跳到主要內容

臺灣博碩士論文加值系統

(34.226.244.254) 您好!臺灣時間:2021/08/02 23:46
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:何明怡
研究生(外文):Ming-Yi Ho
論文名稱:FasL及GM-CSF結合之免疫療法應用於肺癌治療之研究
論文名稱(外文):Combination of Fas ligand and GM-CSF in immunotherapy of lung cancer
指導教授:孫光蕙
指導教授(外文):Kuang-Hui Sun
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:醫學生物技術研究所
學門:醫藥衛生學門
學類:醫學技術及檢驗學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:99
中文關鍵詞:肺癌免疫療法
外文關鍵詞:Fas ligandGM-CSFlung cancerimmunotherapy
相關次數:
  • 被引用被引用:0
  • 點閱點閱:143
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
肺癌為國內十大癌症死亡原因,目前各種治療方式未能完全治癒所有肺癌之病患;而最新發展使用基因療法誘導人體體內產生專一性免疫反應以殺死癌細胞。在之前文獻研究發現FasL或GM-CSF能誘導體內產生專一性抗腫瘤排斥反應,延緩體內腫瘤細胞生長,但未能完全消除腫瘤。因此本次論文研究FasL及GM-CSF結合之免疫療法應用於肺癌治療之可行性,將來可能應用於肺癌之臨床治療。
首先以tetracycline-regulated RevTet-off system使非小細胞肺癌Lewis lung carcinoma -1 (LLC-1)在有無Doxcycline下調控FasL表現;另以pZeoSV表現GM-CSF;構築出單純表現FasL或GM-CSF及同時表現FasL及GM-CSF之LLC-1腫瘤細胞株。以反轉錄-聚合酵素連鎖反應(RT-PCR)、西方墨點法(WB)及GM-CSF dependent cell line (M-NFS-60)對於各種構築的腫瘤細胞株其FasL及GM-CSF表現量進行分析,篩選FasL及GM-CSF表現量較高之腫瘤細胞株,進行小鼠體內測試(in vivo)。將各種構築的腫瘤細胞株以皮下注射入C57BL/6小鼠體內,觀察腫瘤生長特性;發現表現GM-CSF之腫瘤細胞株,有些微抑制腫瘤生長;表現FasL和同時表現FasL、GM-CSF兩者之腫瘤細胞株,腫瘤生長完全受到抑制;且研究得知同時表現FasL、GM-CSF兩者之腫瘤細胞株誘導小鼠體內毒殺性T淋巴細胞活性(CTL activity)比單純表現FasL或GM-CSF之腫瘤細胞株高。另外為證明FasL之角色,先讓小鼠喝Doxcycline三天以抑制FasL表現,之後再打入表現FasL和同時表現FasL、GM-CSF兩者之腫瘤細胞株;發現表現FasL之腫瘤細胞株,腫瘤生長無法受到抑制;同時表現FasL、GM-CSF兩者之腫瘤細胞株,有些微抑制腫瘤生長。將各種構築的腫瘤細胞株當腫瘤疫苗先打入小鼠體內,再打入原生型LLC-1腫瘤細胞觀察其生長;發現表現FasL及同時表現FasL、GM-CSF兩者之腫瘤疫苗的確可誘導小鼠體內產生記憶性免疫反應,延緩之後打入原生型LLC-1腫瘤細胞生長。此外,將各種腫瘤疫苗與原生型LLC-1腫瘤細胞混合打入小鼠體內,發現表現FasL或GM-CSF之腫瘤疫苗除了抑制本生腫瘤生長,也可部分抑制混合之原生型LLC-1腫瘤細胞生長;同時表現FasL、GM-CSF兩者之腫瘤疫苗則具加成效果,可完全抑制混合之原生型LLC-1腫瘤細胞生長。若先種入原生型LLC-1腫瘤細胞於小鼠右腹側,三天或七天後於小鼠左腹側種入各種腫瘤疫苗,發現同時表現FasL、GM-CSF兩者之腫瘤疫苗可抑制已打入遠處之原生型LLC-1腫瘤細胞;而表現FasL之腫瘤疫苗卻無法抑制原生型LLC-1腫瘤細胞生長。
由以上結果推論,共同表現FasL、GM-CSF和只表現FasL之腫瘤細胞株誘發保護性免疫反應比只表現GM-CSF之腫瘤細胞株效果較好。此外,同時表現FasL及GM-CSF之腫瘤細胞株當成腫瘤疫苗的確能有效抑制小鼠已存在之肺癌腫瘤生長,且具有加成效果。因此,FasL結合GM-CSF之免疫療法可應用於小鼠肺癌模式上,在未來肺癌臨床治療上可能具有相當大的潛力。
Lung cancer has the highest mortality among the neoplastic diseases in Taiwan. Since conventional therapeutic methods may not completely cure this disease, gene therapy, a novel therapeutic strategy, is developed to induce specific immune responses to eliminate the tumor cells. It has been reported that Fas ligand (FasL) or granulocyte-macrophage colony stimulating factor (GM-CSF) may induce tumor rejection responses and delay tumor growth. This study was designed to investigate whether the combination of FasL and GM-CSF may efficiently suppress cell growth in lung tumor.
FasL was cloned using the tetracycline-regulated RevTet-off system and the expression of FasL was mediated with and without doxcycline. The GM-CSF gene expression was mediated using the pZeoSV vector. The Lewis lung carcinoma-1 cell line (LLC-1 cells) isolated from non-small- cell lung carcinoma was then transfected with FasL and/or GM-CSF. The expressions of FasL and GM-CSF were then evaluated in vitro by RT-PCR, Western blotting, and bioassay using the GM-CSF dependent cell line M-NFS-60.
To examine the tumorgenicity effects in vivo, B57BL/6 mice were subcutaneously injected with tumor cells. Mice administrated with GM-CSF transduced LLC-1 (LLC-1/GM-CSF) showed a delay tumor onset. Moreover, complete suppression of tumor growth was observed in those administrated with FasL transduced LLC-1 cells (LLC-1/FasL/ pZeoSV) and LLC-1 cells with co-expression of FasL and GM-CSF (LLC-1/FasL/mGM-CSF). Spleen cells from mice injected with LLC-1/FasL/mGM-CSF showed significantly higher cytotixic activity against LLC-1 (higher CTL activity) than those with LLC-1/FasL/ pZeoSV or LLC-1/mGM-CSF.
To determine the role of FasL in tumorgenicity, B57BL/6 mice were subcutaneously injected with LLC-1/FasL/pZeoSV and LLC-1/FasL/ mGM-CSF before oral administration of doxcycline for three days. Although the mice injected with parental LLC-1 cells, and LLC-1/FasL/ mGM-CSF showed mild suppression of tumor growth, no tumor growth suppression was observed in the LLC-1/FasL/pZeoSV group with doxcycline treatment.
Tumor cells transfected with FasL and/or GM-CSF were tested in the mice as tumor vaccines. After injection of LLC-1 cells, memory immune response and delayed tumor growth were generated in the group treated with LLC-1/FasL/pZeoSV or LLC-1/FasL/mGM-CSF. After administrating a mixture of LLC-1 cells and different preparations of tumor vaccines to the mice, tumor formation was partially suppressed in mice treated with LLC-1+LLC-1/FasL/pZeoSV and LLC-1+LLC-1/ mGM-CSF. Moreover, tumor formation was completely suppressed in the LLC-1+LLC-1/FasL/ mGM-CSF treated group. Among the mice injected with LLC-1 cells and administrated with the vaccines 3 or 7 days later, delayed tumor growth was observed in those treated with LLC-1/FasL/ mGM-CSF whereas tumor growth was not significantly influenced by the treatment of LLC-1/FasL/pZeoSV.
Based on the in vivo experiments, the tumor vaccines LLC-1/FasL/ mGM-CSF and LLC-1/FasL/pZeoSV may induce immunity against LLC-1 while LLC-1/mGM-CSF has only a minor effect. These results indicate that co-transducing FasL and GM-CSF into a tumor vaccine (LLC-1/FasL/mGM-CSF) may produced a more effective synergistic anti-tumor immunity and efficiently suppress lung cancer cells in mice. This strategy may be a feasible and effective alternative for clinical cancer gene therapy.
Allison,J., Georgiou,H.M., Strasser,A., and Vaux,D.L. (1997). Transgenic expression of CD95 ligand on islet beta cells induces a granulocytic infiltration but does not confer immune privilege upon islet allografts. Proc. Natl. Acad. Sci. U. S. A 94, 3943-3947.
Arai,H., Gordon,D., Nabel,E.G., and Nabel,G.J. (1997). Gene transfer of Fas ligand induces tumor regression in vivo. Proc. Natl. Acad. Sci. U. S. A 94, 13862-13867.
Arnold,B., Schonrich,G., and Hammerling,G.J. (1993). Multiple levels of peripheral tolerance. Immunol. Today 14, 12-14.
Bellgrau,D., Gold,D., Selawry,H., Moore,J., Franzusoff,A., and Duke,R.C. (1995). A role for CD95 ligand in preventing graft rejection. Nature 377, 630-632.
Bennett,M.W., O'Connell,J., O'Sullivan,G.C., Brady,C., Roche,D., Collins,J.K., and Shanahan,F. (1998). The Fas counterattack in vivo: apoptotic depletion of tumor-infiltrating lymphocytes associated with Fas ligand expression by human esophageal carcinoma. J. Immunol. 160, 5669-5675.
Bianco,S.R., Sun,J., Fosmire,S.P., Hance,K., Padilla,M.L., Ritt,M.G., Getzy,D.M., Duke,R.C., Withrow,S.J., Lana,S., Matthiesen,D.T., Dow,S.W., Bellgrau,D., Cutter,G.R., Helfand,S.C., and Modiano,J.F. (2003). Enhancing antimelanoma immune responses through apoptosis. Cancer Gene Ther. 10, 726-736.
Block,A., Freund,C.T., Chen,S.H., Nguyen,K.P., Finegold,M., Windler,E., and Woo,S.L. (2000). Gene therapy of metastatic colon carcinoma: regression of multiple hepatic metastases by adenoviral expression of bacterial cytosine deaminase. Cancer Gene Ther. 7, 438-445.
Boffetta,P. and Nyberg,F. (2003). Contribution of environmental factors to cancer risk. Br. Med. Bull. 68, 71-94.
Borrello,I. and Pardoll,D. (2002). GM-CSF-based cellular vaccines: a review of the clinical experience. Cytokine Growth Factor Rev. 13, 185-193.
Browning,J.L., Ngam-ek,A., Lawton,P., DeMarinis,J., Tizard,R., Chow,E.P., Hession,C., O'Brine-Greco,B., Foley,S.F., and Ware,C.F. (1993). Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. Cell 72, 847-856.
Brusselmans,K., Bono,F., Maxwell,P., Dor,Y., Dewerchin,M., Collen,D., Herbert,J.M., and Carmeliet,P. (2001). Hypoxia-inducible factor-2alpha (HIF-2alpha) is involved in the apoptotic response to hypoglycemia but not to hypoxia. J. Biol. Chem. 276, 39192-39196.
Cersosimo,R.J. (2002). Lung cancer: a review. Am. J. Health Syst. Pharm. 59, 611-642.
Chen,J.J., Sun,Y., and Nabel,G.J. (1998). Regulation of the proinflammatory effects of Fas ligand (CD95L). Science 282, 1714-1717.
Chiu,C.C., Kang,Y.L., Yang,T.H., Huang,C.H., and Fang,K. (2002). Ectopic expression of herpes simplex virus-thymidine kinase gene in human non-small cell lung cancer cells conferred caspase-activated apoptosis sensitized by ganciclovir. Int. J. Cancer 102, 328-333.
Colombo,M.P., Lombardi,L., Stoppacciaro,A., Melani,C., Parenza,M., Bottazzi,B., and Parmiani,G. (1992). Granulocyte colony-stimulating factor (G-CSF) gene transduction in murine adenocarcinoma drives neutrophil-mediated tumor inhibition in vivo. Neutrophils discriminate between G-CSF-producing and G-CSF-nonproducing tumor cells. J. Immunol. 149, 113-119.
Darland,D.C. and D'Amore,P.A. (1999). Blood vessel maturation: vascular development comes of age. J. Clin. Invest 103, 157-158.
Dranoff,G. (2004). Cytokines in cancer pathogenesis and cancer therapy. Nat. Rev. Cancer 4, 11-22.
Dranoff,G., Jaffee,E., Lazenby,A., Golumbek,P., Levitsky,H., Brose,K., Jackson,V., Hamada,H., Pardoll,D., and Mulligan,R.C. (1993). Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc. Natl. Acad. Sci. U. S. A 90, 3539-3543.
el Deiry,W.S., Tokino,T., Velculescu,V.E., Levy,D.B., Parsons,R., Trent,J.M., Lin,D., Mercer,W.E., Kinzler,K.W., and Vogelstein,B. (1993). WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817-825.
Ellis,R.E., Yuan,J.Y., and Horvitz,H.R. (1991). Mechanisms and functions of cell death. Annu. Rev. Cell Biol. 7, 663-698.
Falk,M.H., Trauth,B.C., Debatin,K.M., Klas,C., Gregory,C.D., Rickinson,A.B., Calender,A., Lenoir,G.M., Ellwart,J.W., Krammer,P.H., and . (1992). Expression of the APO-1 antigen in Burkitt lymphoma cell lines correlates with a shift towards a lymphoblastoid phenotype. Blood 79, 3300-3306.
Fogler,W.E., Volker,K., Watanabe,M., Wigginton,J.M., Roessler,P., Brunda,M.J., Ortaldo,J.R., and Wiltrout,R.H. (1998). Recruitment of hepatic NK cells by IL-12 is dependent on IFN-gamma and VCAM-1 and is rapidly down-regulated by a mechanism involving T cells and expression of Fas. J. Immunol. 161, 6014-6021.
Folkman,J. (1971). Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285, 1182-1186.
Gainer,A.L., Suarez-Pinzon,W.L., Min,W.P., Swiston,J.R., Hancock-Friesen,C., Korbutt,G.S., Rajotte,R.V., Warnock,G.L., and Elliott,J.F. (1998). Improved survival of biolistically transfected mouse islet allografts expressing CTLA4-Ig or soluble Fas ligand. Transplantation 66, 194-199.
Gearing,M., Rebeck,G.W., Hyman,B.T., Tigges,J., and Mirra,S.S. (1994). Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A 91, 9382-9386.
Genestier,L., Kasibhatla,S., Brunner,T., and Green,D.R. (1999). Transforming growth factor beta1 inhibits Fas ligand expression and subsequent activation-induced cell death in T cells via downregulation of c-Myc. J. Exp. Med. 189, 231-239.
Green,D.R. and Ware,C.F. (1997). Fas-ligand: privilege and peril. Proc. Natl. Acad. Sci. U. S. A 94, 5986-5990.
Griffith,T.S., Brunner,T., Fletcher,S.M., Green,D.R., and Ferguson,T.A. (1995). Fas ligand-induced apoptosis as a mechanism of immune privilege. Science 270, 1189-1192.
Gu,J., Zhang,L., Swisher,S.G., Liu,J., Roth,J.A., and Fang,B. (2004). Induction of p53-regulated genes in lung cancer cells: implications of the mechanism for adenoviral p53-mediated apoptosis. Oncogene 23, 1300-1307.
Hanze,J., Eul,B.G., Savai,R., Krick,S., Goyal,P., Grimminger,F., Seeger,W., and Rose,F. (2003). RNA interference for HIF-1alpha inhibits its downstream signalling and affects cellular proliferation. Biochem. Biophys. Res. Commun. 312, 571-577.
Hashimoto,W., Osaki,T., Okamura,H., Robbins,P.D., Kurimoto,M., Nagata,S., Lotze,M.T., and Tahara,H. (1999). Differential antitumor effects of administration of recombinant IL-18 or recombinant IL-12 are mediated primarily by Fas-Fas ligand- and perforin-induced tumor apoptosis, respectively. J. Immunol. 163, 583-589.
Henderson,W.R., Jr. (1994). The role of leukotrienes in inflammation. Ann. Intern. Med. 121, 684-697.
Hirschi,K.K. and D'Amore,P.A. (1996). Pericytes in the microvasculature. Cardiovasc. Res. 32, 687-698.
Hohlbaum,A.M., Gregory,M.S., Ju,S.T., and Marshak-Rothstein,A. (2001). Fas ligand engagement of resident peritoneal macrophages in vivo induces apoptosis and the production of neutrophil chemotactic factors. J. Immunol. 167, 6217-6224.
Holmdahl,R., Andersson,M., Goldschmidt,T.J., Gustafsson,K., Jansson,L., and Mo,J.A. (1990). Type II collagen autoimmunity in animals and provocations leading to arthritis. Immunol. Rev. 118, 193-232.
Hsu,P.N., Lin,H.H., Tu,C.F., Chen,N.J., Wu,K.M., Tsai,H.F., and Hsieh,S.L. (2001). Expression of human Fas ligand on mouse beta islet cells does not induce insulitis but is insufficient to confer immune privilege for islet grafts. J. Biomed. Sci. 8, 262-269.
Inaba,K., Inaba,M., Romani,N., Aya,H., Deguchi,M., Ikehara,S., Muramatsu,S., and Steinman,R.M. (1992). Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J. Exp. Med. 176, 1693-1702.
Itoh,N., Yonehara,S., Ishii,A., Yonehara,M., Mizushima,S., Sameshima,M., Hase,A., Seto,Y., and Nagata,S. (1991). The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66, 233-243.
Jones,T., Stern,A., and Lin,R. (1994). Potential role of granulocyte-macrophage colony-stimulating factor as vaccine adjuvant. Eur. J. Clin. Microbiol. Infect. Dis. 13 Suppl 2, S47-S53.
Ju,S.T., Panka,D.J., Cui,H., Ettinger,R., el Khatib,M., Sherr,D.H., Stanger,B.Z., and Marshak-Rothstein,A. (1995). Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature 373, 444-448.
Kalechman,Y., Strassmann,G., Albeck,M., and Sredni,B. (1998). Up-regulation by ammonium trichloro(dioxoethylene-0,0') tellurate (AS101) of Fas/Apo-1 expression on B16 melanoma cells: implications for the antitumor effects of AS101. J. Immunol. 161, 3536-3542.
Kang,S.M., Hoffmann,A., Le,D., Springer,M.L., Stock,P.G., and Blau,H.M. (1997). Immune response and myoblasts that express Fas ligand. Science 278, 1322-1324.
Kaplan,G., Walsh,G., Guido,L.S., Meyn,P., Burkhardt,R.A., Abalos,R.M., Barker,J., Frindt,P.A., Fajardo,T.T., Celona,R., and . (1992). Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing. J. Exp. Med. 175, 1717-1728.
Kappler,J.W., Roehm,N., and Marrack,P. (1987). T cell tolerance by clonal elimination in the thymus. Cell 49, 273-280.
Kase,S., Osaki,M., Adachi,H., Kaibara,N., and Ito,H. (2002). Expression of Fas and Fas ligand in esophageal tissue mucosa and carcinomas. Int. J. Oncol. 20, 291-297.
Kawano,T., Cui,J., Koezuka,Y., Toura,I., Kaneko,Y., Motoki,K., Ueno,H., Nakagawa,R., Sato,H., Kondo,E., Koseki,H., and Taniguchi,M. (1997). CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. Science 278, 1626-1629.
Kayagaki,N., Kawasaki,A., Ebata,T., Ohmoto,H., Ikeda,S., Inoue,S., Yoshino,K., Okumura,K., and Yagita,H. (1995). Metalloproteinase-mediated release of human Fas ligand. J. Exp. Med. 182, 1777-1783.
Kim,R., Emi,M., Tanabe,K., Uchida,Y., and Toge,T. (2004). The role of Fas ligand and transforming growth factor beta in tumor progression: molecular mechanisms of immune privilege via Fas-mediated apoptosis and potential targets for cancer therapy. Cancer 100, 2281-2291.
Kobayashi,N., Hamamoto,Y., Yamamoto,N., Ishii,A., Yonehara,M., and Yonehara,S. (1990). Anti-Fas monoclonal antibody is cytocidal to human immunodeficiency virus-infected cells without augmenting viral replication. Proc. Natl. Acad. Sci. U. S. A 87, 9620-9624.
Kojima,T., Yamazaki,K., Tamura,Y., Ogura,S., Tani,K., Konishi,J., Shinagawa,N., Kinoshita,I., Hizawa,N., Yamaguchi,E., Dosaka-Akita,H., and Nishimura,M. (2003). Granulocyte-macrophage colony-stimulating factor gene-transduced tumor cells combined with tumor-derived gp96 inhibit tumor growth in mice. Hum. Gene Ther. 14, 715-728.
Korbutt,G.S., Elliott,J.F., and Rajotte,R.V. (1997). Cotransplantation of allogeneic islets with allogeneic testicular cell aggregates allows long-term graft survival without systemic immunosuppression. Diabetes 46, 317-322.
Kosiewicz,M.M., Alard,P., Liang,S., and Clark,S.L. (2004). Mechanisms of tolerance induced by transforming growth factor-beta-treated antigen-presenting cells: CD8 regulatory T cells inhibit the effector phase of the immune response in primed mice through a mechanism involving Fas ligand. Int. Immunol. 16, 697-706.
Larsen,C.P., Alexander,D.Z., Hendrix,R., Ritchie,S.C., and Pearson,T.C. (1995). Fas-mediated cytotoxicity. An immunoeffector or immunoregulatory pathway in T cell-mediated immune responses? Transplantation 60, 221-224.
Lee,S.H., Bar-Haim,E., Goldberger,O., Reich-Zeliger,S., Vadai,E., Tzehoval,E., and Eisenbach,L. (2004). Expression of FasL by tumor cells does not abrogate anti-tumor CTL function. Immunol. Lett. 91, 119-126.
Li,M., Ye,C., Feng,C., Riedel,F., Liu,X., Zeng,Q., and Grandis,J.R. (2002). Enhanced antiangiogenic therapy of squamous cell carcinoma by combined endostatin and epidermal growth factor receptor-antisense therapy. Clin. Cancer Res. 8, 3570-3578.
Li,X.K., Okuyama,T., Tamura,A., Enosawa,S., Kaneda,Y., Takahara,S., Funashima,N., Yamada,M., Amemiya,H., and Suzuki,S. (1998). Prolonged survival of rat liver allografts transfected with Fas ligand-expressing plasmid. Transplantation 66, 1416-1423.
Lim,S.C. (2002). Expression of Fas ligand and sFas ligand in human gastric adenocarcinomas. Oncol. Rep. 9, 103-107.
Liu,Y., Cox,S.R., Morita,T., and Kourembanas,S. (1995). Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5' enhancer. Circ. Res. 77, 638-643.
Mach,N. and Dranoff,G. (2000). Cytokine-secreting tumor cell vaccines. Curr. Opin. Immunol. 12, 571-575.
Mach,N., Gillessen,S., Wilson,S.B., Sheehan,C., Mihm,M., and Dranoff,G. (2000). Differences in dendritic cells stimulated in vivo by tumors engineered to secrete granulocyte-macrophage colony-stimulating factor or Flt3-ligand. Cancer Res. 60, 3239-3246.
Markowicz,S. and Engleman,E.G. (1990). Granulocyte-macrophage colony-stimulating factor promotes differentiation and survival of human peripheral blood dendritic cells in vitro. J. Clin. Invest 85, 955-961.
Micheau,O., Solary,E., Hammann,A., Martin,F., and Dimanche-Boitrel,M.T. (1997). Sensitization of cancer cells treated with cytotoxic drugs to fas-mediated cytotoxicity. J. Natl. Cancer Inst. 89, 783-789.
Midorikawa,Y., Yamashita,T., and Sendo,F. (1990). Modulation of the immune response to transplanted tumors in rats by selective depletion of neutrophils in vivo using a monoclonal antibody: abrogation of specific transplantation resistance to chemical carcinogen-induced syngeneic tumors by selective depletion of neutrophils in vivo. Cancer Res. 50, 6243-6247.
Miller,P.W., Sharma,S., Stolina,M., Butterfield,L.H., Luo,J., Lin,Y., Dohadwala,M., Batra,R.K., Wu,L., Economou,J.S., and Dubinett,S.M. (2000). Intratumoral administration of adenoviral interleukin 7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication. Hum. Gene Ther. 11, 53-65.
Minna,J.D., Roth,J.A., and Gazdar,A.F. (2002). Focus on lung cancer. Cancer Cell 1, 49-52.
Miyashita,T. and Reed,J.C. (1995). Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80, 293-299.
Modiano,J.F., Sun,J., Lang,J., Vacano,G., Patterson,D., Chan,D., Franzusoff,A., Gianani,R., Meech,S.J., Duke,R., and Bellgrau,D. (2004). Fas ligand-dependent suppression of autoimmunity via recruitment and subsequent termination of activated T cells. Clin. Immunol. 112, 54-65.
Moon,C., Oh,Y., and Roth,J.A. (2003). Current status of gene therapy for lung cancer and head and neck cancer. Clin. Cancer Res. 9, 5055-5067.
Murtaza,A., Kuchroo,V.K., and Freeman,G.J. (1999). Changes in the strength of co-stimulation through the B7/CD28 pathway alter functional T cell responses to altered peptide ligands. Int. Immunol. 11, 407-416.
Muschen,M., Moers,C., Warskulat,U., Even,J., Niederacher,D., and Beckmann,M.W. (2000). CD95 ligand expression as a mechanism of immune escape in breast cancer. Immunology 99, 69-77.
Nagata,S. (1999). Fas ligand-induced apoptosis. Annu. Rev. Genet. 33, 29-55.
Nagata,S. and Golstein,P. (1995). The Fas death factor. Science 267, 1449-1456.
Nishizaki,M., Fujiwara,T., Tanida,T., Hizuta,A., Nishimori,H., Tokino,T., Nakamura,Y., Bouvet,M., Roth,J.A., and Tanaka,N. (1999). Recombinant adenovirus expressing wild-type p53 is antiangiogenic: a proposed mechanism for bystander effect. Clin. Cancer Res. 5, 1015-1023.
Nozoe,T., Yasuda,M., Honda,M., Inutsuka,S., and Korenaga,D. (2003). Fas ligand expression is correlated with metastasis in colorectal carcinoma. Oncology 65, 83-88.
O'Connell,J., Houston,A., Bennett,M.W., O'Sullivan,G.C., and Shanahan,F. (2001). Immune privilege or inflammation? Insights into the Fas ligand enigma. Nat. Med. 7, 271-274.
Oehm,A., Behrmann,I., Falk,W., Pawlita,M., Maier,G., Klas,C., Li-Weber,M., Richards,S., Dhein,J., Trauth,B.C., and . (1992). Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J. Biol. Chem. 267, 10709-10715.
Ottonello,L., Tortolina,G., Amelotti,M., and Dallegri,F. (1999). Soluble Fas ligand is chemotactic for human neutrophilic polymorphonuclear leukocytes. J. Immunol. 162, 3601-3606.
Oyaizu,N., McCloskey,T.W., Than,S., Hu,R., Kalyanaraman,V.S., and Pahwa,S. (1994). Cross-linking of CD4 molecules upregulates Fas antigen expression in lymphocytes by inducing interferon-gamma and tumor necrosis factor-alpha secretion. Blood 84, 2622-2631.
Pairon,J.C., Matrat,M., and Brochard,P. (2002). [News in occupational cancers]. Bull. Cancer 89, 283-292.
Park,K.H., Kim,G., Jang,S.H., Kim,C.H., Kwon,S.Y., Yoo,C.G., Kim,Y.W., Kwon,H.C., Kim,C.M., Han,S.K., Shim,Y.S., and Lee,C.T. (2003a). Gene therapy with GM-CSF, interleukin-4 and herpes simplex virus thymidine kinase shows strong antitumor effect on lung cancer. Anticancer Res. 23, 1559-1564.
Pericle,F., Kirken,R.A., Epling-Burnette,P.K., Blanchard,D.K., and Djeu,J.Y. (1996). Direct killing of interleukin-2-transfected tumor cells by human neutrophils. Int. J. Cancer 66, 367-373.
Pettipher,E.R., Salter,E.D., Breslow,R., Raycroft,L., and Showell,H.J. (1993). Specific inhibition of leukotriene B4 (LTB4)-induced neutrophil emigration by 20-hydroxy LTB4: implications for the regulation of inflammatory responses. Br. J. Pharmacol. 110, 423-427.
Qin,L.X. and Tang,Z.Y. (2002). The prognostic molecular markers in hepatocellular carcinoma. World J. Gastroenterol. 8, 385-392.
Redondo,P., Solano,T., VAzquez,B., Bauza,A., and Idoate,M. (2002). Fas and Fas ligand: expression and soluble circulating levels in cutaneous malignant melanoma. Br. J. Dermatol. 147, 80-86.
Reichert,T.E., Strauss,L., Wagner,E.M., Gooding,W., and Whiteside,T.L. (2002). Signaling abnormalities, apoptosis, and reduced proliferation of circulating and tumor-infiltrating lymphocytes in patients with oral carcinoma. Clin. Cancer Res. 8, 3137-3145.
Rensing-Ehl,A., Frei,K., Flury,R., Matiba,B., Mariani,S.M., Weller,M., Aebischer,P., Krammer,P.H., and Fontana,A. (1995). Local Fas/APO-1 (CD95) ligand-mediated tumor cell killing in vivo. Eur. J. Immunol. 25, 2253-2258.
Rescigno,M., Piguet,V., Valzasina,B., Lens,S., Zubler,R., French,L., Kindler,V., Tschopp,J., and Ricciardi-Castagnoli,P. (2000). Fas engagement induces the maturation of dendritic cells (DCs), the release of interleukin (IL)-1beta, and the production of interferon gamma in the absence of IL-12 during DC-T cell cognate interaction: a new role for Fas ligand in inflammatory responses. J. Exp. Med. 192, 1661-1668.
Rose,F., Grimminger,F., Appel,J., Heller,M., Pies,V., Weissmann,N., Fink,L., Schmidt,S., Krick,S., Camenisch,G., Gassmann,M., Seeger,W., and Hanze,J. (2002). Hypoxic pulmonary artery fibroblasts trigger proliferation of vascular smooth muscle cells: role of hypoxia-inducible transcription factors. FASEB J. 16, 1660-1661.
Salgia,R., Lynch,T., Skarin,A., Lucca,J., Lynch,C., Jung,K., Hodi,F.S., Jaklitsch,M., Mentzer,S., Swanson,S., Lukanich,J., Bueno,R., Wain,J., Mathisen,D., Wright,C., Fidias,P., Donahue,D., Clift,S., Hardy,S., Neuberg,D., Mulligan,R., Webb,I., Sugarbaker,D., Mihm,M., and Dranoff,G. (2003). Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma. J. Clin. Oncol. 21, 624-630.
Sandler,A. (2003). State-of-the-art treatment for advanced non-small-cell lung cancer. Oncology (Huntingt) 17, 15-22.
Sauter,B.V., Martinet,O., Zhang,W.J., Mandeli,J., and Woo,S.L. (2000). Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases. Proc. Natl. Acad. Sci. U. S. A 97, 4802-4807.
Scappaticci,F.A., Smith,R., Pathak,A., Schloss,D., Lum,B., Cao,Y., Johnson,F., Engleman,E.G., and Nolan,G.P. (2001). Combination angiostatin and endostatin gene transfer induces synergistic antiangiogenic activity in vitro and antitumor efficacy in leukemia and solid tumors in mice. Mol. Ther. 3, 186-196.
Seino,K., Iwabuchi,K., Kayagaki,N., Miyata,R., Nagaoka,I., Matsuzawa,A., Fukao,K., Yagita,H., and Okumura,K. (1998). Chemotactic activity of soluble Fas ligand against phagocytes. J. Immunol. 161, 4484-4488.
Seino,K., Kayagaki,N., Okumura,K., and Yagita,H. (1997). Antitumor effect of locally produced CD95 ligand. Nat. Med. 3, 165-170.
Semenza,G.L., Roth,P.H., Fang,H.M., and Wang,G.L. (1994). Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J. Biol. Chem. 269, 23757-23763.
Sharma,O.P. and Lamb,C. (2003). Cancer in interstitial pulmonary fibrosis and sarcoidosis. Curr. Opin. Pulm. Med. 9, 398-401.
Sheard,M.A., Vojtesek,B., Janakova,L., Kovarik,J., and Zaloudik,J. (1997). Up-regulation of Fas (CD95) in human p53wild-type cancer cells treated with ionizing radiation. Int. J. Cancer 73, 757-762.
Shimizu,M., Fontana,A., Takeda,Y., Yagita,H., Yoshimoto,T., and Matsuzawa,A. (1999). Induction of antitumor immunity with Fas/APO-1 ligand (CD95L)-transfected neuroblastoma neuro-2a cells. J. Immunol. 162, 7350-7357.
Shudo,K., Kinoshita,K., Imamura,R., Fan,H., Hasumoto,K., Tanaka,M., Nagata,S., and Suda,T. (2001a). The membrane-bound but not the soluble form of human Fas ligand is responsible for its inflammatory activity. Eur. J. Immunol. 31, 2504-2511.
Smith,R.A. and Baglioni,C. (1987). The active form of tumor necrosis factor is a trimer. J. Biol. Chem. 262, 6951-6954.
Smyth,M.J., Crowe,N.Y., Hayakawa,Y., Takeda,K., Yagita,H., and Godfrey,D.I. (2002). NKT cells - conductors of tumor immunity? Curr. Opin. Immunol. 14, 165-171.
Sobue,T. (2001). [Lung cancer]. Gan To Kagaku Ryoho 28, 163-167.
Soiffer,R., Lynch,T., Mihm,M., Jung,K., Rhuda,C., Schmollinger,J.C., Hodi,F.S., Liebster,L., Lam,P., Mentzer,S., Singer,S., Tanabe,K.K., Cosimi,A.B., Duda,R., Sober,A., Bhan,A., Daley,J., Neuberg,D., Parry,G., Rokovich,J., Richards,L., Drayer,J., Berns,A., Clift,S., Dranoff,G., and . (1998b). Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc. Natl. Acad. Sci. U. S. A 95, 13141-13146.
Springer,M.L., Kraft,P.E., and Blau,H.M. (1998). Inhibition of solid tumor growth by Fas ligand-expressing myoblasts. Somat. Cell Mol. Genet. 24, 281-289.
Strand,S., Hofmann,W.J., Hug,H., Muller,M., Otto,G., Strand,D., Mariani,S.M., Stremmel,W., Krammer,P.H., and Galle,P.R. (1996). Lymphocyte apoptosis induced by CD95 (APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion? Nat. Med. 2, 1361-1366.
Suda,T., Takahashi,T., Golstein,P., and Nagata,S. (1993). Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell 75, 1169-1178.
Sumimoto,H., Tani,K., Nakazaki,Y., Tanabe,T., Hibino,H., Hamada,H., Azuma,M., and Asano,S. (1997). GM-CSF and B7-1 (CD80) co-stimulatory signals co-operate in the induction of effective anti-tumor immunity in syngeneic mice. Int. J. Cancer 73, 556-561.
Sumimoto,H., Tani,K., Nakazaki,Y., Tanabe,T., Hibino,H., Wu,M.S., Izawa,K., Hamada,H., and Asano,S. (1998). Superiority of interleukin-12-transduced murine lung cancer cells to GM-CSF or B7-1 (CD80) transfectants for therapeutic antitumor immunity in syngeneic immunocompetent mice. Cancer Gene Ther. 5, 29-37.
Swenson,K.M., Ke,B., Wang,T., Markowitz,J.S., Maggard,M.A., Spear,G.S., Imagawa,D.K., Goss,J.A., Busuttil,R.W., and Seu,P. (1998). Fas ligand gene transfer to renal allografts in rats: effects on allograft survival. Transplantation 65, 155-160.
Szabolcs,P., Moore,M.A., and Young,J.W. (1995). Expansion of immunostimulatory dendritic cells among the myeloid progeny of human CD34+ bone marrow precursors cultured with c-kit ligand, granulocyte-macrophage colony-stimulating factor, and TNF-alpha. J. Immunol. 154, 5851-5861.
Tada,Y., Wang,J., Seimiya,M., Takiguchi,Y., Tatsumi,K., Kuriyama,T., and Tagawa,M. (2002a). Antitumor effects are produced by forced expression of membrane-bound but not soluble Fas ligand in murine lung carcinoma cells. Anticancer Res. 22, 831-836.
Tada,Y., Wang,J., Takiguchi,Y., Tatsumi,K., Kuriyama,T., Okada,S., Tokuhisa,T., Sakiyama,S., and Tagawa,M. (2002b). Cutting edge: a novel role for Fas ligand in facilitating antigen acquisition by dendritic cells. J. Immunol. 169, 2241-2245.
Tada,Y., Wang,J., Wada,A., Takiguchi,Y., Tatsumi,K., Kuriyama,T., Sakiyama,S., and Tagawa,M. (2003a). Fas ligand-expressing tumors induce tumor-specific protective immunity in the inoculated hosts but vaccination with the apoptotic tumors suppresses antitumor immunity. Cancer Gene Ther. 10, 134-140.
Tada,Y., Wang,J., Yu,L., Shimozato,O., Wang,Y.Q., Takiguchi,Y., Tatsumi,K., Kuriyama,T., Takenaga,K., Sakiyama,S., and Tagawa,M. (2003b). T-cell-dependent antitumor effects produced by CD40 ligand expressed on mouse lung carcinoma cells are linked with the maturation of dendritic cells and secretion of a variety of cytokines. Cancer Gene Ther. 10, 451-456.
Tahara,H., Zeh,H.J., III, Storkus,W.J., Pappo,I., Watkins,S.C., Gubler,U., Wolf,S.F., Robbins,P.D., and Lotze,M.T. (1994). Fibroblasts genetically engineered to secrete interleukin 12 can suppress tumor growth and induce antitumor immunity to a murine melanoma in vivo. Cancer Res. 54, 182-189.
Takayama,K., Ueno,H., Nakanishi,Y., Sakamoto,T., Inoue,K., Shimizu,K., Oohashi,H., and Hara,N. (2000). Suppression of tumor angiogenesis and growth by gene transfer of a soluble form of vascular endothelial growth factor receptor into a remote organ. Cancer Res. 60, 2169-2177.
Tanaka,M., Suda,T., Haze,K., Nakamura,N., Sato,K., Kimura,F., Motoyoshi,K., Mizuki,M., Tagawa,S., Ohga,S., Hatake,K., Drummond,A.H., and Nagata,S. (1996). Fas ligand in human serum. Nat. Med. 2, 317-322.
Tanaka,M., Suda,T., Takahashi,T., and Nagata,S. (1995). Expression of the functional soluble form of human fas ligand in activated lymphocytes. EMBO J. 14, 1129-1135.
Thome,M. and Tschopp,J. (2001). Regulation of lymphocyte proliferation and death by FLIP. Nat. Rev. Immunol. 1, 50-58.
Umemura,M., Kawabe,T., Shudo,K., Kidoya,H., Fukui,M., Asano,M., Iwakura,Y., Matsuzaki,G., Imamura,R., and Suda,T. (2004). Involvement of IL-17 in Fas ligand-induced inflammation. Int. Immunol. 16, 1099-1108.
Uzzo,R.G., Rayman,P., Kolenko,V., Clark,P.E., Bloom,T., Ward,A.M., Molto,L., Tannenbaum,C., Worford,L.J., Bukowski,R., Tubbs,R., Hsi,E.D., Bander,N.H., Novick,A.C., and Finke,J.H. (1999). Mechanisms of apoptosis in T cells from patients with renal cell carcinoma. Clin. Cancer Res. 5, 1219-1229.
Verbeke,C.S., Wenthe,U., Grobholz,R., and Zentgraf,H. (2001). Fas ligand expression in Hodgkin lymphoma. Am. J. Surg. Pathol. 25, 388-394.
Wang,J., Nonomura,N., Ichimaru,N., Azuma,H., Hatori,M., Kokado,Y., Matsumiya,K., Miki,T., Takahara,S., and Okuyama,A. (1997). Expression of Fas and Fas ligand in renal grafts with acute and chronic rejection in the rat model. J. Interferon Cytokine Res. 17, 369-373.
Watanabe-Fukunaga,R., Brannan,C.I., Copeland,N.G., Jenkins,N.A., and Nagata,S. (1992). Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature 356, 314-317.
Wen,C.Y. and Lee,H. (2003). Environmental exposure and lung cancer among nonsmokers: an example of Taiwanese female lung cancer. J. Environ. Sci. Health Part C. Environ. Carcinog. Ecotoxicol. Rev. 21, 1-28.
Wendland,M.M. and Sause,W.T. (2003). Induction chemotherapy followed by radical local therapy for locally advanced non-small cell lung cancer. Semin. Surg. Oncol. 21, 111-121.
Whiteside,T.L. (2002). Tumor-induced death of immune cells: its mechanisms and consequences. Semin. Cancer Biol. 12, 43-50.
Wyllie,M.G. and Gilbert,J.C. (1980). Exocytotic release of noradrenaline from synaptosomes. Biochem. Pharmacol. 29, 1302-1303.
Yamamoto,N., Gupta,A., Xu,M., Miki,K., Tsujimoto,Y., Tsuchiya,H., Tomita,K., Moossa,A.R., and Hoffman,R.M. (2003). Methioninase gene therapy with selenomethionine induces apoptosis in bcl-2-overproducing lung cancer cells. Cancer Gene Ther. 10, 445-450.
Zhang,H. and Cai,B. (2003). The impact of tobacco on lung health in China. Respirology. 8, 17-21.
Zhang,H., Yang,Y., Horton,J.L., Samoilova,E.B., Judge,T.A., Turka,L.A., Wilson,J.M., and Chen,Y. (1997). Amelioration of collagen-induced arthritis by CD95 (Apo-1/Fas)-ligand gene transfer. J. Clin. Invest 100, 1951-1957.
Zusman,I., Gurevich,P., Gurevich,E., and Ben Hur,H. (2001). The immune system, apoptosis and apoptosis-related proteins in human ovarian tumors (a review). Int. J. Oncol. 18, 965-972.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
1. FasL、GM-CSF和IL-27應用於肺癌之免疫療法
2. 單鏈分子對T細胞活化與癌症免疫療法應用之研究
3. 建立黑色素瘤抗原特異性癌症免疫療法及於小鼠黑色素瘤模式中評估抗腫瘤效果
4. 利用免疫療法及抑制腫瘤血管新生療法的治療策略應用於原位肝細胞癌動物模式的基因治療之研究
5. 發展人類乳頭瘤狀病毒DNA疫苗以探討子宮頸癌免疫療法之可行性
6. 第一型干擾素訊息在巨噬細胞聚落刺激因子依賴性樹突細胞發育過程中所扮演角色之研究
7. 肺癌免疫療法研究之高良率細胞電融合晶片
8. 探討細胞激素相關調控對於自體免疫糖尿病致病過程中輔助性T淋巴細胞分化的影響:部分腫瘤壞死因子接受器家族成員及IL-27細胞激素之研究
9. IL-6的分泌與肺癌病人存活時間的相關性與抑制IL-6分泌的方法
10. 惡性肋膜積液中肺腺癌細胞顯示糖代謝調控基因的異常表現且該癌細胞之Stat1磷酸化狀態與腫瘤抗藥性相關
11. 原發性痛經之腦部可塑性:功能性與結構性腦造影研究
12. 穿心蓮內酯誘發蛋白磷酸酯酶2A抑制內毒素/干擾素-γ誘發轉錄因子NFκB的活化之分子機轉探討
13. 牛樟芝菌絲體的高壓液相層析分離層可藉由降低人類非小細胞肺癌A549細胞內的4種腫瘤相關基因表現所誘導的細胞凋亡
14. 探討花生四烯酸在TNF-α誘發NF-κB傳訊下促進乳癌增生之調控機制
15. 米基栽植蛹蟲草子實體抑制肺癌生長之研究