• IMMUNE NETWORK
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• 제1권1호
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• pp.45-52
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• 2001

Background: Many types of cancer become resistant to current chemotherapeutic and radiotherapeutic intervention. To overcome this situation application of gene therapy by the introduction of suicide genes followed by their prodrugs may be promising. A viral enzyme, Herpes simplex thymidine kinase (HSV-tk), which converts ganciclovir from an inactive prodrug to a cytotoxic agent by phosphorylation, are being actively investigated for use in gene therapy for cancer. The purpose of this study was to determine whether combining prodrug-activating gene therapy and irradiation might result in enhanced antitumor effects. Methods: The HSV-tk gene was cloned into the retroviral vector, pLXSN and established the clones producing retroviruses carrying the HSV-tk gene. The carcinoma cell line, HCT116 and Huh-7 were transduced with high-titer recombinant retroviruses. These cell lines were treated with ganciclovir before or after irradiation for the defining combinational effect of suicide gene therapy and radiotherapy. Results: The titers of cloned PA3 17 amphotropic retroviruses ranged from 4 to 6 X $10^6CFU/ml4$. After selectional periods, the expression of HSV-tk was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The growth of cells expressing HSV-tk was inhibited as increase of GCV dose after 48 hr and the growth inhibitory effect of GCV was much higher after 72 hr. When the cells transduced with HSV-tk gene were exposed to radiation, the growth inhibitory effect of GCV was significantly increased, as compared with non-transduced parental cells. Conclusions: The results suggest that the addition of HSV-tk gene therapy to standard radiation therapy may improve the effectiveness of treatment for solid tumors.

• 폴리머
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• 제29권1호
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• pp.36-40
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• 2005

폴리(아미노산)유도체는 약물전달시스템의 약물전달체로 많이 연구되고 있으며 그 중 Polysuccinimide(PSI)는 생체적합성과 생분해성 등의 물리화학적 특성을 이용하여 약물전달체로 이용할 수 있는 가능성을 지닌 고분자이다. 축합중합을 이용하여 아스파르트산이 고리를 형성함으로써 PSI를 중합하였다. 이 때 PSI의 중합 최적조건을 관찰하기 위하여 시간과 촉매함량의 변화에 따른 평균분자량의 변화를 확인하였다. 또한 친수성과 소수성으로 이루어진 고분자 미셀을 제조하기 위하여 친수성 사슬인 메톡시폴리(에틸렌 글리콜((MPEG)을 결합시켰다. 합성한 고분자는 1H-NMR, FT-IR 및 GPC를 통하여 특성을 확인하였으며, ELS와 AFM을 통해 미셀의 형성에 대한 특성을 분석하였다. 미셀의 평균크기는 90~130 nm로 측정되었다. 본 연구를 통하여 PSI를 주사슬로 하는 가지 공중합체가 미셀 형태의 약물전달용 전달체로서 가능성을 가지고 있음을 확인할 수 있었다.