Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy
Bibliographic record
Abstract
ABSTRACT We have previously established that adipose tissue adjacent to breast tumors becomes inflamed by tumor‐derived cytokines. This stimulates autotaxin (ATX) secretion from adipocytes, whereas breast cancer cells produce insignificant ATX. Lysophosphatidate produced by ATX promotes inflammatory cytokine secretion in a vicious inflammatory cycle, which increases tumor growth and metastasis and decreases response to chemotherapy. We hypothesized that damage to adipose tissue during radiotherapy for breast cancer should promote lysophosphatidic acid (LPA) signaling and further inflammatory signaling, which could potentially protect cancer cells from subsequent fractions of radiation therapy. To test this hypothesis, we exposed rat and human adipose tissue to radiation doses (0.25–5 Gy) that were expected during radiotherapy. This exposure increased mRNA levels for ATX, cyclooxygenase‐2, IL‐1β, IL‐6, IL‐10, TNF‐α, and LPA 1 and LPA 2 receptors by 1.8‐ to 5.1‐fold after 4 to 48 h. There were also 1.5‐ to 2.5‐fold increases in the secretion of ATX and 14 inflammatory mediators after irradiating at 1 Gy. Inhibition of the radiation‐induced activation of NF‐κB, cyclooxygenase‐2, poly (ADP‐ribose) polymerase‐1, or ataxia telangiectasia and Rad3‐related protein blocked inflammatory responses to γ‐radiation. Consequently, collateral damage to adipose tissue during radiotherapy could establish a comprehensive wound‐healing response that involves increased signaling by LPA, cyclooxygenase‐2, and other inflammatory mediators that could decrease the efficacy of further radiotherapy or chemotherapy.—Meng, G., Tang, X., Yang, Z., Benesch, M. G. K., Marshall, A., Murray, D., Hemmings, D. G., Wuest, F., McMullen, T. P. W., Brindley, D. N. Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy. FASEB J. 31, 4064–4077 (2017). www.fasebj.org —Meng, Guanmin, Tang, Xiaoyun, Yang, Zelei, Benesch, Matthew G. K., Marshall, Alison, Murray, David, Hemmings, Denise G., Wuest, Frank, McMullen, Todd P. W., Brindley, David N., Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy. FASEB J. 31, 4064–4077 (2017)
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".