本文選題：RCC + 免疫組織化學(xué)　； 參考：《第四軍醫(yī)大學(xué)》2014年碩士論文

【摘要】：腎細(xì)胞癌（renal cell carcinoma，RCC）是腎臟惡性腫瘤的最常見類型。RCC對(duì)放療和化療均不敏感，早期RCC通過手術(shù)治療常能取得良好的治療效果。但是對(duì)于進(jìn)展期和晚期RCC，手術(shù)治療則效果欠佳。近年來，雖然已有多種阻斷腫瘤細(xì)胞生長(zhǎng)或血管生成的抗腫瘤藥物用于晚期RCC的治療，但其治療效果仍不夠理想，晚期RCC患者的5年生存率仍很低。 隨著對(duì)腫瘤分子機(jī)制研究的不斷深入，已有多條信號(hào)通路被證實(shí)參與了RCC的發(fā)生和發(fā)展過程。這些信號(hào)通路在正常腎臟細(xì)胞的惡性轉(zhuǎn)化，腫瘤細(xì)胞的增殖、侵襲和轉(zhuǎn)移等多種生物學(xué)過程中發(fā)揮著重要的調(diào)控作用。因此，對(duì)RCC發(fā)生發(fā)展的分子機(jī)制的研究以及針對(duì)這些信號(hào)通路的分子靶向治療藥物的研發(fā)對(duì)于晚期RCC的治療具有重要的意義。 Notch信號(hào)通路對(duì)于胚胎發(fā)育、組織自我更新、細(xì)胞干性維持、細(xì)胞增殖和凋亡等過程均有重要的調(diào)節(jié)作用。近年來，越來越多的研究證明Notch信號(hào)通路參與了多種腫瘤生物學(xué)行為的調(diào)節(jié)，，包括腫瘤細(xì)胞的增殖、分化、凋亡及基因組穩(wěn)定性等。眾多研究表明Notch1在多種腫瘤中具有促進(jìn)腫瘤或抑制腫瘤的效應(yīng)。目前，已有多個(gè)關(guān)于Notch1及Notch信號(hào)通路與RCC的研究，但是，人們對(duì)于RCC中Notch1的作用觀點(diǎn)并不一致，仍需進(jìn)一步探討和明確。 為了明確Notch信號(hào)通路在RCC中的作用，我們應(yīng)用免疫組織化學(xué)染色和Western-blot檢測(cè)了RCC臨床標(biāo)本中Notch1的表達(dá),并對(duì)其與其他臨床病理特征的相關(guān)性進(jìn)行了分析。我們還應(yīng)用Western-blot和RT-qPCR的方法檢測(cè)了Notch1和Hes1在腎細(xì)胞癌786-O細(xì)胞和腎小管上皮細(xì)胞HK-2細(xì)胞中的表達(dá)。免疫組織化學(xué)染色結(jié)果顯示Notch1在RCC腫瘤組織中的陽(yáng)性表達(dá)率明顯低于正常腎組織，其陽(yáng)性率分別為23.2%和73.2%。RT-qPCR的結(jié)果顯示RCC腫瘤組織中Notch1及其下游分子Hes1的mRNA水平較正常腎組織低。統(tǒng)計(jì)分析發(fā)現(xiàn)，晚期(AJCC III+IV)RCC中Notch1的表達(dá)顯著低于早期(AJCC I+II)RCC，并且Fuhrman III的RCC中Notch1的表達(dá)也低于Fuhrman I+II級(jí)RCC中的水平。細(xì)胞檢測(cè)結(jié)果顯示，786-O細(xì)胞中Notch1和Hes1的mRNA水平均明顯低于HK-2細(xì)胞�；谝陨蠈�(shí)驗(yàn)結(jié)果，我們認(rèn)為Notch1和Notch信號(hào)通路可能參與RCC的發(fā)生和發(fā)展，Notch1的低表達(dá)和Hes1的低轉(zhuǎn)錄水平可能提示RCC的惡性程度較高，Notch1的表達(dá)水平和Notch信號(hào)通路的活化程度可作為RCC預(yù)后判斷的一項(xiàng)指標(biāo)。
[Abstract]:Renal cell carcinoma (RCC) is the most common type of renal malignancy. RCCs are not sensitive to radiotherapy and chemotherapy. But for advanced and advanced RCCs, surgical treatment is not effective. In recent years, although many antitumor drugs have been used to block tumor cell growth or angiogenesis in the treatment of advanced RCC, the therapeutic effect is still not satisfactory. The 5-year survival rate of advanced RCC patients is still very low. With the further study of tumor molecular mechanism, several signal pathways have been proved to be involved in the occurrence and development of RCC. These signaling pathways play an important role in many biological processes, such as malignant transformation of normal renal cells, proliferation, invasion and metastasis of tumor cells. Therefore, the study of the molecular mechanism of RCC development and the development of molecular targeted therapy drugs for these signaling pathways are of great significance for the treatment of advanced RCC. The Notch signaling pathway is of great significance for embryonic development and tissue self-renewal. Cell dryness maintenance, cell proliferation and apoptosis all play an important role in regulating the process. In recent years, more and more studies have demonstrated that Notch signaling pathway plays an important role in the regulation of tumor biological behavior, including proliferation, differentiation, apoptosis and genomic stability of tumor cells. Numerous studies have shown that Notch1 has the effect of promoting tumor or inhibiting tumor in many kinds of tumors. At present, there have been many studies on Notch1 and Notch signaling pathway and RCC. However, people do not agree on the role of Notch1 in RCC, so we need to further explore and clarify the role of Notch signaling pathway in RCC. The expression of Notch1 in RCC was detected by immunohistochemistry and Western-blot, and the correlation between Notch1 and other clinicopathological features was analyzed. Western-blot and RT-qPCR were used to detect the expression of Notch1 and Hes1 in 786-O and HK-2 cells of renal cell carcinoma. The expression of Notch1 in RCC tissues was significantly lower than that in normal renal tissues. The positive rates of Notch1 and its downstream molecule Hes1 in RCC tumor tissues were 23.2% and 73.2%, respectively. RT-qPCR showed that the mRNA levels of Notch1 and its downstream molecule Hes1 in RCC were lower than those in normal renal tissues. Statistical analysis showed that the expression of Notch1 in late stage AJCC III IVCC was significantly lower than that in early stage AJCC I IIR CCS, and the expression of Notch1 in Fuhrman III RCC was lower than that in Fuhrman I II RCC. The results showed that the mRNA levels of Notch1 and Hes1 in Hes1 cells were significantly lower than those in HK-2 cells. Based on the above experimental results, We believe that Notch1 and Notch signaling pathway may be involved in the occurrence and development of RCC. The low expression of Notch1 and the low transcription level of Hes1 may suggest that the expression of Notch1 and the activation of Notch signaling pathway may be the prognosis of RCC. A measure of judgment.
【學(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R737.11

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