1999 Fiscal Year Annual Research Report

ミャンマー国肝癌発生要因としてのサラセミア症の鉄過剰症と輸血関連疾患の調査研究

Research Project

Project/Area Number	10042006
Research Institution	Okayama University
Principal Investigator	岡田茂岡山大学, 医学部, 教授 (20033201)
Co-Investigator(Kenkyū-buntansha)	新津洋司郎札幌医科大学, 医学部, 教授 (10045502) 小路武彦長崎大学, 医学部, 教授 (30170179) 石川隆俊東京大学, 医学部, 教授 (30085633)
Keywords	鉄過剰 / 肝癌 / ウイルス性肝炎 / ヤンゴン / ヘモグロビン等電点電気泳動 / 遺伝子検索 / p53変異 / 輸血
Research Abstract	鉄は発癌と強く関連している。ミヤンマー国においては、サラセミアなどの鉄過剰をもたらす遺伝疾患が蔓延しており、また、肝癌の発生が若年者に多く見られる。鉄過剰がウイルス性肝炎病態の悪化因子であることが判明してきたこともあり、同国において、B、C型ウイルス肝炎の広がりと共に、鉄過剰状態を調査した。国立ヤンゴン総合病院、国立小児病院で採決を行った。Cは国立医学研究局で行った。肝癌組織の分子病理学的検索は日本で行った。11年度はマンダレー地方の疾病構造に関する調査を行った。肝癌病患者102名の93%にB型肝炎既往があり、内35%はHBs抗原陽性であった。39%はanti-HCV陽性であり、内79%にHCV-RNAが証明された。肝癌患者28名の内46%はB型肝炎、21%はC型肝炎から発症したものと考えられた。受血者33名の約半数にC型肝炎ウイルス抗体が証明された。供血者にも5.9%に抗C型ウイルス抗体が発見された。遺伝子検索ではhMTH1遺伝子変異が10例中1例見つかったが、アミノ酸変化はなかった。P53変異は5例見られた。4例はコドン159(エクソン5)のGCCからCCCへの変異でAlaからProへの変化を伴い特徴的であった。ヘモグロビン等電点電気泳動16例中3例にヘモグロビンA2、1例にヘモグロビンFが見られた。異常ヘモグロビン症の保因者と考えられるが、対象例と頻度は変わらない。鉄過剰は83%にみられた。マンダレー視察報告:森林を中心とした貧困地帯で、マラリアの蔓延、デング熱の頻発が恒常的である。肝炎の発生症並びに肝癌の発症との関連については、ヤンゴンで見られた状況と大差ないが、輸血と共に麻薬の回し打ちが問題視されており、AIDSとの併発が強く指摘された。この国ではC型肝炎に関する検索は全くなされていなかった。私達の調査により、他の東南アジアと同じ位の蔓延率があることが判明した。対策に緊急を要する。

Research Products
(20 results)

All Other

All Publications (20 results)

[Publications] S.Okada: "Iron and carcinogenesis in laboratory animals and humans:A Mechanistic consideration and a review of literature"Int.J.Clin.Oncol.. 3. 191-203 (1998)
[Publications] Yuxiang Ma: "Sex differences in oxidative damage in ddY mouse kidney treated with a renal carcinogen,iron nitrilotriacetate"Carcinogenesis. 19. 198-198 (1998)
[Publications] H,Kawate: "Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes"Proc.Natl.Acad.Sci.USA. 95. 5116-5120 (1998)
[Publications] T.Sato: "Differentiation induction by a tumor-necrosis-factor mutant 471 in human myelogenous leukemic cells via tumor-necrosis-factor receptor-p55"Int J Cancer. 78. 223-232 (1998)
[Publications] Y.Hirayama: "Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura,aplastic anemia,and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells"Blood. 92. 46-52 (1998)
[Publications] T.Takayama: "Aberant crypt foci if the colon as precursors of adenoma and cancer"New Eng J Med. 339. 1277-1284 (1998)
[Publications] H.K.Kawai: "Shift of hepatitis E virus RNA from hepatocytes to biliary epithelial cells during acute infection of rhesus monky"Journal of Viral Hepatitis. 6. 287-297 (1999)
[Publications] Y.Hishikawa: "Metallothionein expression correlates with metastatic and proliferative potential in squamous cell carcinoma of the oesophagus"British Journal of Cancer. 81. 712-720 (1999)
[Publications] S.Sakamaki: "Transforming growth factor-β1(TGF-β1) induces thrombopoietin from bone marrow stromal cells,witch stimulates theexpression of TGF-β receptor on megakaryocytes and, in turn, renders them susceptible to suppression by TGF-β itself with high specificity"Blood. 94. 1961-1970 (1999)
[Publications] S.Yamano: "Induction of transformation and P53-dependent apoptosis by adenovirus type 5 e4or f6/7 cDNA"J Virol.. 10095-10103 (1999)
[Publications] T.Koji: "In situ localization of gene-specific transcription regulatory factors by southwestern histochemistry"Acta Histochem. Cytochem. 32. 255-260 (1999)
[Publications] K.Ejima: "Induction of apoptosis in placentas of pregnant mice exposed to lipopolysacchardes: Possible involvement of Fas/Fas ligand system"Biology of Peproduction. 62. 178-185 (2000)
[Publications] Kaori Eguchi: "Apoptosis and 8-hydroxydeoxyguanosine levels in renal tissue after an injection of ferric nitrilotriacetate, a renal carcinogen, in male Wistar rats maintained on vitamin E-deficient,-nomal or -supplemented diets"Pathophysiology. 6. 149-156 (1999)
[Publications] Yuxiang Ma: "In terrelations of clinicopathological variables, local immune response and prognosis in esophageal squamous cell carcinoma"APMIS. 107. 514-522 (1999)
[Publications] T,.Ishikawa: "Inhibition DMBA initiation of skin canser by IP6 in vivo initiation -promotion model"Anticancer Reseach. 19. 3749-3752 (1999)
[Publications] Y,Terauchi: "Increased insulin sensitivity and hypoglysaemia in mice lacking the p85α subunit of phosphoinositide 3-kinase"Nature Genetics. 21. 230-240 (1999)
[Publications] Y.Shimizu: "Different frequencies of p53 codon-249 hot-spot mutations in hepatocellular carcinomas in jiangsu province of china"Int.J.Cancer. 82. 187-190 (1999)
[Publications] S.Hiroyasu: "Analysis of Fas system and Bcl-2 in rat liver allograft rejection"J Surg Res. 84. 204-211 (1999)
[Publications] Y.Shimizu: "Benzo [a] pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor"Proc.Natl.Acad.Sci.USA. 97. 779-782 (2000)
[Publications] S.Okada: "High prevalence of hepatitis C in patients with thalassemia and patients with liver diseases in Myanmar(Burma)"Acta.Med.Okayama. (in press). (2000)

1999 Fiscal Year Annual Research Report

ミャンマー国肝癌発生要因としてのサラセミア症の鉄過剰症と輸血関連疾患の調査研究

Principal Investigator

岡田 茂 岡山大学, 医学部, 教授 (20033201)

Research Products

[Publications] S.Okada: "Iron and carcinogenesis in laboratory animals and humans:A Mechanistic consideration and a review of literature"Int.J.Clin.Oncol.. 3. 191-203 (1998)

[Publications] Yuxiang Ma: "Sex differences in oxidative damage in ddY mouse kidney treated with a renal carcinogen,iron nitrilotriacetate"Carcinogenesis. 19. 198-198 (1998)

[Publications] H,Kawate: "Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes"Proc.Natl.Acad.Sci.USA. 95. 5116-5120 (1998)

[Publications] T.Sato: "Differentiation induction by a tumor-necrosis-factor mutant 471 in human myelogenous leukemic cells via tumor-necrosis-factor receptor-p55"Int J Cancer. 78. 223-232 (1998)

[Publications] Y.Hirayama: "Concentrations of thrombopoietin in bone marrow in normal subjects and in patients with idiopathic thrombocytopenic purpura,aplastic anemia,and essential thrombocythemia correlate with its mRNA expression of bone marrow stromal cells"Blood. 92. 46-52 (1998)

[Publications] T.Takayama: "Aberant crypt foci if the colon as precursors of adenoma and cancer"New Eng J Med. 339. 1277-1284 (1998)

[Publications] H.K.Kawai: "Shift of hepatitis E virus RNA from hepatocytes to biliary epithelial cells during acute infection of rhesus monky"Journal of Viral Hepatitis. 6. 287-297 (1999)

[Publications] Y.Hishikawa: "Metallothionein expression correlates with metastatic and proliferative potential in squamous cell carcinoma of the oesophagus"British Journal of Cancer. 81. 712-720 (1999)

[Publications] S.Yamano: "Induction of transformation and P53-dependent apoptosis by adenovirus type 5 e4or f6/7 cDNA"J Virol.. 10095-10103 (1999)

[Publications] T.Koji: "In situ localization of gene-specific transcription regulatory factors by southwestern histochemistry"Acta Histochem. Cytochem. 32. 255-260 (1999)

[Publications] K.Ejima: "Induction of apoptosis in placentas of pregnant mice exposed to lipopolysacchardes: Possible involvement of Fas/Fas ligand system"Biology of Peproduction. 62. 178-185 (2000)

[Publications] Kaori Eguchi: "Apoptosis and 8-hydroxydeoxyguanosine levels in renal tissue after an injection of ferric nitrilotriacetate, a renal carcinogen, in male Wistar rats maintained on vitamin E-deficient,-nomal or -supplemented diets"Pathophysiology. 6. 149-156 (1999)

[Publications] Yuxiang Ma: "In terrelations of clinicopathological variables, local immune response and prognosis in esophageal squamous cell carcinoma"APMIS. 107. 514-522 (1999)

[Publications] T,.Ishikawa: "Inhibition DMBA initiation of skin canser by IP6 in vivo initiation -promotion model"Anticancer Reseach. 19. 3749-3752 (1999)

[Publications] Y,Terauchi: "Increased insulin sensitivity and hypoglysaemia in mice lacking the p85α subunit of phosphoinositide 3-kinase"Nature Genetics. 21. 230-240 (1999)

[Publications] Y.Shimizu: "Different frequencies of p53 codon-249 hot-spot mutations in hepatocellular carcinomas in jiangsu province of china"Int.J.Cancer. 82. 187-190 (1999)

[Publications] S.Hiroyasu: "Analysis of Fas system and Bcl-2 in rat liver allograft rejection"J Surg Res. 84. 204-211 (1999)

[Publications] Y.Shimizu: "Benzo [a] pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor"Proc.Natl.Acad.Sci.USA. 97. 779-782 (2000)

[Publications] S.Okada: "High prevalence of hepatitis C in patients with thalassemia and patients with liver diseases in Myanmar(Burma)"Acta.Med.Okayama. (in press). (2000)

岡田茂岡山大学, 医学部, 教授 (20033201)