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Summary: Monoacylglycerol acyltransferase-2 (MOGAT2), encodes MOGAT enzyme in the re-synthesis of triacylglycerol and protects from metabolism disorders. While, its precise involvement in colorectal cancer (CRC) progression remains inadequately understood. Our study demonstrated that knockout of Mogat2 in Apcmin/+ mice expedited intestinal tumor growth and progression, indicating that Mogat2 plays a tumor-suppressing role in CRC. Mechanically, Mogat2 deletion resulted in a significant alter the gut microbiota, while Fecal Microbiota Transplantation (FMT) experiments demonstrated that the gut microbiota in Mogat2 deleted mice promoted tumor growth. Furthermore, we identified Mogat2 as a functional regulator suppressing CRC cell proliferation and tumor growth by inhibiting the NF-κB signaling pathway in vivo. Collectively, these results provide novel insights into the protective double roles of Mogat2, inhibiting of NF-κB pathway and keeping gut microbiota homeostasis in colorectal cancer, which may help the development of novel cancer treatments for CRC.

Despite being an effective treatment for hepatocellular carcinoma (HCC), resistance to oxaliplatin presents a major obstacle. Here, the authors identify PRMT3-induced methylation of IGF2BP1 resulting in HEG1 stabilisation as a mechanism of oxaliplatin resistance in HCC.

ObjectivesGastric cancer with liver metastasis (GCLM) is highly aggressive and has a poor prognosis. This study aims to evaluate the survival benefit of primary tumor resection (PTR) for gastric cancer with liver metastasis.MethodsData on patients with GCLM was extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. A 1:1 propensity score matching (PSM) analysis was performed to minimize the heterogeneity between the PTR and no-PTR groups. The Kaplan–Meier method and Cox regression analysis were used to assess the impact of primary tumor resection (PTR) on overall survival (OS) and cause-specific survival (CSS).ResultsA total of 3,001 patients with GCLM were included, with 328 patients treated with primary tumor resection (PTR), whereas the other 2,673 patients were not. Patients with PTR had a significantly higher OS and CSS rate than those without PTR in unmatched and PSM cohorts. In an unmatched cohort, the median OS was 12.0 months (95% CI, 10 months to 14 months) for those who underwent PTR and 4 months (95% CI, 4 months to 5 months) for those without PTR; the median CSS for those who underwent PTR was 12.0 months (95% CI, 10 months to14 months) and 4 months (95% CI, 4 months to 5 months) for those without PTR, respectively. After PMS, the median OS was 12.0 months (95% CI, 10 months to 17 months) for those who underwent PTR and 7 months (95% CI, 5 months to 10 months) for those without PTR, respectively; the median CSS for those who underwent PTR was 12.0 months (95% CI, 11 months to 17 months) and 7 months (95% CI, 5 months to 8 months) for those without PTR, respectively. In addition, multivariate Cox analysis in the PSM cohort showed that PTR, age, degree of tumor differentiation, and chemotherapy were independent prognostic factors for OS and CSS in GCLM. Specifically, PTR was a significant protective factor for OS (HR: 0.427; 95% CI, 0.325 to 0.561, P

Abstract Transarterial chemoembolization (TACE) is the major treatment for advanced hepatocellular carcinoma (HCC), but it may cause hypoxic environment, leading to rapid progression after treatment. Here, using high‐throughput sequencing on different models, S100 calcium binding protein A9 (S100A9) is identified as a key oncogene involved in post‐TACE progression. Depletion or pharmacologic inhibition of S100A9 significantly dampens the growth and metastatic ability of HCC. Mechanistically, TACE induces S100A9 via hypoxia‐inducible factor 1α (HIF1A)‐mediated pathway. S100A9 acts as a scaffold recruiting ubiquitin specific peptidase 10 and phosphoglycerate mutase family member 5 (PGAM5) to form a tripolymer, causing the deubiquitination and stabilization of PGAM5, leading to mitochondrial fission and reactive oxygen species production, thereby promoting the growth and metastasis of HCC. Higher S100A9 level in HCC tissue or in serum predicts a worse outcome for HCC patients. Collectively, this study identifies S100A9 as a key driver for post‐TACE HCC progression. Targeting S100A9 may be a promising therapeutic strategy for HCC patients.

Objective:. To evaluate whether this conversion rate to resectability could be increased when patients are treated with transarterial chemoembolization and hepatic arterial infusion chemotherapy (TACE-HAIC) using oxaliplatin plus fluorouracil/leucovorin. Background:. Conventional TACE (c-TACE) is a common regimen for initially unresectable hepatocellular carcinoma (HCC), which converts to curative-intent resection in about 10% of those patients. It is urgent need to investigated better regimen for those patients. Methods:. The data of 83 initially unresectable HCC patients were examined, including 41 patients in the TACE-HAIC group and 42 patients in the c-TACE group. Their response rate, conversion rate to resection, survival outcome, and adverse events were compared. Results:. The conversion rate was significantly better in the TACE-HAIC group than in the c-TACE group (48.8% vs 9.5%; P < 0.001). The TACE-HAIC had marginal superiority in overall response rate as compared to c-TACE (14.6% vs 2.4%; P = 0.107 [RECIST]; 65.9% vs 16.7%; P < 0.001 [mRECIST], respectively). The median progression-free survival was not available and 9.2 months for the TACE-HAIC and cTACE groups, respectively (hazard rate [HR]: 0.38; 95% confidence interval [CI], 0.20–0.70; P = 0.003). The median overall survival was not available and 13.5 months for the TACE-HAIC and c-TACE groups, respectively (HR, 0.63; 95% CI, 0.34–1.17; P = 0.132). The 2 groups had similar rates of grade 3/4 adverse events (all P > 0.05). Conclusions:. TACE-HAIC demonstrated a higher conversion rate and progression-free survival benefit than c-TACE and could be considered as a more effective regimen for patients with initially unresectable HCC. Future prospective randomized trials are needed to confirm it.