has been extensively analyzed. However, at present, no data have been reported on the effect of CBZ on the intracellular content and activity of antimetabolite cytotoxic agents that can be used together with CBZ in the treatment of cancer patients. To investigate this issue, we chronically exposed in vitro the human ovarian cancer cell line SKOV-3 (grown under physiological folate concentrations) to CBZ, thus selecting SKOV-CBZ clones (SKOV-CBZ-50-2, SKOV-CBZ-50-5 and SKOV-CBZ-100-2) able to grow in the continuous presence of the antiepileptic drug. All of the SKOV-CBZ clones were more resistant to methotrexate (MTX) than the parental cells. MTX resistance index, as determined by the ratio between MTX concentrations inhibiting cell growth by 50% (MTX IC(50)) in SKOV-CBZ clones and in the parental cells, ranged between 3- and 5-fold. This resistance was related to a reduced intracellular content of MTX. No alteration activity of the cellular enzymes directly involved in MTX cytotoxicity (dihydrofolate reductase, thymidylate synthase [TS] and folylpolyglutamate synthetase) was observed. SKOV-CBZ clones were cross-resistant to the TS inhibitors tomudex and CB3717, but not to the TS inhibitor 5-fluoro-deoxy uridine and other antineoplastic drugs (cisplatin, doxorubicin, vincristine and taxol), whose cellular uptake is derived from transmembrane transport mechanisms different from folate receptor alpha (FRalpha) or reduced folate carrier (RFC). FRalpha mRNA and protein levels were significantly lower in SKOV-CBZ clones than in the parental cells. The reduced level of FRalpha in SKOV-CBZ clones was associated with a decreased binding capacity of folic acid. No variation of mRNA RFC expression in the SKOV-CBZ clones as compared to the parental cells was observed. Thus, after chronic exposure to CBZ, SKOV-CBZ clones develop resistance towards MTX due to defective MTX uptake.
 ...
PMID:Resistance to methotrexate in SKOV-3 cell lines after chronic exposure to carbamazepine is associated with a decreased expression of folate receptor. 1069 49

A better understanding of the molecular circuitry in normal ovarian tissues and in ovarian cancer will likely provide new targets for diagnosis and therapy. Recently, much has been learned about the genes expressed in ovarian cancer through studies with cDNA arrays and serial analysis of gene expression. However, these methods do not allow highly quantitative analysis of gene expression on a large number of specimens. Here, we have used quantitative real-time RT-PCR in a panel of 39 microdissected ovarian carcinomas of various subtypes to systematically analyze the expression of 13 genes, many of which were previously identified as up-regulated in a subset of ovarian cancers by serial analyses of gene expression. The genes analyzed are glutathione peroxidase 3 (GPX3), apolipoprotein J/clusterin, insulin-like growth factor-binding protein 2, epithelial cell adhesion molecule/GA733-2, Kop protease inhibitor, matrix gla protein, tissue inhibitor of metalloproteinase 3, folate receptor 1, S100A2, signal transducer and activator of transcription 1, secretory leukocyte protease inhibitor, apolipoprotein E, and ceruloplasmin. All of the genes were found overexpressed, some at extremely high levels, in the vast majority of ovarian carcinomas irrespective of the subtype. Interestingly, GPX3 was found at much higher levels in tumors with clear cell histology and may represent a biomarker for this subtype. Some of the genes studied here may thus represent targets for early detection ovarian cancer. The gene expression patterns were not associated with age at diagnosis, stage, or K-ras mutation status in ovarian cancer. We find that several genes are coordinately regulated in ovarian cancer, likely representing the fact that many genes are activated as part of common signaling pathways or that extensive cross-talk exists between several pathways in ovarian cancer. A statistical analysis shows that genes commonly up-regulated in ovarian cancer may result from the aberrant activation of a limited number of pathways, providing promising targets for novel therapeutic strategies.
 ...
PMID:Coordinately up-regulated genes in ovarian cancer. 1135 98

Recent advances in the molecular and cellular biology of malignancy and tumour immunology have stimulated significant progress in the application of immunotherapies as adjuvant treatments in cancer. Oregovomab (OvaRex, AltaRex) is a murine monoclonal antibody with high affinity to the ovarian cancer associated antigen CA125. Infusion of low-dose antibody results in formation of circulating immune complexes which can trigger a cellular immune response targeting CA125 and the ovarian cancer. Oregovomab has activity following initial chemotherapy and in recurrent disease settings and is in Phase III trials to establish its efficacy to prolong time to relapse in patients with advanced ovarian cancer and favourable outcomes to their front-line treatment. Additional studies of antigen processing and combination chemo-immunotherapy are ongoing. The treatment shows promise as a potential new addition to the standard care of ovarian cancer.
 ...
PMID:Immunotherapy of ovarian cancer with antibodies: a focus on oregovomab. 1526 82

Despite the poor prognosis of ovarian cancer and the importance of early diagnosis, there are no reliable noninvasive biomarkers for detection in the early stages of disease. Therefore, to identify novel ovarian cancer markers with potential utility in early-stage screening protocols, we have undertaken an unbiased and comprehensive analysis of gene expression in primary ovarian tumors and normal human ovarian surface epithelium (HOSE) using Serial Analysis of Gene Expression (SAGE). Specifically, we have generated SAGE libraries from three serous adenocarcinomas of the ovary and, using novel statistical tools, have compared these to SAGE data derived from two pools of normal HOSE. Significantly, in contrast to previous SAGE-based studies, our normal SAGE libraries are not derived from cultured cell lines. We have also compared our data with publicly available SAGE data obtained from primary tumors and "normal" HOSE-derived cell lines. We have thus identified several known and novel genes whose expressions are elevated in ovarian cancer. These include but are not limited to CLDN3, WFDC2, FOLR1, COL18A1, CCND1, and FLJ12988. Furthermore, we found marked differences in gene expression patterns in primary HOSE tissue compared with cultured HOSE. The use of HOSE tissue as a control for these experiments, along with hierarchical clustering analysis, identified several potentially novel biomarkers of ovarian cancer, including TACC3, CD9, GNAI2, AHCY, CCT3, and HMGA1. In summary, these data identify several genes whose elevated expressions have not been observed previously in ovarian cancer, confirm the validity of several existing markers, and provide a foundation for future studies in the understanding and management of this disease.
 ...
PMID:Comparative gene expression analysis of ovarian carcinoma and normal ovarian epithelium by serial analysis of gene expression. 1603 Jan 7


1 2 3 4 5 Next >>