Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/14506
標題: 犬貓軟組織及骨頭肉瘤上皮生長因子受體信號傳遞路徑之過度表現
Overexpression of Epidermal Growth Factor Receptor Signal Pathways in Dogs and Cats with Soft Tissue and Bone Sarcomas
作者: 張汝君
Chang, Ju-Chun
關鍵字: 上皮生長因子受體信息傳遞路徑
EGFR signal pathway
犬肉瘤
貓注射部位肉瘤
canine sarcoma
FISS
出版社: 獸醫學系暨研究所
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摘要: 患有無法切除或已轉移肉瘤之犬貓,預後往往不佳。因此針對犬貓軟組織及骨頭肉瘤尋求新的或標靶治療方式,是值得研究的議題。近來多篇研究指出過度表現及活化之EGFR-Akt及EGFR-Stat3訊息傳遞路徑,與腫瘤發展及惡化密切相關。本實驗的目的是觀察EGFR-Akt及EGFR-Stat3訊息傳遞路徑蛋白在各種犬貓肉瘤中的表現及活化情形。實驗材料及方法包括101個犬肉瘤組織、12個貓注射部位肉瘤組織、37個良性腫瘤組織及22個正常組織以免疫組織化學染色法評估路徑中EGFR、Akt及Stat3蛋白的表現量、磷酸化程度及表現位置。結果顯示,纖維肉瘤、脂肪肉瘤、血管肉瘤及骨頭肉瘤中的EGFR-Akt及EGFR-Stat3訊息傳遞路徑蛋白的表現量及活化情形都顯著的比良性腫瘤(包含纖維瘤、脂肪瘤、及血管瘤) (P ≤ 0.023)及正常組織(包含膠原纖維組織、脂肪組織、微血管及骨組織)高(P ≤ 0.049)。100%貓注射部位肉瘤顯示所有的標定蛋白皆為陽性表現,除了EGFR之外,貓注射部位肉瘤的所有標定蛋白的陽性表現率皆顯著高於正常組織(P ≤ 0.029)。此外, EGFR的過度表現與較短的整體存活時間之間有顯著相關(P = 0.022),而p-Akt的強度活化則與腫瘤轉移有顯著的相關性(P = 0.004)。實驗成果闡明EGFR訊息傳遞路徑在犬肉瘤及貓注射部位肉瘤的形成中扮演著重要的角色,而EGFR的過度表現及p-Akt強活化可作為評估肉瘤患犬預後的指標。
The clinical outcome for patients with unresectable or metastatic canine and feline sarcomas is poor, so it is merited to study novel or targeted therapy of canine and feline soft tissue and bone sarcomas. Recently, several studies indicated activation of EGFR-Akt and EGFR-Stat3 signaling pathways play roles in cancer development and progression. The aim of this study is to investigate the expressions and activations of EGFR-Akt and EGFR-Stat3 signaling pathway proteins in various canine sarcomas and feline injection site sarcomas (FISS). The expression and location of endogenous and phosphorylated forms of EGFR, Akt and Stat3 in 101 canine sarcomas, 12 FISS, 37 benign tumors and 22 normal tissues were evaluated by immunohistochemical stain. Results showed that activations of EGFR-Akt and EGFR-Stat3 signal pathways in fibrosarcomas, liposarcomas, hemangiosarcomas, and bone sarcomas were significantly higher than that in benign tumors, including fibromas, lipomas and hemangiomas, and normal tissues, including fibrocollagenous tissues, adipose tissues, capillaries and bone tissues (P ≤ 0.049). 100% FISS showed positive expression of all marker proteins, and the proportion of positive expression of all proteins, except for EGFR, was significantly higher than that in normal tissues (P ≤ 0.029). Beside, overexpression of EGFR significantly associated with shorter overall survival times (P = 0.022), a significant association was shown between strong activation of p-Akt and metastasis (P = 0.004). The findings demonstrated that EGFR signal pathway played an important role in canine sarcomas and FISSs formation, and EGFR overexpression and p-Akt strong activation can be prognostic factors of dogs with sarcomas.
URI: http://hdl.handle.net/11455/14506
其他識別: U0005-1008201214225400
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1008201214225400
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