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)

Endometriosis is a chronic, debilitating disease, associated with pelvic pain and infertility. Recent epidemiological studies suggest that women with endometriosis are at increased risk for ovarian cancer. Although the causative factors for both endometriosis and ovarian cancer remain largely unknown, several similarities between the proposed etiology of ovarian cancer and the observed pathophysiology of endometriosis have been reported. MUC1 glycoprotein is present in endometriotic lesions and overexpressed in epithelial ovarian tumors. We are currently studying immunity to MUC1 antigen in newly emerging preclinical models for endometriosis and ovarian cancer and exploring the potential for immune therapy/prevention with MUC1 in both diseases.
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PMID:MUC1 in endometriosis and ovarian cancer. 1733 83

A link between infertility therapy, especially ovulation induction therapy using gonadotropins, and the development of ovarian cancer has long been an issue of debate since an epidemiological report supporting the possibility appeared in 1992. A number of clinical/epidemiological and biological studies, including a few that we conducted, have revealed various facts regarding this issue. The aim of this short review was to summarize the last 10 years findings and to address the implications of the debates on this issue.
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PMID:LH/hCG action and development of ovarian cancer--a short review on biological and clinical/epidemiological aspects. 1735 87

Orphan nuclear receptors such as germ cell nuclear factor (GCNF), steroidogenic factor 1 (SF-1) and liver receptor homolog-1 (LRH-1), are emerging as important ovarian factors in regulating female reproduction. Within the ovary, GCNF (NR6A1) expression is restricted to the oocyte, while SF-1 (NR5A1) is expressed only in the somatic cells, such as granulosa, thecal and luteal cells, and interstitial cells. LRH-1 (NR5A2), an orphan receptor closely related to SF-1, is expressed only in the granulosa cells of the follicles and luteal cells within the ovary. Recent studies using conditional knockout strategies to bypass the embryonic lethality of GCNF and SF-1 null mice have uncovered important roles of GCNF and SF-1 in the oocyte and granulosa cells, respectively. In this review, we will summarize the major findings of GCNF and SF-1 in the ovary from the studies of conditional GCNF and SF-1 knockout mice. The potential role of LRH-1 in the ovary is also briefly discussed. Understanding the ovarian functions of these orphan nuclear receptors may lead to the development of new agents for regulation of female fertility and new medicines for the treatment of female idiopathic infertility, premature ovarian failure, polycystic ovarian syndrome and ovarian cancer.
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PMID:Orphan nuclear receptor function in the ovary. 1748 8

Although nulliparity has been extensively related to the risk of ovarian, breast and endometrial cancers, with many studies showing the relationship largely attributable to infertility, treatment effects on cancer risk are poorly understood. Two early studies raised substantial concern when ovulation-stimulating drugs were linked with large increases in ovarian cancer, supporting the notion of an important aetiological role of incessant ovulation. Subsequent studies have been mainly reassuring, although some have suggested possible risk increases among nulligravid women, those with extensive follow-up, and those developing borderline tumours. Results regarding effects of fertility drugs on breast cancer risk are conflicting, with some showing no associations and others demonstrating possible risk increases, although for varying subgroups. In contrast, endometrial cancer results are more consistent, with two recent studies showing increased risks related to clomiphene usage. This is of interest given that clomiphene is structurally similar to tamoxifen, a drug extensively linked with this cancer. Given the recent marketing of fertility drugs and the fact that exposed women are only beginning to reach the cancer age range, further follow-up is necessary. This will also be important to fully resolve effects of exposures such as gonadotrophins, used more recently in conjunction with IVF.
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PMID:Long-term effects of ovulation-stimulating drugs on cancer risk. 1762 33

Although oral contraceptives are protective for ovarian cancer, it is unclear how long this protection persists. The authors prospectively assessed this question as well as associations of other, less studied contraceptive methods (tubal ligation, rhythm method, diaphragm, condoms, intrauterine device, foam, spousal vasectomy) and infertility with ovarian cancer risk among 107,900 participants in the US Nurses' Health Study. During 28 years of follow-up (1976-2004), 612 cases of invasive epithelial ovarian cancer were confirmed. Duration of oral contraceptive use was inversely associated with risk (p-trend = 0.02), but no clear trend was observed for years since last use. However, for women using oral contraceptives for >5 years, the rate ratio for ovarian cancer for <or=20 years since last use was 0.58 (95% confidence interval (CI): 0.39, 0.87), with no association found for >20 years since last use (rate ratio (RR) = 0.92, 95% CI: 0.61, 1.39). Tubal ligation (RR = 0.66, 95% CI: 0.50, 0.87) was associated with decreased ovarian cancer risk, whereas intrauterine device use (RR = 1.76, 95% CI: 1.08, 2.85) and infertility (RR = 1.36, 95% CI: 1.07, 1.75) were associated with an increased risk. Results suggest that the beneficial effect of oral contraceptives on ovarian cancer risk attenuates after 20 years since last use. Furthermore, tubal ligation, intrauterine device use, and infertility were associated with ovarian cancer risk.
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PMID:Association of oral contraceptive use, other contraceptive methods, and infertility with ovarian cancer risk. 1765 16

To understand the influence of hormonal and environmental factors on the risk of ovarian cancer, it is important to remember the established risk factors and postulated mechanisms that lead to the development of ovarian cancer. Several risk factors have been identified as increasing the risk of epithelial ovarian cancer, including low pariety, infertility, early age of menarche, and late age of menopause. This article discusses the different hypotheses and focuses on hormonal and environmental risk factors, as well the chemoprevention of epithelial ovarian cancer.
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PMID:Ovarian cancer hormonal and environmental risk effect. 1806 64

In a young woman with gynecologic cancer, preservation of fertility is possible. Fertility-sparing surgery may be safe in early ovarian cancer of certain histological subtypes such as ovarian tumors of low malignant potential, malignant ovarian germ cell tumors, and ovarian sex cord stromal tumors. For women with invasive epithelial ovarian cancer who have early-stage disease, fertility-sparing surgery may be an option. In some cases, fertility-sparing surgery may be followed by postoperative chemotherapy. The concept of fertility-preserving surgery in early cervical cancer has been adopted by several leading centers worldwide as an option for stage Ia and small Ib disease without the presence of lymphovascular involvement. Nonsurgical options such as hormonal therapy may be considered for women with early-stage, low-grade endometrial cancer. Improvements in cancer cure rates and the development of conservative treatments mean that many young women with early gynecologic cancer can hope to start a new pregnancy after the treatment. Patients are generally advised to wait 2 years after treatment for any malignancy before attempting pregnancy, but the optimal interval between cure and conception must be carefully determined by a multidisciplinary team including oncologist and obstetrician. Gynecologic surgery and hemotherapy can have an impact not only on fertility, but also on the course of a next pregnancy (increased risk of miscarriage and premature delivery, etc.) These risks must be taken into account by the obstetrician. Management of young women diagnosed with gynecologic cancer should be individualized, with the risk of conservative therapy balanced against the disadvantages of more radical treatment. The patient and the family should be extensively counseled. The alternatives to the traditional and standard radical procedures should be discussed, and the limitation of data regarding many conservative treatment options should be explained. The patients should be aware that by accepting fertility-sparing treatment they are assuming a small but undefined risk for recurrence of the disease. They need to know that these conservative therapeutic approaches are yet not considered "standard." Furthermore, patients need to be assessed for the realistic probabilities of achieving conception on the basis on their age, history, and infertility evaluation. Some of them will require assisted reproduction technology (ARTS) to help achieve a pregnancy, especially in vitro fertilization (IVF). They may also consider ovarian tissue, oocyte, or embryo cryopreservation before definitive cancer therapies. And, finally, patients also need to understand the risk of premature delivery and the consequences of prematurity. The care of the young patient with gynecologic malignancy is extremely complex and challenging. It necessarily requires a multidisciplinary approach with the close collaboration of gynecologist-oncologist, reproductive endocrinologist, and perinatologist.
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PMID:Fertility after the treatment of gynecologic tumors. 1808 Apr 46

Gamendazole was recently identified as an orally active antispermatogenic compound with antifertility effects. The cellular mechanism(s) through which these effects occur and the molecular target(s) of gamendazole action are currently unknown. Gamendazole was recently designed as a potent orally active antispermatogenic male contraceptive agent. Here, we report the identification of binding targets and propose a testable mechanism of action for this antispermatogenic agent. Both HSP90AB1 (previously known as HSP90beta [heat shock 90-kDa protein 1, beta]) and EEF1A1 (previously known as eEF1A [eukaryotic translation elongation factor 1 alpha 1]) were identified as binding targets by biotinylated gamendazole (BT-GMZ) affinity purification from testis, Sertoli cells, and ID8 ovarian cancer cells; identification was confirmed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry and Western blot analysis. BT-GMZ bound to purified yeast HSP82 (homologue to mammalian HSP90AB1) and EEF1A1, but not to TEF3 or HBS1, and was competed by unlabeled gamendazole. However, gamendazole did not inhibit nucleotide binding by EEF1A1. Gamendazole binding to purified Saccharomyces cerevisiae HSP82 inhibited luciferase refolding and was not competed by the HSP90 drugs geldanamycin or novobiocin analogue, KU-1. Gamendazole elicited degradation of the HSP90-dependent client proteins AKT1 and ERBB2 and had an antiproliferative effect in MCF-7 cells without inducing HSP90. These data suggest that gamendazole may represent a new class of selective HSP90AB1 and EEF1A1 inhibitors. Testis gene microarray analysis from gamendazole-treated rats showed a marked, rapid increase in three interleukin 1 genes and Nfkbia (NF-kappaB inhibitor alpha) 4 h after oral administration. A spike in II1a transcription was confirmed by RT-PCR in primary Sertoli cells 60 min after exposure to 100 nM gamendazole, demonstrating that Sertoli cells are a target. AKT1, NFKB, and interleukin 1 are known regulators of the Sertoli cell-spermatid junctional complexes. A current model for gamendazole action posits that this pathway links interaction with HSP90AB1 and EEF1A1 to the loss of spermatids and resulting infertility.
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PMID:Gamendazole, an orally active indazole carboxylic acid male contraceptive agent, targets HSP90AB1 (HSP90BETA) and EEF1A1 (eEF1A), and stimulates Il1a transcription in rat Sertoli cells. 1821 11

Ovarian cancer is the fifth most frequently occurring cancer among women and leading cause of gynecological cancer deaths in North America. Although the etiology of ovarian cancer is not clear, certain factors are implicated in the etiology of this disease, such as ovulation, gonadotropic and steroid hormones, germ cell depletion, oncogenes and tumor suppressor genes, growth factors, cytokines, and environmental agents. Family history of breast or ovarian cancer is a prominent risk factor for ovarian cancer, with 5-10% of ovarian cancers due to heritable risk. Reproductive factors such as age at menopause and infertility contribute to greater risk of ovarian cancer, whereas pregnancy, tubal ligation, and hysterectomy reduce risk. Oral contraceptive (OC) use has clearly been shown to be protective against ovarian cancer. In contrast, large epidemiologic studies found hormone replacement therapy (HRT) to be a greater risk factor for ovarian cancer. The marked influence of hormones and reproductive factors on ovarian cancer suggests that endocrine disrupters may impact risk; however, there is a notable lack of research in this area. Lifestyle factors such as cigarette smoking, obesity, and diet may affect ovarian cancer risk. Exposure to certain environmental agents such as talc, pesticides, and herbicides may increase risk of ovarian cancer; however, these studies are limited. Further research is needed to strengthen the database of information from which an assessment of environmental and toxicological risk factors for ovarian cancer can be made.
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PMID:Risk factors for ovarian cancer: an overview with emphasis on hormonal factors. 1836 58

Infertility is considered to influence the risk of breast cancer and gynecologic cancers. To assess this association, the authors used data from a large cohort of 54,362 women with a diagnosis of infertility who were referred to Danish fertility clinics between 1963 and 1998. Through 2003, 1,975 cancers were identified by linkage to the Danish Cancer Registry. Cancer risk was assessed through standardized incidence ratios (SIRs) and corresponding 95% confidence intervals, using general and parity-specific cancer incidence rates in the general population of Denmark as a reference. After adjustment for parity status, significantly increased SIRs were observed for breast (SIR = 1.08, 95% confidence interval: 1.01, 1.16) and ovarian (SIR = 1.46, 95% confidence interval: 1.24, 1.71) cancer. The risk of breast cancer increased with follow-up time. Similar risk patterns were observed for the different histologic types of breast cancer and all nonmucinous types of ovarian cancer, whereas the risk of mucinous ovarian cancers seemed not to be increased. These data thus suggest higher risks of breast and ovarian cancer among infertile women. However, since these results could not distinguish the effects of underlying infertility from the effects of fertility treatment, additional studies are needed to disentangle the effects of these two factors.
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PMID:Risk of breast cancer and gynecologic cancers in a large population of nearly 50,000 infertile Danish women. 1844 41


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