The effects of exercise training on antitumor efficacy of doxorubicin in MDA-MB-231 breast cancer xenografts
Bibliographic record
Abstract
1092 In recent years a growing number of reports have examined the role of exercise as a supportive intervention for cancer patients during adjuvant chemotherapy. All studies to date have focused exclusively on the ability of exercise to improve physical functioning or help patients cope with side-effects of treatment in order to improve quality of life. However, a critical and previously unexplored question is whether exercise training influences the efficacy of chemotherapy. To address this question, MDA-MB-231 breast carcinoma cells (5 X 106) were subcutaneously injected into the right flank of female athymic mice (age 3-4 weeks). Following tumor establishment (14 days), mice were stratified by tumor volume and randomly assigned to one of four groups (n=21 per group): (i) control (CO), (ii) exercise only (EX), (iii) chemotherapy only (CT), or (iv) exercise + chemotherapy (EX+CT). Doxorubicin was administered through weekly intravenous lateral tail vein injections at 4mg/kg for 8 weeks. Exercise groups performed progressive treadmill running up to 18m/min at 0% grade for 45mins, 5 days/wk for 8 weeks. Mice were sacrificed when tumor volume reached 1100mm3 as required by institutional guidelines or 48 hours following the final exercise training session. Tumor volume was measured twice weekly. The primary endpoint was tumor growth delay, calculated as the median number of days for tumor burden to reach 1100mm3. Survival times were compared using the log-rank test and all tests were two-sided. Median tumor growth delay was significantly longer in the CT and EX+CT groups compared with the CO (42 days vs. 25 days, RR 0.38, p=0.0084; 36 days vs. 25 days, RR 0.46, p=0.029, respectively) and EX groups (42 days vs. 25 days, RR 0.45, p=0.029; 36 days vs. 25 days, RR 0.54, p=0.080, respectively). There was no significant difference between CT and EX+CT groups (42 days vs. 36 days, RR 1.44, p=0.33). At 56 days, Kaplan-Meier estimates indicated a 35% (95% CI=17% to 54%) survival rate for the CT mice compared with 20% (95% CI=7% to 33 %) in the EX+CT group, 16% (95% CI=2% to 31%) in the EX group and 0% in the CO group. This data suggests that moderate intensity endurance exercise does not significantly influence doxorubicin-induced tumor growth delay in athymic mice implanted with breast carcinoma cell line MDA-MB 231. However, the trend for longer survival with doxorubicin only, suggests that exercise training during chemotherapy may inhibit the efficacy of this therapy. Future studies are underway to explore mechanisms of this potential interaction. This study was supported by a grant from the United States Department of Defense Breast Cancer Research Program - Concept Award.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".