AIM： To examine the impact of imatinib mesylate （Glivec） on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status. METHODS： Thirty-three of 74 （4...AIM： To examine the impact of imatinib mesylate （Glivec） on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status. METHODS： Thirty-three of 74 （44.6%） small bowel gastrointestinal stromal tumor （GIST） patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients. Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients. Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or plateletderived growth factor alpha （PDGFRA）. The mutation type was correlated with clinical outcomes. The antitumor effect and safety of Glivec in group B patients were also assessed. RESULTS： Advanced small bowel GIST patients treated with Glivec had substatntially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response （PR） （67.8%）. Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate （PR） was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate （ORR） of 66.7% （not significant）. CONCLUSION： Glivec significantly prolongs the postrecurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients withadvanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs. There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.展开更多
This review evaluates the role of Glivec in the treatment of chronic myelogenous leukemia and other malignant tumors. Preclinical and clinical evidence showed that Glivec demonstrated a potent and specific inhibition...This review evaluates the role of Glivec in the treatment of chronic myelogenous leukemia and other malignant tumors. Preclinical and clinical evidence showed that Glivec demonstrated a potent and specific inhibition on BCR-ABL positive leukemias and other malignant tumors in which overexpression of c-kit and PDGFR-b played a major role in their pathogenesis. Glivec has induced complete hematologic responses in up to 98% of patients evaluated in clinical trials. It's a very successful drug that supported the idea of targeted therapy through inhibition of tyrosine kinases. Although it's still in the early stages of clinical development and the resistance to Glivec remains to be a problem needed further study, a great deal has been learned from these research and observation. And with the increasing data, molecular targeting therapy will play much more important role in the treatment of malignant tumors. With the better understanding of the pathogenesis of malignant tumors, well-designed drugs targeting the specific molecular abnormalities with higher efficacy and lower side effect will benefit numerous patients with malignant tumors.展开更多
目的:观察在体外环境中使用ICCs(Interstitial cells of Cajal,ICCs)样细胞表面c-kit受体抑制剂Glivec后,豚鼠逼尿肌自主收缩活动的变化,探讨逼尿肌中ICCs样细胞的作用。方法:制作豚鼠膀胱逼尿肌肌条,并在Kreb液中孵育,在体外环境中添加...目的:观察在体外环境中使用ICCs(Interstitial cells of Cajal,ICCs)样细胞表面c-kit受体抑制剂Glivec后,豚鼠逼尿肌自主收缩活动的变化,探讨逼尿肌中ICCs样细胞的作用。方法:制作豚鼠膀胱逼尿肌肌条,并在Kreb液中孵育,在体外环境中添加c-kit受体抑制剂Glivec,通过张力换能器输入生理记录仪记录逼尿肌肌条自主收缩活动的变化。结果:与对照组比较,不同剂量Glivec孵育逼尿肌肌条后,逼尿肌肌条收缩幅度明显下降(100μmol/L:547.87±43.00mg,p<0.01,n=15;300μmol/L:197.47±39.20mg,p<0.01,n=15),逼尿肌肌条收缩频率也明显下降(100μmol/L:2.44±0.16次/分,p<0.05,n=15;300μmol/L:1.11±0.17次/分,p<0.01,n=15)。结论:ICCs样细胞在逼尿肌自发收缩中可能充当起搏细胞的角色。展开更多
文摘AIM： To examine the impact of imatinib mesylate （Glivec） on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status. METHODS： Thirty-three of 74 （44.6%） small bowel gastrointestinal stromal tumor （GIST） patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients. Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients. Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or plateletderived growth factor alpha （PDGFRA）. The mutation type was correlated with clinical outcomes. The antitumor effect and safety of Glivec in group B patients were also assessed. RESULTS： Advanced small bowel GIST patients treated with Glivec had substatntially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response （PR） （67.8%）. Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate （PR） was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate （ORR） of 66.7% （not significant）. CONCLUSION： Glivec significantly prolongs the postrecurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients withadvanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs. There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.
基金This work was supported by a grant from Nanjing Science & Technology Foundation.
文摘This review evaluates the role of Glivec in the treatment of chronic myelogenous leukemia and other malignant tumors. Preclinical and clinical evidence showed that Glivec demonstrated a potent and specific inhibition on BCR-ABL positive leukemias and other malignant tumors in which overexpression of c-kit and PDGFR-b played a major role in their pathogenesis. Glivec has induced complete hematologic responses in up to 98% of patients evaluated in clinical trials. It's a very successful drug that supported the idea of targeted therapy through inhibition of tyrosine kinases. Although it's still in the early stages of clinical development and the resistance to Glivec remains to be a problem needed further study, a great deal has been learned from these research and observation. And with the increasing data, molecular targeting therapy will play much more important role in the treatment of malignant tumors. With the better understanding of the pathogenesis of malignant tumors, well-designed drugs targeting the specific molecular abnormalities with higher efficacy and lower side effect will benefit numerous patients with malignant tumors.
文摘目的:观察在体外环境中使用ICCs(Interstitial cells of Cajal,ICCs)样细胞表面c-kit受体抑制剂Glivec后,豚鼠逼尿肌自主收缩活动的变化,探讨逼尿肌中ICCs样细胞的作用。方法:制作豚鼠膀胱逼尿肌肌条,并在Kreb液中孵育,在体外环境中添加c-kit受体抑制剂Glivec,通过张力换能器输入生理记录仪记录逼尿肌肌条自主收缩活动的变化。结果:与对照组比较,不同剂量Glivec孵育逼尿肌肌条后,逼尿肌肌条收缩幅度明显下降(100μmol/L:547.87±43.00mg,p<0.01,n=15;300μmol/L:197.47±39.20mg,p<0.01,n=15),逼尿肌肌条收缩频率也明显下降(100μmol/L:2.44±0.16次/分,p<0.05,n=15;300μmol/L:1.11±0.17次/分,p<0.01,n=15)。结论:ICCs样细胞在逼尿肌自发收缩中可能充当起搏细胞的角色。
