Sunitinib for Taiwan Residents patients with gastrointestinal stromal tumor after imatinib treatment failure or intolerance

AIM:To report preliminary results of the efficacy and safety of sunitinib in the management of Taiwan Residents gastrointestinal stromal tumors (GIST) patients facing imatinib mesylate (IM) intolerance or failure.METHODS:Between 2001 and May 2010,199 Taiwan Residents patients with metastatic GIST were treated at Chang Gung Memorial Hospital.Among them,23 (11.6%) patients receiving sunitinib were investigated.RESULTS:Sixteen male and 7 female patients with a median age of 59 years (range:24-83 years) received sunitinib.Twenty-two GIST patients changed to sunitinib because of IM failure and 1 because of intolerance.The median duration of sunitinib administration was 6.0 mo (range:2-29 mo).The clinical benefit was 65.2% [2 complete response (CR),4 partial response (PR),and 9 stationary disease (SD);15/23].In 12 patients harboring mutations of the kit gene at exon 11,the clinical benefit rate (CR,PR,and SD) was 75.0% and 6 patients with tumors containing kit exon 9 mutations had a clinical benefit of 50.0% (not significant,P=0.344).The progression free survival (PFS) and overall survival (OS) did not differ between patients whose GISTs had wild type,KIT exon 9,or KIT exon 11 mutations.Hand-foot syndrome was the most common cause of grade Ⅲ adverse effect (26.1%),followed by anemia (17.4%),and neutropenia (13.0%).During the median 7.5-mo follow-up after sunitinib use,the median PFS and OS of these 23 GIST patients after sunitinib treatment were 8.4 and 14.1 mo,respectively.CONCLUSION:Sunitinib appears to be an effective treatment for Taiwan Residents with IM-resistant/intolerant GISTs and induced a sustained clinical benefit in more than 50% of Taiwan Residents advanced GIST patients.

Treatment of patients with advanced gastrointestinal stromal tumor of small bowel: Implications of imatinib mesylate

瞄准：检验 imatinib 的影响耐心的幸存和反应和它的安全上的 mesylate (Glivec ) ，和反应的关联与工具包基因变化地位评价。方法：74 中的 33 个(44.6%) 在药品切除术以后并且不开发了复发的胃肠的基质肿瘤(大意) 病人与 Glivec 对待的小肠是被分类组 A 病人。与 Glivec 对待的 22 个先进的小肠大意病人作为组 B 病人被分类。Clinicopathological 特征，复发以后、全面的幸存率被比较。在组 B 病人的每个肿瘤为工具包或导出血小板的生长因素高山的变化被调查哈(PDGFRA ) 。变化类型与临床的结果被相关。在组 B 病人的 Glivec 的反肿瘤效果和安全也被估计。结果：与 Glivec 对待的先进的小肠大意病人比没与 Glivec 对待的那些有 substatntially 更长的复发以后的幸存和更高全面的幸存率。15 个病人的一个总数有部分回答(PR )(67.8%) 。c 工具包的激活的变化在 19 个测试病人中的 16 个被发现，没有 PDGFRA 异种被识别。在有在 11 个工具包变化上怀有前的大意的 13 个病人，部分反应率(PR ) 是 69.3% ，而有在 9 工具包变化上包含前的肿瘤的三个病人中的二个有 66.7% 的全面反应率(ORR )( 不重要) 。结论：Glivec 显著地与先进大意延长亚洲病人的复发以后、全面的幸存。Glivec 导致持续客观回答在多于有先进的小肠大意的亚洲病人的一半。11 上的工具包前的激活的变化在绝大多数大意是可检测的。在 11 个变化上处于为其大意在 9 上有工具包前的病人和前的 PR 率没有差别。

Advanced gastrointestinal stromal tumor patients with complete response after treatment with imatinib mesylate

瞄准：大多数胃肠的基质肿瘤(大意) 快车组成地激活工具包激酶或导出血小板的生长因素受体高山的变异的 isoforms 哈(PDGFRA ) ，它是为 imatinib mesylate (Glivec ) 的潜在的治疗学的目标。部分反应发生在与 Glivec 对待的几乎三分之二个大意病人。然而，在 Glivec 治疗以后的完全的反应(CR ) 偶发地被报导。这里，我们在 Glivec 治疗以后与 CR 说明了先进大意病人。方法：在 2001 年 1 月和 2005 年 6 月之间， 42 个先进大意病人与 Glivec 被对待。病人们被管理在 100-mg 囊的 Glivec 的 400 mg，每天与食物口头上地拿。到 Glivec 的肿瘤的反应此后在一个月，三个月，和每三个月以后被评估或每当医药需要被显示时。病人的每个肿瘤为工具包或 PDGFRA 的变化被调查。结果：与 Glivec 对待的 42 个先进大意病人的中部的后续时间是 16.9 个月(范围， 1.0-47.0 月) 。总的来说，有的 3 个病人完成反应 CR (7.1%) ， 26 部分反应(67.8%) ， 5 静止疾病(11.9%) ，和 3 进步疾病(11.9%) 。为三个病人的 Glivec 管理的中部的持续时间是 36 个月(范围， 23-36 月) 。在 Glivec 治疗以后的 CR 的中部的时间是 20 个月(范围， 9-26 月) 。11 上的 c 工具包前的删除和插入变化和 9 上的 c 工具包前的插入变化分别地在二种情况和一个案例中被发现。结论：完全的反应(CR ) 能在与 Glivec 对待的选择先进大意病人被完成。在 Glivec 治疗以后的 CR 的中部的时间是 20 个月。11 上的工具包前的删除和插入变化和 9 上的工具包前的插入变化在这些选择盒子中贡献基因特征。

Characterization of a novel rat cholangiocarcinoma cell culture model-CGCCA

AIM:To characterize a culture model of rat CCA cells,which were derived from a transplantable TTA-induced CCA and designated as Chang Gung CCA(CGCCA).METHODS:The CGCCA cells were cultured at in vitro passage 12 times on a culture dish in DMEM medium.To measure the doubling time,103 cells were plated in a 96-well plate containing the growth medium.The cells were harvested 4 to 10 d after seeding,and astandard MTT assay was used to measure the growth.The phenotype of CACCA cell and xenograft was determined by immunohistochemical study.We also determine the chromosomal alterations of CGCCA,G-banding and spectral karyotyping studies were performed.The CGCCA cell line was transplanted into the nude mice for examining its tumorigenicity.2-Deoxy-2-(18F)fluoro-Dglucose(FDG) autoradiography was also performed to evaluate the FDG uptake of the tumor xenograft.RESULTS:The doubling time for the CGCCA cell line was 32 h.After transplantation into nude mice,FDG autoradiography showed that the tumors formed at the cell transplantation site had a latency period of 4-6 wk with high FDG uptake excluding necrosis tissue.Moreover,immunohistochemical staining revealed prominent cytoplasmic expression of c-erb-B2,CK19,c-Met,COX-Ⅱ,EGFR,MUC4,and a negative expression of K-ras.All data confirmed the phenotypic features of the CGCCA cell line coincide with the xenograft mice tumors,indicating cells containing the tumorigenicity of CCA originated from CCA.In addition,karyotypic banding analysis showed that the diploid(2n) cell status combines with ring and giant rod marker chromosomes in these clones;either both types simultaneously appeared or only one type of marker chromosome in a pair appeared in a cell.The major materials contained in the marker chromosome were primarily identified from chromosome 4.CONCLUSION:The current CGCCA cell line may be used as a non-K-ras effect CCA model and to obtain information and reveal novel pathways for CCA.Further applications regarding tumor markers or therapeutic targeting of CCA should be addressed accordingly.

Sporadic somatic mutation of c-kit gene in a family with gastrointestinal stromal tumors without cutaneous hyperpigmentation

没有皮肤的亢奋的色素沉着，我们与胃肠的基质肿瘤(大意) 在一个家庭描述了二个成员。病人是没有皮肤的亢奋的色素沉着的父亲和儿子。组织学的检查证明这些肿瘤是表示 CD34 和 CD117 的大意。从嵌入石蜡的标本提取的肿瘤 DNA 在直接定序分析以后在 11 c 工具包基因上在前在不同鳕鱼 ons 与一个删除变化揭示了体细胞突变。没有细菌线变化在从从父亲和儿子获得的外部白血球提取的 DNA 被检测。我们建议没有细菌线变化和亢奋的色素沉着，大意能被分散的体细胞突变在一个家庭引起。