Naslov
Combined therapy of colon carcinomas with an oncolytic adenovirus and valproic acid

Autori
Bressy, Christian ; Majhen, Dragomira ; Raddi, Najat ; Jdey, Wael ; Cornilleau, Gaetan ; Bawa, Olivia ; Opolon, Paule ; Grellier, Elodie ; Benihoud, Karim

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
ESGCT and NVGCT Collaborative Congress: The Hague - 23 to 26 October Abstracts / - : Mary Ann Liebert, Inc, 2014, A120-A120

Skup
ESGCT and NVGCT Collaborative Congress

Mjesto i datum
Den Haag, Nizozemska, 23.10.2014. - 26.10.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
oncolytic adenoviruses

Sažetak
The anti-tumor potential of oncolytic adenoviruses (CRAds) has been demonstrated in preclinical and clinical studies. While these agents failed to eradicate tumors when used as a monotherapy, they may be more effective if combined with conventional treatments such as radiotherapy or chemotherapy. This study seeks to evaluate the combination of a CRAd bearing a delta24 deletion in E1A with valproic acid (VPA), a histone deacetylase inhibitor for the treatment of human colon carcinomas. This combination led to a strong inhibition of cell growth both in vitro and in vivo compared to treatment with CRAd or VPA alone. This effect did not stem from a better CRAd replication and production in the presence of VPA. Inhibition of cell proliferation and a non-apoptotic cell death were shown to be two mechanisms mediating the effects of the combined treatment. Moreover, whereas cells treated only with CRAd displayed a polyploidy ( > 4N population), this phenotype was strongly increased in cells treated with both CRAd and VPA. In addition, the increase in polyploidy triggered by combined treatment with CRAd and VPA was associated with the enhancement of H2AX phosphorylation (cH2AX), a hallmark of DNA damage. Finally, E1 and/or viral replication were shown to play a key role in the observed effects since no enhancement of polyploidy nor increase in , H2AX were found following cell treatment with a replication-deficient Ad and VPA. Taken together, our results suggest that CRAd and VPA could be used in combination for the treatment of colon carcinomas.

Izvorni jezik
Engleski

POVEZANOST RADA