Pancreatic cancer is malignant and the seventh leading cause of cancer-related deaths worldwide. However, chemotherapy and radiotherapy are—at most—moderately effective, indicating the need for new and different kinds of therapies to manage this disease. It has been proposed that the biologic properties of pancreatic cancer cells are finely tuned by the dynamic microenvironment, which includes extracellular matrix, cancer-associated cells, and diverse immune cells. Accumulating evidence has demonstrated that extracellular vesicles (EVs) play an essential role in communication between heterogeneous subpopulations of cells by transmitting multiplex biomolecules. EV-mediated cell–cell communication ultimately contributes to several aspects of pancreatic cancer, such as growth, angiogenesis, metastasis and therapeutic resistance. In this review, we discuss the role of extracellular vesicles and their cargo molecules in pancreatic cancer. We also present the feasibility of the inhibition of extracellular biosynthesis and their itinerary (release and uptake) for a new attractive therapeutic strategy against pancreatic cancer.

Background/Aim: MicroRNAs (miRNAs) play regulatory roles in pancreatic ductal adenocarcinoma (PDAC). However, it is still required to identify the function of miRNA-301-3p in pancreatic cancer cells. Materials and Methods: Effects of luteolin on cell growth, TRAIL cytotoxicity, and miR-301-3p levels were evaluated. The role of miRNA-301-3p in regulating cell proliferation, target gene expression, and TRAIL cytotoxicity were studied. Results: The levels of miR-301-3p were down-regulated in PANC-1 cells exposed to luteolin, which inhibits the growth of PANC-1 cells and sensitizes cells to TRAIL. The knockdown of miR-301-3p attenuates cell proliferation and enhances TRAIL cytotoxicity. In addition, caspase-8 was directly targeted by miR-301-3p. Conclusion: Our findings unveil a critical biological function of miR-301-3p in regulating cell proliferation and elevating an antiproliferative effect of TRAIL on cancer cells. Our observation of miR-301-3p/caspase-8 relationship can also serve to clarify the role of miR-301-3p in other cancer types and related diseases.Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer and a highly fatal malignancy with lymph node or distant metastases upon diagnosis. PDAC is predicted to be the second principal cause of cancer-related deaths by the year 2030 (1). Despite much progress on pancreatic cancer research over the past decades, surgery is the only attempt towards a curative outcome (2). Insufficient clinical efficacy of chemotherapy and radiation therapy has been reported and attributed to drug resistance in PDAC (3-6). Several signaling pathways, including nuclear factor kappa light chain enhancer of activated B cells (NF-ĸB) signaling, are activated, leading to cell growth and metastasis in PDAC. Mutations in tumor suppressor genes are also detected in PDAC (5, 7-9). A better understanding of the molecular characteristics of PDAC can lead to development of novel treatment strategies to combat PDAC.Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL has been known to inhibit cell growth by inducing cell-cycle arrest (10,11). In addition, anticancer effects of TRAIL can occur through death receptors 4 and 5, which generally regulate the activation of caspases, a family of cysteine proteases (12-14). Upon TRAIL binding, activation of caspase-8 cleaves executioner caspases, such as caspase-3 and -7, by which effective caspases contribute to chromatin condensation and nuclear fragmentation with the formation of apoptotic bodies (12-15). Indeed, TRAIL-induced apoptosis is impeded by the low expression of death receptors and caspases (16-18). Moreover, TRAIL resistance is associated with FADD-like ICE inhibitory proteins (FLIP) and inhibitor of apoptosis (IAP) family, such as cIAP, XIAP, and survivin, which inhibit the activation of caspases (19). Accumulating evidence has shown that combination of TRAIL with cancer therapeutic agents is effective to subdue TRAIL resistance. For instance, trea...

Background Inbred mice have several advantages, including genetic similarity to humans, a well-established gene manipulation system, and strong tolerance to inbreeding. However, inbred mice derived from a limited genetic pool have a small genetic diversity. Thus, the development of new inbred strains from wild mice is needed to overcome this limitation. Hence, in this study, we used a new strain of inbred mice called KWM/Hym. We sequenced the Mx1 gene to elucidate the genetic diversities of KWM/Hym mice and observed the biological alterations of the Mx1 protein upon influenza A infection. Results The Mx1 gene in KWM/Hym mice had 2, 4, and 38 nucleotide substitutions compared to those in the Mx1 gene in A2G, CAST/EiJ, and Mus spretus mice, respectively. Moreover, the Mx1 protein in KWM/Hym mice had 2 and 25 amino acid substitutions compared to those in the Mx1 protein in CAST/EiJ and M. spretus mice, respectively. To elucidate the function of the Mx1 protein, we inoculated the influenza A virus (A/WSN/1933) in KWM/Hym mice. Nine days after infection, all infected KWM/Hym mice survived without any weight loss. Four days after infection, the lungs of the infected KWM/Hym mice showed mild alveolitis and loss of bronchiolar epithelium; however, the pulmonary viral titers of the infected KWM/Hym mice were significantly lower than that in the infected BALB/c mice (2.17 × plaque-forming units mL−1). Conclusions Our results demonstrate that the KWM/Hym mice are resistant to influenza A virus infection. Further, these mice can be used as a model organism to understand the mechanism of influenza A virus susceptibility.