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Fluorescence-guided assessment of bone and soft-tissue sarcomas for predicting the efficacy of telomerase-specific oncolytic adenovirus.
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- المؤلفون: Uotani, Koji1 (AUTHOR); Tazawa, Hiroshi2,3 (AUTHOR) ; Hasei, Joe1 (AUTHOR); Fujiwara, Tomohiro1 (AUTHOR); Yoshida, Aki1 (AUTHOR); Yamakawa, Yasuaki1 (AUTHOR); Omori, Toshinori1 (AUTHOR); Sugiu, Kazuhisa1 (AUTHOR); Komatsubara, Tadashi1 (AUTHOR); Kondo, Hiroya1 (AUTHOR); Morita, Takuya1 (AUTHOR); Kiyono, Masahiro1 (AUTHOR); Yokoo, Suguru1 (AUTHOR); Hata, Toshiaki1 (AUTHOR); Kunisada, Toshiyuki1,4 (AUTHOR); Takeda, Ken1 (AUTHOR); Urata, Yasuo5 (AUTHOR); Fujiwara, Toshiyoshi3 (AUTHOR); Ozaki, Toshifumi1 (AUTHOR)
- المصدر:
PLoS ONE. 2/20/2024, Vol. 19 Issue 2, p1-15. 15p.
- الموضوع:
- معلومة اضافية
- نبذة مختصرة :
Bone and soft-tissue sarcomas are rare malignancies with histological diversity and tumor heterogeneity, leading to the lack of a common molecular target. Telomerase is a key enzyme for keeping the telomere length and human telomerase reverse transcriptase (hTERT) expression is often activated in most human cancers, including bone and soft-tissue sarcomas. For targeting of telomerase-positive tumor cells, we developed OBP-301, a telomerase-specific replication-competent oncolytic adenovirus, in which the hTERT promoter regulates adenoviral E1 gene for tumor-specific viral replication. In this study, we present the diagnostic potential of green fluorescent protein (GFP)-expressing oncolytic adenovirus OBP-401 for assessing virotherapy sensitivity using bone and soft-tissue sarcomas. OBP-401-mediated GFP expression was significantly associated with the therapeutic efficacy of OBP-401 in human bone and soft-tissue sarcomas. In the tumor specimens from 68 patients, malignant and intermediate tumors demonstrated significantly higher expression levels of coxsackie and adenovirus receptor (CAR) and hTERT than benign tumors. OBP-401-mediated GFP expression was significantly increased in malignant and intermediate tumors with high expression levels of CAR and hTERT between 24 and 48 h after infection. Our results suggest that the OBP-401-based GFP expression system is a useful tool for predicting the therapeutic efficacy of oncolytic virotherapy on bone and soft-tissue sarcomas. [ABSTRACT FROM AUTHOR]
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