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原肌球蛋白相关激酶 B 可能是恶性胸腺瘤预后的生物标志物和治疗靶点。

Tropomyosin-related Kinase B Is Potentially a Biomarker of Prognosis and Therapeutic Target for Malignant Thymic Epithelial Tumors.

机构信息

Department of Anatomic Pathology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.

Department of Surgery and Oncology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.

出版信息

Anticancer Res. 2022 Aug;42(8):3779-3787. doi: 10.21873/anticanres.15868.

Abstract

BACKGROUND/AIM: Thymic epithelial tumors (TETs) mainly consist of thymoma and thymic carcinoma. Complete surgical resection is vital for the successful management of these TETs, and adjuvant therapy such as systematic chemotherapy and/or radiotherapy plays important roles in the management of recurrent or metastasized disease. However, there is still a lack of a standard treatment after the failure of these adjuvant therapies. There is thus a need to develop molecular targeted therapies for advanced malignant TETs. In the present study, we evaluated the biological significance of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling for TETs.

MATERIALS AND METHODS

The expression of TrkB in 48 formalin-fixed, paraffin-embedded TET specimens (43 thymoma and 5 thymic carcinoma) collected by surgical resection was evaluated immunohistochemically. A thymic carcinoma cell line was evaluated for the role of BDNF/TrkB signaling pathway in an in vitro assay.

RESULTS

High TrkB expression was related to significantly poor prognosis in patients with TETs. In vitro experiments showed that BDNF/TrkB signaling was involved in the proliferation of Ty-82 cells, but not their invasion and migration.

CONCLUSION

TrkB expression is a biomarker of the prognosis for TETs and the BDNF/TrkB signaling pathway is potentially a new therapeutic target for mTETs.

摘要

背景/目的:胸腺瘤上皮肿瘤(TETs)主要包括胸腺瘤和胸腺癌。完全手术切除对于这些 TETs 的成功治疗至关重要,辅助治疗如系统化疗和/或放疗在复发性或转移性疾病的治疗中发挥重要作用。然而,在这些辅助治疗失败后,仍然缺乏标准的治疗方法。因此,需要为晚期恶性 TETs 开发分子靶向治疗方法。在本研究中,我们评估了脑源性神经营养因子(BDNF)/原肌球蛋白受体激酶 B(TrkB)信号对 TETs 的生物学意义。

材料和方法

通过手术切除收集了 48 例福尔马林固定、石蜡包埋的 TET 标本(43 例胸腺瘤和 5 例胸腺癌),并通过免疫组织化学评估了 TrkB 在其中的表达。在体外实验中评估了 BDNF/TrkB 信号通路在 Ty-82 细胞系中的作用。

结果

高 TrkB 表达与 TET 患者的预后显著相关。体外实验表明,BDNF/TrkB 信号参与了 Ty-82 细胞的增殖,但不参与其侵袭和迁移。

结论

TrkB 表达是 TETs 预后的生物标志物,BDNF/TrkB 信号通路可能是 mTETs 的新治疗靶点。

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