Abstract 455: Hypoxia induced carbonic anhydrase IX is essential for the growth and metastasis of breast tumors
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Abstract Metastasis of primary malignancies is a multi-step process and remains the principal cause of cancer deaths. Carbonic anhydrase IX (CAIX) is a hypoxia inducible protein and a poor prognostic marker for several types of cancer, including breast cancer. However, the functional role of CAIX in the metastatic progression of breast cancer is unclear. Here, we have investigated its role in the growth and metastasis of breast tumors. Orthotopic mouse mammary tumors derived from metastatic 4T1 and 66cl4 cells or non-metastatic 67NR cells were examined for levels of proliferation (BrdU), hypoxia, (pimonidazole), perfusion (DiOC7), vasculature (CD31), apoptosis (TUNEL) and lymphangiogenesis (LYVE-1). Metastatic 4T1 and 66cl4 tumors expressed a hypoxia gene signature and were characterized as being poorly vascularized, with high levels of hypoxia. Large numbers of apoptotic cells and well developed intratumoral lymphatic vessels were also evident. Inhibition of expression of CAIX in the metastatic 4T1 cells by stable expression of short hairpin RNA (shRNA) resulted in cell death and reversal of extracellular acidosis in hypoxia in vitro, dramatic regression of tumors in vivo, and inhibition of metastasis. These properties were rescued by constitutive expression of human CAIX. Treatment of mice harboring 4T1 tumors with a novel CAIX-specific inhibitor resulted in significant inhibition of tumor growth. Interrogation by immunohistochemistry of a large (3992 patient samples) primary breast tumor tissue microarray showed that CAIX expression was significantly associated with worse distant relapse free survival (p<10−16) and was most prominent in the basal breast cancers (51%). Our data show that CAIX-mediated function is required for the survival and metastasis of hypoxic breast tumors, and suggest that CAIX is a promising therapeutic target for metastatic breast cancer. This work was supported by the Canadian Breast Cancer Research Alliance, with special funding from the Canadian Breast Cancer Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 455.
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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 it