血清胸苷激酶1在评估非小细胞肺癌患者化疗疗效中的意义探讨

发布时间：2018-03-02 09:20

本文关键词： 非小细胞肺癌化疗血清胸苷激酶1 动态检测　出处：《安徽医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景:恶性肿瘤是指可对人类生命健康造成严重损害的一大类疾病。在我国乃至世界范围内,肺癌的发病率和病死率均占所有恶性肿瘤的首位。全球每年大约有138万人死于肺癌,因此WHO(世界卫生组织)将肺癌列为21世纪对人类危害最大的疾病。在肺癌的所有病理分型中,NSCLC发病率最高,约占85%以上。而且临床研究发现,NSCLC患者在就诊时绝大部分肿瘤已发生远处转移或进展为晚期,同时也错失了外科手术治疗的最佳时机。尽管近年来肺癌的各种治疗方法在不断的进步和发展(如手术方式的改进、靶向治疗及激素受体治疗的应用),但对于晚期NSCLC患者而言,单一治疗方法的疗效较差,以化疗为主的综合治疗方式仍然被临床广泛认可和接受。肺癌又称原发性支气管肺癌,最先起源于支气管粘膜、腺体或肺泡上皮,其发病原因和机制尚不清楚,多认为与环境污染和吸烟有关。据报道约80%男性和90%女性肺癌的发生与吸烟有关。肺癌发病率和病死率一直居高不下,而且这一趋势还在逐年上升,可见肺癌的早期诊断与治疗对提高肺癌患者的生存率和改善生活质量方面具有十分重要的意义。而肿瘤标志物主要是有肿瘤自身或肿瘤组织与机体相互作用产生的某些物质(主要包括蛋白质、激素、酶等物质),因其能够较早反映肿瘤的发生、发展、复发及疗效等方面的情况,而且能够通过某些特殊的、灵敏度高的检测方法,在人体血液、胸水及其他体液中检测到,已成为近年来国内外学者研究的热点。胸苷激酶(thymidine kinase,TK)是人体DNA合成补救途径的关键酶,它能够在三磷酸腺苷(ATP)和二价镁离子(Mg2+)参与下,催化d Td R(5'羟基胸苷激酶)生成d TMP(脱氧胸苷酸),参与DNA复制、合成,并为其提供原料。TK在人体中主要以两种构型存在,即线粒体胸苷激酶-TK2和细胞质胸苷激酶-TK1:TK2细胞循环独立,其表达与细胞周期之间无相关性;而TK1细胞循环与TK2具有本质区别,其表达与细胞周期之间存在密切相关性,常被称为细胞周期依赖性标志物,是一种与细胞增殖密切相关的激酶。TK1在细胞分裂的G1/S期开始升高,直至G2-M期达最高水平,随后开始下降,至G1前期停止。TK1在细胞S期特异性高表达与绝大多数肿瘤细胞处于S期和G2期基本同步,因此TK1被称为极具生命潜力的肿瘤标志物。血清TK1(STK1)只在机体某些疾病情况下,才会轻微升高,如贫血、感染、免疫系统疾病等,在健康人体或静止期细胞含量极少或检测不到。而当机体发生大量细胞增殖时或者发生癌变时TK1水平会迅速升高,其水平可达到正常人的2-100倍。目前国内外大量研究证明,TK1是一种十分有价值的肿瘤标志物,检测TK1的水平对于肿瘤的筛查,早期诊断,疗效评价,判断复发及预测生存率方面具有十分重要的意义。本文就血清胸苷激酶1在评估NSCLC患者化疗疗效中的意义进行探讨。目的:探究血清胸苷激酶1(serum thymidine kinase 1,STK1)水平在非小细胞肺癌(non-small cell lung cancer,NSCLC)患者4个周期化疗过程中的变化以及其在评估化疗疗效中的意义。方法:应用免疫印迹增强化学发光法检测59例非小细胞肺癌患者化疗前及化疗第1、2、3、4周期后这5个时期的血清胸苷激酶1浓度,结合其化疗疗效对检测结果进行分析。结果:三种化疗方案间STK1水平无明显差异。在化疗有效组,血清TK1、CEA、NSE、CYFRA21-1水平随着化疗的进行均呈下降趋势,第1、2、4周期后血清CEA水平均明显低于化疗前,前3个周期后血清CYFRA21-1水平均明显低于化疗前,4个周期后STK1水平均明显低于化疗前。在化疗无效组中,血清TK1、CEA、NSE、CYFRA21-1水平在第3、4周期后均呈现上升趋势,但化疗后上述指标较化疗前无明显差异;而4个周期后,有效组STK1水平明显降低。在有效组,第3、4周期后STK1阳性率明显低于化疗前;在化疗无效组,第3、4周期化疗后STK1阳性率较化疗前上升,但差异无统计学意义。不区分化疗疗效,化疗前及4个周期化疗后STK1水平在肺鳞癌与肺腺癌中无明显差异。结论:监测血清胸苷激酶1在评估非小细胞肺癌化疗疗效中有重要应用价值,并对后续治疗有指导意义。
[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.

【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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