HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Increased sensitivity of glioma cells to 5-fluorocytosine following photo-chemical internalization enhanced nonviral transfection of the cytosine deaminase suicide gene.

Abstract
Despite advances in surgery, chemotherapy and radiotherapy, the outcomes of patients with GBM have not significantly improved. Tumor recurrence in the resection margins occurs in more than 80% of cases indicating aggressive treatment modalities, such as gene therapy are warranted. We have examined photochemical internalization (PCI) as a method for the non-viral transfection of the cytosine deaminase (CD) suicide gene into glioma cells. The CD gene encodes an enzyme that can convert the nontoxic antifungal agent, 5-fluorocytosine, into the chemotherapeutic drug, 5-fluorouracil. Multicell tumor spheroids derived from established rat and human glioma cell lines were used as in vitro tumor models. Plasmids containing either the CD gene alone or together with the uracil phosphoribosyl transferase (UPRT) gene combined with the gene carrier protamine sulfate were employed in all experiments.PCI was performed with the photosensitizer AlPcS2a and 670 nm laser irradiance. Protamine sulfate/CD DNA polyplexes proved nontoxic but inefficient transfection agents due to endosomal entrapment. In contrast, PCI mediated CD gene transfection resulted in a significant inhibition of spheroid growth in the presence of, but not in the absence of, 5-FC. Repetitive PCI induced transfection was more efficient at low CD plasmid concentration than single treatment. The results clearly indicate that AlPcS2a-mediated PCI can be used to enhance transfection of a tumor suicide gene such as CD, in malignant glioma cells and cells transfected with both the CD and UPRT genes had a pronounced bystander effect.
AuthorsFrederick Wang, Genesis Zamora, Chung-Ho Sun, Anthony Trinidad, Changho Chun, Young Jik Kwon, Kristian Berg, Steen J Madsen, Henry Hirschberg
JournalJournal of neuro-oncology (J Neurooncol) Vol. 118 Issue 1 Pg. 29-37 (May 2014) ISSN: 1573-7373 [Electronic] United States
PMID24610460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antifungal Agents
  • Indoles
  • Organometallic Compounds
  • Photosensitizing Agents
  • aluminum phthalocyanine disulfonate
  • Flucytosine
  • Pentosyltransferases
  • uracil phosphoribosyltransferase
  • Cytosine Deaminase
Topics
  • Antifungal Agents (pharmacology)
  • Cell Line, Tumor (drug effects)
  • Cytosine Deaminase (genetics, metabolism)
  • Dose-Response Relationship, Drug
  • Flucytosine (pharmacology)
  • Glioma (pathology)
  • Humans
  • Indoles (pharmacology)
  • Organometallic Compounds (pharmacology)
  • Pentosyltransferases (genetics, metabolism)
  • Photochemical Processes (drug effects)
  • Photosensitizing Agents (pharmacology)
  • Transfection

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: