Regressions of Established Breast Carcinoma Xenografts by Carboxypeptidase G2 Suicide Gene Therapy and the Prodrug CMDA Are Due to a Bystander Effect
| العنوان: | Regressions of Established Breast Carcinoma Xenografts by Carboxypeptidase G2 Suicide Gene Therapy and the Prodrug CMDA Are Due to a Bystander Effect |
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| المؤلفون: | Richard Marais, Janet L. Martin, Lawrence Davies, Frank Friedlos, Robert A. Spooner, Stephen M. Stribbling, Caroline J. Springer |
| المصدر: | Human Gene Therapy. 11:285-292 |
| بيانات النشر: | Mary Ann Liebert Inc, 2000. |
| سنة النشر: | 2000 |
| مصطلحات موضوعية: | Time Factors, Genetic enhancement, Mice, Nude, Antineoplastic Agents, Apoptosis, Breast Neoplasms, Biology, Mice, Glutamate carboxypeptidase, Glutamates, Carboxypeptidase-G2, Genetics, Carcinoma, medicine, Bystander effect, Animals, Humans, Prodrugs, Molecular Biology, Mice, Inbred BALB C, Body Weight, Genetic Therapy, gamma-Glutamyl Hydrolase, Prodrug, Suicide gene, medicine.disease, Nitrogen Mustard Compounds, Immunology, Cancer research, Molecular Medicine, Female, Breast carcinoma, Neoplasm Transplantation |
| الوصف: | The role of the bystander effect in the treatment of a human breast carcinoma xenograft was studied by suicide gene therapy with carboxypeptidase G2 (CPG2) and CMDA. Cells expressing enzymatically active surface-tethered bacterial CPG2 [stCPG2(Q)3] were mixed with control beta-galactosidase (beta-Gal)-expressing cells to give stCPG2(Q)3:beta-Gal ratios of, respectively: group 1, 0:100; group 2, 10:90; group 3, 50:50; and group 4, 100:0. Four days after injection of the cells into nude mice, the prodrug 4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl-L-glutamic acid (CMDA) was administered. Tumor growth delay correlated well with the levels of stCPG2(Q)3 expression: group 1, 0 day delay; group 2, 10 days; group 3, 16 days; and group 4, 90 days. Similarly, the number of cures was strongly correlated to the levels of stCPG2(Q)3 activity: group 1, zero of six cured; group 2, one of six cured; group 3, three of six cured and group 4, four of six cured. There was a good correlation between CPG2 enzyme activity in the tumors and the number of cures. The majority of cells from groups 2 and 3 were apoptotic whereas those from group 1 were not, indicating a substantial bystander effect in the tumors. These results suggest that a bystander effect plays a major role in suicide gene therapy regimens with stCPG2(Q)3 and CMDA. |
| تدمد: | 1557-7422 1043-0342 |
| DOI: | 10.1089/10430340050016021 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d8204beea73e1f03d721654071ee81ae https://doi.org/10.1089/10430340050016021 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....d8204beea73e1f03d721654071ee81ae |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15577422 10430342 |
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| DOI: | 10.1089/10430340050016021 |