三种化疗方案对不同分期的小细胞肺癌患者髓源抑制细胞分化的影响

发布时间：2018-01-23 19:26

本文关键词： 髓源抑制细胞免疫抑制免疫逃逸 EP方案 TP方案小细胞肺癌　出处：《吉林大学》2015年硕士论文　论文类型：学位论文

【摘要】：研究背景: 肺癌是当前世界范围内最常见的恶性肿瘤，手术治疗联合放化疗还是目前治疗肺癌的方式，但事实上，绝大多数肺癌患者在就诊时或临床确诊时就已经失去了手术治疗的机会，而其中一部分患者，即便进行了手术治疗，仍然存在较高的转移和复发率。因此，在肺癌的治疗手段上需要一种更有效的方法。近年来，肿瘤的生物免疫治疗方法出现在临床应用当中，它可以提高肿瘤患者的抗肿瘤免疫功能。免疫和肿瘤之间关系密切、藕断丝连，免疫在一方面在肿瘤的形成过程中起到了一定作用，如预防肿瘤的形成并形成免疫监视等；但是在慢性炎症等慢性过程的时候，由于其重要的免疫学特性，髓系抑制细胞参与重要的称为肿瘤的免疫抑制和免疫逃逸机制的过程，是影响生物免疫治疗的一个重要因素。随着对肿瘤微环境钻研的深入，髓源抑制细胞（MDSCs）在肿瘤患者外周血和组织中的比例显著高于正常人，是参与免疫抑制和免疫逃逸从而影响肿瘤治疗效果的主要因素之一。目的: 目前已有许多关于MDSCs的研究，，根据表面标记物可以把它分为单核系和粒系，并发现了不同类型肿瘤的髓源抑制细胞的表型和分布数量存在差异。已有的研究发现髓源抑制细胞在各类型的恶性肿瘤中都有异常聚集，并与患者的预后息息相关。本研究则标记MDSCs上的CD14+/CD33+/CD11b+抗体，运用流式细胞仪对III、IV期小细胞肺癌患者化疗前后外周血中单核及粒细胞的百分比检测，分析不同的化疗方案对不同分期的小细胞肺癌患者髓源抑制细胞分化的影响，研究化疗方案与预后是否相关，并进一步探讨其临床意义。方法: 1.选取吉林省长春市吉林大学中日联谊医院呼吸内科2013年10月-2014年11月期间就诊并采用不同化疗方案的小细胞肺癌III期、IV期患者80例，病理学均已明确小细胞癌的诊断（详见论文后附图1、2）。平均分成八组，每组10人，选取正常健康人群10例。将这些人群统一编号成A、B、C、D、E、F、G、H、I，这些组中A、B、C、G患者为III期、D、E、F、H为IV期，I组为健康人群，A、D两组为EP方案；B、E两组为TP方案；C、F两组均有化疗禁忌症；G、H两组为TP+EP。 2.通过对这些人群中外周血的采取、对以上人群的CD11b+、CD14+、CD33+进行标记，通过流式细胞仪进行检测，可对肿瘤患者用药前后的髓源抑制细胞的含量进行分析，对健康人群中髓源抑制细胞的含量进行分析。最终对采集来的数据进行有效的归纳总结和处理。对分组采集后的结果通过卡方检验、t检验以及平均数±标准差的办法进行统计学的量化。并对统计的结果进行比对确定髓源抑制细胞和小细胞肺癌之间的关系、髓源抑制细胞和EP化疗方案之间的关系、髓源抑制细胞和TP化疗方案之间的关系、不同分期的小细胞肺癌与TP化疗方案之间的关系、不同分期的小细胞肺癌与EP化疗方案之间的关系、TP化疗方案与EP化疗方案之间的关系、髓源抑制细胞与正常人之间的关系。结果: 1.EP方案在小细胞肺癌III期患者的效果较明显 2.TP方案在小细胞肺癌IV期患者的作用效果较明显 3.两种方案联合后数值并没有出现明显的变化 4.通过肿瘤人群与正常人群的对比，髓源抑制细胞的含量可与肿瘤的发生发展过程有着密切的联系（P0.05） 5.通过用药后与用药前的人群对比，化疗药物是通过抑制髓源抑制细胞的生成来达到对小细胞肺癌的控制作用（P0.05） 6. TP方案与EP方案的选择上，无论选择哪种方案，都对髓源抑制细胞增殖的抑制有着重要的作用（P0.05）结论: 1.在小细胞肺癌III期、IV期患者当中运用EP化疗方案会有更显著的疗效 2.两种方案联合与单一用药疗效差异不显著 3.髓源抑制细胞在肿瘤患者的机体内具有更大的出现比例 4.肿瘤患者在使用化疗方案后髓源抑制细胞的数量可以下降到接近于正常人群的水平
[Abstract]:Research background:
Lung cancer is currently the world's most common malignant tumor, surgical treatment combined with radiotherapy and chemotherapy is the treatment of lung cancer, but in fact, the vast majority of lung cancer patients in the clinic or clinical diagnosis have lost the opportunity of surgical treatment, and some patients, even if the surgical treatment, recurrence and metastasis still exist the higher the rate. Therefore, the need for a more effective method in the treatment of lung cancer means. In recent years, the biological immune therapy of cancer in clinical application, it can improve the anti-tumor immune function of tumor patients. The relationship between immune and tumor immune ouduansilian closely, on the one hand, in the formation of tumor in the play a role, such as the prevention of tumor formation and the formation of immune surveillance; but when the chronic inflammation and chronic process, because of its important immunological characteristics, Myeloid suppressor cells participate in the important process known as immune suppression and tumor immune escape mechanisms, is an important factor affecting the immune therapy of the tumor microenvironment. With the in-depth study, myeloid derived suppressor cells (MDSCs) in the peripheral blood and tissues than patients was higher than that of normal. Is one of the main factors involved in immune suppression and immune escape and thus influence the tumor therapeutic effect.
Objective:
There are many studies about MDSCs, according to the surface markers can be divided into granulocyte and monocyte lineages, and found different tumor types of myeloid derived suppressor cells phenotype and the distribution of the number of differences. It has been found that myeloid derived suppressor cells are in various types of malignant tumors and abnormal aggregation. Closely related to the prognosis of the patients. This study is labeled CD14+/CD33+/CD11b+ antibody on MDSCs, the use of III flow cytometry, the percentage of IV phase detection before and after chemotherapy in patients with non-small cell lung cancer in peripheral blood monocytes and granulocytes, analysis of the effect of different chemotherapy regimens for different patients with small cell lung cancer staging of myeloid cell differentiation inhibition the study on whether chemotherapy and prognosis, and further explore its clinical significance.
Method:
1. city of Jilin province were Changchun Japan Union Hospital of Jilin University Department of respiratory medicine in October 2013 -2014 year in November during the visit and the chemotherapy in small cell lung cancer of stage III, 80 cases of IV patients, the pathological diagnosis of small cell carcinoma have been clear (see the figure 1,2). The average divided into eight groups, each group of 10 people select normal, 10 cases of healthy people. These people number into A, B, C, D, E, F, G, H, I, B, A groups, C, G in patients with stage III, D, E, F, H, IV, I group of healthy people. A D, the two group was EP B, two E; group C, F TP; the two groups had contraindications to chemotherapy; G, H two group was TP+EP.
2. by taking on these populations of peripheral blood, the people of more than CD11b+, CD14+, CD33+ markers were detected by flow cytometry, analyzing the content of tumor patients before and after treatment of myeloid derived suppressor cells, the content of bone marrow derived in healthy population cells were analyzed. The final acquisition of the data were summarized and effective treatment. After the collection of packet results through chi square test, t test and quantitative statistical average standard deviation method. And the statistical results were compared to determine the relationship between myeloid derived suppressor cells and small cell lung cancer, myeloid derived suppressor cells and the relationship between EP chemotherapy, myeloid derived suppressor cells and the relationship between TP chemotherapy, the relationship between the different stages of the small cell lung cancer with TP chemotherapy, different stages of small cell lung cancer with EP regimen between Relationship, the relationship between the TP chemotherapy regimen and the EP chemotherapy regimen, the relationship between the myelinated suppressor cells and the normal person.
Result:
The effect of 1.EP scheme in patients with stage III of small cell lung cancer is more obvious
The effect of 2.TP scheme in patients with stage IV of small cell lung cancer is more obvious
3. there are no obvious changes in the combined value of the two schemes.
4. through the contrast between the tumor population and the normal population, the content of the myelinated suppressor cells can be closely related to the development of the tumor (P0.05).
5. the chemotherapeutic drugs are controlled by inhibiting the formation of myelinated suppressor cells to control small cell lung cancer (P0.05).
The selection of the 6. TP scheme and the EP scheme, regardless of which option, has an important effect on the inhibition of the proliferation of myelinated myeloid cells (P0.05)
Conclusion:
1. in phase III of small cell lung cancer, the use of EP chemotherapy in IV patients will have a more significant effect.
2. the difference between the combination of the two schemes and the single medication was not significant
3. medullary suppressor cells have a greater proportion in the body of the cancer patients
4. the number of medullary suppressor cells in the cancer patients can fall to the level of the normal population after using the chemotherapy regimen.

【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R734.2

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