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新女性医学大系 41 婦人科腫瘍の分子・細胞生物学

出版社：	中山書店
著者：	武谷雄二(総編集) 青野敏博(編集) 麻生武志(編集) 中野仁雄(編集) 野澤志朗(編集) 和気徳夫(担当編集)
発行日：	2001-06-30
分野：	臨床医学：外科 > 産婦人科学
ISBN：	9784521543512
電子書籍版：	2001-06-30 （第1版第1刷）

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遺伝子レベルにおける研究成果から癌遺伝子や癌抑制遺伝子について概説し、細胞生物学の見知から浸潤、転移、血管新生のメカニズムを考察する。さらに子宮癌、卵巣癌など婦人科腫瘍の分子機構を解き、臨床への展望を示す。

表紙
執筆者一覧
目次
癌の分子遺伝学
I 癌の分子遺伝学総論
1. RNAがんウイルス , がん遺伝子 , プロトがん遺伝子
a. RNAがんウイルスからがん遺伝子へ
b. がん遺伝子とプロトがん遺伝子
c. ヒトがん遺伝子の発見
2. がん抑制遺伝子
a. がん抑制遺伝子の発見
b. DNAがんウイルスとがん抑制遺伝子の出会い
c. がん抑制遺伝子 , RBとp53
d. RBとp53 , 細胞周期 , アポトーシス
e. 種々のがん抑制遺伝子
3. ウイルスとがん
4. ゲノムの不安定性 , DNA複製エラー (RER) とがん
5. アポトーシスとがん
6. 老化とがん
II 癌遺伝子とシグナル伝達
A. rasとそのシグナル伝達系
l. ras遺伝子の発見
2. その他のrasスーパーファミリー
3. Rasタンパク質の生化学
a. Rasタンパク質の構造
b. Rasタンパク質の活性制御機構
c. 翻訳後修飾
4. 癌化に関与するシグナル伝達とRasタンパク質
5. Rasを介するシグナル伝達系
a. Rafを介する経路
b. ホスファチジルイノシトール3キナーゼ (PI3K) を介する経路
c. RalGDS
d. その他の標的
6. Rasの機能
a. 細胞増殖
b. アポトーシス
c. 浸潤 , 転移
7. 治療への応用
B. c-oncとキナーゼ遺伝子
1. 癌遺伝子産物としてのプロテインキナーゼ
2. 癌におけるプロテインキナーゼの活性化機構
3. 受容体型チロシンキナーゼの構造
4. 受容体型チロシンキナーゼを介した細胞増殖シグナルの伝達機構
5. プロテインキナーゼを分子標的とした癌治療の可能性と現状
III 癌抑制遺伝子と細胞増殖制御
A. RB , p53と細胞増殖制御
1. RBタンパク質とp53
2. 細胞増殖制御のメカニズム
a. 細胞周期
b. チェックポイント機構
3. RB
a. RBタンパク質の構造と機能の関連
b. RBタンパク質の作用
c. RBタンパク質の活性の制御メカニズム
d. 癌におけるRB経路の障害
e. RBタンパク質のファミリー
4. p53
a. p53の構造と機能との関連
b. p53の活性化メカニズム
c. p53の作用
d. 癌におけるp53経路の障害
e. p53のファミリー
5. 細胞癌化の抑制におけるp53経路とRB経路の協調
B. その他の癌抑制遺伝子
1. APC遺伝子
a. APC遺伝子と大腸癌
b. APC遺伝子の機能
c. APC遺伝子産物の構造と機能
d. APCタンパク質とWntシグナル伝達経路
e. APCタンパク質とAsefの相互作用
2. BRCA遺伝子
a. BRCA遺伝子と家族性乳癌 / 卵巣癌
b. BRCA遺伝子の機能 : ゲノム安定性
c. BRCA遺伝子産物の機能 : 相同組換え修復
3. TGF-β受容体およびSmad2 , 4
a. TGF-βファミリーの機能
b. TGF-βシグナル伝達経路
c. TGF-β受容体の癌細胞での異常
d. Sinadの癌細胞での異常
4. PTEN / MMAC1
a. PTEN / MMAC1と癌
b. PTEN / MMAC1遺伝子産物の構造
c. PTEN / MMAC1遺伝子産物の機能
d. PTEN / MMAC1とアポトーシス
IV ゲノム安定性 , DNA修復
1. 悪性腫瘍にみられるゲノム変化
a. 高等生物のゲノム構造
b. 悪性腫瘍にみられるゲノム変化の階層構造
2. ゲノム変化とDNA修復
a. 点突然変異とミスマッチ修復
b. 比較的大きなゲノム変化とDNA修復
3. 婦人科腫瘍とゲノム変化
a. 婦人科腫瘍におけるマイクロサテライト不安定性
b. 婦人科腫瘍における大きいレベルのゲノム変化
V アポトーシス
1. アポトーシスとその生理的意義
a. アポトーシスとは
b. アポトーシスの生理的・病態的意義
2. アポトーシスの分子機構
a. death receptorを介したアポトーシス
b. ミトコンドリアを介するアポトーシス
c. カスパーゼカスケードとアポトーシスの決定
d. アポトーシスを制御する細胞内因子
3. アポトーシスと癌
a. アポトーシスと癌とのかかわり
b. 癌形成とアポトーシス
VI ゲノムインプリンティング
1. ゲノムインプリンティング総論
a. ゲノムインプリンティング (GI) とは
b. GIモデルとしてのマウス
c. GI遺伝子とは
d. 生物学的意義
e. 分子機構
2. GIの異常に基づく疾患群
a. Prader-Willi / Angelman症候群 (PWS / AS)
b. PWS / ASの分子遺伝学的分類
c. Beckwith-Wiedemann症候群 (BWS)
d. Silver-Russell症候群 (SRS)
3. GIと癌化
a. Wilms腫瘍 (WT)
b. 神経芽細胞腫 (NB)
c. 絨毛癌 (CC)
VII 細胞老化 , 不死化 , 癌化とテロメラーゼ
1. 細胞老化 , 細胞死 , 不死化の概念
2. テロメアとは
3. 細胞分裂に伴うテロメアの短縮
4. テロメアの短縮と細胞の老化
5. 癌細胞におけるテロメラーゼの活性化
6. 婦人科腫瘍のテロメラーゼ活性
7. テロメラーゼ活性と癌の病態
8. 正常組織におけるテロメラーゼ活性
9. テロメラーゼの構成要素と機能
10. hTERT遺伝子発現の分子機構
11. テロメラーゼ活性の臨床応用
12. テロメラーゼ活性の制御と癌の遺伝子治療への応用
VIII 細胞周期
1. 細胞周期のカスケード
2. cdc2ファミリー
3. サイクリンファミリー
4. 細胞周期阻止因子
5. G1期チェックポイント
6. S期の調節
7. G2期チェックポイント
8. M期の調節
9. 細胞周期異常と癌化
10. 細胞周期因子と不死化
IX ユビキチン―プロテアソームシステム
1. 概要
a. プロテアソームの構造と機能
b. ユビキチン化反応
2. ユビキチンシステムの分子機構と生理機能
a. ユビキチンリガーゼの分類と多様性
b. ユビキチン―プロテアソームシステムによる細胞周期の制御
c. ユビキチンシステムによるシグナル伝達制御
3. タンパク質分解の異常と疾患
a. ユビキチン―プロテアソームシステムと細胞癌化
b. その他の疾患とタンパク質分解系の異常
癌の細胞生物学
I 癌細胞の細胞生物学的特性
1. 浸潤
2. 転移
a. nm23
b. KA11
c. KiSS-1
3. 血管新生
a. 血管内皮増殖因子 (VEGF)
b. チミジンホスホリラーゼ (TP)
c. 線維芽細胞増殖因子(FGF)
d. 血管新生抑制因子
e. アンジオスタチン
f. エンドスタチン
g. PEX
4. 血管新生阻害薬の開発
a. Flk-1 / KDR阻害薬
b. TP阻害薬
c. MMP阻害薬
d. インテグリン阻害薬
II 浸潤と転移のメ力ニズム
A. 浸潤
1. 癌細胞の生物学的特性とは
2. 癌細胞による浸潤能獲得の分子機構
3. 浸潤の分子メカニズム
a. 癌細胞膜上での酵素活性発現カスケード
b. ウロキナーゼ受容体の構造と作用
c. 癌細胞膜上でウロキナーゼが再活性化されるメカニズム
4. 浸潤のコントロール
a. 浸潤抑制のための実験的試み
b. 生理的な浸潤 , 転移抑制物質の開発
5. 血管新生とその阻害
a. 腫瘍血管新生の過程
b. 血管新生阻害療法の特徴および将来像
B. 転移
1. 癌転移プロセスにかかわる細胞生物学
a. 原発巣からの遊離 , 離脱
b. 癌細胞と脈管との関係
c. 標的臓器での増殖と抑制
2. 転移に関連する遺伝子
a. 癌遺伝子 , 癌抑制遺伝子
b. 転移遺伝子と転移抑制遺伝子
3. 癌の転移に対する新しい治療の方向性
III 血管新生
1. 血管新生とその過程
2. 血管新生阻害薬
3. 女性生殖器における血管新生の特徴
4. 女性生殖器癌における血管新生とその制御
a. 子宮頸癌における血管新生とその制御
b. 卵巣癌における血管新生とその制御
c. 子宮内膜癌における血管新生とその制御
IV ECMとプロテアーゼ
1. ECM分解酵素の分類
2. MMPの概要
a. MMPの種類とその性質
b. MMPの活性制御機構
c. 膜型MMPとゼラチナーゼA活性化
d. 間質細胞のMMP産生
3. 婦人科癌とMMP
a. 婦人科癌組織におけるMMP活性
b. 腹膜による卵巣癌細胞のMMP分泌の促進
4. 癌と細胞表面ペプチダーゼ
a. 細胞表面ペプチダーゼとは
b. アミノペプチダーゼN (APN / CD13)
c. アミノペプチダーゼA (APA)
d. ニュートラルエンドペプチダーゼ (NEP / CD10)
e. ジペプチジルペプチダーゼIV (DPP　IV / CD26)
5. プロテアーゼインヒビターの癌治療における臨床応用
V 増殖因子 , サイトカイン
1. 増殖因子 , サイトカインによるシグナル伝達
a. 受容体型チロシンキナーゼ
b. 非受容体型チロシンキナーゼ
c. サイトカイン受容体ファミリー
d. MAPキナーゼ
2. 婦人科腫瘍発生に関与するサイトカイン , 増殖因子
VI ウイルス発癌
1. ウイルスの発癌的感染
a. 腫瘍ウイルスの発見
b. 腫瘍ウイルス研究の意義
2. 腫瘍ウイルスの種類・構造
3. 腫瘍ウイルスの癌遣伝子
4. 腫瘍ウイルスによる癌化のメカニズム
5. ヒトの癌ウイルス
6. ヒトウイルス発癌とリスク因子 : まとめにかえて
腫瘍マーカーの細胞生物学
I 腫瘍マーカーの臨床における意義と複合糖質関連マーカー
1. 糖鎖抗原関連腫瘍マーカー
a. コアタンパク関連腫瘍マーカー
b. 基幹糖鎖関連腫瘍マーカー
c. 母核糖鎖関連腫瘍マーカー
2. 腫瘍マーカーのコンビネーションアッセイ
3. 腫瘍細胞における糖鎖構造の変化
a. 抗子宮体癌モノクローナル抗体
b. MSN-1の認識する連鎖抗原の局在
4. 糖転移酵素
a. GAT (癌関連ガラクトース転移酵素) の特性
b. GATと健常人由来のGalTとの関連について
c. 卵巣癌に対する腫瘍マーカーGAT
d. 卵巣腫瘍の良性・悪性の鑑別
II SCC抗原
1. SCC抗原の構造
2. SCC抗原遺伝子の発現調節機構
3. SCC抗原の組織局在
4. SCC抗原の生物作用
a. 標的酵素
b. アポトーシスとSCC抗原
5. SCC抗原の生物学的意義
6. SCC抗原の臨床的意義
III タンパク関連マーカー
A. 胎児タンパク
1. α-フェトプロテイン (AFP)
2. 癌胎児性抗原(CEA)
a. CEAの分子生物学
b. CEAの臨床
3. basic fetoprotein(BFP)
4. 胎児性抗原1 (FA1)
5. 胎児性抗原2 (FA2)
B. 胎盤タンパク
1. hCG
a. hCG分子の構造とその多様性
b. hCG測定
c. hCG測定に際しての注意
d. β-core fragment (β-CF) の臨床応用
2. SP1
3. hPL
4. PP5
5. PP10
6. PP12
7. PP14
8. PP19
9. PP26
C. 細胞骨格関連タンパク
1. 中間径フィラメントの血清診断マーカーとしての応用
a. tissue polypeptide antigen (TPA)
b. サイトケラチン-19
2. 病理組織マーカーとしての中間径フィラメント
a. ケラチン
b. ビメンチン
c. デスミン
d. グリア線維酸性タンパク
e. ニューロフイラメント
分子腫瘍学の臨床
I 婦人科癌と高発癌家系
1. 高発癌家系における原因遺伝子
2. 婦人科癌における高発癌家系
a. 子宮内膜癌
b. 家族性卵巣癌
II 婦人科癌の薬剤耐性機構
1. 薬剤耐性の種々のメカニズム
a. プラチナ耐性
b. タキサン耐性
2. 薬剤耐性の克服 (将来的な展望)
a. プラチナ耐性の克服
b. タキサン耐性の克服
III 遺伝子を標的とした治療
1. 悪性腫瘍に対する遺伝子治療法
a. 導入経路-ex vivoとin vivo
b. 導入法
2. 癌遺伝子治療の戦略
a. 癌遺伝子の抑制
b. 癌抑制遺伝子の導人
c. 自殺遺伝子
d. 免疫遺伝子
e. 多剤耐性遺伝子
3. 婦人科癌の遺伝子治療
a. 卵巣癌
b. 子宮頸癌
4. 遺伝子治療の展望
IV 子宮頸癌
A. 子宮頸癌の分子機構
1. HPVと子宮頸部腫瘍
2. 子宮頸部腫瘍にみられる遺伝子変化
3. HLAの役割
4. 遺伝子障害と病変の進行
5. ホルモン環境
6. HPV陰性の子宮頸部腫瘍
7. 結論
B. HPVと頸癌の臨床
1. HPVの診断法
2. HPVのタイプと子宮頸部病変
3. HPVを用いた前癌病変の管理
a. 子宮頸部異形成から子宮頸癌へ進展するリスク
b. HPVテストを併用した前癌病変の管理
4. HPVを用いた頸癌の管理
V 子宮体癌
A. 子宮体癌の分子機構
1. 子宮体癌の発生に関与する遺伝子群
a. ホルモン , 増殖因子 , サイトカインとその受容体の異常
b. 癌原遺伝子の活性化
c. 癌抑制遺伝子の不活性化
d. 不死化・アポトーシス関連遺伝子
e. MSI
f. 外来性ウイルス遺伝子
2. 子宮体癌の進展に関連する遺伝子
a. 癌細胞のクローナル選択と不死化
b. 浸潤・転移に関する遺伝子群
3. 子宮体癌発生の分子機構
a. 子宮体癌の臨床病理学的特徴
b. 子宮体癌発生の多様性
4. 遺伝子の臨床応用
a. 微量材料を用いた遺伝子診断
b. 癌に対する治療法の選択指標
c. 遺伝子治療
d. 家族性癌の診断
B. 増殖因子とホルモン
1. 子宮体癌と性ホルモン
2. 子宮体癌のエストロゲン反応性とその作用機序
3. 性ホルモン誘導性増殖因子
4. 子宮体癌のエストロゲン誘導性増殖因子と増殖因子受容体
5. 結語
VI　卵巣癌の分子機構
1. 散発性卵巣癌の分子病理学
a. 癌遺伝子
b. 癌抑制遺伝子
2. 卵巣癌の遺伝子治療
VII 絨毛癌の分子機構
1. 絨毛性疾患の分類
a. 部分奇胎
b. 全奇胎
2. 絨毛癌化機構へのアプローチ
a. 絨毛癌の発生起源
b. ゲノムインプリンティングと絨毛癌化
c. 絨毛癌化の分子機構
Glossary
索引
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欧文索引
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癌の分子遺伝学

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新女性医学大系 41 婦人科腫瘍の分子・細胞生物学

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癌の分子遺伝学

癌の細胞生物学

腫瘍マーカーの細胞生物学

分子腫瘍学の臨床

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