Liver and kidney cancers are notorious for drug resistance. Due to the complexity, redundancy and interpatient heterogeneity of resistance mechanisms, most efforts targeting a single pathway were unsuccessful. Novel personalized therapies targeting multiple essential drug resistance pathways in parallel hold a promise for future cancer treatment. Exploiting the multitarget characteristic of microRNAs (miRNAs), we developed a new therapeutic strategy by the combinational use of miRNA and anticancer drugs to increase drug response. By a systems approach, we identified that miR-27b, a miRNA deleted in liver and kidney cancers, sensitizes cancer cells to a broad spectrum of anticancer drugs in vitro and in vivo. Functionally, miR-27b enhances drug response by activating p53-dependent apoptosis and reducing CYP1B1-mediated drug detoxification. Notably, miR-27b promotes drug response specifically in patients carrying p53-wild-type or CYP1B1-high signature. Together, we propose that miR-27b synergizes with anticancer drugs in a defined subgroup of liver and kidney cancer patients.

Objective: The effects of hepatocellular carcinoma (HCC) tumor size on clinical presentation and treatment selection and its role as a prognostic factor remain unclear. The present study is a comprehensive analysis of the clinical correlation between tumor size at diagnosis and pathological grades, clinical staging, disparities of treatment, and survival of patients with HCC. Materials and methods: Patients with HCC were separated into groups according to tumor size as follows: 0.1–2.0, 2.1–5.0, 5.1–10.0, and 10.1–20.0 cm. Logistic regression analysis was used to determine the relationship between tumor size at diagnosis and pathological grade, Surveillance, Epidemiology, and End Results (SEER) historic stage A, and treatment selection. The survival of HCC patients stratified by tumor size was estimated by Kaplan–Meier and 5-year survival analyses using the log-rank test. Multivariable analysis of overall survival was performed using the Cox proportional hazards model. Tumor size at diagnosis was an independent risk factor of pathological grade, and SEER historic stage A was revealed by logistic regression analysis. Results: The 5-year survival rate was 21.9% vs 14.3% vs 9.2% vs 7.7% for all HCC patients and 31.2% vs 23.6% vs 20.3% vs 15.5% for patients who underwent surgery with tumor sizes of 0.1–2.0 vs 2.1–5.0 and 5.1–10.0 vs 10.1–20.0 cm, respectively; multivariable Cox regression analysis identified tumor size at diagnosis as an independent predictor of survival risk with HR of 1.00 vs 1.66 vs 2.92 vs 3.67, respectively. Conclusion: Tumor size at diagnosis could be used as an independent risk predictor associated with histological grade, stage, selection of surgery, and survival in HCC.

Mesenchymal stem cells (MSCs) have been studied for the treatment of acute liver failure (ALF) for several years. MSCs may exert their effect via complex paracrine mechanisms. Heme oxygenase (HO) 1, a rate-limiting enzyme in heme metabolism, exerts a wide range of anti-inflammatory, anti-apoptotic and immunoregulatory effects in a variety of diseases. However, the relationship between MSCs and HO-1 in the treatment of ALF is still unclear. We investigated the preventive and therapeutic potential of intravenously administered BMSCs. Bone marrow-derived mesenchymal stem cells (BMSCs) obtained from Sprague–Dawley rats were isolated and cultured. We employed BMSCs, hemin (a HO-1 inducer) and zinc protoporphyrin (ZnPP, the HO-1 activity inhibitor) in D-galactosamine (D-Gal)/lipopolysaccharides (LPS)-induced ALF rats. Rats were sacrificed at days 1, 3, 5, and 7 post-transfusion, respectively. Blood samples and liver tissues were collected. Hepatic injury, HO-1 activity, chemokines, inflammatory cytokines, the number and oxidative activity of neutrophils, ki67, and TUNEL-positive cells were evaluated. HO-1 induction or BMSCs transplantation attenuated D-galactosamine/lipopolysaccharide-induced increases in alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBIL), ammonia, and inflammatory cytokines. Treatment with hemin or BMSCs also inhibited neutrophil infiltration, oxidative activity, and hepatocyte apoptosis. The protective effect of BMSCs was partially neutralized by ZnPP, suggesting the key role of HO-1 in the process. These findings may correlate with inhibition of nuclear factor-κ B activation. BMSCs ameliorated ALF by increasing the HO-1 expression, which reduced PMN infiltration and function, and played an important anti-inflammatory and anti-apoptotic role. Proposed mechanism by which BMSCs reduce inflammation, neutrophil activation, and hepatocyte apoptosis and promote hepatocyte proliferation via HO-1. BMSCs increase HO-1 expression in liver via Nrf2. HO-1 protects against LPS/D-Gal-induced ALF by inhibiting neutrophil infiltration and inflammatory burst, and hepatocyte apoptosis and necrosis. HO-1 also promotes hepatocyte proliferation.