本文選題：骨髓增生異常綜合癥 + 細胞株��； 參考：《浙江大學(xué)》2005年博士論文

【摘要】：骨髓增生異常綜合征(myelodysplastic syndromes,MDS)是一組起源于造血干/祖細胞的惡性克隆性疾病,以骨髓病態(tài)造血、外周血細胞減少及高風(fēng)險轉(zhuǎn)化為急性髓細胞性白血病(acute myelocytic leukaemia,AML)為主要特征。迄今MDS的發(fā)病機制不明,仍無標準有效的治療方案。因此,迫切需要尋找新的有效的治療藥物。三氧化二砷(arsenic trioxide,ATO),是目前研究的熱點之一。多年來ATO用于治療初發(fā)或復(fù)發(fā)難治性急性早幼粒細胞白血病(acute promyelocytic leukemia,APL)療效顯著;ATO治療APL至少通過兩種機制:一種是降解融合蛋白PML RARa,去除它對網(wǎng)絡(luò)信號傳導(dǎo)和誘導(dǎo)分化的負性抑制作用,另一種是誘導(dǎo)細胞凋亡。而ATO治療MDS的療效報道不一,其機制不明。沙利度胺(Thalidomide,THAL)曾經(jīng)是治療妊娠反應(yīng)的老藥,近年來由于它的免疫調(diào)節(jié)、抗炎、抗腫瘤等作用又重新用于臨床,治療多發(fā)性骨髓瘤和部分實體瘤獲得較滿意的效果。CC5013(為Thalidomide的類似物)治療MDS 5q-患者療效明顯,但其機制不清楚。研究疾病發(fā)病機理和篩選治療藥物的最好載體之一是動物模型,迄今國內(nèi)外未見有成功建立MDS動物模型的文獻報道。我們試圖通過建立人MDS荷瘤小鼠模型,以探討ATO、THAL單用及聯(lián)用治療在MDS荷瘤小鼠的體內(nèi)抗瘤作用及其機制,為臨床治療MDS病人提供新的思路和理論依據(jù)。
[Abstract]:Myelodysplastic syndrome (MDS) is a group of malignant clonal diseases originating from hematopoietic stem / progenitor cells. Myelodysplastic syndrome is characterized by morbid hematopoiesis, decreased peripheral blood cells and high risk of acute myelocytic leukemia. So far, the pathogenesis of MDS is unknown, and there is still no standard and effective treatment. Therefore, there is an urgent need to find new and effective treatment drugs. Arsenic trioxide (as _ 2O _ 3) is one of the hotspots in recent years. Over the years, ATO has been used in the treatment of acute promyelocytic leukemia (promyelocytic). The effect of ATO on acute promyelocytic leukemia (promyelocytic) is at least two mechanisms: one is to degrade the fusion protein, PML RaRaa, and to remove it from network signal transduction and induction. The negative inhibitory effect of differentiation, The other is to induce apoptosis. However, the therapeutic effect of ATO on MDS is not reported, and its mechanism is unclear. Thalidomide Thalidomide THALA was once an old drug for the treatment of pregnancy response, and has been reused in clinic in recent years due to its immunomodulation, anti-inflammatory and anti-tumor effects. Satisfactory results were obtained in the treatment of multiple myeloma and some solid tumors. CC5013 (a Thalidomide analogue) was effective in the treatment of MDS 5q- patients, but the mechanism was not clear. The animal model is one of the best carriers for studying the pathogenesis of disease and screening the drug for treatment. So far, there have been no reports on the successful establishment of MDS animal model at home and abroad. We try to establish human MDS tumor-bearing mice model to explore the anti-tumor effect and its mechanism of ATOTHAL alone and combined therapy in MDS mice, and to provide new ideas and theoretical basis for clinical treatment of MDS patients.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2005
【分類號】：R551.3;R-332

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相關(guān)期刊論文 前6條

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