1991 Fiscal Year Annual Research Report

肝炎ウイルスと肝発がん

Research Project

Project/Area Number	03151066
Research Institution	Japanese Foundation For Cancer Research
Principal Investigator	小池克郎 (財)癌研究会, 癌研究所, 部長 (30085625)
Co-Investigator(Kenkyū-buntansha)	小俣政男千葉大学, 医学部, 講師 (90125914) 宮村達男国立予防衛生研究所, 室長 (90100099) 下遠野邦忠国立癌センター研究所, 部長 (10000259) 小池和彦東京大学, 医学部, 助手 (90234658) 鎌田武信大阪大学, 医学部, 教授 (80028399)
Keywords	B型肝炎ウイルス / C型肝炎ウイルス / 慢性肝炎 / X遺伝子 / 肝がん / 肝発がん / HCVRNA / C100ー3抗体
Research Abstract	本年度の研究成果の概要は下記の如くである。また、疫学的にはヒト肝がんの9割以上がB型肝炎ウイルス(HBV)およびC型肝炎ウイルス(HCV)の感染に関係していることが分かってきた。 1.HBVと肝発がんについては、密接に関係していると考えられるX遣伝子の研究が進展した。 (1)、HBVのX蛋白質が細胞がん遺伝子をトランスに活性化し、また、培養細胞をがん化させることが知られ、メカニズムの研究が一段と進展した。X蛋白質にプロテア-ゼインヒビタ-との構造類似性が見出され、相互作用するプロテア-ゼが明らかにされた。(2)、X遺伝子を導入したトランスジェニックマウスが作製された。観察の結果、炎症や肝細胞壊死が認められないにもかかわらず、85%に肝腫瘍が発生した。肝がん中に高いXmRNA発現が認められた。(3)、HBV関連の肝がんには肝硬変を経過しないものがあることが示された。 2.HCVについては、RNAウイルスであることが1989年に明らかにされたばかりであり、その後、ゲノム構造および肝炎、肝がん組織中でのゲノムの存在様式の研究が始まったところである。 (1)、HCVゲノムが約9.5kb一本鎖RNAであることが明らかにされ、このゲノムからコ-ドされる前駆体タンパク質の産生が成功した。また、個々の遺伝子産物が大腸菌またはワクシニアの系で発現され、ウイルス抗体の検出系の開発に用いられた。(2)、1人1人の健康保因者からHCVのゲニムをクロ-ン化し塩基配列を比較すると、NSー1領域がきわめて変異に富むことが明らかにされた。また、母子間にHCVの感染があることが示された。(3)、肝がん96例について検討すると、HCVRNAあるいはC100ー3抗体陽性が61例であった。さらに、C型肝炎では肝病変が進行してもHCVの増殖が継続している例が認められた。

Research Products

(30 results)

All Other

All Publications (30 results)

[Publications] Arii,M.: "Identification of three essential regions of hepatitis B virus X protein for trans-activation function." Oncogene. 7. (1992)
[Publications] Ishihara,H.: "Specific uptake of asialofetuinーtacked liposomes encapsulating interferonーγ by human hepatoma cells and its inhibitory effect on hepatitis B virus replication." Biochem.Biophys.Res.Comm.174. 839-845 (1991)
[Publications] Takada,S.: "X protein of hepatitis B virus resembles a serine protease inhibitor." Jpn.J.Cancer Res.81. 1191-1194 (1990)
[Publications] Hagiwara,H.: "Detection of hepatitis C virus RNA in chronic non-A non-B liver disease." Gasteroenterology. 102. 692-694 (1992)
[Publications] Hagiwara,H.: "Detection of hepatitis C virus RNA sequences in serum during treatment for chronic hepatitis C with interferon alpha." Hepatology. 15. 37-41 (1992)
[Publications] Haruna,Y.: "Expression of X protein and hepatitis B virus replication in chronic hepatitis." Hepatology. 13. 417-421 (1991)
[Publications] M.Omata: "Resolution of acute hepatitis C after therapy with natural beta interferon." Lancet. 338. 914-915 (1991)
[Publications] M.Omata: "Detection of hepatitis C virus infection by enzyme-linked immunosolbent assay system using core protein expressed in Escherichia coli." Jpn.J.Cancer Res.82. 879-882 (1991)
[Publications] Naito,A.: "In vitro "progression" of bovine papilomavirus transformed cells:loss of contact sensitivity after multiple rouunds of selection." Int.J.Cancer. 48. 889-894 (1991)
[Publications] Naito,A.: "Homologous recombination in bovine papilomavirus shuttlevector:Effect of relative orientation of substrate sequences." Biochem.Biophys.Res.Comm.174. 305-312 (1991)
[Publications] Yoshikura,H.: "Detection and typing of multiple genital human papilomaviruses by DNA amplification with consensus primers." Jpn.J.Canocer Res.82. 524-531 (1991)
[Publications] Sugimura,H.: "The Histopathology of the liver in older patients with hepatitis B virus surface antigenemia" Virchow's Archives (A). 419. 409-415 (1991)
[Publications] Kohara,K.: "A second group of hepatitis C virus." Virus Genes. 5. 243-254 (1991)
[Publications] Kohara,K.: "Internal ribosome entry site within hepatitis C virus RNA." J.Virology. (1992)
[Publications] Inoue,Y.: "Maternal transfer of HCV" Nature. 353. 609 (1991)
[Publications] Chiba,J.: "Serodiagnosis of hepatitis C virus(HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus." Proc.Natl.Acad.Sci.USA. 88. 4641-4645 (1991)
[Publications] Matsuura,Y.: "Expression of processed envelope protein of hepatitis C virus in mammalian and insect cells." J.Virology. (1992)
[Publications] M.Omata: "Mutations in the precore region of hepatitis B virus DNA in patients with fulminant and severe hepatitis." New Engl.J.Med.324. 1699-1704 (1991)
[Publications] Hijikata,M.: "Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis." Proc.Natl.Acad.Sci.USA. 88. 5547-5551 (1991)
[Publications] Hijikata,M.: "Hypervariable regions in the putative glycoprotein of hepatitis C virus.(1991,Biochem.Biophys.Res.Commun.,175:220-228)" Biochem.Biophys.Res.Comm.175. 220-228 (1991)
[Publications] Muraiso,K.: "Detection of hepatitis C virus infection by enzyme-linked immunosolbent assay system using core protein expressed in escherichia coli." Jpn.J.Cancer Res.82. 879-882 (1991)
[Publications] Takamizawa,A.: "Structure and organization of the hepatitis C virus genome isolated from human carriers." J.Virology. 65. 1105-1113 (1991)
[Publications] Igarashi,M.: "Weel^+ーlike gene in human cells." Nature. 353. 80-83 (1991)
[Publications] Kume,K.: "Oncogenic signal-induced ability to enter S phase in the absence of anchorage is the mechanism for the growth of transformed NRK cells in soft agar." New Biologist. (1992)
[Publications] Kim,C.: "HBx gene of hepatitis B virus induces liver cancer in transgenic mice.(1991,Nature,351:317-320)" Nature. 351. 317-320 (1991)
[Publications] Iino,S.: "Interferon therapy for non-A,non-B chronic hepatitis." Gasteroenterologia Japonica. 26. 224-229 (1991)
[Publications] Koike,K.: "Activation of retrovirus in transgenic mouse:association with the development of olfactory neuroblastoma." J.Virol.64. 3988-3991 (1990)
[Publications] Mahe,Y.: "Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis elements." J.Biol.Chem.266. 13759-13763 (1991)
[Publications] Yanagi,Y.: "Hepatitis C virus in fulminant hepatic failure." New Engl.J.Med.324. 1895-1896 (1991)
[Publications] Kuno,K.: "Evidence for binding at least two factors,including T-rich strand-binding factor(s) to the single-stranded ARSI sequence in Saccharomyces cerevisiae." Mol.Gen.Genet.(1992)

1991 Fiscal Year Annual Research Report

肝炎ウイルスと肝発がん

Principal Investigator

小池 克郎 (財)癌研究会, 癌研究所, 部長 (30085625)

Research Products

[Publications] Arii,M.: "Identification of three essential regions of hepatitis B virus X protein for trans-activation function." Oncogene. 7. (1992)

[Publications] Ishihara,H.: "Specific uptake of asialofetuinーtacked liposomes encapsulating interferonーγ by human hepatoma cells and its inhibitory effect on hepatitis B virus replication." Biochem.Biophys.Res.Comm.174. 839-845 (1991)

[Publications] Takada,S.: "X protein of hepatitis B virus resembles a serine protease inhibitor." Jpn.J.Cancer Res.81. 1191-1194 (1990)

[Publications] Hagiwara,H.: "Detection of hepatitis C virus RNA in chronic non-A non-B liver disease." Gasteroenterology. 102. 692-694 (1992)

[Publications] Hagiwara,H.: "Detection of hepatitis C virus RNA sequences in serum during treatment for chronic hepatitis C with interferon alpha." Hepatology. 15. 37-41 (1992)

[Publications] Haruna,Y.: "Expression of X protein and hepatitis B virus replication in chronic hepatitis." Hepatology. 13. 417-421 (1991)

[Publications] M.Omata: "Resolution of acute hepatitis C after therapy with natural beta interferon." Lancet. 338. 914-915 (1991)

[Publications] M.Omata: "Detection of hepatitis C virus infection by enzyme-linked immunosolbent assay system using core protein expressed in Escherichia coli." Jpn.J.Cancer Res.82. 879-882 (1991)

[Publications] Naito,A.: "In vitro "progression" of bovine papilomavirus transformed cells:loss of contact sensitivity after multiple rouunds of selection." Int.J.Cancer. 48. 889-894 (1991)

[Publications] Naito,A.: "Homologous recombination in bovine papilomavirus shuttlevector:Effect of relative orientation of substrate sequences." Biochem.Biophys.Res.Comm.174. 305-312 (1991)

[Publications] Yoshikura,H.: "Detection and typing of multiple genital human papilomaviruses by DNA amplification with consensus primers." Jpn.J.Canocer Res.82. 524-531 (1991)

[Publications] Sugimura,H.: "The Histopathology of the liver in older patients with hepatitis B virus surface antigenemia" Virchow's Archives (A). 419. 409-415 (1991)

[Publications] Kohara,K.: "A second group of hepatitis C virus." Virus Genes. 5. 243-254 (1991)

[Publications] Kohara,K.: "Internal ribosome entry site within hepatitis C virus RNA." J.Virology. (1992)

[Publications] Inoue,Y.: "Maternal transfer of HCV" Nature. 353. 609 (1991)

[Publications] Chiba,J.: "Serodiagnosis of hepatitis C virus(HCV) infection with an HCV core protein molecularly expressed by a recombinant baculovirus." Proc.Natl.Acad.Sci.USA. 88. 4641-4645 (1991)

[Publications] Matsuura,Y.: "Expression of processed envelope protein of hepatitis C virus in mammalian and insect cells." J.Virology. (1992)

[Publications] M.Omata: "Mutations in the precore region of hepatitis B virus DNA in patients with fulminant and severe hepatitis." New Engl.J.Med.324. 1699-1704 (1991)

[Publications] Hijikata,M.: "Gene mapping of the putative structural region of the hepatitis C virus genome by in vitro processing analysis." Proc.Natl.Acad.Sci.USA. 88. 5547-5551 (1991)

[Publications] Hijikata,M.: "Hypervariable regions in the putative glycoprotein of hepatitis C virus.(1991,Biochem.Biophys.Res.Commun.,175:220-228)" Biochem.Biophys.Res.Comm.175. 220-228 (1991)

[Publications] Muraiso,K.: "Detection of hepatitis C virus infection by enzyme-linked immunosolbent assay system using core protein expressed in escherichia coli." Jpn.J.Cancer Res.82. 879-882 (1991)

[Publications] Takamizawa,A.: "Structure and organization of the hepatitis C virus genome isolated from human carriers." J.Virology. 65. 1105-1113 (1991)

[Publications] Igarashi,M.: "Weel^+ーlike gene in human cells." Nature. 353. 80-83 (1991)

[Publications] Kume,K.: "Oncogenic signal-induced ability to enter S phase in the absence of anchorage is the mechanism for the growth of transformed NRK cells in soft agar." New Biologist. (1992)

[Publications] Kim,C.: "HBx gene of hepatitis B virus induces liver cancer in transgenic mice.(1991,Nature,351:317-320)" Nature. 351. 317-320 (1991)

[Publications] Iino,S.: "Interferon therapy for non-A,non-B chronic hepatitis." Gasteroenterologia Japonica. 26. 224-229 (1991)

[Publications] Koike,K.: "Activation of retrovirus in transgenic mouse:association with the development of olfactory neuroblastoma." J.Virol.64. 3988-3991 (1990)

[Publications] Mahe,Y.: "Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis elements." J.Biol.Chem.266. 13759-13763 (1991)

[Publications] Yanagi,Y.: "Hepatitis C virus in fulminant hepatic failure." New Engl.J.Med.324. 1895-1896 (1991)

[Publications] Kuno,K.: "Evidence for binding at least two factors,including T-rich strand-binding factor(s) to the single-stranded ARSI sequence in Saccharomyces cerevisiae." Mol.Gen.Genet.(1992)

小池克郎 (財)癌研究会, 癌研究所, 部長 (30085625)