Regression of primary breast tumor and blockage of osteolytic skeletal metastasis by a non-RGD based integrin binding peptide (ATN-161) targeting α5β1 and αvβ3 in a xenograft model of breast cancer
Bibliographic record
Abstract
Proc Amer Assoc Cancer Res, Volume 45, 2004 4001 Breast cancer is commonly associated with osteolytic skeletal metastasis which results in considerable morbidity and mortality. In the late stages of this malignancy, tumor cells become hormone insensitive and metastasize to several organs including skeleton. ATN-161 is a 5-mer capped peptide that binds to activated α5β1 and ανβ 3 and is currently completing a Phase I trial in patients with advanced solid cancer. In the current study, we have evaluated the ability of ATN-161 to block primary tumor growth and the development of skeletal metastases in a xenograft model of breast cancer. Human breast cancer cells MDA-231 (1 X 105) transfected with green fluorescent protein (MDA-231-GFP) were inoculated into the mammary fat pad of female Balb/c nu/nu mice. After staging of tumors to 50 mm3, animals were infused with vehicle alone or ATN-161 (1 mg/kg 3x/week) i.v. for 6 weeks. Tumor volume of control animals infused with vehicle alone continued to increase over time. In contrast, tumors in experimental animals receiving ATN-161 either regressed or grew significantly more slowly than tumors inbc ontrol animals. In other studies, mice were infused with vehicle alone or ATN-161 for 10 weeks after intracardiac (i.c.) inoculation of tumor cells. Animals were monitored weekly by Faxitron for the development of skeletal metastases. At the end of the study, control and experimental animals were euthanized and and the organs analyzed for the presence of microscopic tumor metastases. While fluorescent metastatic tumor cells were routinely seen in the lungs, liver and spleen of control animals, treatment with ATN-161 resulted in a significant decrease in the number of tumor metastases in these organs. Radiological analysis of long bones demonstrated that ATN-161 treatment completely blocked the development of osteolytic skeletal metastases in the femora and tibia of 3/10 animals and led to a significant decrease in the number and size of osteolytic lesions in 7/10 animals. Bone histomorphometric analysis showed a significant decrease in the total area of osteolysis and tumor/bone ratio in the ATN-161 treated mice. Collectively, these studies demonstrate that ATN-161 can inhibit the progression of primary breast cancer and the development of tumor metastases to soft tissues and skeleton. These studies provide rationale for the development of ATN-161 as an effective therapeutic strategy for patients with late stage breast cancer.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.002 | 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".