1,720,966 research outputs found
Clinical function of estrogen receptors in endometrial cancer.
No full textApproximately 70-80% of endometrial carcinomas, type I carcinomas, are associated with endometrial hyperplasia, hyperestrogenism, and expression of estrogen receptor (ER). The aim of this review was to clarify the role of ER in endometrial diseases carcinoma. The estrogens exert their effect via two estrogen receptor: α and β. The ERs modulate transcriptional process by binding directly to the estrogen response elements (ERE) located in the target gene, or in non classical mode through protein-protein tethering with other transcription factors. There are also orphan receptors (their natural ligands have not been identified). Among this group, estrogen receptor-related receptors (ERRs) were identified by their sequences similar to those of ERs. Since the ERRs have shown a high similarity in DNA binding domain with ERs can interfere with estrogen signalling strengthening the hypothesis of an estrogen-ER-ERR crosstalk. Recently, the ERs and estrogen enzymes emerge as pharmacological targets in different disorders, as well as ERRs, and they may represent the reliable biomarkers in endometrial disease
Mucinous tumor of uncertain malignant potential of the appendix mimicking ovarian cancer: a case report.
No full textReceptorial and mitochondrial apoptotic pathways in normal and neoplastic human endometrium
No full textUnder normal conditions, in human endometrium, apoptotic and antiapoptotic factors play an important role in tissue homeostasis. Abnormalities of apoptosis, a process implicated in several events in the reproductive organs, may contribute to neoplastic transformation. The present study aimed to investigate the involvement of both the receptorial and the mitochondrial pathways of apoptosis in normal endometrium and in endometrial carcinoma, by measuring caspase-3 and caspase-8 activities and cytosolic cytochrome c levels. Twelve endometrial carcinomas and nine normal endometrial specimens (four in mild proliferative phase, five in late secretory phase) were included in this study. Cytosolic fractions, obtained by differential centrifugation of tissue homogenates, were analyzed for caspase-3 and caspase-8 activities, as well as for cytochrome c content. Caspase-8 activity in normal secretory phase endometrium was higher than that in the proliferative phase and in the endometrial carcinoma. Moreover, higher cytochrome c levels were detected in endometrial carcinoma with respect to normal secretive endometrium. No significant differences were found in caspase-3 activity between normal and pathologic endometrium. The results obtained suggest that in normal endometrium, apoptosis takes place through the activation of both receptorial and mitochondrial pathways. Defects in both these pathways may contribute to the development of endometrial carcinoma
Involvement of estrogen receptor-related receptors in human ovarian endometriosis
No full textObjective: To determine whether decreased estrogen receptor alpha (ER-alpha) expression in endometriotic lesions could be balanced by an increased expression of estrogen receptor-related receptors (ERRs). To evaluate whether ERR-alpha expression is influenced by hormonal change in fertile and menopausal women. Design: Prospective controlled study. Setting: University Hospital, Department of Gynecology. Patient(s): Twenty-five women: 20 women of reproductive age with (n = 10) and without (control; n = 10) endometriosis and 5 menopausal women. Intervention(s): Real-time polymerase chain reaction (qPCR). Immunohistochemistry. Main Outcome Measure(s): The ER and ERR expression levels were studied by reverse transcriptase-qPCR, ELISA, and immunohistochemistry using endometriotic and normal endometrial tissues. The ERR-alpha protein distribution was performed by immunohistochemistry in fertile and menopausal women. Result(s): Increased levels of ER-beta were associated with ER-alpha, ERR-alpha, and ERR-gamma reductions in ectopic tissue but not in eutopic and normal endometria. Similar levels of ERR-beta were found in women with and without endometriosis. The ERR-alpha expression was similar in proliferative and secretory endometrial samples, whereas a down-regulation of this receptor was found in atrophic tissue. Conclusion(s): Our data confirm the up-regulation of ER-beta as the principal receptor involved in the progression of human endometriosis. In addition, we found that ERR-alpha seems to be unresponsive to hormonal changes during the menstrual cycle. (Fertil Steril (R) 2011;96:102-6. (C)2011 by American Society for Reproductive Medicine.
Prevalence of human papillomavirus infection in a clinic sample of transsexuals in Italy
Full text linkAbstract
OBJECTIVES:
Detectable human papillomavirus (HPV) DNA is the most common sexually transmitted infection. Reports on the prevalence of detectable HPV DNA among transsexuals (not sex workers) are scarce. The objective of the study was to determine the prevalence of detectable HPV DNA in a clinic sample of transsexuals and to assess the relationship between detectable HPV DNA and cytological outcomes.
METHODS:
Clinical samples (oral, anal, vaginal, cervicovaginal and penile scraped cells) from 35 transsexuals (surgically treated and surgically untreated) who attended the outpatient Clinic of Gender Identity Dysphoria of the Department of Obstetrics and Gynecology of Policlinico Hospital (Bari, Italy) were collected for cytological analysis and HPV DNA detection and typing. All enrolled subjects answered an anonymous structured questionnaire about their sexual habits. Serological status for other sexually transmitted diseases (hepatitis B virus (HBV), hepatitis C virus (HCV), HIV and syphilis) was also evaluated.
RESULTS:
HPV DNA was detected in 14 of 35 patients (40.0%). The prevalence of detectable HPV DNA was 38.2% (13/34) in tested anal samples, 9.1% (2/22) in vaginal samples and 8.3% (1/12) in penile samples. Oncogenic HPV genotypes have been detected in 93% of HPV-positive transsexuals. More than one-third (35.7%) of HPV-positive transsexuals were infected with at least one of the four vaccine-preventable genotypes, 6, 11, 16 and 18.
CONCLUSIONS:
The high rate of detectable HPV DNA by oncogenic types suggests that periodic cytological screening and clinical evaluation may be necessary since transsexuals are at high risk of anogenital cancer. Also promoting HPV vaccination in younger subjects may be advisable.
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Estrogen receptor (ER) and ER-related receptor expression in normal and atrophic human vagina
No full textObjectives: The estrogen level decline in menopausal status is involved in physiological alterations of different human tissues including vaginal mucosa. In this study, we have evaluated the estrogen receptor (ER) and estrogen receptor-related receptor (ERR) expression in tissue samples of posterior vaginal wall obtained from pre- and post-menopausal women. Methods: The nuclear receptor expression was determined by quantitative real-time PCR (qPCR). Results: The qPCR results showed the presence of the three isoforms of the ERR family (ERR alpha, ERR beta and ERR gamma) that were coexpressed with ERs in all vaginal tissue samples examined. The ERR alpha and ERR-gamma mRNA levels decreased from normal vagina of the pre-menopausal women to atrophic vaginal tissue in post-menopausal women. This trend was also observed for the ER beta subtype. Conclusions: The ERRs, such as ERs, are present in human vagina at the mRNA level and the cessation of ovarian estrogen secretion, that is the key event during the post-menopause, may be linked to ER beta, ERR alpha and ERR gamma mRNA decline in human vaginal mucosa. These findings may provide a biological rationale for the clinical susceptibility of the post-menopausal vagina to local estrogen treatment. (c) 2008 Published by Elsevier Ireland Ltd
p38alpha is required for ovarian cancer cell metabolism and survival
No full textIntroduction: Ovarian cancer is highly sensitive to chemotherapy but also shows a high rate of recurrence and drug resistance. These negative outcomes mostly depend on altered apoptotic pathways, making the design of new therapeutic strategies based on the induction of other types of cell death highly desirable. Several lines of research are now addressing cancer-specific features to specifically target tumor cells, thus reducing adverse effects. In this light, a great deal of attention has been devoted to the metabolic reprogramming occurring in cancer cells, which display increased levels of glycolysis compared with their normal counterparts. We recently showed that inhibition of p38 alpha impairs key metabolic functions of colorectal cancer cells, inducing growth arrest, autophagy, and cell death both in vivo and in vitro. These effects are mediated by a switch from hypoxia-inducible factor 1 alpha (HIF1 alpha) to forkhead transcription factor O (Fox)-dependent transcription. Methods: We first characterized p38 expression in OVCAR-3, A2780, and SKOV-3 ovarian cancer cell lines. Then, we treated these cells with the p38 alpha/p38A-specific inhibitor SB202190 and performed a morphological, proliferation, and survival analyses. Finally, we studied HIF1 alpha and FoxO3A expressions and signaling pathways to evaluate their role in SB202190-induced effects. Results: p38 alpha blockade induces the formation of intracellular autophagic vacuoles and reduces growth and viability of ovarian cancer cells. As in colorectal cancer, the underlying molecular mechanism seems to rely on a shift from HIF1 alpha- to FoxO3A-dependent transcription, which is promoted by the activation of the adenosine monophosphate-activated protein kinase pathway. Conclusions: These data corroborate the hypothesis that pharmacological modulation of genes involved in cancer-specific homeostasis, such as p38 alpha, might be exploited to design new therapeutic approaches to cancer treatment
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