本土胸腺腫瘤之臨床特徵與潛力標靶治療方向之研究

胸腺腫瘤，包括胸腺瘤與胸腺癌為發生於縱膈腔之罕見腫瘤。由於發生率較低，目前全球都較少有系統性之單中心或多中心的病例研究，關於台灣本土案例的特徵，亦缺乏大樣本數的資料；我們在臨床上觀察到，胸腺腫瘤患者的表現大相逕庭，就算擁有相同的細胞型態，往往卻也表現不同的惡性程度與預後。手術治療一直以來都是胸腺腫瘤的標準治療，完整的腫瘤切除提供了非常好的預後；然而，手術以外的輔助療法，只有手術後的放射線治療被證明確實對預後有幫助，其餘已知的化學治療、標靶治療都無法達到顯著的治療效果。為了得到更多關於這個疾病的知識，我們擬執行此病例研究，探討本土胸腺腫瘤案例的特徵。此外，我們也會從胸腺腫瘤病人組織中，探查一些參與癌化的因子之表現情形，藉以尋找可能的標靶治療方向。結合台灣大學醫學院附設醫院以及中國醫藥大學附設醫院的胸腺腫瘤患者共155 人，針對其臨床因子做分析，在分子生物研究方面，執行 RNA 之全基因陣列分析、血清之酵素免疫分析法、組織之免疫組織染色分析、組織癌化相關蛋白質表現之西方墨點分析。藉由此病例研究，我們認識了本土胸腺腫瘤病例的臨床表現特徵，可以幫助在未來找出高風險、預後較差的患者族群，提供適當的醫療與追蹤策略；並根據分子生物學的研究結果，針對 SOCS5、RON、HSP90 等治療標的於胸腺腫瘤上的特殊表現做進一步的分析，希望有朝一日，可以應用在胸腺腫瘤患者的治療上。

關鍵字

胸腺腫瘤；胸腺瘤；胸腺癌

並列摘要

Thymic epithelial tumors, including thymomas and thymic carcinomas, are rare epithelial tumors of the thymus. Adequate surgical resection is the main treatment of this tumor. However, there is no effective target therapy for thymic tumor according to previous research. Because of its rarity and low grade malignant, there are only few researches of thymus in Taiwan. In order to find out the clinical features of Taiwanese patients, and potential treatment targets, we are going to perform this study. A total of 155 patients from National Taiwan University Hospital and China Medical University Hospital are included. According to our analysis, WHO classification and Masaoka stage are still the potential predictors of survival. Residence of patients and type II DM maybe correlate with invasiveness of tumor. According to our molecular biological results, unique expression features of SOCS5, RON and HSP90 in thymic tumor tissue are detected by Western blot. Synchronous performance of EGFR and SOCS5 are found in 6 pairs of tissue. Interesting, overexpression of HSP90 in tumor part is found in 7 pairs of tissue, which has never been reported. These may be the potential therapeutic target of this disease in the future.

並列關鍵字

Thymic tumor ； thymoma ； thymic carcinoma

參考文獻

 Ahmad, U., Yao, X., Detterbeck, F., Huang, J., Antonicelli, A., Filosso, P. L., . . . Rimner, A. (2015). Thymic carcinoma outcomes and prognosis: results of an international analysis. J Thorac Cardiovasc Surg, 149(1), 95-100, 101 e101-102. doi:10.1016/j.jtcvs.2014.09.124

 Bedano, P. M., Perkins, S., Burns, M., Kessler, K., Nelson, R., Schneider, B. P., ... & Loehrer, P. J. (2008). A phase II trial of erlotinib plus bevacizumab in patients with recurrent thymoma or thymic carcinoma. . Journal of Clinical Oncology, 26(15_suppl), 19087-19087.

 Bernard, C., Frih, H., Pasquet, F., Kerever, S., Jamilloux, Y., Tronc, F., . . . Seve, P. (2016). Thymoma associated with autoimmune diseases: 85 cases and literature review. Autoimmun Rev, 15(1), 82-92. doi:10.1016/j.autrev.2015.09.005

 Chao, Y. K., Liu, Y. H., Hsieh, M. J., Wu, Y. C., Chen, T. P., Lu, M. S., . . . Liu, H. P. (2015). Long-term outcomes after thoracoscopic resection of stage I and II thymoma: a propensity-matched study. Ann Surg Oncol, 22(4), 1371-1376. doi:10.1245/s10434-014-4068-9

 Engels, E. A. (2010). Epidemiology of thymoma and associated malignancies. J Thorac Oncol, 5(10 Suppl 4), S260-265. doi:10.1097/JTO.0b013e3181f1f62d

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本土胸腺腫瘤之臨床特徵與潛力標靶治療方向之研究

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