Systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.

Clinical trials have confirmed the safety of selectively oncolytic adenoviruses for treatment of advanced cancers. However, increasingly effective viruses could result in more toxicity and therefore it would be useful if replication could be abrogated if necessary. We analyzed viruses containing the...

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Autores principales:	Anna Kanerva, Sergio Lavilla-Alonso, Mari Raki, Lotta Kangasniemi, Gerd J Bauerschmitz, Koichi Takayama, Ari Ristimäki, Renee A Desmond, Akseli Hemminki
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7fb6106d4cef4be68550981943378884
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spelling	oai:doaj.org-article:7fb6106d4cef4be685509819433788842021-11-25T06:11:13ZSystemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.1932-620310.1371/journal.pone.0002917https://doaj.org/article/7fb6106d4cef4be685509819433788842008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18698374/?tool=EBIhttps://doaj.org/toc/1932-6203Clinical trials have confirmed the safety of selectively oncolytic adenoviruses for treatment of advanced cancers. However, increasingly effective viruses could result in more toxicity and therefore it would be useful if replication could be abrogated if necessary. We analyzed viruses containing the cyclooxygenase-2 (Cox-2) or vascular endothelial growth factor (VEGF) promoter for controlling replication. Anti-inflammatory agents can lower Cox-2 protein levels and therefore we hypothesized that also the promoter might be affected. As Cox-2 modulates expression of VEGF, also the VEGF promoter might be controllable. First, we evaluated the effect of anti-inflammatory agents on promoter activity or adenovirus infectivity in vitro. Further, we analyzed the oncolytic potency of the viruses in vitro and in vivo with and without the reagents. Moreover, the effect of on virus replication was analyzed. We found that RGD-4C or Ad5/3 modified fibers improved the oncolytic potency of the viruses in vitro and in vivo. We found that both promoters could be downregulated with dexamethasone, sodium salicylate, or salicylic acid. Oncolytic efficacy correlated with the promoter activity and in vitro virus production could be abrogated with the substances. In vivo, we saw good therapeutic efficacy of the viruses in a model of intravenous therapy of metastatic cervical cancer, but the inhibitory effect of dexamethasone was not strong enough to provide significant differences in a complex in vivo environment. Our results suggest that anti-inflammatory drugs may affect the replication of adenovirus, which might be relevant in case of replication associated side effects.Anna KanervaSergio Lavilla-AlonsoMari RakiLotta KangasniemiGerd J BauerschmitzKoichi TakayamaAri RistimäkiRenee A DesmondAkseli HemminkiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 8, p e2917 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna Kanerva Sergio Lavilla-Alonso Mari Raki Lotta Kangasniemi Gerd J Bauerschmitz Koichi Takayama Ari Ristimäki Renee A Desmond Akseli Hemminki Systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.
description	Clinical trials have confirmed the safety of selectively oncolytic adenoviruses for treatment of advanced cancers. However, increasingly effective viruses could result in more toxicity and therefore it would be useful if replication could be abrogated if necessary. We analyzed viruses containing the cyclooxygenase-2 (Cox-2) or vascular endothelial growth factor (VEGF) promoter for controlling replication. Anti-inflammatory agents can lower Cox-2 protein levels and therefore we hypothesized that also the promoter might be affected. As Cox-2 modulates expression of VEGF, also the VEGF promoter might be controllable. First, we evaluated the effect of anti-inflammatory agents on promoter activity or adenovirus infectivity in vitro. Further, we analyzed the oncolytic potency of the viruses in vitro and in vivo with and without the reagents. Moreover, the effect of on virus replication was analyzed. We found that RGD-4C or Ad5/3 modified fibers improved the oncolytic potency of the viruses in vitro and in vivo. We found that both promoters could be downregulated with dexamethasone, sodium salicylate, or salicylic acid. Oncolytic efficacy correlated with the promoter activity and in vitro virus production could be abrogated with the substances. In vivo, we saw good therapeutic efficacy of the viruses in a model of intravenous therapy of metastatic cervical cancer, but the inhibitory effect of dexamethasone was not strong enough to provide significant differences in a complex in vivo environment. Our results suggest that anti-inflammatory drugs may affect the replication of adenovirus, which might be relevant in case of replication associated side effects.
format	article
author	Anna Kanerva Sergio Lavilla-Alonso Mari Raki Lotta Kangasniemi Gerd J Bauerschmitz Koichi Takayama Ari Ristimäki Renee A Desmond Akseli Hemminki
author_facet	Anna Kanerva Sergio Lavilla-Alonso Mari Raki Lotta Kangasniemi Gerd J Bauerschmitz Koichi Takayama Ari Ristimäki Renee A Desmond Akseli Hemminki
author_sort	Anna Kanerva
title	Systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.
title_short	Systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.
title_full	Systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.
title_fullStr	Systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.
title_full_unstemmed	Systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.
title_sort	systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/7fb6106d4cef4be68550981943378884
work_keys_str_mv	AT annakanerva systemictherapyforcervicalcancerwithpotentiallyregulatableoncolyticadenoviruses AT sergiolavillaalonso systemictherapyforcervicalcancerwithpotentiallyregulatableoncolyticadenoviruses AT mariraki systemictherapyforcervicalcancerwithpotentiallyregulatableoncolyticadenoviruses AT lottakangasniemi systemictherapyforcervicalcancerwithpotentiallyregulatableoncolyticadenoviruses AT gerdjbauerschmitz systemictherapyforcervicalcancerwithpotentiallyregulatableoncolyticadenoviruses AT koichitakayama systemictherapyforcervicalcancerwithpotentiallyregulatableoncolyticadenoviruses AT ariristimaki systemictherapyforcervicalcancerwithpotentiallyregulatableoncolyticadenoviruses AT reneeadesmond systemictherapyforcervicalcancerwithpotentiallyregulatableoncolyticadenoviruses AT akselihemminki systemictherapyforcervicalcancerwithpotentiallyregulatableoncolyticadenoviruses
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Systemic therapy for cervical cancer with potentially regulatable oncolytic adenoviruses.

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