Killer genes in pancreatic cancer therapy

被引:7
作者
Fogar, P
Greco, E
Basso, D
Navaglia, F
Plebani, M
Pedrazzoli, S [1 ]
机构
[1] Univ Hosp Padova, Dept Med & Surg Sci, Padua, Italy
[2] Univ Hosp Padova, Dept Lab Med, Padua, Italy
关键词
pancreatic cancer; killer genes; cytotoxic bacterial toxins; viral and non-viral delivery systems;
D O I
10.1170/T598
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This review describes: 1. the main genetic alterations found in pancreatic cancer (EGF-R overexpression, SST-2 somatostatin receptor loss of expression, k-ras, p53 mutations and DPC4 mutations) and the effect of their replacements by gene therapy on tumor growth; 2. the use of suicide genes (HSV-TK and CD) for pancreatic cancer gene therapy in vitro and in vivo; 3. the implications for pancreatic cancer treatment when using cytotoxic bacterial toxins; 4. viral and non-viral delivery systems for the transfer of therapeutical genes into pancreatic cancer cells. Overall both the correction of pancreatic cancer cells main genetic alterations and the use of suicide genes allow only partial tumor regression in vitro and in vivo. The lack of a 100% effect for any studied strategy considered alone, indicates the need for combined therapies to achieve a satisfactory treatment of this tumor.
引用
收藏
页码:61 / 76
页数:16
相关论文
共 135 条
[21]   Somatostatin receptor gene transfer inhibits established pancreatic cancer xenografts [J].
Celinski, SA ;
Fisher, WE ;
Amaya, F ;
Wu, YQ ;
Yao, Q ;
Youker, KA ;
Li, M .
JOURNAL OF SURGICAL RESEARCH, 2003, 115 (01) :41-47
[22]  
Chandler LA, 1998, INT J CANCER, V78, P106, DOI 10.1002/(SICI)1097-0215(19980925)78:1<106::AID-IJC17>3.0.CO
[23]  
2-9
[24]   Smad4/DPC4-dependent regulation of biglycan gene expression by transforming growth factor-β in pancreatic tumor cells [J].
Chen, WB ;
Lenschow, W ;
Tiede, K ;
Fischer, JW ;
Kalthoff, H ;
Ungefroren, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (39) :36118-36128
[25]  
COLLIER RJ, 1971, J BIOL CHEM, V246, P1496
[26]   TIEG proteins join the Smads as TGF-β-regulated transcription factors that control pancreatic cell growth [J].
Cook, T ;
Urrutia, R .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2000, 278 (04) :G513-G521
[27]   The genetics of pancreatic cancer [J].
Cowgill, SM ;
Muscarella, P .
AMERICAN JOURNAL OF SURGERY, 2003, 186 (03) :279-286
[28]  
Delesque N, 1997, CANCER RES, V57, P956
[29]   Cytokines in cancer pathogenesis and cancer therapy [J].
Dranoff, G .
NATURE REVIEWS CANCER, 2004, 4 (01) :11-22
[30]   Restoration of SMAD4 by gene therapy reverses the invasive phenotype in pancreatic adenocarcinoma cells [J].
Duda, DG ;
Sunamura, M ;
Lefter, LP ;
Furukawa, T ;
Yokoyama, T ;
Yatsuoka, T ;
Abe, T ;
Inoue, H ;
Motoi, F ;
Egawa, S ;
Matsuno, S ;
Horii, A .
ONCOGENE, 2003, 22 (44) :6857-6864