结直肠癌P53蛋白定量分析及其与肿瘤生物学行为的关系

应用MD-20显微图象分析仪对30例结直肠癌的P53蛋白免疫组织化学反应产物进行定量测定,以观察P53蛋白相对含量与肿瘤生物学行为的关系.结果显示:结直肠癌P53蛋白MOD值与PCNA增殖指数呈正相关(P<0.05).P53蛋白MOD值大的肿瘤多里浸润性生长方式,且浸润至浆膜外者多(PM<0.01,P<0.05).淋巴结转移与MOD值无明显关系(P>0.05).结果提示:结直肠癌P53蛋白相对含量对肿瘤的生物学行为有重要影响.     

Anticancer and structure-activity relationship evaluation of 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide analogs of chalcone

To identify new potent chemotherapeutic agents, we synthesized compounds with 3-(naphthalen-2-yl)-N,5-diphenyl-pyrazoline-1-carbothioamide (NDPC) skeletons and evaluated their cytotoxicities using a clonogenic long-term survival assay. Their half-maximal cell growth inhibitory concentrations ranged from a few hundred nanomolars to a few micromolars. Further biological experiments including flow cytometry and western blotting analysis were performed with the derivative showing the best cytotoxicity. To identify a target protein of the selected compound, an in vitro kinase assay was carried out, which revealed that aurora kinases A and B were inhibited by the test compound, and this was confirmed using western blot analysis. The molecular binding mode between the selected compound and the kinases was elucidated using in silico docking. The structural conditions required for good cytotoxicity were identified based on the quantitative relationships between the physicochemical properties of the derivatives and their cytotoxicities.     

Serum miR‐92a‐1 is a novel diagnostic biomarker for colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers worldwide, with high mortality. Abnormally expressed microRNAs (miRNAs) are considered novel biomarkers in cancer diagnosis. The aim of this study was to investigate the diagnostic value of miR‐92a‐1 in patients with CRC. Serum samples were collected from 148 patients pathologically diagnosed with CRC and 68 gender‐ and age‐matched healthy volunteers. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to measure serum miR‐92a‐1 level. Relationship between miR‐92a‐1 and clinicopathological features of CRC cases was analysed via chi‐square test. Receiver operating characteristic (ROC) curve was plotted to estimate the diagnostic value of miR‐92a‐1 in CRC. Serum miR‐92a‐1 was significantly up‐regulated in CRC patients compared with healthy individuals (P < .001). Moreover, miR‐92a‐1 expression was correlated with TNM stage (P = .02), histological stage (P = .003), lymph node metastasis (P = .003) and distant metastasis (P < .001). ROC analysis showed that the area under the ROC curve (AUC) was 0.914, suggesting high diagnostic accuracy of miR‐92a‐1 in ROC. The optimal cut‐off value was 1.485, with a sensitivity of 81.8% and a specificity of 95.6%. MiR‐92a‐1 is increased in CRC patients and correlated with aggressive clinical characteristics. Serum miR‐92a‐1 may be a potential diagnostic biomarker for CRC.     

结直肠癌肝转移患者血清OPN、YKL-40、HGF和VEGF-A水平及其危险因素分析

目的:检测结直肠癌肝转移患者血清骨桥蛋白(Osteopontin,OPN)、人类软骨糖蛋白-39(Human cartilage gp-39,YKL-40)、肝细胞生长因子(Hepatocyte growth factor,HGF)和血管内皮生长因子A(Vascular endothelial growth factor A,VEGF-A)水平,并分析直肠癌患者发生肝转移的危险因素。方法:收集56例发生肝转移的直结肠癌患者和50例未发生肝转移的直结肠癌患者,采用酶联免疫法检测两组患者血清OPN、YKL-40、HGF和VEGF-A的水平。收集所有患者的临床资料,分析直肠癌患者发生肝转移的危险因素。结果:结直肠癌肝转移患者血清OPN、YKL-40、HGF和VEGF-A水平均显著高于未发生肝转移的直结肠癌患者(P0.05);糖尿病、肿瘤最大直径、病理类型、分化程度、浸润深度、淋巴结转移、盆腹膜种植、肝外转移、吸烟史均与结直肠癌发生肝转移相关(P0.05);而HGF、VEGF-A、糖尿病、肿瘤最大直径≥5 cm、淋巴结转移、盆腹膜种植、肝外转移是直肠癌发生肝转移的独立危险因素(P0.05)。结论:结直肠癌肝转移患者血清OPN、YKL-40、HGF和VEGF-A明显升高,HGF、VEGF-A、糖尿病、肿瘤最大直径≥5 cm、淋巴结转移、盆腹膜种植、肝外转移是直肠癌发生肝转移的独立危险因素。     

单切口腹腔镜在结直肠手术中的应用效果及对炎症因子与应激反应的影响

目的:探讨单切口腹腔镜在结直肠手术中的应用效果及对炎症因子与应激反应的影响。方法:选择2018年1月至2019年10月我院接诊的98例结直肠癌患者,通过随机数表法分为2组,每组49例。观察组使用单切口腹腔镜结直肠癌根治术,对照组使用传统腹腔镜结直肠癌根治术,常规5孔操作法。比较两组围术期相关情况、手术前后血清炎症因子水平的变化、手术后应激反应及并发症的发生情况。结果:两组淋巴结清扫个数、中转开腹例数、术后排气时间比较差异均无统计学意义(P0.05),观察组手术时间明显长于对照组,脐切口长度、住院时间、术中出血量均显著短于或低于对照组;两组术后1 d、3 d、5 d时高敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、去甲肾上腺素(NE)、肾上腺素(E)、皮质醇(Cor)水平均明显高于术前(P0.05);且观察组术后1d、3d、5d时hs-CRP、TNF-α、IL-6、NE、E、Cor较对照组显著降低(P0.05);两组吻合口瘘、吻合口狭窄、吻合口出血、小肠穿孔、肠梗阻、感染的总发生率比较差异无统计学意义(P0.05)。结论:和传统5孔操作法相比,单切口腹腔镜结直肠癌根治术治疗结直肠癌患者的手术时间更长,但术后炎症因子表达更低,应激反应更小,有利于患者术后恢复。     

结直肠癌患者血清GDF-15、G-CSF水平与临床病理特征及预后的关系

摘要 目的：探究结直肠癌血清生长分化因子-15（GDF-15）、粒细胞集落刺激因子（G-CSF）水平与患者临床病理参数、预后的关系,并分析其对结直肠癌的诊断价值。方法：采集结直肠癌患者、结直肠腺瘤患者及健康体检志愿者的血清样本,酶联免疫吸附测定（ELISA）实验检测血清GDF-15、G-CSF;分析结直肠癌患者血清GDF-15、G-CSF水平与患者临床病理参数的关系;Kaplan Meier生存曲线分析血清GDF-15、G-CSF水平与患者预后的关系;受试者工作特征曲线（ROC）分析血清GDF-15、G-CSF水平对结直肠癌的诊断价值。结果：结直肠癌患者血清GDF-15、G-CSF水平高于结直肠腺瘤患者及健康体检志愿者（均P<0.05）;血清GDF-15水平与肿瘤直径、分化程度、远处转移及TNM分期相关（均P<0.05）;血清G-CSF水平与肿瘤分化程度、远处转移及TNM分期相关（均P<0.05）;Kaplan Meier生存曲线结果显示,血清GDF-15低表达、G-CSF低表达患者的术后5年总生存率及中位生存时间均分别高于血清GDF-15高表达、G-CSF高表达患者（均P<0.05）;ROC分析结果表明,血清GDF-15、G-CSF有较好的诊断结直肠癌的价值,血清GDF-15、G-CSF联合应用的敏感度、特异度分别为0.876、0.863。结论：结直肠癌患者血清GDF-15、G-CSF水平升高,且均与患者病情恶性进展、不良预后相关;血清GDF-15、G-CSF是诊断结直肠癌的潜在指标。     

花生四烯酸通过COX-2酶代谢氧化失活PTEN促进结直肠癌生长

摘要 目的：本研究旨在阐明过表达COX-2的结直肠癌中花生四烯酸代谢与PTEN及其下游通路的相互关系。方法：利用过表达COX-2结直肠癌细胞系CT26和Apc ^Min/+小鼠腺瘤模型,联合花生四烯酸、COX-2抑制剂NS-398和COX-2基因敲除的干预,采用流式细胞仪检测细胞凋亡、细胞周期及活性氧的产生;Transwell和克隆形成试验观察细胞的迁移和增殖能力;Western blot和免疫组化检测PTEN及其下游相关蛋白的表达。结果：花生四烯酸通过COX-2酶代谢产生活性氧并失活PTEN抑癌基因表达,从而激活PI3K-AKT蛋白促进CT26结直肠癌细胞迁移和增殖,抑制细胞凋亡;而COX-2抑制剂NS-398阻止了花生四烯酸在CT26结直肠癌细胞中的恶性生物学行为。同时,在COX-2基因敲除Apc ^Min/+小鼠腺瘤组织中,减弱了氧化应激水平,增加了PTEN表达,抑制了PI3K-AKT磷酸化,进一步抑制腺瘤生长,提高小鼠生存率。结论：花生四烯酸通过COX-2酶代谢产生活性氧下调PTEN活性,并激活PI3K-AKT促进结直肠癌生长;COX-2抑制剂可间接促进PTEN表达,抑制结直肠癌生长,能够作为CRC的潜在治疗靶点。     

The efficacy of 18F-FDG PET/CT-based diagnostic model in the diagnosis of colorectal cancer regional lymph node metastasis

In order to assess the efficacy of ¹⁸F-FDG PET/CT-based diagnostic model in diagnosing colorectal cancer (CRC) lymph node metastasis (LNM), the ¹⁸F-FDG PET/CT medical records of CRC patients were acquired, and the CRC regional LNM diagnostic model was constructed through the combination of image and grain factors of ¹⁸F-FDG PET/CT. The specific analysis methods include univariate analysis, multivariate analysis, ROC curve analysis, and statistical analysis. The research results showed statistical differences in TNM staging, intestinal obstructions, tumor infiltration, regional lymph node (LN) SUVmax, regional LN minimum dimension, and remote metastasis between the CRC patients in the LNM positive group and the LNM negative group. Through the comparisons between the diagnostic model proposed in the research and other diagnostic methods, it was found that the AUC (95%CI) and sensitivity of the proposed diagnostic model were the highest, the comprehensive diagnostic efficacy of the diagnostic model was optimal. Therefore, it was concluded that the diagnostic model was of significant application values, which provided the basis for subsequent clinical diagnosis of CRC.     

结直肠癌患者手术前后血清PCT、ADPN和 IL 6水平变化及其与肠道菌群失调的相关性

目的探讨结直肠癌患者手术前后血清降钙素(PCT)、白介素6(IL-6)和人脂联素(ADPN)的水平变化及其与肠道菌群失调的相关性。方法选取我院2016年3月至2018年10月收治的120例择期进行手术的结直肠癌患者为研究对象,其中肠道菌群正常者49例,Ⅰ度菌群失调者46例,Ⅱ度菌群失调者25例。比较3类患者一般资料、手术前后血清PCT、ADPN和IL-6水平之间的差异,分析血清PCT、ADPN和IL-6水平与菌群失调之间的相关性。结果 3类患者年龄、侵袭深度、临床分型、DUKE分期之间的差异均有统计学意义(均P0.05)。治疗后,不同程度菌群失调患者血清PCT、ADPN和IL-6之间的差异有统计学意义(均P0.05)。经两两比较,血清ADPN随患者菌群异常程度的升高而降低,PCT、IL-6随患者菌群异常程度的升高而升高(均P0.05)。随着患者菌群失调情况的加重,患者肠道球菌数量增加,杆菌数量降低(均P0.05)。患者血清PCT、ADPN水平与患者肠道乳杆菌、双歧杆菌以及真杆菌数量呈正相关(r=0.352、0.699、0.223、0.165、0.356、0.621,P=0.035、0.002、0.001、0.045、0.003、0.001),与肠球菌数量呈负相关(r=-0.756、-0.465,P=0.002、0.002)。患者血清IL-6水平与患者的乳杆菌、双歧杆菌以及真杆菌数量呈负相关(r=-0.263、-0.362、-0.250,P=0.012、0.022、0.001),与肠球菌数量呈正相关(r=0.175,P=0.002)。结论结直肠癌患者手术后血清ADPN、IL-6显著下降,PCT显著升高,且随着患者菌群失调程度的变化而变化,提示可将益生菌治疗作为降低局部炎性反应的措施之一。     

结直肠息肉切除术患者肠道微生态失调分析及其与癌变进展的相关性

目的分析结直肠息肉切除术患者肠道微生态失调情况及其与癌变进展的相关性。方法前瞻性选择2015年7月至2016年7月在我院行结直肠息肉切除术的89例患者为研究对象,评价所有研究对象手术前后肠道菌群计数、肠道菌群失调情况,采用单因素和多因素Logistic回归分析结直肠息肉切除术患者癌变的影响因素。结果结直肠息肉患者术后大肠埃希菌计数(10.85±0.50)、粪肠球菌计数(10.12±0.55)显著高于术前(8.34±0.41,7.76±0.37)(均P0.01),结直肠息肉患者术后双歧杆菌计数(2.56±0.68)、乳杆菌计数(2.83±0.71)显著低于术前(5.20±1.06,5.93±0.88)(均P0.01)。结直肠息肉患者术后Ⅰ度菌群失调比例(23.60%)显著低于术前(55.06%)(P0.05),结直肠息肉患者术后Ⅱ、Ⅲ度菌群失调比例(50.56%,25.84%)显著高于术前(34.83%,10.11%)(均P0.05)。随访3年显示89例结直肠息肉切除术患者癌变率为33.71%,性别、病理类型不同的结直肠息肉切除术患者癌变率差异无统计学意义(均P0.05),年龄、遗传史、息肉直径、肠道菌群失调程度不同的结直肠息肉切除术患者癌变率差异具有统计学意义(均P0.05)。年龄、遗传史、肠道菌群失调程度是结直肠息肉切除术患者癌变的影响因素(均P0.05)。结论结直肠息肉切除术患者存在明显肠道微生态失调情况,肠道微生态失调是结直肠息肉切除术患者癌变的危险因素,这对临床防治结直肠息肉切除术患者癌变有重要指导意义。