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 language | English |
|---|---|
| Pages (from-to) | 6505-6514 |
| Number of pages | 10 |
| Journal | Clinical Cancer Research |
| Volume | 14 |
| Issue number | 20 |
| DOIs | |
| Publication status | Published - Oct 15 2008 |
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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 journal › Article
}
TY - JOUR
T1 - Bevacizumab increases viral distribution in human anaplastic thyroid carcinoma xenografts and enhances the effects of E1A-defective adenovirus d/922-947
AU - Libertini, Silvana
AU - Lacuzzo, Irma
AU - Perruolo, Giuseppe
AU - Scala, Stefania
AU - Leranò, Caterina
AU - Franco, Renato
AU - Hallden, Gunnel
AU - Portella, Giuseppe
PY - 2008/10/15
Y1 - 2008/10/15
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.
AB - 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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U2 - 10.1158/1078-0432.CCR-08-0200
DO - 10.1158/1078-0432.CCR-08-0200
M3 - Article
C2 - 18927290
AN - SCOPUS:58149190793
VL - 14
SP - 6505
EP - 6514
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 20
ER -