Digestive malignancies are the leading cause of mortality among all neoplasms, contributing to estimated 3 million deaths in 2012 worldwide. The mortality rate hassurpassed lung cancer and prostate cancer in recent years. The transcription factor Forkhead Box O1 (FOXO1) is a key member of Forkhead Box family, regulating diverse cellular functions during tumor initiation, progression and metastasis. In this review, we focus on recent studies investigating the antineoplastic role of FOXO1 in digestive malignancy. This review aims to serve as a guide for further research and implicate FOXO1 as a potent therapeutic target in digestive malignancy.

Acute liver failure (ALF) is a complicated clinical syndrome associated with high mortality, with liver transplantation as the only treatment option. Treatment of mesenchymal stem cells has shown a potential therapeutic option for acute liver failure. However, the lack of random clinical trials and large non-human primate studies makes it necessary to assess the efficacy and safety in the clinic. We treated the monkeys with peripheral delivery of human umbilical MSCs (hUC-MSCs) and investigated the role of hUC-MSCs in modulating the progress of acute liver failure. The use of early peripheral infusion of human umbilical cord MSC infusion did not improve liver regeneration or modulate adaptive immunity. However, it significantly suppressed the hepatic aggregation and maturation of circulating monocytes and their IL-6 secretion, greatly improving liver histology, systemic homeostasis, and survival. Our study reveals the critical role of monocyte-derived IL-6 in initiating and accelerating acute liver failure and hUC-MSC treatment can disrupt the development of the inflammatory cascade by inhibiting monocyte activation. Early hUC-MSC treatment disrupts the development of the inflammatory cascade, indicating a potential clinical solution for acute liver failure.

Loss of ZG16 is regulated by miR-196a and contributes to stemness and progression of colorectal cancer Loss of ZG16 is regulated by miR-196a and contributes to stemness and progression of colorectal cancer

To survive, cells need to avoid excessive volume change that jeopardizes structural integrity and stability of the intracellular milieu. Searching for the molecular identity of volume‑regulated anion channel (VRAC) has yielded multiple potential candidates, but none has been confirmed. Recently, it is reported that leucine‑rich repeat‑containing 8A (LRRC8A) is a main molecular determinant of VRAC current. The biological functions of LRRC8 family proteins are poorly understood, particularly in cancer. In the present study, we investigated LRRC8A in the most common cancers of the digestive system. LRRC8A proteins were found to be abundantly expressed in the esophagus, stomach, duodenum, colon, rectum, liver and pancreas. LRRC8A was elevated in 60% of colorectal cancer patient tissues, which was higher than that in patients with cancer of the esophagus, stomach, duodenum, liver and pancreas. Colon cancer patients with high‑ expressed LRRC8A had a survival time of 54.9±5.5 months, shorter than that of patients with low‑expressed LRRC8A (77.1±3.7). Moreover, survival time (52.6±7.3 months) of patients with metastases in the lymph nodes was shorter than that of patients without positive lymph nodes (72.2±3.6); patients with positive lymph nodes and an elevated LRRC8A expression had the highest mortality rate (~80%). These rates were not observed in rectal cancer. After LRRC8A protein was knocked down in colon cancer HCT116 cells, VRAC currents, migration and tumorigenesis in nude mice were significantly inhibited. In conclusion, we propose that LRRC8A could be a novel prognostic biomarker for colon cancer patient survival, and that the elevated expression of LRRC8A may enhance cancer cell growth and metastasis, and worsen the outcome of patients.

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.

Gastric cancer (GC) has been an increasingly serious problem in public health. However, there is still a lack of efficient approach to diagnosis and treatment in time, especially in the field of targeted therapy. Increasing evidences demonstrated that DNA methylation plays an essential role in tumorigenesis and progression of GC. Thus the present study aims to identify DNA methylation-based prognostic biomarkers in GC. Two methylation array datasets (GSE25869 and GSE30601) and RNA-seq based gene profiling dataset (TCGA-STAD) were employed for exploring candidate DNA methylation-based biomarkers. Univariate Cox regression analysis was used to select the most efficient prognostic genes in GC patients. Weighted gene correlation network analysis (WGCNA) was performed to screen the cluster of co-expressed genes. As a result, our data proved that NRP1 was a hypomethylated / upregulated gene in GC tissues, and PDGFRB was strongly co-expressed with it. Both of them were significantly associated with the overall survival of patients. More importantly, high expression levels of NRP1 and PDGFRB were associated with malignant phenotypes in GC patients, including Laurén histological diffuse type and higher histological grade. Patients carrying high expression level of NRP1 and PDGFRB had a nearly two-fold increased death risk than others. In summary, the hypomethylated gene, NRP1, and its co-expressed gene, PDGFRB, were significantly correlated with tumor malignant phenotypes, which might serve as potential prognostic biomarkers for GC patients.