TNF-A基因多态性及其单体型与新疆维、汉民族胃癌的关系

目的:探讨新疆维吾尔族(维族)和汉族胃癌患者肿瘤坏死因子-α基因(TNF-A)rs1800629和rs361525位点多态性及其单体型与胃癌易感性的关系。方法:采用Snapshot技术分析322例胃癌患者(其中维族93例,汉族229例)和作为对照的487例非胃癌患者(其中维族231例,汉族256例)TNF-A基因rs1800629和rs361525位点基因型的分布;利用SHEsis软件分析其构成的单体型在病例组和对照组中的分布频率,比较基因型和单体型在病例组和对照组间的分布差异。结果:在维族人群中,TNF-A基因rs1800629和rs361.525位点不论是等位基因位点、基因型还是单体型在病例组和对照组中的分布频率差异均无统计学意义(P>0.05)。在汉族人群中,TNF-A基因rs361525位点AA+GA基因型在病例组和对照组之间的分布差异有统计学意义(χ=4.56,P=0.03),即携带A等位基因者发生胃癌的风险增加(OR=2.41,95%CI:1.06～5.49);rs1800629位点基因型与胃癌之间未发现明显关联;A-A单体型在病例组及对照组分布频率分别为0.92%和0.86%,差异有统计学意义(χ~2=7.03,P=0.01)。结论:TNF-A基因单核苷酸多态性与汉族人群胃癌发病风险相关,这种相关性具有民族差异。     

预后营养指数对腹腔镜直肠癌根治术后并发症的预测价值

目的:探讨预后营养指数(PNI)对腹腔镜直肠癌根治术后并发症的预测价值。方法:回顾性分析2016年1月至2020年5月在我院普外科行腹腔镜直肠癌根治术的220例直肠癌患者的临床资料。根据术后有无发生并发症分为并发症组(n=63例)和无并发症组(n=157例)。比较两组临床病理特征;采用多因素Logistic回归分析影响腹腔镜直肠癌根治术后并发症的危险因素。结果:220例接受腹腔镜直肠癌根治术患者中63例(28.64％)术后发生了并发症;两组年龄、性别、BMI、术前有合并疾病、肿瘤位置、TNM分期、肿瘤直径、手术时间、PNI组间比较差异有统计学意义(P＜0.05);多因素Logistic回归分析显示,年龄、性别、术前合并疾病、肿瘤位置、手术时间和PNI是腹腔镜直肠癌根治术后并发症发生的独立危险因素(P＜0.05)。结论:术前低PNI是腹腔镜直肠癌根治术后并发症的独立危险因素,临床上可通过PNI评估患者术前营养状况,必要时术前予以营养支持治疗。     

RNAi沉默肺腺癌A549细胞系PD-L1基因表达对其增殖和凋亡的影响

目的:沉默肺癌细胞系A549的程序性死亡配体1(programmed death ligand 1,PD-L1)基因,观察其对A549细胞增殖和凋亡的影响。方法:构建PD-L1 shRNA重组质粒p GPU6/PD-L1,并应用脂质体转染法将其转染入A549细胞。RT-PCR法检测PD-L1基因的表达;Western blotting法检测PD-L1蛋白的表达;MTT法检测p GPU6/PD-L1对A549细胞增殖的影响;AnnexinⅤ-FITC/PI双染法检测p GPU6/PD-L1对A549细胞凋亡的影响。结果:成功将p GPU6/PD-L1转染入A549细胞;RT-PCR结果显示p GPU6/PD-L1使A549细胞PD-L1基因表达水平降低;Western blotting结果显示p GPU6/PD-L1转染A549细胞使PDL1蛋白表达减少;MTT结果显示p GPU6/PD-L1能够抑制A549细胞增殖;AnnexinⅤ-FITC/PI双染法检测结果显示p GPU6/PD-L1能够诱导A549细胞凋亡。结论:p GPU6/PD-L1能够下调肺癌细胞A549 PD-L1的表达,抑制细胞增殖,并诱导细胞凋亡。     

MicroRNA-200a suppresses the Wnt/β-catenin signaling pathway by interacting with β-catenin

The Wnt/β-catenin signaling pathway is crucial for human organ development and is involved in tumor progression of many cancers. Accumulating evidence suggests that the expression of β-catenin is, in part, regulated by specific microRNAs (miRNAs). The purpose of this study was to determine the expression of a recently identified epithelial to mesenchymal transition (EMT)-associated tumor suppressor microRNA (miR)-200a, in cancer cells. We also aimed to identify specific miR-200a target genes and to investigate the antitumor effects of miR-200a on the Wnt/β-catenin signaling pathway. We employed TOP/FOP flash luciferase assays to identify the effect of miR-200a on the Wnt/β-catenin pathway and we confirmed our observations using fluorescence microscopy. To determine target genes of miR-200a, a 3' untranslated region (3' UTR) luciferase assay was performed. Cell viability, invasion and wound healing assays were carried out for functional analysis after miRNA transfection. We further investigated the role of miR-200a in EMT by Western blot analysis. We found fluctuation in the expression of miR-200a that was accompanied by changes in the expression of members of the Wnt/β-catenin signaling pathway. We also determined that miR-200a can directly interact with the 3' UTR of CTNNB1 (the gene that encodes β-catenin) to suppress Wnt/β-catenin signaling. MiR-200a could also influence the biological activities of SGC790 and U251 cells. Our results demonstrate that miR-200a is a new tumor suppressor that can regulate the activity of the Wnt/β-catenin signaling pathway via two mechanisms. MiR-200a is a candidate target for tumor treatment via its regulation of the Wnt/β-catenin signaling pathway.     

Frequent hypermethylation of RASSF1A and TSLC1, and high viral load of Epstein-Barr Virus DNA in nasopharyngeal carcinoma and matched tumor-adjacent tissues

We examined the promoter hypermethylation of tumor-suppressor genes RASSF1A and TSLC1, quantitated EBV DNA load in nasopharyngeal carcinoma (NPC) tissues (T tissues), and matched tumor-adjacent tissues outside 0.5 cm (P tissues) and outside 1.0 cm (Z tissues) to evaluate the role of promoter hypermethylation of RASSF1A and TSLC1 as well as viral load in the pathogenesis of NPC. Methylation-specific polymerase chain reaction (PCR) for RASSF1A and TSLC1 and quantitative real-time PCR analysis of EBV DNA were performed on matched T, P, and Z tissues (n = 28) as well as chronic nasopharyngitis tissues (n = 8). Hypermethylated RASSF1A was frequently detected in the T (82%) and P tissues (75%), but less frequently in Z tissues (46%). he average quantities of EBV DNA (copies/microg DNA) in matched T, P, and Z tissues were 673,000, 90,000, and 7000. The differences of promoter hypermethylation of RASSF1A and EBV viral load among T, P, and Z tissues were statistically significant, with more frequent methylation and higher viral load detected when tissues examined were nearer to the NPC tissues. Our results suggest that aberrant hypermethylation of RASSF1A and high EBV load might be important events in NPC pathogenesis, and they may be useful molecular diagnostic markers for this cancer.     

伴有钙化的乳腺浸润性导管癌病理特征及预后分析

目的 乳腺癌已成为世界范围内女性恶性肿瘤中最常见的死因,伴有钙化的乳腺癌占乳腺癌30％～50％.探讨伴有钙化的乳腺浸润性导管癌(invasive ductal carcinoma,IDC)的临床病理特征及预后的影响因素.方法 收集2012-06-01-2013-06-30新疆医科大学附属肿瘤医院收治的初治可手术女性乳腺癌患者307例的临床病理资料和随访资料,根据乳腺X射线图像特征分为钙化组与非钙化组,回顾性分析其临床病理特征及3年无病生存率(disease-free survival,DFS).结果 钙化组在病理类型(P＜0.001)、淋巴结转移(P=0.037)、人表皮生长因子受体2(human epidermal growth fator gene-2,HER2)过表达(P=0.005),组织学分级(P=0.043)、临床分期(P=0.021)与非钙化组比较差异有统计学意义.钙化是淋巴结转移及HER2过表达的相关风险因素.钙化组淋巴结转移的风险是非钙化组的1.736倍;钙化组HER2过表达的风险是非钙化组的2.297倍.钙化组和非钙化组3年DFS分别为87.5％和94.9％.肿瘤直径(P=0.025)和淋巴结(P=0.009)是影响乳腺IDC无病生存时间的独立预后因素.结论 钙化组乳腺IDC更具有肿瘤转移性,预后较非钙化组差.     

Normalizing GDNF expression in the spinal cord alleviates cutaneous hyperalgesia but not ongoing pain in a rat model of bone cancer pain

Bone cancer pain (BCP) is the most common complication in patients with bone cancer. Glial cell line‐derived neurotrophic factor (GDNF) is believed to be involved in chronic pain conditions. In this article, the expression and roles of GDNF were studied in a rat model of BCP induced by tibia injection of Walker 256 rat mammary gland carcinoma cells. Significant mechanical and thermal hyperalgesia and ongoing pain were observed beginning as early as day 5 post injection. The expression level of GDNF protein examined on day 16 after tibia injection was decreased in the L3 dorsal root ganglion (DRG) and lumbar spinal cord, but not in other spinal levels or the anterior cingulate cortex. Phosphorylation of Ret, the receptor for GDNF family ligands, was also decreased. Furthermore, normalizing GDNF expression with lentiviral vector constructs in the spinal cord significantly reduced mechanical and thermal hyperalgesia, spinal glial activation, and pERK induction induced by tibia injection, but did not affect ongoing pain. Together these findings provide new evidence for the use of GDNF as a therapeutic treatment for bone cancer pain states.     

鼻咽癌中国1992、2008分期和国际抗癌联盟2010分期标准的比较研究

目的 比较鼻咽癌中国1992、2008分期和国际抗癌联盟(UICC)2010分期标准之间的一致性,评价它们在预测鼻咽癌放疗疗效中的价值.方法 回顾分析2000-2005年间347例无远处转移的初治鼻咽癌患者临床资料,对每例患者分别用中国1992、2008和UICC2010分期标准进行T、N和临床分期.采用Kappa法分析3种分期标准间各期病例数分布的一致性.采用Kaplan-Meier法分别计算3种分期标准的5年总生存率、局部无复发和无远处转移生存率,并用Logrank检验其差异.结果 中国2008分期和UICC 2010分期标准之间的临床分期、T和N分期的病例构成比例的一致性均优于它们各自与1992分期之间的比较,Kappa值分别为0.700、0.881和0.722.3种分期标准下各临床分期的总生存曲线比较只发现Ⅲ与Ⅳ期间的不同,其中2008分期和UICC2010分期标准下Ⅲ与Ⅳ期间的不同(χ2=4.48,P=0.034和χ2=8.88,P=0.003),而1992分期则相似(χ2=0.40,P=0.526).3种分期标准的局部无复发生存率各T1与T2和T2与T3及T3与T4期间的比较均相似(χ2=1.85、0.53、0.50,P=0.174、0.467、0.479和χ2=1.25、2.10、1.99,P=0.264、0.148、0.159及χ2=0.77、0.60、0.87,P=0.381、0.441、0.350).在3种分期标准的各期无远处转移生存率中,1992分期标准的N0与N1、N1与N2、N2与N3间均相似(χ2=3.71、3.11、2.01,P=0.054、0.078、0.156),2008分期标准的N1与N2、N2与N3间不同(χ2=10.49、5.06,P=0.001、0.024);UICC 2010分期标准中仅N1与N2间不同(χ2=7.73,P=0.005).结论 中国2008分期和UICC2010分期标准对鼻咽癌放疗疗效的预测价值相近,且均优于1992分期.

Abstract：

Objective To compare the agreement among Chinese 1992, 2008 and UICC 2010 staging systems of nasopharyngeal carcinoma (NPC) and evaluate their predictive value of radiotherapeutic prognosis.Methods 347 NPC patients without distant metastasis treated in our hospital from 2000 to 2005 were retrospectively analyzed.Every patient was categorized into T, N, and clinical stage by Chinese 1992, 2008 and UICC 2010 staging systems, respectively.Kappa value was used to evaluate the agreement among three systems.Kaplan-Meier method was used to analyze the 5-year overall survival (OS), local-free survival (LFS) and distant metastasis-free survival (DMFS), the difference between subgroup was tested by Logrank.Results The agreement of clinical stage, T and N stage between Chinese 2008 and UICC 2010 staging system was better than that of them compared to 1992 staging system, Kappa value were 0.700、0.881 and 0.722.The agreement of T stage was better than N and clinical stage among these three staging system.The difference of OS between stageⅢ and stage Ⅳ was significant in Chinese 2008 and UICC 2010 staging system (χ2=4.48,P=0.034;χ2=8.88,P=0.003), and with no different in 1992 staging system (χ2=0.40,P=0.526).There was no significant difference of LFS between T1 and T2,T2 and T3,T3 and T4 in all staging systems (χ2=1.85,0.53,0.50,P=0.174,0.467,0.479;χ2=1.25,2.10,1.99,P=0.264,0.148,0.159;χ2=0.77,0.60,0.87, P=0.381,0.441,0.350).There were no significant differencesin 1992 staging system, while there was significant differences of DMFS between N1 and N2, N2 and N3 in 2008 stage system, N1 and N2 in UICC 2010 stage system.Conclusions The predictive value of Chinese 2008 and UICC 2010 staging system for prognosis were similar, and were better than that of 1992 staging system in NPC.     

Ⅲa期非小细胞肺癌新辅助化疗的疗效分析及应用价值

背景与目的 新辅助化疗应用于可手术切除的Ⅲa期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的确切疗效及安全性尚存争议.本研究旨在探讨新辅助化疗对可手术切除Ⅲa期NSCLC患者的近期疗效,并分析其与术后并发症的相关性.方法 根据纳入及排除标准,回顾性分析2011年1月-2013年10月重庆医科大学附属第一医院收治的明确临床诊断为Ⅲa期NSCLC 370例患者完整资料,根据术前是否接受新辅助化疗分为两组,其中A组为新辅助化疗+手术组97例,B组为直接手术组273例,比较两组患者的临床资料,分析新辅助化疗后肿瘤降期率,并将两组患者的手术情况、术后并发症进行对比,统计两组患者3年无病生存期(disease-free survival,DFS).结果 A组患者新辅助化疗后肿瘤总降期率为65.98%(64/97);两组患者R0切除率分别为96.91%(94/97)和90.48%(247/273),手术时间、术中出血量、术后平均住院日差异均无统计学意义(P>0.05);术后并发症总发生率A组稍高于B组,分别为76.29%(74/97)和72.52%(198/273),差异无统计学意义(P>0.05);所有患者术后随访2个月-36个月,中位随访时间12.7个月,两组患者术后总体复发转移率分别为63.92%(62/97)和94.87%(259/273),有统计学差异(P<0.05);A、B两组患者中位DFS分别为19.46个月和11.34个月,差异有统计学意义(P<0.001).结论 新辅助化疗可使Ⅲa期NSCLC患者受益,能有效降低肿瘤分期,提高肿瘤切除率,可降低术后局部复发率及远处转移率,提高患者的无进展生存期;且并不明显增加术后并发症的发生率.