Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/12792
標題: mTOR信號傳遞路徑在犬貓軟組織及骨頭肉瘤的表現
The mammalian target of rapamycin (mTOR) signaling pathway in canine and feline soft tissue and bone sarcomas
作者: 蕭慧貞
Hsiao, Hui-Chen
關鍵字: mTOR
mTOR
canine
feline
soft tissue sarcomas
bone sarcomas


軟組織肉瘤
骨肉瘤
出版社: 獸醫學系暨研究所
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摘要: 犬貓軟組織及骨頭來源肉瘤是具有高度侵犯性,高復發性及低至中度轉移潛力的腫瘤。由於其侵犯能力,此類腫瘤最常面臨的問題為手術治療後的復發。而對於重症或是已轉移的病例目前未有有效的治療方式。此外,已有報告指出PI3K-Akt-mTOR信號傳遞路徑的破壞與肉瘤的形成有關。因此,阻斷此路徑可望成為治療肉瘤的方法。在人醫方面,以mTOR抑制劑治療已轉移的肉瘤病患已有相當不錯的成效。本實驗的研究目的為調查mTOR信號傳遞路徑分子在犬貓軟組織及骨頭來源肉瘤中的表現。實驗對象及方法為25個肉瘤組織以西方免疫墨點法偵測內源性及磷酸化Akt、mTOR及S6K的蛋白表現;59個腫瘤組織以免疫組織化學染色法調查路徑中蛋白質表現的位置及強度。結果顯示,Akt-mTOR-S6K路徑蛋白質常在犬貓肉瘤中表現並呈現活化態。犬肉瘤中mTOR的表現與初診轉移相關並且mTOR,S6K及p-S6K的強表現和初診轉移相關。p-mTOR的強表現和第三級貓注射部位肉瘤相關。由以上結果可以得知,在犬貓肉瘤治療選擇中,mTOR路徑的表現具有極大的潛力,但需要更多臨床的試驗及研究來證實此路徑在犬貓軟組織及骨頭肉瘤治療的應用。
Canine and feline soft tissue and bone origin sarcomas have highly invasive ability with high rate of recurrence and low to moderate metastatic potentiality. Owing to their invasiveness, the most common problem is the recurrence after conservative surgical treatment. Nevertheless, it is rarely curable and few treatments that are efficacious in advanced or metastatic sarcomas. In addition, it is reported that in various sarcomas, disruptions in phosphatidylinositaol 3-kinase (PI3K)-Akt-mTOR signaling pathway are associated with malignant transformation. Therefore, the blockade of this pathway represents an emerging target for therapy of sarcomas. It has demonstrated that mTOR inhibitors showed promising outcome in patients with metastatic sarcomas (Vemulapalli et al., 2011). The objective of our study is to investigate activation of mTOR signaling pathway in canine and feline soft tissue and bone origin sarcomas. In immunoblotting, 25 sarcomas were used to assess the expression of endogenous and phosphorylated Akt, mTOR, and S6K. The immunohistochemical (IHC) staining was performed in 59 tumors to aid investigating in localization and intensity of each component in the pathway. Results indicated Akt/mTOR/S6K pathway proteins were frequently expressed and activated in canine and feline sarcomas. The expression of mTOR may play a role in metastasis. Strong staining intensities of mTOR, p-S6K, and S6K were correlated with first admittance metastasis in canine sarcomas. Strong staining intensity of p-mTOR was related to grade III FISS. Further researches were needed for elucidating the complexity of mechanism. The results above have presented a promising potential of mTOR pathway proteins in canine and feline sarcomas, and opened an exciting avenue for further clinical and translational studies that will hopefully to reach the best efficacy in the treatment of canine and feline soft tissue and bone origin sarcomas.
URI: http://hdl.handle.net/11455/12792
其他識別: U0005-0401201216481400
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