Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/14474
標題: 犬圓形細胞瘤之P-glycoprotein表現
P-glycoprotein expression in canine round cell tumors
作者: 許峰旗
Hsu, Feng-Chi
關鍵字: 犬圓形細胞瘤
P-glycoprotein
化療抗性
免疫組織化學染色
Round cell tumors
MDR1 gene
Drug resistance
Immunohistochemical staining
出版社: 獸醫學系暨研究所
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摘要: P-glycoprotein (P-gp) 屬於ATP-binding cassette (ABC) 的一員,於細胞中扮演排除生理代謝物、毒物及藥物的角色,在腫瘤細胞中,藉由P-gp降低細胞內藥物濃度來達到限制化學治療藥物作用於反應位,因此腫瘤細胞過度表現P-gp被視為與化學治療抗性有相關。免疫組織化學染色法與免疫反應計分系統主要用於評估P-gp於腫瘤細胞的表現;將腫瘤組織以全RNA萃取後,以RT-PCR將1054-bp MDR1基因產物增幅進行定序。結果,傳染性花柳性腫瘤中95% (19/10) P-gp為陽性,其中75%為強染色性、20%為弱染色性;在肥大細胞瘤中染色性為陰性占40例中的16例(40%),弱染色性與強染色性分別占25%及35%;所有的皮膚型淋巴瘤與93.9%多中心型淋巴瘤(31/33)為陰性,只有兩例多中心型淋巴瘤(6.1%)為弱染色性;大部分的髓外漿細胞瘤(93.3%)和所有的組織細胞瘤皆為陰性,只有一例(6.5%)髓外漿細胞瘤為弱染色性;進行定序的組織當中未發現MDR1基因序列異常。總結,犬圓形細胞瘤中,P-gp不是唯一與化學療法抗性有關之因子,抑或部分犬圓形細胞瘤中P-gp調控基因MDR1可能發生突變。
P-Glycoprotein (P-gp) is one of the ATP-binding cassette superfamily which plays a role as efflux pump for secreting physiological metabolites, toxicants, and drugs. In tumor cells, P-gp decreases intracellular drug concentrations, thereby limiting access of chemotherapeutic substrates to the site of action. Overexpression of P-gp in cancers was suggested to be resistant to chemotherapy. To evaluate P-gp protein expression in canine round cell tumors, the immunohistochemical staining and immunoreactive score system were used in this study. Partial tumor tissues were sequenced for MDR1 gene followed by total RNA extraction, reverse transcription polymerase chain reaction (RT-PCR). Results showed that the positive expression was found in 95% (19/20) of transmissible venereal tumors; among them 75% was strong and 20% was weak. The negative immune-staining was found in 16 of the 40 (40%) MCTs, and the weak immune-staining and the strong immune-staining were seen in 10 of the 40 (25%) MCTs and 14 of the 40 (35%) MCTs respectively. All (100%) of the cutaneous lymphomas and 93.9% (31/33) of multicentric lymphomas showed negative immunostaining of P-gp, 2 (6.1%) of the multicertric lymphomas were revealed weak immunoreaction. Most (93.3%) of extramedullary plasmacytic tumors and all of the histiocytic tumors showed negative expression of P-gp and the remaining one (6.7%) extramedullary plasmacytic tumor showed weak immunelabelling. No MDR1 gene sequence mutation was found in round cell tumors. In conclusion, P-gp probably may not be the only one factor for chemotherapy resistance in canine round cell tumors or mutation of MDR1 gene down-regulation in cancer cells may exist in some round cell tumors.
URI: http://hdl.handle.net/11455/14474
其他識別: U0005-1707201310395700
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1707201310395700
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