Arid1a mutation suppresses TGF-β signaling and induces cholangiocarcinoma

Activating KRAS mutations and functional loss of members of the SWI/SNF complex, including ARID1A, are found together in the primary liver tumor cholangiocarcinoma (CC). How these mutations cooperate to promote CC has not been established. Using murine models of hepatocyte and biliary-specific lineage tracing, we show that Kras and Arid1a mutations drive the formation of CC and tumor precursors from the biliary compartment, …

Continue reading Arid1a mutation suppresses TGF-β signaling and induces cholangiocarcinoma

Ten-Year Outcomes of Liver Transplant and Downstaging for Hepatocellular Carcinoma

National guidelines on transplant selection have adopted successful downstaging to within Milan criteria (MC) as a viable option for the treatment of hepatocellular carcinoma (HCC) before liver transplant (LT). Recurrence of HCC after LT carries a poor prognosis, and treatment modalities remain challenging.Objective To establish the 10-year outcomes of patients with HCC after LT in …

Continue reading Ten-Year Outcomes of Liver Transplant and Downstaging for Hepatocellular Carcinoma

Dual stromal targeting sensitizes pancreatic adenocarcinoma for anti-PD-1 therapy

Background and AimsThe stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and enhance immunotherapy efficacy by targeting multiple stromal components through both intracellular and extracellular mechanisms.MethodsA murine liver metastasis syngeneic model of PDAC was treated with focal adhesion kinase inhibitor (FAKi), anti-PD-1 antibody …

Continue reading Dual stromal targeting sensitizes pancreatic adenocarcinoma for anti-PD-1 therapy

Incidence of New-Onset Type 2 Diabetes After Cancer: A Danish Cohort Study

For patients with cancer, prevalent type 2 diabetes at the date of cancer diagnosis is associated with increased cancer-specific and all-cause mortality (1,2). Yet, despite potential health implications, there is limited knowledge on whether cancer is also a risk factor for type 2 diabetes. Moreover, the impact of new-onset type 2 diabetes after cancer diagnosis …

Continue reading Incidence of New-Onset Type 2 Diabetes After Cancer: A Danish Cohort Study

Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease

Predicting liver cancer riskNonalcoholic fatty liver disease (NAFLD) raises the risk of developing hepatocellular carcinoma (HCC), but this risk can be difficult to quantify and disease onset can still be difficult to catch early. Fujiwara et al. developed hepatic transcriptome and serum secretome–derived signatures to predict NAFLD-related HCC in patients over 15 years of observation. …

Continue reading Molecular signatures of long-term hepatocellular carcinoma risk in nonalcoholic fatty liver disease