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通过靶向宫颈癌中的卷曲同源物10(FZD10)开发钇免疫放射疗法。

Development of immune radiotherapy with yttrium by targeting Frizzled homologue 10 (FZD10) in cervical cancer.

作者信息

Okuma Yuki, Ikeda Yuji, Kobayashi Osamu, Kamata Saki, Matsuda Erina, Nakajima Takahiro, Saito Keisuke, Tomita Naoko, Nakanishi Yoko, Harada Yosuke, Chung Suyoun, Park Jae-Hyun, Masuda Shinobu, Nakamura Yusuke, Kawana Kei

机构信息

Department of Obstetrics and Gynecology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku Tokyo 173-8610, Japan.

Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi-kamimachi, Itabashi-ku Tokyo 173-8610, Japan.

出版信息

Gynecol Oncol Rep. 2025 Apr 17;59:101736. doi: 10.1016/j.gore.2025.101736. eCollection 2025 Jun.

Abstract

OBJECTIVE

Radioimmunotherapy (RIT) is a combination of the therapeutic properties of radioisotopes and specific antibodies used to eliminate tumors. Y-OTSA101 was developed by labeling Frizzled homologue 10 (FZD10) antibody with Yttrium- (Y). Because cervical cancer exhibits good radiosensitivity, the present study aimed to assess for prevalence of FZD10 in cervical cancer tissue and investigate the potential of Y-OTSA101 treatment for cervical cancer.

METHODS

The expression of FZD10 was evaluated via immunohistochemistry using formalin-fixed paraffin blocks collected from 84 patients with cervical cancer who underwent surgery. Normal cervical from 10 patients, normal ovarian tissues from 10, uterine carcinomas from 10, and uterine sarcomas from 9 were used for comparison.Mice inoculated with the SiHa cell line, which is derived from cervical squamous cell carcinoma, were used to examine the effects of Y-OTSA101.

RESULTS

The evaluation results indicated that 70 (91 %) of the cervical cancer cases expressed FZD10 more frequently than 3 (30 %), 1 (10 %), 2 (20 %), and 0 (0 %) of the normal cervix, normal ovary, uterine carcinoma, and uterine sarcoma cases, respectively. The group treated with 3.7 MBq of Y-OTSA101 demonstrated greater antitumor effects, defined as tumor shrinkage or growth suppression, than the group treated with 1.85 MBq. No significant difference in body weight was observed between the groups during the observation period.

CONCLUSIONS

FZD10 may be an appropriate target and Y-OTSA101 may have potential for the treatment of cervical cancer.

摘要

目的

放射免疫疗法(RIT)是一种将放射性同位素的治疗特性与用于消除肿瘤的特异性抗体相结合的疗法。Y-OTSA101是通过用钇(Y)标记卷曲同源物10(FZD10)抗体而开发的。由于宫颈癌具有良好的放射敏感性,本研究旨在评估FZD10在宫颈癌组织中的普遍性,并研究Y-OTSA101治疗宫颈癌的潜力。

方法

使用从84例接受手术的宫颈癌患者收集的福尔马林固定石蜡块,通过免疫组织化学评估FZD10的表达。将10例患者的正常宫颈组织、10例正常卵巢组织、10例子宫癌组织和9例子宫肉瘤组织用于比较。接种源自宫颈鳞状细胞癌的SiHa细胞系的小鼠用于研究Y-OTSA101的作用。

结果

评估结果表明,70例(91%)宫颈癌病例中FZD10的表达频率高于正常宫颈组织中的3例(30%)、正常卵巢组织中的1例(10%)、子宫癌组织中的2例(20%)和子宫肉瘤组织中的0例(0%)。与接受1.85MBq Y-OTSA101治疗的组相比,接受3.7MBq Y-OTSA101治疗的组表现出更大的抗肿瘤作用,即肿瘤缩小或生长抑制。在观察期内,两组之间的体重没有显著差异。

结论

FZD10可能是一个合适的靶点,Y-OTSA101可能具有治疗宫颈癌的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eed5/12433755/fd74bddea509/gr1.jpg

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