涎腺腺样囊性癌基因治疗的实验研究
摘要
目的:涎腺腺样囊性癌(adenoid cystic carcinoma,ACC),是一种常见的涎腺恶性肿瘤。其恶性程度高,侵袭性强,易复发、易早期转移。且对放疗、化疗不敏感,手术治疗难以根除。因此,寻求有效的辅助性治疗手段非常必要。肿瘤基因治疗已成为最引人瞩目的研究领域,是继手术、放疗、化疗、免疫治疗之后的第5种治疗模式。而自杀基因疗法是目前有效治疗肿瘤中最有前景的基因治疗策略之一。本研究目的在于探讨腺病毒载体介导的单纯疱疹病毒胸苷激酶(HSV-tk)与免疫因子白细胞介素-2(IL-2)联合应用对涎腺腺样囊性癌的抑制和杀伤作用。可望为该肿瘤基因治疗的临床研究提供可靠的理论依据和实验室数据。
材料与方法:1材料(1)实验材料:人涎腺腺样囊性癌高转移细胞系(ACC-M)。(2)药品:腺病毒介导的单纯疱疹病毒胸苷激酶(HSV-tk),腺病毒介导白细胞介素-2(IL-2),丙氧鸟苷(GCV)(3)实验动物:20只SPF级雌性Balb/c裸小鼠,4~5周龄。2方法:(1)动物模型建立:ACC-M细胞培养于RPMI1640含胎牛血清和双抗的培养液中,37℃恒温孵育,收集细胞并调整为2×10~7/ml的细胞悬液。将ACC-M细胞悬液接种于裸鼠皮下,每只注射左前背部和右后背部2点,每点0.2ml,待移植瘤直径达约1.0cm,随机分组。(2)分组与给药:共分4组,每组5只。均采取瘤体内注射。A组空白对照组,每移植瘤注射与实验组等量生理盐水。B组
Objective: Salivary adenoid cystic carcinoma (SACC) is a very common malignancy of salivary gland. Recurrence and early metastasis are its biological properties. It is difficult to be entirely resected surgically and is invalid to radiotherapy and chemotherapy. So the long-term prognosis of patients is very dismal. Therefore, it is imperative to find a perfect auxiliary therapeutic treatment. As a new method for tumor therapy, gene therapy has a large development. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) method is one of the most frequently utilized measures of gene therapy. However, suicide gene therapy alone cannot completely eliminate tumor cells, so it is necessary to combine suicide gene therapy with other therapy to improve performance. This study is to observe the depressing kill effect on SACC animal model in nude mice by union treated with HSV-TK and IL-2 adenovirus vector.
Materials and Methods: 1 Materials: (1) Cell line:a human adenoid cystic carcinoma cell line with high tendency of lung metastasi(sACC-M); (2) Drug: adenovirus vector HSV-TK, adenovirus vector IL-2, ganciclovir (GCV); (3) Animal: Twenty SPF grade, 4~6 week-old female Balb/c nude mice were used in this study. 2 Methods: (1) animal model: ACC-M cells were
材料与方法:1材料(1)实验材料:人涎腺腺样囊性癌高转移细胞系(ACC-M)。(2)药品:腺病毒介导的单纯疱疹病毒胸苷激酶(HSV-tk),腺病毒介导白细胞介素-2(IL-2),丙氧鸟苷(GCV)(3)实验动物:20只SPF级雌性Balb/c裸小鼠,4~5周龄。2方法:(1)动物模型建立:ACC-M细胞培养于RPMI1640含胎牛血清和双抗的培养液中,37℃恒温孵育,收集细胞并调整为2×10~7/ml的细胞悬液。将ACC-M细胞悬液接种于裸鼠皮下,每只注射左前背部和右后背部2点,每点0.2ml,待移植瘤直径达约1.0cm,随机分组。(2)分组与给药:共分4组,每组5只。均采取瘤体内注射。A组空白对照组,每移植瘤注射与实验组等量生理盐水。B组
Objective: Salivary adenoid cystic carcinoma (SACC) is a very common malignancy of salivary gland. Recurrence and early metastasis are its biological properties. It is difficult to be entirely resected surgically and is invalid to radiotherapy and chemotherapy. So the long-term prognosis of patients is very dismal. Therefore, it is imperative to find a perfect auxiliary therapeutic treatment. As a new method for tumor therapy, gene therapy has a large development. Herpes simplex virus thymidine kinase/ganciclovir (HSV-TK/GCV) method is one of the most frequently utilized measures of gene therapy. However, suicide gene therapy alone cannot completely eliminate tumor cells, so it is necessary to combine suicide gene therapy with other therapy to improve performance. This study is to observe the depressing kill effect on SACC animal model in nude mice by union treated with HSV-TK and IL-2 adenovirus vector.
Materials and Methods: 1 Materials: (1) Cell line:a human adenoid cystic carcinoma cell line with high tendency of lung metastasi(sACC-M); (2) Drug: adenovirus vector HSV-TK, adenovirus vector IL-2, ganciclovir (GCV); (3) Animal: Twenty SPF grade, 4~6 week-old female Balb/c nude mice were used in this study. 2 Methods: (1) animal model: ACC-M cells were
引文
1 Mesnil M, Yamasaki H. Bystander effect in herpes simplex virus thymidine kinase/Ganciclovir cancer gene therapy: Role of gapjunctional intercellular communication. Cancer Res.2000, 60(15): 3989-3999
2 Smiley WR, Laubert B, Howard BD, et al. Establishment of parameters for optimal transduction efficiency and antitumor effects with purified hightiter HSV-tk retroviral vector in established solid tumors. Hum Gene Ther, 1997,8:965-977
3 Elion GB, Furman PA, Fyfe JA, etal. Selectivity of action of an antiherpetic agent,9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci USA, 1997, 74:5716-5720
4 Oliver S, Bubley G, Crumpacker C, et al. Inhibition of HSV-transformed murrine cells by nucleoside analogs, 2-NDG and 2}-nor-cGMP: mechanisms of inhibition and reveral by exogenous nucleosides. Virology, 1995, 145: 84-93
5 Miller WH, Mille RL. Phosphorylation of acyclivor (acycloguanosine) monophosphate by GMP kinase. J Biol Chem, 1980, 255:7204-7208
6 Mar EC, Chiou JF, Cheng YC, etal. Inhibition of cellular DNA polymerase alpha and human cytomegalovirus-induced DNA polymerase by the triphosphate of 9-(2- hydroxyethoxymethl) guanine and9-(1,3-dihydroxy-2- propoxymethyl) guanine. J Virol, 1985, 53:776-780
7 Vile RG, Catleden S, Marshall J, et al. Generation of an antitumor immune response in a non-immunogenic tumor: HSV-tk killing in vivo stimulates mononuclear cell infiltrate and a TH1-like profile of intratumoral cytokine expression. Int J Cancer, 1997, 71:267-274
8 Hamel W, Mannelli L, Chiaruni VP, et al. Herpoes simplex virus kinase/gancicliv-mediated apoptotic death of bystander cells. Cancer Res, 1996, 56(12): 2697
9 Beltinger C, Fulda S, Kammertoens T, et al. Mitochondrial amplification of death signals determines thymidine kinaselganciclovir-triggered activation of apoptosis. Cancer Res, 2000, 60(12); 3212-3217
10 Beltinger C, Fulda S, Kammertoens T, et al. Herpes simplex virus thymidine ldnaselganciclovir-induced apoptosis involves ligand-indepent death receptor aggregation and activation of caspases. Proc Natl Acad Sci USA, 1999, 96:8699-8704
11 Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst, 1992, 84(24): 875-881
12 Natalie S, Larsen I. Angiogenesis research yields new approaches to cancer treatment and prognosis. J Nat Cancer Inst, 1993, 85:1629-1636
13 Li pX , Ngo D , Brade AM , etal.Differential chemosensitivity of breast cancer cells to ganciclovir treatlnent following adenovirus-mediated Perpes simPlex virus thymidine kinase genetransfer. Cancer Gene Ther, 1999,6(2):179-190
14 CraPeri D, Vicat JM,Nissou NF, etal. Increased bax expression 15 associated with cell death induced by ganciclovir in a herpes thymidine kinase gene-expressing glioma cell line. Hum Gen Ther, 1999, 10(4): 679-688.
15 Kaneko Y, Tsukamoto A.Gene therapy of the patoma:bystander effects and non-apoptotic cell death induced by thymidine kinase and ganciclovir Cancer Lett, 1995,96(1):105-110
16 刑毅飞,肖亚军,鲁功成. HSV-tk/GCV 系统诱导前列腺癌细胞死亡机理的初步探讨.中国泌尿外科杂志,2003,24(6):418
17 Sewell DA,Li D,Duan L,et al.Optimizing suicide gene therapy for head and neck cancer. Laryngoscope,1997,107(11 Ptl):1490-1495
18 Folkman J.What is the evidence that tumors are angiogenesis dependent? J Nat Cancerlnst,1990,82:4-10
19 Yanase T, Tamuram M,Fujitan K. Inhibitory effect of angiogenesis inhibiter TNp-470 on tumor growth and metastasis of human cell lines in vitro and vivo. Cancer Res, 1993, 53:2566-2571
20 于波,李世拥,安萍,等.腺病毒介导 HSV-TK 自杀基因联合野生型 p53 基因对直肠癌细胞的杀伤作用. 实用癌症杂志,2001, 16(3):248~250
21 Matsubara H, Kawamura K, Sugaya M, et al. Differential virus-thymidine kinase gene reflects the status of IL-2 gene in human esophageal cancer cells. Anticancer Res, 1999, 19(2): 4157~4160
22 黄强, 浦佩玉, 夏之柏,等. p53 基因优化恶性胶质瘤HSV-TK/GCV 治疗的体外研究. Chin Clin J Neurosurg, 2003, 8(1): 44~46
23 何球藻,吴厚生. 医学免疫学.上海医科大学出版社,1998,72-86
24 Taniguchi T, Matsui H, Fujita T, et al. Structure and expression of a cloned cDNA for human interleukin-2. Nature, 1983, 302(5906): 305~310
25 金晓凌,井清源,王炳生,等. 瘤体内直接注射白介素-2 质粒复合物治疗小鼠肝癌.中国肿瘤临床,2001, 10: 779~782
26 Gagandeep S, Brow R Green B, et al. Prodrug-activated gene therapy: involvrnent of an immunological component in the bystander effect. Cancer Res, 1996, 3: 83-88
27 Kianmanish AR,Perrin H, Panis Y, et al. A "distant" bystander effect of suicide gene therapy: regression of nontransduced tumors together with a distant transduced tumor. Hum Gene Ther, 1997, 8: 1807-1814
28 Vile RG, Catleden S, Marshall J, et al. Generation of an antitumor immune response in a non-immunogenic tumor:HSV-tk killing in vivo stimulates a mononuclear cell infiltrate and a TH1-like profile of intratumoral cytokine expression. Int J Cancer, 1997, 71:267-274
29 Marble, Michelle, Key, etal. Distant bystander effect exhibited in HSV-tk gene therapy. Cancer Weekly Plus, 1996; 2:10
30 Dive C, Hickman JA. Drug-target interactions: only the first step in the conunitment to a programmed cell death. Br J Cancer, 1991, 64:192-198
31 Evans DL, Tilby M, Dive C. Defferential sensitivity to the induction of apoptosis by cisplatinum in proliferating and immature rat thymocytes is independent of the levels of drug acummulation and DNA adduct formation. Cancer Res, 1994, 54:1596-1603
32 Malley BW, Cope KA, Chen SH, et al. Combination gene therapy for oral cancer in a murine model. Cancer Res, 1996,56:1737-1741
33 Hall SJ,Mutehnik SE,Chen SH,et al Adenovirus-mediated HSV-tk gene and GCV therapy lead to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer. Int J Cancer 1997, 70:183-187
34 郑书深,王洁,董福生等. HSV-TK 与 IL-2 基因对涎腺多形性腺瘤细胞的杀伤作用.中国肿瘤临床,2005,32(10):544-547
1 于世风主编,口腔组织病理学,人民卫生出版社,2003,261
2 Freeman SM, McCune C, Angel C, et al. Treatment of ovarian cancer using HSV TK gene modified vaccine-regulatory issues. Hum Gene Ther, 1992, 3:342-349
3 Eck SL, Alavi JB, Alavi A, et al. Treatment of advanced CNS malignancies with the recombinant adenovirus HS.010 RSVTK: a phase I trial. Hum Gene Ther, 1996, 7: 1465-1482
4 Klatxmann D, Valery CA, Bensimon G, et al. A phase I/II study of herpes simplex virus type I thymidine kinase "suicide" gene therapy for recurrent glioblastoma. Hum Gene Ther, 1998, 9: 2595-2604
5 Alvarez RD,Curiel DT. A phase I study of recombinant adenoviral vector-mediated intraperitoneal delivery of herpes simplex virus thymidine kinase gene and intravenous ganciclovir for previously treated ovarian cancer and extraovarian cancer patients. Hum Gene Ther, 1997, 8: 597-613
6 Schwarzenberger P, Harrison L, Weinacker A, et al. Clinical protocol: gene therapy for malignant mesothelioma: a novel approach for an incurable cancer with increased incidencein Louisiana. Hum Gene Ther, 1998, 9:2641-2649
7 Sterman DH, Treat J, Litzky LA, et al. Adenovirus-mediated herpes simple virus thymidine kinase/ganciclovir genetherapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma Hum Gene Ther, 1998, 9: 1083-1092
8 Niculescu-Duvaz D, Niculescu-Duvaz I, Springer CJ. Design of prodrugs for suicide gene therapy. Methods Mol Med, 2004, 90:161~202
9 Springer CJ. Introduction to vectors for suicide gene therapy. Methods Mol Med, 2004, 90: 29~45
10 Moolten FL. Tumor chemosensitivity conferred by inserted herpes thymidine kinase gene: paradigm for a prospective cancer control strategy. Cancer Res, 1986, 46: 5276-5281
11 Whartenby KA, Marrogi AJ, Ramesh R, et al. The biology of cancer gene therapy. Lab Invest, 1995, 72: 131-141
12 Mullan CA, Kilstrup M and Blaese RM. Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine:a negative selection system. Proc Natl Acad Sci USA, 1992, 89: 33-37
13 Huber BE, Austin EA, Good SS, et al. In vivo antitumor activity of 5-fluorocytosine on human colorectal carcinoma cells genetically modified to express cytosine deaminase. Cancer Res, 1993; 3: 4419-4626
14 Maatta AM, Tenhunen A, Pasanen T, et al. Non-small cell lung cancer as a target disease for herpes simplex type 1 thymidine kinase-ganciclovir gene therapy. Int J Oncol, 2004, 24 (4): 943~949
15 Hoggarth JH, Jones E, Ensser A, et al. Functional expression of thymidine kinase in human leukaemic and colorectal cells, delivered as EGFP fusion protein by herpesvirus saimiri-based vector. Cancer Gene Ther, 2004, 11(7): 512~518
16 FL Moolten. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res, 1986, 46(10): 5276~5281
17 Moolten FL, Wells JM. Curability of tumors bearing herpes thymidine kinase genes transferred by retroviral vectors. J Natl Cancer Inst, 1990, 82(4): 297~ 300
18 O’Malley BW , Li D. Combination gene therapy for salivary gland cancer. Ann NY Acad Sci, 1998, 842: 163~170
19 孙春晓,何荣根,张志愿,等. 涎腺腺样囊性癌自杀基因治疗的实验研究.中华口腔医学杂志, 2000, 35 (1): 34~37
20 Yamamoto S, Suzuki S, Hoshio A, et al. HSV-tkIGCV mediated killing of tumor cells induces tumor-specific cytotoxic T cells in mice. Cancer Gene Ther, 1997, 4(2): 91-96
21 Hall SJ, Mutehnik SE, Chen SH, etal. Adenovirus mediated HSV-tk gene and GCV therapy lead to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer. Int J Cancer,1997,70(2): 183-187
22 Kianmanesh AP, Perrin H, Panis Y, et al. A "distant" bystander effect of suicide gene therapy: regression of nontransduced tumor. Hum Gene Ther, 1997, 8(15): 1807-1814
23 Marble, Michelle, Key, et al. Distant bystander effect exhibited in HSV-tk gene therapy. Cancer Weekly Plus, 1996, 2:10
24 何球藻,吴厚生. 医学免疫学.上海医科大学出版社,1998,72-86
25 Taniguchi T, Matsui H, Fujita T, et al. Structure and expression of a cloned cDNA for human interleukin-2. Nature, 1983, 302(5906): 305~310
26 金晓凌,井清源,王炳生,等. 瘤体内直接注射白介素-2质粒复合物治疗小鼠肝癌.中国肿瘤临床,2001, 10: 779~782
27 O'Malley BW, Cope KA, Chen SH, et al. Combination gene therapy for oral cancer in a murine model. Cancer Res, 1996, 56(8): 1734~1741
28 Benedetti S, Dimeco F, Pollo B, et al. Limited efficacy of the HSV-TK/GCV system for gene therapy of malignant gliomas and perspectives for the combined transduction of the interleukin-4 gene .Hum Gene Ther, 1997, 8(11): 1345~1353
29 Chen SH, Kosai K, Xu B, et al. Combination suicide and cytokine gene therapy for hepatic metastases of coloncarcinoma: sustained antitumor or immunity prolongs animal suavival. Cancer Res, 1996, 56(16): 3578-3762
30 Freeman SM, Ramesh R, Marrogi A. Immune system in suicide gene therapy. Lancet, 1997; 349(9044): 2-3
31 Pizzato M, Franchin E, Calvi P, et al. Production and characterization of a bicistronic moloney-based retroviral vector expressing human IL-2 and HSV-tk for gene therapy of cancer. Gene Therapy, 1997, 4:1322-1329
32 Felzmann T, Ramsey WJ, Blaese RM, et al. Characterization of the antitumor immune response generated by treatment of marine tumors with recombinant adenoviruses expressing HSV-tk, IL-2, IL-6, or B7.1.Gene Therapy, 1997, 4:1322-1329
33 Larchian WA, Horiguchi Y, Nair SK, et al. Effectiveness of combined interleukin2 and B7.1 vaccinations trategy is dependent on the sequence and order: aliposome-mediated gene therapy treatment for bladder cancer. Clin Cancer Res, 2000, 6 (7): 2913~2920
34 Barzon L, Bonaguro R, Castagliuolo I, et al. Gene therapy of thyroid cancer via retrovirally driven combined expression of human interleukin2 and herpes simplex virus thymidine kinase Eur J Endocrinol, 2003, 148 (1): 73~80
35 Tsuchiyama T, Kaneko S, Nakamoto Y, et al. Enhanced antitumor effects of abicistronic adenovirus vector expressing both herpes simple virus thymidine kinase and monocyte chemo attractant protein 1 against hepatocellular carcinima. Cancer Gene Ther, 2003, 10 (4): 260~269
36 温玉明,李文,王昌美, 等. nm23-h1 基因导入对腺样囊性癌分化的影响. 临床口腔医学杂志, 2001,17 (3): 163-164
37 王石光,司徒镇强,吴军正. c-myc 反义寡核苷酸对粘液表皮样癌细胞生长的抑制作用. 实用口腔医学杂志, 2000, 16 (5): 391-393
38 Wilda M,Fuchs U,Wossmann W. Killing of leukemic cells with a BCR/ ABL fusion gene by RNA lntefference(RNAI). Onco-gene, 2002, 21: 5716 -5724
39 Cioca DP,Aoki Y,Xiyosawa K. RNA intefference is a functional pathway with therapeutic potential in human myeloid leukemia cell lines. Cancer gene The, 2003, 10: 125-133
2 Smiley WR, Laubert B, Howard BD, et al. Establishment of parameters for optimal transduction efficiency and antitumor effects with purified hightiter HSV-tk retroviral vector in established solid tumors. Hum Gene Ther, 1997,8:965-977
3 Elion GB, Furman PA, Fyfe JA, etal. Selectivity of action of an antiherpetic agent,9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci USA, 1997, 74:5716-5720
4 Oliver S, Bubley G, Crumpacker C, et al. Inhibition of HSV-transformed murrine cells by nucleoside analogs, 2-NDG and 2}-nor-cGMP: mechanisms of inhibition and reveral by exogenous nucleosides. Virology, 1995, 145: 84-93
5 Miller WH, Mille RL. Phosphorylation of acyclivor (acycloguanosine) monophosphate by GMP kinase. J Biol Chem, 1980, 255:7204-7208
6 Mar EC, Chiou JF, Cheng YC, etal. Inhibition of cellular DNA polymerase alpha and human cytomegalovirus-induced DNA polymerase by the triphosphate of 9-(2- hydroxyethoxymethl) guanine and9-(1,3-dihydroxy-2- propoxymethyl) guanine. J Virol, 1985, 53:776-780
7 Vile RG, Catleden S, Marshall J, et al. Generation of an antitumor immune response in a non-immunogenic tumor: HSV-tk killing in vivo stimulates mononuclear cell infiltrate and a TH1-like profile of intratumoral cytokine expression. Int J Cancer, 1997, 71:267-274
8 Hamel W, Mannelli L, Chiaruni VP, et al. Herpoes simplex virus kinase/gancicliv-mediated apoptotic death of bystander cells. Cancer Res, 1996, 56(12): 2697
9 Beltinger C, Fulda S, Kammertoens T, et al. Mitochondrial amplification of death signals determines thymidine kinaselganciclovir-triggered activation of apoptosis. Cancer Res, 2000, 60(12); 3212-3217
10 Beltinger C, Fulda S, Kammertoens T, et al. Herpes simplex virus thymidine ldnaselganciclovir-induced apoptosis involves ligand-indepent death receptor aggregation and activation of caspases. Proc Natl Acad Sci USA, 1999, 96:8699-8704
11 Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst, 1992, 84(24): 875-881
12 Natalie S, Larsen I. Angiogenesis research yields new approaches to cancer treatment and prognosis. J Nat Cancer Inst, 1993, 85:1629-1636
13 Li pX , Ngo D , Brade AM , etal.Differential chemosensitivity of breast cancer cells to ganciclovir treatlnent following adenovirus-mediated Perpes simPlex virus thymidine kinase genetransfer. Cancer Gene Ther, 1999,6(2):179-190
14 CraPeri D, Vicat JM,Nissou NF, etal. Increased bax expression 15 associated with cell death induced by ganciclovir in a herpes thymidine kinase gene-expressing glioma cell line. Hum Gen Ther, 1999, 10(4): 679-688.
15 Kaneko Y, Tsukamoto A.Gene therapy of the patoma:bystander effects and non-apoptotic cell death induced by thymidine kinase and ganciclovir Cancer Lett, 1995,96(1):105-110
16 刑毅飞,肖亚军,鲁功成. HSV-tk/GCV 系统诱导前列腺癌细胞死亡机理的初步探讨.中国泌尿外科杂志,2003,24(6):418
17 Sewell DA,Li D,Duan L,et al.Optimizing suicide gene therapy for head and neck cancer. Laryngoscope,1997,107(11 Ptl):1490-1495
18 Folkman J.What is the evidence that tumors are angiogenesis dependent? J Nat Cancerlnst,1990,82:4-10
19 Yanase T, Tamuram M,Fujitan K. Inhibitory effect of angiogenesis inhibiter TNp-470 on tumor growth and metastasis of human cell lines in vitro and vivo. Cancer Res, 1993, 53:2566-2571
20 于波,李世拥,安萍,等.腺病毒介导 HSV-TK 自杀基因联合野生型 p53 基因对直肠癌细胞的杀伤作用. 实用癌症杂志,2001, 16(3):248~250
21 Matsubara H, Kawamura K, Sugaya M, et al. Differential virus-thymidine kinase gene reflects the status of IL-2 gene in human esophageal cancer cells. Anticancer Res, 1999, 19(2): 4157~4160
22 黄强, 浦佩玉, 夏之柏,等. p53 基因优化恶性胶质瘤HSV-TK/GCV 治疗的体外研究. Chin Clin J Neurosurg, 2003, 8(1): 44~46
23 何球藻,吴厚生. 医学免疫学.上海医科大学出版社,1998,72-86
24 Taniguchi T, Matsui H, Fujita T, et al. Structure and expression of a cloned cDNA for human interleukin-2. Nature, 1983, 302(5906): 305~310
25 金晓凌,井清源,王炳生,等. 瘤体内直接注射白介素-2 质粒复合物治疗小鼠肝癌.中国肿瘤临床,2001, 10: 779~782
26 Gagandeep S, Brow R Green B, et al. Prodrug-activated gene therapy: involvrnent of an immunological component in the bystander effect. Cancer Res, 1996, 3: 83-88
27 Kianmanish AR,Perrin H, Panis Y, et al. A "distant" bystander effect of suicide gene therapy: regression of nontransduced tumors together with a distant transduced tumor. Hum Gene Ther, 1997, 8: 1807-1814
28 Vile RG, Catleden S, Marshall J, et al. Generation of an antitumor immune response in a non-immunogenic tumor:HSV-tk killing in vivo stimulates a mononuclear cell infiltrate and a TH1-like profile of intratumoral cytokine expression. Int J Cancer, 1997, 71:267-274
29 Marble, Michelle, Key, etal. Distant bystander effect exhibited in HSV-tk gene therapy. Cancer Weekly Plus, 1996; 2:10
30 Dive C, Hickman JA. Drug-target interactions: only the first step in the conunitment to a programmed cell death. Br J Cancer, 1991, 64:192-198
31 Evans DL, Tilby M, Dive C. Defferential sensitivity to the induction of apoptosis by cisplatinum in proliferating and immature rat thymocytes is independent of the levels of drug acummulation and DNA adduct formation. Cancer Res, 1994, 54:1596-1603
32 Malley BW, Cope KA, Chen SH, et al. Combination gene therapy for oral cancer in a murine model. Cancer Res, 1996,56:1737-1741
33 Hall SJ,Mutehnik SE,Chen SH,et al Adenovirus-mediated HSV-tk gene and GCV therapy lead to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer. Int J Cancer 1997, 70:183-187
34 郑书深,王洁,董福生等. HSV-TK 与 IL-2 基因对涎腺多形性腺瘤细胞的杀伤作用.中国肿瘤临床,2005,32(10):544-547
1 于世风主编,口腔组织病理学,人民卫生出版社,2003,261
2 Freeman SM, McCune C, Angel C, et al. Treatment of ovarian cancer using HSV TK gene modified vaccine-regulatory issues. Hum Gene Ther, 1992, 3:342-349
3 Eck SL, Alavi JB, Alavi A, et al. Treatment of advanced CNS malignancies with the recombinant adenovirus HS.010 RSVTK: a phase I trial. Hum Gene Ther, 1996, 7: 1465-1482
4 Klatxmann D, Valery CA, Bensimon G, et al. A phase I/II study of herpes simplex virus type I thymidine kinase "suicide" gene therapy for recurrent glioblastoma. Hum Gene Ther, 1998, 9: 2595-2604
5 Alvarez RD,Curiel DT. A phase I study of recombinant adenoviral vector-mediated intraperitoneal delivery of herpes simplex virus thymidine kinase gene and intravenous ganciclovir for previously treated ovarian cancer and extraovarian cancer patients. Hum Gene Ther, 1997, 8: 597-613
6 Schwarzenberger P, Harrison L, Weinacker A, et al. Clinical protocol: gene therapy for malignant mesothelioma: a novel approach for an incurable cancer with increased incidencein Louisiana. Hum Gene Ther, 1998, 9:2641-2649
7 Sterman DH, Treat J, Litzky LA, et al. Adenovirus-mediated herpes simple virus thymidine kinase/ganciclovir genetherapy in patients with localized malignancy: results of a phase I clinical trial in malignant mesothelioma Hum Gene Ther, 1998, 9: 1083-1092
8 Niculescu-Duvaz D, Niculescu-Duvaz I, Springer CJ. Design of prodrugs for suicide gene therapy. Methods Mol Med, 2004, 90:161~202
9 Springer CJ. Introduction to vectors for suicide gene therapy. Methods Mol Med, 2004, 90: 29~45
10 Moolten FL. Tumor chemosensitivity conferred by inserted herpes thymidine kinase gene: paradigm for a prospective cancer control strategy. Cancer Res, 1986, 46: 5276-5281
11 Whartenby KA, Marrogi AJ, Ramesh R, et al. The biology of cancer gene therapy. Lab Invest, 1995, 72: 131-141
12 Mullan CA, Kilstrup M and Blaese RM. Transfer of the bacterial gene for cytosine deaminase to mammalian cells confers lethal sensitivity to 5-fluorocytosine:a negative selection system. Proc Natl Acad Sci USA, 1992, 89: 33-37
13 Huber BE, Austin EA, Good SS, et al. In vivo antitumor activity of 5-fluorocytosine on human colorectal carcinoma cells genetically modified to express cytosine deaminase. Cancer Res, 1993; 3: 4419-4626
14 Maatta AM, Tenhunen A, Pasanen T, et al. Non-small cell lung cancer as a target disease for herpes simplex type 1 thymidine kinase-ganciclovir gene therapy. Int J Oncol, 2004, 24 (4): 943~949
15 Hoggarth JH, Jones E, Ensser A, et al. Functional expression of thymidine kinase in human leukaemic and colorectal cells, delivered as EGFP fusion protein by herpesvirus saimiri-based vector. Cancer Gene Ther, 2004, 11(7): 512~518
16 FL Moolten. Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. Cancer Res, 1986, 46(10): 5276~5281
17 Moolten FL, Wells JM. Curability of tumors bearing herpes thymidine kinase genes transferred by retroviral vectors. J Natl Cancer Inst, 1990, 82(4): 297~ 300
18 O’Malley BW , Li D. Combination gene therapy for salivary gland cancer. Ann NY Acad Sci, 1998, 842: 163~170
19 孙春晓,何荣根,张志愿,等. 涎腺腺样囊性癌自杀基因治疗的实验研究.中华口腔医学杂志, 2000, 35 (1): 34~37
20 Yamamoto S, Suzuki S, Hoshio A, et al. HSV-tkIGCV mediated killing of tumor cells induces tumor-specific cytotoxic T cells in mice. Cancer Gene Ther, 1997, 4(2): 91-96
21 Hall SJ, Mutehnik SE, Chen SH, etal. Adenovirus mediated HSV-tk gene and GCV therapy lead to systemic activity against spontaneous and induced metastasis in an orthotopic mouse model of prostate cancer. Int J Cancer,1997,70(2): 183-187
22 Kianmanesh AP, Perrin H, Panis Y, et al. A "distant" bystander effect of suicide gene therapy: regression of nontransduced tumor. Hum Gene Ther, 1997, 8(15): 1807-1814
23 Marble, Michelle, Key, et al. Distant bystander effect exhibited in HSV-tk gene therapy. Cancer Weekly Plus, 1996, 2:10
24 何球藻,吴厚生. 医学免疫学.上海医科大学出版社,1998,72-86
25 Taniguchi T, Matsui H, Fujita T, et al. Structure and expression of a cloned cDNA for human interleukin-2. Nature, 1983, 302(5906): 305~310
26 金晓凌,井清源,王炳生,等. 瘤体内直接注射白介素-2质粒复合物治疗小鼠肝癌.中国肿瘤临床,2001, 10: 779~782
27 O'Malley BW, Cope KA, Chen SH, et al. Combination gene therapy for oral cancer in a murine model. Cancer Res, 1996, 56(8): 1734~1741
28 Benedetti S, Dimeco F, Pollo B, et al. Limited efficacy of the HSV-TK/GCV system for gene therapy of malignant gliomas and perspectives for the combined transduction of the interleukin-4 gene .Hum Gene Ther, 1997, 8(11): 1345~1353
29 Chen SH, Kosai K, Xu B, et al. Combination suicide and cytokine gene therapy for hepatic metastases of coloncarcinoma: sustained antitumor or immunity prolongs animal suavival. Cancer Res, 1996, 56(16): 3578-3762
30 Freeman SM, Ramesh R, Marrogi A. Immune system in suicide gene therapy. Lancet, 1997; 349(9044): 2-3
31 Pizzato M, Franchin E, Calvi P, et al. Production and characterization of a bicistronic moloney-based retroviral vector expressing human IL-2 and HSV-tk for gene therapy of cancer. Gene Therapy, 1997, 4:1322-1329
32 Felzmann T, Ramsey WJ, Blaese RM, et al. Characterization of the antitumor immune response generated by treatment of marine tumors with recombinant adenoviruses expressing HSV-tk, IL-2, IL-6, or B7.1.Gene Therapy, 1997, 4:1322-1329
33 Larchian WA, Horiguchi Y, Nair SK, et al. Effectiveness of combined interleukin2 and B7.1 vaccinations trategy is dependent on the sequence and order: aliposome-mediated gene therapy treatment for bladder cancer. Clin Cancer Res, 2000, 6 (7): 2913~2920
34 Barzon L, Bonaguro R, Castagliuolo I, et al. Gene therapy of thyroid cancer via retrovirally driven combined expression of human interleukin2 and herpes simplex virus thymidine kinase Eur J Endocrinol, 2003, 148 (1): 73~80
35 Tsuchiyama T, Kaneko S, Nakamoto Y, et al. Enhanced antitumor effects of abicistronic adenovirus vector expressing both herpes simple virus thymidine kinase and monocyte chemo attractant protein 1 against hepatocellular carcinima. Cancer Gene Ther, 2003, 10 (4): 260~269
36 温玉明,李文,王昌美, 等. nm23-h1 基因导入对腺样囊性癌分化的影响. 临床口腔医学杂志, 2001,17 (3): 163-164
37 王石光,司徒镇强,吴军正. c-myc 反义寡核苷酸对粘液表皮样癌细胞生长的抑制作用. 实用口腔医学杂志, 2000, 16 (5): 391-393
38 Wilda M,Fuchs U,Wossmann W. Killing of leukemic cells with a BCR/ ABL fusion gene by RNA lntefference(RNAI). Onco-gene, 2002, 21: 5716 -5724
39 Cioca DP,Aoki Y,Xiyosawa K. RNA intefference is a functional pathway with therapeutic potential in human myeloid leukemia cell lines. Cancer gene The, 2003, 10: 125-133