Ck19、Galectin-3及HBME-1在甲状腺乳头状癌中的表达及临床意义

摘 要：［目的］ 探讨细胞角蛋白19(CK19)、半乳糖凝集素(Galectin-3)、间皮瘤抗原-1 (HBME-1)在甲状腺乳头状癌中的表达及临床意义。［方法］ 采用免疫组织化学方法检测60例甲状腺良恶性病变（甲状腺乳头状癌40例,癌旁甲状腺组织40例,结节性甲状腺肿20例）中CK19、Galectin-3和HBME-1的表达。［结果］ CK19在甲状腺乳头状癌组织、癌旁甲状腺组织及结节性甲状腺肿组织中表达的阳性率分别为95.0%(38/40)、32.5%(13/40)和15.0%(3/20),Galectin-3表达的阳性率分别为92.5%(37/40)、5.0%(2/40)和20.0%(4/20),HBME-1的表达的阳性率分别为92.5%(37/40)、0和5.0%(1/20);三种抗体在甲状腺乳头状癌和癌旁甲状腺组织、结节性甲状腺肿组织的阳性表达率差异均具有统计学意义(χ2=45.115,P<0.001;χ2=66.646,P<0.001;χ2=84.048,P<0.001)。［结论］ CK19、Galectin-3和HBME-1在甲状腺乳头状癌组织中的表达明显高于癌旁组织和良性病变组织,三种标志物联合检测将进一步提高甲状腺乳头状癌的诊断准确性。     

CK19、Galectin-3、HBME-1、p27及CyclinD1在甲状腺乳头状癌中的表达及意义

背景与目的:甲状腺乳头状癌的诊断有时会很困难,而淋巴结转移是甲状腺乳头状癌局部复发的主要原因并影响预后.本研究探讨CK19、Galectin-3、HBME-1、p27及CyclinD1在甲状腺乳头状癌中的表达特点和诊断价值以及p27、CyclinD1与乳头状癌淋巴结转移间的关系.方法:收集2005年1月至2008年12月间在我院手术的50例甲状腺良性病变患者 (结节性甲状腺肿40例,甲状腺腺瘤10例)及50例甲状腺乳头状癌(经典型40例,滤泡型10例) 患者的手术标本,用免疫组化EnViSion法检测CK19、HBME-1、Galectin-3、p27及CyclinD1的表达.结果:细胞质或细胞膜均有CK19、Galectin-3和HBME-1三种标志物表达,但p27和CyclinD1则在细胞核表达.CK19、HBME-1、Galectin-3在甲状腺乳头状癌中的表达阳性率分别为100%、96%和100%,而在良性病变中则为10%、10%和6%,两者比较差异有显著性(P<0.01).p27在甲状腺乳头状癌的表达阳性率为14%,而在良性病变中则为84%,两者比较差异有显著性(P<0.01).CyclinD1在甲状腺良、恶性病变中的表达阳性率分别为68%和78%,两者间差异无显著性(P>0.05).在甲状腺乳头状癌患者中,CK19、Galectin-3和HBME-1共同表达者占98%(49/50),其中伴p27低表达者占90%(45/50),而在良性病变者中则分别为2%(1/50)和0%(0/50),前两者与后者之间相比,差异有显著性(P<0.01).p27低表达与CyclinD1表达(转移组阳性率72.7%,未转移组71.4%)与甲状腺乳头状癌淋巴结转移间无显著相关性(P>0.05).结论:联合检测CK19、Galectin-3和HBME-1对甲状腺乳头状癌的诊断与鉴别诊断具有重要价值,而p27的低表达与CyclinD1表达对甲状腺乳头状癌的淋巴结转移无提示作用.     

Ras相关区域家族1A半乳糖凝集素3和甲状腺过氧化物酶mRNA在甲状腺乳头状癌组织中的表达及临床意义

目的 探讨Ras相关区域家族1A(RASSF1A)、半乳糖凝集素3(Galectin-3)和甲状腺过氧化物酶(TPO)mRNA在甲状腺乳头状癌组织及其他滤泡源性良性病变组织中的表达情况和临床意义.方法 收集73例甲状腺肿块手术标本,其中甲状腺乳头状癌23例,结节性甲状腺肿16例,甲状腺腺瘤29例,桥本氏病5例.采用逆转录聚合酶链反应(RT-PCR),检测73例甲状腺组织标本中RASSF1A、Galectin-3和TPO mRNA的表达情况.结果 RASSF1A、Galectin-3和TPO mRNA在23例甲状腺乳头状癌组织中的阳性表达率分别为26.1%、82.6%和21.7%,均与其他滤泡源性良性病变中的表达率差异有统计学意义(均P<0.05);RASSF1A、Galectin-3和TPO mRNA在各滤泡源性良性病变中的表达率差异均无统计学意义(均P>0.05).在甲状腺滤泡源性良恶性病变中,RASSF1AmRNA与Galectin-3 mRNA的表达呈负相关(Pearson点相关系数=-0.4090,χ2=12.2088,P=0.000);RASSFIA mRNA与TPO mRNA的表达旱正相关(Pearson点相关系数=0.2763,χ2=4.8217,P=0.028).结论 RASSF1A和TPO mRNA在甲状腺乳头状癌组织中的表达普遍缺失,而Galectin-3mRNA表达率较高.RASSF1A、Galectin-3和TPO mRNA与甲状腺乳头状癌的发生和发展密切相关,可作为诊断和鉴别诊断甲状腺乳头状癌的标志物,且联合检测的结果 更可靠.     

应用组织芯片技术研究抑癌候选基因NDRG2在甲状腺肿瘤组织中的表达及其意义

目的:应用组织芯片技术分析抑癌候选基因NDRG2在人类甲状腺癌组织、甲状腺正常组织及甲状腺良性病变组织中的表达情况.方法:采用小鼠抗NDRG2单克隆抗体的免疫组织化学ABC法,研究NDRG2在不同甲状腺组织的表达,并分析NDRG2在不同甲状腺组织中的表达差异.结果:免疫组化结果显示,甲状腺癌组织与甲状腺良性病变组织中DNRG2的表达相比较呈显著性差异(P＜0.05),甲状腺癌组织与正常甲状腺组织中DNRG2的表达相比较呈显著性差异(P＜0.05).甲状腺良性病变组织与正常甲状腺组织中DNRG2的表达相比较呈显著性差异(P＜0.05).结论:NDRG2在甲状腺癌组织中呈低表达,提示其可能对甲状腺癌的发生或发展有重要作用,这不仅为研究甲状腺癌的发病机制进一步提供了线索,而且对甲状腺癌的诊断和治疗具有重要意义.     

免疫组化技术在甲状腺液基细胞学诊断为Ⅲ类-意义不明确细胞非典型病变中的应用价值

目的:探讨利用免疫组化技术在甲状腺液基细胞学诊断为Ⅲ类-意义不明确细胞非典型病变中的应用价值。方法:选取96例甲状腺细针穿刺液基细胞学诊断为Ⅲ类-意义不明确细胞非典型病变病例,所选病例均通过手术获得术后组织病理诊断结果,细胞涂片完成后利用剩余液基保存液制作细胞块,将术后组织病理与细胞块同时进行CK19、Galectin-3、HBME-1、TPO四种抗体免疫组织化学检测。依据组织病理结果将选取病例分为甲状腺乳头状癌组和良性组,分析两组中四种抗体在细胞块免疫组化染色中的表达情况,并进行对比分析,以验证在免疫组化中细胞块与组织病理表达的一致性。结果:选取的96例甲状腺细针穿刺液基细胞学Ⅲ类病例,其中18例因剩余细胞量少蜡块制作不成功,78例细胞块制作成功的病例依据组织学诊断分为甲状腺癌组及良性组。甲状腺癌组中CK19、Galectin-3、HBME-1表达率明显高于良性组（P均=0.000）,而TPO在良性组中的表达率明显高于甲状腺癌组（P=0.000）,差异均具有统计学意义（P＜0.05）,四种免疫组化标记物诊断甲状腺癌均具有较高的敏感性、准确性和特异性。甲状腺癌组中免疫组化结果对比分析CK19、Galectin-3、HBME-1、TPO在细胞块与组织病理中的表达一致,无统计学差异（P＞0.05）。结论:细胞块免疫组化在甲状腺细针穿刺液基细胞学诊断为Ⅲ类-意义不明确细胞非典型病变中应用价值较大,其结果与术后组织病理符合率高,能提高细胞学诊断的准确率。     

应用组织芯片技术研究抑癌候选基因NDRG2在甲状腺肿瘤组织中的表达及其意义

目的：应用组织芯片技术分析抑癌候选基因NDRG2在人类甲状腺癌组织、甲状腺正常组织及甲状腺良性病变组织中的表达情况。方法：采用小鼠抗NDRG2单克隆抗体的免疫组织化学ABC法,研究NDRG2在不同甲状腺组织的表达,并分析NDRG2在不同甲状腺组织中的表达差异。结果：免疫组化结果显示,甲状腺癌组织与甲状腺良性病变组织中DNRG2的表达相比较呈显著性差异（P〈0．05）,甲状腺癌组织与正常甲状腺组织中DNRG2的表达相比较呈显著性差异（P〈0．05）。甲状腺良性病变组织与正常甲状腺组织中DN—RG2的表达相比较呈显著性差异（P〈0．05）。结论：NDRG2在甲状腺癌组织中呈低表达,提示其可能对甲状腺癌的发生或发展有重要作用,这不仅为研究甲状腺癌的发病机制进一步提供了线索,而且对甲状腺癌的诊断和治疗具有重要意义。     

NCOA5在40例甲状腺乳头状癌中的表达及临床意义

摘 要：［目的］ 探讨NCOA5蛋白在甲状腺乳头状癌中的表达及临床意义。［方法］ 应用免疫组化方法（SP法）检测NCOA5蛋白在40例甲状腺乳头状癌组织及配对癌旁甲状腺组织中的表达,并探讨其与临床病理特征及预后的关系。［结果］ NCOA5蛋白在甲状腺癌组织中的阳性表达率(75%)高于癌旁组织(20%)(χ2=24.261,P<0.01)。NCOA5表达与肿瘤分期（TNM分期）和淋巴结转移有关（χ2=4.126,P<0.05;χ2=4.043,P<0.05）;与甲状腺乳头状癌的预后指数呈正相关（r=5.647,P<0.05）。［结论］ NCOA5在甲状腺乳头状癌中高表达,对甲状腺癌的诊疗和预后评估具有指导意义。     

Galectin-3对甲状腺乳头状癌早期病变的诊断意义

 目的 比较Galectin-3（Gal-3）在甲状腺乳头状癌及其早期病变和甲状腺良性病变中的表达差异，明确其临床意义。方法 采用免疫组化EnVision二步法检测329例甲状腺手术标本中Gal-3蛋白的表达情况。结果 Gal-3蛋白在甲状腺乳头状微癌及甲状腺乳头状非典型增生中的表达阳性率分别为83．3％、77．8％，显著高于结节性甲状腺肿（30．9％）、腺瘤（43．7％）及甲状腺炎（16．1％）。结论 甲状腺Gal-3表达在甲状腺乳头状微癌及非典型增生组织中显著高于甲状腺良性病变，Gal-3检测使甲状腺乳头状癌早期病变易于发现。     

MCM2、Ki67、CyclinD1在甲状腺滤泡性癌和滤泡性腺瘤组织中的表达及与Galectin-3、CK19的对比研究

目的 探讨MCM2、Ki67、CyclinD1在甲状腺滤泡性癌和甲状腺滤泡性腺瘤组织中表达的意义,并与Galectin-3、CK19进行对比.方法 应用免疫组织化学EnVision法检测32例甲状腺滤泡性癌及23例甲状腺滤泡性腺瘤组织中MCM2、Ki67、CyclinD1、Galectin-3和CK19的表达情况.结果 MCM2、Ki67、CyclinD1的阳性率在甲状腺滤泡性癌组织中分别为96.9%、46.9%、96.9%,在甲状腺滤泡性腺瘤中分别为65.2%、26.1%、100.0%,两者MCM2的阳性率比较差异有统计学意义（χ2=9.799,P=0.002）,而两者Ki67和CyclinD1的阳性率比较差异无统计学意义（χ2=2.450、0.732,P=0.118、0.392）.在滤泡性癌和滤泡性腺瘤组织中,MCM2、ki67、CyclinD1者的标志指数分别为（31.51±19.43）和（11.12±10.79）、（6.58±6.40）和（4.03±5.14）、（50.00±21.70）和（40.33±22.55）,MCM2的标志指数比较差异有统计学意义（t=10.522,P〈0.001）,Ki67和CyclinD1的标志指数比较差异无统计学意义（t=1.589、1.634,P=0.122、0.115）.Galectin-3和CK19的阳性率在滤泡性癌组织中分别为62.5%和75.0%,在滤泡性腺瘤组织中分别为26.1%和60.9%,Galectin-3的阳性率比较差异有统计学意义（χ2=7.118,P=0.008）,CK19的阳性率比较差异无统计学意义（χ2=1.251,P=0.263）.结论 MCM2、Galectin-3在甲状腺滤泡性癌与滤泡性腺瘤组织中的表达有明显差异,对两者的诊断和鉴别诊断有价值,而Ki67、CyclinD1、CK19则无价值.     

CK-20和LGALS4在甲状腺乳头状癌中的表达及临床意义

目的 探讨角蛋白-20（cytokeratin-20，CK-20）和半乳糖凝集素4（galectin-4，LGALS4）在甲状腺乳头状癌中的表达及其临床意义。方法 选取2010年1月—2014年6月在张家口市第一医院手术且经病理证实的甲状腺乳头状癌患者128例为研究对象，免疫组化检测癌组织及相应癌旁正常甲状腺组织CK-20、LGALS4的表达；ROC曲线分析CK-20、LGASL4对甲状腺乳头状癌的诊断价值；多因素Cox回归分析影响患者无病生存期（disease-free survival，DFS）的因素。结果 甲状腺乳头状癌组织中CK-20阳性表达率高于癌旁正常组织，而LGALS4阳性表达率低于癌旁正常组织（均P＜0.05）；CK-20高表达、LGALS4低表达均与肿瘤远处转移、TNM分期、淋巴结转移有关（均P＜0.05）；CK-20与LGALS4表达水平呈负相关（r=-0.531，P＜0.001）；CK-20、LGALS4联合诊断甲状腺乳头状癌的曲线下面积、敏感度均优于其单独诊断（均P＜0.05）；CK-20阳性表达患者5年DFS低于阴性表达患者，而LGALS4阳性表达患者5年DFS高于阴性表达患者（均P＜0.05）；CK-20高表达、远处转移、淋巴结转移是DFS的独立危险因素，而LGALS4高表达是DFS的保护因素（均P＜0.05）。结论 甲状腺乳头状癌组织中CK-20与LGALS4表达呈负相关，CK-20高表达预示预后不良，而LGALS4高表达预示预后良好，两者有望成为监测甲状腺乳头状癌预后的生物标志分子。     

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.     

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。     

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.     

Fruit and vegetables and cancer risk

The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.     

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.