RESUMO
Metastatic disease is the leading cause of death due to prostate cancer (PCa). Although the hypermethylated in cancer 1 (HIC1) gene has been observed to be epigenetically modified in PCa, its intrinsic role and mechanism in PCa metastasis still remain uncertain. Here, we show that hypermethylation of the HIC1 promoter markedly reduces its suppressive function in metastatic PCa tissues as compared with primary and adjacent normal prostate tissues, and is associated with poor patient survival. PCas in cancer-prone mice homozygous for a prostate-targeted Hic1 conditional knockout showed stronger metastatic behaviour than those in heterozygous mice, as a result of epithelial-mesenchymal transition (EMT). Moreover, impairment of HIC1 expression in PCa cells induced their migration and metastasis through EMT, by enhancing expression of Slug and CXCR4, both of which are critical to PCa metastasis; the CXCL12-CXCR4 axis promotes EMT by activating the extracellular signal-regulated kinase (ERK) 1/2 pathway. Taken together, our results suggest that evaluation of HIC1-CXCR4-Slug signalling may provide a potential predictor for PCa aggressiveness. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Assuntos
Transição Epitelial-Mesenquimal/genética , Fatores de Transcrição Kruppel-Like/genética , Neoplasias da Próstata/genética , Animais , Quimiocina CXCL12/metabolismo , Metilação de DNA , DNA de Neoplasias/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Fatores de Transcrição Kruppel-Like/deficiência , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Metástase Neoplásica , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Prognóstico , Regiões Promotoras Genéticas , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptores CXCR4/metabolismo , Transdução de Sinais/fisiologia , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/fisiologia , Células Tumorais CultivadasRESUMO
OBJECTIVE: To study the water soluble constituents from Amomum villosum. METHOD: The constituents were separated and purified with chromatographic methods, identified by NMR, MS, UV and IR. RESULT: Two quercetin glycosides: quercitrin (quercetin-3-O-alpha-L-rhamnoside I) and isoquercitrin (quercetin-3-O-beta-D-glucoside II) were isolated and identified. CONCLUSION: I and II were isolated for the first time from A. villosum.
Assuntos
Amomum/química , Plantas Medicinais/química , Quercetina/análogos & derivados , Quercetina/isolamento & purificação , Frutas/química , Quercetina/químicaRESUMO
OBJECTIVE: To explore the therapeutic schemes for refractory ascites of advanced schistosomiasis. METHODS: The advanced schistosomiasis patients with refractory ascites were randomly divided into 4 groups: a conventional group, high-dose albumin group, high-dose diuretic group, and comprehensive group, and the course of the treatment was 4 weeks. The abdominal circumference, urine volume, and weight changes were observed daily, and B-ultrasound, liver function, and renal function were performed weekly. RESULTS: In the total effective rates, recurrence rates and A/G and renal function changes, the high-dose albumin group and comprehensive group were superior to the conventional group and high-dose diuretic group (P < 0.01). The death rate of the comprehensive group was the lowest among the 4 groups. CONCLUSION: The therapeutic scheme of the comprehensive group is optimum.
Assuntos
Albuminas/uso terapêutico , Ascite/tratamento farmacológico , Diuréticos/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Esquistossomose/complicações , Adulto , Ascite/etiologia , Feminino , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-IdadeRESUMO
Recently, the succinate dehydrogenase subunit D (SDHD) gene has been reported as one of the major susceptibility genes for pheochromocytoma (PCC) and paraganglioma (PGL). In addition, loss of heterozygosity (LOH) on chromosome 11, mainly in 11q23 and 11q13, is observed frequently in PGL. Based on the fact that mutation frequency of the SDHD gene is less than that of allelic loss at chromosome11q, where the SDHD gene is located, this region may contain other candidate tumor-suppressor genes involved in pathogenesis of PCC/PGL. The tumor-suppressor gene Men1 located in 11q13 is responsible for multiple endocrine neoplasia type 1 (Men1). However, the involvement of the Men1 gene in tumorigenesis of sporadic PCC/PGL is yet to be determined. To understand the roles of the two tumor-suppressor genes and LOH on chromosome 11q in Chinese patients with sporadic PCC or PGL, we performed mutation detection of the SDHD and Men1 genes in tumors from 35 Chinese patients with PCC/PGL; we also did LOH analysis at chromosome 11q for 25 patients out of the 35. No mutation was found in all of 35 patients. However, LOH was detected at one or more loci in 11 of the 25 (44%) tumor samples. The highest frequency of LOH occurred at D11S2006 (41%). Our results suggested that mutation in SDHD or Men1 gene was not found in Chinese patients with sporadic PCC/PGL. However the loss of chromosome 11q might be critical in development of PCC or PGL.