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)

The ability of two supposed DNA-repair inhibitors to modulate cisplatin-induced cytotoxicity in a human ovarian cancer cell line (CAOV-3) and a human cervical cancer cell line (Me-180) was investigated using a short-term chemosensitivity assay based on bioluminescence of cellular adenosine triphosphate (ATP). Cisplatin concentrations bracketing the reported peak plasma concentration (2.5 micrograms/ml) were used and the 50% inhibitory concentrations were determined by linear regression of log-transformed survival data. At 2.5 mM, the methylxanthine caffeine enhanced cisplatin sensitivity 2.9-fold in CAOV-3 cells and 2.7-fold in Me-180 cells. At 2.5 mM, pentoxifylline, a closely related methylxanthine, increased cisplatin sensitivity 2.9-fold in CAOV-3 cells and 3.4-fold in Me-180 cells. Chemical modification of cisplatin-induced cytotoxicity by assumed inhibition of DNA-repair mechanisms may hold promise for clinical application in the treatment of gynecological cancer.
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PMID:Potentiation of cisplatin cytotoxicity by methylxanthines in vitro. 222 31

This article reviews 18 years of research on the carcinogenic effects of both caffeine and coffee. Caffeine, the most widely consumed drug in the United States, has been the subject of numerous studies. It has been found to both increase and decrease malignant cell development, on the cellular and subcellular level, depending on the carcinogen it is used with, the type of host cell, and the stage of cell cycle in which it is introduced. No causal relationship has been established between coffee intake and lower urinary tract cancer, pancreatic cancer, breast cancer or fibrocystic breast disease, ovarian cancer, or large bowel cancer.
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PMID:The carcinogenicity of caffeine and coffee: a review. 389 47

In cell culture, caffeine has been shown to enhance the lethality of DNA-damaging agents including ultraviolet rays, X-irradiation, and alkylating agents. We have previously reported a Phase I clinical trial demonstrating the feasibility of intraperitoneal radioimmunotherapy in patients with refractory ovarian cancer using 131I-labeled monoclonal antibody OC125. We are now exploring the possibility of using caffeine to enhance the toxicity of 131I-irradiation in target cells. As an in vitro model we tested this hypothesis using Chinese hamster ovary (CHO) cells exposed to 131I-labeled human serum albumin at various doses (4 to 70 microCi/ml) for 24 hr followed by 24 hr of incubation with caffeine. Cytotoxicity was measured by clonogenic survival and a nuclear fragmentation assay. The results show that caffeine, at a concentration of 7.7 mM, significantly enhances the cytotoxicity of 131I-irradiation.
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PMID:Enhancement of 131I-mediated cytotoxicity by caffeine. 915 34

Coffee, alcohol and tobacco use have been examined in many epidemiologic studies of ovarian cancer but findings have generally been inconclusive. To explain prior inconsistent findings, we sought to determine whether associations with these exposures might vary by histologic subtype of ovarian cancer or menopausal status at diagnosis. We conducted a population-based case-control study in eastern Massachusetts and New Hampshire involving 549 women with newly-diagnosed epithelial ovarian cancer and 516 control women selected either by random digit dialing or through lists of residents. Coffee and alcohol consumption was assessed through a semi-quantitative food-frequency questionnaire, and information on tobacco smoking was collected through personal interview. Consumption of coffee and caffeine was associated with increased risk for ovarian cancer but only among premenopausal women. There was no increase in risk for ovarian cancer overall associated with tobacco or alcohol use in either pre- or post-menopausal women. Association of borderline significance for tobacco and invasive serous cancers and alcohol and mucinous cancers were observed but reduced after adjustment for coffee consumption. We conclude that coffee and caffeine consumption may increase risk for ovarian cancer among premenopausal women and are findings that have some epidemiologic and biologic support.
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PMID:Population based study of coffee, alcohol and tobacco use and risk of ovarian cancer. 1100 86

Our objective was to identify factors that correlate with CA125 concentrations in healthy postmenopausal women and to introduce recommendations for reporting and interpreting individual CA125 assay results. We analyzed repeated serum CA125 levels, as measured by the CA125II assay, in 18,748 postmenopausal women who participated in the ST: Bartholomew's/Royal London Hospital Ovarian Cancer screening trial from 1986 to 1994 and were not diagnosed with ovarian cancer during the 12-year follow-up period. We found that race is a substantial predictor of normal levels of CA125, with average CA125II concentration from African (median, 9.0; 95% range, 4.0-26.0 units/ml) and Asian women (median, 13.0; range, 5.9-33.3 units/ml) lower than that in Caucasian women (median, 14.2; range, 6.0-41.0 units/ml; P < 0.001). Women with a hysterectomy have lower CA125II values (median, 13.6; range 5.5-39.0 units/ml; P < 0.001), and women with a prior cancer diagnosis other than ovarian cancer have higher levels of CA125 II (median, 16.0; range, 6.0-49.0 units/ml; P < 0.003). Regular smoking and caffeine consumption decrease CA125 levels (P < 0.001). A woman's age, age at menarche, age at menopause, and history of a previous ovarian cyst (P < 0.05) are also predictive of baseline CA125 levels. Parity, history of hormone replacement therapy or unilateral oopherectomy, and previous use of oral contraceptives or talcum powder are not significant predictors of CA125 concentrations (P > 0.05). We concluded that clinically significant differences in individual patient characteristics need to be reflected in the screening algorithms that use CA125II so that designed performance characteristics (sensitivity and specificity) are maintained in practice.
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PMID:Factors influencing serum CA125II levels in healthy postmenopausal women. 1135 59

Aromatic hydrocarbon hydroxylase (CYP1A1) is involved in the metabolism of many substrates and the subject of cancer studies. This study examined the association between two polymorphic variants of CYP1A1 and ovarian cancer risk. The frequencies of the Msp1 and Ile/Val variants of CYP1A1 were determined in 445 ovarian cancer cases and 472 general population controls in New England. Overall relative risks were calculated as well as those within subgroups of various exposures. There was no increased risk for ovarian cancer associated with possession of either the Msp1 or Ile/Val polymorphism of CYP1A1. Elevated risk for ovarian cancer was found in those who carried an Ile/Val variant and who consumed more than median levels of caffeine (risk ratio = 2.69; 95% confidence interval, 1.18-6.18). No variation by histological type of ovarian cancer was observed. Significant interaction may exist between polymorphic variants of CYP1A1 and caffeine that could explain weak or inconsistent associations between caffeine and ovarian cancer when genotype has not been considered.
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PMID:Interaction between CYP1A1 polymorphic variants and dietary exposures influencing ovarian cancer risk. 1264 5

Coffee and caffeine consumption has been associated with ovarian cancer risk in several epidemiological studies. CYP1A2 is a key enzyme in the metabolism of coffee and in the activation of heterocyclic aromatic compounds that may be carcinogenic. Data from a preliminary investigation conducted in Hawaii of 164 epithelial ovarian cancer cases and 194 controls were used to examine the hypothesis that coffee and caffeine intake increases the risk of ovarian cancer and that these relations are modified by the CYP1A2 high-inducibility A/A genotype. A personal interview and blood specimen were collected in the subjects' homes. A significant positive trend (p = 0.02) in the odds ratios (ORs) was found with increasing intake of caffeine but not with tea or soda. Regular coffee drinkers were at significantly increased risk (OR = 1.8, 95% confidence interval, CI = 1.1-2.8) of ovarian cancer compared with women who did not drink regular coffee. Women with any CYP1A2 C allele were at similar risk of ovarian cancer (OR = 1.1, 95% CI = 0.7-1.7) compared with women with the A/A genotype. The associations of caffeine and coffee intake with risk were stronger among women with the A/A genotype than among women with any C allele. Somewhat stronger relations of coffee and caffeine intake to risk were found among women with cruciferous vegetable consumption above the median and among cases with mucinous histology. These preliminary data suggest a modest positive association of caffeine and coffee consumption with the OR for ovarian cancer that may be modified by CYP1A2 genotype and exposures, such as cruciferous vegetable consumption, that influence CYP1A2 expression.
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PMID:Association of caffeine intake and CYP1A2 genotype with ovarian cancer. 1292

The milk sugar lactose is an hypothesized risk factor for epithelial ovarian cancer because of possible direct toxic effects of its metabolites on oocytes or by compensatory gonadotropin stimulation. Women are presently encouraged to consume dairy products as a source of calcium to prevent osteoporosis. The objective of our study was to prospectively assess lactose, milk and milk product consumption in relation to ovarian cancer risk among 80326 participants in the Nurses' Health Study who had no history of cancer other than nonmelanoma skin cancer. Participants in the Nurses' Health Study reported on known and suspected ovarian cancer risk factors in questionnaires mailed biennially from 1976 to 1996. Food frequency questionnaires were included in the years 1980, 1984, 1986 and 1990. Newly reported ovarian cancer was documented by review of medical records. During 16 years of follow-up (1980-1996), 301 cases of invasive epithelial ovarian cancer were confirmed. Pooled logistic regression was used to control for age, body mass index (kg/m(2)), caffeine intake, oral contraceptive use, smoking history, parity and tubal ligation. For all subtypes of invasive ovarian cancer combined, we observed a nonsignificant 40% greater risk for women in the highest category of lactose consumption compared to the lowest (multivariate relative risk (RR) 1.40, 95% confidence interval (CI), 0.98-2.01). We observed a 2-fold higher risk of the serous ovarian cancer subtype among those in the highest category of lactose consumption compared to the lowest (RR 2.07, 95% CI, 1.27-3.40). For each 11-gram increase in lactose consumption (the approximate amount in one glass of milk), we observed a 20% increase in risk of serous cancers (RR 1.20, 95% CI, 1.04-1.39). Skim and low-fat milk were the largest contributors to dietary lactose. Women who consumed one or more servings of skim or low-fat milk daily had a 32% higher risk of any ovarian cancer (RR 1.32, 95% CI, 0.97-1.82) and a 69% higher risk of serous ovarian cancer (RR 1.69, 95% CI, 1.12-2.56) compared to women consuming 3 or less servings monthly. Controlling for fat intake did not change our findings. Our findings provide some support for the hypothesis that lactose intake increases risk of epithelial ovarian cancer. However, the observed excess risk appeared limited to the serous subtype of ovarian cancer in our study.
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PMID:A prospective study of dietary lactose and ovarian cancer. 1506 93

Resveratrol is one of the most extensively studied cancer chemopreventive agents; however, its mechanisms of action are not completely understood. Here, we observed that resveratrol induces S phase arrest via Tyr15 phosphorylation of Cdc2 in human ovarian carcinoma Ovcar-3 cells. Overexpression of Cdc2AF, a mutant resistant to Thr14 and Tyr15 phosphorylation, ablated resveratrol-induced S phase arrest. Further upstream, we observed that resveratrol causes phosphorylation of cell division cycle 25C (Cdc25C) tyrosine phosphatase via the activation of checkpoint kinases Chk1 and Chk2, which in turn were activated via ATM (ataxia telangiectasia mutated)/ATR (ataxia telangiectasia-Rad3-related) kinase in response to DNA damage, as resveratrol also increased phospho-H2A.X (Ser139), which is known to be phosphorylated by ATM/ATR in response to DNA damage. The involvement of these molecules in resveratrol-induced S phase was also supported by the studies showing that addition of ATM/ATR inhibitor caffeine reverses resveratrol-caused activation of ATM/ATR-Chk1/2 as well as phosphorylation of Cdc25C, Cdc2 and H2A.X, and S phase arrest. In additional studies assessing whether observed effects of resveratrol are specific to Ovcar-3 cells, we observed that it also induces S phase arrest and H2A.X (Ser139) phosphorylation in other ovarian cancer cell lines PA-1 and SKOV-3, albeit at different levels; whereas, resveratrol showed only marginal S phase arrest in normal human foreskin fibroblasts with undetectable level of phospho-H2A.X (Ser139). These findings for the first time identify that resveratrol causes Cdc2-tyr15 phosphorylation via ATM/ATR-Chk1/2-Cdc25C pathway as a central mechanism for DNA damage and S phase arrest selectively in ovarian cancer cells, and provide a rationale for the potential efficacy of ATM/ATR agonists in the prevention and intervention of cancer.
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PMID:Resveratrol causes Cdc2-tyr15 phosphorylation via ATM/ATR-Chk1/2-Cdc25C pathway as a central mechanism for S phase arrest in human ovarian carcinoma Ovcar-3 cells. 1597 56

Coffee has become a popular beverage worldwide. Caffeine, a major ingredient of coffee, has been proposed to have a favorable affect on the modulation of circulating estrogen levels and therefore may be of importance in developments on hormone-related cancers. However, epidemiological evidence is limited and inconsistent. We examined the relationship between intake of coffee and hormone-related cancer risk among Japanese women using data from the hospital-based epidemiological research program at Aichi Cancer Center (HERPACC). In total, 2122 breast, 229 endometrial and 166 ovarian cancer cases were included, and 12 425 women, confirmed as free of cancer, were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. A statistically significant inverse association between risk of endometrial cancer and coffee consumption was noted in Japanese women, with no clear association evident for breast and ovarian cancer risk. Compared to non-drinker, the OR of daily drinking of 1-2 cups and 3 or more cups per day for endometrial cancer were 0.64 (95% CI: 0.43-0.94) and 0.41 (95% CI: 0.19-0.87), respectively, and the linear trend was also statistically significant (P < 0.01). However, there was no statistically significant association between caffeine intake and endometrial cancer. In summary, the results of the present study suggest that coffee consumption reduces the risk of endometrial cancer in Japanese subjects. Given the scarcity of studies of coffee intake and endometrial cancer and other hormone-dependent cancer risk, additional investigations are warranted.
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PMID:Coffee consumption and the risk of endometrial cancer: Evidence from a case-control study of female hormone-related cancers in Japan. 1727 30


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