Connexin 26 enhances the bystander effect in HSVtk/GCV gene therapy for human bladder cancer by adenovirus/PLL/DNA gene delivery

Gene Therapy
M TanakaH B Grossman

Abstract

Herpes simplex thymidine kinase/ganciclovir (HSVtk/GCV) gene therapy has been used for the treatment of a variety of cancers. Its efficacy is enhanced by the bystander effect that helps overcome the delivery problems commonly observed in current gene therapy. Connexins encode proteins that produce gap junctions, which enable intercellular communication and the bystander effect. We previously demonstrated that decreased Cx 26 expression and loss of gap junctional intercellular communication were associated with human bladder cancer. To investigate the efficacy of the bystander effect in HSVtk/GCV gene therapy, the Cx 26 gene was introduced into UM-UC-3 and UM-UC-14 bladder cancer cell lines by an adenovirus poly-L-lysine conjugate using a multigenic expression plasmid that expressed both the HSVtk and Cx 26 genes. We found significantly increased cytotoxicity in HSVtk/GCV gene therapy after introduction of the HSVtk and Cx 26 genes together compared with the cytotoxicity seen after introduction of the HSVtk gene and LacZ genes in vitro and in vivo. Cytotoxicity correlated with Cx 26 expression and the induction of functional gap junctions. This study indicates that combination gene therapy with co-expression of the HSVtk and Cx ...Continue Reading

References

Jun 19, 1992·International Journal of Cancer. Journal International Du Cancer·K K WilgenbusO Traub
Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·D ZhuC C Naus
May 13, 1991·Neuroscience Letters·C C NausJ X Wilson
Mar 1, 1991·Neuron·M V BennettJ C Sáez
Oct 1, 1986·The Journal of Urology·H B GrossmanB Cox
May 1, 1993·Trends in Neurosciences·R Dermietzel, D C Spray
Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·R J CristianoS L Woo
Nov 1, 1993·Journal of Neurosurgery·D BarbaF H Gage
Mar 5, 1996·Proceedings of the National Academy of Sciences of the United States of America·M MesnilH Yamasaki
Jan 1, 1997·Journal of the National Cancer Institute·J A Roth, R J Cristiano
Jan 4, 1997·Lancet·S M FreemanA J Marrogi
Jul 1, 1997·The Journal of Urology·M S CooksonW R Fair
Apr 10, 1999·Comptes rendus de l'Académie des sciences. Série III, Sciences de la vie·H YamasakiY Omori
Apr 14, 1999·CA: a Cancer Journal for Clinicians·S H LandisP A Wingo
Aug 10, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·P MarconiJ C Glorioso

❮ Previous
Next ❯

Citations

Feb 11, 2003·The Journal of Urology·Jason GeeH Barton Grossman
Jun 12, 2013·Toxicology·Xuhui TongLiang Tao
Jun 2, 2016·Expert Opinion on Drug Delivery·Kristen L KozielskiJordan J Green
Jun 20, 2017·Biochimica Et Biophysica Acta. Biomembranes·Jérôme GilleronGeorges Pointis
Apr 13, 2013·International Journal of Molecular Sciences·Xin LiZhiwen Chen
Jun 4, 2005·Chembiochem : a European Journal of Chemical Biology·Haralabos Zorbas, Bernhard K Keppler
Dec 31, 2016·International Journal of Oncology·Paweł KoniecznyMarcin Majka

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.