Injection of Encapsulated Cells Producing an Ifosfamide‐Activating Cytochrome P450 for Targeted Chemotherapy to Pancreatic Tumors
Injection of Encapsulated Cells Producing an Ifosfamide‐Activating Cytochrome P450 for Targeted Chemotherapy to Pancreatic Tumors
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注射产生异环磷酰胺激活细胞色素 P450 的封装细胞用于胰腺肿瘤的靶向化疗
DOI：
10.1111/j.1749-6632.1999.tb09537.x
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发表时间：
1999
影响因子：
5.2
通讯作者：
M. Löhr
中科院分区：
文献类型：
--
作者：
P. Müller;R. Jesnowski;P. Karle;R. Renz;R. Saller;H. Stein;K. Püschel;K. von Rombs;H. Nizze;S. Liebe;T. Wagner;W. Günzburg;Brian Salmons;M. Löhr
翻译后摘要：胰腺癌的预后差，目前的药物治疗大多是无效的。本研究的目的是在动物模型系统中设计一种新的治疗方式。我们在这里描述了一种新的治疗策略，采用胰腺癌的小鼠模型系统。对胚胎肾上皮细胞进行遗传修饰，使其在巨细胞病毒（CMV）立即早期启动子的控制下表达细胞色素P450亚酶2B1。该CYP2B1基因将异环磷酰胺转化为其活性细胞毒性化合物磷酰胺芥（可使DNA烷基化）和丙烯醛（可使蛋白质烷基化）。然后将细胞包封在硫酸纤维素制剂中，并植入预先建立的源自人胰腺肿瘤细胞系的肿瘤中。对接受包封细胞的荷瘤小鼠腹腔内给予低剂量异环磷酰胺可导致部分或甚至完全肿瘤消融。这种在免疫保护环境中利用遗传修饰细胞的原位化疗策略可能被证明对人类实体瘤治疗有用。
Abstract: The prognosis of pancreatic cancer is poor, and current medical treatment is mostly ineffective. The aim of this study was to design a new treatment modality in an animal model system. We describe here a novel treatment strategy employing a mouse model system for pancreatic carcinoma. Embryonal kidney epithelial cells were genetically modified to express the cytochrome P450 subenzyme 2B1 under the control of a cytomegalovirus (CMV) immediate early promoter. This CYP2B1 gene converts ifosfamide to its active cytotoxic compounds, phosphoramide mustard, which alkylates DNA, and acrolein, which alkylates proteins. The cells were then encapsulated in a cellulose sulphate formulation and implanted into preestablished tumors derived from a human pancreatic tumor cell line. Intraperitoneal administration of low‐dose ifosfamide to tumor bearing mice that received the encapsulated cells results in partial or even complete tumor ablation. Such an in situ chemotherapy strategy utilizing genetically modified cells in an immunoprotected environment may prove useful for solid tumor therapy in man.
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影响因子：
11.2
作者：
L. Chen;D. Waxman
通讯作者：
L. Chen;D. Waxman
DOI：
10.1073/pnas.90.18.8392
发表时间：
1993-09-15
影响因子：
11.1
作者：
PEAR, WS;NOLAN, GP;BALTIMORE, D
通讯作者：
BALTIMORE, D
层粘连蛋白片段E8通过与细胞表面β1,4半乳糖基转移酶结合来介导PC12细胞神经突生长。
影响因子：
7.8
作者：
Begovac, P C;Hall, D E;Shur, B D
通讯作者：
Shur, B D
功能独特的细胞色素 P450IIB1 变体的分子基础。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Kedzie,KM;Balfour,CA;Escobar,GY;Grimm,SW;He,YA;Pepperl,DJ;Regan,JW;Stevens,JC;Halpert,JR
通讯作者：
Halpert,JR