Limits...
Bystander-mediated regression of murine neuroblastoma via retroviral transfer of the HSV-TK gene.

Cho HS, Lee HR, Kim MK - J. Korean Med. Sci. (2004)

Bottom Line: A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to ganciclovir (GCV) killing.Immunohistochemical staining showed many CD4+ and CD8+ cell infiltration but did not show anti-connexin 43+ cells.In conclusion, a strong bystander effect was observed in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Hallym University College of Medicine, Seoul, Korea.

ABSTRACT
Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase (HSV-TK) gene to murine neuroblastoma cell line (neuro-2a) in vitro and in vivo, and we examined whether the mechanism of bystander effect in neuroblastoma would also depend on connexin-dependent gap junction and/or immune response. A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to ganciclovir (GCV) killing. Implanted mixtures of wildtype cells and HSV-TK transduced cells showed a potent bystander effect upon administration of GCV in A/J mice. HSV-TK/GCV system in murine neuroblastoma induced systemic immunity. Immunohistochemical staining showed many CD4+ and CD8+ cell infiltration but did not show anti-connexin 43+ cells. In conclusion, a strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma might be dependent on immune response and/or on other mechanism such as protein phosphorylation or transfer of apoptotic vesicle, rather than connexin-dependent gap junction.

Show MeSH

Related in: MedlinePlus

Expression of CD 4, CD 8 and connexin-43 antigen. Paraffin-embedded sections were reacted with goat polyclonal antibodies to CD4 (A), rabbit polyclonal antibodies to CD8 (B) and not reacted with mouse anti-connexin 43 antibody (C). (A, B) Cell membrane staining of subcutaneous tissue of the tumor-regressed site. Magnification was at ×1,000. (C) Solid area of neuroblastoma before GCV. Magnification was at ×400.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2822245&req=5

Figure 4: Expression of CD 4, CD 8 and connexin-43 antigen. Paraffin-embedded sections were reacted with goat polyclonal antibodies to CD4 (A), rabbit polyclonal antibodies to CD8 (B) and not reacted with mouse anti-connexin 43 antibody (C). (A, B) Cell membrane staining of subcutaneous tissue of the tumor-regressed site. Magnification was at ×1,000. (C) Solid area of neuroblastoma before GCV. Magnification was at ×400.

Mentions: Immunohistochemical staining showed a migration of CD4+ (Fig. 4A) and CD8+ cells into the tumor, which injected with 25% HSV-TK-positive cells and followed by GCV treatment (Fig. 4B). However, the murine neuroblastoma did not show anti-connexin 43+ cells (Fig. 4C).


Bystander-mediated regression of murine neuroblastoma via retroviral transfer of the HSV-TK gene.

Cho HS, Lee HR, Kim MK - J. Korean Med. Sci. (2004)

Expression of CD 4, CD 8 and connexin-43 antigen. Paraffin-embedded sections were reacted with goat polyclonal antibodies to CD4 (A), rabbit polyclonal antibodies to CD8 (B) and not reacted with mouse anti-connexin 43 antibody (C). (A, B) Cell membrane staining of subcutaneous tissue of the tumor-regressed site. Magnification was at ×1,000. (C) Solid area of neuroblastoma before GCV. Magnification was at ×400.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2822245&req=5

Figure 4: Expression of CD 4, CD 8 and connexin-43 antigen. Paraffin-embedded sections were reacted with goat polyclonal antibodies to CD4 (A), rabbit polyclonal antibodies to CD8 (B) and not reacted with mouse anti-connexin 43 antibody (C). (A, B) Cell membrane staining of subcutaneous tissue of the tumor-regressed site. Magnification was at ×1,000. (C) Solid area of neuroblastoma before GCV. Magnification was at ×400.
Mentions: Immunohistochemical staining showed a migration of CD4+ (Fig. 4A) and CD8+ cells into the tumor, which injected with 25% HSV-TK-positive cells and followed by GCV treatment (Fig. 4B). However, the murine neuroblastoma did not show anti-connexin 43+ cells (Fig. 4C).

Bottom Line: A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to ganciclovir (GCV) killing.Immunohistochemical staining showed many CD4+ and CD8+ cell infiltration but did not show anti-connexin 43+ cells.In conclusion, a strong bystander effect was observed in vitro and in vivo.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Hallym University College of Medicine, Seoul, Korea.

ABSTRACT
Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase (HSV-TK) gene to murine neuroblastoma cell line (neuro-2a) in vitro and in vivo, and we examined whether the mechanism of bystander effect in neuroblastoma would also depend on connexin-dependent gap junction and/or immune response. A strong bystander effect was observed in vitro, whereby nontransduced tumor cells in proximity to transduced cells acquired susceptibility to ganciclovir (GCV) killing. Implanted mixtures of wildtype cells and HSV-TK transduced cells showed a potent bystander effect upon administration of GCV in A/J mice. HSV-TK/GCV system in murine neuroblastoma induced systemic immunity. Immunohistochemical staining showed many CD4+ and CD8+ cell infiltration but did not show anti-connexin 43+ cells. In conclusion, a strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma might be dependent on immune response and/or on other mechanism such as protein phosphorylation or transfer of apoptotic vesicle, rather than connexin-dependent gap junction.

Show MeSH
Related in: MedlinePlus