Abstract 1778: Anticancer activities and regulatory effects on apoptotic gene expression of Bufalin in the orthotopic transplantation model of human colorectal cancer in nude mice
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Bibliographic record
Abstract
Abstract Background: Bufalin, a natural small-molecule compound from the Traditional Chinese Medicine “Chansu”, shows inhibitory effects on many human cancer cells. However, whether or not Bufalin has anticancer activity in human colorectal cancer (CRC), and its possible underlying mechanism, remains unclear. Objectives: 1) To investigate anticancer activities of Bufalin in human CRC using an orthotopic transplantation model in nude mice and 2) to study possible underlying mechanisms related to apoptosis. Materials and methods: An orthotopic transplantation tumor model was established by implanting human CRC HCT-116 cells into the colon of nude mice. Sixty mice were randomly divided into five treatment groups (12 mice in each group): normal saline group, 5-FU group, and 3 Bufalin groups with low (BL), medium (BM), and high (BH) doses. After cell transplantation, 0.2 ml normal saline, 25 mg/kg 5-Fu, or 0.5 mg/kg, 1 mg/kg, 1.5 mg/kg Bufalin was injected intraperitoneally in mice in each corresponding group, daily for 7 days (days 15 to 21). Six mice in each group were sacrificed on day 24. Tumor size, growth inhibition rate, and morphological changes of tumor cell under microscopy were recorded. Apoptosis was determined by TUNEL staining, mRNA and protein expressions of Bcl-xl and Bax were evaluated with real-time RT-PCR and immunohistochemical staining, respectively. The overall survival (OS) was determined in the remaining 6 mice in each group. Results: The tumor size in mice treated with 5-Fu, BL, BM, or BH was significantly smaller than that in mice treated with normal saline (p<0.05), with the tumor inhibitor rates of 64.3%, 51.4%, 48.7%, and 36.3%, respectively. Under microscopy, increased tumor necrosis was observed in the 5-Fu, BM and BH groups. The tumor apoptotic rate in each of 3 Bufalin treated groups was significantly higher than that in the normal saline group (p<0.05). Real time RT-PCR and immunohistochemical staining showed both mRNA and protein expressions of Bcl-xl were decreased, whereas the expression of Bax increased, in tumor treated with Bufalin. The OS was prolonged in groups of BL and BM (p<0.05). Conclusion: Bufalin has significant anticancer activity in a human CRC orthotopic transplantation model in nude mice, and induces tumor cell apoptosis, which may be associated with the down-regulation of Bcl-xl and up-regulation of Bax in tumor cells. 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 1778. doi:10.1158/1538-7445.AM2011-1778
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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 | 0.001 | 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