Bevacizumab increases viral distribution in human anaplastic thyroid carcinoma xenografts and enhances the effects of E1A-defective adenovirus d/922-947

Silvana Libertini, Irma Lacuzzo, Giuseppe Perruolo, Stefania Scala, Caterina Leranò, Renato Franco, Gunnel Hallden, Giuseppe Portella

Research output: Contribution to journalArticle

Abstract

Purpose: Anaplastic thyroidcarcinoma is a prime target for innovative therapy because it represents one of the most lethal human neoplasms andis refractory to conventional treatments such as chemotherapy andradiotherapy.We have evaluated a novel therapeutic approach based on the oncolytic replication-selective adenovirus dl 922-947. Experimental Design: The antitumor efficacies of the E1AδCR2 (dl922-947) and AE1B55K (dl1520) mutants were comparedin human thyroid anaplastic carcinoma cells in culture andin xenografts in vivo. To enhance the effects of dl922-947, anaplastic thyroidcarcinoma tumor xenografts were treatedwith dl922-947 in combination with bevacizumab. Results: We showedthat the efficacy of dl922-947 exceeded that of dl1520 in all testedana-plastic thyroidcarcinoma cells in vitro and in vivo.Furthermore, bevacizumab in combination with dl922-947 significantly reduced tumor growth compared with single treatments alone. Bevacizumab treatment significantly improvedviral distribution in neoplastic tissues. Conclusions: Our data showed that dl922-947 hada higher oncolytic activity compared with dl1520 in anaplastic thyroidcarcinoma cell lines andmight represent a better option for virother-apy of anaplastic thyroidcarcinoma. Moreover, bevacizumab increasedthe oncolytic effects of dl922-947 by enhancing viral distribution in tumors. The results described herein encourage the use of the dl922-947 virus in combination with bevacizumab.

Original languageEnglish
Pages (from-to)6505-6514
Number of pages10
JournalClinical Cancer Research
Volume14
Issue number20
DOIs
Publication statusPublished - Oct 15 2008

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Heterografts
Adenoviridae
Neoplasms
Investigational Therapies
Therapeutics
Plastics
Research Design
Cell Culture Techniques
Bevacizumab
Anaplastic Thyroid Carcinoma
Viruses
Drug Therapy
Cell Line
Growth
ONYX015

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Bevacizumab increases viral distribution in human anaplastic thyroid carcinoma xenografts and enhances the effects of E1A-defective adenovirus d/922-947. / Libertini, Silvana; Lacuzzo, Irma; Perruolo, Giuseppe; Scala, Stefania; Leranò, Caterina; Franco, Renato; Hallden, Gunnel; Portella, Giuseppe.

In: Clinical Cancer Research, Vol. 14, No. 20, 15.10.2008, p. 6505-6514.

Research output: Contribution to journalArticle

Libertini, Silvana ; Lacuzzo, Irma ; Perruolo, Giuseppe ; Scala, Stefania ; Leranò, Caterina ; Franco, Renato ; Hallden, Gunnel ; Portella, Giuseppe. / Bevacizumab increases viral distribution in human anaplastic thyroid carcinoma xenografts and enhances the effects of E1A-defective adenovirus d/922-947. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 20. pp. 6505-6514.
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AU - Libertini, Silvana

AU - Lacuzzo, Irma

AU - Perruolo, Giuseppe

AU - Scala, Stefania

AU - Leranò, Caterina

AU - Franco, Renato

AU - Hallden, Gunnel

AU - Portella, Giuseppe

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N2 - Purpose: Anaplastic thyroidcarcinoma is a prime target for innovative therapy because it represents one of the most lethal human neoplasms andis refractory to conventional treatments such as chemotherapy andradiotherapy.We have evaluated a novel therapeutic approach based on the oncolytic replication-selective adenovirus dl 922-947. Experimental Design: The antitumor efficacies of the E1AδCR2 (dl922-947) and AE1B55K (dl1520) mutants were comparedin human thyroid anaplastic carcinoma cells in culture andin xenografts in vivo. To enhance the effects of dl922-947, anaplastic thyroidcarcinoma tumor xenografts were treatedwith dl922-947 in combination with bevacizumab. Results: We showedthat the efficacy of dl922-947 exceeded that of dl1520 in all testedana-plastic thyroidcarcinoma cells in vitro and in vivo.Furthermore, bevacizumab in combination with dl922-947 significantly reduced tumor growth compared with single treatments alone. Bevacizumab treatment significantly improvedviral distribution in neoplastic tissues. Conclusions: Our data showed that dl922-947 hada higher oncolytic activity compared with dl1520 in anaplastic thyroidcarcinoma cell lines andmight represent a better option for virother-apy of anaplastic thyroidcarcinoma. Moreover, bevacizumab increasedthe oncolytic effects of dl922-947 by enhancing viral distribution in tumors. The results described herein encourage the use of the dl922-947 virus in combination with bevacizumab.

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