chiniofon and Pancreatic-Neoplasms

GRP78 (glucose-regulated protein, 78 kDa) is a key regulator of endoplasmic reticulum (ER) stress signaling. Cancer cells are highly proliferative and have high demand for protein synthesis and folding, which results in significant stress on the ER. To respond to ER stress and maintain cellular homeostasis, cells activate the unfolded protein response (UPR) that promotes either survival or apoptotic death. Cancer cells utilize the UPR to promote survival and growth. In this study, we describe the discovery of a series of novel hydroxyquinoline GRP78 inhibitors. A representative analogue, YUM70, inhibited pancreatic cancer cell growth

Topics: A549 Cells; Animals; Apoptosis; Cell Line, Tumor; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Reticulum Stress; Female; HCT116 Cells; Heat-Shock Proteins; HT29 Cells; Humans; Hydroxyquinolines; MCF-7 Cells; Mice; Mice, Nude; Pancreatic Neoplasms; Unfolded Protein Response; Xenograft Model Antitumor Assays

Five years after the identification of the von Hippel-Lindau (VHL) gene, physicians, scientists and concerned VHL family members met to review the current state of knowledge on the diagnosis and treatment of VHL and to summarize the latest information on the biochemistry of the VHL protein (pVHL). The NIH and University of Pennsylvania groups reported the detection of germ-line mutations in 100% (93 of 93) of VHL families studied. Several studies determined the frequency of VHL germ-line mutations in individuals with a single manifestation of VHL without a family history of VHL. National groups to improve the diagnosis and treatment of individuals with VHL disease have been established in Great Britain, Denmark, France, Holland, Italy, Japan, Poland, and the United States. Evidence for the existence of genes that modify the expression of VHL was presented. The VHL protein appears to have several distinct functions: (a) down-regulation of hypoxia-inducible mRNAs; (b) proper assembly of the extracellular fibronectin matrix; (c) regulation of exit from the cell cycle; and (d) regulation of expression of carbonic anhydrases 9 and 12.

Topics: Animals; Carcinoma, Renal Cell; Central Nervous System Neoplasms; Cystadenoma, Papillary; Disease Models, Animal; DNA Mutational Analysis; Exons; Genes, Lethal; Genetic Testing; Genotype; Hemangioblastoma; Hemangioma; Humans; Hydroxyquinolines; Kidney Neoplasms; Ligases; Mice; Mice, Knockout; Mice, Nude; Neoplasms; Neovascularization, Pathologic; Nephrectomy; Pancreatic Neoplasms; Paraganglioma; Phenotype; Polymerase Chain Reaction; Proteins; Radiosurgery; Retinal Neoplasms; Trophoblasts; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; von Hippel-Lindau Disease; Von Hippel-Lindau Tumor Suppressor Protein

Topics: Adenoma, Islet Cell; Administration, Topical; Adult; Buttocks; Erythema; Female; Glucagonoma; Groin; Humans; Hydroxyquinolines; Iodoquinol; Pancreatic Neoplasms; Recurrence; Skin Diseases, Infectious