Increased hepatic expression of insulin-like growth factor-Ⅰreceptor in chronic hepatitis C

AIM： Although increased insulin-like growth factor-I receptor （IGF-IR） gene expression has been reported in hepatocellular carcinoma, studies assessing IGF-IR in chronic hepatitis C （CHC） and cirrhosis are scarce. We therefore aimed to evaluate IGF-IR and IGF-I rnRNA expression in liver from patient with CHC. METHODS： IGF-IR and IGF-I rnRNA content were determined by semi-quantitative RT-PCR and IGF-IR protein expression was determined by immunohistochemistry in hepatic tissue obtained from patients with CHC before （34 patients） and after （10 patients） therapy with interferon-α and ribavirin. RESULTS： An increase of IGF-IR rnRNA content was observed in hepatic tissue obtained from all CHC patients as well as from 6 cadaveric liver donors following orthopic transplantation （an attempt to evaluate normal livers） in comparison to normal liver, while no relevant modifications were detected in IGF-I mRNA content. The irnrnunohistochemical results showed that the raise in IGF-IR rnRNA content was related both to ductular reaction and to increased IGF-IR expression in hepatocytes. A decrease in IGF-IR rnRNA content was observed in patients who achieved sustained virological response after therapy, suggesting an improvement in hepatic damage. CONCLUSION： The up-regulation of IGF-IR expression in hepatocytes of patients with CHC could constitute an attempt to stimulate hepatocyte regeneration. Considering that liver is the organ with the highest levels of IGF-I, our finding of increased IGF-IR expression after both acute and chronic hepatic damage highlights the need for additional studies to elucidate the role of IGF-I in liver regeneration.

靶向IGF-ⅠR的RNA干扰技术抑制胃癌细胞增殖的研究

目的观察特异的小干扰RNAs(small interfering RNAs,siRNAs)对胃癌细胞胰岛素样生长因子-Ⅰ受体(In-sulin-like growth factor-Ⅰ receptor,IGF-ⅠR)基因表达的抑制作用,研究其对肿瘤增殖的影响。方法设计并体外合成2条靶向IGF-ⅠR的siRNAs,脂质体法瞬时转染MGC803细胞,转染前后均使用WesternBlot法检测IGF-ⅠR的表达水平,MTT法检测细胞增殖,细胞计数并描记生长曲线。结果MGC803细胞中有IGF-ⅠR的强烈表达。转染后48h,干扰组(siRNA2-L组、siRNA2-H组、siRNA1组)IGF-ⅠR表达抑制率分别为64.41%±4.11%、74.14%±6.15%、89.8%±4.10%;siRNA1组转染后第2-5天细胞增殖逐渐减少(分别达49.9%±1.2%、45.9%±4.4%、39.1%±5.1%、29%±4.0%);同期细胞计数分别为对照组的65.58%±4.89%、55.59%±0.82%、44.18%±3.17%、21.15%±1.1%。结论特异的siRNAs可显著抑制胃癌细胞中的IGF-ⅠR基因的表达从而显著抑制细胞的增殖。

大肠癌血管内皮生长因子与雌激素受体的表达及临床意义

目的 探讨VEGF、ER在大肠癌组织中的表达和临床意义。方法 应用免疫组织化学SP法研究 45例大肠癌组织中VEGF、ER的表达。结果 45例大肠癌中VEGF阳性表达率显著高于ER(χ2 =9.3 9,P <0 .0 1) ,在淋巴结转移组VEGF、ER表达分别为72 .2 %和 16.7% ,在无淋巴结转移组分别为 2 5 .9% (χ2 =9.3 8,P <0 .0 1)和 48.1% (χ2 =4.67,P <0 .0 5 ) ;在分化好组VEGF、ER表达分别为 5 6.3 %和 68.8% ,而分化差组分别为 3 7.9% (χ2 =1.40 ,P <0 .0 5 )和 17.2 % (χ2 =11.94,P <0 .0 1)。ER的表达与临床病理分期 (Dukes)差异有显著意义 (χ2 =8.15 ,P <0 .0 5 ) ,而VEGF则与之无关。结论 联合检测VEGF、ER的表达可作为大肠癌的预后指标 ,有助于对术后病人放、化疗或内分泌治疗的选择提供依据。

厄洛替尼的研究进展

非小细胞肺癌(NSCLC)是世界上最常见的恶性肿瘤之一,已成为我国城市人口恶性肿瘤死亡原因的第一位。厄洛替尼是一种小分子选择性表皮生长因子受体酪氨酸激酶抑制剂。临床用于一线化疗失败的局部晚期或转移的非小细胞肺癌(NSCLC)的三线治疗。本文对厄洛替尼的药物制备、细胞活性、药理作用、药剂学性质以及临床研究等做一综述。