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Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity

Gene Therapy volume 8, pages 508–514 (2001)Cite this article

Abstract

Although peritoneal dissemination of cancer cells often occurs at the advanced stages of pancreatic, gastric or ovarian cancers, no effective therapy has been established. Cationic lipid-mediated gene transfer into peritoneal dissemination may offer a prospect of safe therapies, but vector improvements are needed with regard to the efficiency and specificity of the gene transfer. In this study, the intraperitoneal injection of plasmid DNA:polyethylenimine (PEI) complexes into mice was evaluated as a gene delivery system for the peritoneal disseminations. The luciferase and β-galactosidase genes were used as marker genes. PEI was more efficient than the cationic lipids examined in this study in vivo, and the transgene was preferentially expressed in the tumors. Although PCR analysis showed that the injected DNA was delivered to various organs, the distributed DNA became undetectable by 6 months after the gene transfer. Blood chemistry and histological analysis showed no significant toxicity in the injected mice. This study demonstrated that the intraperitoneal injection of DNA:PEI is a promising delivery method to transduce a gene into disseminated cancer nodules in the peritoneal cavity.

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References

  1. Ghaneh P et al. Adjuvant therapy for pancreatic cancer World J Surg 1999 23: 937–945

    Article  CAS  PubMed  Google Scholar 

  2. Foo ML, Gunderson LL . Adjuvant postoperative radiation therapy +/− 5-FU in resected carcinoma of the pancreas Hepatogastroenterology 1998 45: 613–623

    CAS  PubMed  Google Scholar 

  3. Slavin J et al. The future of surgery for pancreatic cancer Ann Oncol 1999 10 (Suppl. 4): 285–290

    Article  PubMed  Google Scholar 

  4. Howard TJ . Pancreatic adenocarcinoma Curr Probl Cancer 1996 20: 281–328

    Article  CAS  PubMed  Google Scholar 

  5. Lechanteur C et al. Combined suicide and cytokine gene therapy for peritoneal carcinomatosis Gut 2000 47: 343–348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Al-Hendy A et al. Ovarian cancer gene therapy: repeated treatment with thymidine kinase in an adenovirus vector and ganciclovir improves survival in a novel immunocompetent murine model Am J Obstet Gynecol 2000 182: 553–559

    Article  CAS  PubMed  Google Scholar 

  7. Kasuya H et al. Intraperitoneal delivery of hrR3 and ganciclovir prolongs survival in mice with disseminated pancreatic cancer J Surg Oncol 1999 72: 136–141

    Article  CAS  PubMed  Google Scholar 

  8. Cao G et al. In vivo gene transfer of a suicide gene under the transcriptional control if the carcinoembrionic antigen promoter results in bone marrow transduction duct but can avoid bone marrow suppression Int J Oncol 1999 15: 107–112

    CAS  PubMed  Google Scholar 

  9. Kim J et al. Intraperitoneal gene therapy with adenoviral-mediated p53 tumor suppressor gene for ovarian cancer model in nude mouse Cancer Gene Ther 1999 6: 172–178

    Article  CAS  PubMed  Google Scholar 

  10. Tai YT, Strobel T, Kufe D, Cannistra SA . In vivo cytotoxicity of ovarian cancer cells through tumor-selective expression of the BAX gene Cancer Res 1999 59: 2121–2126

    CAS  PubMed  Google Scholar 

  11. Alvarenz RD et al. A cancer gene therapy approach utilizing an anti-erbB-2-single chain antibody-encoding adenovirus (AD21): a phase I trial Clin Cancer Res 2000 6: 3081–3087

    Google Scholar 

  12. Mori A et al. Soluble Flt-1 gene therapy for peritoneal metastases using HVJ-cationic liposomes Gene Ther 2000 7: 1027–1033

    Article  CAS  PubMed  Google Scholar 

  13. Tanaka F et al. The anti-human tumor effect and generation of human cytotoxic T cells in SCID mice given human peripheral blood lymphocytes by the in vivo transfer of the interleukin-6 gene using adenovirus vector Cancer Res 1997 57: 1335–1343

    CAS  PubMed  Google Scholar 

  14. Aoki K, Yoshida T, Sugimura T, Terada M . Liposome-mediated in vivo gene transfer of antisense K-ras construct inhibits pancreatic tumor dissemination in the murine peritoneal cavity Cancer Res 1995 55: 3810–3816

    CAS  PubMed  Google Scholar 

  15. Aoki K et al. Gene therapy for peritoneal dissemination of pancreatic cancer by liposome-mediated transfer of herpes simplex virus thymidine kinase gene Hum Gene Ther 1997 8: 1105–1113

    Article  CAS  PubMed  Google Scholar 

  16. Gao X, Huang L . Cationic liposome-mediated gene transfer Gene Therapy 1995 2: 710–722

    CAS  PubMed  Google Scholar 

  17. Kay MA, Liu D, Hoogerbrugge PM . Gene therapy Proc Natl Acad Sci USA 1997 94: 12744–12746

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Felgner PL et al. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure Proc Natl Acad Sci USA 1987 84: 7413–7417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Behr JP, Demeneix B, Loeffler JP, Perez-Mutul J . Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA Proc Natl Acad Sci USA 1989 86: 6982–6986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Felgner JH et al. Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations J Biol Chem 1994 269: 2550–2561

    CAS  PubMed  Google Scholar 

  21. Boussif O et al. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine Proc Natl Acad Sci USA 1995 92: 7297–7301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Abdallah B et al. A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain: polyethylenimine Hum Gene Ther 1996 7: 1947–1954

    Article  CAS  PubMed  Google Scholar 

  23. Goula D et al. Size, diffusibility and transfection performance of linear PEI/DNA complexes in the mouse central nervous system Gene Therapy 1998 5: 712–717

    Article  CAS  PubMed  Google Scholar 

  24. Coll JL et al. In vivo delivery to tumors of DNA complexed with linear polyethylenimine Hum Gene Ther 1999 10: 1659–1666

    Article  CAS  PubMed  Google Scholar 

  25. Goula D et al. Polyethylenimine-based intravenous delivery of transgenes to mouse lung Gene Therapy 1998 5: 1291–1295

    Article  CAS  PubMed  Google Scholar 

  26. Bragonzi A et al. Comparison between cationic polymers and lipids in mediating systemic gene delivery to the lungs Gene Therapy 1999 6: 1995–2004

    Article  CAS  PubMed  Google Scholar 

  27. Zou SM, Erbacher P, Remy JS, Behr JP . Systemic linear polyethylenimine (L-PEI)-mediated gene delivery in the mouse J Gene Med 2000 2: 128–134

    Article  CAS  PubMed  Google Scholar 

  28. Chemin I et al. Liver-directed gene transfer: a linear polyethlenimine derivative mediates highly efficient DNA delivery to primary hepatocytes in vitro and in vivo J Viral Hepat 1998 5: 369–375

    Article  CAS  PubMed  Google Scholar 

  29. Namiki Y, Takahashi T, Ohno T . Gene transduction for disseminated intraperitoneal tumor using cationic liposomes containing non-histone chromatin proteins: cationic liposomal gene therapy of carcinomatosa Gene Therapy 1998 5: 240–246

    Article  CAS  PubMed  Google Scholar 

  30. Kikuchi A et al. Development of novel cationic liposomes for efficient gene transfer into peritoneal disseminated tumor Hum Gene Ther 1999 10: 947–955

    Article  CAS  PubMed  Google Scholar 

  31. Hug P, Sleight RG . Liposomes for the transformation of eukaryotic cells Biochim Biophys Acta 1991 1097: 1–17

    Article  CAS  PubMed  Google Scholar 

  32. Kiyasu Y, Kaneshima S, Koga S . Morphogenesis of peritoneal metastasis in human gastric cancer Cancer Res 1981 41: 1236–1239

    CAS  PubMed  Google Scholar 

  33. Niedbala MJ, Crickard K, Bernacki RJ . Interaction of human ovarian tumor cells with human mesothelial cells grown on extracellular matrix Exp Cell Res 1985 160: 499–513

    Article  CAS  PubMed  Google Scholar 

  34. Shi Y, Fard A, Vermani P, Zalewski A . Transgene expression in the coronary circulation: transcatheter gene delivery Gene Therapy 1994 1: 408–414

    CAS  PubMed  Google Scholar 

  35. Takeshita S et al. Increased gene expression after liposome-mediated arterial gene transfer associated with intimal smooth muscle cell proliferation. In vitro and in vivo findings in a rabbit model of vascular injury J Clin Invest 1994 93: 652–661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Labat-Moleur F et al. An electron microscopy study into the mechanism of gene transfer with lipopolyamines Gene Therapy 1996 3: 1010–1017

    CAS  PubMed  Google Scholar 

  37. Wilke M et al. Efficacy of a peptide-based gene delivery system depends on mitotic activity Gene Therapy 1996 3: 1133–1142

    CAS  PubMed  Google Scholar 

  38. Miyazaki J et al. Expression vector system based on the chicken beta-actin promoter directs efficient production of interleukin-5 Gene 1989 79: 269–277

    Article  CAS  PubMed  Google Scholar 

  39. Niwa H, Yamamura K, Miyazaki J . Efficient selection for high-expression transfectants with a novel eukaryotic vector Gene 1991 108: 193–199

    Article  CAS  PubMed  Google Scholar 

  40. Yanagi K, Onda M, Uchida E . Effect of angiostatin on liver metastasis of pancreatic cancer in hamsters Jpn J Cancer Res 2000 91: 723–730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Dr Jun-ichi Miyazaki for providing vector pCAGGS, and Miss Kimiko Yoshida for her technical help. This work was supported in part by a grant-in-aid for the 2nd Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health and Welfare of Japan, by grants-in-aid for Cancer Research from the Ministry of Health and Welfare of Japan and from the Ministry of Education, Science, Sports and Culture of Japan. S Furuhata and K Hatanaka are awardees of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research.

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Authors and Affiliations

  1. Section for Studies on Host–Immune Response, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan

    K Aoki

  2. Genetics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan

    S Furuhata, K Hatanaka, M Terada & T Yoshida

  3. Experimental Pathology and Chemotherapy Division, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan

    M Maeda

  4. Laboratoire de Chimie Genetique, URA 1386, Faculté de Pharmacie, Universite Louis Pasteur, Strasbourg, France

    J S Remy & J-P Behr

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  1. K Aoki
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  2. S Furuhata
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  3. K Hatanaka
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  4. M Maeda
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  5. J S Remy
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  6. J-P Behr
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  8. T Yoshida
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Aoki, K., Furuhata, S., Hatanaka, K. et al. Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity. Gene Ther 8, 508–514 (2001). https://doi.org/10.1038/sj.gt.3301435

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