title: Pancreatic carcinogenesis: apoptosis and angiogenesis.
abstract: Apoptosis and angiogenesis are critical biologic processes that are altered during carcinogenesis. Both apoptosis and angiogenesis may play an important role in pancreatic carcinogenesis. Despite numerous advances in the diagnosis and treatment of pancreatic cancer, its prognosis remains dismal and a new therapeutic approach is much needed. Recent research has revealed that apoptosis and angiogenesis are closely interrelated. Several reports show that a tumor suppresser gene that is expressed in pancreatic carcinoma and related to malignant potential can induce apoptosis and also inhibit angiogenesis. At present, it is generally accepted that tumor growth in cancers, including pancreatic cancer, depends on angiogenesis. We have identified 2 new angiogenesis inhibitors from a conditioned medium of human pancreatic carcinoma cell line (BxPC-3): antiangiogenic antithrombin III (aaAT-III) and vitamin D binding protein-macrophage activating factor (DBP-maf). These molecules were able to regress tumors in severe combined immunodeficiency disease (SCID) mice, demonstrating potent inhibition of endothelial cell proliferation. Moreover, the angiogenesis inhibitors induced tumor dormancy in the animal model. These results suggest that antiangiogenic therapy using angiogenesis inhibitors may become a new strategy for treatment of pancreatic cancer in the near future.
authors.affiliation: Department of Surgery, National Nagasaki Medical Center, Japan. sonizuka@nmc.hosp.go.jp
authors.forename: Shinya
authors.initials: S
authors.lastname: Onizuka
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kawakami
authors.forename: Ken
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Hikaru
authors.initials: H
authors.lastname: Fujioka
authors.forename: Kosei
authors.initials: K
authors.lastname: Miyashita
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D006801:Humans; D016215:Macrophage-Activating Factors; D051379:Mice; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D014809:Vitamin D-Binding Protein
chemical_list: D020533:Angiogenesis Inhibitors; D016215:Macrophage-Activating Factors; D014809:Vitamin D-Binding Protein; C101908:vitamin D-binding protein-macrophage activating factor