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。     

CRNDE和miR-181a在结直肠癌中的表达及临床意义

摘 要：［目的］ 研究结直肠癌癌组织中长链非编码RNA（long-noncoding RNA,LncRNA）CRNDE及微小RNA（microRNA,miR）-181a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89例结直肠癌癌组织和癌旁组织中CRNDE及miR-181a的表达,分析组间CRNDE及miR-181a表达差异及两者表达与临床病理特征的关系。Kaplan-Meier生存分析比较不同水平CRNDE、miR-181a患者3年总体生存率（OS）的差异。［结果］ 与癌旁组织相比,结直肠癌组织中CRNDE表达水平明显升高,miR-181a表达水平明显降低（P均<0.05）。结直肠癌癌组织中CRNDE、miR-181a表达与肿瘤分期、肿瘤分化有关（P均<0.05）,与性别、年龄、肿瘤大小、肿瘤位置及淋巴结转移无关（P均>0.05）。癌组织中CRNDE与miR-181a表达呈显著负相关（r=-0.558,P=0.008）。Kaplan-Meier分析表明癌组织中CRNDE高表达患者3年OS明显低于CRNDE低表达者（P<0.05）,而高表达miR-181a与低表达miR-181a患者3年OS无明显差异（P>0.05）。［结论］ 结直肠癌组织中CRNDE表达升高,而miR-181a表达降低,两者均参与结直肠癌的发生发展过程,有可能成为新的肿瘤标志物。     

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。     

miR-127-3P在乳腺癌患者中的表达及意义

摘 要：［目的］ 探讨乳腺癌患者血浆miR-127-3P表达及其临床意义。［方法］ 采用实时荧光定量PCR法检测60例乳腺癌患者癌及癌旁组织miR-127-3P的表达,并进一步检测60例乳腺癌患者和20名正常志愿者血浆miR-127-3P的表达。［结果］ miR-127-3P在乳腺癌患者治疗前血浆中的表达（8.15±1.10）高于正常人血浆（3.85±0.54）（P<0.05）。miR-127-3P在乳腺癌组织中的表达高于癌旁组织（P<0.05）。 治疗前血浆中miR-127-3P表达与癌组织miR-127-3P表达呈正相关（r=0.812,P=0.000）;治疗前血浆中miR-127-3P表达与CA153表达呈正相关（r=0.786,P=0.000）。［结论］ miR-127-3P在乳腺癌患者血浆中表达水平明显上调,其表达能够反映癌组织中miR-127-3P的表达水平,乳腺癌患者血浆中miR-127-3P能成为乳腺癌筛查的一个潜在指标。     

MiR-1271靶向ZEB1抑制甲状腺乳头状癌细胞增殖和转移

摘 要：［目的］ 探讨miR-1271对甲状腺乳头状癌细胞增殖和转移的影响及其作用机制。［方法］ 收集20例手术切除甲状腺乳头状癌患者的癌组织和对应的癌旁组织标本。采用RT-qPCR检测组织和细胞系中miR-1271和ZEB1的表达水平；CCK-8检测K1细胞增殖活力；Transwell检测K1细胞侵袭和迁移能力；Western blot检测蛋白的表达水平；双荧光素酶报告基因验证miR-1271与ZEB1的靶向关系。［结果］ miR-1271在甲状腺乳头状癌组织中的表达水平低于癌旁组织组织（1.175±0.534 vs 3.918±0.512，P<0.001)。与人甲状腺滤泡上皮正常细胞（0.985±0.062）相比，miR-1271在癌细胞系（TPC-1：0.752±0.052，K1：0.318±0.042，BCPAP：0.584±0.045）中的表达水平明显下调(P均<0.05)，且在K1细胞中表达最低（P=0.016）。双荧光素酶报告基因结果显示，miR-1271通过结合ZEB1基因的3′UTR，进而抑制其表达水平。过表达ZEB1可明显缓解miR-1271对K1细胞增殖和转移的抑制作用。［结论］ miR-1271通过靶向下调ZEB1的表达，进而抑制K1细胞增殖、侵袭、迁移和EMT。     

miR-218-5p靶向N-cadherin调节胃癌细胞迁移、侵袭分析

摘 要：［目的］ 研究miR-218-5p靶向N-钙黏蛋白（N-cadherin）调节胃癌细胞迁移、侵袭的作用及机制。［方法］ 收集28例胃癌组织及癌旁组织，检测miR-218-5p及N-cadherin的表达水平；培养MNK45胃癌细胞，分为转染阴性对照（NC）mimic的NC组和转染miR-218-5p mimic的miR-218-5p组，检测细胞的迁移及侵袭数目、N-cadherin的mRNA及蛋白表达水平、N-cadherin双荧光素酶报告基因的荧光活力。［结果］胃癌组织中miR-218-5p的表达水平（0.45±0.09）显著低于癌旁组织的（0.71±0.22）（P<0.05），N-cadherin的表达水平（0.93±0.20）显著高于癌旁组织的（0.67±0.14）（P<0.05），且miR-218-5p的表达水平与N-cadherin的表达水平呈负相关（r=-0.201，P<0.05）。miR-218-5p组MNK45胃癌细胞的迁移数目（65.57±11.49）及侵袭数目（67.11±10.34）均少于NC组（113.84±20.13，98.72±18.57；P均<0.05），N-cadherin的mRNA及蛋白表达水平、野生型N-cadherin双荧光素酶报告基因的荧光活力低于NC组（P<0.05）。［结论］ miR-218-5p在胃癌中低表达，过表达miR-218-5p能够抑制胃癌细胞的迁移和侵袭，靶向抑制N-cadherin是可能的分子机制。     

miR-629对胰腺癌细胞增殖和迁移的影响

摘 要：［目的］ 探讨miR-629在胰腺癌组织中的表达及其对胰腺癌细胞增殖和迁移的影响。［方法］ 选取手术切除的胰腺癌组织及其癌旁组织各72例，采用RT-PCR检测miR-629的mRNA表达水平。构建NC-shRNA和miR-629-shRNA慢病毒稳定细胞系，采用CCK-8法检测miR-629对细胞增殖的影响；采用Transwell检测miR-629对细胞迁移的影响；采用双荧光素酶报告基因和Western blot验证miR-629与SIRT3的靶向关系。［结果］ 与癌旁组织（0.40±0.04）比较，胰腺癌组织中miR-629的mRNA相对表达水平（1.71±0.15）显著增加（t=3.901，P<0.001）；与NC-shRNA细胞比较，miR-629-shRNA细胞的增殖能力均显著下降（F=2.719，P<0.001）；与NC-shRNA细胞（140.22±19.37）比较，miR-629-shRNA细胞的迁移能力（63.91±7.44）显著下降（t=4.612，P<0.001）；荧光素酶报告基因显示，转染SIRT3-WT后，miR-629-shRNA细胞的相对荧光素酶活性（0.33±0.05）较NC-shRNA细胞（1.25±0.12）显著增加（t=4.109，P<0.001）；western blot结果表明miR-629-shRNA细胞中SIRT3的蛋白表达水平（0.44±0.03）较NC-shRNA细胞（1.31±0.11）明显增加（t=3.692，P<0.001）。［结论］ miR-629在胰腺癌组织中高表达，可能通过靶向下调SIRT3的表达促进胰腺癌细胞的增殖和迁移，有望为胰腺癌的临床诊疗提供新的思路。     

miR-21、PDCD4表达对Ⅱ期食管鳞癌术后患者生存期的影响

摘 要：［目的］ 探讨微小RNA 21（microRNA-21,miR-21）和细胞程序性死亡蛋白（programmed cell death protein 4,PDCD4）在Ⅱ期食管鳞癌术后患者癌组织中表达,分析其与临床病理特征的关系及对预后的影响。［方法］ 收集胸中段Ⅱ期食管癌术后患者标本97例,将样本组织脱蜡提取总RNA;应用实时免疫荧光定量聚合酶链反应（RT-PCR）法检测所有标本癌组织、癌旁组织miR-21的表达情况;免疫组化法检测测癌组织和癌旁组织PDCD4蛋白表达水平。 ［结果］ miR-21在Ⅱ期食管鳞癌术后患者癌组织中的表达较癌旁组织升高（t=12.06,P＜0.01）,PDCD4在癌组织中的表达较癌旁组织降低（t=8.36,P＜0.01）。miR-21和PDCD4在癌组织中的表达呈负相关（r=-0.41,P＜0.01）,在癌旁组织中的表达呈正相关（r=0.51,P＜0.01）。癌组织中miR-21的表达与食管鳞癌的浸润深度、淋巴结转移、内镜下病变长度呈正相关（r=0.23,P=0.02;r=0.22,P=0.03;r=0.38,P＜0.01）、与分化程度呈负相关（r=-0.60,P＜0.01）,PDCD4蛋白的表达与食管鳞癌的浸润深度、淋巴结转移、内镜下病变长度负相关（r=-0.21,P=0.04;r=-0.24,P=0.01;r=-0.37,P＜0.01）、与分化程度呈正相关（r=0.53,P＜0.01）,二者与年龄、性别、位置不相关（P＞0.05）。COX回归模型发现Ⅱ期食管鳞癌患者肿瘤浸润深度、淋巴结转移、分化程度、内镜下病变长度、miR-21表达、PDCD4表达均为影响患者PFS的因素（?字2=10.36,P=0.01;?字2=7.89,P＜0.01;?字2=6.48,P=0.02;?字2=5.32,P=0.03;?字2=9.56,P=0.01;?字2=5.40,P=0.02）。miR-21对于术后3年PFS、OS预测曲线下面积分别为73.5%、81.0%（P<0.01）;PDCD4对于术后3年PFS、OS预测曲线下面积分别为77.3%、73.2%（P<0.01）。miR-21、PDCD4高、低表达组PFS差异有统计学意义（?字2=19.6,P＜0.01;?字2=11.45,P＜0.01）,OS差异也有统计学意义（?字2=27.84,P＜0.01;?字2=21.35,P＜0.01）。［结论］Ⅱ期食管鳞癌术后患者癌组织与癌旁正常组织中miR-21、PDCD4蛋白表达存在明显差异。高表达miR-21提示预后较差,而高表达PDCD4提示预后较好。     

miR-155-5p通过调控hMLH1促进甲状腺乳头状癌增殖侵袭的研究

摘 要：［目的］ 探讨microRNA-155-5p（miR-155-5p）在甲状腺乳头状癌（papillary thyroid carcinoma,PTC）中的表达及作用,验证其对靶基因错配修复酶人类mutL同系物1（human mutL homologue 1,hMLH1）的调控作用。［方法］采用实时定量PCR法检测miR-155-5p在PTC组织和细胞中的表达水平。采用MTT增殖实验、Transwell侵袭实验观察miR-155-5p对PTC细胞增殖和侵袭能力的影响。采用蛋白免疫印迹技术（Western blot）和荧光素酶报告实验验证miR-155-5p对hMLH1的表达调控。［结果］与癌旁正常组织相比,miR-155-5p在PTC组织中的表达水平明显增加,差异有统计学意义（t=3.492,P=0.002）;转染miR-155-5p mimics的PTC细胞中miR-155-5p的表达水平相比对照组明显增加,差异有统计学意义（TPC-1细胞株：t=4.214,P=0.002,BCPAP细胞株：t=4.268,P=0.002）;转染miR-155-5p mimics的PTC细胞相比对照组增殖能力明显增强,差异有统计学意义（TPC-1细胞株：48h t=4.378,P=0.012;BCPAP细胞株：48h t=22.106,P<0.001）;转染miR-155-5p mimics组通过Matrigel基质胶的细胞数量明显多于对照组,差异具有统计学意义（TPC-1细胞株：t=3.182,P=0.013;BCPAP细胞株：t=7.872,P<0.001）;转染miR-155-5p mimics的PTC细胞中hMLH1蛋白表达明显低于对照组,差异有统计学意义（TPC-1细胞株：t=5.137,P=0.007;BCPAP细胞株：t=3.684,P=0.021）。［结论］ miR-155-5p促进PTC增殖侵袭,其机制可能是通过调控hMLH1实现,这为PTC的治疗提供新的靶点。     

MiR-655对结直肠癌细胞奥沙利铂化疗敏感性的影响

摘 要：［目的］ 探讨miR-655对结直肠癌细胞奥沙利铂化疗敏感性的影响。［方法］ 通过qRT-PCR 验证奥沙利铂耐药和敏感结直肠癌组织蜡块中miR-655的相对表达量；CCK-8法检测细胞活性；Transwell检测细胞侵袭能力；流式细胞术检测细胞周期。［结果］ 相比于癌旁的正常组织，对奥沙利铂耐药的结直肠癌组织中miR-655表达量相对较低（1.24±0.28 vs 0.25±0.12，P<0.01），而对奥沙利铂敏感的结直肠癌组织中miR-655表达量相对较高（1.24±0.28 vs 2.68±0.76，P<0.01）。QRT-PCR鉴定miR-655转染效率结果显示，在miR-655 mimics组中miR-655表达水平相对于miR-NC组显著升高（1.70±0.10 vs 0.83±0.07，P=0.004）。CCK-8检测细胞活性结果显示，与L-OHP/miR-NC组相比，L-OHP/miR-655 mimics组细胞活性降低（48h：0.79±0.05 vs 0.56±0.03，P=0.0015；72h：0.65±0.05 vs 0.25±0.05，P=0.0081）。Transwell法检测细胞的侵袭能力结果显示，与L-OHP/miR-NC组相比，L-OHP/miR-655 mimic组细胞侵袭数量减少（845±85 vs 613±36，P=0.0292）。流式细胞术检测细胞周期结果显示，与L-OHP/miR-NC组G0/G1期相比，L-OHP/miR-655 mimics组细胞比例增加（5.16±0.22 vs 45.53±0.75，P=0.022），与L-OHP/miR-NC组S期相比，L-OHP/miR-655 mimics组细胞比例降低（44.83±1.17 vs 20.75±0.36，P=0.015），与L-OHP/miR-NC组G2/M期相比，L-OHP/miR-655 mimics组细胞比例减少(22.86±1.21 vs 3.85±0.35，P=0.0023）。［结论］MiR-655能够提高结直肠癌细胞对奥沙利铂的化疗敏感性，miR-655可能成为联同奥沙利铂治疗结直肠癌的新靶点。     

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.     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

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.     

New and emerging radiosensitizers and radioprotectors

The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.