本文關(guān)鍵詞： 非小細(xì)胞肺癌 化療 血清胸苷激酶1 動(dòng)態(tài)檢測(cè)　出處：《安徽醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：背景:惡性腫瘤是指可對(duì)人類生命健康造成嚴(yán)重?fù)p害的一大類疾病。在我國(guó)乃至世界范圍內(nèi),肺癌的發(fā)病率和病死率均占所有惡性腫瘤的首位。全球每年大約有138萬(wàn)人死于肺癌,因此WHO(世界衛(wèi)生組織)將肺癌列為21世紀(jì)對(duì)人類危害最大的疾病。在肺癌的所有病理分型中,NSCLC發(fā)病率最高,約占85%以上。而且臨床研究發(fā)現(xiàn),NSCLC患者在就診時(shí)絕大部分腫瘤已發(fā)生遠(yuǎn)處轉(zhuǎn)移或進(jìn)展為晚期,同時(shí)也錯(cuò)失了外科手術(shù)治療的最佳時(shí)機(jī)。盡管近年來(lái)肺癌的各種治療方法在不斷的進(jìn)步和發(fā)展(如手術(shù)方式的改進(jìn)、靶向治療及激素受體治療的應(yīng)用),但對(duì)于晚期NSCLC患者而言,單一治療方法的療效較差,以化療為主的綜合治療方式仍然被臨床廣泛認(rèn)可和接受。肺癌又稱原發(fā)性支氣管肺癌,最先起源于支氣管粘膜、腺體或肺泡上皮,其發(fā)病原因和機(jī)制尚不清楚,多認(rèn)為與環(huán)境污染和吸煙有關(guān)。據(jù)報(bào)道約80%男性和90%女性肺癌的發(fā)生與吸煙有關(guān)。肺癌發(fā)病率和病死率一直居高不下,而且這一趨勢(shì)還在逐年上升,可見(jiàn)肺癌的早期診斷與治療對(duì)提高肺癌患者的生存率和改善生活質(zhì)量方面具有十分重要的意義。而腫瘤標(biāo)志物主要是有腫瘤自身或腫瘤組織與機(jī)體相互作用產(chǎn)生的某些物質(zhì)(主要包括蛋白質(zhì)、激素、酶等物質(zhì)),因其能夠較早反映腫瘤的發(fā)生、發(fā)展、復(fù)發(fā)及療效等方面的情況,而且能夠通過(guò)某些特殊的、靈敏度高的檢測(cè)方法,在人體血液、胸水及其他體液中檢測(cè)到,已成為近年來(lái)國(guó)內(nèi)外學(xué)者研究的熱點(diǎn)。胸苷激酶(thymidine kinase,TK)是人體DNA合成補(bǔ)救途徑的關(guān)鍵酶,它能夠在三磷酸腺苷(ATP)和二價(jià)鎂離子(Mg2+)參與下,催化d Td R(5'羥基胸苷激酶)生成d TMP(脫氧胸苷酸),參與DNA復(fù)制、合成,并為其提供原料。TK在人體中主要以兩種構(gòu)型存在,即線粒體胸苷激酶-TK2和細(xì)胞質(zhì)胸苷激酶-TK1:TK2細(xì)胞循環(huán)獨(dú)立,其表達(dá)與細(xì)胞周期之間無(wú)相關(guān)性;而TK1細(xì)胞循環(huán)與TK2具有本質(zhì)區(qū)別,其表達(dá)與細(xì)胞周期之間存在密切相關(guān)性,常被稱為細(xì)胞周期依賴性標(biāo)志物,是一種與細(xì)胞增殖密切相關(guān)的激酶。TK1在細(xì)胞分裂的G1/S期開(kāi)始升高,直至G2-M期達(dá)最高水平,隨后開(kāi)始下降,至G1前期停止。TK1在細(xì)胞S期特異性高表達(dá)與絕大多數(shù)腫瘤細(xì)胞處于S期和G2期基本同步,因此TK1被稱為極具生命潛力的腫瘤標(biāo)志物。血清TK1(STK1)只在機(jī)體某些疾病情況下,才會(huì)輕微升高,如貧血、感染、免疫系統(tǒng)疾病等,在健康人體或靜止期細(xì)胞含量極少或檢測(cè)不到。而當(dāng)機(jī)體發(fā)生大量細(xì)胞增殖時(shí)或者發(fā)生癌變時(shí)TK1水平會(huì)迅速升高,其水平可達(dá)到正常人的2-100倍。目前國(guó)內(nèi)外大量研究證明,TK1是一種十分有價(jià)值的腫瘤標(biāo)志物,檢測(cè)TK1的水平對(duì)于腫瘤的篩查,早期診斷,療效評(píng)價(jià),判斷復(fù)發(fā)及預(yù)測(cè)生存率方面具有十分重要的意義。本文就血清胸苷激酶1在評(píng)估NSCLC患者化療療效中的意義進(jìn)行探討。目的:探究血清胸苷激酶1(serum thymidine kinase 1,STK1)水平在非小細(xì)胞肺癌(non-small cell lung cancer,NSCLC)患者4個(gè)周期化療過(guò)程中的變化以及其在評(píng)估化療療效中的意義。方法:應(yīng)用免疫印跡增強(qiáng)化學(xué)發(fā)光法檢測(cè)59例非小細(xì)胞肺癌患者化療前及化療第1、2、3、4周期后這5個(gè)時(shí)期的血清胸苷激酶1濃度,結(jié)合其化療療效對(duì)檢測(cè)結(jié)果進(jìn)行分析。結(jié)果:三種化療方案間STK1水平無(wú)明顯差異。在化療有效組,血清TK1、CEA、NSE、CYFRA21-1水平隨著化療的進(jìn)行均呈下降趨勢(shì),第1、2、4周期后血清CEA水平均明顯低于化療前,前3個(gè)周期后血清CYFRA21-1水平均明顯低于化療前,4個(gè)周期后STK1水平均明顯低于化療前。在化療無(wú)效組中,血清TK1、CEA、NSE、CYFRA21-1水平在第3、4周期后均呈現(xiàn)上升趨勢(shì),但化療后上述指標(biāo)較化療前無(wú)明顯差異;而4個(gè)周期后,有效組STK1水平明顯降低。在有效組,第3、4周期后STK1陽(yáng)性率明顯低于化療前;在化療無(wú)效組,第3、4周期化療后STK1陽(yáng)性率較化療前上升,但差異無(wú)統(tǒng)計(jì)學(xué)意義。不區(qū)分化療療效,化療前及4個(gè)周期化療后STK1水平在肺鱗癌與肺腺癌中無(wú)明顯差異。結(jié)論:監(jiān)測(cè)血清胸苷激酶1在評(píng)估非小細(xì)胞肺癌化療療效中有重要應(yīng)用價(jià)值,并對(duì)后續(xù)治療有指導(dǎo)意義。
[Abstract]:Background: malignant tumor is a major disease which can cause serious damage to human health. In China and worldwide, the morbidity and mortality of lung cancer accounted for all malignant tumors. About 1 million 380 thousand people died of lung cancer in the world every year, so WHO (WHO) will be listed as the most damaging lung cancer on twenty-first Century. In all human diseases and pathological typing of lung cancer, the incidence of NSCLC was highest, accounting for more than 85%. And the clinical study found that NSCLC patients in the treatment of most tumor metastatic or progression to advanced, but also missed the best time of surgery. Although various treatment methods of lung cancer in recent years. In the constant progress and development (such as improved surgical application of targeted therapy and hormone receptor therapy), but for advanced NSCLC patients, poor efficacy of single treatment method, in order to Comprehensive treatment based therapy is still widely recognized and accepted. Lung cancer is also known as primary lung cancer, first originated in the bronchial mucosa, gland or alveolar epithelium, the pathogenesis is not clear, that is related to environmental pollution and smoking. It is reported that about 80% of men and 90% of women with lung cancer smoking related lung cancer. The incidence rate and mortality rate has been high, and this trend is still increasing year by year, early diagnosis and treatment of visible lung cancer has very important significance to improve the survival rate and improve the quality of life of patients with lung cancer. The tumor marker is something tumor itself or tumor tissue and body interaction the (including proteins, hormones, enzymes and other substances), because it can reflect the tumor occurrence, development, recurrence and effect of the situation, but also by Some special, detection method with high sensitivity, in human blood, pleural fluid and other body fluids detected, has become the focus of domestic and foreign scholars in recent years. Thymidine kinase (thymidine kinase TK) is a key enzyme in DNA synthesis of human remedy, it can in three phosphoric acid (ATP) and adenosine two the price of magnesium ion (Mg2+) in the presence of Td R catalyzed D (5'hydroxy thymidine kinase) to generate d TMP (DT), involved in DNA replication, synthesis, and provide the raw material.TK in the body mainly in two configurations, namely mitochondrial thymidine kinase -TK2 and thymidine kinase -TK1:TK2 cell cycle independent, no correlation between its expression and cell cycle of TK1 cell cycle and TK2; and has the essential difference, there is a close correlation between the expression and the cell cycle, often called cell cycle dependent marker, is a kind of cell proliferation related kinase.TK1 in G1/S phase of cell division began to rise, until the G2-M period and reached the highest level, then decreased to G1 stop early high expression of.TK1 in S cell stage specific and the vast majority of tumor cells in S phase and G2 phase basic synchronization, so TK1 is known as the very life potential tumor markers of serum TK1 (STK1). Only in the body of certain diseases, only slightly elevated, such as anemia, infection, immune system diseases, not in the cell content of healthy human or resting little or detection. And when the body of a lot of cell proliferation or cancerous TK1 level will rise quickly, 2-100 times its level can reach normal people. At present, a large number of domestic and foreign research shows that TK1 is a valuable tumor marker to evaluate the level of detection of TK1 for tumor screening, early diagnosis, curative effect, has ten important judgment and prediction of survival rate of recurrence . this paper discusses the serum thymidine kinase 1 in curative effect of chemotherapy in patients with NSCLC. Objective: to assess the significance of serum thymidine kinase 1 (serum thymidine 1 kinase, STK1) level in patients with non-small cell lung cancer (non-small cell lung cancer, NSCLC) changes in patients with 4 cycles of chemotherapy and its significance in curative effect evaluation of chemotherapy. Methods: Western blot enhanced serum thymidine kinase 5 in chemiluminescence detection in 59 cases of non-small cell lung cancer patients before chemotherapy and chemotherapy in 1,2,3,4 cycle after 1 concentration, analysis of test results were combined with the chemotherapy efficacy. Results: there was no significant difference in STK1 level of three kinds of chemotherapy in between. The chemotherapy effective group, serum TK1, CEA, NSE, CYFRA21-1 levels with chemotherapy were decreased, the 1,2,4 cycle after the serum level of CEA was significantly lower than that before chemotherapy, 3 cycles after the serum level of CYFRA21-1 significantly Significantly lower than before chemotherapy, after 4 cycles of STK1 were significantly lower than before chemotherapy. The chemotherapy ineffective group, serum TK1, CEA, NSE, CYFRA21-1 levels were increased in the 3,4 period, but the index after chemotherapy than before chemotherapy had no significant difference; and after 4 cycles, the level of STK1 group decreased obviously. In the effective group, the 3,4 cycle after STK1 were significantly lower than before chemotherapy in the chemotherapy group; invalid, the 3,4 positive rate after STK1 cycles of chemotherapy before chemotherapy was increased, but the difference was not statistically significant. Do not distinguish between the efficacy of chemotherapy before chemotherapy and after 4 cycles of chemotherapy STK1 level in lung squamous cell carcinoma and adenocarcinoma of lung cancer had no significant difference. Conclusion: monitoring of serum thymidine kinase 1 in the evaluation of non-small cell lung cancer chemotherapy has important application value, and has guiding significance for further treatment.

【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R734.2

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