Background and aims: Radiation therapy of abdominal and pelvic solid tumours results in late intestinal toxicity of a severe nature in approximately 5%of cases. These manifestations may include ischaemia and stricture...Background and aims: Radiation therapy of abdominal and pelvic solid tumours results in late intestinal toxicity of a severe nature in approximately 5%of cases. These manifestations may include ischaemia and stricture formation,which may present as “webs". These webs are likely to play a role in the pathogenesis of recurrent bowel obstruction. The mechanisms of microvascular injury to the bowel in the setting of radiation have not been defined. We hypothesised that microvascular dysfunction with impaired vasodilation to acetylcholine (Ach) would be a n acquired pathophysiological abnormality in radiation and “web" formation. Met hods: A 40 year old patient treated with radiation, two years previously, for an anal squamous cell cancer presented with recurrent small bowel obstruction. “W ebs" in the distal ileum were detected using wireless capsule endoscopy, after s mall bowel barium radiographs failed to demonstrate a lesion. Following resectio n, freshly isolated 50-150 μmdiameter arterioles from the “web" and adjacent normal calibre bowel were analysed with histology and microvessel physiological studies. Results: After constriction (30-50%) with endothelin, dilation to gra ded doses of Ach (10-9-10-4 M) was observed in vessels dissected from the str icture and the adjacent normal calibre area. Ach dilation was reduced in vessels from “web" (mean diameter 7 (2)%; n = 3, p < 0.01) compared with the adjacent unaffected bowel (mean diameter 85 (5)%). Dihydroethidine and dichlorofluoresc ein diacetate intravital staining demonstrated increased reactive oxygen species production in microvessels from “web" compared with adjacent normal calibre bo wel. Histology from the structured bowel demonstrated narrowing of the arterial lumen due to intimal and muscularis propria fibrosis, with endothelial preservat ion. Conclusions: External radiation is associated with acquired microvascular e ndothelial dysfunction and “web" formation in the small bowel.展开更多
The striking gender disparity observed in the incidence of hepatocellutar carcinoma （HCC） suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise ro...The striking gender disparity observed in the incidence of hepatocellutar carcinoma （HCC） suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor （ER） and androgen receptor （AR） in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro, in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC.展开更多
文摘Background and aims: Radiation therapy of abdominal and pelvic solid tumours results in late intestinal toxicity of a severe nature in approximately 5%of cases. These manifestations may include ischaemia and stricture formation,which may present as “webs". These webs are likely to play a role in the pathogenesis of recurrent bowel obstruction. The mechanisms of microvascular injury to the bowel in the setting of radiation have not been defined. We hypothesised that microvascular dysfunction with impaired vasodilation to acetylcholine (Ach) would be a n acquired pathophysiological abnormality in radiation and “web" formation. Met hods: A 40 year old patient treated with radiation, two years previously, for an anal squamous cell cancer presented with recurrent small bowel obstruction. “W ebs" in the distal ileum were detected using wireless capsule endoscopy, after s mall bowel barium radiographs failed to demonstrate a lesion. Following resectio n, freshly isolated 50-150 μmdiameter arterioles from the “web" and adjacent normal calibre bowel were analysed with histology and microvessel physiological studies. Results: After constriction (30-50%) with endothelin, dilation to gra ded doses of Ach (10-9-10-4 M) was observed in vessels dissected from the str icture and the adjacent normal calibre area. Ach dilation was reduced in vessels from “web" (mean diameter 7 (2)%; n = 3, p < 0.01) compared with the adjacent unaffected bowel (mean diameter 85 (5)%). Dihydroethidine and dichlorofluoresc ein diacetate intravital staining demonstrated increased reactive oxygen species production in microvessels from “web" compared with adjacent normal calibre bo wel. Histology from the structured bowel demonstrated narrowing of the arterial lumen due to intimal and muscularis propria fibrosis, with endothelial preservat ion. Conclusions: External radiation is associated with acquired microvascular e ndothelial dysfunction and “web" formation in the small bowel.
文摘The striking gender disparity observed in the incidence of hepatocellutar carcinoma （HCC） suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor （ER） and androgen receptor （AR） in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro, in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC.
