胰腺癌生物治疗进展及展望
夏璐, 袁耀宗,上海第二医科大学附属瑞金医院消化科 上海市 200025
通讯作者:袁耀宗, 200025, 上海市瑞金二路197号, 上海第二医科大学附属瑞金医院消化科. yyz28@medmail.com.cn
电话: 021-64370045
收稿日期: 2005-01-06 接受日期: 2005-01-13
摘要
生物治疗是肿瘤传统治疗方法的重要辅助手段.本文对基因治疗、免疫治疗、诱导肿瘤细胞凋亡和抑制肿瘤新生血管等方面在胰腺癌中的研究进行回顾.随着生物科学技术的发展以及对胰腺癌发生发展机制了解的深入，目前对胰腺癌生物治疗的研究和临床应用也取得了很大进展，但其临床疗效仍十分有限，如何发挥生物治疗在胰腺癌治疗中的作用尚需更多基础研究和临床资料的积累.
, http://www.100md.com
夏璐, 袁耀宗. 胰腺癌生物治疗进展及展望. 世界华人消化杂志 2005;13(6):769-771
MacKenzie MJ. Molecular therapy in pancreatic adenocarcinoma. Lancet Oncol 2004;5:541-549
2 Laheru D, Biedrzycki B, Thomas AM, Jaffee EM. Development of a cytokine-modified allogeneic whole cell pancreatic
cancer vaccine. Methods Mol Med 2004;103:299-328
3 Brett BT, Smith SC, Bouvier CV, Michaeli D, Hochhauser D, Davidson BR, Kurzawinski TR, Watkinson AF, Van Someren
, 百拇医药
N, Pounder RE, Caplin ME. Phase II study of anti-gastrin-17 antibodies, raised to G17DT, in advanced pancreatic cancer.
J Clin Oncol 2002;20:4225-4231
4 Brickelmaier M, Carmillo A, Goelz S, Barsoum J, Qin XQ. Cytotoxicity of combinations of IFN-beta and
chemotherapeutic drugs. J Interferon Cytokine Res 2002;22:873-880
5 Thomas AM, Santarsiero LM, Lutz ER, Armstrong TD, Chen YC, Huang LQ, Laheru DA, Goggins M, Hruban RH, Jaffee
, http://www.100md.com
EM. Mesothelin-specific CD8(+)T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells
in vaccinated pancreatic cancer patients. J Exp Med 2004;200:297-306
6 Sivinski CL, Kohlgraf KG, VanLith ML, Morikane K, Tempero RM, Hollingsworth MA. Molecular requirements for
CD8-mediated rejection of a MUC1-expressing pancreatic carcinoma: implications for tumor vaccines. Cancer
, 百拇医药
Immunol Immunother 2002;51:327-340
7 Tang ZH, Qiu WH, Wu GS, Yang XP, Zou SQ, Qiu FZ. The immunotherapeutic effect of dendritic cells vaccine modified
with interleukin-18 gene and tumor cell lysate on mice with pancreatic carcinoma. World J Gastroenterol 2002;
8:908-912
8 Gjertsen MK, Buanes T, Rosseland AR, Bakka A, Gladhaug I, Soreide O, Eriksen JA, Moller M, Baksaas I, Lothe
, 百拇医药
RA, Saeterdal I, Gaudernack G. Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating
factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma. Int J
Cancer 2001;92:441-450
9 Jaffee EM, Hruban RH, Biedrzycki B, Laheru D, Schepers K, Sauter PR, Goemann M, Coleman J, Grochow L, Donehower
, http://www.100md.com RC, Lillemoe KD, O'Reilly S, Abrams RA, Pardoll DM, Cameron JL, Yeo CJ. Novel allogeneic
granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of
safety and immune activation. J Clin Oncol 2001;19:145-156
10 Ramirez PJ, Vickers SM. Current status of gene therapy for pancreatic cancer. Curr Surg 2004;61:84-92
, http://www.100md.com
11 Wang J, Lu XX, Chen DZ, Li SF, Zhang LS. Herpes simplex virus thymidine kinase and ganciclovir suicide gene
therapy for human pancreatic cancer. World J Gastroenterol 2004;10:400-403
12 Wang XP, Yazawa K, Yang J, Kohn D, Fisher WE, Brunicardi FC. Specific gene expression and therapy for
pancreatic cancer using the cytosine deaminase gene directed by the rat insulin promoter. J Gastrointest Surg 2004;8:
, http://www.100md.com
98-108
13 Hajri A, Wack S, Lehn P, Vigneron JP, Lehn JM, Marescaux J, Aprahamian M. Combined suicide gene therapy
for pancreatic peritoneal carcinomatosis using BGTC liposomes. Cancer Gene Ther 2004;11:16-27
14 Stoll V, Calleja V, Vassaux G, Downward J, Lemoine NR. Dominant negative inhibitors of signalling through
the phosphoinositol 3-kinase pathway for gene therapy of pancreatic cancer. Gut 2005;54:109-116
, http://www.100md.com
15 Duxbury MS, Matros E, Ito H, Zinner MJ, Ashley SW, Whang EE. Systemic siRNA-mediated gene silencing: a
new approach to targeted therapy of cancer. Ann Surg 2004;240:667-674
16 夏璐, 鲍英, 袁耀宗, 张学军. 全反式维甲酸和Caspase抑制剂Z-VAD-FMK对胰腺癌细胞凋亡的作用.
胰腺病学 2003;3:198
17 夏璐, 鲍英, 袁耀宗, 张学军. 全反式维甲酸诱导胰腺癌细胞凋亡机制研究. 中华消化杂志 2004;7:391
18 Lee WN, Guo P, Lim S, Bassilian S, Lee ST, Boren J, Cascante M, Go VL, Boros LG. Metabolic sensitivity of
, http://www.100md.com
pancreatic tumour cell apoptosis to glycogen phosphorylase inhibitor treatment. Br J Cancer 2004;91:2094-2100
19 Chandler NM, Canete JJ, Callery MP. Caspase-3 drives apoptosis in pancreatic cancer cells after treatment
with gemcitabine. J Gastrointest Surg 2004;8:1072-1078
20 Schuch G, Kisker O, Atala A, Soker S. Pancreatic tumor growth is regulated by the balance between positive
, 百拇医药
and negative modulators of angiogenesis. Angiogenesis 2002;5:181-190
21 Hwang RF, Yokoi K, Bucana CD, Tsan R, Killion JJ, Evans DB, Fidler IJ. Inhibition of platelet-derived growth factor
receptor phosphorylation by STI571(Gleevec)reduces growth and metastasis of human pancreatic carcinoma in
an orthotopic nude mouse model. Clin Cancer Res 2003;9:6534-6544
, 百拇医药 22 Prox D, Becker C, Pirie-Shepherd SR, Celik I, Folkman J, Kisker O. Treatment of human pancreatic cancer in mice
with angiogenic inhibitors. World J Surg 2003;27:405-411
23 Nie SL, Yuan SZ. Experimental study of gene therapy with angiostatin gene in pancreatic cancer. Hepatobiliary
Pancreat Dis Int 2002;1:452-457
24 Takahashi T, Omuro Y, Matsumoto G, Sakamaki H, Maeda Y, Hiruma K, Tsuruta K, Sasaki T. Nonmyeloablative
, http://www.100md.com
allogeneic stem cell transplantation for patients with unresectable pancreatic cancer. Pancreas 2004;28:e65-e69
25 Mroczko B, Szmitkowski M, Wereszczynska-Siemiatkowska U, Jurkowska G. Stem cell factor and
macrophage-colony stimulating factor in patients with pancreatic cancer. Clin Chem Lab Med 2004;42:256-260
26 Esposito I, Kleeff J, Bischoff SC, Fischer L, Collecchi P, Iorio M, Bevilacqua G, Buchler MW, Friess H. The stem
cell factor-c-kit system and mast cells in human pancreatic cancer. Lab Invest 2002;82:1481-1492
27 Mizumoto K, Tanaka M. Detection of telomerase activity in patients with pancreatic cancer. Methods Mol
Med 2004;103:199-206
编辑 张海宁, 百拇医药( 夏 璐,袁耀宗)
通讯作者:袁耀宗, 200025, 上海市瑞金二路197号, 上海第二医科大学附属瑞金医院消化科. yyz28@medmail.com.cn
电话: 021-64370045
收稿日期: 2005-01-06 接受日期: 2005-01-13
摘要
生物治疗是肿瘤传统治疗方法的重要辅助手段.本文对基因治疗、免疫治疗、诱导肿瘤细胞凋亡和抑制肿瘤新生血管等方面在胰腺癌中的研究进行回顾.随着生物科学技术的发展以及对胰腺癌发生发展机制了解的深入，目前对胰腺癌生物治疗的研究和临床应用也取得了很大进展，但其临床疗效仍十分有限，如何发挥生物治疗在胰腺癌治疗中的作用尚需更多基础研究和临床资料的积累.
, http://www.100md.com
夏璐, 袁耀宗. 胰腺癌生物治疗进展及展望. 世界华人消化杂志 2005;13(6):769-771
MacKenzie MJ. Molecular therapy in pancreatic adenocarcinoma. Lancet Oncol 2004;5:541-549
2 Laheru D, Biedrzycki B, Thomas AM, Jaffee EM. Development of a cytokine-modified allogeneic whole cell pancreatic
cancer vaccine. Methods Mol Med 2004;103:299-328
3 Brett BT, Smith SC, Bouvier CV, Michaeli D, Hochhauser D, Davidson BR, Kurzawinski TR, Watkinson AF, Van Someren
, 百拇医药
N, Pounder RE, Caplin ME. Phase II study of anti-gastrin-17 antibodies, raised to G17DT, in advanced pancreatic cancer.
J Clin Oncol 2002;20:4225-4231
4 Brickelmaier M, Carmillo A, Goelz S, Barsoum J, Qin XQ. Cytotoxicity of combinations of IFN-beta and
chemotherapeutic drugs. J Interferon Cytokine Res 2002;22:873-880
5 Thomas AM, Santarsiero LM, Lutz ER, Armstrong TD, Chen YC, Huang LQ, Laheru DA, Goggins M, Hruban RH, Jaffee
, http://www.100md.com
EM. Mesothelin-specific CD8(+)T cell responses provide evidence of in vivo cross-priming by antigen-presenting cells
in vaccinated pancreatic cancer patients. J Exp Med 2004;200:297-306
6 Sivinski CL, Kohlgraf KG, VanLith ML, Morikane K, Tempero RM, Hollingsworth MA. Molecular requirements for
CD8-mediated rejection of a MUC1-expressing pancreatic carcinoma: implications for tumor vaccines. Cancer
, 百拇医药
Immunol Immunother 2002;51:327-340
7 Tang ZH, Qiu WH, Wu GS, Yang XP, Zou SQ, Qiu FZ. The immunotherapeutic effect of dendritic cells vaccine modified
with interleukin-18 gene and tumor cell lysate on mice with pancreatic carcinoma. World J Gastroenterol 2002;
8:908-912
8 Gjertsen MK, Buanes T, Rosseland AR, Bakka A, Gladhaug I, Soreide O, Eriksen JA, Moller M, Baksaas I, Lothe
, 百拇医药
RA, Saeterdal I, Gaudernack G. Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating
factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma. Int J
Cancer 2001;92:441-450
9 Jaffee EM, Hruban RH, Biedrzycki B, Laheru D, Schepers K, Sauter PR, Goemann M, Coleman J, Grochow L, Donehower
, http://www.100md.com RC, Lillemoe KD, O'Reilly S, Abrams RA, Pardoll DM, Cameron JL, Yeo CJ. Novel allogeneic
granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of
safety and immune activation. J Clin Oncol 2001;19:145-156
10 Ramirez PJ, Vickers SM. Current status of gene therapy for pancreatic cancer. Curr Surg 2004;61:84-92
, http://www.100md.com
11 Wang J, Lu XX, Chen DZ, Li SF, Zhang LS. Herpes simplex virus thymidine kinase and ganciclovir suicide gene
therapy for human pancreatic cancer. World J Gastroenterol 2004;10:400-403
12 Wang XP, Yazawa K, Yang J, Kohn D, Fisher WE, Brunicardi FC. Specific gene expression and therapy for
pancreatic cancer using the cytosine deaminase gene directed by the rat insulin promoter. J Gastrointest Surg 2004;8:
, http://www.100md.com
98-108
13 Hajri A, Wack S, Lehn P, Vigneron JP, Lehn JM, Marescaux J, Aprahamian M. Combined suicide gene therapy
for pancreatic peritoneal carcinomatosis using BGTC liposomes. Cancer Gene Ther 2004;11:16-27
14 Stoll V, Calleja V, Vassaux G, Downward J, Lemoine NR. Dominant negative inhibitors of signalling through
the phosphoinositol 3-kinase pathway for gene therapy of pancreatic cancer. Gut 2005;54:109-116
, http://www.100md.com
15 Duxbury MS, Matros E, Ito H, Zinner MJ, Ashley SW, Whang EE. Systemic siRNA-mediated gene silencing: a
new approach to targeted therapy of cancer. Ann Surg 2004;240:667-674
16 夏璐, 鲍英, 袁耀宗, 张学军. 全反式维甲酸和Caspase抑制剂Z-VAD-FMK对胰腺癌细胞凋亡的作用.
胰腺病学 2003;3:198
17 夏璐, 鲍英, 袁耀宗, 张学军. 全反式维甲酸诱导胰腺癌细胞凋亡机制研究. 中华消化杂志 2004;7:391
18 Lee WN, Guo P, Lim S, Bassilian S, Lee ST, Boren J, Cascante M, Go VL, Boros LG. Metabolic sensitivity of
, http://www.100md.com
pancreatic tumour cell apoptosis to glycogen phosphorylase inhibitor treatment. Br J Cancer 2004;91:2094-2100
19 Chandler NM, Canete JJ, Callery MP. Caspase-3 drives apoptosis in pancreatic cancer cells after treatment
with gemcitabine. J Gastrointest Surg 2004;8:1072-1078
20 Schuch G, Kisker O, Atala A, Soker S. Pancreatic tumor growth is regulated by the balance between positive
, 百拇医药
and negative modulators of angiogenesis. Angiogenesis 2002;5:181-190
21 Hwang RF, Yokoi K, Bucana CD, Tsan R, Killion JJ, Evans DB, Fidler IJ. Inhibition of platelet-derived growth factor
receptor phosphorylation by STI571(Gleevec)reduces growth and metastasis of human pancreatic carcinoma in
an orthotopic nude mouse model. Clin Cancer Res 2003;9:6534-6544
, 百拇医药 22 Prox D, Becker C, Pirie-Shepherd SR, Celik I, Folkman J, Kisker O. Treatment of human pancreatic cancer in mice
with angiogenic inhibitors. World J Surg 2003;27:405-411
23 Nie SL, Yuan SZ. Experimental study of gene therapy with angiostatin gene in pancreatic cancer. Hepatobiliary
Pancreat Dis Int 2002;1:452-457
24 Takahashi T, Omuro Y, Matsumoto G, Sakamaki H, Maeda Y, Hiruma K, Tsuruta K, Sasaki T. Nonmyeloablative
, http://www.100md.com
allogeneic stem cell transplantation for patients with unresectable pancreatic cancer. Pancreas 2004;28:e65-e69
25 Mroczko B, Szmitkowski M, Wereszczynska-Siemiatkowska U, Jurkowska G. Stem cell factor and
macrophage-colony stimulating factor in patients with pancreatic cancer. Clin Chem Lab Med 2004;42:256-260
26 Esposito I, Kleeff J, Bischoff SC, Fischer L, Collecchi P, Iorio M, Bevilacqua G, Buchler MW, Friess H. The stem
cell factor-c-kit system and mast cells in human pancreatic cancer. Lab Invest 2002;82:1481-1492
27 Mizumoto K, Tanaka M. Detection of telomerase activity in patients with pancreatic cancer. Methods Mol
Med 2004;103:199-206
编辑 张海宁, 百拇医药( 夏 璐,袁耀宗)
