Citations

AbstractObjectiveThe study's aims were (1) to investigate the prevalence and (2) to assess the risk of Helicobacter pylori (H. pylori) infection in kidney transplant recipients.MethodsA comprehensive literature search was performed from inception until September 2016. Studies that reported prevalence, relative risks, odd ratios, or hazard ratios of H. pylori among kidney transplant recipients were included. Pooled risk ratios and 95% CI were calculated using a random‐effect model.ResultsEleven observational studies with 2545 kidney transplant recipients were enrolled. Between year 1990 and 2000, the estimated prevalence of H. pylori among people with kidney transplant was 50% (95% CI: 31% to 68%), with a prevalence of 46% (95% CI: 23% to 70%) in high‐income countries and 55% (95% CI: 22% to 86%) in middle‐income countries, respectively. From year 2000 to 2016, the estimated prevalence of H. pylori among people with kidney transplant was 35% (95% CI: 26% to 45%), with a prevalence of 28% (95% CI: 19% to 37%) in high‐income countries and 45% (95% CI: 38% to 51%) in middle‐income countries. Data regarding prevalence of H. pylori infection in low‐income countries were limited. The pooled RR of H. pylori in kidney transplant recipients was 0.57 (95% CI: 0.33 to 1.00) when compared to people with non‐transplant.ConclusionsThere has been a decline in prevalence of H. pylori in kidney transplant recipients with the overall estimated prevalence of H. pylori in kidney transplant recipients of 35%, particularly in both high‐income and middle‐income countries. Also, our meta‐analysis demonstrates a potential decreased risk of H. pylori infection in kidney transplant recipients compared with non‐transplant populations.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies lacking effective therapeutic strategies. Here, we show that the noncanonical IκB-related kinase, IKBKE, is a critical oncogenic effector during KRAS-induced pancreatic transformation. Loss of IKBKE inhibits the initiation and progression of pancreatic tumors in mice carrying pancreatic-specific KRAS activation. Mechanistically, we demonstrate that this protumoral effect of IKBKE involves the activation of GLI1 and AKT signaling and is independent of the levels of activity of the NF-κB pathway. Further analysis reveals that IKBKE regulates GLI1 nuclear translocation and promotes the reactivation of AKT post-inhibition of mTOR in PDAC cells. Interestingly, combined inhibition of IKBKE and mTOR synergistically blocks pancreatic tumor growth. Together, our findings highlight the functional importance of IKBKE in pancreatic cancer, support the evaluation of IKBKE as a therapeutic target in PDAC, and suggest IKBKE inhibition as a strategy to improve efficacy of mTOR inhibitors in the clinic. Cancer Res; 77(2); 320–9. ©2017 AACR.

Abstract Previous preclinical studies and a phase I clinical trial suggested that myo-inositol may be a safe and effective lung cancer chemopreventive agent. We conducted a randomized, double blind, placebo-controlled phase IIb study to determine the chemopreventive effects of myo-inositol in smokers with bronchial dysplasia. Smokers with ≥1 site of dysplasia identified by autofluorescence bronchoscopy-directed biopsy were randomly assigned to receive oral placebo or myo-inositol, 9 g once a day for 2 weeks, and then twice a day for 6 months. The primary endpoint was change in dysplasia rate after 6 months of intervention on a per-participant basis. Other trial endpoints reported herein include Ki-67 labeling index, blood and bronchoalveolar lavage fluid (BAL) levels of proinflammatory, oxidant/antioxidant biomarkers, and an airway epithelial gene expression signature for PI3K activity. Seventy-four (n = 38 myo-inositol and n = 36 placebo) participants with a baseline and 6-month bronchoscopy were included in all efficacy analyses. The complete response and the progressive disease rates were 26.3% versus 13.9% and 47.4% versus 33.3%, respectively, in the myo-inositol and placebo arms (P = 0.76). Compared with placebo, myo-inositol intervention significantly reduced IL6 levels in BAL over 6 months (P = 0.03). Among those with a complete response in the myo-inositol arm, there was a significant decrease in a gene expression signature reflective of PI3K activation within the cytologically normal bronchial airway epithelium (P = 0.002). The heterogeneous response to myo-inositol suggests a targeted therapy approach based on molecular alterations is needed in future clinical trials to determine the efficacy of myo-inositol as a chemopreventive agent. Cancer Prev Res; 9(12); 906–14. ©2016 AACR.

Abstract Donor organ shortage is the main limitation to liver transplantation as a treatment for end-stage liver disease and acute liver failure. Liver regenerative medicine may in the future offer an alternative form of therapy for these diseases, be it through cell transplantation, bioartificial liver (BAL) devices, or bioengineered whole organ liver transplantation. All three strategies have shown promising results in the past decade. However, before they are incorporated into widespread clinical practice, the ideal cell type for each treatment modality must be found, and an adequate amount of metabolically active, functional cells must be able to be produced. Research is ongoing in hepatocyte expansion techniques, use of xenogeneic cells, and differentiation of stem cell-derived hepatocyte-like cells (HLCs). HLCs are a few steps away from clinical application, but may be very useful in individualized drug development and toxicity testing, as well as disease modeling. Finally, safety concerns including tumorigenicity and xenozoonosis must also be addressed before cell transplantation, BAL devices, and bioengineered livers occupy their clinical niche. This review aims to highlight the most recent advances and provide an updated view of the current state of affairs in the field of liver regenerative medicine.