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2010年我国癌症发病率为235.23/10万,新发病例309.3万例,死亡率为148.81/10万,死亡病例195.7万例。我国恶性肿瘤发病第1位的是肺癌,发病率为46.08/10万,占所有恶性肿瘤19.59%,新发病例约61万,恶性肿瘤死亡第1位的也是肺癌,占所有恶性肿瘤死亡的24.87%,年死亡约49万,死亡率为37.00/10万~([1])。与其他癌症相比,由于缺乏早期发现的有效手段,大部分肺癌患者发现时已经失去了手术的机会,全身治疗是主要的治疗手段,但是治疗效果不理想。20世纪70年代以后,化学药物成为晚期非小细胞肺癌(non-small cell lung cancer,NS…
在过去的十几年时间里,随着我们对肺癌,特别是非小细胞肺癌(non small celllung cancer,NSCLC)的生物学基础的深入研究,相应的治疗策略也发生了翻天覆地的变化(图1)。仅从病理学类型来区分肺癌已经远远小能满足”精准癌诊断”的需求。肺癌携带高比例的体细胞突变,染色体间和染色体内的重排和基因拷贝数的改变。目前,基因水平的肺癌诊断已经成为临床实践的常规,也应是规范诊断的必须要求。
随着肿瘤基础研究和基因分子生物学技术的不断发展,以特定基因变异为治疗靶点的药物陆续涌现,掀开了恶性肿瘤个体化治疗的新篇章。从第一个非小细胞肺癌(non-small

这个 cell lung cancer,NSCLC)靶向治疗药物吉非替尼的出现,近年来用于NSCLC治疗的靶向药物如埃克替尼、克唑替尼和色瑞替尼等给患者带来了更好的生存获益和更小的治疗不良反应~([1~3]),但同时也有相当一批患者无法从靶向治疗中获益,因此筛选合适的目标治疗人群在临床决策时就显得尤为重要。
AIM: To investigate the roles and interactions of mut T homolog(MTH)-1 and hypoxia-inducible factor(HIF)-1α

in human colorectal cancer(CRC).METHODS: The expression and distribution of HIF-1α and MTH-1 proteins were detected Alisertib研究购买 in human CRC tissues by immunohistochemistry and quantitative realtime polymerase chain reaction(q RT-PCR). SW480 and HT-29 cells were exposed to normoxia or hypoxia. Protein and m RNA levels of HIF-1α and MTH-1 were analyzed by western blotting and q RT-PCR, respectively. In order to determine the effect of HIF-1α on the expression of MTH-1 and the amount of 8-oxodeoxyguanosine triphosphate(d

GTP) in SW480 and HT-29 cells, HIF-1α was silenced with small interfering RNA(si RNA). Growth studies were conducted on cells with HIF-1α inhibition using 查找协议 a xenograft tumor model. Finally, MTH-1 protein was detected by western blotting in vivo.RESULTS: High MTH-1 m RNA expression was detected in 64.2% of cases(54/84), and this was significantly correlated with tumor stage(P = 0.023) and size(P = 0.043). HIF-1α protein expression was correlated significantly with MTH-1 expression(R = 0.640; P < 0.01) in human CRC tissues. Hypoxic stress induced m RNA and protein expression of MTH-1 in SW480 and HT-29 cells. Inhibition of HIF-1α by si RNA decreased the expression of MTH-1 and led to the accumulation of 8-oxo-d GTP in SW480 and HT-29 cells. In the in vivo xenograft tumor model, expression of MTH-1 was decreased in the HIF-1α si RNA group, and the tumor volume was much smaller than that in the mock si RNA group.CONCLUSION: MTH-1 expression in CRC cells was upregulated via HIF-1α in response to hypoxic stress, emphasizing the crucial role of HIF-1α-induced MTH-1 in tumor growth.