Sensitization of Carboplatinum- and Taxol-Resistant High-Grade Serous Ovarian Cancer Cells Carrying p53, BRCA1/2 Mutations by Emblica officinalis (Amla) via Multiple Targets
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
Background: Ovarian cancer (OC), the most lethal gynecologic malignancy, is highly resistant to current treatment strategies. High-grade serous epithelial ovarian cancer (HGSOC) cells with increased somatic mutations and genomic instability and the resulting heterogeneous mutant phenotypes are highly resistant to therapy. Plant-derived natural products, including Amla (Emblica officinalis) extract (AE), have demonstrated potent anti-neoplastic properties. Recently we demonstrated that AE inhibits cell growth and the expression of angiogenic factors in OVCAR3 and SKOV3 OC cells in vitro as well as in xenografts in vivo. The goal of this study was to determine the anti-proliferative, anti-angiogenic and anti-metastatic effects of AE on carboplatinum-and taxol-resistant HGSOC cells carrying p53, BRCA1/2 mutations. Methods: Anti-proliferative and anti-metastatic effects of AE on recently characterized carboplatinum-and taxol-resistant HGSOC cells (TOV3041G, OV866(2), OV4453 and, OV4485) was determined using the MTT, migration, invasion and spheroid assays in vitro. To understand the mechanism of AE-induced changes in angiogenesis-related hypoxia-inducible factor 1 (HIF-1) and insulin growth factor receptor 1 (IGF1R), and EMT-associated SNAIL1 and E-cadherin proteins were studied using immunostaining and Western blotting. In vivo effects of AE were determined using mouse xenograft tumor model of OC developed by subcutaneous injection of OV4485 cells that carry mutant p53 and BRCA1, most aggressive and resistant among HGSOC cell lines used in this study. Tumor growth was measured using morphometry. Immunostaining and Western blotting were used to determine changes in Ki67 (proliferation marker), CD31 (angiogenesis marker) as well as changes in HIF-1, IGF1R, SNAIL1 and E-cadherin proteins. Results: AE significantly attenuated migration and invasiveness properties of all tested HGSOC cell phenotypes (P0.001), significantly reduced the expression of HIF-1, IGF1R, and SNAIL1 and increased the expression of E-cadherin in all tested HGSOC cell lines (P=<0.05). Oral administration of AE for 4 weeks caused a significant regression of mouse xenograft tumor (>60%) that derived from OV4855 cells and decreased the expression of endothelial cell antigen-CD31, HIF-1, IGF1R and SNAIL1 and increased the expression of E-cadherin in tumor tissues. Conclusions: AE sensitizes platinum-and taxol-resistant heterogenous HGSOC cells carrying mutations in p53, BRCA1/2 genes, and attenuates their malignant characteristics through targeting key signaling mechanisms of angiogenesis and metastasis. AE is a potential adjunct therapeutic agent for treating resistant, mutant, heterogenous OC.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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