An oncolytic virus as a promising candidate for the treatment of radioresistant oral squamous cell carcinoma.

An oncolytic virus as a promising candidate for the treatment of radioresistant oral squamous cell carcinoma.
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溶瘤病毒是治疗辐射耐药性口服鳞状细胞癌的有前途的候选者。

DOI:
10.1016/j.omto.2022.10.001
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发表时间:
2022-12-15
期刊:
MOLECULAR THERAPY ONCOLYTICS
影响因子:
--
通讯作者:
Nakayama, Hideki
Nakayama, Hideki
中科院分区:
其他
文献类型:
--
作者:
Gohara, Shunsuke;Shinohara, Kosuke;Yoshida, Ryoji;Kariya, Ryusho;Tazawa, Hiroshi;Hashimoto, Masashi;Inoue, Junki;Kubo, Ryuta;Nakashima, Hikaru;Arita, Hidetaka;Kawaguchi, Sho;Yamana, Keisuke;Nagao, Yuka;Iwamoto, Asuka;Sakata, Junki;Matsuoka, Yuichiro;Takeshita, Hisashi;Hirayama, Masatoshi;Kawahara, Kenta;Nagata, Masashi;Hirosue, Akiyuki;Kuwahara, Yoshikazu;Fukumoto, Manabu;Okada, Seiji;Urata, Yasuo;Fujiwara, Toshiyoshi;Nakayama, Hideki

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我们评估了一种溶瘤病毒(苏拉特腺病毒;OBP-301)对抗放射抵抗口腔鳞状细胞癌的有效性。我们证实了人端粒酶逆转录酶和柯萨奇病毒和腺病毒受体在细胞系中的表达。此外,我们还检查了一名接受了OBP-301治疗的现有疗法的患者的潜在存在。我们评估了:(1)OBP-301单独和联合放射治疗对放射抵抗细胞株的抗肿瘤作用;(2)联合治疗增加放射增敏效应和细胞死亡的分子机制;(3)体内异种移植模型(小鼠放射抵抗细胞系来源的异种移植和患者来源的异种移植)联合治疗的抗肿瘤作用。人端粒酶逆转录酶、柯萨奇病毒和腺病毒受体在所有细胞系中均有表达。OBP-301以浓度依赖的方式抑制这些细胞株的增殖活性,并显著增强辐射的抗肿瘤作用。经OBP-301处理后,与细胞凋亡和自噬相关的磷酸化STAT3及其下游分子的表达发生了显著变化。在两种异种移植模型中,联合治疗与单纯放射治疗相比具有显著的抗肿瘤效果。OBP-301联合放射治疗具有协同作用,有望成为治疗口腔鳞状细胞癌的有效方案。放射抵抗是口腔鳞状细胞癌(OSCC)需要克服的挑战之一。在这项研究中,我们发现一种肿瘤溶解病毒OP-301对克服口腔鳞癌细胞的辐射抵抗是有用的。这项研究的结果可能会导致抗辐射口腔鳞癌的新疗法的发展。
We evaluated the usefulness of an oncolytic virus (Suratadenoturev; OBP-301) against radioresistant oral squamous cell carcinoma. We confirmed the expression of human telomerase reverse transcriptase and the coxsackievirus and adenovirus receptor in cell lines. Also, we examined the potential presence in a patient who has received existing therapy that is amenable to treatment with OBP-301. We evaluated: (1) the antitumor effects of OBP-301 alone and in combination with radiotherapy on radioresistant cell lines, (2) the molecular mechanism underlying the radiosensitizing effect and cell death increased by the combination therapy, and (3) the antitumor effect of the combination therapy in vivo using xenograft models (a radioresistant cell line-derived xenograft in mouse and a patient-derived xenograft). Human telomerase reverse transcriptase and the coxsackievirus and adenovirus receptor were expressed in all cell lines. OBP-301 decreased the proliferative activity of these cell lines in a concentration-dependent manner, and significantly enhanced the antitumor effect of irradiation. Phosphorylated STAT3 and its downstream molecules, which correlated with apoptosis and autophagy, showed significant changes in expression after treatment with OBP-301. The combination therapy exerted a significant antitumor effect versus radiotherapy alone in both xenograft models. Combination of OBP-301 with radiotherapy exerts a synergistic effect and may represent a promising treatment for radioresistant oral squamous cell carcinoma. Radioresistance is one challenge to overcome in oral squamous cell carcinoma (OSCC). In this study, we found that a tumor-lysing virus, OP-301, is useful for overcoming radioresistance in OSCC cells. The results of this study may lead to the development of new therapies for radioresistant OSCC.
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