MicroRNA-30b在胃癌中的功能及新辅助化疗应用于进展期胃癌的研究
发布时间：2019-06-05 18:01
【摘要】：研究背景：早期诊断困难、化疗耐药、缺乏有效的预后指标是目前胃癌研究领域的重要难题,限制了胃癌患者昀总体预后。寻找新的诊断标记物,深入了解胃癌发生、发展机制,逆转化疗耐药是改善胃癌患者预后的重要手段。MicroRNAs (miRNAs)是一类长约22个核苷酸的非编码单链小分子RNA,在肿瘤发生、发展、增殖、侵袭、转移及化疗耐药等多个方面发挥重要作用。MiR-30b在结直肠癌、宫颈癌、乳腺癌等肿瘤中表达降低,参与多种肿瘤生物学表型的调控。但是其在胃癌中的表达水平、调控作用及机制尚不明确。因此,检测胃癌中miR-30b的表达水平,深入研究miR-30b的调控作用及机制,对于明确其在胃癌诊断、判断预后等方面具有重要的意义。新辅助化疗作为肿瘤综合治疗的一部分,已经逐渐被引用至局部进展期胃癌的治疗上。新辅助化疗应用于胃癌的手术之前,具有以下优点：提高切除率,降低肿瘤的分期,相比于单纯手术,还可以减少淋巴结和血管的转移。术前患者的营养状况良好,可以更好的耐受化疗的副反应。近年来,国内外关于胃癌新辅助化疗的研究都显示新辅助化疗有明显的效果。但是,新辅助化疗方案没有统一的标准,化疗药物、化疗周期的选择及疗效评价的时间都存在争议。目的：(1)探讨血清癌胚抗原(CEA)、糖类抗原19-9(CA19-9)、糖类抗原242(CA242)及糖类抗原50(CA50)联合检测在胃癌患者诊断、临床病理因素及预后判断的价值。(2)探索miR-30b对胃癌细胞株增殖、凋亡、侵袭及迁移等恶性表型的调控作用。明确miR-30b的调控的靶基因及信号通路。(3)评估进展期胃癌患者行新辅助治疗后的临床病理特征及效果。评估空肠穿刺置管早期肠内营养支持治疗对接受新辅助化疗并手术胃癌患者的营养状况和并发症的影响。方法：(1)收集18I例于我院行手术治疗的胃癌患者临床资料,回顾性分析其术前血清CEA、CA19-9, CA242及CA50的水平。通过ROC曲线,对四项肿瘤标志物单独和不同组合方式诊断胃癌的敏感性进行比较分析。单因素及多因素生存分析探讨肿瘤标志物与患者术后病理及生存预后的关系。(2)通过实时定量PCR法检测miR-30b的表达水平；CCK8法检测细胞增殖；流式细胞术检测细胞凋亡；transwell法检测细胞侵袭和迁移能力；western blot检测蛋白表达水平；双萤光素酶报告基因实验验证miR-30b的靶基因。(3)分析2007年2月至2015年3月于北京协和医院收治接受术前化疗和手术的115例胃癌患者的临床病例资料,所有患者采用Xelox化疗方案,奥沙利铂130mg/m2静脉滴入2h,第一天；口服卡培他滨1000mg/m2,第1-2周,后休息一周。三周为一疗程,患者至少接受2周期的术前化疗。评估新辅助化疗的疗效、毒副反应及与患者预后的关系。通过检测临床及实验室指标,评估空肠穿刺置管肠内营养对胃癌患者术后营养状况及并发症的影响。结果(1)肿瘤标志物CEA、CA19-9、CA242及CA50检测胃癌的阳性率分别为17.67,17.12,20.44和13.81%。四项肿瘤标志物联合检测的阳性率为36.57%。术前血清CEA、CA19-9、CA242和CA50升高的胃癌患者,其肿瘤临床分期也较晚,并且有较差的总生存率。术前血清CEA、CA19-9、CA242和CA50升高的胃癌患者,5年生存率分别为28.12,25.83,27.02和24.05%,而术前此四项肿瘤标志物正常的患者5年生存率则分别为55.01,55.37,56.36,54.51%(P0.01)。Cox比例风险模型行多因素分析示升高的CA242可作为判断胃癌预后差的独立因素。(2)miR-30b表达水平在胃癌组织中明显下降。miR-30b低表达与淋巴结转移密切相关,miR-30b在23对胃癌组织中的表达与患者的年龄、性别和Lauren分型无明显相关性。(3)CCK-8实验结果显示,过表达miR-30b可明显抑制胃癌细胞的生长。相反,将miR-30b inhibitor转染至胃癌细胞降低miR-30b的表达,结果显示明显促进了胃癌细胞生长。流式细胞仪检测了miR-30b对于胃癌细胞凋亡的影响,表明过表达miR-30b可以诱导胃癌细胞的凋亡。在胃癌细胞中过表达miR-30b,可以显著的抑制穿过小室孔膜的细胞数,抑制胃癌细胞侵袭迁移能力。相反,转染inhibitor下调miR-30b在胃癌细胞的表达水平,则促进了胃癌细胞的侵袭转移。(4)通过构建包含种子区的野生型和突变型双萤光素酶报告基因载体,并分别与miR-30b mimics或mimics control共转染293T细胞,发现共转染mimics与野生型载体的细胞的荧光素酶活性显著低于共转染mimics与突变型载体,mimics control与野生型载体,提示EIF5A2是miR-30b的直接靶基因。(5)miR-30b可能通过下调EIF5A2进而激活上皮间质转化的相关指标E-cadherin口β-catenin,抑制了肿瘤细胞的侵袭转移。(6)对新辅助化疗并行手术治疗的患者进行分析,完全缓解(CR)2例,部分缓解(PR)55例,稳定(SD)47例,进展(PD)有11例,化疗有效率为49.6%,疾病控制率为90.4%。术前T分期的降期率为48.7%。化疗后最常见的不良反应为白细胞减少(16.5%)和胃肠道反应(12.2%),多为I-II度。经过对症治疗后均可得到缓解。接受新辅助化疗和手术的患者中位生存期48个月,5年生存率42.4%。化疗疗效为PR的患者生存期明显优于SD和PD的患者,差异具有统计学意义(P0.001)。GPS评分(Glasgow prognostic score)较低的患者对于术前化疗有较好的缓解(P=0.028)。多因素回归比例模型分析显示化疗反应性(P=0.026)、肿瘤pTNM分期(P=0.037)、Lauren分型(P=0.033)和GPS评分(P=0.002)为新辅助化疗胃癌患者预后的独立因素。(7)术后第3、7天,置管的肠内营养组白蛋白水平要高于不置管的肠外营养组患者；术后第3天,前白蛋白水平在置管组要高于不置管组。经空肠穿刺管营养可以促进患者早日排气,并且对肝功能具有保护作用。两组患者的生存期尚未观察到明显差别。结论：(1)联合检测CEA、CA19-9、CA242%和CA50可以提高胃癌诊断的阳性率。CA242有较高的诊断价值。在可切除的胃癌患者中,术前的CA242与胃癌的分期有关,其是胃癌患者预后的独立预测因子；(2)miR-30b在胃癌组织中及胃癌细胞中低表达；过表达miR-30b可以抑制胃癌细胞增殖、促进细胞凋亡,抑制胃癌细胞的侵袭转移；(3) EIF5A2是miR-30b的直接靶基因,miR-30b可能通过下调EIF5A2进而激活上皮间质转化的相关指标E-cadherin和β-catenin,抑制了肿瘤细胞的侵袭转移；(4) Xelox新辅助化疗方案对于进展期胃癌患者有较好的有效率,化疗毒副反应不重。新辅助化疗后取得明显临床缓解的患者预后要好。化疗反应性、术后病理分期、Lauren分型和GPS评分可以作为新辅助化疗并手术治疗的胃癌患者预后的独立因素；(5)接受新辅助化疗手术的患者经空肠营养管早期肠内营养安全方便,可以改善患者术后早期的营养状况。
[Abstract]:Background: The early diagnosis is difficult, the resistance of chemotherapy and the lack of effective prognostic index are important problems in the research field of gastric cancer, and the overall prognosis of patients with gastric cancer is limited. It is an important means to find a new diagnostic marker for deep understanding of the occurrence and development mechanism of gastric cancer and to reverse the resistance of chemotherapy to the prognosis of patients with gastric cancer. MicroRNAs (miRNAs) are a class of non-coding single-chain small-molecule RNA with a length of about 22 nucleotides, which play an important role in the aspects of tumorigenesis, development, proliferation, invasion, metastasis and chemotherapy resistance. The expression of MiR-30b in the tumors, such as colorectal cancer, cervical cancer, and breast cancer, is reduced and involved in the control of various tumor biological phenotypes. But its expression level, regulation and mechanism in gastric cancer are not clear. Therefore, it is of great significance to study the expression level of miR-30b in gastric cancer and to study the regulation and mechanism of miR-30b. Neoadjuvant chemotherapy, as part of the comprehensive treatment of the tumor, has been gradually referred to the treatment of local progressive gastric cancer. The new adjuvant chemotherapy is applied to the operation of gastric cancer, and has the following advantages of improving the resection rate and reducing the stage of the tumor, and can also reduce the metastasis of the lymph node and the blood vessel compared with the simple operation. The nutritional status of the pre-operation patients is good, and the side effects of the chemotherapy can be better tolerated. In recent years, the research on neoadjuvant chemotherapy of gastric cancer both at home and abroad has shown that the new adjuvant chemotherapy has obvious effect. However, there is no uniform standard for the new adjuvant chemotherapy regimen, and there is a dispute between the selection of the chemotherapy drug and the chemotherapy period and the time of the evaluation of the curative effect. Objective: (1) To study the value of serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 242 (CA242) and carbohydrate antigen 50 (CA50) in the diagnosis, clinical pathology and prognosis of gastric cancer. (2) To explore the effects of miR-30b on the proliferation, apoptosis, invasion and migration of gastric cancer cell line. And a target gene and a signal path for determining the regulation of the miR-30b. (3) To evaluate the clinical and pathological features and effects of the new adjuvant therapy for patients with advanced gastric cancer. To evaluate the effect of early enteral nutrition support on the nutritional status and complications of patients undergoing neoadjuvant chemotherapy and operation of gastric cancer. Methods: (1) The clinical data of 18 patients with gastric cancer treated by operation in our hospital were collected, and the levels of serum CEA, CA19-9, CA242 and CA50 were analyzed retrospectively. The sensitivity of four tumor markers to the diagnosis of gastric cancer was compared and analyzed by ROC curve. The relationship between tumor markers and postoperative pathology and survival was discussed by single factor and multi-factor survival analysis. (2) the expression level of miR-30b was detected by real-time quantitative PCR; the cell proliferation was detected by the method of CCK8; the cell apoptosis was detected by flow cytometry; the cell invasion and the migration ability were detected by transwell method; the expression level of the protein was detected by western blot; and the target gene of the miR-30b was verified by the double luciferase reporter gene. (3) To analyze the clinical data of 115 patients with gastric cancer who received pre-operative chemotherapy and operation from February 2007 to March 2015. All patients received the Xelerox chemotherapy, oxaliplatin 130 mg/ m2 for 2 hours, the first day, oral capecitabine 1000 mg/ m2, week 1-2, The rest of the week. Three weeks for a course of treatment, the patient received at least 2 cycles of pre-operative chemotherapy. To evaluate the effect of neoadjuvant chemotherapy, the side-side reaction and the relationship with the prognosis of the patients. To evaluate the effect of enteral nutrition on the nutritional status and complications of patients with gastric cancer by detecting the clinical and laboratory parameters. Results (1) The positive rates of CEA, CA19-9, CA242 and CA50 in the detection of gastric cancer were 17.67, 17.12, 20.44 and 13.81%, respectively. The positive rate of the four tumor markers was 36.57%. Pre-operative serum CEA, CA19-9, CA242 and CA50 increased patients with gastric cancer, and their clinical stages were later, and there was a poor overall survival rate. The 5-year survival rates of the pre-operative serum CEA, CA19-9, CA242 and CA50 were 28.12, 25.83, 27.02, and 24.05%, respectively, while the 5-year survival rate of the four tumor markers was 55.01, 55.37, 56.36, 54.51% (P0.01). (2) The expression level of miR-30b was significantly decreased in gastric cancer tissue. The low expression of miR-30b is closely related to lymph node metastasis, and the expression of miR-30b in the tissue of gastric cancer has no significant correlation with the age, sex and Lauren type of the patient. (3) The results of CCK-8 show that the expression of miR-30b can significantly inhibit the growth of gastric cancer cells. In contrast, the transfection of miR-30b in human gastric cancer cells to the expression of miR-30b in gastric cancer cells revealed a significant increase in the growth of gastric cancer cells. The effect of miR-30b on the apoptosis of gastric cancer cells was detected by flow cytometry. It was shown that the expression of miR-30b could induce the apoptosis of gastric cancer cells. The expression of the miR-30b in the gastric cancer cell can significantly inhibit the number of cells passing through the cell membrane and inhibit the invasion and migration of the gastric cancer cells. In contrast, down-regulation of the expression level of miR-30b in gastric cancer cells by transfectitor promoted the invasion and metastasis of gastric cancer cells. (4) By constructing the wild-type and mutant double-luciferase reporter gene vector containing the seed region and co-transfecting the 293T cells with the miR-30b misitics or the mimics control, the luciferase activity of the cells of the co-transfected mimics and the wild-type vector was found to be significantly lower than that of the co-transfected mimetics and the mutant vectors, The micionics control is similar to the wild type vector, suggesting that EIF5A2 is a direct target gene of miR-30b. (5) miR-30b may inhibit the invasion and metastasis of tumor cells by down-regulating EIF5A2 and then activating the relevant index E-cadherin of EIF5A2. (6) The patients who were treated with the new adjuvant chemotherapy were analyzed, the complete response (CR) was 2, the partial response (PR) was 55, the stability (SD) was 47, the progress (PD) was 11, the effective rate of the chemotherapy was 49.6%, and the disease control rate was 90.4%. The pre-operative T staging was 48.7%. The most common adverse reactions after chemotherapy were leukopenia (16.5%) and gastrointestinal (12.2%), mostly I-II. Can be relieved after symptomatic treatment. The median survival in patients receiving neoadjuvant chemotherapy and surgery was 48 months and the 5-year survival rate was 42.4%. The survival time of patients with PR was significantly better than that of SD and PD (P = 0.001). The patients with low level of Glasgow prognostic score had a better response to preoperative chemotherapy (P = 0.028). The multi-factor regression model analysis showed that the response of chemotherapy (P = 0.026), tumor pTNM stage (P = 0.037), Lauren type (P = 0.033) and GPS (P = 0.002) were independent factors for the prognosis of patients with gastric cancer with neoadjuvant chemotherapy. (7) In the third and seventh day of the operation, the level of the intestinal nutrition group of the tube was higher than that of the parenteral nutrition group without the tube, and the pre-albumin level was higher than that of the non-set tube group on the third day after the operation. The nutrition of the jejunal puncture tube can promote the early exhaust of the patient, and has a protective effect on the liver function. There was no significant difference in the survival of the two groups. Conclusion: (1) The positive rate of CEA, CA19-9, CA242% and CA50 in the diagnosis of gastric cancer can be increased. CA242 has high diagnostic value. In the patients with gastric cancer, the preoperative CA242 is related to the stage of gastric cancer, which is an independent predictor of the prognosis of the gastric cancer. (2) The miR-30b is expressed in the gastric cancer tissues and the gastric cancer cells, and the overexpression of the miR-30b can inhibit the proliferation of the gastric cancer cells and promote the cell apoptosis. (3) EIF5A2 is a direct target gene of miR-30b, and miR-30b may further activate the relevant indexes E-cadherin and antigen-catenin of epithelial-mesenchymal transition by down-regulating EIF5A2, and the invasion and metastasis of tumor cells are inhibited; (4) Xelerox neoadjuvant chemotherapy is effective in the patients with advanced gastric cancer. The prognosis of patients with significant clinical remission after neoadjuvant chemotherapy is good. the chemotherapy, the postoperative pathological stage, the Lauren type and the GPS score can be used as independent factors for the prognosis of the gastric cancer patients with neoadjuvant chemotherapy and operation treatment; and (5) the patients receiving the neoadjuvant chemotherapy operation are safe and convenient to the early enteral nutrition of the jejunal nutrition tube, Can improve the nutritional status of the early postoperative patients.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R735.2
本文编号：2493723
[Abstract]:Background: The early diagnosis is difficult, the resistance of chemotherapy and the lack of effective prognostic index are important problems in the research field of gastric cancer, and the overall prognosis of patients with gastric cancer is limited. It is an important means to find a new diagnostic marker for deep understanding of the occurrence and development mechanism of gastric cancer and to reverse the resistance of chemotherapy to the prognosis of patients with gastric cancer. MicroRNAs (miRNAs) are a class of non-coding single-chain small-molecule RNA with a length of about 22 nucleotides, which play an important role in the aspects of tumorigenesis, development, proliferation, invasion, metastasis and chemotherapy resistance. The expression of MiR-30b in the tumors, such as colorectal cancer, cervical cancer, and breast cancer, is reduced and involved in the control of various tumor biological phenotypes. But its expression level, regulation and mechanism in gastric cancer are not clear. Therefore, it is of great significance to study the expression level of miR-30b in gastric cancer and to study the regulation and mechanism of miR-30b. Neoadjuvant chemotherapy, as part of the comprehensive treatment of the tumor, has been gradually referred to the treatment of local progressive gastric cancer. The new adjuvant chemotherapy is applied to the operation of gastric cancer, and has the following advantages of improving the resection rate and reducing the stage of the tumor, and can also reduce the metastasis of the lymph node and the blood vessel compared with the simple operation. The nutritional status of the pre-operation patients is good, and the side effects of the chemotherapy can be better tolerated. In recent years, the research on neoadjuvant chemotherapy of gastric cancer both at home and abroad has shown that the new adjuvant chemotherapy has obvious effect. However, there is no uniform standard for the new adjuvant chemotherapy regimen, and there is a dispute between the selection of the chemotherapy drug and the chemotherapy period and the time of the evaluation of the curative effect. Objective: (1) To study the value of serum carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 242 (CA242) and carbohydrate antigen 50 (CA50) in the diagnosis, clinical pathology and prognosis of gastric cancer. (2) To explore the effects of miR-30b on the proliferation, apoptosis, invasion and migration of gastric cancer cell line. And a target gene and a signal path for determining the regulation of the miR-30b. (3) To evaluate the clinical and pathological features and effects of the new adjuvant therapy for patients with advanced gastric cancer. To evaluate the effect of early enteral nutrition support on the nutritional status and complications of patients undergoing neoadjuvant chemotherapy and operation of gastric cancer. Methods: (1) The clinical data of 18 patients with gastric cancer treated by operation in our hospital were collected, and the levels of serum CEA, CA19-9, CA242 and CA50 were analyzed retrospectively. The sensitivity of four tumor markers to the diagnosis of gastric cancer was compared and analyzed by ROC curve. The relationship between tumor markers and postoperative pathology and survival was discussed by single factor and multi-factor survival analysis. (2) the expression level of miR-30b was detected by real-time quantitative PCR; the cell proliferation was detected by the method of CCK8; the cell apoptosis was detected by flow cytometry; the cell invasion and the migration ability were detected by transwell method; the expression level of the protein was detected by western blot; and the target gene of the miR-30b was verified by the double luciferase reporter gene. (3) To analyze the clinical data of 115 patients with gastric cancer who received pre-operative chemotherapy and operation from February 2007 to March 2015. All patients received the Xelerox chemotherapy, oxaliplatin 130 mg/ m2 for 2 hours, the first day, oral capecitabine 1000 mg/ m2, week 1-2, The rest of the week. Three weeks for a course of treatment, the patient received at least 2 cycles of pre-operative chemotherapy. To evaluate the effect of neoadjuvant chemotherapy, the side-side reaction and the relationship with the prognosis of the patients. To evaluate the effect of enteral nutrition on the nutritional status and complications of patients with gastric cancer by detecting the clinical and laboratory parameters. Results (1) The positive rates of CEA, CA19-9, CA242 and CA50 in the detection of gastric cancer were 17.67, 17.12, 20.44 and 13.81%, respectively. The positive rate of the four tumor markers was 36.57%. Pre-operative serum CEA, CA19-9, CA242 and CA50 increased patients with gastric cancer, and their clinical stages were later, and there was a poor overall survival rate. The 5-year survival rates of the pre-operative serum CEA, CA19-9, CA242 and CA50 were 28.12, 25.83, 27.02, and 24.05%, respectively, while the 5-year survival rate of the four tumor markers was 55.01, 55.37, 56.36, 54.51% (P0.01). (2) The expression level of miR-30b was significantly decreased in gastric cancer tissue. The low expression of miR-30b is closely related to lymph node metastasis, and the expression of miR-30b in the tissue of gastric cancer has no significant correlation with the age, sex and Lauren type of the patient. (3) The results of CCK-8 show that the expression of miR-30b can significantly inhibit the growth of gastric cancer cells. In contrast, the transfection of miR-30b in human gastric cancer cells to the expression of miR-30b in gastric cancer cells revealed a significant increase in the growth of gastric cancer cells. The effect of miR-30b on the apoptosis of gastric cancer cells was detected by flow cytometry. It was shown that the expression of miR-30b could induce the apoptosis of gastric cancer cells. The expression of the miR-30b in the gastric cancer cell can significantly inhibit the number of cells passing through the cell membrane and inhibit the invasion and migration of the gastric cancer cells. In contrast, down-regulation of the expression level of miR-30b in gastric cancer cells by transfectitor promoted the invasion and metastasis of gastric cancer cells. (4) By constructing the wild-type and mutant double-luciferase reporter gene vector containing the seed region and co-transfecting the 293T cells with the miR-30b misitics or the mimics control, the luciferase activity of the cells of the co-transfected mimics and the wild-type vector was found to be significantly lower than that of the co-transfected mimetics and the mutant vectors, The micionics control is similar to the wild type vector, suggesting that EIF5A2 is a direct target gene of miR-30b. (5) miR-30b may inhibit the invasion and metastasis of tumor cells by down-regulating EIF5A2 and then activating the relevant index E-cadherin of EIF5A2. (6) The patients who were treated with the new adjuvant chemotherapy were analyzed, the complete response (CR) was 2, the partial response (PR) was 55, the stability (SD) was 47, the progress (PD) was 11, the effective rate of the chemotherapy was 49.6%, and the disease control rate was 90.4%. The pre-operative T staging was 48.7%. The most common adverse reactions after chemotherapy were leukopenia (16.5%) and gastrointestinal (12.2%), mostly I-II. Can be relieved after symptomatic treatment. The median survival in patients receiving neoadjuvant chemotherapy and surgery was 48 months and the 5-year survival rate was 42.4%. The survival time of patients with PR was significantly better than that of SD and PD (P = 0.001). The patients with low level of Glasgow prognostic score had a better response to preoperative chemotherapy (P = 0.028). The multi-factor regression model analysis showed that the response of chemotherapy (P = 0.026), tumor pTNM stage (P = 0.037), Lauren type (P = 0.033) and GPS (P = 0.002) were independent factors for the prognosis of patients with gastric cancer with neoadjuvant chemotherapy. (7) In the third and seventh day of the operation, the level of the intestinal nutrition group of the tube was higher than that of the parenteral nutrition group without the tube, and the pre-albumin level was higher than that of the non-set tube group on the third day after the operation. The nutrition of the jejunal puncture tube can promote the early exhaust of the patient, and has a protective effect on the liver function. There was no significant difference in the survival of the two groups. Conclusion: (1) The positive rate of CEA, CA19-9, CA242% and CA50 in the diagnosis of gastric cancer can be increased. CA242 has high diagnostic value. In the patients with gastric cancer, the preoperative CA242 is related to the stage of gastric cancer, which is an independent predictor of the prognosis of the gastric cancer. (2) The miR-30b is expressed in the gastric cancer tissues and the gastric cancer cells, and the overexpression of the miR-30b can inhibit the proliferation of the gastric cancer cells and promote the cell apoptosis. (3) EIF5A2 is a direct target gene of miR-30b, and miR-30b may further activate the relevant indexes E-cadherin and antigen-catenin of epithelial-mesenchymal transition by down-regulating EIF5A2, and the invasion and metastasis of tumor cells are inhibited; (4) Xelerox neoadjuvant chemotherapy is effective in the patients with advanced gastric cancer. The prognosis of patients with significant clinical remission after neoadjuvant chemotherapy is good. the chemotherapy, the postoperative pathological stage, the Lauren type and the GPS score can be used as independent factors for the prognosis of the gastric cancer patients with neoadjuvant chemotherapy and operation treatment; and (5) the patients receiving the neoadjuvant chemotherapy operation are safe and convenient to the early enteral nutrition of the jejunal nutrition tube, Can improve the nutritional status of the early postoperative patients.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R735.2
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中国期刊全文数据库 前8条
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