RESUMO
Antagonists of growth hormone-releasing hormone (GHRH) inhibit the growth of various tumors, including endometrial carcinomas (EC). However, tumoral receptors that mediate the antiproliferative effects of GHRH antagonists in human ECs have not been fully characterized. In this study, we investigated the expression of mRNA for GHRH and splice variants (SVs) of GHRH receptors (GHRH-R) in 39 human ECs and in 7 normal endometrial tissue samples using RT-PCR. Primers designed for the PCR amplification of mRNA for the full length GHRH-R and SVs were utilized. The PCR products were sequenced, and their specificity was confirmed. Nine ECs cancers (23%) expressed mRNA for SV1, three (7.7%) showed SV2 and eight (20.5%) revealed mRNA for SV4. The presence of SVs for GHRH-Rs could not be detected in any of the normal endometrial tissue specimens. The presence of specific, high affinity GHRH-Rs was also demonstrated in EC specimens using radioligand binding studies. Twenty-four of the investigated thirty-nine tumor samples (61.5%) and three of the seven corresponding normal endometrial tissues (42.9%) expressed mRNA for GHRH ligand. Our findings suggest the possible existence of an autocrine loop in EC based on GHRH and its tumoral SV receptors. The antiproliferative effects of GHRH antagonists on EC are likely to be exerted in part by the local SVs and GHRH system.
Assuntos
Processamento Alternativo , Neoplasias do Endométrio , Hormônio Liberador de Hormônio do Crescimento/genética , Receptores de Neuropeptídeos/genética , Receptores de Hormônios Reguladores de Hormônio Hipofisário/genética , Primers do DNA , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/genética , Feminino , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Hormônio Liberador de Hormônio do Crescimento/farmacologia , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: Patients with positive screening results and persistence of high-risk human papillomavirus (HPV) infection represent the population at the highest risk for developing cervical cancer. To describe the epidemiology in this high-risk population, data were collected and analysed at the referral centre for patients with positive cytology. STUDY DESIGN: Between January 1997 and December 2002 the authors performed 3480 virus identifications using the Digene Hybrid Capture system in a female population with positive cytology at cervical cancer screening. Age-specific prevalence data were evaluated and compared between the age groups by running the chi(2) and Pearson chi(2) tests. Subgroup analysis was performed to estimate monthly clearance rates among eligible women with positive HR-HPV results. RESULTS: Low-risk (LR), high-risk (HR) and double infections were detected in 91 cases (2.6%), 1072 cases (30.8%) and 59 cases (1.7%), respectively. A significantly higher incidence of high-, rather than low-risk HPV infections was found in all age groups (p<0.001). Also, in this high-risk population with positive screening a significant decrease was detected in the prevalence of both high- and low-risk infections beyond 35 years of age (p<0.001). However, the decline in the HR-HPV types occurred later than in the case of LR infections, and HR-HPV was of remarkable frequency in the older age groups, which might represent both incidental and prevalent cases. Subgroup analysis for estimating monthly clearance rates revealed no significant differences between the various age groups and between women with various cytology results. CONCLUSIONS: In a population with positive cytology the prevalence of HPV drops with age while the relative frequency of high-risk HPV infection remains at the same level as that of the youngest age group.
