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A GSDMB enhancer-driven HSV thymidine kinase-expressing vector for controlling occult peritoneal dissemination of gastric cancer cells.

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  • Additional Information
    • Source:
      Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : BioMed Central, [2001-
    • Subject Terms:
      Genetic Therapy*; Neoplasm Proteins/*genetics ; Peritoneal Neoplasms/*therapy ; Stomach Neoplasms/*therapy ; Thymidine Kinase/*genetics; Animals ; Genetic Vectors/therapeutic use ; Humans ; Mice ; Peritoneal Cavity/pathology ; Peritoneal Neoplasms/genetics ; Peritoneal Neoplasms/pathology ; Peritoneum/pathology ; Primary Cell Culture ; Promoter Regions, Genetic/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Simplexvirus/enzymology ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Thymidine Kinase/biosynthesis
    • Abstract:
      Background: Gastric cancer (GC) is one of the major malignant diseases worldwide, especially in Asia, and Japan and Korea have the highest incidence in the world. Because most of the cases that are refractory to therapies die due to peritoneal dissemination (PD) of the cancer cells, controlling PD is important for patient survival. GSDMB is a member of the gasdermin gene family. Because GSDMB is expressed in many types of cancer, including GC, it is likely that the gene contains a regulatory region that is utilized for therapy of occult PD through cancer cell-specific expression of cytotoxic genes.
      Methods: We performed reporter assays to identify the regulatory region for the cancer cell-specific expression. We also constructed a lentiviral therapeutic vector that expresses herpes simplex virus thymidine kinase (HSVtk) in a GC cell-specific manner, and tested it in a mouse model of PD.
      Results: We identified the regulatory region at +496 to +989 from the GSDMB transcription start site and designated it as a GSDMB enhancer. The lentiviral therapeutic vector suppressed proliferation of a GC cell line, 60As6, in vitro in the presence of ganciclovir, and intraperitoneal administration of the vector prolonged the survival term of mice that were intraperitoneally inoculated with 60As6 one week prior to the administration.
      Conclusions: The GSDMB-driven HSVtk expression vector had a therapeutic effect on the occult PD model mice. This strategy can potentially be used to treat GC patients with PD.
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    • Accession Number:
      0 (GSDMB protein, human)
      0 (Neoplasm Proteins)
      EC 2.7.1.21 (Thymidine Kinase)
    • Publication Date:
      Date Created: 20150529 Date Completed: 20160125 Latest Revision: 20181113
    • Publication Date:
      20250114
    • Accession Number:
      PMC4446855
    • Accession Number:
      10.1186/s12885-015-1436-1
    • Accession Number:
      26016667