G31P, CXCR1/2 inhibitor, with cisplatin inhibits the growth of mice hepatocellular carcinoma and mitigates high-dose cisplatin-induced nephrotoxicity
Bibliographic record
Abstract
Cisplatin (DDP), a cytotoxic antitumor drug, functions in a dose-dependent manner. However, the pursuit for high‑dose therapeutic effects leads to more serious side effects including kidney toxicity. Nephrotoxicity caused due to endothelial cell dysfunction and neutrophils infiltration in kidneys. Interleukin-8 (IL-8) is an ELR+ chemokine binds with CXCR1/2 receptors and its role is primarily in neutrophils recruitment and also involved in invasion, angiogenesis and metastasis of different solid tumors including liver cancer. G31P, a CXCR1/2 antagonist, binds with CXCR1/2 with high affinity, and acts as an anti-inflammatory and antitumor agent. In the present study, we examined the antitumor effects of G31P and DDP on mouse liver cancer cells, and the effects exerted by G31P on cisplatin-induced renal injury. In vitro, effects of the G31P and DDP regimen on H22 cell proliferation were investigated by MTT assay. In vivo BALB/c mice were inoculated subcutaneously with 1x106 H22 cells and treated after one week with a high single dose of DDP with and without G31P on alternative days until the experiment was terminated. On the 15th day the mice were sacrificed, dissected and kidney tissues were analyzed using H&E staining. Myeloperoxidase (MPO) activity was assessed and RT-PCR was performed to detect inflammatory cytokines. Solid tumors were weighed for tumor growth and performed pathological examination, immunohistochemistry and western blotting were performed to detect tissue-related protein expressions in tumor tissue. The tumor inhibitory rate of DDP, G31P and DDP+G31P groups was 38.40, 40.74 and 74.80%, respectively, and the general state of mice in the DDP+G31P group was significantly improved as compared to the DDP group. The results indicated that G31P with DDP significantly inhibited the proliferation while the growth of H22 cell carnimona in vitro and in vivo enhanced the efficacy of cisplatin in cancer treatment with reduced side effects on acute renal failure.
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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 | 0.001 |
| 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".