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研究生:張孟雅
研究生(外文):Chang, Meng-Ya
論文名稱:反轉錄病毒及腺病毒載體在老鼠膀胱癌免疫基因治療上之應用
論文名稱(外文):Immuno-gene Therapy for Murine Bladder Cancer with Retroviral and Adenoviral Vectors
指導教授:吳昭良
指導教授(外文):Wu, Chiao-Liang
學位類別:碩士
校院名稱:國立成功大學
系所名稱:生物化學研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:1998
畢業學年度:86
語文別:中文
論文頁數:79
中文關鍵詞:反轉錄病毒載體腺病毒載體前胸腺激素膀胱癌免疫基因治療
外文關鍵詞:retroviral vectoradenoviral vectorprothymosin alphabladder cancerimmuno-gene therapy
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基因治療在許多癌症、遺傳性缺失及感染性的疾病上,已成為一種具發
展性的治療方式。在許多的動物實驗模式中均證實將細胞素(cytokine)
基因引入細胞中表現,可以引發相對應的免疫刺激作用及抗腫瘤反應。
前胸腺激素 (prothymosin a;ProTa) 是由許多酸性氨基酸所組成的蛋
白質,其分子量為12.5 kDa。早期所知ProTa在生理上的主要功能是當
作一種胸腺賀爾蒙 (thymic hormone) ,它能夠促進淋巴細胞的成熟,
並具有調節免疫功能的作用。然而,近來許多的研究報告顯示,因
ProTa C端的序列 (KKQK) 為一段高保留性的入核序列
(nuclear localization signal; NLS) ,故使其能進入細胞核內與其
他因子作用,進而促進細胞的增殖。
由於小鼠膀胱癌細胞株MBT-2在病源學及病理組織學上均與人類膀胱癌
甚為相似,因此我們的實驗皆以其為模式來從事有關膀胱癌基因治療的
研究工作。在我們先前的報告中,已證實了利用反轉錄病毒
(retrovirus) 來攜帶ProTa基因至膀胱癌細胞中,可以有效地引發宿主
的免疫反應,並展現了對抗腫瘤生長的能力。因此,為了增強ProTa
抗腫瘤的效應且同時防止刺激腫瘤細胞的增生,我們使用聚合 連鎖
反應 (polymerase chain reaction, PCR) 將ProTa的入核序列加以去
除,構築ProTa的突變株 (ProTaDNLS) 。此外,在基因的傳遞上,不
同的病毒載體各有其優缺點,所以我們選用了兩種載體來攜帶所要表
現的基因。我們將ProTa及ProTaDNLS分別構築到反轉錄病毒及腺病毒
載體 (adenoviral vector) 上。我們利用這些重組病毒,來對老鼠膀
胱癌進行各種基因治療的策略。
經由實驗結果,我們發現在反轉錄病毒載體所執行的基因治療上,
ProTa及ProTaDNLS均展現了抗腫瘤的效益,而其中突變株ProTaDNLS的
治療效果確實較ProTa 為佳;然而在腺病毒載體方面,兩者所得到的
治療效果卻是相仿的,並無明顯的差異存在。再者,由於近年來的研
究報告指出,介白素12 (interleukin 12;IL-12) 在許多的腫瘤模式
中均表現出極顯著的抗癌效益,因此我們結合ProTa、ProTaDNLS及
IL-12,研究綜合性基因治療在膀胱癌上的可行性。結果顯示,利用混
合性基因治療來對抗腫瘤生長上的可行性頗高。綜合上述結果,
ProTaDNLS及綜合性基因治療在臨床膀胱癌的治療上應是極為可行的
策略。

Gene-based therapies for cancer have been developed and
employed to achieve antitumor effects, and the current
strategies include mutation compensation, molecular
chemotherapy, and genetic immunopotentiation. Introduction of
cytokine genes to enhance immunity against tumors have
demonstrated promise in animal models.
Prothymosin a (ProTa) is a highly acidic protein of 12.5 kDa
and is earlier considered as a thymic hormone that promotes
T-cell maturation. However, accumulating results suggest that
ProT* is a nuclear protein related to cell proliferation. Our
previous studies have shown that retroviruses expressing
ProTa gene inhibited tumor growth and induced antitumor
responses in the murine MBT-2 bladder tumor model. In order
to prevent ProTa gene-transduced cells from proliferation and
yet retain its antitumor activities, a ProTa mutant
ProTaDNLS lacking its nuclear localization signal was
generated. We constructed replication-defective adenoviruses
and retroviruses carrying either ProTa or the mutant
ProTaDNLS, and aimed to test the feasibility of ProTa or
ProTaDNLS gene therapy for murine bladder cancer. C3H/HeN
mice injected with MBT-2 cells admixed with retroviuses or
adenoviruses expressing ProTa or ProTaDNLS showed smaller
tumor mass and higher survival rate than the controls.
Moreover, retroviruses expressing ProTaDNLS were more
efficacious than those expressing ProTa in antitumor effects.
As recent studies suggest that interleukin-12 (IL-12)
possesses the most potent single-cytokine antitumor efficacy
in a variety of tumor models, we also employed ProTa,
ProTaDNLS, and IL-12 to investigate the feasibility of
combined gene therapy for bladder cancer. In conclusion,
ProTa, ProTaDNLS and combined gene therapies with the IL-12
gene may be highly effective approaches for the treatment
of bladder cancer.

中文摘要.....................................................................................................I
英文摘要..................................................................................................III
誌謝...........................................................................................................IV
目錄............................................................................................................V
圖目錄......................................................................................................IX
表目錄......................................................................................................XI
縮寫及符號............................................................................................XII
壹、緒論
A. 前胸腺激素的特性及生物功能........................................................1
B. 膀胱癌模式之介紹...........................................................................5
C. 反轉錄病毒載體(retroviral vector)之介紹.................................8
D. 腺病毒載體( adenviral vector )之介紹......................................11
E. 研究的目的及實驗策略..................................................................13
貳、材料與方法
A. 材料
A.1 實驗試劑來源............................................................................15
A.2 質體............................................................................................16
A.3 寡核酸....................................................................................16
A.4 菌種............................................................................................17
A.5 細胞株........................................................................................17
A.6 實驗動物....................................................................................18
A.7 細菌培養液..............................................................................18
A.8 細胞培養液..............................................................................18
A.9 溶液..........................................................................................19
B. 方法
B.1 質體備置
B.1.1 小量抽質體的方法(miniprep)...................................19
B.1.2 大量抽質體的方法(maxiprep)..................................20
B.1.3 DNA濃度的測量.............................................................21
B.2 DNA操作
B.2.1 限制切割質體DNA....................................................21
B.2.2 DNA的膠體電泳.............................................................21
B.2.3 回收膠體內的DNA片段...............................................22
B.2.4 接合反應(ligation)....................................................22
B.2.5 轉形作用(transformation).........................................23
B.2.6 以PCR進行基因的改變(mutagenesis)....................23
B.2.7 DNA之定序
B.2.7.1 質體定序法................................................................24
B.2.7.2 定序反應後產物的urea-polyacrylamide膠體電泳
.............................................................................25
B.3 細胞培養
B.3.1 細胞的次培養.................................................................26
B.3.2 細胞的計數.....................................................................26
B.3.3 哺乳類細胞之質體轉形作用(transfection).............27
B.3.4 以基因重組之反轉錄病毒感染細胞.............................28
B.3.5 細胞DNA合成的測定..................................................28
B.3.6 重組腺病毒質體之共同轉形作用................................28
B 3.7 基因重組腺病毒的定量(titration)..........................29
B.4 動物實驗
B4.1 ProTa或 ProTaDNLS重組反轉錄病毒對腫瘤抑制效
果之研究
B4.1.1實驗一.......................................................................29
B4.2 ProTa或 ProTaDNLS重組腺病毒對腫瘤抑制效果之
研究
B4.2.1 實驗二...................................................................30
B4.2.2 實驗三...................................................................31
4.3 綜合性基因治療(combined gene therapy)對腫瘤抑
制效果之研究
B4.3.1實驗四.....................................................................31
參、結果
Part I
A. ProTa突變株(ProTaDNLS)的構築......................................33
B. 構築基因重組的反轉錄病毒載體pRUFNeo/ProTaDNLS......33
C. 持續產生反轉錄病毒載體之包裝細胞株之建立.....................34
D. ProTaDNLS基因重組的MBT-2細胞株之建立.....................34
E. MBT-2/ ProTaDNLS細胞株增殖速率之比較 ....................... 35
F. ProTa及 ProTaDNLS基因重組的反轉錄病毒對MBT-2細
胞致癌性之影響
(1).腫瘤發生率.......................................................................35
(2).腫塊大小...........................................................................36
(3).小鼠存活率.......................................................................36
Part II
A. 構築基因重組的腺病毒載體AdI2/ProTa及AdI2/ProTaDNLS
.................................................................................................37
B. 重組腺病毒之建立.....................................................................37
C. 重組腺病毒之PCR分析...........................................................38
D. ProTa及 ProTaDNLS基因重組的腺病毒對MBT-2細胞致
癌性之影響.
(1).腫塊大小............................................................................38
(2).小鼠存活率........................................................................39
E. 綜合性基因治療對MBT-2細胞致癌性之影響
(1).腫塊大小............................................................................39
(2).小鼠存活率........................................................................39
肆、討論............................................................................................41
伍、參考文獻.........................................................................48
陸、圖................................................................................................58
柒、表....................................................................................77
捌、附錄................................................................................78
玖、自述................................................................................79

Abe, J., Wakimoto, H., Yoshida, Y., Aoyagi, M., and Hieakawa, K. Antitumor effect induced by granulocyte/macrophage-colony-stimulating factor gene-modified tumor vaccination: comparison of adenovirus- and retrovirus-mediated genetic transduction. J. Cancer. Res. Clin. Oncol. 121(9-10): 587-592, 1995.
Addison, C. L., Braciak, T., Ralston, R., Muller, W. J., Gauldie, J., and Graham, F. L. Intratumor injection of an adenovirus expressing interleukin 2 induces regression and immunity in a murine breast cancer model. Proc. Natl. Acad. Sci. USA. 92: 8522-8526, 1995.
Baxevanis, C. N., Reclos, G. J., Papamichail, M. and Tsokos, G. C. Prothymosin a restores the depressed autologous and allogeneic mixed lymphocyte responses in patients with systemic lupus erythematosus. Immunopharmacol. Immunotoxicol. 9: 429-440, 1987.
Baxevanis, C. N., Reclos, G. J., Panneerselvam, C. and Papamichail, M. Enhancement of human T lymphocyte functions by prothymosin a. I. Augmentation of mixed lymphocyte culture reactions and soluble protein-induced proliferative responses. Immunopharmacology. 15: 73-84, 1988.
Baxevanis, C. N., Thanos, D., Reclos, G. J., Anastasopoulos, E., Tsokos, G. C., Papamatheakis, G. J. and Papamichail, M Prothymosin a enhances human and murine MHC class II surface antigen expression and messenger RNA accumulation. J. Immunol. 148: 1979-1984, 1992.
Baxevanis, C. N., Reclos, G. J., Gritzapis, A. D., Dedousis, G. V. Z., Missitzis, I., and Papamichail, M. Elevated prostaglandin E2 production by monocytes is responsible for the depressed levels of natural killer and lymphokine- activated killer cell function in patients with breast cancer. Cancer. 72:491-501, 1993a.
Baxevanis, C. N., Reclos, G. J. and Papamichail, M. Prothymosin a restores depressed allogenic cell-mediated lympholysis and natural-killer-cell activity in patients with cancer. Int. J. Cancer. 53: 264-268, 1993b.
Baxevanis, C. N., Gritzapis, A. D., Dedoussis, G. V. Z., Papadopoulos, N. G. Tsolas, O. and Papamichail, M. Induction of lymphokine-activated killer activity in mice by prothymosin a. Cancer Immunol. Immunother. 38: 281-286, 1994.
Baxevanis, C. N., Gritxapis, A. D.,Spanakos, G., Tsitsilonis, O. E. and Papamichail, M. Induction of tumor-specific T lymphocyte responses in vivo by prothymosin a. Cancer Immunol. Immunother. 40: 410-418, 1995.
.
Bestwick, R. K., Kozak, S. L. and Kabat, D. Overcoming interference to retroviral superinfection results in amplified expression and transmission of cloned genes. Proc. Natl. Acad. Sci. USA. 85: 5404-5408, 1988.
Bodine, D. M., McDonagh, K. T., Brandt, S. J., Ney, P. A., Agricola, B., Byrne, E. and Nienhuis, A. W. Development of a high-titer retrovirus producer cell line capable of gene transfer into rhesus monkey hematopoietic stem cells. Proc. Natl. Acad. Sci. USA. 87: 3738-3742, 1990.
Burchill, S. A., Neal, D. E., and Lunce, J. Frequency of H-ras mutations in human bladder cancer detected by direct sequencing. Br. J. Urol. 73: 516-521, 1994.
Cass R. A. M., Hosker, M. E., and McDonald, D. M. et al., Tumors of urinary bladder in workmen engaged in manufacture and use of certain dye-stuff intermediates in British chemical industry: Role of aniline, benzidine, alpha-naphthylamine, and beta-naphthylamine. Br. J. Industr. Med. 11: 75-104, 1954.
Cass R. A. M., and Hosker, M. E. Tumor of the urinary bladder as an occupational disease in the rubber industry in England and Wales. Br. Prev.Soc. Med. 89: 39-50, 1954.
Castro, J. M., and Barcia, M. G. Localization of prothymosin a in the nucleus. Biochem. Biophys. Res. Commun. 224: 140-146, 1996.
Chiang, H. S., Guo, H. R., Hong, C. L., Lin S. M. and Lee, E. F. The incidence of bladder cancer in the black foot disease endemic area in Taiwan. Brit. J. Urol. 71: 274-278, 1993.
Chung, C. T. and Miller, R. H. A rapid and convenient method for the preparation and storage of competent bacterial cells. Nucleic acids Res. 16: 3580, 1988.
Clinton, M., Graeve, L., E1-Dorry, H., and Horecker, B. L. Evidence for nuclear targeting of prothymosin and parathymosin synthesized in situ. Proc. Natl. Acad. Sci.USA. 88: 6608-6612, 1991.
Connor, J., Bannerji, R., Saito, S., Heston, W., Fair, W. and Gilboa, E. Regression of bladder tumor in mice treated with interleukin 2 gene-modified tumor cells. J. Exp. Med. 177: 1127-1134, 1993.
Conteas, C. N., Mutchnick, M. G., Palmer, K. C., Weller, F. E., Luk, G. D., Naylor, P. H., Erdos, M. R., Goldstein, A. L., Panneerselvam, C. and Horecker, B. L. Cellular levels of thymosin immunoreactive peptides are linked to proliferative events: evidence for a nuclear site of action. Proc. Natl. Acad. Sci. USA. 87: 3269-3273, 1990.
Cordero, O. J., Sarandeses, C. S., Lopez, J. L., Cancio, E., Regueiro, B. J. and Nogueira, M. Prothymosin a enhances interleukin 2 receptor expression in normal human T-lymphocytes. Int. J. Immunopharmacol. 13: 1059-1065, 1991.
Cordero, O. J., Sarandeses, C., Lopez, L. and Nogueira, M. Prothymosin a ehances human natural killer cell cytotoxicity: role in mediating signals for NK activity. Lymphokine Cytokine Res. 11: 277-285, 1992.
Cordero, O. J., Sarandeses, C. and Nogueira, M. Prothymosin a receptors on peripherl blood mononuclear cells. FEBS Lett. 341: 23-27, 1994.
Cordero, O. J., Sarandeses, C. and Nogueira, M. Prothymosin a receptors on lymphocytes. J. Interferon Cytokine Res. 15: 731-737, 1995.
Danos, O. and Mulligan, R. C. Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc. Natl. Acad. Sci. USA. 85: 6460-6464, 1988.
Davis, B. M., Koc, O. N., Lee, K. and Gerson, S. L. Current progress in the gene therapy of cancer. Curr. Opin. Oncol. 8: 499-508, 1996.
Del-Senno, L., Maestril, I. and Piva, R. Differential hypomethylation of the c-myc protooncogene in bladder cancers at different stages and grades. J. Urol. 142: 146-149, 1989.
Eckert, K., Garbin, F., Maurer, H. R., Buttner, P., Garbe, C. and Czarnecki, J. Prothymosin a modulates lymphokine-activated killer cell activity and IL-2 production by peripheral blood lymphocytes from melanoma patients in vitro. Int. J. Immunopharmacol. 17: 555-561, 1995.
Economou, M., Seferiadis, K., Frangou-Lazaridis, M., Horecker, B. L. and Tsolas, O. Isolation and partial characterization of prothymosin a from porcrine tissues. FEBS Lett. 233: 342-346, 1988.
Eschendfeldt, W. H. and Berger, S. L. The human prothymosin a gene is polymorphic and induced upon growth stimulation: evidence using a cloned cDNA. Proc. Natl. Acad. Sci. USA. 83; 9403-9407, 1986.
Franco, F. J., Diaz, C., Barcia, M., Arias, P., Gomez-Marquez, J., Soriano, F., Mendez, E. and Freire, M. Synthesis and apparent secretion of prothymosin a by different subpopulations of calf and rat thymocytes. Immunology. 67: 263-268, 1989.
Frillingos, S., Frangou-Lazaridis, M., Seferiadis, K. Hulmes, J. D., Pan, Y.-C. E. and Tsolas, O. Isolation and partial sequence of goat spleen prothymosin a. Mol. Cell. Biochem. 108: 85-94, 1991.
Frillingos, S., Seferiadis, K., Papanastasiou, M., Baxevanis, C. N., Frangou-Lazaridis, M., Economou, M., Papamichail, M. and Tsolas, O. Appearance of thymosin a1 in supernatants of monocytes incubated with prothymosin a. Arch. Biochem. Biophys. 296: 256-263, 1992.
Garbin, F., Eckert, K., Buttner, P., Garbe, C. and Maurer, H. R. Prothymosin a augments deficient antitumor activity of monocytes from melanoma patients in vitro. Anticancer Res. 14: 2405-2412, 1994.
Garbin, F., Eckert, K., Immenschuh, P., Kreuser, E. D., and Maurer, H. R. Prothymosin a1 effects, in vitro, on the antitumor acitivity and cytokine production of blood monocytes from colorectal tumor patients. Int.. J. Immunopharmac. 19:323-332, 1997
Gaubatz, S., Meichle, A. and Eilers, M. An E-box element localized in the first intron mediates regulation of the prothymosin a gene by c-myc. Mol. Cell. Biol. 14: 3853-3862, 1994.
Goldstein, A. L., Slater, F. D. and White, A. Preparation, assay and purification of a thymic lymphocytopoietic factor (thymosin). Proc. Natl. Acad. Sci. USA. 56: 1010-1017, 1966.
Gomez-Marquez, J., Segade, F., Dosil, M., Pichel, J. G., Bustelo, X. R. and Freire, M. The expression of prothymosin a gene in T lymphocytes and leukemic lymphoid cells is tied to lymphocyte proliferation. J. Biol. Chem. 264: 8451-8454, 1989.
Goodall, G. L., Dominguez, F. and Horecker, B. L. Molecular cloning of cDNA for human prothymosin a. Proc.Natl. Acad. Sci. USA. 83: 8926-8928, 1986.
Graham, F. L., Smiley, J., Russell, W. C., and Nairin, R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J. Gen. Virol. 36: 59-72, 1977.
Greber, U. F., Willetts, M., Webster, P., and Helenius, A. Stepwise dismantling of adenovirus 2 during entry into cells. Cell. 75: 477-486, 1993.
Haritos, A. A., Goodall, G. J. and Horecker, B. L. Prothymosin alpha: isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus. Proc. Natl. Acad. Sci. USA. 81: 1008-1011, 1984a.
Haritos, A. A., Tsolas, O. and Horecker, B. L. Distribution of prothymosin a in rat tissues. Proc. Natl. Acad. Sci. USA. 81: 1391-1393, 1984b.
Haritos, A. A., Blacher, R., Stein, S., Caldarella, J. and Horecker, B. L. Primary structure of rat thymus prothymosin alpha. Proc. Natl. Acad. Sci. USA. 82: 343-346, 1985.
Horowitz, J. M., Parks, H., Begemman, E., Cheng, J. C., Yandell, D. W. Kaye, F. J., Minna, J. D., Dryja, T. P. and Weinberg, R. A. Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumors. Proc. Ntal. Acad. Sci. USA. 87: 2775-2779, 1990.
Ish-Horawicz, D. and Burke, J. F. Rapid and efficient cosmid cloning. Nucleic acids Res. 9: 2989-2998, 1981.
Jackson, A. M. and James, K. Understanding the most successful immunotherapy for cancer. The Immunologist 2: 208-215, 1994.
Knowles, M. A., Elder, P. A., Willianmson, M., Cairns J. P., Shaw, M. E., and Law, M. G. Alleotype of human bladder cancer. Cancer. Res. 54: 531-538, 1994.
Kroft, S. H. and Oyasu, R Urinary bladder cancer: mechanisms of development and progression. Lab. Invest. 71: 158-174, 1994.
Kubota, S., Adachi, Y., Copeland, T. D. and Oroszlan, S. Binding of human prothymosin a to the leucine-motif/activation domains of HTLV-I Rex and HIV-1 Rev. Eur. J. Biochem. 233: 48-54, 1995.
Lopez-Rodriguez, J. L., Cordero, O. J., Sarandeses, C., Vinuela, J. and Nogueira, M. Interleukin-2 killer cells: in vitro evaluation of combination with prothymosin a. Lymphokine Cytokine Res. 13: 175-182, 1994.
Makarova, T., Grebenshikov, N., Egorov, C., Vartapetian, A. and Bogdanov, A. Prothymosin a is an evolutionary conserved protein covalently linked to a small RNA. FEBS Lett. 257: 247-250, 1989.
Manrow, R. E., Sburlati, A. R., Hanover, J. A. and Berger S. L. Nuclear targeting of prothymosin a. J. Biol. Chem. 266: 3916-3924, 1991.
Masters, J. R., Vesey, S. G. and Munn, C. F. C-myc oncoprotein levels in bladder cancer. Urol. Res. 16: 341-344, 1988.
McGrory, W. J., Bautista, D. S., and Graham, F. L. A simple technique for the rescue of early region 1 mutations into infectious human adenovirus type 5. Virology. 163: 614-617, 1997.
Miller, D. G., Adam, M. A. and Miller, A. D. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol. Cell. Biol. 10: 4239-4242, 1990.
Miller, A. D., Miller, D. G., Garcia, J. V. and Lynch, C. M. Use of retroviral vectors for gene transfer and expression. Methods Enzymol. 217: 581-599, 1993.
Miyamoto, H., Kubota, Y., Shuin, T., Torigoe, S., Dobashi, Y. and Hosaka, M. Expression of transforming growth factor-beta 1 in human bladder cancer. Cancer. 75: 2565-2570, 1995.
Morgan, R. A. and Anderson, W. F. Human gene therapy. Ann. Rev. Biochem. 62: 191-217, 1993.
Morgan, E. Interaction of adenoviral proteins with pRB and p53. FASEB. 7: 880-885, 1993.
Mulligan, R. C. The basic science of gene therapy. Science 260: 926-936, 1993.
Nobori, T., Miura, K., Wu, D. J., Lois, A., Takabayashi, K., and Carson, D.A. Deletions of the cyclin-dependent kinase-4 inhibitor gene in mutiple human cancers. Nature 368: 753-756, 1994.
Nseyo, U. O., and Lamm, D. Therapy of superficial bladder cancer. Semin. Oncol. 23: 598-604, 1996.
Oates, K. K. and Goldstein, A. L. Thymosin. In Biologic therapy of cancer. Lippincott: Philadelphia, USA, 1995
Palvimo, J., and Linnala-Kankkunen, A. Idification of a low-Mr acidic nuclear protein as prothymosin alpha. FEBS Lett. 277: 257-260, 1990.
Pan, L.-X., Haritos, A. A., Wideman, J., Komiyama, T., Chang, M., -Stein, S., Salvin, S. B. and Horecker, B. L. Human prothymosin a: amino a, cid sequence and immunologic properties. Arch. Biochem. Biophys. 250: 197-201, 1986.
Panneerselvam, C., Haritos, A. A., Caldarella, J. and Horecker, B. L. Prothymosin a in human blood. Proc. Natl. Acad. Sci. USA. 84: 4465-4469, 1987.
Panneerselvam, C.,Wellner, D. and Horecker, B. L. The amino acid sequence of bovine thymus prothymosin a. Arch. Biochem. Biophys. 265: 454-457, 1988.
Papamarcaki, T. and Tsolas, O. Prothymosin a binds to histone H1 in vitro. FEBS Lett. 345: 71-75, 1994.
Papanastasiou, M., Baxevanis, C. N. and Papamichail, M. Promotion of murine antitumor activity by prothymosin a treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumor necrosis factor a. Cancer Immunol. Immunother. 35: 145-150, 1992.
Ravery, V., Jouanneau, J., Gil, S., Abbou, C. C., Caruelle, J. P., Barritault, D., and Chopin, D. K. Immunohistochemical detection of acidic fibroblast growth factor in bladder transitional cell carcinoma. Urol. Res. 20: 211-214, 1992.
Rayner, J. R. and Gonda, T. A simple and efficient procedure for generating stable expression libraries by cDNA cloning in a retroviral vector. Mol. Cell. Biol. 14: 880-887, 1994.
Reclos, G. J., Baxevanis, C. N., Sfagos, C., Papageorgiou, C., Tsokos, G. C. and Papamichail, M. Multiple sclerosis: II. Effects of prothymosin a on the autologous and allogeneic MLR in patients with multiple sclerosis. Clin. Exp. Immunol. 70: 336-344, 1987.
Reznikoff, C. A., Belair, C. D., Yeager, T. R., Savelieva, E., Blelloch, R. H., Puthenveettil, J. A., and Cuthill, S. A molecular genetic model of human bladder cancer pathogenesis. Semin. Oncol. 23: 571-584, 1996.
Robbins, P. D., Tahara, H., and Ghivizzani, S. C. Viral vectors for gene therapy. Trends. Biotechnol. 16: 35-40, 1998.
Rosenfeld, M. E., BA and Curiel, D. T. Gene therapy stragies for novel cancer therapeutics. Curr. Opin. Oncol. 8: 72-77, 1996.
Ross, R. K., Paganini-Hill, A., and Henderson, B. E. Epideriology of bladder cancer, in Skinner D, Lieskovsky G (eds): Diagnosis and management of genitourinary cancer. Philadelphia, PA, Saunders. 23-31, 1988.
Sburlati, A. R., Manrow, R. E. and Berger, S. L. Prothymosin a antisense oligomers inhibit myeloma cell division. Proc. Natl. Acad. Sci. USA. 88: 253-257, 1991.
Schmidt, G. and Werner, D. Nucleotide sequence of the murine prothymosin a cDNA and its deduced primary and secondary protein structure. Biochim. Biophys. Acta. 1088: 442-444, 1991.
Smith, M. R., Al-Katib, A., Mohammad, R., Silverman, A., Szabo, P., Khilnani, S., Kohler, W., Nath, R. and Mutchnick, M. G. Prothymosin a gene expression correlates with proliferation, not differentiation, of HL60 cells. Blood. 82: 1127-1132, 1993.
Smith, M. R. Prothymosin a: in search of a function. Leukemia Lymphoma. 18: 209-214, 1995.
Spruck III, C. H., Ohneseit, P. E., Gonzalez-Zulueta, M., Esrig, D., Miyao, N., Tsai, Y. C., Lerner, S. P., Schmutte, C., Yang, A. S., and Cote, R. Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res. 54: 784-788, 1994.
Thomas, K. A. Fibroblast growth factors. FASEB. 1: 434-440, 1987.
Trainin, N., Rotter, V., Yakir, Y., Leve, R., Handzel, Z., Shohat, B. and Zaizov, R. Biochemical and biological properties of THF in animal and human models. Ann. N. Y. Acad. Sci. 322: 9-22, 1979.
Vile, R. G. and Russell, S. J. Retroviruses as vectors. Brit. Med. Bull. 51: 12-30, 1995.
Watts, J. D., Cary, P. D. and Crane-Robinson, C. Prothymosin a is a nuclear protein. FEBS Lett. 245: 17-20, 1989.
Weatherall, D. J. Scope and limitations of gene therapy. Brit. Med. Bull. 51: 1-11, 1995.
Whartenby, K. A., Abboud, C. N., Marrogi, A. J., Ramesh, R. and Freeman, S. M. The biology of cancer gene therapy. Lab. Invest. 72: 131-145, 1995.
Wright, C., Mellonk, Neal, D. E., Johnston, P., Corbett, I. P. and Horne, C. H. Expression of c-erb B-2 protein product in bladder cancer. Brit. J. Cancer. 62: 764-765, 1990.
Wu, C. L., Shiau, A. L. and Lin, C. S. Prothymosin alpha promotes cell proliferation in NIH3T3 cells. Life sci. 61(21):2091-2101, 1997
Zhau, H. E., Xhang, X., Von Eschenbach, A. C., Scorsone, K., Babaian, R. J., Ro, J. Y. and Hung, M. C. Amplification and expression of the c-erb B-2/neu oncogene in human bladder cancer. Mol. Carcinogen. 3: 254-257, 1990.
Ginsberg, H. S. The adenoviruses. ( Plenum, New York ), 1984.
林宜蓉。老鼠胸腺激素的基因結構及細胞活性之研究。 國立成功大學碩士論文,1995。
林佩儒。前胸腺激素基因治療在老鼠膀胱癌模式之研究。國立成功大學碩士論文,1996。
參考文獻
Abe, J., Wakimoto, H., Yoshida, Y., Aoyagi, M., and Hieakawa, K. Antitumor effect induced by granulocyte/macrophage-colony-stimulating factor gene-modified tumor vaccination: comparison of adenovirus- and retrovirus-mediated genetic transduction. J. Cancer. Res. Clin. Oncol. 121(9-10): 587-592, 1995.
Addison, C. L., Braciak, T., Ralston, R., Muller, W. J., Gauldie, J., and Graham, F. L. Intratumor injection of an adenovirus expressing interleukin 2 induces regression and immunity in a murine breast cancer model. Proc. Natl. Acad. Sci. USA. 92: 8522-8526, 1995.
Baxevanis, C. N., Reclos, G. J., Papamichail, M. and Tsokos, G. C. Prothymosin a restores the depressed autologous and allogeneic mixed lymphocyte responses in patients with systemic lupus erythematosus. Immunopharmacol. Immunotoxicol. 9: 429-440, 1987.
Baxevanis, C. N., Reclos, G. J., Panneerselvam, C. and Papamichail, M. Enhancement of human T lymphocyte functions by prothymosin a. I. Augmentation of mixed lymphocyte culture reactions and soluble protein-induced proliferative responses. Immunopharmacology. 15: 73-84, 1988.
Baxevanis, C. N., Thanos, D., Reclos, G. J., Anastasopoulos, E., Tsokos, G. C., Papamatheakis, G. J. and Papamichail, M Prothymosin a enhances human and murine MHC class II surface antigen expression and messenger RNA accumulation. J. Immunol. 148: 1979-1984, 1992.
Baxevanis, C. N., Reclos, G. J., Gritzapis, A. D., Dedousis, G. V. Z., Missitzis, I., and Papamichail, M. Elevated prostaglandin E2 production by monocytes is responsible for the depressed levels of natural killer and lymphokine- activated killer cell function in patients with breast cancer. Cancer. 72:491-501, 1993a.
Baxevanis, C. N., Reclos, G. J. and Papamichail, M. Prothymosin a restores depressed allogenic cell-mediated lympholysis and natural-killer-cell activity in patients with cancer. Int. J. Cancer. 53: 264-268, 1993b.
Baxevanis, C. N., Gritzapis, A. D., Dedoussis, G. V. Z., Papadopoulos, N. G. Tsolas, O. and Papamichail, M. Induction of lymphokine-activated killer activity in mice by prothymosin a. Cancer Immunol. Immunother. 38: 281-286, 1994.
Baxevanis, C. N., Gritxapis, A. D.,Spanakos, G., Tsitsilonis, O. E. and Papamichail, M. Induction of tumor-specific T lymphocyte responses in vivo by prothymosin a. Cancer Immunol. Immunother. 40: 410-418, 1995.
.
Bestwick, R. K., Kozak, S. L. and Kabat, D. Overcoming interference to retroviral superinfection results in amplified expression and transmission of cloned genes. Proc. Natl. Acad. Sci. USA. 85: 5404-5408, 1988.
Bodine, D. M., McDonagh, K. T., Brandt, S. J., Ney, P. A., Agricola, B., Byrne, E. and Nienhuis, A. W. Development of a high-titer retrovirus producer cell line capable of gene transfer into rhesus monkey hematopoietic stem cells. Proc. Natl. Acad. Sci. USA. 87: 3738-3742, 1990.
Burchill, S. A., Neal, D. E., and Lunce, J. Frequency of H-ras mutations in human bladder cancer detected by direct sequencing. Br. J. Urol. 73: 516-521, 1994.
Cass R. A. M., Hosker, M. E., and McDonald, D. M. et al., Tumors of urinary bladder in workmen engaged in manufacture and use of certain dye-stuff intermediates in British chemical industry: Role of aniline, benzidine, alpha-naphthylamine, and beta-naphthylamine. Br. J. Industr. Med. 11: 75-104, 1954.
Cass R. A. M., and Hosker, M. E. Tumor of the urinary bladder as an occupational disease in the rubber industry in England and Wales. Br. Prev.Soc. Med. 89: 39-50, 1954.
Castro, J. M., and Barcia, M. G. Localization of prothymosin a in the nucleus. Biochem. Biophys. Res. Commun. 224: 140-146, 1996.
Chiang, H. S., Guo, H. R., Hong, C. L., Lin S. M. and Lee, E. F. The incidence of bladder cancer in the black foot disease endemic area in Taiwan. Brit. J. Urol. 71: 274-278, 1993.
Chung, C. T. and Miller, R. H. A rapid and convenient method for the preparation and storage of competent bacterial cells. Nucleic acids Res. 16: 3580, 1988.
Clinton, M., Graeve, L., E1-Dorry, H., and Horecker, B. L. Evidence for nuclear targeting of prothymosin and parathymosin synthesized in situ. Proc. Natl. Acad. Sci.USA. 88: 6608-6612, 1991.
Connor, J., Bannerji, R., Saito, S., Heston, W., Fair, W. and Gilboa, E. Regression of bladder tumor in mice treated with interleukin 2 gene-modified tumor cells. J. Exp. Med. 177: 1127-1134, 1993.
Conteas, C. N., Mutchnick, M. G., Palmer, K. C., Weller, F. E., Luk, G. D., Naylor, P. H., Erdos, M. R., Goldstein, A. L., Panneerselvam, C. and Horecker, B. L. Cellular levels of thymosin immunoreactive peptides are linked to proliferative events: evidence for a nuclear site of action. Proc. Natl. Acad. Sci. USA. 87: 3269-3273, 1990.
Cordero, O. J., Sarandeses, C. S., Lopez, J. L., Cancio, E., Regueiro, B. J. and Nogueira, M. Prothymosin a enhances interleukin 2 receptor expression in normal human T-lymphocytes. Int. J. Immunopharmacol. 13: 1059-1065, 1991.
Cordero, O. J., Sarandeses, C., Lopez, L. and Nogueira, M. Prothymosin a ehances human natural killer cell cytotoxicity: role in mediating signals for NK activity. Lymphokine Cytokine Res. 11: 277-285, 1992.
Cordero, O. J., Sarandeses, C. and Nogueira, M. Prothymosin a receptors on peripherl blood mononuclear cells. FEBS Lett. 341: 23-27, 1994.
Cordero, O. J., Sarandeses, C. and Nogueira, M. Prothymosin a receptors on lymphocytes. J. Interferon Cytokine Res. 15: 731-737, 1995.
Danos, O. and Mulligan, R. C. Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc. Natl. Acad. Sci. USA. 85: 6460-6464, 1988.
Davis, B. M., Koc, O. N., Lee, K. and Gerson, S. L. Current progress in the gene therapy of cancer. Curr. Opin. Oncol. 8: 499-508, 1996.
Del-Senno, L., Maestril, I. and Piva, R. Differential hypomethylation of the c-myc protooncogene in bladder cancers at different stages and grades. J. Urol. 142: 146-149, 1989.
Eckert, K., Garbin, F., Maurer, H. R., Buttner, P., Garbe, C. and Czarnecki, J. Prothymosin a modulates lymphokine-activated killer cell activity and IL-2 production by peripheral blood lymphocytes from melanoma patients in vitro. Int. J. Immunopharmacol. 17: 555-561, 1995.
Economou, M., Seferiadis, K., Frangou-Lazaridis, M., Horecker, B. L. and Tsolas, O. Isolation and partial characterization of prothymosin a from porcrine tissues. FEBS Lett. 233: 342-346, 1988.
Eschendfeldt, W. H. and Berger, S. L. The human prothymosin a gene is polymorphic and induced upon growth stimulation: evidence using a cloned cDNA. Proc. Natl. Acad. Sci. USA. 83; 9403-9407, 1986.
Franco, F. J., Diaz, C., Barcia, M., Arias, P., Gomez-Marquez, J., Soriano, F., Mendez, E. and Freire, M. Synthesis and apparent secretion of prothymosin a by different subpopulations of calf and rat thymocytes. Immunology. 67: 263-268, 1989.
Frillingos, S., Frangou-Lazaridis, M., Seferiadis, K. Hulmes, J. D., Pan, Y.-C. E. and Tsolas, O. Isolation and partial sequence of goat spleen prothymosin a. Mol. Cell. Biochem. 108: 85-94, 1991.
Frillingos, S., Seferiadis, K., Papanastasiou, M., Baxevanis, C. N., Frangou-Lazaridis, M., Economou, M., Papamichail, M. and Tsolas, O. Appearance of thymosin a1 in supernatants of monocytes incubated with prothymosin a. Arch. Biochem. Biophys. 296: 256-263, 1992.
Garbin, F., Eckert, K., Buttner, P., Garbe, C. and Maurer, H. R. Prothymosin a augments deficient antitumor activity of monocytes from melanoma patients in vitro. Anticancer Res. 14: 2405-2412, 1994.
Garbin, F., Eckert, K., Immenschuh, P., Kreuser, E. D., and Maurer, H. R. Prothymosin a1 effects, in vitro, on the antitumor acitivity and cytokine production of blood monocytes from colorectal tumor patients. Int.. J. Immunopharmac. 19:323-332, 1997
Gaubatz, S., Meichle, A. and Eilers, M. An E-box element localized in the first intron mediates regulation of the prothymosin a gene by c-myc. Mol. Cell. Biol. 14: 3853-3862, 1994.
Goldstein, A. L., Slater, F. D. and White, A. Preparation, assay and purification of a thymic lymphocytopoietic factor (thymosin). Proc. Natl. Acad. Sci. USA. 56: 1010-1017, 1966.
Gomez-Marquez, J., Segade, F., Dosil, M., Pichel, J. G., Bustelo, X. R. and Freire, M. The expression of prothymosin a gene in T lymphocytes and leukemic lymphoid cells is tied to lymphocyte proliferation. J. Biol. Chem. 264: 8451-8454, 1989.
Goodall, G. L., Dominguez, F. and Horecker, B. L. Molecular cloning of cDNA for human prothymosin a. Proc.Natl. Acad. Sci. USA. 83: 8926-8928, 1986.
Graham, F. L., Smiley, J., Russell, W. C., and Nairin, R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J. Gen. Virol. 36: 59-72, 1977.
Greber, U. F., Willetts, M., Webster, P., and Helenius, A. Stepwise dismantling of adenovirus 2 during entry into cells. Cell. 75: 477-486, 1993.
Haritos, A. A., Goodall, G. J. and Horecker, B. L. Prothymosin alpha: isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus. Proc. Natl. Acad. Sci. USA. 81: 1008-1011, 1984a.
Haritos, A. A., Tsolas, O. and Horecker, B. L. Distribution of prothymosin a in rat tissues. Proc. Natl. Acad. Sci. USA. 81: 1391-1393, 1984b.
Haritos, A. A., Blacher, R., Stein, S., Caldarella, J. and Horecker, B. L. Primary structure of rat thymus prothymosin alpha. Proc. Natl. Acad. Sci. USA. 82: 343-346, 1985.
Horowitz, J. M., Parks, H., Begemman, E., Cheng, J. C., Yandell, D. W. Kaye, F. J., Minna, J. D., Dryja, T. P. and Weinberg, R. A. Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumors. Proc. Ntal. Acad. Sci. USA. 87: 2775-2779, 1990.
Ish-Horawicz, D. and Burke, J. F. Rapid and efficient cosmid cloning. Nucleic acids Res. 9: 2989-2998, 1981.
Jackson, A. M. and James, K. Understanding the most successful immunotherapy for cancer. The Immunologist 2: 208-215, 1994.
Knowles, M. A., Elder, P. A., Willianmson, M., Cairns J. P., Shaw, M. E., and Law, M. G. Alleotype of human bladder cancer. Cancer. Res. 54: 531-538, 1994.
Kroft, S. H. and Oyasu, R Urinary bladder cancer: mechanisms of development and progression. Lab. Invest. 71: 158-174, 1994.
Kubota, S., Adachi, Y., Copeland, T. D. and Oroszlan, S. Binding of human prothymosin a to the leucine-motif/activation domains of HTLV-I Rex and HIV-1 Rev. Eur. J. Biochem. 233: 48-54, 1995.
Lopez-Rodriguez, J. L., Cordero, O. J., Sarandeses, C., Vinuela, J. and Nogueira, M. Interleukin-2 killer cells: in vitro evaluation of combination with prothymosin a. Lymphokine Cytokine Res. 13: 175-182, 1994.
Makarova, T., Grebenshikov, N., Egorov, C., Vartapetian, A. and Bogdanov, A. Prothymosin a is an evolutionary conserved protein covalently linked to a small RNA. FEBS Lett. 257: 247-250, 1989.
Manrow, R. E., Sburlati, A. R., Hanover, J. A. and Berger S. L. Nuclear targeting of prothymosin a. J. Biol. Chem. 266: 3916-3924, 1991.
Masters, J. R., Vesey, S. G. and Munn, C. F. C-myc oncoprotein levels in bladder cancer. Urol. Res. 16: 341-344, 1988.
McGrory, W. J., Bautista, D. S., and Graham, F. L. A simple technique for the rescue of early region 1 mutations into infectious human adenovirus type 5. Virology. 163: 614-617, 1997.
Miller, D. G., Adam, M. A. and Miller, A. D. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol. Cell. Biol. 10: 4239-4242, 1990.
Miller, A. D., Miller, D. G., Garcia, J. V. and Lynch, C. M. Use of retroviral vectors for gene transfer and expression. Methods Enzymol. 217: 581-599, 1993.
Miyamoto, H., Kubota, Y., Shuin, T., Torigoe, S., Dobashi, Y. and Hosaka, M. Expression of transforming growth factor-beta 1 in human bladder cancer. Cancer. 75: 2565-2570, 1995.
Morgan, R. A. and Anderson, W. F. Human gene therapy. Ann. Rev. Biochem. 62: 191-217, 1993.
Morgan, E. Interaction of adenoviral proteins with pRB and p53. FASEB. 7: 880-885, 1993.
Mulligan, R. C. The basic science of gene therapy. Science 260: 926-936, 1993.
Nobori, T., Miura, K., Wu, D. J., Lois, A., Takabayashi, K., and Carson, D.A. Deletions of the cyclin-dependent kinase-4 inhibitor gene in mutiple human cancers. Nature 368: 753-756, 1994.
Nseyo, U. O., and Lamm, D. Therapy of superficial bladder cancer. Semin. Oncol. 23: 598-604, 1996.
Oates, K. K. and Goldstein, A. L. Thymosin. In Biologic therapy of cancer. Lippincott: Philadelphia, USA, 1995
Palvimo, J., and Linnala-Kankkunen, A. Idification of a low-Mr acidic nuclear protein as prothymosin alpha. FE

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