PDGFRA强阳性表达是诊断GIST较为特异性标志

胃肠道间质肿瘤(GIST)是腹腔最常见的间叶性肿瘤,来自于Cajal间质细胞或其前体细胞。大多数GISTs有c-kit癌基因的突变,c-kit(CD117)阳性被认为是诊断GIST的金标准,也是格列为治疗GIST的必要条件。近来研究发现PDGFRA基因突变作为另一个癌变机制可见于部分缺乏c-kit突变的GIST中,然而,PDGFRA免疫组化检测在GIST诊断中的价值还未见报道。作者应用免疫组化方法检测了39例GISTs和20例其它腹腔内间叶性肿瘤中PDGFRA的表达,同时进行了CD117免疫组化染色和PDGFRA和c-kit基因的突变分析。39例GISTs中,胃24例、小肠10例、大…     

DOG1是一种敏感和特异性的胃肠道间质瘤的标记物

胃肠道间质瘤（GIST）是胃肠道最常见的间叶性肿瘤，大多数含有受体酪氨酸激酶基因c-KIT或PDGFRA的活化突变。GIST的诊断主要依赖于免疫组化KIT／CD117蛋白的表达，然而有4％～15％的GIST不表达CD117，导致诊断困难。DOG1是应用基因表达谱技术发现的一种高度表达于GIST的基因，作者采用2种新的鼠单克隆DOGI抗体（DOG1．1和DOG1．3），     

PDGFRA突变的胃肠道间质肿瘤的诊断形态学特征

胃肠道间质肿瘤(GIST)是胃肠道最常见的间叶性肿瘤,其中胃是最常发生的部位。尽管KIT蛋白的表达或c-kit基因突变被证明是诊断GIST的特征性标记,并在其病理发生中起着重要作用,但仍有一部分GIST不表达KIT或c-kit野生型。近来研究发现PDGFRA活化突变在大多数KIT阴性的GIST中被检测到,并发现PDGFRA突变的GIST形态学特征不同于c-kit突变的GIST。为了证实这种发现,作者检测了60例胃GIST中c-kit和PDGFRA的突变状态。60例胃GIST中,男27例,女33例,年龄12~92岁,平均63.8岁,其中仅有1例发生于21岁前。52例有肿瘤大小的记录,直…     

KIT阴性的胃肠道间质肿瘤

胃肠道间质肿瘤 (gastrointestinalstromaltumor,GIST)是消化道最常见的间叶源性肿瘤 ,显示出类似Cajal间质细胞的形态学特点和免疫表型 ,特征性表达KIT蛋白(CD117)。多数GIST具有KIT癌基因突变 ,从而导致细胞增殖。KIT抑制剂伊马替尼 (商品名格列卫 )治疗GIST显效证实了KIT在GIST发病机制中的重要作用。然而 ,某些肿瘤具有GIST的临床病理特征 ,但KIT阴性。这类肿瘤是否真是GIST以及伊马替尼治疗是否有效尚存争议。作者研究了 2 5例具有GIST临床病理特征但KIT免疫组化阴性的肿瘤。此组患者发病年龄 (2 9～ 79岁 )和肿瘤…     

多发性胃肠道间质瘤

胃肠道间质瘤（GISTs）起源于转化的肿瘤性前驱Cajal间质细胞（ICC），是最常见的胃肠道间叶性肿瘤。多发性胃肠道间质瘤（GISTs）罕见，通常合并神经纤维瘤病1型和家族性GIST。在GISTs的肿瘤形成过程中，KIT和PDGFRA的激活似乎是主要的肿瘤形成事件。CD117免疫组化测定KIT蛋白表达，几乎是GISTs和KIT突变的诊断标准，见于60％-90％病例，但其预后意义尚未充分阐明。[第一段]     

野生型胃肠道间质瘤研究进展

胃肠道间质瘤(gastrointestinal stromal tumor,GIST)是胃肠道中常见的间叶性肿瘤。经研究证实,大多数肿瘤存在KIT/PDGFRA基因的激活突变。其中,约85%的儿童GIST和10%～15%的成人GIST无KIT/PDGFRA基因突变,其被定义为野生型GIST。该文现对野生型GIST常见突变类型的分子特征、发病机制和治疗进行综述。     

GIST外科治疗新探

GIST(胃肠道间质瘤)是一类特殊的,通常CD117免疫表型阳性的胃肠道最常见的间叶源性肿瘤.组织学上由梭形细胞、上皮样细胞、偶或多形性细胞排列成束状或弥漫状图像,免疫表型上表达c-kit基因蛋白产物KIT,由突变的c-kit或血小板源生长因子受体(PDGFRA)基因驱动.本文主要运用文献资料法、逻辑推理法以及笔者多年工作经验,针对GIST外科治疗进行论述,希望能进一步促进GIST治疗手段的进步.     

c-kit基因分析在胃肠间质瘤病理诊断和靶向药物治疗中的应用

胃肠间质瘤（gastrointestinal stromal tumors,GIST）是消化道最常见的问叶性肿瘤。c-kit基因的过表达被视为是诊断GIST非常重要的指标之一。c-kit基因过表达是由于c-kit基因发生获得性功能突变,属于激活型或致瘤性突变,引起c-kit基因蛋白自动磷酸化,进而激活下游信号转导蛋白发生磷酸化,对细胞增殖、凋亡和黏附发挥调节作用。     

胃肠道恶性间质瘤的临床病理分析

目的探讨胃肠道恶性间质瘤(GIST)的临床病理特征. 方法分析了6例GIST的临床及病理特征.结果 6例恶性GIST均无消化道梗阻.临床表现无特异性,广泛分布于胃(60%), 小肠(30%)和其它部位(10%),10%～30%GIST是恶性的,表现为腹腔内的扩散或肝转移; 常规病理学检查,GIST与平滑肌瘤/肉瘤等其它类型的梭形细胞肿瘤不易区别,确诊需要免疫组化或/和电镜检查;免疫组化CD34(+),Vimenti(+),Desmin(-),Actin (-) , S-100(-);恶性GIST应行根治性手术,影响预后的因素较多.结论 GIST具有独特免疫组化表型,是有别于平滑肌肿瘤的一类成分复杂的间叶性肿瘤.     

发生于儿童和年轻人胃部的胃肠道间质肿瘤

胃肠道间质肿瘤(GIST)是指主要发生于胃肠道,KIT或PDGFRA阳性的间质肿瘤,特异性表达KIT。约60%发生于胃部,成人多见,绝大多数患者出现功能型KIT或PDGFRA突变,但在儿童或年轻人中,该病的临床病理及分子遗传学特征尚不明确。作者选取44例21岁以下胃部GIST病例,其中女性32例(8～21     

Dose-guided radiotherapy for lung tumors

The transit in vivo dosimetry performed by an electronic portal imaging device (EPID) is a very practical method to check error sources in radiotherapy. Recently, the present authors have developed an in vivo dosimetry method based on correlation functions, F (w, L), defined as the ratio between the transit signal, S _t (w, L), by the EPID and the mid-plane dose, D _m (w, L), in a solid water phantom as a function of the phantom thickness, w, and of the field dimensions, L. In particular, generalized correlation functions F (w, L) for 6, 10 and 15 MV X-ray beams supplied by a pilot Varian linac, are here used by other three linacs operating in two centers. This way the workload, due to measurements in solid water phantom, needed to implement the in vivo dosimetry method was avoided. This article reports a feasibility study on the potentiality of this procedure for the adaptive radiotherapy of lung tumors treated by 3D conformal radiotherapy techniques. In particular, the dose reconstruction at the isocenter point D _iso in the lung tumor has been used as dose-guided radiotherapy (DGRT), to detect the inter-fraction tumor anatomy variations that can require new CT scans and an adaptive plan. When a difference greater than 6% between the predicted dose by the treatment planning system (TPS), D _iso,TPS and the D _iso was observed, the clinical action started to detect possible anatomical lung tumor changes. Twelve over twenty patients examined presented in vivo dose discrepancies due to the tumor morphological changes during treatments, and these results were successively confirmed by new CT scans. In this work, for a patient that showed for all beams, D _iso values over the tolerance level, the new CT scan was used for an adaptive plan. The lung dose volume histogram for D _iso,TPS = 2 Gy per fraction suggested the adaptive plan. In particular, the lung volume included in 2 Gy increased from 350 cm³ of the original plan to 550 cm³ of the hybrid plan, while for the adaptive plan the lung volume included in 2 Gy decreased to 15 cm³. Moreover, the mean doses to the organs at risk were reduced to 70%. The results of this research show that the DGRT procedure by the D _iso reconstruction, integrated with radiological imaging, was feasible for periodic investigation on morphological lung tumor changes. This feasibility study takes into account the accuracy of two algorithms based on the pencil beam and collapsed cone convolution models for dose calculations where large density inhomogeneities are present.     

抗肿瘤血管生成主动免疫治疗研究进展

肿瘤血管生成在肿瘤生长、侵袭、转移中具有十分重要的作用。调控血管生成的因子很多,包括血管内皮细胞生长因子（VEGF）、成纤维细胞生长因子（FGF）、表皮细胞生长因子（EGF）等。近年来抗血管生成的肿瘤治疗已经取得较大进展,特别是抗肿瘤血管形成主动免疫治疗,已经成为抗肿瘤研究的热点。因而,以异种同源分子和非异种同源分子为疫苗的研究很有意义。     

Gene therapy for pituitary tumors

Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas.     

Suicide gene therapy for pediatric tumors

Tumor gene therapy is potentially very specific and efficacious. Suicide genes are promising tools in the arsenal of tumor gene therapy. However, problems of tumor targeting, low in vivo efficacy of nucleic acid transfer, and recent reports of adverse effects hinder the translation of this approach into clinical practice. Therefore vector design, tumor targeting, mechanisms of cell kill and killing of untransfected tumor cells must be improved. Once these problems are solved in vitro and in animal models, gene therapy holds great promise for pediatric oncology given the abundance of specific targets in pediatric tumors. This review describes the current state of preclinical research in tumor suicide gene therapy, provides an outline of pediatric suicide gene therapy protocols, and identifies potential targets in pediatric malignancies.     

Testing tumors for microsatellite instability.

The methods for determining microsatellite instability in tumors are highly heterogeneous. Recently a 5-marker panel of microsatellites was suggested for this purpose. In this review attention is drawn to the fact that microsatellite instability can be assessed by analyzing tumor DNA with a single marker, BAT-26, and that normal tissue DNA from the same individual needs to be analyzed only when an aberrant allele is seen in the tumor. Whilst this simple procedure does not distinguish between different types and degrees of instability, it should be sufficient for many purposes, such as screening colorectal cancers for mismatch repair deficiency.