Gastrointestinal stromal tumours(GISTs) are mesen-chymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential...Gastrointestinal stromal tumours(GISTs) are mesen-chymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential of GISTs is variable ranging from small lesions with a benign behaviour to fatal sarcomas. The majo-rity of the tumours stain positively for the CD-117(KIT) and discovered on GIST-1(DOG-1 or anoctamin 1) expression, and they are characterized by the presence of a driver kinase-activating mutation in either KIT or platelet-derived growth factor receptor α. Although surgery is the primary modality of treatment, almost half of the patients have disease recurrence following surgery, which highlights the need for an effective adjuvant therapy. Traditionally, GISTs are considered chemotherapy and radiotherapy resistant. With the advent of targeted therapy(tyrosine kinase inhibitors), there has been a paradigm shift in the management of GISTs in the last decade. We present a comprehensive review of targeted therapy in the management of GISTs.展开更多
There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific wit...There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific with reduced toxicity leading to further increases in patients' overall survival; the ongoing progress in understanding recurrence, resistant and spread also needs to be maintained. Better understanding of breast cancer pathology, molecular biology and progression as well as identification of some of the underlying factors involved in breast cancer tumourgenesis and metastasis has led to the identification of novel therapeutic targets. Over a number of years interest has risen in breast tumour kinase(Brk) also known as protein tyrosine kinase 6; the research field has grown and Brk has been described as a desirable therapeutic target in relation to tyrosine kinase inhibition as well as disruption of its kinase independent activity. This review will outline the current "state of play" with respect to targeted therapy for breast cancer, as well as discussing Brk's role in the processes underlying tumour development and metas-tasis and its potential as a therapeutic target in breast cancer.展开更多
Objective:To compare the protein patterns from the extracts of the mutant clone T9/94-M1-1(b3)induced by pyrimethamine,and the original parent clone T9/94 following separation of parasite extracts by two-dimensional e...Objective:To compare the protein patterns from the extracts of the mutant clone T9/94-M1-1(b3)induced by pyrimethamine,and the original parent clone T9/94 following separation of parasite extracts by two-dimensional electrophoresis(2-DE).Methods:Proteins were solubilized and separated according to their charges and sizes.The separated protein spots were then detected by silver staining and analyzed for protein density by the powerful image analysis software.Results:Differentially expressed protein patterns(up—or down-regulation)were separated from the extracts from the two clones.A total of 223 and 134 protein spots were detected from the extracts of T9/94 and T9/94-M1-1(b3)clones,respectively.Marked reduction in density of protein expression was observed with the extract from the mutant(resistant)clone compared with the parent(sensitive)clone.A total of 25 protein spots showed at least two-fold difference in density,some of which exhibited as high as ten-fold difference.Conclusions:These proteins may be the molecular targets of resistance of Plasmodium falciparum to pyrimethamine.Further study to identify the chemical structures of these proteins by mass spectrometry is required.展开更多
Heat shock protein (HSP) is a kind of protein that mainly acts as a molecular chaperone to participate in the synthesis and folding of proteins, maintain the spatial conformation of proteins and protect cells from dam...Heat shock protein (HSP) is a kind of protein that mainly acts as a molecular chaperone to participate in the synthesis and folding of proteins, maintain the spatial conformation of proteins and protect cells from damage and other important biological functions. HSP90 plays an important role in maintaining molecular chaperone structure, regulating cell cycle and apoptosis, coordinating hormone signal transduction and promoting wound healing. And HSP90 also plays an important role in the occurrence and progression of tumors. In recent years, HSP90 inhibitors have made some achievements in molecular targeted therapy for malignant tumors, but further research is needed in clinical application. In this paper, the research status of the relationship between hepatocellular carcinoma targeted by heat shock protein 90 was reviewed.展开更多
目的:运用计算机辅助药物设计寻找川芎抗血栓活性成分。方法:以"血栓症"为关键词,从治疗靶蛋白数据库中搜索筛选川芎抗血栓靶蛋白;再从蛋白质数据库中查询目标靶蛋白并下载其三维结构,采用蛋白质预处理工具确定活性区域中心坐...目的:运用计算机辅助药物设计寻找川芎抗血栓活性成分。方法:以"血栓症"为关键词,从治疗靶蛋白数据库中搜索筛选川芎抗血栓靶蛋白;再从蛋白质数据库中查询目标靶蛋白并下载其三维结构,采用蛋白质预处理工具确定活性区域中心坐标,应用PyRx和Discovery Studio Visualizer软件对从台湾中医药资料库下载的247个川芎小分子与靶蛋白进行分子对接,通过结合能筛选出活性成分并分析结合作用力。结果:筛选出4个活性成分即新绿原酸、1-H-苯并咪唑-2-胺、3,8-二羟基酰内酯、川芎三萜,其分别与凝血酶、抗凝血酶Ⅲ、凝血因子Ⅹa、血栓调节蛋白具有较高结合活性,结合能分别为-6.1、-4.5、-7.7、-8.6 k J/mol;分析结果显示范德华力、静电作用力在对接中发挥着重要作用。结论:新绿原酸、1-H-苯并咪唑-2-胺、3,8-二羟基酰内酯、川芎三萜可能是中药川芎抗血栓的活性成分。展开更多
文摘Gastrointestinal stromal tumours(GISTs) are mesen-chymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential of GISTs is variable ranging from small lesions with a benign behaviour to fatal sarcomas. The majo-rity of the tumours stain positively for the CD-117(KIT) and discovered on GIST-1(DOG-1 or anoctamin 1) expression, and they are characterized by the presence of a driver kinase-activating mutation in either KIT or platelet-derived growth factor receptor α. Although surgery is the primary modality of treatment, almost half of the patients have disease recurrence following surgery, which highlights the need for an effective adjuvant therapy. Traditionally, GISTs are considered chemotherapy and radiotherapy resistant. With the advent of targeted therapy(tyrosine kinase inhibitors), there has been a paradigm shift in the management of GISTs in the last decade. We present a comprehensive review of targeted therapy in the management of GISTs.
文摘There have been significant improvements in the detection and treatment of breast cancer in recent decades. However, there is still a need to develop more effective therapeutic techniques that are patient specific with reduced toxicity leading to further increases in patients' overall survival; the ongoing progress in understanding recurrence, resistant and spread also needs to be maintained. Better understanding of breast cancer pathology, molecular biology and progression as well as identification of some of the underlying factors involved in breast cancer tumourgenesis and metastasis has led to the identification of novel therapeutic targets. Over a number of years interest has risen in breast tumour kinase(Brk) also known as protein tyrosine kinase 6; the research field has grown and Brk has been described as a desirable therapeutic target in relation to tyrosine kinase inhibition as well as disruption of its kinase independent activity. This review will outline the current "state of play" with respect to targeted therapy for breast cancer, as well as discussing Brk's role in the processes underlying tumour development and metas-tasis and its potential as a therapeutic target in breast cancer.
基金Supported by the Thailand Research Fund(TRF),Rachadaphisck Sompok Research FundChulalongkorn University,the National Research University(NRU)Project of ThailCHE-RES Project,Office of Higher Education Commissionand Ministry of Education of Thailand
文摘Objective:To compare the protein patterns from the extracts of the mutant clone T9/94-M1-1(b3)induced by pyrimethamine,and the original parent clone T9/94 following separation of parasite extracts by two-dimensional electrophoresis(2-DE).Methods:Proteins were solubilized and separated according to their charges and sizes.The separated protein spots were then detected by silver staining and analyzed for protein density by the powerful image analysis software.Results:Differentially expressed protein patterns(up—or down-regulation)were separated from the extracts from the two clones.A total of 223 and 134 protein spots were detected from the extracts of T9/94 and T9/94-M1-1(b3)clones,respectively.Marked reduction in density of protein expression was observed with the extract from the mutant(resistant)clone compared with the parent(sensitive)clone.A total of 25 protein spots showed at least two-fold difference in density,some of which exhibited as high as ten-fold difference.Conclusions:These proteins may be the molecular targets of resistance of Plasmodium falciparum to pyrimethamine.Further study to identify the chemical structures of these proteins by mass spectrometry is required.
文摘Heat shock protein (HSP) is a kind of protein that mainly acts as a molecular chaperone to participate in the synthesis and folding of proteins, maintain the spatial conformation of proteins and protect cells from damage and other important biological functions. HSP90 plays an important role in maintaining molecular chaperone structure, regulating cell cycle and apoptosis, coordinating hormone signal transduction and promoting wound healing. And HSP90 also plays an important role in the occurrence and progression of tumors. In recent years, HSP90 inhibitors have made some achievements in molecular targeted therapy for malignant tumors, but further research is needed in clinical application. In this paper, the research status of the relationship between hepatocellular carcinoma targeted by heat shock protein 90 was reviewed.
文摘目的:运用计算机辅助药物设计寻找川芎抗血栓活性成分。方法:以"血栓症"为关键词,从治疗靶蛋白数据库中搜索筛选川芎抗血栓靶蛋白;再从蛋白质数据库中查询目标靶蛋白并下载其三维结构,采用蛋白质预处理工具确定活性区域中心坐标,应用PyRx和Discovery Studio Visualizer软件对从台湾中医药资料库下载的247个川芎小分子与靶蛋白进行分子对接,通过结合能筛选出活性成分并分析结合作用力。结果:筛选出4个活性成分即新绿原酸、1-H-苯并咪唑-2-胺、3,8-二羟基酰内酯、川芎三萜,其分别与凝血酶、抗凝血酶Ⅲ、凝血因子Ⅹa、血栓调节蛋白具有较高结合活性,结合能分别为-6.1、-4.5、-7.7、-8.6 k J/mol;分析结果显示范德华力、静电作用力在对接中发挥着重要作用。结论:新绿原酸、1-H-苯并咪唑-2-胺、3,8-二羟基酰内酯、川芎三萜可能是中药川芎抗血栓的活性成分。
