title: Tumour blood vessel normalisation by prolyl hydroxylase inhibitor repaired sensitivity to chemotherapy in a tumour mouse model.
abstract: Blood vessels are important tissue structures that deliver oxygen and nutrition. In tumour tissue, abnormal blood vessels, which are hyperpermeable and immature, are often formed; these tissues also have irregular vascularisation and intravasation. This situation leads to hypoperfusion in tumour tissue along with low oxygen and nutrition depletion; this is also called the tumour microenvironment and is characterised by hypoxia, depleted nutrition, low pH and high interstitial pressure. This environment induces resistance to anticancer drugs, which causes an increase in anticancer drug doses, leading to increased side effects. We hypothesised that normalised tumour blood vessels would improve tumour tissue perfusion, resupply nutrition and re-oxygenate the tumour tissue. Chemotherapy would then be more effective and cause a decrease in anticancer drug doses. Here we report a neovascularisation-inducing drug that improved tumour vascular abnormalities, such as low blood flow, blood leakage and abnormal vessel structure. These results could lead to not only an increased chemo-sensitivity and tissue-drug distribution but also an up-regulated efficiency for cancer chemotherapy. This suggests that tumour blood vessel normalisation therapy accompanied by angiogenesis may be a novel strategy for cancer therapy.
authors.affiliation: Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan.|Division of Otolaryngology, Head and Neck Surgery, Department of Sensory and Motor Organs, Tottori University Faculty of Medicine, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Koyama
authors.affiliation: Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan.|Department of Pharmacology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Matsunaga
authors.affiliation: Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Imanishi
authors.affiliation: Department of Parasitology Gifu University Graduate School of Medicine, Japan.|Domain of Integrated Life Systems, Gifu Center for Highly Advanced Integration of Nanosciences and Life Sciences (G-CHAIN), Gifu University, Gifu, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Maekawa
authors.affiliation: Division of Otolaryngology, Head and Neck Surgery, Department of Sensory and Motor Organs, Tottori University Faculty of Medicine, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kitano
authors.affiliation: Division of Otolaryngology, Head and Neck Surgery, Department of Sensory and Motor Organs, Tottori University Faculty of Medicine, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Division of Molecular Pharmacology, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Japan.|Department of Pharmacology, Osaka City University Graduate School of Medicine, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tomita
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D064800:Prolyl-Hydroxylase Inhibitors / Q000008:administration & dosage*; D000072258:Tumor Hypoxia; D059016:Tumor Microenvironment
chemical_list: D000600:Amino Acids, Dicarboxylic; D000970:Antineoplastic Agents; D064800:Prolyl-Hydroxylase Inhibitors; C040947:oxalylglycine