Abstract 2540: Evaluation of novel <i>bis</i>-amidine osmium complex as anti-proliferative agents
Bibliographic record
Abstract
Abstract Introduction. Despite improvement in current treatment strategies, including surgery, chemotherapy (CT) and radiotherapy (RT), survival of cancer patients in advanced stages has not improved significantly over the last decade. Organometallic complexes of platinum (cisplatin, carboplatin and oxaliplatin) are in use as chemotherapeutic agents worldwide. However, acquired drug resistance to these platinum complexes has necessitated the search for novel strategies to overcome this limitation, which includes combination therapies and the development of novel platinum or non-platinum complexes as drugs. Methods. Anti-proliferative effects of a bis-amidine complex (Os-Sh1) was determined by measuring the inhibition of cell proliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry-based cell-cycle analysis, annexin V dye binding assay and TUNEL assay in endometrial cancer (Hec1A and KLE) and cervical cancer (HeLa) cells. Results: Cell viability (MTT) assays revealed inhibition of cell proliferation on treatment with the bis-amidine osmium complex (Os-Sh1) in HEC1A, KLE and HeLa cell lines in a dose- (1μM – 50μM) and time-dependent manner (24h – 96h). Cell-cycle analysis showed increased cell death, i.e. the sub-G0 fraction, with G0/G1-arrest and reduction in the G2/M phase of cell cycle on treatment with the Os-Sh1 in these cell lines. Results of annexin V assay suggested apoptosis as the mechanisms of Os-complex induced cell death. Apoptosis was further confirmed by TUNEL assay using flow cytometry analysis. Western blot analysis showed cleavage of caspase 9, caspase 3 and poly-ADP ribose polymerase (PARP), suggesting activation of the intrinsic mitochondrial pathway of apoptosis. Interestingly, Os-Sh1 was more effective in inhibiting cell proliferation at a lower dose and shorter period of time (LD50=20 μM, 48h) in comparison to cisplatin, carboplatin and oxaliplatin in HEC1A, KLE and HeLa cell lines. Conclusions: Our in vitro data clearly demonstrated anti-proliferative effects of a novel bis-amidine osmium complex in endometrial and cervical cancer cells at a lower dose and in shorter period of time in comparison to platinum drugs. Based on these results, we hypothesize that such osmium complex has the potential as effective cytotoxic agents wherein cancer cells acquire resistance to commonly used platinum drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2540. doi:10.1158/1538-7445.AM2011-2540
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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".