Adenoviral-mediated herpes simplex virus-thymidine kinase gene transfer in vivo for treatment of experimental human melanoma.
Adenoviral-mediated herpes simplex virus-thymidine kinase gene transfer in vivo for treatment of experimental human melanoma.
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腺病毒介导的单纯疱疹病毒胸苷激酶基因体内转移用于治疗实验性人类黑色素瘤。
DOI：
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发表时间：
1996
影响因子：
6.5
通讯作者：
R. Roop
中科院分区：
文献类型：
--
作者：
B. Bonnekoh;D. Greenhalgh;D. Bundman;K. Kosai;S. Chen;M. Finegold;T. Krieg;S. Woo;R. Roop
为了评估体内腺病毒介导的细胞毒性基因治疗的功效，在裸鼠中建立人黑素瘤，并用单纯疱疹病毒胸苷激酶（tk）转导，然后用更昔洛韦（GCV）治疗。在最初的实验中，使用含有β-半乳糖苷酶报告基因的腺病毒（adv）来确定体外黑色素瘤细胞的感染性。与鼠黑色素瘤细胞系B16和K1735-M2相比，人A375-SM细胞对腺病毒转导的敏感性高10倍，与人表皮HaCaT细胞的感染性程度相似。此外，人A375-SM黑色素瘤细胞在体外对tk-adv转导和GCV治疗的细胞毒性作用表现出更高的敏感性，这是由强的旁观者效应介导的。在体内，用1.2 X IO 9 pfu的tk-adv瘤内注射相对较大的人黑素瘤（160 mm 3），随后腹膜内GCV处理（60 mg/kg，每日两次）4天，与模拟或未处理的对照相比，通常导致黑素瘤生长速率降低50%。此外，采用严格的计算机化成像系统进行的组织计量分析显示，tk-adv/GCV治疗组中残留的存活肿瘤面积仅为溶剂对照组的五分之一。这些数据表明adv是一种治疗实验性人类黑色素瘤的高效体内基因递送系统。与先前的鼠黑色素瘤研究相比，人黑色素瘤似乎对这种体内细胞毒性治疗表现出更大的敏感性，这可能为开发治疗人类黑色素瘤的有效基因治疗方式带来重大希望。
To assess the efficacy of an in vivo adenoviral-mediated cytotoxic gene therapy, human melanomas were established in nude mice and transduced with herpes simplex virus-thymidine kinase (tk) followed by treatment with ganciclovir (GCV). In initial experiments, adenovirus (adv) containing the beta-galactosidase reporter gene was employed to determine melanoma cell infectivity in vitro. In comparison to murine melanoma cell lines B16 and K1735-M2, human A375-SM cells exhibited up to a 10-fold greater susceptibility to adenoviral transduction, similar to the degree of infectivity found for human epidermal HaCaT cells. In addition, human A375-SM melanoma cells exhibited a greater sensitivity in vitro to the cytotoxic effects of transduction with tk-adv and treatment with GCV, which was mediated by a strong bystander effect. In vivo, intratumoral injection of relatively large human melanomas (160 mm3) with 1.2 X 109 pfu of tk-adv, followed by intraperitoneal GCV treatment (60 mg/kg twice daily) over 4 days, typically resulted in a 50% reduction in melanoma growth rate compared to mock or untreated controls. Moreover, histometrical analysis employing a rigorous computerized imaging system revealed that the residual viable tumor area in the tk-adv/GCV-treated group was only one-fifth that of solvent controls. These data show that adv is a highly efficient in vivo gene delivery system to treat experimental human melanomas. In comparison to a previous murine melanoma study, human melanomas appeared to exhibit a greater sensitivity to this cytotoxic treatment in vivo, which may hold significant promise for development of effective gene therapy modalities to treat melanoma in humans.
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DOI：
10.1093/jnci/72.4.913
发表时间：
1984-04
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
J. Kozlowski;J. Kozlowski;I. Hart;I. Fidler;N. Hanna
通讯作者：
J. Kozlowski;J. Kozlowski;I. Hart;I. Fidler;N. Hanna
K-1735 鼠黑色素瘤体细胞杂交体中转移表型的优势。
影响因子：
11.2
作者：
Staroselsky,AH;Pathak,S;Chernajovsky,Y;Tucker,SL;Fidler,IJ
通讯作者：
Fidler,IJ
腺病毒载体感染对培养的原代人气道上皮细胞增殖的影响。
DOI：
10.1089/hum.1995.6.8-1045
发表时间：
1995
期刊：
Human gene therapy.
影响因子：
--
作者：
Teramoto,S;Johnson,LG;Huang,W;Leigh,MW;Boucher,RC
通讯作者：
Boucher,RC
细胞因子基因治疗：癌症患者管理的新策略。
DOI：
--
发表时间：
1994
期刊：
Natural immunity
影响因子：
--
作者：
Foa,R;Guarini,A;Cignetti,A;Cronin,K;Rosenthal,F;Gansbacher,B
通讯作者：
Gansbacher,B
实验性脑肿瘤治疗中的旁观者肿瘤杀伤作用。
影响因子：
4.8
作者：
Wu,JK;Cano,WG;Meylaerts,SA;Qi,P;Vrionis,F;Cherington,V
通讯作者：
Cherington,V