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書籍詳細

未契約
書籍名 テロメア・テロメラーゼ
出版社 日本医学館
発行日 1999-07-30
著者
  • 山木戸道郎(編著)
ISBN 4890444130
ページ数 269
版刷巻号 第1版第1刷
分野
閲覧制限 未契約

第一線研究者によるわかりやすい概説と臨床指針。 テロメア,テロメラーゼ研究の決定版。

目次

  • 表紙
  • 執筆者一覧
  • 目次
  • 序論
  • テロメア・テロメラーゼ研究の進歩
  • I. 基礎
    • 1. ヒト細胞の老化と不死化
      • ヒト体細胞には分裂寿命がある
      • 細胞分裂のたびにテロメアDNAが短縮する
      • テロメアは分裂時計である
      • 遺伝的早老症とテロメア代謝異常
      • 活性酸素とテロメア代謝異常
      • 分裂寿命がつきた細胞の増殖停止の仕組み
      • 細胞老化を表すシグナル伝達プロセス
      • 遺伝的早老症の原因遺伝子の機能
      • 分裂寿命の延長は容易であるが不死化は難しい
      • Bリンパ球も容易には不死化しない
      • 細胞の不死化
      • テロメラーゼ
      • ヒト培養細胞のテロメラーゼ活性
      • ヒト組織のテロメラーゼ活性
      • テロメラーゼの発現によって細胞は不死化するか
      • 細胞の老化とヒトの老化
    • 2. テロメア・テロメラーゼの構造と機能
      • テロメアの構造と機能
      • テロメラーゼは鋳型RNAを内在する逆転写酵素である
      • テロメラーゼ逆転写酵素: テロメラーゼの触媒蛋白質サブユニット
      • その他のテロメラーゼ付属蛋白質(telomerase-associated protein)
      • テロメアに作用するものはテロメラーゼだけではない
    • 3. テロメラーゼ活性制御因子とテロメア結合蛋白
      • サブユニット蛋白・RNAの発現調節を介するテロメラーゼ酵素活性の制御
      • ヒト3番染色体短腕(3p)に存在する細胞老化誘導/テロメラーゼリプレッサー遺伝子
      • テロメアDNA結合蛋白
    • 4. リンパ細胞におけるテロメラーゼ誘導シグナル
      • テロメラーゼ活性を誘導するシグナルとその細胞内伝達経路
      • シグナルの最終ターゲットは何か
      • なぜリンパ細胞の活性化に伴い, テロメラーゼ活性も誘導されるのか
    • 5. 正常上皮細胞のテロメラーゼ活性と幹細胞
      • 正常細胞のテロメラーゼ
      • 正常上皮細胞のテロメラーゼ活性の強さ
      • テロメラーゼ活性が検出される正常組織
      • 正常細胞のテロメラーゼ活性の特性
      • 上皮組織を構成する細胞サブセット
      • すべての基底層細胞がテロメラーゼ活性をもつわけではない
      • テロメラーゼ活性をもたない細胞サブセット
  • II. 測定法
    P.75閲覧
    • 6. テロメア長測定
      • テロメア(TRF)長測定
      • テロメア長変化の判定法
    • 7. テロメアのin situによる検出方法(FISH/PRINS)
      • ペプチド核酸によるFISH法を用いたテロメア配列の検出
      • Cycling PRINS法
      • FISH/PRINS法の実際
    • 8. テロメラーゼ活性測定法
      • a. TRAPアッセイ
        • 測定法
      • b. Non-RIによるテロメラーゼ活性の検出法
        • PCR-ELISA法
        • TRAP-HPA法
        • F-TRAP法
      • c. In situ telomeric repeat amplification protocol(TRAP)法
        • In situ TRAP法
        • In situ TRAP法の実際
        • 組織 in silu TRAP
      • d. Stretch PCR法
        • Stretch PCR法の特徴
        • Stretch PCR法のプロトコール
        • Stretch PCR法の実際
        • Stretch PCR法とTRAP法の比較
        • Stretch PCR法の問題点
    • 9. テロメア, テロメラーゼ関連遺伝子の検出
      • AGPC法を用いたRT-PCR grade RNAの調整法
      • RT-PCR法によるテロメラーゼ関連遺伝子の検出
  • III. ヒト正常細胞・癌細胞のテロメア長・テロメラーゼ活性
    P.137閲覧
    • 10. 早老症とテロメア
      • 早老症
      • ウェルナー症候群とプロジェリア
      • 早老症細胞の分裂寿命とテロメア短縮, テロメラーゼ
      • 早老症遺伝子と分裂寿命とテロメアの異常
      • 糖尿病, 高血圧とテロメア短縮
    • 11. リンパ球・免疫疾患のテロメア長・テロメラーゼ活性
      • リンパ球のテロメア長
      • 末梢血リンパ球のテロメラーゼ活性
      • 組織中のリンパ球テロメラーゼ活性
      • リンパ球のテロメラーゼ活性はテロメア長を安定に保てるか?
      • 免疫疾患のテロメラーゼ活性
    • 12. 造血幹細胞, 造血器腫瘍のテロメア長,テロメラーゼ
      • 造血幹細胞のテロメラーゼ動態
      • 造血細胞のテロメア動態
      • 正常人末梢血単核球でのテロメア長とテロメラーゼ活性
      • 急性白血病のテロメア
      • 急性白血病のテロメラーゼ
      • 慢性骨髄性白血病のテロメア動態
      • 骨髄異形成症候群におけるテロメラーゼ活性
    • 13. 肺癌のテロメア長・テロメラーゼ活性
      • 肺癌原発巣におけるテロメア長・テロメラーゼ活性
      • 肺癌転移巣におけるテロメア長・テロメラーゼ活性
      • 前癌病変におけるテロメラーゼ活性・hTR発現
      • テロメラーゼ活性を指標とした肺癌の存在診断
      • テロメラーゼ活性を指標とした肺癌の生物学的特性の診断
      • テロメラーゼをターゲットとした抗癌戦略への期待
    • 14. 消化管・消化器腫瘍のテロメア長・テロメラーゼ
      • 正常の消化管のテロメア, テロメラーゼ
      • 消化管由来の癌におけるテロメア長とテロメラーゼ活性
      • 消化器実質臓器のテロメラーゼ活性
    • 15. 膀胱癌, 乳癌におけるテロメラーゼ活性とその臨床応用
      • 材料と方法
      • 膀胱癌でのテロメラーゼ活性
      • 乳癌におけるテロメラーゼ活性
      • テロメラーゼインヒビターは存在するか
      • 臨床応用の可能性
    • 16. 皮膚・毛包・皮膚腫瘍のテロメラーゼ活性
      • 正常皮膚でのテロメラーゼ活性
      • テロメラーゼ陽性の基底細胞は幹細胞か
      • 日光曝露部皮膚でのテロメラーゼ活性
      • 口光曝露部皮膚でのテロメラーゼ活性とp53遺伝子変異
      • 毛包におけるテロメラーゼ
      • ヒト皮膚腫瘍におけるテロメラーゼ活性
      • テロメラーゼ・サブユニットの発現と皮膚腫瘍におけるテロメラーゼ活性との関連
      • 皮膚におけるテロメラーゼ活性の制御
    • 17. 婦人科組織のテロメラーゼ活性
      • 婦人科腫瘍のテロメラーゼ活性
      • 前癌, 良性病変のテロメラーゼ活性
      • 癌の臨床病理学的特徴とテロメラーゼ活性の関係
      • 子宮内膜のテロメラーゼ活性
      • 絨毛組織のテロメラーゼ活性
      • テロメラーゼ活性の測定による癌診断の可能性
      • テロメラーゼサブユニットの発現
      • テロメラーゼ活性の生物学的意義
    • 18. 小児固形腫瘍のテロメア長・テロメラーゼ
      • 発生とテロメア・テロメラーゼ
      • 神経芽細胞腫のテロメア・テロメラーゼ
      • 網膜芽細胞腫のテロメア・テロメラーゼ
      • 腎芽腫のテロメア・テロメラーゼ
      • 肝芽腫のテロメア・テロメラーゼ
      • 奇形腫のテロメア・テロメラーゼ
      • その他の小児固形腫瘍のテロメア・テロメラーゼ
      • 小児固形悪性腫瘍のテロメア・テロメラーゼの特徴
    • 19. 頭頚部腫瘍, 甲状腺腫瘍, 脳腫瘍, その他の腫瘍/組織
      • 頭頚部癌
      • 甲状腺腫瘍
      • 副腎腫瘍
      • 骨軟部腫瘍/組織
      • 脳腫瘍
      • 前立腺腫瘍
      • 腎腫瘍
  • IV. 新薬開発
    P.221閲覧
    • 20. テロメア・テロメラーゼをターゲットとした新薬開発
      • テロメラーゼ阻害剤の開発
      • テロメア機能の阻害剤
      • テロメア・テロメラーゼ機能阻害剤の問題点
      • テロメラーゼ発現による分裂寿命延長の試み
  • おわりに
    P.229閲覧
    • テロメアの旅から
  • 略語
    P.237閲覧
  • キーワード
    P.241閲覧
  • 索引
    P.251閲覧
  • 奥付

参考文献

序論

P.6 掲載の参考文献

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  • 27) Tahara H, Nakanishi T, Kitamoto M, Nakashio R, Shay JW, et al.:Telomerase activity in human liver tissues:comparison between chronic liver disease and hepatocellular carcinomas. Cancer Res. 55:2734-2736, 1995.
  • 28) Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, et al.:Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J. Immunol. 155:3711-3715, 1995.
  • 35) Taylor RS, Ramirez RD, Ogoshi M, Chaffins M, Piatyszek MA, et al.:Detection of telomerase activity in malignant and nonmalignant skin conditions. J. Invest. Dermatol. 106:759-765, 1996.
  • 38) Tatematsu K, Nakayama J, Danbara M, Shionoya S, Sato H, et al.:A novel quantitative'stretch PCR assay', that detects a dramatic increase in telomerase activity during the progression of myeloid leukemias. Oncogene 13:2265-2274, 1996.
  • 43) Ohyashiki K, Ohyashiki JH, Nishimaki J, ToyamaK, Ebihara Y, et al.:Cytological detection of telomerase activity using an in situ telomeric repeat amplification protocol assay. Cancer Res. 57:2100-2103, 1997.
  • 45) Meyerson M, Counter CM, Eaton EN, Ellisen LW, Steiner P, et al.:hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 90:785-795, 1997.
  • 56) Tahara H, Kuniyasu H, Yokozaki H, Yasui W, Shay JW, et al.:telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions. Clin. Cancer Res. 1:1245-1251, 1995.
  • 57) Yashima K, Litzky LA, Kaiser L, Rogers T, Lam S, et al.:Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas. Cancer Res. 57:2373-2377, 1997.
  • 58) Harle-Bachor C, Boukamp P:Telomerase activity in the regenerative basal layer of the epidermis in human skin and in immortal and carcinoma derived skin keratinocytes. Proc. Natl. Acad. Sci. USA 93:6476-6481, 1996.
  • 62) Vaziri H, Schachter F, Uchida I, Wei L, Zhu X, et al.:Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am. J. Hum. Genet. 52:661-667, 1993.
  • 67) Ulaner GA, Hu JF, Vu TH, Giudice LC, Hoffmann AR:Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts. Cancer Res. 58:4168-4172, 1998.

I. 基礎

P.20 掲載の参考文献

  • 1) 井出利憲:ヒト細胞の老化と不死化(単著). 羊土社, 1994.
  • 5) Martin GM, Sprague CA, Epstein CJ:Replicative life-span of cultivated human cells. Effects of donor's age, tissue, and genotype. Lab. Invest. 23:86-92, 1970.
  • 6) Goldstein S:生物学的老化の早期開始ならびに亢進性の特徴をもつヒト遺伝疾患, in The genetics of Aging(訳:老化の遺伝性生化学) . Schneider EL ed. 東京大学出版会, 1981, p171-230.
  • 7) Makarpv VL, Hirose Y, Langmore JP:Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 88:657-666, 1997.
  • 13) Vaziri H, Schachter F, Uchida I, Wei L, Zhu X, et al.:Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am. J. Hum. Genet. 52:661-667, 1993.
  • 19) Tahara H, Sato E, Noda A, Ide T:Increase in expression of p21 sdi1/cip1/waf1 with increasing division age in both normal and SV40-transformed human fibroblasts. Oncogene 10:835-840, 1995.
  • 20) Tresini M, Mawal-Dewan M, Cristofalo VJ, Sell C:A phosphatidylinositol 3-kinase inhibitor induces a senescent-like growth arrest in human diploid fibroblasts. Cancer Res. 58:1-4, 1998.
  • 32) Meyerson M, Counter CM, Eaton EN, Ellisen LW, Steiner P, et al.:hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 90:785-795, 1997.

P.32 掲載の参考文献

  • 18) Greider CW, Collins K, Autexier C:Tlomerases. In DNA Replication in Eukaryotic Cells. (DePamphilis ML ed. ), Cold Spring Harbor Laboratory Press, New York, 1996, p619-638.
  • 32) Lendvay TS, Morris DK, Sah J, Balasubramanian B, Lundblad V:Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes. Genetics 144:1399-1412, 1996.
  • 34) Meyerson M, Counter CM, Eaton EN, Ellisen LW, Steiner P, et al.:hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 90:785-795, 1997.
  • 45) Ghandi L, Collins K:Interaction of recombinant Tetrahymena telomerase proteins p80 and p95 with telomerase RNA and telomerc DNA substrates. Genes Dev. 12:721-733, 1998.

P.45 掲載の参考文献

  • 2) Konig P, Rhodes D:Recognition of telomeric DNA. Trends Biochem. Sci. 22:43-47, 1997.
  • 6) Meyerson M, Counter CM, Eaton EN, Ellisen LW, Steiner P, et al.:hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell 90:785-795, 1997.
  • 13) Ramakrishnan S Eppenberger U, Mueller H, Shinkai Y, Narayanan R:Expression profile of the putative catalytic subunit of the telomerase gene. Cancer Res. 58:622-625, 1998.
  • 19) Ku WC, Cheng AJ, Wang TC:Inhibition of telomerase activity by PKC inhibitors in human nasopharyngeal cancer cells in culture. Biochem. Biophys. Res. Commun. 241:730-736, 1998.
  • 25) Albanell J, Han W, Menado B, Gunawardane R, Scher HI, et al.:Telomerase activity is repressed during differentiation of maturation-sensitive but not resistant human tumor cell lines. Cancer Res. 56:1503-1508, 1996.
  • 26) Bestilny LJ, Brown CB, Miura Y, Robertson LD, Riabowol KT:Selective inhibition of telomerase activity during terminal differentiation of immortal cell lines. Cancer Res. 56:3796-3802, 1996.
  • 52) Ulaner GA, Hu JF, Vu TH, Giudice LC, Hoffman AR:Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts. Cancer Res. 58:4168-4172, 1998.
  • 53) Li H, Zhao L, Yang Z, Funder JW, Liu JP:Telomerase is controlled by protein kinase Cα in human breast cancer cells. J. Biol. Chem. 273:33436-33442, 1998.
  • 55) Takakura M, Kyo S, Kanaya T, Hirano H, Takeda J, et al.:Cloning of human telomerase catalytic subunit (hTERT) gene promoter and identification of proximal core promoter sequences essential for transcriptional activation in immortalized and cancer cells. Cancer Res. 59:551-557, 1999.
  • 56) Horikawa I, Cable PL, Afshari C, Barrett JC:Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. Cancer Res. 59:826-830, 1999.

P.58 掲載の参考文献

  • 9) Ramakrishnan S, Eppenberger U, Muller H, Shinkai Y, Narayanan R:Expression profile of the catalytic subunit of the telomerase gene. Cancer Res. 58:622-625, 1998.
  • 10) Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, et al.:Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J. Immunol. 155:3711-3715, 1995.
  • 12) Weng NP, Levine BL, June CH, Hodes RJ:Regulated expression of telomerase activity in human T lymphocyte development and activation. J. Exp. Med. 183:2471-2479, 1996.
  • 16) Weng NP, Levine BL, June CH, Hodes RJ:Regulation of telomerase RNA template expression in human T lymphocyte development and activation. J. Immunol. 158:3215-3220, 1997.
  • 17) Igarashi H, Sakaguch N:Telomerase activity is induced in human peripheral B lymphocytes by the stimulation to antigen receptor. Blood 89:1299-1307, 1997.
  • 18) Hu BT, Lee SC, Marin E, Ryan DH, Insel RA:Telomerase is up-regulated in human germinal center B cells in vivo and can be re-expressed in memory B cells activated in vitro. J. Immunol. 159:1068-1071, 1997.
  • 20) Metcalf JA, Parkhill J, Campbell L, Stacey M, Biggs P, et al.:Accelerated telomerase shortening in ataxia telangiectasia. Nature Genet. 13:350-353, 1996.
  • 21) Beamish H, Williams R, Chen P, Khanna KK, Hobson K, et al.:Rapamycin resistance in ataxia-telangiectasia. Oncogene 13:963-970, 1996.
  • 22) Murata K, Wu J, Brautigan DL:B cell receptor-associated protein α4 displays rapamycin-sensitive binding directly to the catalytic subunit of protein phosphatase 2A. Proc. Natl Acad. Sci. USA 94 10624-10629, 1997.
  • 23) Inui S, Sanjo H, Maeda K, Yamamoto H, Miyamoto E, et al.:Ig receptor binding protein 1 (α4) is associated with a rapamycin-sensitive signal transduction in lymphocytes through direct binding to the catalytic subunit of protein phosphatase 2A. Blood 92:1-9, 1998.
  • 27) 清宮啓之, 鶴尾 隆:白血球細胞の分化誘導に伴うテロメラーゼ活性のダウンレギュレーション. 日本臨床 56:29-33, 1998.
  • 28) Norrback KF, Dahlenborg K, Carlsson R, Roos G:Telomerase activation in normal B lymhocytes and non-Hodgkin's lymphomas. Blood 88:222-229, 1996.

P.72 掲載の参考文献

  • 3) Yasumoto S, Kunimura C, Kikuchi K, Tahara H, Ohji H, et al.:Telomerase activity in normal human epithelial cells. Oncogene 13:433-439, 1996.
  • 4) Kunimura C, Kikuchi K, Ahmed N, Shimizu A, Yasumoto S:Telomerase activity in a specific cell subset co-expressing integrin β1/EGFR but not p75NGFR/bc12/integrin β4 in normal human epithelial cells. Oncogene 17:187-197, 1998.
  • 5) Harle-Bachor C, Boukamp P:Telomerase activity in the regenerative basal layer of the epidermis in human skin and in immortal and carcinoma-derived skin keratinocytes. Proc. Natl. Acad. Sci. USA 93:6476-6481, 1996.
  • 7) Kyo S, Takakura M, Kohama T, Inoue M:Telomerase activity in human endometrium. Can-cer Res. 57:610-614, 1997.
  • 8) Hsiao R, Sharma HW, Ramakrishnan S, Keith E, Narayanan R:Telomerase activity in normal human endothelial cells. Anticancer Res. 17:827-832, 1997.
  • 9) Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, et al.:Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J. Immunol. 155:3711-3715, 1995.
  • 20) Bestilny L, Brown CB, Miura Y, Robertson LD, Riabowol KT:Selective inhibition of telomerase activity during terminal differentiation of immortal cell lines. Cancer Res. 56:3796-3802, 1996.
  • 22) Albannell J, Han W, Mellando B, Gunawardane R, Scher HI, et al.:Telomerase activity is repressed during differentiation of maturation-sensitive but not resistant human tumor cell lines. Cancer Res. 56:1503-1508, 1996.
  • 23) Morrison SJ, Uchida N, Weissman LL:The biology of hematopoietic stem cells. Annu. Rev. Cell Dev. Biol. 11:35-71, 1994.

II. 測定法

P.86 掲載の参考文献

  • 10) Hiyama K, Shirotani Y, Ishioka S, Hiyama E, Yokoyama T, et al.:Cancer-cell proliferation and alteration in length of telomeric repeats. Tiss. Cult. Res. Commun. 12:291-297, 1993.
  • 11) Hiyama K, Ishioka S, Shirotani Y, Inai K, Hiyama E, et al.:Alterations in telomeric repeat length in lung cancer are associated with loss of heterozygosity in p53 and Rb. Oncogene 10:937-944, 1995.
  • 13) Mehle C, Ljungberg B, Roos G:Telomere shortening in renal cell carcinoma. Cancer Res. 54:236-241, 1994.

P.93 掲載の参考文献

  • 4) Freshney R I:Culture of Animal cells. A Manual of Basic Technique. 2nd ed. Alan R Liss, Inc., New York, 1987, p175-179.
  • 9) Musio A, Rainaldi G:Cycling-PRINS. A method to improve the accuracy of telomeric sequence detection in mammalian chromosomes. Mutant. Res. 390:1-4, 1997.

P.99 掲載の参考文献

P.103 掲載の参考文献

  • 6) Ohyashiki JH, Ohyashiki K, Toyama K, Shay JW:A non-radioactive fluorescellce-based telomeric repeat amplification protocol to detect and quantitate telomerase activity. Trends Genet. 12:395-396, 1996.

P.108 掲載の参考文献

  • 1) Harley CB:Telomeres and ageing. in Telomeres. (eds. Blackburn EH, Greider CW), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1995, p247-263.
  • 4) Ohyashiki K, Ohyashiki JH, Nishimaki J, Toyama K, Ebihara Y, et al.:Cytological detection of telomerase activity using an in situ telomeric repeat amplification protocol assay. Cancer Res. 57:2100-2103, 1997.
  • 6) Ohyashiki K, Yahata N, Ohyashiki JH, Iwamaa H, Hayashi S, et al.:A combilation of semiquantitative telomerase assay and in cell telomerase activity measurement using exfoliated urothelial cells for the detection of urothelial neoplasia. Cancer 83:2554 2560, 1998.

P.116 掲載の参考文献

  • 1) Tatematsu K, Nakayama J, Danbara M, Shionoya S, Sato H, et al.:A novel quantitative stretch PCR assay that detects a dramatic increase in telomerase activity during the progression of myeloid leukemias. Oncogene 13:2265-2274, 1996.
  • 3) Kyo S, Takakura M, Tanaka M, Murakami K, Saitoh R, et al.:Quantitative difference of telomerase activity among ovarian malignant and premalignant lesions. Clin, Cancer Res. 4:399-406, 1998.

P.135 掲載の参考文献

  • 2) Avilion AA, Piatyszek MA, Gupta J, Shay JW, Bacchetti S, et al.:Cancer Res. 56:645-650, 1996.
  • 6) Nakamura TM, Morin GB, Chapman KB, Weinrich SL, Andrews WH, et al.:Science 277:955959, 1997.
  • 13) Yasui W, Tahara E, Tahara H, Fujimoto J, Naka K, et al.:Jpn. J. Cancer Res. (in press)

III. ヒト正常細胞・癌細胞のテロメア長・テロメラーゼ活性

P.146 掲載の参考文献

  • 1) Martin GM:Genetic modulation of telomeric terminal restriction-fragment length:relevance for clonal aging and late-life disease. Am J. Hum. Genet, 55:866-869, 1994.
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  • 19) Vaziri H, Schachter F, Uchida I, Wei L, Zhu X, et al.:Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. Am. J. Hum. Genet. 52:661, 1993.
  • 20) Sikora E, Radziszewska E, Kmiec T, Maslinska D:The impaired transcription factor AP-1 DNA binding activity in lymphocytes derived from subjects with some symptoms of premature aging. Acta Biochim. Pol. 40:269-272, 1993.
  • 21) Salvitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, et al.:A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268:1749-1753, 1995.
  • 23) 名倉 潤, 叶 林, 森島淳之, 三木哲郎:ヘリカーゼ変異と早老症-転写異常症候群-. 最新医学 53(9):2110-2117, 1998.

P.153 掲載の参考文献

  • 2) Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, et al.:Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J, Immunol. 155:3711-3715, 1995.
  • 11) Monteiro J, Batliwalla F, Ostrer H, Gregersen PK:Shortened telomeres in clonany expanded CD28+CD8+T cells imply a replicative history that is distinct from their CD28+CD8+counterparts. J. Immunol. 156:3587-3590, 1996.
  • 18) Norrback K-F, Dahlenborg K, Carlsson R, Roos G:telomerase activation in normal B lymphocytes and non-Hodgkin's lymphomas. Blood 88:222-229, 1996.
  • 22) Weng NP, Levine BL, June CH, Hodes RJ:Regulation of telomerase RNA template expression in human T lymphocyte development and activation. J. Immunol. 158:3215-3220, 1997.
  • 23) Igarashi H, Sakaguchi N: Telomerase activity is iuduced in human peripheral B lymphocytes by the stimulation to antigen receptor. Blood 89:1299-1307, 1997.
  • 24) Brousset P, al Saati T, Chaouche N, Zenou RC, Schlaifer D, et al.:Telomerase activity in reactive and neoplastic lymphoid tissues:infrequent detection of activity in Hodgkin's disease. Blood 89:26-31, 1997.
  • 27) De Boer RJ, Noest A:T cell renewal rates, telomerase, and Telomere length shortening. J. Immunol. 160:5832-5837, 1998.
  • 28) Yamanishi Y, Hiyama K, Maeda H, Ishioka S, Murakami T, et al.:telomerase activity in rheumatoid synovium correlates, with the mononuclear cell infiltration level and disease aggresiveness of rheumatoid arthritis. J. Rheumatol. 25:214-220, 1998.
  • 30) Chadeneau C, Hay K, Hirte HW, Gallinger S, Bacchetti S:Telomerase activity associated with acquisition of malignancy in human coIorectal cancer. Cancer Res, 55:2533-2536, 1995.
  • 32) Tahara H, Nakanishi T, Kitamoto M, Nakashio R, Shay JW, et al.:Telomerase activity in human liver tissues:comparison between chronic liver disease and hepatocellular carcinomas. Cancer Res. 55:2734-2736, 1995.

P.161 掲載の参考文献

  • 1) Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, et al.:Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J. Immunol. 155:3711-3715, 1995.
  • 4) Iwama H, Ohyashiki K, Ohyashiki JH, Hayashi S, Yahata N, et al.:Telomere length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals. human Genet. 102:397-402, 1998.
  • 5) Norrback K-F, Dahlenborg K, Carlsson R, Ross G:Telomerase activity in normal B lymphocytes and Non-Hodgkin's lymphomas. Blood 82:222-229, 1996.
  • 12) Zhang W, Piatyszeck MA, Kobayashi T, Estey E, Andreeff M, et al.:Telomerase activity in human acute myelogenous leukemia:inhibition of telomerase activity by differentiation-inducing agents. Clin. Cancer Res. 2:799-803, 1996.
  • 15) Ohyashiki JH, Iwama H, Yahata N, Ando K, Hayashi S, et al.:Telomere stability is frequently impaired in high risk groups of ptients with myelodysplatic syndromes. Clin. Cancer Res. (inpress).

P.167 掲載の参考文献

  • 1) 檜山桂子, 石岡伸一, 山木戸道郎:肺癌におけるテロメア長変化と遺伝子変異. 「肺癌の予後因子」(小倉 剛, 安光 勉編) , 中山書店, 東京, 1995, p154-161.
  • 3) Hiyama K, Ishioka S, Shirotani Y, Inai K, Hiyama E, et al.:Alterations in telomeric repeat length in lung cancer are associated with loss of heterozygosity in p53 and Rb. Oncogene 10:937-944, 1995.
  • 5) Ahrendt SA, Yang SC, WU L, Westra WH, Jen J, et al.:Comparison of oncogene mutation detection and telomerase activity for the molecular staging of Non-small cell lung cancer. Clin. Cancer Res. 3:1207-1214, 1997.
  • 7) Yashima K, Litzky LA, Kaiser L, Rogers T, Lam S, et al.:Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas. Cancer Res. 52:2373-2377, 1997.
  • 12) Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, et al.:Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J. Immunol. 155:3711-3715, 1995.

P.177 掲載の参考文献

  • 2) Chadeneau C, Hay K, Hirte HW, Ganinger S, Bacchetti S:Telomerase activity associated with acquisition of malignancy in human colorectal cancer. Cancer Res. 55:2533-2536, 1995.
  • 3) Tahara H, Kuniyasu H, Yokozaki H, Yasui W, Shay JW, et al.:Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions. Clin. Cancer Res. 1:1245-1251, 1995.
  • 4) Hiyama E, Yokoyama T, Tatsumoto N, Hiyama K, Imamura Y, et al.:Telomerase activity in gastric cancer. Cancer Res. 55:3258-3262, 1995.
  • 6) Hiyama K, Hirai Y, Kyoizumi S, Akiyama M, Hiyama E, et al.:Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J. Immunol. 155:3711-3715, 1995.
  • 8) Hohaus S, Voso MT, Orta LBE, Cavano S, Bellacosa A, et al.:Telomerase activity in human hematopoietic progenitor cells. Haematologica 82:262-268, 1997.
  • 10) Harle-Bachor C, Boukamp P:Telomerase activity in the regenerative basal layer of the epidermis in human skin and in immortal and carcinoma-derived skin keratinocytes. Proc. Natl. Acad. Sci. USA 93:6476-6481, 1996.
  • 11) Yasumoto S, Kunimura C, Kikuchi K, Tahara H, Ohji H, et al.:Telomerase activity in normal human epithelial cells. Oncogene 13:433-439, 1996.
  • 14) Hiyama K, Ishioka S, Shirotani Y, Inai K, Hiyama E, et al.:Alterations in telomeric repeat length in lung cancer are associated with loss of heter-ozygosity in p53 and Rb. Oncogene 10:937-944, 1995.
  • 20) 池口正英, 貝原信明:食道癌における癌巣, 非癌部粘膜のテロメラーゼ活性. 日本臨床 56:1176-1180, 1998.
  • 21) 丸山保彦, 花井洋行, 金子栄蔵:胃の腸上皮化生, 腺腫, 分化型腺癌におけるテロメア長, テロメラーゼ活性. 日本臨床 56:1186-1189, 1998.
  • 23) Engelhardt M, Drullinsky P, Guillem J, Moore MA:Telomerase and telomere length in the development and progression of premalignant lesions to colorectal cancer. Clin. Cancer Res. 3:1931-1941, 1997.
  • 24) 小川健治, 若杉慎司, 服部隆男・他:胃癌組織におけるテロメラーゼ活性と臨床病理学的諸因子との関連. 日本臨床 56:1194-1198, 1998.
  • 25) Tahara H, Nakanishi T, Kitamoto M, Nakashio R, Shay JW, et al.:Telomerase activity in human liver tissues:comparison between chronic liver disease and hepatocellular carcinomas. Cancer Res. 55:2734-2736, 1995.

P.183 掲載の参考文献

  • 12) Hiyama E, Yokoyama T, Tatsumoto N, Hiyama K, Imamura Y, et al.:Telomerase activity in gastric cancer. Cancer Res. 55:3258-3262, 1995.
  • 14) Tahara H, Nakanishi T, Kitamoto M, Nakasho R, Shay JW, et al.:Telomerase activity in human liver tissues:Comparison between chronic liver disease and hepatocellular carcinomas. Cancer Res. 55:2734-2736, 1995.
  • 15) Tahara H, Kuniyasu H, Yasui W, Yokozaki H, Shay J, V, et al.:Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions. Clin. Cancer Res. 1:1245-1251, 1995.

P.189 掲載の参考文献

  • 1) Harle-Bachor C, Boukamp P:telomerase activity in the regenerative basal layer of the epidermis in human skin and in immortal and carcinoma-derived skin keratinocytes. Proc. Natl. Acad. Sci. USA 93:6476-6481, 1996.
  • 2) Yasumoto S, Kunimura C, Kikuchi K, Tahara H, 0hji H, et al.:Telomerase activity in normal human epithelial cells. Oncogene 13:433-439, 1996.
  • 3) Taylor RS, Ramirez RD, Ogoshi M, Chaffins M, Piatyszek MA, et al.:Detection of telomerase activity in malignant and nonmalignant skin conditions. J. Invest. Dermatol. 106:759-765, 1996.
  • 4) Ueda M, Ouhtit A, Bito T, Nakazawa K, Lubbe J, et al.:Evidence for UV-associated activation of telomerase in human skin. Cancer Res. 57:370-374, 1997.
  • 11) Ouhtit A, Ueda M, Nakazawa H, Ichihashi M, Dumaz N, et al.:Quantitative detection of ultraviolet-specific p53 mutations in normal skin from Japanese patients. Cancer Epidemiol. Biomarkers Prev. 6:433-438, 1997.
  • 15) Prakash H and e M, Balajee AS, Natarajan AT:Induction of telomerase activity by UV-irradiationin Chinese hamster cells. Oncogene 15:1747-1752, 1997.

P.200 掲載の参考文献

  • 1) Kyo S, Kanaya T, Ishikawa H, Ueno H, Inoue M:Telomerase activity in gynecologic tumor. Clin. Cancer Res. 2:2023-2028, 1996.
  • 3) Kyo S, Takakura M, Tanaka M, Murakami K, Saitoh R, et al.:Quantitative difference of telomerase activity among ovarian malignant and premalignant lesions. Clin. Cancer Res. 4:399-406, 1998.
  • 4) Hiyama E, Yokoyama T, Tatsumoto N, Hiyama K, Imamura Y, et al.:Telomerase activity in gastric cancer. Cancer Res. 55:3258-3262, 1995.
  • 9) Kyo S, Takakura M, Ishikawa H, Sasagawa T, Satake S, et al.:Application of telomerase assay for the screening of cervical lesions. Cancer Res. 57:1863-1867, 1997.
  • 15) Takakura M, Kyo S, Kanaya T, Tanaka M, InoueM:Expression of telomerase subunits and correlation with telomerase activity in cervical cancer. Cancer Res. 58:1558-1561, 1998.
  • 19) Kyo S, Takakura M, Kanaya T, Inoue M:Expression of telomerase subunits in ovarian Inalignant, premalignant and benign lesions, Int. J. Cancer. (in press) .
  • 21) Ito H, Kyo S, Kanaya T, Takakura M, Inoue M, et al.:Expression of human telomerase subunits and correlation with telomerase activity in urothelial cancer. Clin. Cancer Res. 4:1603-1608, 1998

P.209 掲載の参考文献

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  • 13) Fong CT, White PS, Peterson K, Sapienza C, Cavenee WK, et al.:Loss of heterozygosity for chromosomes 1 or 14 defines subsets of advanced neuroblastomas. Cancer Res. 52:1780-1785, 1992.
  • 18) Bove KE, McAdamsn AJ:The nephroblastomatosis complex and its relationship to Wilms' tumor:a clinicopathologic treatise. Perspect. Pediatr. Pathol. 3:185-223, 1976.
  • 21) Bolande RP, Brough AJ, Izant RJJ:Congenital mesoblastic nephroma of infancy. A report of eight cases and the relationship to Wilms' tumor. Pediatrics 40:272-278, 1967.
  • 23) Ulbright TM, Roth LM:Recellt developments in the pathology of germ cell tumors. Semin. Diagn. Pathol. 4:304-319, 1987.

P.218 掲載の参考文献

  • 2) Mutirangura A, Supiyaphun P, Trirekapan S, Sriuranpong V, Sakuntabhai A, et al.:Telomerase activity in oral letlkoplakia and head and necksquamous cell carcinoma. Cancer Res. 56:3530-3533, 1996.
  • 3) Hohaus S, Cavallo S, Benacosa A, Genuardi M, Galli J, et al.:Telomerase activity in human laryngeal squamous cell carcinomas. Clin. Cancer Res. 2:1895-1900, 1996.
  • 4) Mao L, El NA, Fan YH, Lee JS, Lippman SM, et al.:Telomerase activity in head and neck squamous cell carcinoma and adjacent tissues. Cancer Res. 56:5600-5604, 1996.
  • 5) Califano J, Ahrendt SA, Meininger G, Westra WH, Koch WM, et al.:Detection of telomerase activity in oral rinses from head and neck squamous cell carcinoma patients. Cancer Res. 56:5720-5722, 1996.
  • 6) Kannan S, Tahara H, Yokozaki H, Mathew B, Nalinakumari KR, et al.:Telomerase activity in premalignant and malignant lesions of humali oral mucosa. Cancer Epidemiol Biomarkers Prev. 6:413-420, 1997,
  • 8) Umbricht CB, Saji M, Westra WH, Udelsman R, Zeiger MA, et al.:Telomerase activity:a marker to distinguish fonicular thyroid adenoma from carcinoma. Cancer Res. 57:2144-2147, 1997.
  • 11) Brousset P, al ST, Chaouche N, Zenou RC, Schlaifer D, et al.:Telomerase activity in reactive and neoplastic lymphoid tissues:infrequent detection of activity in Hodgkin's disease. Blood 89:26-31, 1997.
  • 14) Cheng AJ, Lin JD, Chang T, Wang TC:Telomerase activity in benign and malignant human thyroid tissues. Br. J. Cancer 77:2177-21801998.
  • 19) Engelhardt M, Albanen J, Dnnlinsky P, Han W, Guillem J, et al.:Relative contribution of normal and neoplastic cells determines telomerase activity and telomere Iength in primary cancers of the prostate, colon, and sarcoma. Clin. Cancer Res. 3:1849 1857, 1997.
  • 25) Sallinen P, Miettinen H, Sallinen SL, Haapasalo H, Helin H, et al.:Increased expression of telomerase RNA component is associated with increased cell proliferation in human astrocytomas. Am. J. Pathol. 150:1159-1164, 1997.
  • 29) Hiraga S, Ohnishi T, Izumoto S, Miyahara E, Kanemnra Y, et al.:Telomerase activity and alterations in telomere length in human brain tumors. Cancer Res. 58:2117-2125, 1998.
  • 30) Zhu LS, Anthony EC, Greider CW, Black PM:Telornerase activity in human gliomas. Neurosurgery 42:1120-1124, 1998.
  • 34) Sommerfeld HJ, Meeker AK, Piatyszek MA, Bova GS, Shay JW, et al.:Telomerase activity:a prevalent marker of malignant human prostate tissue. Cancer Res. 56:218-222, 1996.
  • 39) Zhang W, Kapusta LR, Slingerland JM, Klotz LH:Telomerase activity in prostate cancer, prostatic intraepithelial neoplasia, and benign prostatic epithelium. Cancer Res. 58:619-621, 1998.
  • 41) Mehle C, Piatyszek MA, Ljungberg B, Shay JW, Roos G:Telomerase activity in human renal cell carcinoma. Oncogene 13:161-166, 1996.
  • 47) Mehle C, Ljungberg B, Roos G:Telomere shortening in renal cell carcinoma. Cancer Res. 54:236-241, 1994.

IV. 新薬開発

P.227 掲載の参考文献

  • 11) Melana SM, Holland JF, Pogo BJ:Inhibition of cell growth and telomerase activity of breast cancer cells in vitro by 3'-azido-3'-deoxythymidine. Clin. Cancer Res. 4:693-696, 1998.
  • 12) Pai RB, Pai SB, Kukhanova M, Dntschman GE, Guo X, et al.:Telornerase from human leukemia cells:properties and its interaction with deoxynucleoside analogues. Cancer Res. 58:1909-1913, 1998.
  • 15) Yamakuchi M, Nakata M, Kawahara K, Kitajima I, Maruyama I:New quinolones, ofloxacin and levofloxacin, inhibit telomerase activity in transitional cell carcimona cell lines. Cancer Lett. 119:213・219, 1997.
  • 16) Sogawa K, Sumida T, Harnakawa H, Yamada T, Matsumoto K, et al.:Inhibitory effect of a marine microalgal polysaccharide on the telomerase activity in K562 cells. Res. Commun. Mol. Pathol. Phamacol. 99:259-265, 1998.