口腔鱗狀細(xì)胞癌患者治療前后外周血免疫細(xì)胞的檢測及其臨床意義的研究
發(fā)布時(shí)間：2018-07-29 20:22
【摘要】：背景與目的:口腔鱗狀細(xì)胞癌是口腔頜面部最常見的惡性腫瘤,好發(fā)于舌、牙齦、唇、頰、頜骨等部位。目前,該疾病的治療方法仍以手術(shù)為主,并輔以局部放療、全身化療等綜合治療,患者雖在組織保存和整體生活質(zhì)量方面有所受益,但卻由于創(chuàng)傷大、高復(fù)發(fā)率、高轉(zhuǎn)移率等而導(dǎo)致預(yù)后欠佳。因此,越來越多的學(xué)者致力于口腔頜面部鱗狀細(xì)胞癌的病因研究,以期從病因入手,尋求更有效的治療辦法。隨著免疫學(xué)和分子生物學(xué)的進(jìn)展,免疫因素逐漸引起關(guān)注。本研究旨在運(yùn)用流式細(xì)胞術(shù),通過對口腔鱗狀細(xì)胞癌患者手術(shù)及化療前后外周血免疫細(xì)胞表達(dá)水平的研究,探討機(jī)體自身免疫功能狀態(tài)的不同,從免疫學(xué)角度對口腔鱗狀細(xì)胞癌的發(fā)病機(jī)制做進(jìn)一步研究,有助于優(yōu)化免疫治療方案和增強(qiáng)抗腫瘤免疫應(yīng)答的靶向治療效果,為口腔鱗狀細(xì)胞癌的免疫治療提供可靠的理論依據(jù)。資料與方法:1.臨床資料:選擇鄭州大學(xué)第一附屬醫(yī)院口腔頜面外科2015年2月至2016年8月經(jīng)術(shù)后病理檢查確診為口腔鱗狀細(xì)胞癌的患者40例,全部病例均有明確的病理診斷及完整的臨床資料。其中男性22例,女性18例;年齡29~81歲�；颊呷朐呵拔催M(jìn)行過任何抗腫瘤治療;排除全身淋巴系統(tǒng)來源性疾病;發(fā)病部位包括舌、頰、牙齦、口底等部位。另選取15例健康查體者作為健康對照組。2.方法:化療藥物選用氟尿嘧啶注射液,連用5天;奧沙利鉑注射液,第1天。治療組病人分別于手術(shù)前2天、手術(shù)后3周即術(shù)后第一周期化療前2天、第一周期化療后2周即第二周期化療前2天、第二周期化療后2周采集新鮮外周血。健康對照組常規(guī)采集新鮮外周血。采集的血液樣本經(jīng)流式細(xì)胞術(shù)檢測其中的T淋巴細(xì)胞亞群CD3+、CD4~+、CD8+的百分率及CD4~+/CD8+的比值;B淋巴細(xì)胞(CD19+)百分率;NK細(xì)胞(CD56+)百分率。結(jié)果:1.手術(shù)前口腔鱗狀細(xì)胞癌患者外周血CD3+、CD4~+、CD8+、NK及B細(xì)胞的所占比例與健康對照組人群比較,手術(shù)前患者CD3+、CD4~+和B細(xì)胞的表達(dá)降低,CD8+和NK細(xì)胞的表達(dá)增加,CD4~+/CD8+比值下降或倒置,差別均有統(tǒng)計(jì)學(xué)意義(P㩳0.05)。2.手術(shù)3周后檢測口腔鱗狀細(xì)胞癌患者外周血免疫細(xì)胞,CD3+的表達(dá)仍明顯低于健康對照組,與術(shù)前數(shù)據(jù)比較雖然顯示有小范圍的提高,但經(jīng)統(tǒng)計(jì)計(jì)算二者間差別無統(tǒng)計(jì)學(xué)意義(P㧐0.05)。CD4~+的表達(dá)也低于健康對照組(P㩳0.05),但與術(shù)前比較,有較大幅度的升高(P㩳0.05)。CD8+的表達(dá)明顯低于術(shù)前狀態(tài)(P㩳0.05),且與健康對照組相比差別有統(tǒng)計(jì)學(xué)意義(P㩳0.05)。NK細(xì)胞的表達(dá)與健康對照組比較差別無顯著性(P㧐0.05),但手術(shù)前后NK細(xì)胞的表達(dá)卻有著明顯的變化(P㩳0.05),表現(xiàn)為手術(shù)后口腔鱗狀細(xì)胞癌患者外周血中NK細(xì)胞的表達(dá)較手術(shù)前有所下降。術(shù)后B細(xì)胞的表達(dá)顯著低于健康對照組的表達(dá)水平(P㩳0.05),與術(shù)前相比雖略有升高,但差別無統(tǒng)計(jì)學(xué)意義(P0.05)。CD4~+/CD8+的比值盡管仍未恢復(fù)至健康對照組水平(P㩳0.05),但其值和術(shù)前相比也有了一定程度的回升(P㩳0.05)。3.術(shù)后3周檢測結(jié)果即為第一周期化療前2天檢測指標(biāo)。經(jīng)一個(gè)周期化療結(jié)束后2周前來復(fù)診,抽取外周血檢測各免疫細(xì)胞表達(dá)情況,即為第一周期化療后檢測結(jié)果。第一周期化療后口腔鱗狀細(xì)胞癌患者外周血中CD3+的表達(dá)仍低于健康對照組且較化療前相比變化不大(P㧐0.05)。CD4~+的表達(dá)與化療前相比無顯著性差別(P㧐0.05),同樣低于健康對照組(P㩳0.05)。CD8+的表達(dá)與化療前相比有著顯著的差別(P㩳0.05),主要表現(xiàn)為化療后口腔鱗狀細(xì)胞癌患者外周血中CD8+的表達(dá)較化療前大幅度下降,且與健康對照組比較差別無顯著性(P㧐0.05)。NK細(xì)胞的表達(dá)與化療前相比變化不大(P㧐0.05),但仍略高于健康對照組(P㧐0.05)。B細(xì)胞在低于健康對照組(P㩳0.05)的情況下與化療前相比有了一定的改善(P㧐0.05)。CD4~+/CD8+的比值盡管仍未恢復(fù)至健康對照組水平(P㩳0.05),但較化療前有所升高(P㧐0.05)。4.第一周期化療后2周復(fù)診檢測結(jié)果即為第二周期化療前2天檢測指標(biāo)。再經(jīng)第二個(gè)周期化療結(jié)束后2周前來復(fù)診,抽取外周血檢測各免疫細(xì)胞表達(dá)情況,即為第二周期化療后檢測結(jié)果。第二周期化療后口腔鱗狀細(xì)胞癌患者外周血中CD3+的表達(dá)較化療前有小幅度的升高,低于健康對照組(P㧐0.05)。CD4~+和B細(xì)胞與化療前相比表達(dá)水平明顯增高(P㩳0.05),稍低于健康對照組水平(P0.05)。CD8+和NK細(xì)胞化療后較化療前表達(dá)均有所下降(P0.05),但尚未降至健康對照組水平(P0.05)。CD4~+/CD8+的比值較化療前有了一定程度的回升(P㩳0.05),接近健康對照組水平(P0.05)。結(jié)論:1.口腔鱗狀細(xì)胞癌患者較正常人存在著免疫抑制現(xiàn)象。2.手術(shù)后及經(jīng)奧沙利鉑加氟尿嘧啶的兩周期化療后,口腔鱗狀細(xì)胞癌患者的免疫功能仍處于低下狀態(tài)。手術(shù)及化療時(shí)的營養(yǎng)支持治療對患者的免疫狀態(tài)可起到一定的改善作用,解除機(jī)體內(nèi)部分免疫功能受到抑制的現(xiàn)象,有利于腫瘤患者的治療。3.外周血中免疫細(xì)胞的表達(dá)水平可以作為口腔癌患者治療過程中評估機(jī)體免疫狀態(tài)的臨床監(jiān)測指標(biāo)。
[Abstract]:Background and objective: oral squamous cell carcinoma is the most common malignant tumor in the oral and maxillofacial region. It is well distributed in the tongue, gingival, lip, cheek and jaw. At present, the treatment of this disease is still based on surgery, combined with local radiotherapy, systemic chemotherapy and other comprehensive treatment, although the patient has benefited from the preservation of the tissue and the quality of the whole life. Therefore, more and more scholars are devoted to the study of the etiology of oral and maxillofacial squamous cell carcinoma in order to seek more effective treatment from the cause of the disease. With the progress of immunology and molecular biology, the immune factors gradually attract attention. This study aims to use flow. Through the study of the expression level of immune cells in peripheral blood of patients with oral squamous cell carcinoma before and after chemotherapy and before and after chemotherapy, a further study on the pathogenesis of oral squamous cell carcinoma is further studied from the immunological point of view, which helps to optimize the immunotherapy scheme and enhance the immune response to the tumor. The effect of targeted therapy provides a reliable theoretical basis for the immunotherapy of oral squamous cell carcinoma. Data and methods: 1. clinical data: 40 cases of oral squamous cell carcinoma were diagnosed in oral and maxillofacial surgery of the First Affiliated Hospital of Zhengzhou University from February 2015 to 8 menstruation after 8 menstruation, and all cases had clear pathology. Diagnosis and complete clinical data, of which 22 men, 18 women, age 29~81 years old. The patients were not treated with any antitumor treatment before admission; the systemic lymphoid diseases were excluded; the sites included the tongue, cheeks, gums, and the bottom of the mouth. 15 healthy subjects were selected as the healthy control group.2. method: the chemotherapeutic drug fluoruria was selected. Injection of pyrimidine for 5 days; Oxaliplatin Injection, first days. The patients in the treatment group were 2 days before the operation, 3 weeks after the operation, 2 days before the first cycle of chemotherapy, 2 days before the first cycle of chemotherapy, 2 days before the second cycle of chemotherapy, and 2 weeks after the second cycle of chemotherapy. The healthy control group collected the blood from the fresh peripheral blood. The percentage of CD3+, CD4~+, CD8+, and CD4~+/CD8+, the percentage of B lymphocyte (CD19+), and the percentage of NK cells (CD56+) were measured by flow cytometry, and the percentage of NK cells (CD56+) in the peripheral blood of 1. patients with oral squamous cell carcinoma before operation was compared with those of the healthy control group compared with those of the healthy control group. The expression of CD3+, CD4~+ and B cells decreased, the expression of CD8+ and NK cells increased, the CD4~+/CD8+ ratio decreased or inverted, the difference was statistically significant (P? 0.05).2. operation 3 weeks after the detection of the peripheral blood immune cells in patients with oral squamous cell carcinoma. The expression of CD3+ was still significantly lower than that in the healthy control group. There was no statistically significant difference between the two groups (P? 0.05).CD4~+ was also lower than the healthy control group (P? 0.05), but compared with pre operation, the expression of.CD8+ was significantly lower than that before the operation (P? 0.05), and compared with the healthy control group, the difference was statistically significant (P? 0.05).NK cells. There was no significant difference between the control group and the healthy control group (P? 0.05), but the expression of NK cells before and after operation was obviously changed (P? 0.05). The expression of NK cells in the peripheral blood of the patients with oral squamous cell carcinoma after operation was lower than that before operation. The expression of B cells after operation was significantly lower than that of the healthy control group (P? 0.05), and the operation of the cells was significantly lower than that of the healthy control group. Although the former was slightly higher, the difference was not statistically significant (P0.05), although the ratio of.CD4~+/CD8+ was still not restored to the level of the healthy control group (P? 0.05), but the value of the difference was also increased to a certain extent compared to the preoperative (P? 0.05).3. after the 3 week of the first cycle chemotherapy, which was 2 weeks before the end of one cycle chemotherapy. After the first cycle chemotherapy, the expression of CD3+ in the peripheral blood of the patients with oral squamous cell carcinoma after the first cycle was still lower than that in the healthy control group and compared with that before the chemotherapy (P? 0.05).CD4~+ expression was not significantly different from that before chemotherapy (P? 0.05). Compared with the healthy control group (P? 0.05), the expression of.CD8+ was significantly different from that before chemotherapy (P? 0.05). The expression of CD8+ in the peripheral blood of patients with oral squamous cell carcinoma after chemotherapy was significantly lower than that before chemotherapy, and there was no significant difference between the healthy control group and the healthy control group (P? 0.05).NK cells. Big (P? 0.05), but still slightly higher than the healthy control group (P? 0.05).B cells in lower than the healthy control group (P? 0.05), compared with pre chemotherapy (P? 0.05).CD4~+/CD8+ ratio although still not recovered to the level of health control group (P? 0.05), but higher than before chemotherapy (P? 0.05).4. first cycle after the first period of chemotherapy after 2 review detection knot The results were 2 days before second cycles of chemotherapy. After second cycles of chemotherapy, the results were taken 2 weeks after the end of chemotherapy, and the expression of the immune cells was detected in the peripheral blood, that is, after the second cycles of chemotherapy. The expression of CD3+ in the peripheral blood of the patients with oral squamous cell carcinoma after second cycles of chemotherapy was slightly higher than that before the chemotherapy. The expression level of.CD4~+ and B cells in the healthy control group (P? 0.05) was significantly higher than that before chemotherapy (P? 0.05). The ratio of.CD8+ and NK cells in the healthy control group (P0.05) was lower than that before chemotherapy (P0.05), but the ratio of the level (P0.05).CD4~+/CD8+ of the healthy control group had not been reduced to a certain extent before the chemotherapy. P? 0.05), close to the level of health control group (P0.05). Conclusion: 1. oral squamous cell carcinoma patients have immune suppression after.2. surgery and after two cycles of oxaliplatin plus fluorouracil, the immune function of patients with oral squamous cell carcinoma is still low. The immune state can be improved and the immune function of the body is suppressed. The expression level of the immune cells in the peripheral blood of.3. can be used as a clinical monitoring index to evaluate the immune state of the oral cancer patients during the treatment process.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R739.8
本文編號：2153899
[Abstract]:Background and objective: oral squamous cell carcinoma is the most common malignant tumor in the oral and maxillofacial region. It is well distributed in the tongue, gingival, lip, cheek and jaw. At present, the treatment of this disease is still based on surgery, combined with local radiotherapy, systemic chemotherapy and other comprehensive treatment, although the patient has benefited from the preservation of the tissue and the quality of the whole life. Therefore, more and more scholars are devoted to the study of the etiology of oral and maxillofacial squamous cell carcinoma in order to seek more effective treatment from the cause of the disease. With the progress of immunology and molecular biology, the immune factors gradually attract attention. This study aims to use flow. Through the study of the expression level of immune cells in peripheral blood of patients with oral squamous cell carcinoma before and after chemotherapy and before and after chemotherapy, a further study on the pathogenesis of oral squamous cell carcinoma is further studied from the immunological point of view, which helps to optimize the immunotherapy scheme and enhance the immune response to the tumor. The effect of targeted therapy provides a reliable theoretical basis for the immunotherapy of oral squamous cell carcinoma. Data and methods: 1. clinical data: 40 cases of oral squamous cell carcinoma were diagnosed in oral and maxillofacial surgery of the First Affiliated Hospital of Zhengzhou University from February 2015 to 8 menstruation after 8 menstruation, and all cases had clear pathology. Diagnosis and complete clinical data, of which 22 men, 18 women, age 29~81 years old. The patients were not treated with any antitumor treatment before admission; the systemic lymphoid diseases were excluded; the sites included the tongue, cheeks, gums, and the bottom of the mouth. 15 healthy subjects were selected as the healthy control group.2. method: the chemotherapeutic drug fluoruria was selected. Injection of pyrimidine for 5 days; Oxaliplatin Injection, first days. The patients in the treatment group were 2 days before the operation, 3 weeks after the operation, 2 days before the first cycle of chemotherapy, 2 days before the first cycle of chemotherapy, 2 days before the second cycle of chemotherapy, and 2 weeks after the second cycle of chemotherapy. The healthy control group collected the blood from the fresh peripheral blood. The percentage of CD3+, CD4~+, CD8+, and CD4~+/CD8+, the percentage of B lymphocyte (CD19+), and the percentage of NK cells (CD56+) were measured by flow cytometry, and the percentage of NK cells (CD56+) in the peripheral blood of 1. patients with oral squamous cell carcinoma before operation was compared with those of the healthy control group compared with those of the healthy control group. The expression of CD3+, CD4~+ and B cells decreased, the expression of CD8+ and NK cells increased, the CD4~+/CD8+ ratio decreased or inverted, the difference was statistically significant (P? 0.05).2. operation 3 weeks after the detection of the peripheral blood immune cells in patients with oral squamous cell carcinoma. The expression of CD3+ was still significantly lower than that in the healthy control group. There was no statistically significant difference between the two groups (P? 0.05).CD4~+ was also lower than the healthy control group (P? 0.05), but compared with pre operation, the expression of.CD8+ was significantly lower than that before the operation (P? 0.05), and compared with the healthy control group, the difference was statistically significant (P? 0.05).NK cells. There was no significant difference between the control group and the healthy control group (P? 0.05), but the expression of NK cells before and after operation was obviously changed (P? 0.05). The expression of NK cells in the peripheral blood of the patients with oral squamous cell carcinoma after operation was lower than that before operation. The expression of B cells after operation was significantly lower than that of the healthy control group (P? 0.05), and the operation of the cells was significantly lower than that of the healthy control group. Although the former was slightly higher, the difference was not statistically significant (P0.05), although the ratio of.CD4~+/CD8+ was still not restored to the level of the healthy control group (P? 0.05), but the value of the difference was also increased to a certain extent compared to the preoperative (P? 0.05).3. after the 3 week of the first cycle chemotherapy, which was 2 weeks before the end of one cycle chemotherapy. After the first cycle chemotherapy, the expression of CD3+ in the peripheral blood of the patients with oral squamous cell carcinoma after the first cycle was still lower than that in the healthy control group and compared with that before the chemotherapy (P? 0.05).CD4~+ expression was not significantly different from that before chemotherapy (P? 0.05). Compared with the healthy control group (P? 0.05), the expression of.CD8+ was significantly different from that before chemotherapy (P? 0.05). The expression of CD8+ in the peripheral blood of patients with oral squamous cell carcinoma after chemotherapy was significantly lower than that before chemotherapy, and there was no significant difference between the healthy control group and the healthy control group (P? 0.05).NK cells. Big (P? 0.05), but still slightly higher than the healthy control group (P? 0.05).B cells in lower than the healthy control group (P? 0.05), compared with pre chemotherapy (P? 0.05).CD4~+/CD8+ ratio although still not recovered to the level of health control group (P? 0.05), but higher than before chemotherapy (P? 0.05).4. first cycle after the first period of chemotherapy after 2 review detection knot The results were 2 days before second cycles of chemotherapy. After second cycles of chemotherapy, the results were taken 2 weeks after the end of chemotherapy, and the expression of the immune cells was detected in the peripheral blood, that is, after the second cycles of chemotherapy. The expression of CD3+ in the peripheral blood of the patients with oral squamous cell carcinoma after second cycles of chemotherapy was slightly higher than that before the chemotherapy. The expression level of.CD4~+ and B cells in the healthy control group (P? 0.05) was significantly higher than that before chemotherapy (P? 0.05). The ratio of.CD8+ and NK cells in the healthy control group (P0.05) was lower than that before chemotherapy (P0.05), but the ratio of the level (P0.05).CD4~+/CD8+ of the healthy control group had not been reduced to a certain extent before the chemotherapy. P? 0.05), close to the level of health control group (P0.05). Conclusion: 1. oral squamous cell carcinoma patients have immune suppression after.2. surgery and after two cycles of oxaliplatin plus fluorouracil, the immune function of patients with oral squamous cell carcinoma is still low. The immune state can be improved and the immune function of the body is suppressed. The expression level of the immune cells in the peripheral blood of.3. can be used as a clinical monitoring index to evaluate the immune state of the oral cancer patients during the treatment process.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R739.8
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 吳梅娜,劉敘儀,方健,王潔,安彤同;長春瑞濱聯(lián)合順鉑方案治療晚期非小細(xì)胞肺癌[J];中國癌癥雜志;2004年02期
2 林萬隆,陳強(qiáng);奧沙利鉑的藥理作用及臨床應(yīng)用[J];中國腫瘤臨床;2000年11期
相關(guān)碩士學(xué)位論文 前1條
1 梁冠中;肺癌患者外周血CD8~+CD28~-及CD4~+CD25~(high)CD127~(low)調(diào)節(jié)性T細(xì)胞表達(dá)及臨床意義的探討[D];山西醫(yī)科大學(xué);2012年
，本文編號：2153899
本文鏈接：http://sikaile.net/yixuelunwen/zlx/2153899.html
最近更新
教材專著
