Prevention of Radiation-enhancement Dermatitis and Breast Cancer Cell Invasion by an Anti-Inflammatory Agent
Bibliographic record
Abstract
For women with early stage breast cancer, the primary tumour is removed by conservative surgery. However, malignant microfoci are often scattered in the breast. To eliminate these cells radiotherapy is designed to irradiate the whole breast. But the dose is not calculated to eliminate all residual cancer cells but rather to optimize long-term results with minimal complications to normal tissues such as fibrosis. These complications are mainly caused by the induction of an inflammation, associated with the upregulation of the cyclooxygenase-2 (COX-2). Furthermore the inhibition of COX-2 decreases matrix metalloproteinases (MMPs) expression, such as MMP-2 and MMP-9, both playing a central role in breast cancer cell invasion. The aim of this study is to further improve radiotherapy of breast cancer by preventing radiation-enhancement dermatitis and breast cancer cell invasion with the administration of NS-398, a COX-2 specific inhibitor. Female Balb/c mice were irradiated on a healthy thigh followed by the s.c. injection of MC7-L1 mammary cancer cells. NS-398 was injected i.p. before and after irradiation. Controls without irradiation and without cancer cells were also performed. For 3 and 6 weeks the degree of skin inflammation was scored and cancer cell invasion was monitored by contrast-enhanced magnetic resonance imaging. Tumors and surrounding tissues were subsequently removed and processed for histological analysis and zymography. We have shown that radiation actually enhances the invasiveness of breast cancer cells. MC7-L1 cells grown mainly under the skin in non irradiated thighs but invaded into the muscle fibers in irradiated thighs. These patterns were distinct 4 weeks after irradiation, but more pronounced on the 6th week. The calculated apparent invasion tumor volume was significantly greater in irradiated thighs. The activity of MMP-2 and -9 were enhanced in muscle and skin after irradiation. Our preliminary results with the COX-2 inhibitor NS-398 demonstrated an improvement of skin tolerance and a decrease of the invasion marker MMP-2 in the irradiated area. The NS-398 seemed also to reduce cancer cells proliferation and invasion. Our promising preliminary data showed that the NS-398, a specific COX-2 inhibitor, might improve the efficacy of radiotherapy for breast cancer by preventing radiation-induced dermatitis and radiation-enhancement of cancer cell invasion.
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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 | 0.000 |
| 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".