Post-transplant methotrexate administration leads to improved curability of mice bearing a mammary tumor transplanted with marrow transduced with a mutant human dihydrofolate reductase cDNA Journal Article

  

Authors:	Zhao, S. C.; Banerjee, D.; Mineishi, S.; Bertino, J. R.
Article Title:	Post-transplant methotrexate administration leads to improved curability of mice bearing a mammary tumor transplanted with marrow transduced with a mutant human dihydrofolate reductase cDNA
Abstract:	To test the concept that protection of bone marrow progenitor cells via introduction of a drug resistance gene would allow larger and curative doses of chemotherapy to be administered, we used mice bearing a transplanted breast cancer as a model system. Mice bearing the E0771 tumor were treated with lethal doses of cyclophosphamide (CPA) and rescued from toxicity by administration of bone marrow transduced with a mutant dihydrofolate reductase (DHFR) cDNA (Ser-31) in a retroviral construct. Animals receiving marrow not transduced with mutant DHFR cDNA died from methotrexate (MTX) toxicity, whereas mice transduced with mutant DHFR cDNA containing marrow were able to tolerate MTX treatment post-transplant; 44% of the mice had no demonstrable tumor when sacrificed on day 52. Another control group of mice treated with CPA and transplanted but not treated with MTX post-transplant succumbed to tumor regrowth. These data provide a strong rationale for the use of drug resistance genes to protect marrow from drug toxicity because the increase in dose tolerated may result in an improved cure rate of chemosensitive tumors.
Keywords:	cancer chemotherapy; cancer survival; controlled study; drug tolerability; cancer recurrence; multimodality cancer therapy; nonhuman; combined modality therapy; methotrexate; animal cell; mouse; animals; mice; antimetabolites, antineoplastic; animal experiment; animal model; cyclophosphamide; drug resistance; genetic transduction; transduction, genetic; stem cell; survival time; cancer regression; breast tumor; gene therapy; thrombocyte count; bone marrow cell; neoplasm transplantation; point mutation; dihydrofolate reductase; tetrahydrofolate dehydrogenase; bone marrow transplantation; cell protection; complementary dna; bone marrow toxicity; retrovirus; colony forming unit gm; dna, complementary; mammary neoplasms, experimental; cancer transplantation; humans; female; article
Journal Title:	Human Gene Therapy
Volume:	8
Issue:	8
ISSN:	1043-0342
Publisher:	Mary Ann Liebert, Inc
Date Published:	1997-05-20
Start Page:	903
End Page:	909
Language:	English
PUBMED:	9195212
PROVIDER:	scopus
DOI:	10.1089/hum.1997.8.8-903
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0030999647&partnerID=40&md5=acd952b62e516908585f7619af8c2b6f
Notes:	Article -- Export Date: 17 March 2017 -- Source: Scopus

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