title: TRAIL mediated signaling in pancreatic cancer.
abstract: Research over the years has progressively shown substantial broadening of the tumor necrosis factor alpha- related apoptosis-inducing ligand (TRAIL)-mediated signaling landscape. Increasingly it is being realized that pancreatic cancer is a multifaceted and genomically complex disease. Suppression of tumor suppressors, overexpression of oncogenes, epigenetic silencing, and loss of apoptosis are some of the extensively studied underlying mechanisms. Rapidly accumulating in vitro and in vivo evidence has started to shed light on the resistance mechanisms in pancreatic cancer cells. More interestingly a recent research has opened new horizons of miRNA regulation by DR5 in pancreatic cancer cells. It has been shown that DR5 interacts with the core microprocessor components Drosha and DGCR8, thus impairing processing of primary let-7. Xenografting DR5 silenced pancreatic cancer cells in SCID-mice indicated that there was notable suppression of tumor growth. There is a paradigm shift in our current understanding of TRAIL mediated signaling in pancreatic cancer cells that is now adding new layers of concepts into the existing scientific evidence. In this review we have attempted to provide an overview of recent advances in TRAIL mediated signaling in pancreatic cancer as evidenced byfindings of in vitro and in vivo analyses. Furthermore, we discuss nanotechnological advances with emphasis on PEG-TRAIL and four-arm PEG cross-linked hyaluronic acid (HA) hydrogels to improve availability of TRAIL at target sites.
authors.affiliation: Department of Industrial Pharmacy, Health Science Center, Federal University of Santa Maria, Santa Maria-RS, Brazil E-mail : ammadahmad638@yahoo.com.
authors.forename: Daniele Rubert
authors.initials: DR
authors.lastname: Nogueira
authors.forename: Ilhan
authors.initials: I
authors.lastname: Yaylim
authors.forename: Qurratulain
authors.initials: Q
authors.lastname: Aamir
authors.forename: Ozlem Timirci
authors.initials: OT
authors.lastname: Kahraman
authors.forename: Sundas
authors.initials: S
authors.lastname: Fayyaz
authors.forename: Syed
authors.initials: S
authors.lastname: Kamran-ul-Hassan Naqvi
authors.forename: Ammad Ahmad
authors.initials: AA
authors.lastname: Farooqi
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand