KIT

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  • 文章类型: Journal Article
    胃肠道间质瘤(GIST)是最常见的间充质起源的恶性肿瘤。GIST涵盖广泛的临床范围,从基本上没有转移潜力的肿瘤到恶性和危及生命的传播疾病。KIT或PDGFRA受体酪氨酸激酶中的功能增益突变是大多数GIST的关键驱动因素,在整个疾病过程中负责肿瘤的发生和发展。靶向这些受体的酪氨酸激酶抑制剂的引入大大改善了这种以前化学抗性癌症的结果。截至今天,五种药物获得GIST治疗的监管批准:伊马替尼,舒尼替尼,Regorafenib,里替尼,和阿瓦替尼.这个,反过来,代表了罕见肿瘤的成功。在过去的二十年里,GIST已成为癌症多学科工作的典范模型,考虑到肿瘤生物学和肿瘤进化方面的疾病特异性。在这里,我们回顾了目前可用的GIST管理证据.本临床实践指南是由多学科专家小组(肿瘤学家,病理学家,外科医生,分子生物学家,放射科医生,和代表来自西班牙肉瘤研究小组的患者\'倡导团体),它的构思是为了提供,从批判的角度来看,诊断的标准方法,治疗,和后续行动。
    Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin. GIST spans a wide clinical spectrum that ranges from tumors with essentially no metastatic potential to malignant and life-threatening spread diseases. Gain-of-function mutations in KIT or PDGFRA receptor tyrosine kinases are the crucial drivers of most GISTs, responsible for tumor initiation and evolution throughout the entire course of the disease. The introduction of tyrosine kinase inhibitors targeting these receptors has substantially improved the outcomes in this formerly chemoresistant cancer. As of today, five agents hold regulatory approval for the treatment of GIST: imatinib, sunitinib, regorafenib, ripretinib, and avapritinib. This, in turn, represents a success for a rare neoplasm. During the past two decades, GIST has become a paradigmatic model in cancer for multidisciplinary work, given the disease-specific particularities regarding tumor biology and tumor evolution. Herein, we review currently available evidence for the management of GIST. This clinical practice guideline has been developed by a multidisciplinary expert panel (oncologist, pathologist, surgeon, molecular biologist, radiologist, and representative of patients\' advocacy groups) from the Spanish Group for Sarcoma Research, and it is conceived to provide, from a critical perspective, the standard approach for diagnosis, treatment, and follow-up.
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  • 文章类型: Journal Article
    Gastrointestinal stromal sarcomas (GISTs) are the most common mesenchymal tumours originating in the digestive tract. They have a characteristic morphology, are generally positive for CD117 (c-kit) and are primarily caused by activating mutations in the KIT or PDGFRA genes(1). On rare occasions, they occur in extravisceral locations such as the omentum, mesentery, pelvis and retroperitoneum. GISTs have become a model of multidisciplinary work in oncology: the participation of several specialties (oncologists, pathologists, surgeons, molecular biologists, radiologists…) has forested advances in the understanding of this tumour and the consolidation of a targeted therapy, imatinib, as the first effective molecular treatment in solid tumours. Following its introduction, median survival of patients with advanced or metastatic GIST increased from 18 to more than 60months. Sunitinib and Regorafenib are two targeted agents with worldwide approval for second- and third-line treatment, respectively, in metastatic GIST.
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  • 文章类型: Comparative Study
    丁型肝炎病毒(HDV)是导致暴发性肝炎和肝功能衰竭的原因,并加速了乙型肝炎病毒(HBV)感染患者的肝硬化和肝细胞癌的发展。迄今为止,治疗依赖于长期给予聚乙二醇化α-干扰素,30%的患者有持续的病毒学应答.最近,新,有希望的抗HDV疗法已经被开发出来,并且已经被用于临床试验。HDVRNA病毒载量(HDVL)监测必须是感染患者管理的组成部分。然而,HDV属的特征是具有很高的遗传变异性,分为八种基因型(HDV-1至-8),和大多数可用的内部或商业测定仅对有限的基因型子集有用。此处报道了用于HDVL定量的新试剂盒的性能与2005年开发的法国国家HDV参考实验室的一致内部测定的比较结果。总共611个具有各种HDVL值的所有HDV基因型的临床样本,包括36名患者几年来的连续样本,被研究过。一种特异性,灵敏度,使用HDV阳性临床样本进行可重复性评估,甲型肝炎,B,C和E(HAV,HBV,HCV,HEV,分别)和艾滋病毒单感染样本,和WHOHDVRNA国际标准。两种测定之间的总体结果严格可比(中位数差异,0.07logIU/ml),具有较高的诊断精度和能力。总之,这种新试剂盒在HDVL的检测/定量方面表现出高性能,不管使用的感染菌株的基因型,并且似乎是患者管理的合适工具。
    Hepatitis D virus (HDV) is responsible for fulminant hepatitis and liver failure and accelerates evolution toward cirrhosis and hepatocellular carcinoma in hepatitis B virus (HBV)-infected patients. To date, treatment relies upon long-term administration of pegylated alpha-interferon with a sustained virological response in 30% of the patients. Very recently, new, promising anti-HDV therapies have been developed and are already being used in clinical trials. HDV RNA viral load (HDVL) monitoring must be an integral part of the management of the infected patients. However, HDV genus is characterized by a high genetic variability into eight genotypes (HDV-1 to -8), and most available in-house or commercial assays are useful for only a limited subset of genotypes. Results of a comparison of the performance of a new kit for HDVL quantification with the consensus in-house assay of the French National Reference Laboratory for HDV developed in 2005 are reported here. A total of 611 clinical samples of all HDV genotypes with various HDVL values, including several consecutive samples over several years from 36 patients, were studied. A specificity, sensitivity, and reproducibility evaluation was conducted using HDV-positive clinical samples, hepatitis A, B, C and E (HAV, HBV, HCV, and HEV, respectively) and HIV mono-infected samples, and the WHO HDV RNA international standard. Overall results were strictly comparable between the two assays (median difference, 0.07 log IU/ml), with high diagnosis precision and capacity. In summary, this new kit showed high performance in detection/quantification of HDVL, regardless of the genotype of the infecting strain used, and seems to be a suitable tool for patient management.
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