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| Content Provider | PubMed Central |
|---|---|
| Author | Behan, James W. Yun, Jason P. Proektor, Marina P. Ehsanipour, Ehsan A. Arutyunyan, Anna Moses, Ara S. Avramis, Vassilios I. Louie, Stan G. Butturini, Anna Nora, Heisterkamp Mittelman, Steven D. |
| Abstract | Obesity is associated with increased cancer incidence and mortality. We have previously found that obesity in children is associated with a 50% increased recurrence of acute lymphoblastic leukemia (ALL) in high-risk patients. We have therefore developed novel in vivo and in vitro preclinical models to study the mechanism(s) of this association. Obesity increased relapse after monotherapy with vincristine (p=0.03) in obese mice injected with syngeneic ALL cells. This occurred even though the drug was dosed proportionally to body weight, equalizing blood and tissue drug levels. In co-culture, 3T3-L1 adipocytes significantly impaired the anti-leukemia efficacy of vincristine, as well as 3 other chemotherapies (p<0.05). Interestingly, this protection was independent of cell-cell contact, and it extended to human leukemia cell lines as well. Adipocytes prevented chemotherapy-induced apoptosis, and this was associated with increased expression of the two pro-survival signals Bcl-2 and Pim-2. These findings highlight the role of the adipocyte in fostering leukemia chemotherapy resistance, and may help explain the increased leukemia relapse rate in obese children and adults. Given the growing prevalence of obesity worldwide, these effects are likely to have increasing importance to cancer treatment. |
| Related Links | http://dx.doi.org/10.1158/0008-5472.CAN-09-0800 |
| Starting Page | 7867 |
| File Format | |
| ISSN | 15387445 |
| e-ISSN | 15387445 |
| Journal | Cancer research |
| Issue Number | 19 |
| Volume Number | 69 |
| Language | English |
| Publisher Date | 2009-10-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology |
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