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研究生:張德寬
研究生(外文):De-Kuan Chang
論文名稱:肺癌專一性標的胜肽之尋找及標的治療之發展
論文名稱(外文):Identification of a Novel Peptide Specifically Binding to Lung Cancer for Targeted Therapy
指導教授:吳漢忠林欽塘林欽塘引用關係
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:病理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:英文
論文頁數:50
中文關鍵詞:腫瘤標的胜肽肺癌
外文關鍵詞:tumor-homing peptidesNSCLC
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全世界,每年約有一千萬人被診斷出患有癌症,而一年之中,更有超過六百萬人死於此疾病。而其中最為普遍的癌症分別為,佔12.3%的肺癌、10.4%的乳癌、以及9.4%的結腸直腸癌。肺癌於工業化國家中擁有高致死率,是所有因癌症死亡的病例中最為顯著的。人們患有非小細胞肺癌的病患其五年的存活率低於15%。缺乏癌細胞專一性標的物質一直是化學療法中的一重大問題,由於不具有專一性而使得副作用的產生,進而限制了藥物的劑量而無法根除癌細胞。在此研究中,我們運用噬菌體展示法,分離出能專一性結合非小細胞肺癌之十二個胺基酸胜肽。表現此特殊胜肽〈P5-2〉的噬菌體〈PC5-2〉具有專一性結合至非小細胞肺癌細胞株,且不會與正常細胞有結合現象。而針對移植非小細胞肺癌的SCID老鼠,此PC5-2噬菌體能專一性地瞄準腫瘤組織結合。此外,PC5-2噬菌體的導向能力,能進一步地被合成的P5-2胜肽所競爭而失去結合能力。更甚之,當將包含VNB抗癌藥物的微脂體連接P5-2胜肽〈P5-2-Lipo-VNB〉後,抑制腫瘤的生長能力較只帶有VNB的微脂體〈Lipo-VNB〉佳,且不會產生副作用。這些結果都指出P5-2胜肽將抗癌藥物送到癌組織並加強了藥物殺死SCID老鼠中肺癌組織的效力。此腫瘤專一性胜肽深具標的治療肺癌的潛力,並且可以發展肺癌的診斷試劑。
The most common cancers worldwide are lung (12.3 % of all cancers), breast (10.4 %) and colorectal cancer (9.4 %). Lung cancer is the predominant cause of cancer deaths in industrialized countries with a high death rate. The five-year survival rate is less than 15 % for patients with advanced non-small-cell lung cancer (NSCLC). Lack of tumor specificity remains a major problem with chemotherapies in that side effects prevent the delivery of essential dosages of drugs to eliminate majority cancer cells. In this report, we describe the isolation of a 12-mer peptide (P5-2) specifically binding to NSCLC from peptide-presenting phage libraries. The phage displayed P5-2 (PC5-2) were able to bind to NSCLC cell lines and did not bind to normal cells. In SCID mice bearing NSCLC xenografts, the PC5-2 could target to the tumor mass specifically. The homing activity of PC5-2 clones could be further competitively inhibited by synthetic P5-2. Furthermore, the P5-2-Lipo-vinorelbine (VNB) repressed tumor growth better than Lipo-VNB and without side effect. These results indicate that P5-2 enhanced the therapeutic efficacy of the drug against lung cancer xenografts in SCID mice. This tumor-specific peptide has a potential for targeted drug delivery to treat lung cancer and may be useful for designing targeted gene transfer vectors as well as diagnostic tools for this disease.
中文摘要……………………………1
Abstract……………………………2
Introduction………………………3
Materials and methods…………10
Results……………………………18
Discussion ………………………23
Figures……………………………29
Reference…………………………41
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