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)

Assays measuring SMRP (mesothelin) and HE4 (a secreted protease) in serum and other body fluids (including urine for SMRP) are likely to be clinically useful for patients with ovarian cancer, as data indicate that they complement CA125 for diagnosis and monitoring of patients. Both markers have temporal stability, as does CA125, which may be utilized to facilitate earlier diagnosis by performing longitudinal studies on high risk subjects. Preliminary data show autoantibodies to native mesothelin in some patients with ovarian carcinoma and in some healthy women. We are presently studying their relationship to the patients' clinical state to learn whether measurements of antibody levels provide information that can aid diagnosis and monitoring of treated patients. Prospective studies are needed to establish the clinical relevance of our findings.
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PMID:SMRP and HE4 as biomarkers for ovarian carcinoma when used alone and in combination with CA125 and/or each other. 1854 15

Human epididymal secretory protein E4 (HE4, also known as WAP four-disulphide core domain protein 2) is a new promising biomarker for ovarian cancer but its specificity against ovarian endometriotic cysts is only superficially known. We, thus, analysed serum HE4 concentrations together with a tumour marker CA125 in serum samples of women diagnosed with various types of endometriosis, endometrial cancer or ovarian cancer, and in samples from healthy controls. The mean serum concentration of HE4 was significantly higher in serum samples of patients with both endometrial (99.2 pM, P<0.001) and ovarian (1125.4 pM, P<0.001) cancer but not with ovarian endometriomas (46.0 pM) or other types of endometriosis (45.5 pM) as compared with healthy controls (40.5 pM). The serum CA125 concentrations were elevated in patients with ovarian cancer, advanced endometriosis with peritoneal or deep lesions, or ovarian endometriomas, but not in the patients with endometrial cancer. The microarray results revealed that the mRNA expression of the genes encoding HE4 and CA125 reflected the serum protein concentrations. Taken together, measuring both HE4 and CA125 serum concentrations increases the accuracy of ovarian cancer diagnosis and provides valuable information to discriminate ovarian tumours from ovarian endometriotic cysts.
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PMID:Serum HE4 concentration differentiates malignant ovarian tumours from ovarian endometriotic cysts. 1951 69

There is currently no effective therapy for patients with advanced ovarian cancer. To address the need for a more effective treatment for this deadly disease, we conducted preclinical tests in ovarian tumor-bearing mice to evaluate the therapeutic efficacy of using a cationic biodegradable poly(beta-amino ester) polymer as a vector for nanoparticulate delivery of DNA encoding a diphtheria toxin suicide protein (DT-A). The promoter sequences of two genes that are highly active in ovarian tumor cells, MSLN and HE4, were used to target DT-A expression to tumor cells. Administration of DT-A nanoparticles directly to s.c. xenograft tumors and to the peritoneal cavity of mice bearing primary and metastatic ovarian tumors resulted in a significant reduction in tumor mass and a prolonged life span compared to control mice. Minimal nonspecific tissue and blood chemistry toxicity was observed following extended treatment with nanoparticles. DT-A nanoparticle therapy suppressed tumor growth more effectively than treatment with clinically relevant doses of cisplatin and paclitaxel. Our findings suggest that i.p. administration of polymeric nanoparticles to deliver DT-A encoding DNA, combined with transcriptional regulation to target gene expression to ovarian tumor cells, holds promise as an effective therapy for advanced-stage ovarian cancer.
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PMID:Nanoparticle-delivered suicide gene therapy effectively reduces ovarian tumor burden in mice. 1964 34

Ovarian cancer remains a deadly threat to women as the disease is often diagnosed in the late stages when the chance of survival is low. There are no good biomarkers available for early detection and only a few markers have shown clinical utility for prognosis, response to therapy and disease recurrence. We mined conditioned media of four ovarian cancer cell lines (HTB75, TOV-112D, TOV-21G and RMUG-S) by two-dimensional liquid chromatography-mass spectrometry. Each cell line represented one of the major histological types of epithelial ovarian cancer. We identified 2039 proteins from which 228 were extracellular and 192 were plasma membrane proteins. Within the latter list, we identified several known markers of ovarian cancer including three that are well established, namely, CA-125, HE4, and KLK6. The list of 420 extracellular and membrane proteins was cross-referenced with the proteome of ascites fluid to generate a shorter list of 51 potential biomarker candidates. According to Ingenuity Pathway Analysis, two of the top 10 diseases associated with the list of 51 proteins were cancer and reproductive diseases. We selected nine proteins for preliminary validation using 20 serum samples from healthy women and 10 from women with ovarian cancer. Of the nine proteins, clusterin (increase) and IGFBP6 (decrease) showed significant differences between women with or without ovarian cancer. We conclude that in-depth proteomic analysis of cell culture supernatants of ovarian cancer cell lines can identify potential ovarian cancer biomarkers that are worth further clinical validation.
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PMID:Comprehensive analysis of conditioned media from ovarian cancer cell lines identifies novel candidate markers of epithelial ovarian cancer. 1966

Ovarian cancer is a leading cause of cancer mortality in women. The aim of this study was to elucidate whether whey acidic protein (WAP) genes on chromosome 20q13.12, a region frequently amplified in this cancer, are expressed in serous carcinoma, the most common form of the disease. Herein, we report that a trio of WAP genes (HE4, SLPI, and Elafin) is overexpressed and secreted by serous ovarian carcinomas. To our knowledge, this is the first report linking Elafin to ovarian cancer. Fluorescence in situ hybridization analysis of primary tumors demonstrates genomic gains of the Elafin locus in a majority of cases. In addition, a combination of peptidomimetics, RNA interference, and chromatin immunoprecipitation experiments shows that Elafin expression can be transcriptionally upregulated by inflammatory cytokines through activation of the nuclear factor kappaB pathway. Importantly, using a clinically annotated tissue microarray composed of late-stage, high-grade serous ovarian carcinomas, we show that Elafin expression correlates with poor overall survival. These results, combined with our observation that Elafin is secreted by ovarian tumors and is minimally expressed in normal tissues, suggest that Elafin may serve as a determinant of poor survival in this disease.
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PMID:Overexpression of elafin in ovarian carcinoma is driven by genomic gains and activation of the nuclear factor kappaB pathway and is associated with poor overall survival. 2012 74

There has been a concerted effort over the last decade to improve our understanding of the complex biology of ovarian cancer. A linear growth in published proteogenomic studies has addressed a variety of questions regarding its molecular pathogenesis. A number of genes have been identified by transcriptomic approaches, some of which are being investigated as putative tumor markers (HE4, OPN, Ep-CAM and Mesothelin), whilst others are potential targets for molecular therapeutic approaches (VEGF, IO4, EGFR, MUC1, CLDN4 and SLPI). Proteogenomics has the potential to further change our current characterization and treatment of ovarian cancer. Additional advances will depend on integrated study designs, interdisciplinary collaborations, use of robust high-throughput platforms, as well as uniform guidelines for bioinformatic analyses.
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PMID:Proteogenomic studies in epithelial ovarian cancer: established knowledge and future needs. 2047 44

Neoplasms of the ovary present an increasing challenge to the physician. Neoplastic ovarian cysts can resemble endometriomas in ultrasound imaging and need to be carefully considered in the differential diagnosis. We report the case of a woman with a strong family history of hereditary breast and ovarian cancer, who presented with a pelvic mass. The young girl refused oncogenetic counseling and genetic testing, even though she had a 50% a priori probability of being a BRCA1 mutation carrier. Pelvic magnetic resonance imaging (MRI) and a comparative analysis of the serum concentration of HE-4 and CA125 biomarkers provided accuracy and sensitivity in the diagnosis of a benign ovarian pathology. Based on this experience, we propose that the sensitivity of a screening program based on a HE4 and CA125 assay and MRI in high risk patients with mutations in the BRCA1 and BRCA2 genes may be considered a useful pre-operative tool for the differential diagnosis of pelvic masses.
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PMID:HE4 in the differential diagnosis of a pelvic mass: a case report. 2134 4

Establishing a cancer screening biomarker's intended performance requires "phase III" specimens obtained in asymptomatic individuals before clinical diagnosis rather than "phase II" specimens obtained from symptomatic individuals at diagnosis. We used specimens from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to evaluate ovarian cancer biomarkers previously assessed in phase II sets. Phase II specimens from 180 ovarian cancer cases and 660 benign disease or general population controls were assembled from four Early Detection Research Network or Ovarian Cancer Specialized Program of Research Excellence sites and used to rank 49 biomarkers. Thirty-five markers, including 6 additional markers from a fifth site, were then evaluated in PLCO proximate specimens from 118 women with ovarian cancer and 474 matched controls. Top markers in phase II specimens included CA125, HE4, transthyretin, CA15.3, and CA72.4 with sensitivity at 95% specificity ranging from 0.73 to 0.40. Except for transthyretin, these markers had similar or better sensitivity when moving to phase III specimens that had been drawn within 6 months of the clinical diagnosis. Performance of all markers declined in phase III specimens more remote than 6 months from diagnosis. Despite many promising new markers for ovarian cancer, CA125 remains the single-best biomarker in the phase II and phase III specimens tested in this study.
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PMID:Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. 2137 29

Zinc-finger protein 217 (ZNF217), which is overexpressed during cancer progression, can promote tumor cell immortalization. To examine the function of ZNF217, a global expression profile was carried out using Affymetrix Gene Chip analysis with HG-U133 plus 2.0 arrays in the ovarian cancer cell line HO-8910 after silencing of the ZNF217 gene. The results were analyzed using the Gene Ontology program to investigate the functional network affected by ZNF217 in ovarian cancer cells. Changes in the mRNA expression of the affected genes were confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the ZNF217 gene is a key regulator of ovarian cancer, as the silencing of ZNF217 resulted in significant down-regulation by at least 8-fold of 164 genes in the HO-8910 cell line compared to non-silenced control cells. Among these down-regulated genes were ALOX15, CD1D, FXYD3, GAS6, KRT4, LIN7B, MMP-24, PDZK1, PEX6, PRSS8, SLC2A9, STRN and WFDC2. Down-regulation was confirmed by real-time RT-PCR after the silencing of ZNF217 (p<0.05). The results suggest that ZNF217 plays a central role in malignant processes in ovarian cancer.
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PMID:Microarray analysis of gene expression in the ovarian cancer cell line HO-8910 with silencing of the ZNF217 gene. 2147 12

This paper reviews current screening techniques as well as novel biomarkers and their potential role in early detection of ovarian cancer. Ovarian cancer is one of the most common reproductive cancers and has the highest mortality rate amongst gynecologic cancers. Because most ovarian cancer diagnoses occur in the late stages of the disease, five-year survival rates fall below 20%. To improve survival rates and to lower mortality rates for ovarian cancer, improved detection at early stages of the disease is needed. Current screening approaches include tumor markers, ultrasound, or a combination. Efforts are underway to discover new biomarkers of ovarian cancer in order to surmount the obstacles in early-stage diagnosis. Among serum protein markers, HE4 and mesothelin can augment CA125 detection providing higher sensitivity and specificity due to the presence of these proteins in early-stage ovarian cancer. Detection testing that includes methylation of the MCJ gene and increased expression of vascular endothelial growth factor is correlated to poor prognosis and may predict patient survival outcome. Detection testing of biomarkers with long-term stability and combination panels of markers, will likely lead to effective screening strategies with high specificity and sensitivity for early detection of ovarian cancer.
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PMID:Potential markers for detection and monitoring of ovarian cancer. 2157 60


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