Gastrointestinal stromal tumors (GIST) are an uncommon group of tumors of mesenchymal origin. GIST of the anal canal is extremely rare. At present, only 10 cases of c-kit positive anal GIST have been reported in the l...Gastrointestinal stromal tumors (GIST) are an uncommon group of tumors of mesenchymal origin. GIST of the anal canal is extremely rare. At present, only 10 cases of c-kit positive anal GIST have been reported in the literature. There is no widely accepted treatment approach for this neoplasia. Literature is sparse on imaging evaluation of anal canal GIST, usually described as a lesion in the intersphincteric space. We describe the case of a 73-year-old man with a mass in the anal canal, and no other symptoms. Endoanal ultrasound and magnetic resonance imaging showed a well circumscribed solid nodule in the intersphincteric space. The patient was treated by local excision. Gross pathological examination showed a 7 cm × 3.5 cm × 3 cm mass, and histological examination showed a proliferation of spindle cells, with prominent nuclear palisading. The mitotic count was of 12 mitoses/50 HPF. The tumor was positive for KIT protein, CD34 and vimentin in the majority of cells, and negative for desmin and S100. A diagnosis of GIST, with high risk aggressive behavior was made. An abdomino-perineal resection was discussed, but refused. The follow-up included clinical evaluation and anal ultrasound. After 5 years the patient is well, with maintained continence and no evidence of local recurrence.展开更多
The pharmaceutical compounds were analyzed in 14 sampling sites and pointed out the pollution sources related to raw sewage input and urban drainage discharge. Five medicine compounds, one illicit drug, and its metabo...The pharmaceutical compounds were analyzed in 14 sampling sites and pointed out the pollution sources related to raw sewage input and urban drainage discharge. Five medicine compounds, one illicit drug, and its metabolite were the higher measured content using analytical improvements tailored to identify and quantify organic compounds in low water content. The use of SPE cartridges followed by liquid chromatography with tandem mass spectrometry (LC-ESI-MS/MS) points out the Guavirutuba tributary as the primary water pollution source with higher concentrations in 2011 for pharmaceuticals, cocaine, and benzoylecgonine (metabolite) in the range of 6.7 ± 0.9 ng L-1 to 27.386 ± 142 ng L-1. The Jaceguay stream also located in Guarapiranga was the most preserved area and provided analytical values correspondent which lowered contamination content. Such concentrations mean a possible and feasible water restoration target. The most common compounds (above 90% samples) were: caffeine, atenolol, carbamazepine, cocaine, and benzoylecgonine. The integrated risk index for aquatic chemical pollution (IRICAP) confirms the higher contamination near Guavirutuba stream and the lower near the Jaceguay stream. Published results of cocaine and benzoylecgonine content in Guarapiranga basin corroborated with the analytical results.展开更多
The mammalian carboxylesterase 1(Ces1/CES1)family comprises several enzymes that hydrolyze many xenobiotic chemicals and endogenous lipids.To investigate the pharmacological and physiological roles of Ces1/CES1,we gen...The mammalian carboxylesterase 1(Ces1/CES1)family comprises several enzymes that hydrolyze many xenobiotic chemicals and endogenous lipids.To investigate the pharmacological and physiological roles of Ces1/CES1,we generated Ces1 cluster knockout(Ces1^(-/-))mice,and a hepatic human CES1 transgenic model in the Ces1^(-/-)background(TgCES1).Ces1^(-/-)mice displayed profoundly decreased conversion of the anticancer prodrug irinotecan to SN-38 in plasma and tissues.TgCES1 mice exhibited enhanced metabolism of irinotecan to SN-38 in liver and kidney.Ces1 and hCES1 activity increased irinotecan toxicity,likely by enhancing the formation of pharmacodynamically active SN-38.Ces1^(-/-)mice also showed markedly increased capecitabine plasma exposure,which was moderately decreased in TgCES1 mice.Ces1^(-/-)mice were overweight with increased adipose tissue,white adipose tissue inflammation(in males),a higher lipid load in brown adipose tissue,and impaired blood glucose tolerance(in males).These phenotypes were mostly reversed in TgCES1 mice.TgCES1 mice displayed increased triglyceride secretion from liver to plasma,together with higher triglyceride levels in the male liver.These results indicate that the carboxylesterase 1 family plays essential roles in drug and lipid metabolism and detoxification.Ces1^(-/-)and TgCES1 mice will provide excellent tools for further study of the in vivo functions of Ces1/CES1 enzymes.展开更多
文摘Gastrointestinal stromal tumors (GIST) are an uncommon group of tumors of mesenchymal origin. GIST of the anal canal is extremely rare. At present, only 10 cases of c-kit positive anal GIST have been reported in the literature. There is no widely accepted treatment approach for this neoplasia. Literature is sparse on imaging evaluation of anal canal GIST, usually described as a lesion in the intersphincteric space. We describe the case of a 73-year-old man with a mass in the anal canal, and no other symptoms. Endoanal ultrasound and magnetic resonance imaging showed a well circumscribed solid nodule in the intersphincteric space. The patient was treated by local excision. Gross pathological examination showed a 7 cm × 3.5 cm × 3 cm mass, and histological examination showed a proliferation of spindle cells, with prominent nuclear palisading. The mitotic count was of 12 mitoses/50 HPF. The tumor was positive for KIT protein, CD34 and vimentin in the majority of cells, and negative for desmin and S100. A diagnosis of GIST, with high risk aggressive behavior was made. An abdomino-perineal resection was discussed, but refused. The follow-up included clinical evaluation and anal ultrasound. After 5 years the patient is well, with maintained continence and no evidence of local recurrence.
文摘The pharmaceutical compounds were analyzed in 14 sampling sites and pointed out the pollution sources related to raw sewage input and urban drainage discharge. Five medicine compounds, one illicit drug, and its metabolite were the higher measured content using analytical improvements tailored to identify and quantify organic compounds in low water content. The use of SPE cartridges followed by liquid chromatography with tandem mass spectrometry (LC-ESI-MS/MS) points out the Guavirutuba tributary as the primary water pollution source with higher concentrations in 2011 for pharmaceuticals, cocaine, and benzoylecgonine (metabolite) in the range of 6.7 ± 0.9 ng L-1 to 27.386 ± 142 ng L-1. The Jaceguay stream also located in Guarapiranga was the most preserved area and provided analytical values correspondent which lowered contamination content. Such concentrations mean a possible and feasible water restoration target. The most common compounds (above 90% samples) were: caffeine, atenolol, carbamazepine, cocaine, and benzoylecgonine. The integrated risk index for aquatic chemical pollution (IRICAP) confirms the higher contamination near Guavirutuba stream and the lower near the Jaceguay stream. Published results of cocaine and benzoylecgonine content in Guarapiranga basin corroborated with the analytical results.
基金funded in part by the China Scholarship Council(CSC Scholarship No.201506240145 to Changpei Gan)。
文摘The mammalian carboxylesterase 1(Ces1/CES1)family comprises several enzymes that hydrolyze many xenobiotic chemicals and endogenous lipids.To investigate the pharmacological and physiological roles of Ces1/CES1,we generated Ces1 cluster knockout(Ces1^(-/-))mice,and a hepatic human CES1 transgenic model in the Ces1^(-/-)background(TgCES1).Ces1^(-/-)mice displayed profoundly decreased conversion of the anticancer prodrug irinotecan to SN-38 in plasma and tissues.TgCES1 mice exhibited enhanced metabolism of irinotecan to SN-38 in liver and kidney.Ces1 and hCES1 activity increased irinotecan toxicity,likely by enhancing the formation of pharmacodynamically active SN-38.Ces1^(-/-)mice also showed markedly increased capecitabine plasma exposure,which was moderately decreased in TgCES1 mice.Ces1^(-/-)mice were overweight with increased adipose tissue,white adipose tissue inflammation(in males),a higher lipid load in brown adipose tissue,and impaired blood glucose tolerance(in males).These phenotypes were mostly reversed in TgCES1 mice.TgCES1 mice displayed increased triglyceride secretion from liver to plasma,together with higher triglyceride levels in the male liver.These results indicate that the carboxylesterase 1 family plays essential roles in drug and lipid metabolism and detoxification.Ces1^(-/-)and TgCES1 mice will provide excellent tools for further study of the in vivo functions of Ces1/CES1 enzymes.
