Usefulness of repeated direct intratumoral gene transfer using hemagglutinating virus of Japan-liposome method for cytosine deaminase suicide gene therapy

Cancer Res. 2001 Jan 1;61(1):14-8.

Abstract

To investigate the feasibility of repeated gene transfection in suicide gene therapy against human solid tumors by a combination of 5- fluorocytosine (5-FC) and its converting enzyme, cytosine deaminase (CD), we repeatedly transfected the yeast CD gene into the human pancreatic cancer cell line BXPC3 using the hemagglutinating virus of Japan-liposome in a new gene transfer method. The in vivo growth of the s.c. transplanted BXPC3 tumor in nude mice given CD-gene transfection was significantly suppressed by i.p. injection of 5-FC when compared with tumors treated with the control vector. Furthermore, the tumor transfected with the CD gene during a 7-day interval was suppressed much more than that of a single transfection. These results suggest that repeated transfection of the suicide gene together with the combination of 5-FC and the yeast CD gene using the hemagglutinating virus of Japan-liposome gene transfer method may be useful for the treatment of human solid tumors, including pancreatic cancer.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / pharmacokinetics
  • Antimetabolites, Antineoplastic / pharmacology
  • Cell Division / drug effects
  • Cytosine Deaminase
  • Feasibility Studies
  • Female
  • Flucytosine / pharmacokinetics
  • Flucytosine / pharmacology
  • Fluorouracil / pharmacokinetics
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Humans
  • Injections, Intralesional
  • Liposomes
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nucleoside Deaminases / biosynthesis
  • Nucleoside Deaminases / genetics*
  • Nucleoside Deaminases / metabolism
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Respirovirus / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transfection
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antimetabolites, Antineoplastic
  • Liposomes
  • RNA, Messenger
  • Flucytosine
  • Nucleoside Deaminases
  • Cytosine Deaminase
  • Fluorouracil