河南林州食管癌高发区食管癌和癌前病变患者血清蛋白质质谱

背景与目的:食管癌和癌前病变组织中部分分子改变可在血液中反映出来,但这些指标的灵敏度和特异性较低,临床应用受到限制。血清蛋白质质谱分析技术有助于筛选癌变密切相关蛋白。本研究通过探讨食管癌高发区人群食管正常粘膜(normal,NOR)、食管上皮基底细胞过度增生(basalcellhyperplasia,BCH)、不典型增生(dysplasia,DYS)和食管癌(esophagealcarcinomc,EC)患者的血清蛋白质质谱的变化特征,为筛选和建立早期诊断和高危人群检测的血清学指标提供理论依据。方法:采用弱阳离子结合芯片(WCX2)及表面增强激光解吸电离飞行时间质谱仪(SELDI-TOF-MS)检测EC高发区无症状普查人群130人(NOR63人、BCH40人、DYS27人)和高发区EC30人的血清蛋白质质谱进行分析。应用BiomarkerPattern软件建立决策树分类模型,经10倍交叉验证得到该分类模型进行验证,测试组病变人群的诊断率和特异性(排除率)。结果:BCH组质荷比(M/Z)为M9306.61u的一种、DYS组M/Z为M13765.90u的一种及EC组M/Z为M2942.15u和M15953.40u的两种蛋白质分别建立决策树分类模型,训练组BCH、DYS和EC的敏感性(检出率)分别为57.5%(23/40)、88.8%(24/27)和96.6%(29/30),特异性分别为96.8%(61/63)、63.4%(40/63)和92.0%(58/63);测试组BCH、DYS和EC敏感性分别为57.5%(23/40)、66.6%(18/27)和60.0%(18/30),特异性为95.2%(60/63)、71.4%(45/63)和84.1%(53/63)。结论:M/Z为M9233.09u、M13657.15u、M2918.91u和M15827.37u的4种蛋白质可能包含有可用于食管癌高发区人群筛查的血清标记物,血清蛋白质质谱检测为食管癌和癌前病变的诊断和筛查提供了新的手段。     

β—胡萝卜素对荷瘤小鼠腹腔巨噬细胞吞噬功能和自然杀伤细胞活性的影响

作者以正常的或荷瘤的(荷实体型ERLICH乳腺癌)ICR系小鼠的腹腔巨噬细胞(简称Mφ)和脾脏组织为材料,观察了β-胡萝卜素对小鼠Mφ功能和自然杀伤(NK)细胞活性的影响。结果表明:β-胡萝卜素(15mg/kg,po d_(1-15)),对正常小鼠Mφ功能和NK细胞活性影响不明显(P>0.05)。但给予β-胡萝卜素(15mg/kg po d_(1-22)),能提高荷瘤小鼠Mφ的吞噬功能(P<0.05)和NK细胞活性(P<0.01),并能对抗环磷酰胺的免疫抑制作用,与单用环磷酰胺的小鼠比较,有显著的差异(P<0.05)。     

无细胞短棒状杆菌纳米级制剂抗肿瘤作用及机理研究

目的 :研究无细胞短棒状杆菌纳米级制剂 (NCPP)体内抗肿瘤作用及机理。方法 :小鼠腹腔注射NCPP与短棒状杆菌制剂 (CPP) 14d后测定脾指数。小鼠腹腔注射艾氏腹水癌细胞 ,于注射癌细胞前 1d及注射后次日起 ,连续 (间隔 1d)腹腔注射NCPP与CPP 5次 ,计算小鼠存活率。小鼠腹腔注射NCPP和CPP 10d后测定腹腔巨噬细胞 (Mφ)吞噬率、吞噬指数、过氧化氢 (H2 O2 )和一氧化氮 (NO)水平、脾脏自然杀伤 (NK)细胞杀伤率及T细胞增殖指数。结果 :NCPP组和CPP组与对照组相比 :均有明显的抑瘤作用 ;脾指数均大于 2 .0 ;腹腔Mφ吞噬率、吞噬指数、产生过氧化氢 (H2 O2 )和一氧化氮 (NO)水平均有显著性提高 (P <0 .0 1) ;脾脏NK细胞杀伤率均有明显提高 (P <0 .0 5 ) ;脾脏T细胞增殖指数均无明显差异。上述所有实验中 ,NCPP和CPP 2组间均无明显差异。结论 :NCPP具有与CPP相同的脾激活及抑瘤作用 ,其机理主要是通过激活Mφ及NK细胞吞噬、杀伤功能所致。     

原癌基因与细胞凋亡

PJ-CW是新抗癌剂济南假单胞菌苗(PJV)的第二代制剂。本文总结了PJ-CW对荷瘤小鼠免疫功能调节的观察。结果显示,PJ-CW不仅能促进和调节荷瘤小鼠腹腔Mφ吞噬功能、CTL杀伤活性、NK活性和外周血ANAE~ 细胞数量以及人胎脾LAK细胞的杀伤活性,还能促进小鼠腹腔渗出细胞和淋巴细胞环核苷酸的含量,为PJ-CW的抗癌作用提供了实验依据。     

河南林县人群血浆V_A和α—V_E水平与EC关系的初步探讨

林县是我国食管癌(EC)高发区之一,死亡率为129.18/10万(男)和79.41/10万(女)。病因学研究指出,除亚硝胺类、霉菌毒素等化学致癌物和遗传易感性等因素外,营养因素、尤其是某些维生素的缺乏与EC高发密切相关。流行病学回顾和前     

食管癌高发区人群维生素防癌试验和血浆V_A及α-V_E的HPLC检测

林县、辉县地处河南省西北部太行山区,是我国食管癌(EC)高发区之一,该病年死亡率均在130/10万以上。病因学研究指出,营养与EC高发密切相关。流行病学回顾和前瞻调查表明,血浆维生素A(V_A)水平与癌的发生呈负相关;α-生育酚(α-V_E)     

肝癌及肝硬化组织中巨噬细胞和NK细胞的研究

目的探讨巨噬细胞(Mφ)、肝脏自然杀伤(NK)细胞在原发性肝细胞癌(HCC)及肝硬化组织中的数量和分布规律,及其两者的相互关系。方法应用免疫组织化学二步法检测60例HCC,62例单纯性肝硬化,23例正常肝组织中的巨噬细胞标志物CD68和NK细胞标志物CD57的表达,对阳性细胞数进行形态定量比较与相关分析。结果(1)各组Mφ平均数从高到低为:癌旁组织、肝硬化、正常肝、HCC(P<0.05);NK细胞平均数从高到低为:HCC、癌旁组织、正常肝、肝硬化(P<0.05)。(2)HCC中Mφ细胞数量随分化程度降低而减少(P<0.05);NK细胞数量与组织学分级无明显关系。(3)HCC和癌旁组织中Mφ细胞分布与临床TNM分期无关;HCC中NK细胞随着临床分期的发展有下降的趋势(P<0.05)。(4)HCC中15月内有转移组的Mφ细胞数少于无转移组(P<0.05);15月内转移复发组HCC和癌旁的NK细胞计数均明显少于无转移复发组(P<0.01)。(5)在HCC中Mφ、NK细胞数呈线性正相关(r=0.344,P<0.05)。结论Mφ数量与HCC分化程度密切相关,并与肝脏NK细胞数量呈正相关。Mφ和NK细胞计数可能是反映机体抗肿瘤免疫状态和生物学行为以及判断患者预后的重要指标。     

三奇注射液对肝癌小鼠巨噬细胞吞噬功能和IL-2水平影响的实验研究

目的: 本试验通过研究三奇注射液(SQ)对H:2肝癌小鼠的巨噬细胞(Mф)吞噬功能和白细胞介素2(IL-2)水平的影响来探讨其抑瘤作用及免疫功能的作用机理.方法: 将小鼠造模后随机分为5组:荷瘤对照组、SQ高、中、低剂量组和5-氟尿嘧啶(5-Fu)组,腹腔注射给药,进行对比观察,计算抑瘤率;用放免法测IL-2水平;用酶联检测仪测定小鼠腹腔Mф吞噬功能;解剖小鼠,分别称出各组小鼠的脾脏和胸腺重量,测定脾脏和胸腺指数.结果: SQ不仅改善了H22型肝癌小鼠的整体状况,而且提高了小鼠血清IL-2水平及胸腺指数、脾脏指数和Mф吞噬功能,虽然在抑瘤方面不如5-Fu明显,但对小鼠生命质量的改善明显优于5-Fu组.结论: SQ的抗癌机理可能与体内Mф吞噬功能增强和IL-2水平升高有关.     

原发性肝癌患者术后免疫状态变化观察

手术是早期肝癌治疗的主要手段,但手术麻醉及创伤对机体免疫功能均有影响,国内外对此已有许多研究,但以淋巴细胞功能的研究较多,巨噬细胞(以下简称Mφ)活性方面研究尚少。本文观察肝癌手术后患者Mφ活性的动态改变以及淋转水平和OT皮试反应变化。     

维生素 D 的抗肿瘤作用与食管癌

维生素 D 是人体必需的脂溶性维生素,属于类固醇衍生物。维生素 D 的许多生物学功能都是通过其受体介导调 节靶基因转录来实现的。已发现维生素 D 缺乏与多种肿瘤的发生、发展相关,充足的维生素 D 水平可降低多种肿瘤的发生 率,并能改善某些肿瘤患者的存活率及预后。维生素D 及其类似物不仅能调节体内钙磷代谢,而且可通过抑制肿瘤细胞增 殖、诱导细胞分化、促进细胞凋亡、抗血管生成、抑制肿瘤细胞浸润与转移以及抑制炎症等方式来发挥抗肿瘤作用。然而, EC 患病风险与维生素D 水平之间的相关性仍存在争议。不同研究中维生素D 与 EC 患病风险相关性的显著差异可能与研 究对象的性别,年龄及EC的分型、分化等组织学特征有关。相关体外及动物模型研究表明,维生素D能抑制EC细胞增殖。 另有学者发现,EC 患者中 VDR 高表达者预后较好,VDR 基因的多态性可能与 EC 相关。本文主要就维生素 D 及其受体的 结构、功能和抗肿瘤作用机制以及其与 EC 关系的研究作一综述。     

食管癌及其癌前病变患者血清铁蛋白水平及意义

本文对65例食管癌,43例食管上皮重增,34例轻增,41例食管上皮正常及28例良性疾病患者进行了血清铁蛋白测定。均值分别为:214.86,104.90,81.61,54.75和98.89ng/ml。相互比较的结果显示:癌显著高于其他各组(P<0.01);重增、轻增也显著高于食管上皮正常组;但重增和轻增间,重增、轻增与良性病间的差别无显著性(P>0.05)。本研究结果表明:血清铁蛋白在食管癌患者中同样也表现出异样升高,并在癌前病变时即可出现;血清铁蛋白尚不能独立作为食管癌早期诊断指标;作为初筛指标,可能有一定的潜在价值。     

Barrett's esophagus and esophageal cancer: an overview

Although esophageal cancer (EC) is the eighth most common cancer in several European countries, it is one of deadliest worldwide. The most frequent predisposing factor implicated in its development is Barrett's esophagus (BE), an acquired metaplastic transformation of the esophageal lining cells from normal squamous epithelium into specialised or intestinal-like columnar epithelium. The major risk factor for BE is gastroesophageal reflux disease. Although BE is in itself a benign and often asymptomatic disorder, its clinical importance stems from the recognition that it represents the main precursor lesion for the development of esophageal adenocarcinoma (AC), a tumor that is rapidly increasing especially in developed countries and is associated with a low survival rate. This paper provides an overview of the epidemiology and natural history of BE as well as of the possible pathogenetic mechanisms underlying the development of BE and its progressive transition to AC. New diagnostic tests are described, recommendations for screening and surveillance are provided and surgical and ablative procedures to treat dysplastic lesions and early neoplasia are discussed. Claimed chemopreventive agents and biomarkers that in the near future may help identify people with a higher risk of EC are also considered.     

荆豆凝集素(UEA-Ⅰ)受体的定位分布对诊断鼻咽癌前病变的初步观察

用亲合组织化学技术,以UEA—I,ConA,PNA三种凝集素对30例鼻咽上皮重度不典型增生、化生(癌前病变),70例鼻咽癌及30例正常鼻咽粘膜上皮进行观察对比,了解其分布定位及含量的差异。结果发现:荆豆凝集素(UEA—I)在正常鳞状上皮多呈膜性分布;鼻咽癌癌细胞多呈阴性反应;而鼻咽癌前病变的细胞则显示膜性及胞浆性强阳性反应,与正常上皮及癌巢对比鲜明,UEA—I还能显示间质异常增生的血管,说明它是一种协助诊断鼻咽癌前病变很有希望的一种凝集素。而PNA及ConA则对鼻咽癌前病变的诊断价值不大。     

Labeling index and labeling distribution of cells in esophageal epithelium of individuals at increased risk for esophageal cancer in Huixian, China

The pattern of proliferation of epithelial cells in esophageal epithelium was studied by means of [3H]deoxythymidine labeling of esophageal epithelium in subjects from Huixian, Henan Province, China, a high-risk geographical region for esophageal cancer. Comparisons were made among patterns of cell proliferation observed in normal esophagus, in hyperplasia, in mild dysplasia, and in moderate dysplasia in a total of 118 subjects. The amount of cell proliferation observed was lowest in normal esophageal epithelium and increased progressively in subjects having hyperplasia, mild dysplasia, and moderate dysplasia. The location of proliferating cells was limited mainly to the base of the esophageal epithelium in normal esophagus, but expanded toward the surface of the esophageal lining in individuals with hyperplasia and dysplasia. The larger total numbers of proliferating cells in the esophageal epithelium and the progressive expansion of the proliferative compartment toward the epithelial surface found in hyperplasia and in dysplasia could both facilitate the screening of subjects for esophageal cancer risk and serve as intermediate biomarkers in prophylactic dietary or pharmacological intervention studies.     

食管癌组织P110α和pAKT蛋白的表达及其临床意义

目的:探讨食管癌组织中P110α、pAKT的表达与食管癌临床病理特征之间的关系.方法:收集2010年5月至2011年5月苏州大学附属第一医院76例患者的食管癌组织标本,25例正常对照食管黏膜组织标本来自解放军第101医院病理科.免疫组织化学SP法检测食管癌及正常食管黏膜组织中P110α及pAKT的表达水平.结果:76例食管癌组织pAKT表达阳性率为72.4％ (55/76)、P110α表达阳性率为57.9％ (44/76),均明显高于对照组(PpAKT=0.001,PP110α=0.025).食管癌组织中pAKT、P110α的高表达与食管癌淋巴结转移相关(PpAKT=0.017,PP110α=0.009),与其他临床病理特征无关.食管癌组织中pAKT与P110α双阳性率为52.6％(40/76),两者的表达呈正相关(r=0.486,P =0.001).结论:食管癌组织中P110α、pAKT表达与淋巴结转移相关,有可能成为临床检测食管癌淋巴结转移的生物指标.     

喉癌癌变过程中CyclinE和p53表达的临床病理学意义

目的研究喉癌癌变过程中ＣｙｃｌｉｎＥ和ｐ５３表达的临床病理学意义。方法用免疫组化检测２０例喉正常粘膜、４０例不典型增生病变和６０例喉癌组织中ＣｙｃｌｉｎＥ和ｐ５３的表达。结果ＣｙｃｌｉｎＥ和ｐ５３阳性表达均定位于细胞核。在喉癌癌变过程中,喉正常粘膜、不典型增生病变和喉癌中ＣｙｃｌｉｎＥ阳性表达率分别为５．０％（１／２０）、２０．０％（８／４０）和４５．０％（２７／６０）（Ｐ＜０．００１）。ｐ５３阳性表达率分别为０、３０．０％（１２／４０）和６１．７％（３７／６０）（Ｐ＜０．００１）。淋巴结转移组ＣｙｃｌｉｎＥ阳性表达率明显高于非淋巴结转移组;ＣｙｃｌｉｎＥ和ｐ５３阳性表达显著性相关（Ｐ＜０．０５）。结论ＣｙｃｌｉｎＥ和ｐ５３异常表达可能是喉癌发生中早期分子事件,对喉癌发展起重要作用。     

Expression and roles of keratinocyte growth factor and its receptor in esophageal cancer cells

The keratinocyte growth factor receptor (KGFR), also known as FGFR2 IIIb, is mainly localized in epithelial cells and is activated by the keratinocyte growth factor (KGF) that is predominantly synthesized by mesenchymal cells. In this study, we examined the roles of KGFR and KGF in human esophageal cancer (EC). In noncancerous esophageal tissues, KGFR was localized in epithelial cells from the basal region of the epithelium to the lower one-third of the epithelium, and KGF was weakly localized in the basal to parabasal epithelial cells. On the other hand, Ki-67 was localized in the parabasal cells. In EC tissues, KGFR and KGF were expressed in cancer cells in 22 and 37 of 54 patients, respectively. The coexpression of KGFR and KGF in cancer cells was detected in 14 of 54 (26%) patients. Clinicopathologically, KGFR expression correlated with the well-differentiated cell type of EC (p<0.001), and KGF expression correlated with lymphatic invasion and lymph node metastasis (p=0.004 and 0.021, respectively). The coexpression of KGFR and KGF in cancer cells correlated with the well-differentiated cell type of EC (p=0.001). KGFR-positive, KGF-positive and KGFR/KGF coexpression patients tended to have shorter survival rates, but the survival rates were not statistically significantly different (p=0.44, 0.059 and 0.112, respectively). In human EC cell lines (TE-1, TE-8 and TE-11), KGFR mRNA was expressed but no KGF mRNA was detected. The KGFR mRNA level was highest in TE-1 cells, derived from well-differentiated SCC and lowest in TE-8 cells. KGFR was detected in the cancer cell lines by Western blot analysis. Recombinant human KGF significantly stimulated the growth of TE-8 and -11 cells, derived from moderately differentiated SCC, but had no effect on TE-1 cell growth. These results suggest that KGFR expression correlates with the differentiation of a normal esophageal epithelium and the well-differentiated cell type of EC. On the other hand, KGF may induce the growth of some EC cells in a paracrine manner and closely correlates with lymphatic invasion and lymph node metastasis.     

Demographic study of clinically atypical (dysplastic) nevi in patients with melanoma and comparison subjects

We examined 296 patients with a history of melanoma and 145 controls for the presence of atypical (dysplastic) nevi. We found that 34% of patients with melanoma and 7% of controls had clinically atypical (dysplastic) nevi. Patients and controls with atypical (dysplastic) nevi had more nevi than the subjects without. The number of nevi varies negatively and significantly with age (r = 0.37, P less than 0.001). Ten % of patients and controls had hypopigmented halos around one or more nevi. Both patients and comparison subjects with atypical (dysplastic) nevi tended to have this subtle variant of halo nevi more often than those without (r = 0.17, P less than 0.01). The number of nevi on the irides of melanoma patients was greater than that in the comparison group. The results of this study suggest that patients with a melanoma exhibit more commonly cutaneous and ocular pigmentary lesions than comparison subjects without a melanoma.     

血清总唾液酸在食管癌早诊中的研究

 目的：探讨血清总唾液酸对食管癌早诊的作用。方法：采用化学比色法对我国食管癌高发区之一—磁县1510例普查人群的血清总唾液酸(TSA)分析研究。结果：高发人群血清TSA含量随食管上皮细胞增生加重逐渐增加。方差分析显示食管癌、近癌、重增Ⅱ与重增Ⅰ、轻增、正常人群血清TSA含量具有显著性差异(P<0.01),食管各级病变血清TSA含量两两比较的q检验结果表明：在食管上皮细胞重增Ⅱ时TSA含量与正常人群就有显著性差异(P<0.01),而重增Ⅰ、轻增和正常人群TSA无显著性差异(P>0.05)。结论：提示血清TSA含量可作为一种食管癌早诊指标用于人群筛查工作。