Buthionine sulfoximine pretreatment potentiates the effect of isolated lung perfusion with doxorubicin Journal Article
| Authors: | Port, J. L.; Hochwald, S. N.; Wang, H. Y.; Burt, M. E. |
| Article Title: | Buthionine sulfoximine pretreatment potentiates the effect of isolated lung perfusion with doxorubicin |
| Abstract: | Background.: Although surgical resection remains the mainstay of treatment for metastatic pulmonary sarcoma, 5-year survival approaches only 25%. Chemotherapy has been limited by tumor resistance and systemic toxicity. We assessed the efficacy of l-buthionine-SR-sulfoximine, an inhibitor of glutathione synthesis, as a sensitizer for isolated lung perfusion. Methods.: In experiment 1, sarcoma-bearing rats (n = 20) received either buthionine sulfoximine via intraperitoneal injection or Hespan. After the last injection, tumor glutathione levels were measured. In experiment 2, rats (n = 60) were injected with sarcoma intravenously. On day 6, animals were pretreated with either buthionine sulfoximine or Hespan intraperitoneally. On day 7, rats underwent isolated lung perfusion (Hespan or doxorubicin) or intravenous therapy (Hespan or doxorubicin). On day 14, tumor nodules were counted. Results.: Buthionine sulfoximine effectively depleted tumor glutathione. Animals treated with intravenous therapy had no response to therapy, whereas those animals treated with doxorubicin isolated lung perfusion alone had a limited response. Buthionine-sulfoximine pretreatment in combination with doxorubicin isolated lung perfusion led to a 13-fold reduction in tumor nodules and 5 complete responses. Conclusions.: Buthionine-sulfoximine pretreatment in combination with doxorubicin isolated lung perfusion is superior to intravenous doxorubicin and doxorubicin isolated lung perfusion alone for the treatment of metastatic pulmonary sarcoma. © 1995 The Society of Thoracic Surgeons. |
| Keywords: | controlled study; doxorubicin; nonhuman; conference paper; animal; antimetabolites, antineoplastic; lung neoplasms; animal experiment; animal model; drug synergism; lung metastasis; liver; rat; hetastarch; rats; tumor resistance; glutathione; intravenous drug administration; rats, inbred f344; lung sarcoma; sarcoma, experimental; perfusion, regional; intraperitoneal drug administration; male; priority journal; glutathione metabolism; buthionine sulfoximine; lung perfusion; methionine sulfoximine |
| Journal Title: | Annals of Thoracic Surgery |
| Volume: | 60 |
| Issue: | 2 |
| ISSN: | 0003-4975 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 1995-08-01 |
| Start Page: | 239 |
| End Page: | 244 |
| Language: | English |
| DOI: | 10.1016/0003-4975(95)00362-o |
| PUBMED: | 7544099 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work