Abstract 2054: A novel Bcl-2/Bcl-XL inhibitor APG-1252-12A as a potential therapeutic strategy for gastric carcinoma
Bibliographic record
Abstract
Abstract Background: Gastric cancer (GC) is the fourth most common type of malignant tumor and is the second leading cause of cancer-related mortality. Surgery and chemotherapy play important role in the treatment of GC, however the overall survival of gastric cancer patients is not promising. APG-1252-12A specifically binding to Bcl-2 and Bcl-xl has shown efficacy in some solid tumor. We intend to investigate the anticancer effect and combination enhancement of Fluorouracil (5-FU) in gastric cancer. Materials and methods: Human gastric cancer cell lines (AGS, NCI-N87, SGC7901, BGC823, MKN45 and NUGC3) were treated with different concentrations and time of APG-1252-12A. CCK-8, survival assays, flow cytometry and western blot were used to assess cell survival, cell cycle progression and apoptosis. In vivo, xenograft mouse models (NCI-N87) were established to analyze the anticancer effect and combination enhancement of 5-FU. Results: In vitro, APG-1252-12A inhibited proliferation of gastric cancer cell lines, without cell-cycle arrest. Meanwhile, APG-1252-12A increased protein expression of apoptosis signal pathway. The combination of APG-1252-12A and 5-FU resulted in the accumulation of apoptosis protein such as PARP and cleaved caspase3, which indicating an increasing of chemosensitivity. In xenograft mouse models, single therapy with APG-1252-12A obviously suppressed tumor growth, especially in 100mg/kg group. Combination group delayed tumor growth more significantly compared with APG-1252-12A and 5-FU single therapy. By analyzing proliferation marker Ki67 in xenograft tumor specimens, we found that the number of proliferating cells significantly decreased in tumors receiving combination treatment of APG-1252-12A and 5-FU compared with tumors receiving single treatment. The results strongly confirmed the antitumor capacity of APG-1252-12A combined with 5-FU. Conclusions: The results strongly suggest that Bcl-2 and Bcl-xl inhibitor APG-1252-12A may serve not only as a single therapy, but also as an effective adjunct to current chemotherapeutic regimens for treating gastric cancer through apoptosis signal pathway. Citation Format: Xianglei Yan, Hanjie Yi, Qiuyun Luo, Luping Yuan, Suna Zhou, Wentao Pan, Lin Zhang, Miaozhen Qiu, Dajun Yang. A novel Bcl-2/Bcl-XL inhibitor APG-1252-12A as a potential therapeutic strategy for gastric carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2054.
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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) | 0.000 | 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 | 0.001 |
| 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".