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Characterization of drug and radiation sensitivity mechanisms in human hepatocellular carcinoma Hep G2 cells after fractionated gamma-irradiation.

机译:分级γ射线照射后人肝细胞癌Hep G2细胞的药物敏感性和放射敏感性机制的表征。

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摘要

Liver cancer is one of the major types of cancer in Hong Kong. The treatment of liver cancer includes chemotherapy, radiotherapy and surgery. Although surgery is the most common form of treatment for liver cancer, the unresectable liver cancer is mostly treated by chemo- or radiotherapy. The failure of radiotherapy and chemotherapy is usually associated with the development of radiation resistance and drug resistance in cells. In clinical practice, radiation such as X-rays or gamma rays, is usually administered as daily fractions. It is known as fractionated radiotherapy. It has been observed that some patients who have previously undergone radiotherapy have a lower rate of response to subsequent chemotherapy and radiotherapy. However, there were only a few cellular models available to study the relationship between radiation resistance and drug resistance in those liver cancer cells survived from treatment of radiation.; In the present study, two sublines of human hepatocellular carcinoma Hep G2 cells were established by exposing cells to two different irradiation regimes (137 Cesium gamma radiation), 2 Gy for 10 days or 10 Gy for 2 days, respectively. Their drug and radiation sensitivity were then examined. Compared to parent cells, radiation conditioned Hep G2 cells were found to be more resistant to radiation, more sensitive to doxorubicin (DOX), taxol (TAXOL) and vincristine (VCR) but had similar sensitivity to cisplatin (CP) and etoposide (EP).; By using Western blot analysis, Northern blot analysis, RT-PCR based differential display and cDNA microarray, the gene expression profile between radiation conditioned Hep G2 cells and parent cells were compared. Among the genes identified to demonstrate differential expression between parent and radiation conditioned cells, the molecules in Raf-1 signaling pathway are believed to contribute radiation resistance in cells. However, the sensitivity to DOX and the anticancer drugs is suggested to be correlated with drug induced apoptosis. The results from the present study suggested that cells survived from radiation therapy have alteration of their response to drug and radiation.
机译:肝癌是香港的主要癌症之一。肝癌的治疗包括化学疗法,放射疗法和外科手术。尽管外科手术是肝癌最常见的治疗方法,但不可切除的肝癌大多通过化学疗法或放射疗法进行治疗。放射疗法和化学疗法的失败通常与细胞中放射线抗性和药物抗性的发展有关。在临床实践中,通常将X射线或伽马射线等辐射作为日常剂量。这被称为分级放疗。已经观察到一些先前接受过放射治疗的患者对随后的化学疗法和放射治疗的响应率较低。然而,只有少数细胞模型可用于研究那些在放射治疗后存活下来的肝癌细胞中的抗辐射性和耐药性之间的关系。在本研究中,通过将细胞暴露于两种不同的辐射方案(137 Cesiumγ辐射)中,分别将2 Gy暴露10天或10 Gy暴露2天,建立了人类肝细胞癌Hep G2细胞的两个亚系。然后检查了它们的药物和放射敏感性。与亲代细胞相比,经辐射调节的Hep G2细胞被发现对辐射更具抵抗力,对阿霉素(DOX),紫杉醇(TAXOL)和长春新碱(VCR)更加敏感,但对顺铂(CP)和依托泊苷(EP)的敏感性相似。;通过Western印迹分析,Northern印迹分析,基于RT-PCR的差异显示和cDNA微阵列,比较了辐射条件下的Hep G2细胞和亲代细胞之间的基因表达谱。在鉴定出可证明亲本细胞和辐射条件化细胞之间差异表达的基因中,Raf-1信号传导途径中的分子被认为对细胞具有辐射抗性。然而,对DOX和抗癌药的敏感性被认为与药物诱导的细胞凋亡有关。本研究的结果表明,放射治疗后存活的细胞对药物和放射的反应有所改变。

著录项

  • 作者

    Tang, Wan-yee.;

  • 作者单位

    The Chinese University of Hong Kong (People's Republic of China).;

  • 授予单位 The Chinese University of Hong Kong (People's Republic of China).;
  • 学科 Chemistry Biochemistry.; Health Sciences Radiology.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 212 p.
  • 总页数 212
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;预防医学、卫生学;
  • 关键词

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