【摘要】：背景：上尿路移行上皮癌術(shù)后膀胱及對(duì)側(cè)上尿路腫瘤的發(fā)生鮮有報(bào)道，就目前的研究看，對(duì)于此現(xiàn)象的文獻(xiàn)因素尚未確定。此外，一些病例報(bào)道描述了復(fù)發(fā)腫瘤及對(duì)側(cè)腫瘤的特點(diǎn)，以及兩者之間的聯(lián)系。 方法：對(duì)大連醫(yī)科大學(xué)附屬二院近10年來882例移行上皮癌的原始文件進(jìn)行整理，剔除原發(fā)膀胱腫瘤及遠(yuǎn)處轉(zhuǎn)移，對(duì)112例的11個(gè)變量進(jìn)行多因素分析，確定上尿路移行上皮癌的復(fù)發(fā)因素。 結(jié)果：一側(cè)上尿路移行上皮癌術(shù)后，膀胱和對(duì)側(cè)上尿路腫瘤的再發(fā)率分別是31.2％和5.8％。上尿路多發(fā)腫瘤是其術(shù)后再發(fā)膀胱癌的危險(xiǎn)因素，合并膀胱腫瘤及腎功不全是對(duì)側(cè)上尿路移行上皮癌再發(fā)腫瘤的危險(xiǎn)因素。再發(fā)的膀胱腫瘤和對(duì)側(cè)上尿路腫瘤在復(fù)發(fā)的時(shí)間和腫瘤的分期上有明顯的區(qū)別。 結(jié)論：對(duì)原發(fā)性上尿路移行上皮癌的患者定期行膀胱鏡檢查是必要的，對(duì)具有復(fù)發(fā)對(duì)側(cè)上尿路腫瘤高危因素的患者在行膀胱鏡檢查的同時(shí)，應(yīng)施行靜脈尿路造影（IVU）或CT尿路造影（CTU）。 葡萄糖合酶激酶3β（Glycogen synthase kinase3β,GSK3β）是一個(gè)牽涉到多個(gè)生物進(jìn)程，，特別是胰島素通路及Wnt通路中的多功能絲/蘇氨酸激酶，同樣GSK3β可以被蛋白激酶B(protein kinase B,PKB)磷酸化。對(duì)于GSK3β的氮端Arg4和Arg6突變?yōu)楸彼釙?huì)明顯的削弱Ser9的自磷酸化。盡管這樣的實(shí)驗(yàn)結(jié)果已經(jīng)在前期報(bào)道過，在分子水平具體的自抑制機(jī)理并未完全清楚。在我們的研究中，Arg4和Arg6突變?yōu)楸彼釙?huì)明顯的削弱PKB和GSK3β之間的親和力，與野生型相比，突變導(dǎo)致了在原子水平的損失是有意義的。我們從四個(gè)方面（構(gòu)象、殘基運(yùn)動(dòng)、氫鍵和結(jié)合自由能）分析了突變復(fù)合體的重要變化。突變體親和力的降低會(huì)明顯的削弱對(duì)GSK3β的磷酸化，同樣也會(huì)削弱GSK3β的自抑制。這對(duì)解釋GSK3β的自抑制機(jī)理具有相當(dāng)大的意義，或許可以應(yīng)用到2型糖尿病及腫瘤的機(jī)制研究及藥物開發(fā)中。
[Abstract]:Background: the occurrence of bladder and contralateral upper urinary tract tumors after operation of transitional epithelial carcinoma of upper urinary tract is rarely reported. According to the current study, the literature factors of this phenomenon have not been determined. In addition, some case reports describe the characteristics of recurrent tumors and contralateral tumors, as well as the relationship between them. Methods: the original files of 882 cases of transitional epithelial carcinoma in the second affiliated Hospital of Dalian Medical University in recent 10 years were sorted out, the primary bladder tumor and distant metastasis were eliminated, and 11 variables of 112 cases were analyzed by multivariate analysis. To determine the recurrence factors of transitional epithelial carcinoma of upper urinary tract. Results: after operation, the recurrence rate of bladder and contralateral upper urinary tract tumors was 31.2% and 5.8%, respectively. Multiple tumors of upper urinary tract are the risk factors of recurrent bladder cancer after operation, and bladder tumors and renal insufficiency are the risk factors of recurrent tumors of contralateral transitional epithelial carcinoma of upper urinary tract. The recurrence time and stage of recurrent bladder tumor and contralateral upper urinary tract tumor were significantly different from those of contralateral upper urinary tract tumor. Conclusion: it is necessary to perform cystoscopy regularly in patients with primary transitional epithelial carcinoma of upper urinary tract. Patients with recurrent contralateral upper urinary tract tumors are examined by cystoscopy at the same time. Intravenous urography (IVU) or CT urography (CTU). Should be performed Glucokinase 3 尾 (Glycogen synthase kinase3 尾 (GSK3 尾) is a multifunctional serine / threonine kinase involved in many biological processes, especially insulin pathway and Wnt pathway. GSK3 尾 can also be phosphorylated by protein kinase B (protein kinase B. For the nitrogen terminal Arg4 and Arg6 mutation of GSK3 尾 to alanine, the autophosphorylation of Ser9 was significantly weakened. Although such experimental results have been reported earlier, the specific self-inhibition mechanism at the molecular level is not fully understood. In our study, the mutation of Arg4 and Arg6 into alanine significantly weakens the affinity between PKB and GSK3 尾. Compared with the wild type, it is meaningful that the mutation leads to the loss at the atomic level. We analyze the important changes of the mutant complex from four aspects (conformational, residue movement, hydrogen bond and binding free energy). The decrease of affinity of mutants significantly weakened the phosphorylation of GSK3 尾 and the self-inhibition of GSK3 尾. This is of great significance to explain the autoinhibition mechanism of GSK3 尾, and may be applied to the study of the mechanism of type 2 diabetes mellitus and tumor and the development of drugs.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.1

【共引文獻(xiàn)】

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