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肾细胞癌的基因治疗:神奇子弹还是悲剧性的疯狂行为?

Gene therapy on renal-cell carcinoma: magic bullet or tragic insanity?

作者信息

Mickisch G H

机构信息

Department of Urology, Erasmus University, Rotterdam, The Netherlands.

出版信息

World J Urol. 1995;13(3):178-85. doi: 10.1007/BF00184876.

Abstract

Correction of the aberrant genetic code as a means of rational therapy has been a challenge since the first discoveries of an abnormal genetic link to expression of certain disorders. Our growing understanding of the molecular basis of cancer has also led us into a new era in cancer therapy. The possibility of gene therapy represents one of the biggest potential returns on the investment in molecular biology research over the past several years. As a massive gene therapy attack mounts against many forms of malignancy employing various techniques, strategies, and concepts, there appears to be reason to be optimistic, with expectations thus far decidedly outweighing results. Scientists and clinicians have joined together to target directly the molecular basis of tumorigenesis through the restoration of tumor-suppressor gene function or inhibition of oncogene expression. In addition, scientists mapping the human genome have supplied us with a number of genes that can be used to destroy cancer cells selectively [e.g., the herpes simplex-thymidine kinase (HS-tk) gene], induce a potent antitumor immune response (e.g., interleukin 2), and afford protection to normal tissues from the toxic effects of standard chemotherapy [e.g., multidrug resistance gene type 1 (mdr 1)]. These new anticancer tools provide new opportunities for more specific tumor cell destruction in vivo without the common regional and systemic side effects related to conventional forms of chemotherapy, immunotherapy, radiation, and surgery. Hence, over the next 5-10 years, gene therapy is likely to become a realistic treatment option for certain cancers.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

自首次发现某些疾病的异常基因表达关联以来,纠正异常遗传密码作为一种合理治疗手段一直是一项挑战。我们对癌症分子基础的日益了解也引领我们进入了癌症治疗的新时代。基因治疗的可能性是过去几年分子生物学研究投资的最大潜在回报之一。随着采用各种技术、策略和概念对多种恶性肿瘤发起大规模基因治疗攻击,似乎有理由保持乐观,目前期望远远超过了实际成果。科学家和临床医生联合起来,通过恢复肿瘤抑制基因功能或抑制癌基因表达,直接针对肿瘤发生的分子基础。此外,绘制人类基因组图谱的科学家为我们提供了许多可用于选择性破坏癌细胞的基因[例如单纯疱疹胸苷激酶(HS-tk)基因]、诱导强大的抗肿瘤免疫反应(例如白细胞介素2),并保护正常组织免受标准化疗的毒性影响[例如多药耐药基因1型(mdr 1)]。这些新的抗癌工具为在体内更特异性地破坏肿瘤细胞提供了新机会,而不会产生与传统化疗、免疫疗法、放疗和手术相关的常见局部和全身副作用。因此,在未来5到10年,基因治疗可能会成为某些癌症切实可行的治疗选择。(摘要截选于250字)

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