Pathogenesis of Radiation-Induced Capsular Contracture in Tissue Expander and Implant Breast Reconstruction
Bibliographic record
Abstract
BACKGROUND: Capsular contracture is the main complication in postmastectomy tissue expander and implant breast reconstruction in patients requiring radiotherapy. There is evidence that the wingless signaling pathway plays a central role in the pathogenesis of fibroproliferation in fibromatosis and hyperplastic skin wounds, involving multiple linked events leading to up-regulation of target genes and fibroproliferation. Here, the authors tested their hypothesis that the wingless signaling pathway may also regulate radiotherapy-induced fibroproliferation in capsular tissue around expanders/implants in breast reconstruction. METHODS: Biopsies of the periprosthetic capsule were obtained from patients undergoing bilateral expander breast reconstruction in which one side was radiated and the other side was not radiated. Capsular biopsies were snap-frozen and stored at -80 degrees C for Western blot assays to determine protein content of phospho-glycogen-synthase-kinase-3beta (phospho-GSK-3beta), total GSK-3beta, beta-catenin, cyclooxygenase-2 (COX-2), and collagen types I and III (n = three to five patients), normalized to beta-actin. Immunostaining for beta-catenin in radiated and nonradiated capsular tissue was also performed. Slides were scanned and analyzed using Zeiss Mirax Scan. RESULTS: The following protein content levels were significantly (p < 0.01) increased in radiated capsule compared with nonradiated capsule: phospho-GSK-3beta (6.7-fold), total GSK-3beta (3.0-fold), beta-catenin (2.3-fold), COX-2 (2.8-fold), and collagen type I (1.6-fold) and type III (1.8-fold). Immunohistochemical staining demonstrated increased fibroblast cytosolic beta-catenin staining and evidence of beta-catenin nuclear translocation in radiated compared with nonradiated capsular tissue. CONCLUSION: Results from this study highlight the importance of the wingless signaling pathway in the pathogenesis of radiation-induced fibroproliferation associated with capsular contracture in expander/implant breast reconstruction.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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".