Glycosylation of ascites-derived exosomal CD133: a potential prognostic biomarker in patients with advanced pancreatic cancer.

Cancer cells surviving in ascites exhibit cancer stem cell (CSC)-like features. This study analyzed the expression of the CSC marker CD133 in the ascites-derived exosomes obtained from patients with unresectable pancreatic cancer. In addition, inverse correlation of CD133 expression with prognosis was examined.

High expression of CD44v9 and xCT in chemoresistant hepatocellular carcinoma: Potential targets by sulfasalazine.

CD44v9 is expressed in cancer stem cells (CSC) and stabilizes the glutamate-cystine transporter xCT on the cytoplasmic membrane, thereby decreasing intracellular levels of reactive oxygen species (ROS). This mechanism confers ROS resistance to CSC and CD44v9-expressing cancer cells. The aims of the present study were to assess: (i) expression status of CD44v9 and xCT in hepatocellular carcinoma (HCC) tissues, including those derived from patients treated with hepatic arterial infusion chemoembolization (HAIC) therapy with cisplatin (CDDP); and (ii) whether combination of CDDP with sulfasalazine (SASP), an inhibitor of xCT, was more effective on tumor cells than CDDP alone by inducing ROS-mediated apoptosis.

STAT3 deficiency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury.

Aim: To elucidate the role of STAT3 in hepatocarcinogenesis and biliary ductular proliferation following chronic liver injury.

Methods: We investigated thioacetamide (TAA)-induced liver injury, compensatory hepatocyte proliferation, and hepatocellular carcinoma (HCC) development in hepatic STAT3-deficient mice. In addition, we evaluated TAA-induced biliary ductular proliferation and analyzed the activation of sex determining region Y-box9 (SOX9) and Yes-associated protein (YAP), which regulate the transdifferentiation of hepatocytes to cholangiocytes.

Pigment Epithelium-Derived Factor (PEDF) Prevents Hepatic Fat Storage, Inflammation, and Fibrosis in Dietary Steatohepatitis of Mice.

Background And Aims: Pigment epithelium-derived factor (PEDF) has been shown to be a potent inhibitor of inflammation through its anti-oxidative property. Since oxidative response is considered to play the pivotal role of the development and progression of nonalcoholic steatohepatitis (NASH), it is conceivable that PEDF may play a protective role against NASH. In this study, we examined whether administration of PEDF slowed the progression of NASH in mice models.

Pancreatic Neuroendocrine Tumors and EMT Behavior Are Driven by the CSC Marker DCLK1.

Doublecortin-like kinase 1 (DCLK1), a marker for intestinal and pancreatic cancer stem cells, is highly expressed in neuroblastomas. This study was conducted to assess DCLK1 expression levels in pancreatic neuroendocrine tumor (PNET) tissues and to explore the roles of this molecule in clinical tissue from multiple PNET patients, cells (BON1, QGP1, and CM) and tumor xenografts. Immunohistochemically, all PNET tissues highly and diffusely expressed DCLK1 as a full-length isoform, identical to that detected in primary liver NETs.

Antiangiogenic and Antitumor Activities of Aflibercept, a Soluble VEGF Receptor-1 and -2, in a Mouse Model of Hepatocellular Carcinoma.

Background & Aim: Aflibercept known as ziv-aflibercept in the United States is a soluble decoy receptor of both vascular endothelial growth factor (VEGF) receptor-1 and -2 known to inhibit the binding of VEGF and placental growth factor (PlGF) to VEGF receptor-1 and -2. Here, we analyzed the mechanisms of the antitumor effects of aflibercept in mouse hepatoma models.

Methods: In in vitro studies, we determined the effects of aflibercept on human umbilical vein cell (HUVEC) proliferation and bone marrow (BM) cell differentiation to endothelial progenitor cells (EPCs).

Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis.

Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34(+) cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl4 twice weekly for 3 weeks before administration of CD34(+) cells.

High expression of the putative cancer stem cell marker, DCLK1, in rectal neuroendocrine tumors.

Doublecortin-like kinase 1 (DCLK1), a microtubule-associated protein, is known to regulate neuronal differentiation, migration and neurogenesis. Recent evidence suggests that the protein is a putative marker for intestinal and pancreatic stem cells, including their cancer stem cell counterparts. The present study conducted immunohistochemical analyses for DCLK1 and the stemness marker, NANOG, in human intestinal neuroendocrine tumors (NETs), as their expression had not been previously investigated in these tumors.

Inhibition of hypoxia-inducible factor via upregulation of von Hippel-Lindau protein induces "angiogenic switch off" in a hepatoma mouse model.

"Angiogenic switch off" is one of the ideal therapeutic concepts in the treatment of cancer. However, the specific molecules which can induce "angiogenic switch off" in tumor have not been identified yet. In this study, we focused on von Hippel-Lindau protein (pVHL) in hepatocellular carcinoma (HCC) and investigated the effects of sulfoquinovosyl-acylpropanediol (SQAP), a novel synthetic sulfoglycolipid, for HCC.