五种异质性弥漫大B细胞淋巴瘤微环境细胞PD-1表达及意义

目的弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)是一组具有明显异质性的大细胞淋巴瘤,通过多种检查手段早期识别DLBCL预后较差的亚群,对于预后判断和治疗选择具有重要作用。本研究选择了几种相对少见免疫表型表达的DLBCL类型(C-myc/Bcl-2共表达、NF-κB/p65阳性、CD5阳性及CD30阳性的DLBCL)和EB病毒(epstein-barr virus,EBV)阳性的DLBCL病例进行研究,通过检测肿瘤微环境细胞中程序性死亡受体-1(programmed death receptor-1,PD-1)表达情况,探讨PD-1表达相关的影响因素及其表达对相应DLBCL发生和发展的影响。方法收集贵州医科大学附属医院2010-01-01-2018-08-31诊断的120例DLBCL患者资料,通过普通免疫组化染色(C-myc、Bcl-2、NF-κB/p65和CD30)、免疫组化双标(CD5、PAX5)及EBER原位杂交检测筛选出上述特殊类型的病例并分组,普通免疫组化染色检测肿瘤微环境中PD-1蛋白表达情况。收集临床病理资料并随访,对实验数据进行统计学分析。结果120例DLBCL患者中,PD-1肿瘤浸润淋巴细胞(tumor infiltraling lymphoeytes,TILs)阳性病例共有63例(52.5%,63/120);其中C-myc/Bcl-2共表达组中PD-1(+)-TILs病例27例(69.25%,27/39),NF-κB/p65阳性组30例(68.2%,30/44),CD30阳性组17例(73.9%,17/23),CD5阳性组14例(77.8%,14/18),EBV阳性组中为5例(55.6%,5/9)。PD-1(+)-TILs与PD-1(-)-TILs组病例之间IPI评分(χ^2=4.514,P=0.034)和Ann Arbor分期(χ^2=4.760,P=0.029)差异有统计学意义,PD-1(+)-TILs组分期晚、IPI指数高;PD-1-TILs表达在阳性组C-myc/Bcl-2共表达(χ^2=6.485,P=0.011)、NF-κB/p65(χ^2=6.851,P=0.009)、CD30(χ^2=5.232,P=0.022)、CD5(χ^2=5.426,P=0.040)表达率明显高于阴性组,差异有统计学意义;PD-1-TILs表达在EBV阳性组与阴性组之间差异无统计学意义,χ^2=0.001,P=0.970。生存分析98例随访病例中,PD-1(+)-TILs组病例的总生存率(overall survival,OS)明显低于PD-1(-)-TILs组患者,χ^2=14.652,P<0.001;在C-myc/Bcl-2共表达(χ^2=4.071,P=0.049)、NF-κB/p65的核表达(χ^2=4.833,P=0.025)及CD30阳性DLBCL(χ^2=5.207,P=0.024)中PD-1(+)-TILs组的生存状况也明显较PD-1(-)-TILs组病例差;多因素回归分析显示,PD-1(+)-TILs是DLBCL的独立危险因素,HR=38.170,P=0.036。结论PD-1表达在C-myc/Bcl-2共表达阳性、NF-κB/p65阳性、CD30阳性和CD5阳性的DLBCL中明显增高,在EBV阳性的DLBCL中增加不明显,PD-1在肿瘤微环境细胞中的表达可能是(C-myc/Bcl-2共表达阳性、NF-κB/p65阳性和CD30阳性)DLBCL不良预后评估的相关因素。     

肺癌组织Survivin和CD105表达与预后关系的探讨

目的:探讨Survivin和CD105在肺癌组织中的表达与预后的关系。方法:应用免疫组化检测化疗组(35例)和非化疗组(35例)的肺癌患者中Survivin和CD105的表达水平,比较Survivin和CD105的表达与生存率的关系。结果:Survivin和CD105在肺癌组织中的阳性表达率分别为74.3%(52/70)和67.1%(47/70),两者呈正相关,χ2=0.525,P=0.000;化疗组Survivin和CD105不同表达的患者与非化疗组的中位生存时间(MST)差异有统计学意义,χ2=57.978,P=0.000;化疗组中Survivin和CD105表达阴性者生存时间明显长于阳性表达者。结论:Survivin与CD105在肺癌组织中表达是判断化疗疗效和预后的重要指标。     

Calreticulin在弥漫大B细胞淋巴瘤中的表达及临床意义

背景与目的:淋巴瘤是最常见的淋巴造血系统恶性肿瘤,其中B细胞型非霍奇金淋巴瘤(non-Hodgkin’s lymphoma,NHL)发病占淋巴瘤的90%以上,而NHL中最常见的亚型为弥漫大B细胞淋巴瘤(diffuselargeB-cell lymphoma,DLBCL)。探讨钙网蛋白(calreticulin)在DLBCL中的表达及其临床意义。方法:应用免疫组织化学染色,检测复旦大学附属中山医院2015-2018年收治的143例DLBCL患者肿瘤组织中calreticulin等蛋白的表达情况,并分析calreticulin表达与DLBCL患者临床病理学特征及预后的关系。结果:143例DLBCL患者中,calreticulin阳性表达者92例,阳性表达率为64.3%。Calreticulin阳性组死亡患者的比例(26.1%)明显高于calreticulin阴性组(9.8%),差异有统计学意义(χ2=5.381,P=0.020)。Kaplan-Meier生存曲线显示,calreticulin阳性表达组较阴性表达组生存期短(χ2=5.285,P=0.022)。结论:DLBCL患者中,calreticulin表达与DLBCL预后密切相关,检测calreticulin的表达可以作为判断DLBCL预后的依据之一。     

ERβ和PTEN在人乳腺癌组织中的表达及其临床意义

目的探讨ERβ和PTEN在乳腺癌组织中的表达与临床病理特征及患者预后的关系。方法回顾性收集2008—2009年在第三军医大学西南医院乳腺外科手术切除的110例乳腺癌组织标本,运用免疫组织化学方法检测组织标本中ERβ和PTEN的表达。采用χ2检验分析其表达与临床病理特征之间的关系,ERβ和PTEN相关性分析采用Spearman方法,运用Kaplan-Meier生存分析方法分析两者的表达与患者生存的关系。结果 ERβ在乳腺癌组织中阳性率为62.7%(69/110),PTEN在乳腺癌组织中阳性率为59.1%(65/110)。ERβ和PTEN在乳腺癌组织中的表达呈正相关(r=0.276,P=0.003)。ERβ的表达与临床分期和淋巴结转移有关(χ2=11.766,P=0.003;χ2=9.919,P=0.007)。PTEN的表达也与与临床分期和淋巴结转移有关(χ2=9.014,P=0.011;χ2=12.201,P=0.002)。患者随访时间为8~70个月,中位随访时间为39个月。生存分析结果显示,ERβ阳性患者较阴性患者具有更好的5年DFS(χ2=7.707,P=0.005)。PTEN的表达也与较好的5年DFS有关(χ2=7.057,P=0.008)。笔者将ERβ和PTEN组合起来分为ERβ阳性PTEN阴性组(48例)、ERβ阴性PTEN阳性组(17例)、ERβ阳性PTEN阳性组(21例)以及ERβ阴性PTEN阴性组(24例)4个组进行生存分析,结果显示:组间差异有统计学意义(χ2=16.790,P0.001),ERβ阴性PTEN阴性组患者5年DFS显著低于ERβ阴性PTEN阳性组、ERβ阳性PTEN阴性组、ERβ阳性PTEN阳性3个组(χ2=4.162,P=0.041;χ2=4.835,P=0.028;χ2=12.640,P0.001)。结论 ERβ和PTEN表达均阴性的乳腺癌患者预后较差,两者联合可以作为乳腺癌患者判断预后的分子标记。     

弥漫大B细胞淋巴瘤免疫表型及临床参数与其预后的关系

目的探讨采用R-CHOP方案治疗的弥漫大B细胞淋巴瘤(DLBCL)的免疫表型及临床参数与其预后的关系。方法采用免疫组化SP法,检测57例DLBCL中CD10、bcl-6、MUMl和CD5的表达,根据Hans分型将其分为GCB型和non-GCB型。结果 57例DLBCL中表达CD10、bcl-6、MUM1和CD5分别有9例(15.8%)、36例(63.2%)、34例(59.6%)、4例(7.0%);GCB型17例(29.8%)、non-GCB型40例(70.2%)。57例DLBCL中死亡19例,GCB型预后与non-GCB型相比差异无统计学意义(P=0.132);CD5阳性患者死亡率高,但与CD5阴性者相比差异无统计学意义(P=0.594)。Ⅲ~Ⅳ期和年龄>60岁DLBCL患者死亡率高(P=0.001、P=0.017)。结论应用R-CHOP方案治疗的DLBCL其预后与患者年龄和肿瘤临床分期有关,与Hans分型无关。     

CD30在EBV阳性弥漫性大B细胞淋巴瘤中的表达及其预后意义北大核心

目的:探讨CD30在EBV阳性弥漫性大B细胞淋巴瘤(EBV-positive diffuse large B-cell lymphoma,EBV+DLBCL)中的表达及预后意义。方法:回顾性分析322例DLBCL中EBV+DLBCL与EBV-DLBCL病例临床病理参数之间的关系,以及CD30在EBV+DLBCL中的表达及预后意义。结果:CD30在EBV+DLBCL病例中的表达多于EBV-DLBCL病例(P=0.002);EBV-DLBCL中双表达的病例多于EBV+DLBCL(P=0.044);在63例EBV+DLBCL中,CD30阳性表达多见于B症状患者(P=0.015);另外有2例EBV+DLBCL病例出现BCL6基因重排。随访139例患者中,共表达CD30和EBER的患者预后较差(P=0.002);在EBV+DLBCL中,CD30阳性提示预后更差(P=0.028)。结论:CD30在EBV+DLBCL病例中具有较高的表达率,且与患者不良预后相关,进一步为靶向药物的使用提供理论依据。     

不同激素受体状态乳腺癌趋化因子CCL5的表达及临床意义

目的探讨不同激素受体状态乳腺癌组织中趋化因子CCL5表达的临床意义。方法应用免疫组织化学SP法检测2008年1月至2010年1月芜湖市第二人民医院121例浸润性乳腺癌手术患者组织石蜡样本中CCL5的表达,采用χ2检验分析CCL5与临床病理因素关系,并运用单因素和多因素生存分析不同激素受体状态乳腺癌组织中CCL5表达的预测价值。结果乳腺癌组织中CCL5表达与淋巴结状态有关(χ~2=18.676,P0.001)。CCL5阳性组的5年DFS显著低于CCL5阴性组(χ~2=5.089,P=0.024),淋巴结状态阳性组的5-DFS显著低于淋巴结状态阴性组(χ~2=26.105,P0.001)。进一步多因素分析显示,淋巴结状态是乳腺癌患者5年DFS的独立预后因素(RR=5.453,95%CI:2.589~11.485,P0.001)。激素受体阳性患者中,CCL5阳性组的5年DFS显著低于CCL5阴性组(χ2=10.535,P=0.001),淋巴结状态阳性组的5年DFS显著低于淋巴结状态阴性组(χ~2=11.439,P=0.001),不同组织学分级组患者间5年DFS差异具有统计学意义(χ~2=6.024,P=0.049),进一步多因素分析显示,CCL5是激素受体阳性乳腺癌患者5年DFS的独立预后因素(RR=3.205,95%CI:1.052~9.762,P=0.040),淋巴结状态是激素受体阳性乳腺癌患者5年DFS的独立预后因素(RR=3.915,95%CI:1.191~12.872,P=0.025)。结论不同激素受体状态乳腺癌组织中CCL5的表达,能为乳腺癌内分泌治疗提供更准确诊疗依据。     

程序性死亡受体配体1和2及磷酸化蛋白激酶B在弥漫大B细胞淋巴瘤中的表达及其临床意义

目的 探讨弥漫大B细胞淋巴瘤(DLBCL)患者程序性死亡受体配体1(PD-L1)、PD-L2及磷酸化蛋白激酶B(p-AKT)的表达情况,并分析其与临床病理特征和预后的关系.方法 选取山西省肿瘤医院2010年1月至2012年12月有详细随访记录的68例DLBCL患者存档石蜡标本,应用免疫组织化学法检测PD-L1、PD-L2和p-AKT蛋白的表达情况.结果 DLBCL患者PD-L1蛋白阳性率为22.1%(15/68),与是否为生发中心B细胞(GCB)亚型(χ^2=5.591,P=0.018)、临床分期(χ2=3.969,P=0.046)、国际预后指数(IPI)评分(χ^2=4.178,P=0.041)和治疗缓解率(χ^2=6.587,P=0.010)有关;PD-L2蛋白阳性率为14.7%(10/68),与是否结外转移有关(χ^2=6.772,P=0.009);p-AKT蛋白阳性率为61.8%(42/68),与年龄是否≥60岁(χ^2=6.227,P=0.013)、美国东部肿瘤协作组(ECOG)评分(χ^2=4.005,P=0.045)、B症状(χ^2=10.187,P=0.001)和治疗缓解率(χ^2=4.096,P=0.043)有关.单因素分析显示PD-L1蛋白阳性表达组总生存(OS)率及无进展生存(PFS)率低于阴性表达组(均P<0.05).非GCB亚型患者PD-L1蛋白阳性表达组的OS率及PFS率均低于阴性表达组(均P<0.05).p-AKT蛋白阳性表达组较阴性表达组有较差的OS率及PFS率(均P<0.05).相关性分析显示PD-L1蛋白表达与PD-L2、p-AKT蛋白表达相关(r=0.380,P=0.001;r=0.273,P=0.025),且PD-L1、p-AKT共表达提示预后更差(P<0.05).多因素分析显示PD-L1和p-AKT蛋白高表达均是DLBCL独立的预后危险因素(均P<0.05).结论 PD-L1和p-AKT蛋白表达可能参与了DLBCL的发生发展,阻断程序性死亡受体1(PD-1)及相关配体的通路或联合阻断可能为临床治疗带来更多希望.     

乳腺癌患者肿瘤组织及外周血多药耐药基因表达的临床意义

目的:检测多药耐药基因在乳腺癌患者肿瘤组织及外周血中的表达,探讨其临床意义。方法:荧光定量RT-PCR法检测40例原发性乳腺癌患者肿瘤组织及外周血、13例辅助化疗后乳腺癌患者外周血及10例乳腺良性疾病组织与外周血中mdr1的表达情况。结果:40例原发性乳腺癌患者肿瘤组织mdr1阳性表达率为67.5%(27/40),与对照组组织(无阳性表达)相比差异有统计学意义,χ2=14.380,P=0.001;乳腺癌患者外周血mdr1阳性表达率为22.5%(9/40),高于对照组(无阳性表达),χ2=4.486,P=0.034;化疗后乳腺癌患者外周血中mdr1的表达率为53.8%(7/13),高于化疗前外周血mdr1的表达,二者差异有统计学意义,χ2=12.345,P=0.001。结论:乳腺癌患者存在先天性和获得性耐药性,检测肿瘤组织和外周血mdr1表达对制定个体化化疗方案有指导意义。     

HBV感染弥漫大B细胞淋巴瘤的临床特点和预后分析

目的探讨乙肝病毒（hepatitis B virus,HBV）感染弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma,DLBCL）患者的临床特征和预后。方法回顾性分析235例初治DLBCL患者,分为HBs Ag阳性组76例和HBs Ag阴性组159例,对两组患者的临床特征、化疗期间肝功能损害及总生存情况比较分析。结果与HBs Ag阴性组比较,HBs Ag阳性DLBCL患者发病中位年龄较小（47岁vs 58岁,P〈0.01）,脾脏和肝脏受累多见（26.3%vs 15.1%,P=0.039;11.8%vs 4.4%,P=0.034）,化疗期间肝功能损害发生率较高（47.4%vs 26.2%,P=0.001）。HBs Ag阳性组中位总生存（overall survival,OS）为48月,3年OS为64.1%;HBs Ag阴性组中位OS为42月,3年OS为61.7%,差异无统计学意义（χ^2=0.988,P=0.320）;无进展时间（progression-free survival,PFS）差异亦无统计学意义（χ^2=2.658,P=0.103）。采用Cox回归多因素分析,HBs Ag阳性DLBCL患者的不良预后因素包括年龄〉60岁、B症状和肝脏受累,肝功能损害不影响其总生存。结论 HBs Ag阳性DLBCL患者发病年龄较轻,肝脾受累多见,且化疗相关肝功能损害发生率较高,但在总生存和无进展生存方面与HBs Ag阴性患者无显著差异。     

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.