目的 探究M2型肿瘤相关巨噬细胞(TAM)通过调控胃癌细胞程序性死亡配体-1(PD-L1)表达影响肿瘤细胞转移和免疫抑制因子分泌的机制.方法 人单核细胞株THP-1经佛波酯(PMA)和白细胞介素-4(IL-4)诱导建立M2型TAM模型,免疫荧光染色检测M2型TAM表面标记物CD206的表达.将人胃癌细胞系MKN-45分为对照组(未经转染的MKN-45细胞)、siPD-L1组(将siPD-L1转染至MKN-45细胞)、M2组(在Transwell小室上室接种M2型TAM,下室接种MKN-45细胞)和siPD-L1+M2组(在Transwell小室上室接种M2型TAM,下室接种转染siPD-L1的MKN-45细胞).RT-qPCR检测转染效果;免疫荧光染色和流式细胞术检测各组MKN-45细胞PD-L1的表达;划痕实验检测各组MKN-45细胞划痕愈合率;Transwell实验检测各组MKN-45细胞迁移与侵袭;ELISA测定各组MKN-45细胞培养液上清中血管内皮生长因子(VEGF)、转化生长因子-β(TGF-β)和白细胞介素-6(IL-6)水平.结果 THP-1细胞经PMA与IL-4诱导后,细胞贴壁生长,形态多样且伸出伪足,细胞内CD206荧光染色强度明显增加,说明M2型TAM构建成功.转染siPD-L1的MKN-45细胞内PD-L1相对表达量降低,表示转染成功.与对照组比较,M2组的MKN-45细胞内PD-L1荧光强度增强,细胞表面PD-L1表达升高,划痕愈合率、细胞迁移及侵袭数目升高/增加,VEGF、TGF-β和IL-6含量也增加,差异均有统计学意义(P<0.05).与M2组比较,siPD-L1+M2组的MKN-45细胞内PD-L1荧光强度减弱,细胞表面PD-L1表达降低,划痕愈合率、细胞迁移及侵袭数目降低/减少,VEGF、TGF-β和IL-6水平降低,差异均有统计学意义(P<0.05).结论 M2型TAM能够促进胃癌细胞迁移与侵袭,并增加免疫抑制因子分泌,从而促进肿瘤细胞转移及免疫逃逸,该作用可能与调控PD-L1表达有关.
目的 观察奥沙利铂联合卡培他滨(XELOX)化疗联合肠益方治疗老年晚期结直肠癌的临床疗效及其对患者生存质量、免疫功能及血浆硫酸类肝素蛋白多糖2(SDC2)、胞裂蛋白9(SEPT9)水平的影响.方法 回顾性分析2021年1月至2022年6月期间在海南医学院第二附属医院接受治疗的84例老年晚期结直肠癌患者,按治疗方案不同分为两组,每组各42例.观察组在XELOX化疗基础上结合肠益方治疗,对照组仅予以XELOX化疗治疗,均3周为1个周期,治疗4个周期.比较两组患者的临床疗效、生存质量、免疫功能及SDC2、SEPT9阳性率.结果 观察组患者的近期总有效率为78.57%,明显高于对照组(52.38%),差异有统计学意义(P<0.05).治疗后,观察组患者的CD4+、CD4+/CD8+水平分别为(40.58±2.51)%、1.68±0.37,均明显高于对照组[(30.22±2.39)%、1.25±0.31],差异均有统计学意义(P<0.05);两组患者治疗后CD8+比较,差异无统计学意义(P>0.05).观察组患者的生存质量改善率为73.81%,明显高于对照组(42.86%),差异有统计学意义(P<0.05).观察组患者治疗后的SDC2阳性率、SEPT9阳性率分别为9.52%、16.67%,均明显低于对照组(30.95%、38.10%),差异均有统计学意义(P<0.05).结论 XELOX化疗联合肠益方治疗老年晚期结直肠癌可取得满意的近期疗效,有助于改善患者的机体免疫功能,并可提高患者的生存质量,且有助于下调SDC2、SEPT9阳性表达.
Objective:To probe the mechanism of anti-pancreatic cancer of dendritic cell (DC)-biopsy xenograft of pancreatic carcinoma line-3 (BxPC-3) vaccine by high-throughput sequencing of mRNA.Methods:A total of50 ml of peripheral venous blood was separated by lymphocyte separation fluid, and DCs and systematic immune effector cells (SIECs) were obtained by adherent culture, and then proliferation of DCs was induced. When DCs were sensitized, BxPC-3∶DCs=1∶1; when the experiments on the inhibition and apoptosis were done in BxPC-3, DCs∶SIECs∶target cells=1∶20∶2. The mRNA high-energy sequencing, cell counting kit-8 (CCK-8), Annexin V-fluoresceine isothiocyanate (FITC), and propidium iodide (PI) methods were used for detection.Results:The CCK-8 assay showed that the survival rate of BxPC-3 in the sensitized DCs group and DCs-BxPC-3 fusion vaccine group was 56.7% and 23.2% respectively (Dunnett’13 test, t=11.160, P<0.05). Apoptosis experiments showed that the sensitized DCs group and DCs-BxPC-3 tumor vaccine group had an apoptosis rate of (23.12±1.05)% and (80.86±5.09)% for BxPC-3, and the difference between two groups was statistically significant ( t=19.240, P<0.05). Gene ontology (GO) analysis of differential mRNA showed that the tumor vaccine group was enriched in functions such as catalytic activity, molecular signaling activity, immune system, metabolic process, and biological regulation. The kyoto encyclopedia of genes and genomes (KEGG) results showed that differential genes were mainly enriched in interfering with tumor cell amino acid metabolism and lipid transport. Conclusion:The antitumor effect of DC tumor vaccine to induce immune effector cells is better than that of tumor lysate-sensitized DC.
目的 分析海南热带地区胰腺癌患者临床特征,为及时发现、合理诊治胰腺癌提供依据.方法 基于电子病历(electronic medical record,EMR)系统收集胰腺癌患者临床资料,应用SPSS 22.0软件进行统计学分析.结果 352例患者男女性别比1∶0.66,年龄(65±13)岁;黄疸占40.3%、腹痛36.1%;无转移占33.5%、有转移66.5%.百分位数法显示淋巴细胞及其比率、葡萄糖(glucose,Glu)、丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(aspartic acid aminotransferase,AST)、直接胆红素(direct bilirubin,DB)、间接胆红素(indirect bilirubin,IB)、癌胚抗原(carcinogenic antigen,CEA)、肿瘤标志物糖链抗原(tumor marker sugar chain antigen 19-9,CA19-9)与正常参考值范围比较有差异.Mann-Whitney U检验显示白细胞、中性粒细胞及其比率、中性粒细胞与淋巴细胞比值(ratio of neutrophils to lymphocytes,NLR)、ALT、AST、DB、IB、CEA 组间有差异(均有P<0.05).二分类Logistic回归分析模型显示NLR≥3.7是NLR<3.7时发生转移风险的4.958(1.896~ 12.964)倍,IB与转移风险呈负关联.结论 65岁左右具有黄疸、腹痛症状者,淋巴细胞及其比率、Glu、ALT、AST、DB、IB、CEA、CA19-9检查有助于胰腺癌的及时发现;NLR及IB对胰腺癌的合理治疗具有指导意义.
Objective:Pancreatic cancer is one of the highly malignant tumors of the digestive tract. The pathogenesis is still unclear. The clinical manifestations are mainly upper abdominal pain, jaundice, weight loss and fatigue, and even mental and neurological disorders. However, these symptoms did not manifest in the early stage,leading to early detection, early diagnosis, early treatment, and poor prognosis. Therefore, research on clinical indicators of pancreatic cancer has become a hot topic, such as Tumor marker, albumin/globulin ratio and neutrophil/ lymphocyte ratio, collagen type VI α1 chain, constitutive photomorpho-genesis 9 signaloSome,Soluble UL16-binding protein 2 etc.These indic- ators are one of the commonly used diagnostic methods after pathology and imaging diagnosis.This article reviews and analyzes the indicators related to pancreatic cancer in recent years and reports the following.