miR-155与SOCS1在非小细胞肺癌中表达及临床意义

摘 要：［目的］ 研究非小细胞肺癌（non-small-cell lung cancer,NSCLC）癌组织中微小RNA（microRNA,miR）-155及细胞因子信号传导抑制因子1（suppressor of cytokine signaling 1,SOCS1）的表达及其临床意义。［方法］ 应用荧光实时定量PCR（quantitative real-time PCR,qRT-PCR）检测96例NSCLC癌组织和瘤旁组织中miR-155与SOCS1的表达。统计分析不同组间miR-155与SOCS1表达差异及其与临床病理特征之间的关系。Cox比例风险模型分析影响NSCLC患者预后的危险因素。［结果］ 癌组织与癌旁组织miR-155相对表达量分别为3.13±0.31、1.05±0.22,SOCS1相对表达量分别为1.26±0.25、4.02±0.33。与癌旁组织相比,NSCLC癌组织中miR-155表达明显较高,而SOCS1表达明显较低（P均<0.05）。癌组织中miR-155及SOCS1表达与肿瘤分期有关（P＜0.05）,而与性别、年龄、病理类型、肿瘤大小、组织学分级及淋巴结转移无关（P均>0.05）。96例NSCLC患者随访3～36个月,中位随访时间23.2个月,高miR-155表达组患者3年OS明显低于低表达组（χ2=4.315,P=0.034）,低SOCS1表达组患者3年OS明显低于高表达组（χ2=3.924,P=0.048）。NSCLC癌组织中高miR-155表达、低SOCS1表达、高肿瘤TNM分期是影响患者生存预后的独立危险因素。［结论］ NSCLC癌组织中miR-155表达升高,SOCS1表达降低,两者均与与肿瘤分期有关,有希望成为NSCLC新的肿瘤标志物。     

miR-92a 在结直肠癌中的表达及其对肿瘤血管生成的作用*

目的:探讨miR-92a 在结直肠癌中的表达及其对肿瘤血管新生功能的影响和作用机制。方法:采用qRT-PCR方法检测广东医学院附属深圳南山医院2014年6 月至2015年12月经手术切除的25例结直肠癌组织和对应癌旁组织及4 种结直肠癌细胞（HCT 116、SW620、SW480、HT29）中miR-92a 的表达;免疫组织化学法检测结直肠癌和癌旁组织中CD31阳性表达的微血管密度（microvesseldensity,MVD）,Pearson相关性分析探讨miR-92a 表达与肿瘤血管新生MVD的相关性。通过转染miR-92a-mimic、inhibitor 上调或抑制结直肠癌细胞HCT 116、SW620 中miR-92a 的表达水平,采用小管形成实验检测miR-92a 不同表达对HUVEC小管形成的影响,免疫印迹法检测对其下游潜在靶点PTEN的蛋白表达的影响。结果:结直肠癌组织miR-92a 的表达水平显著高于对应癌旁组织（P < 0.01）;4 种人结肠癌细胞系miR-92a 的表达水平均显著高于正常肠上皮组织（P < 0.05）;结直肠癌组织CD31阳性微血管密度显著高于癌旁组织（P < 0.01）,miR-92a 表达水平与结直肠癌血管新生MVD呈显著正相关（r = 0.580,P = 0.01）;上调miR-92a 表达的HCT 116 细胞培养上清液可以显著促进HUVEC小管形成（P < 0.05）;上调miR-92a 表达可以显著抑制HCT116 细胞中PTEN蛋白表达水平（P < 0.01）。 结论:miR-92a 在结直肠癌细胞和组织中高表达,与肿瘤血管新生增加密切相关;miR-92a 可能通过抑制PTEN的表达发挥促进结直肠癌血管新生的生物学功能。      

MicroRNA-34a调控KLF4转录因子

摘 要：［目的］ 研究microRNA-34a（miR-34a）与其靶基因KLF4转录因子在结直肠癌发生化疗耐药中的作用。［方法］ 利用miRDB和microRNA公共数据库筛选出miR-34a的直接作用靶点KLF4 3′-UTR区。运用real-time PCR方法检测人5-氟尿嘧啶（5-Fu）耐药和敏感的结直肠癌组织及癌旁组织中miR-34a与KLF4的表达水平;建立5-Fu抵抗性结直肠癌细胞系,运用real-time PCR方法检测耐药细胞中KLF4的表达;上调5-Fu耐药结直肠癌细胞中miR-34a的表达,明确在结直肠癌5-Fu耐药细胞系中miR-34a对KLF4的调控作用。［结果］ 在40例5-Fu耐药的结直肠癌组织中miR-34a呈低表达,KLF4呈高表达,且miR-34a在癌组织及癌旁组织中的表达与KLF4呈显著负相关（r=-0.678,P<0.001）;在5-Fu耐药结直肠癌细胞系HCT-8/5-Fu和SW-480/5-Fu中KLF4呈高表达,且上调耐药细胞中miR-34a可抑制耐药细胞中KLF4的表达。［结论］ KLF4转录因子在5-Fu化疗耐药的结直肠癌组织中呈低表达,并与miR-34a呈负相关,上调miR-34a的表达可直接抑制KLF4的表达,提示miR-34a负向调控KLF4具有逆转结直肠癌细胞化疗耐药的可能。     

宫颈癌组织中YB-1、miR-29a、Nek2的表达与细胞增殖、侵袭基因的相关性

摘 要：［目的］ 评价宫颈癌组织中YB-1、miR-29a、Nek2表达与细胞增殖、侵袭基因的相关性。［方法］ 选取2017年1月至2018年1月我院收治的宫颈癌患者60例,取宫颈癌患者手术切除癌组织及癌旁组织标本,检测癌组织、癌旁组织中YB-1、miR-29a、Nek2、细胞增殖基因和细胞侵袭基因表达情况。［结果］ 癌组织中YB-1 mRNA、Nek2 mRNA表达量为（1.52±0.36、1.96±0.35）高于癌旁组织（1.00±0.10、1.00±0.13）,miR-29a mRNA表达量为（0.98±0.10）低于癌旁组织（1.06±0.23）（P均<0.05）。癌组织细胞增殖基因YAP1 mRNA、Piwil2 mRNA、EZH2 mRNA、PKCε mRNA表达量高于癌旁组织（P均<0.05）。癌组织细胞侵袭基因Rab11 mRNA、TUG1 mRNA、Gli1 mRNA、FoxM1 mRNA表达量高于癌旁组织（P均<0.05）。［结论］ YB-1、Nek2在宫颈癌组织中高表达,miR-29a在宫颈癌组织中低表达,且与癌细胞增殖、侵袭基因相关,其表达异常可促进细胞增殖、侵袭。     

XRCC2在结直肠癌中的表达及其临床意义

摘 要：［目的］ 探讨XRCC2在结直肠癌组织中的表达及其临床意义。［方法］ 收集101例结直肠癌患者的标本及临床病理资料,通过qRT-PCR及免疫组化染色检测XRCC2在结直肠癌及癌旁组织中的表达,分析其与临床病理及预后之间的关系。［结果］ qRT-PCR结果表明癌组织中XRCC2 mRNA表达水平高于相对应的癌旁组织（P<0.001）;免疫组化结果显示67.3%(68/101)的结直肠癌组织XRCC2蛋白表达阳性。XRCC2蛋白表达与肿瘤大小、肿瘤T分期、M分期、TNM分期、Duke’s分期、淋巴结转移和肝脏转移有关（P<0.05）。Kaplan-Meier生存分析显示,高表达XRCC2的结直肠癌患者预后差,与XRCC2低表达的患者相比,XRCC2高表达的患者中位生存期及无复发中位生存时间明显缩短（P<0.05）。Cox回归分析显示XRCC2表达是影响结直肠癌患者预后的独立因素。［结论］ XRCC2在结直肠癌组织中呈高表达,其可能成为预测结直肠癌发生发展及预后的生物标志物。     

结直肠癌组织中Vav1、Rac1、CyclinD1、p21表达的意义

摘 要：［目的］ 通过检测Vav1、Ras相关的C3肉毒素底物1（Rac1）、细胞周期蛋白D1（CyclinD1）、p21蛋白在结直肠癌组织中的表达情况,分析Vav1蛋白与Rac1、CyclinD1、p21的关系及意义。［方法］ 180例结直肠癌肿瘤组织和162例癌旁组织的石蜡组织标本进行免疫组化染色,检测肿瘤组织和癌旁组织中Vav1、Rac1、CyclinD1、p21蛋白表达。［结果］ 结直肠癌肿瘤组织中Vav1 、Rac1、CyclinD1蛋白表达高于癌旁组织,p21蛋白在癌组织表达低于癌旁组织(P<0.05)。Vav1蛋白表达与肿瘤的浸润深度、分化情况及淋巴结转移有关;Rac1与肿瘤的分化情况、淋巴结转移有关;CyclinD1表达与肿瘤的浸润深度、淋巴结转移有关（均P<0.05）。 Spearman相关分析显示,肿瘤组织中Vav1蛋白表达与Rac1、CyclinD1蛋白呈正相关,与p21负相关(P<0.05)。［结论］ Vav1在结直肠癌组织中的表达与肿瘤增殖的指标有关,可能通过调节Rac1、CyclinD1、p21促进肿瘤的生长。     

miR-34a-3p、DDX27在结直肠癌组织中的表达水平及临床意义

目的:检测结直肠癌患者组织中微小RNA-34a-3p（miR-34a-3p）、DEAD盒多肽27（DDX27）的表达水平,并探讨二者表达水平与结直肠癌预后的相关性。方法:选取2016年01月至2017年04月于本院住院的102例结直肠癌癌组织作为结直肠癌组,选取其癌旁正常组织作为癌旁对照组。采用实时荧光定量PCR（qRT-PCR）法检测组织miR-34a-3p、DDX27 mRNA表达水平;分析结直肠癌患者组织中miR-34a-3p、DDX27 mRNA表达水平与患者临床病理特征的关系;Kaplan-Meier法分析结直肠癌组织中miR-34a-3p、DDX27表达水平与患者生存率的相关性;多因素Cox回归分析影响结直肠癌预后的因素。结果:Targetscan网站在线预测结果显示miR-34a-3p与DDX27的3' UTR之间存在碱基互补关系。双荧光素酶实验结果显示,与miR-NC相比,miR-34a-3p-mimics与野生型3' UTR区（WT-DDX27）共转出现了荧光减弱,而与突变3' UTR区（MUT-DDX27）共转后荧光强度未出现明显变化;Ualcan数据库中,结肠癌组织中DDX27水平高于正常结肠组织（P＜0.05）;结直肠癌组DDX27 mRNA水平高于癌旁对照组,miR-34a-3p水平低于癌旁对照组（P＜0.05）,且DDX27表达趋势与Ualcan数据库一致;miR-34a-3p、DDX27表达与肿瘤大小、组织分化程度、淋巴结转移、TNM分期有关（P＜0.05）;miR-34a-3p低表达组三年内存活率（64.00%）低于高表达组（94.23%）,DDX27高表达组三年内存活率（66.67%）低于低表达组（92.16%）,差异均有统计学意义（P＜0.05）;DDX27、组织分化程度、TNM分期是影响结直肠癌不良预后的独立危险因素（P＜0.05）,miR-34a-3p是影响结直肠癌不良预后的保护因素（P＜0.05）。结论:结直肠癌组织中miR-34a-3p、DDX27表达水平与组织分化程度、TNM分期等临床病理特征密切相关,且均是影响结直肠癌预后的因素,可对结直肠癌的病情评价及治疗提供一定理论依据。     

miR-145在非小细胞肺癌中的表达及临床病理意义

摘 要：［目的］ 探讨miR-145在配对的非小细胞肺癌 (non-small cell lung cancer,NSCLC) 患者肿瘤组织和癌旁组织中的表达情况,分析其与临床病理因素和预后的关系。［方法］ 应用实时定量聚合酶链反应（q-RT-PCR）检测miR-145在配对的NSCLC患者肿瘤组织和癌旁组织中的表达水平。［结果］ miR-145在NSCLC患者肿瘤组织中的表达水平明显低于癌旁组织（P＜0.001)。miR-145诊断NSCLC的ROC曲线下面积为0.895。miR-145在Ⅲ~Ⅳ期和中低分化的NSCLC患者肿瘤组织中的表达水平明显低于Ⅰ~Ⅱ期和高分化的肿瘤组织（P＜0.05）。miR-145低表达组的总生存率明显低于miR-145高表达组（P＜0.05）。［结论］ miR-145在NSCLC组织中的表达下调,在NSCLC的发生中可能发挥抑癌基因的作用,可能是NSCLC的诊断及预后标志物之一。     

Bacteria and cancer--antagonisms and benefits

There is considerable historical and recent evidence concerning the antagonisms between acute bacterial infections or their toxins and cancer and allied diseases. These data provide renewed incentives to undertake clinical programmes with mixed bacterial vaccines in many countries at the present time.     

Religiosity and physical and emotional functioning among African American and White colorectal and lung cancer patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

Genetic polymorphisms of alcohol and aldehyde dehydrogenases and risk for esophageal and head and neck cancers

Alcoholic beverages are causally related to cancer of the oral cavity, pharynx, larynx and esophagus. Ethanol is oxidized to acetaldehyde and then to acetate by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), both of which have genetic polymorphisms. A review of case-control studies of the effects of ALDH2, ADH2 and ADH3 genotypes shows consistently positive associations between inactive heterozygous ALDH2 and the less-active ADH2 genotypes and the risk for esophageal cancer in East Asian heavy drinkers and this enzyme-related vulnerability may extend to light-to-moderate drinkers. Some studies suggest similar associations with the risk for head and neck cancer in moderate-to-heavy-drinking Japanese. An established carcinogen in experimental animals, acetaldehyde can interact with human DNA. ALDH2-associated cancer susceptibility fits into a scenario in which acetaldehyde plays a critical role in the development of human cancer. Alcohol flushing and drinking behavior may partly explain this carcinogenic effect in carriers of less-active ADH2 genotypes. Whether the ADH3 genotype influences head and neck cancer risk in Western nations is controversial. Professional and public education about risky conditions connected to the ALDH2 and ADH2 genotypes and environmental factors is important in a new strategic approach to the prevention of alcohol-related cancers in East Asians. The use of simple tests to identify inactive ALDH2 on the basis of alcohol flushing responses could benefit many people, by helping them to identify their own cancer risks. Such testing could also help clinicians diagnose esophageal cancer earlier, through the use of endoscopic screening in the high-risk population.     

Religiosity and Physical and Emotional Functioning Among African American and White Colorectal and Lung Cancer Patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

Renal irradiation and the pharmacology and toxicity of methotrexate and cisplatinum

We used a rat model to study the effects of renal irradiation on the pharmacology of methotrexate (MTX) and cisplatinum (cis-Pt). Unanesthetized rats were given bilateral kidney irradiation (20 Gy in 9 fractions). At 9 months after irradiation, 3% of the animals had died and survivors showed moderately impaired renal function. At 15 months, 30% of the animals had died and survivors showed severely impaired renal function. Some animals were given i.v. MTX 1 week to 15 months after irradiation. In irradiated rats, the area under the MTX plasma clearance curve equaled that of controls through 6 months, and was significantly above controls from 9 months on. Other animals were given i.p. cis-Pt 1 week to 9 months after irradiation. The acute toxicity of cis-Pt was the same in control and irradiated rats when cis-Pt was given immediately before or after irradiation. Beginning 3 months after irradiation there was a progressive increase in cis-Pt toxicity and a simultaneous decrease in urinary platinum excretion. Irradiated animals that survived cis-Pt treatment showed increased radiation nephritis; the greatest effect occurred when cis-Pt was given 3 months or more after irradiation. MTX and cis-Pt clearance decreased when renal dysfunction was first observed and changes in renal function preceded changes in drug clearance and toxicity.