HLA 抗原和肝细胞癌的可能相关

 本文研究了34例肝细胞癌患者的组织相容性抗原(HLA)和肝细胞癌易感性的可能相关。采用 NIH 标准的补体依赖的淋巴细胞微量细胞毒试验,用480个HLA 抗血清检测了70个 HLA 抗原特异性:A 位点18个,B 位点34个,C 位点8个和 DR 位点10个。结果显示肝癌病人中 A3抗原频率明显增加,达26.4％(9/34)。与对照组相比,X²=9.66,纠正 P 值<0.05;DRW9抗原频率在肝癌病人中也显著增加(Pc<0.05)。A3阳性的肝癌病人和 DRW9阳性的肝癌病人血清中 HBsAg,HBcAb 的携带率与阴性者相比,无统计学上的明显差异。     

晚期宫颈癌与HLA关联的初步探讨

关于宫颈癌与人类白细胞抗原(HLA)的关联研究,文献报导甚少。在研究白种人宫颈癌与HLA的关联方面,1973年TakasujiM等报告,癌组的A1、A9和B12抗原频率虽与对照组有差别,但无统计学差异;1974年Terasaki P I等报告,本癌与任何HLA单倍型无关联;1980年Simons M,J.等报告,癌组的B12、DRW7频率和B12-DRW7     

肺癌病人自然杀伤细胞活性改变与HLA Ⅰ类无关联

目的研究发现控制自然杀伤(NK)细胞低活性的基因与HLAⅠ类基因相关联.在此基础上,检测肺癌病人NK细胞活性和HLAⅠ类抗原,以期发现肺癌的HLAⅠ类基因分布的特点及其与NK细胞活性的关系.方法采用国际标准的微量细胞毒分型方法对46例肺癌病人和34例正常人对照进行HLA-A、-B分型;采用乳酸脱氢酶释放法测定其NK细胞活性;数据的统计学处理采用t′检验及卡方检验或Fisher精确概率法.另外,46例肺癌病人与已知其单倍型的96例正常人进行了传统的疾病关联分析.结果发现肺癌病人的NK细胞活性(41.87±25.44)明显低于对照组(62.65±47.50),t′=2.32,P<0.05.肺癌病人NK细胞活性下降与HLA的型别分布无关,肺癌与HLA-A,-B抗原均无显著关联.结论肺癌的发生及其自然杀伤细胞活性下降与HLAⅠ类无关联.     

硒蛋白S基因G-105A、G-254A位点多态性与湖南汉族人群胃癌遗传易感性的相关研究

目的 探讨湖南汉族人群硒蛋白S(SelS)基因G-105A、G-254A位点多态性与胃癌遗传易感性的相关研究.方法 采用聚合酶链反应—限制性片断长度多态性(PCR-RFLP)方法,检测113例湖南汉族胃癌患者及111例健康对照者基因型和等位基因频率,分析胃癌患者与健康对照者G-105A、G-254A位点等位基因频率及基因型频率的差异.结果 G-105A位点GG、GA和AA基因型在胃癌组和健康对照组间分别为100.0％、0.0％、0.0％和100.0％、0.0％、0.0％;G、A等位基因频率在胃癌组和健康对照组分别为100.0％、0.0％和100.0％、0.0％,胃癌组和健康对照组基因型和等位基因频率分布无差异.G-254A位点CC、CT和TT基因型在胃癌和健康对照组间分别为50.0％、37.2％、12.8％和65.8％、28.8％、5.4％;C、T等位基因频率在胃癌组和健康对照组分别为69.0％、31.0％和80.2％、19.8％.胃癌组和健康对照组基因型和等位基因频率分布差异有统计学意义(P＜0.05).湖南汉族人群中携带T等位基因的个体患胃癌的风险是CC基因型个体的1.89倍(OR=1.89,95％CI:1.10～ 3.23).结论 SelSG-254A位点多态性与胃癌的发病具有相关性,T等位基因可能是湖南汉族人群胃癌发病的危险因素之一;湖南汉族人群可能无G-105A这一位点的多态性分布.     

LPAK细胞的体外增殖,杀伤活性及治疗晚期肝癌的初步研究

LPAK细胞在体外培养的增殖效应显著高于LAK细胞(P<0.05),而对K562细胞、Raji细胞的杀伤活性与LAK细胞无显著差别(P>0.05),对SGC—7901胃癌细胞和小鼠S180肉瘤细胞亦有较强的杀伤活性.用异体同型血LPAK细胞加白细胞介质2(Interleukin 2,IL—2)治疗晚期肝癌5例,其中2例治疗后无变化,3例肿病分别缩小47.0％,39.6％和35.7％.     

人类白细胞抗原表达对喉癌预后的影响

目的 研究HLA－ABC、HLA－DR抗原的表达异常与喉癌的预后的关系。方法 用免疫组织化学SP方法检测经随访的34例喉癌组织标本的HLA表达情况，各计算HLA－ABC、HLA－DR抗原阴性、阳性患者的生存率曲线，用COX比例风险模型作多变量分析。结果 HLA－ABC抗原阴性患者的无癌5年生存率为16％，阳性患者为67％，经多变量分析两者有显著性差异（P＝0．02）；HLA－DR阴性患者无癌5年生存率为40％，阳性患者为72％，经多变量分析，两者无显著性差异（P＝0．95）。结论 HLA－ABC、HLA－DR抗原在喉癌中发生了改变，HLA－ABC抗原的下降可能与喉癌的预后差异有关，而HLA－DR抗原的变化可能与喉癌的预后无关。     

改良胃管留置途径的胃肠减压护理

目的 探讨胃癌围手术期腹壁(输入袢造口置管)留置胃肠减压护理,是否可为此类病人术后护理恢复提供有效支持。方法 62例胃癌毕II式吻合术加肠间吻合术病人,其中实验组28例术中行腹壁胃管,对照组34例术前经鼻咽置入胃管,应用相应护理措施,观察病人术后排痰、睡眠、腹痛腹胀、肠蠕动恢复、并发症等情况。结果 对照组病人睡眠不佳和排痰不利的发生率显著高于实验组(P＜0.05)。实验组平均恢复肠蠕动时间显著少于对照组(P＜0.01)。两组病人均有腹痛腹胀症状,差别无统计学意义(P＞0.05)。对照组并发症高于实验组,差别无统计学意义(P＞0.05)。结论 评价腹壁胃肠减压护理是可行的、安全的,有利于病人术后快速康复,消除不良心理,保持病人更舒适心态。     

幽门螺杆菌CagA与GSTM1缺失对胃癌的交互作用研究

[目的]探讨幽门螺杆菌CagA感染与胃癌的关系，及其与代谢酶基因多态性的交互作用对胃癌易感性的影响。[方法]以社区为基础的病例对照研究。肠型胃癌病例经胃镜及病理确诊，有效分析样本包括：完成CagA抗体检测胃癌108例，对照217例：完成CagA抗原检测病例107例，对照284例。[结果]胃癌组H.Pylori CagA抗体阴性率为85.1％，显著高于别照组的49．31％，OR值为5．91(95％Cl：3．26～10．71,P=0．001)；在CagA抗体阴性时，胃癌组CagA抗原阳性率达12．50％，显著高于对照组的1．82％，OR值为7．71（95％CI：1.01～59.18，P=0．023)，在CagA抗体阳性组则未见两者有显著性差异；调整混杂因素后，GSTMl缺失基因型与H.Pylorr CagA抗原之间有明显的相乘交互作用，γ为19.58，交互作用OReg达10．49，与H.Pylori CagA抗体之间也有明显的交互作用。[结论]H．Pylori—CagA毒株感染后产牛拘CagA抗体是保护性因素，而H.PyloriCagA抗原为胃癌的危险性指标；H.Pylori CagA感染与GSTMl缺失基因型对胃癌发生有明显的交互作用。     

HLA分型在胃肠肿瘤患者中的分布

目前,我室开展MAGE,CEA肽类联合DC细胞治疗消化道肿瘤的研究.MAGE,CEA作为一种抗原肽需要特定的人类白细胞抗原(HLA)分子相结合,才能被DC细胞所递呈.因此需要对病人进行HLA测定,筛选出与MAGE,CEA相匹配的HLA分型的患者.在实验以血清学分型,采用国际上标准的淋巴细胞毒实验.标本取自1998.6～1999.5入我院腹科治疗的部分病人的外周血,共50例,其中HLA-A2,A24,A11及三者的组合共35例,胃癌26例,肠癌9例.结果:     

胃癌及癌前病变中树突状细胞浸润、HLA-DR抗原表达的临床意义

 目的　探讨S 10 0 + DC浸润、HLA DR抗原的表达在胃癌发生、发展中的作用及临床意义。方法　应用免疫组织化学方法对 4 3例胃癌、2 4例癌前病变组织中的S 10 0 + DC、HLA DR进行检测。结果　S 10 0 + DC、HLA DR在胃癌组、癌前病变组中的表达均显著高于正常胃粘膜组 (P <0 .0 5 )。在低分化、淋巴结转移和远处转移胃癌患者中S 10 0 + DC数目明显减少 (P <0 .0 1)。HLA DR在低分化胃癌中的阳性表达率显著降低 (P <0 .0 5 )。S 10 0 + DC与HLA DR的表达有正相关性。结论　胃粘膜中S 10 0 + DC与HLA DR的变化反映了胃癌局部免疫状态 ,二者在胃癌发生、发展中起重要作用。     

CYP2E1基因多态性与客家人群胃癌易感性的研究

目的：通过研究细胞色素P4502E1（CYP2E1）基因多态性位点rs2031920与客家人群胃癌遗传易感性的相关性,探讨遗传和环境因素在胃癌发病中的作用。方法采取病例-对照研究,选择经胃镜和病理检查确诊的梅州地区客家人群51例胃癌患者（胃癌组）和52例正常对照（对照组）,对CYP2E1 rs2031920（C-1053T）位点进行基因型及等位基因检测,分析其在两组间的分布特征。结果CYP2E1 rs2031920位点在梅州地区客家人群中存在 CC、CT、TT 多态性,各基因型在胃癌组的分布频率为62．75％（32／51）、33．33％（17／51）、3．92％（2／51）,在对照组的分布频率为59．62％（31／52）、34．61％（18／52）、5．77％（3／52）,两组之间的差异无统计学意义（χ2＝0．235,P ＝0．889）。CYP2E1基因rs2031920位点的等位基因 C、T 在胃癌组和对照组构成比分别为79．41％（81／102）、20．59％（21／102）和76．92％（80／104）、23．08％（24／104）,差异无统计学意义（χ2＝0．186,P ＝0．666）。经性别、年龄分层分析结果显示也无统计学意义（χ2＝4．412,P ＝0．129;χ2＝0．898,P ＝0．473）。结论 CYP2E1的基因多态性位点 rs2031920与客家人群胃癌的易感性不相关。     

胃癌中抑癌基因Kruppel样因子6 mRNA与蛋白的表达及其意义

目的 研究Kruppel样因子6（KLF6）基因表达与胃癌发生、发展的关系.方法 采用免疫组织化学（SP法）与反转录-聚合酶链反应（RT-PCR）对73例胃癌及癌旁组织的KLF6蛋白与mRNA表达进行检测,分析KLF6表达与临床病理因素间的关系.结果 KLF6蛋白在胃癌及癌旁组织中的表达率分别为39.7％（29/73）、90.4％（66/73） （P＜0.01）,在低、高-中分化癌组织中的表达率分别为25.0％（10/40）、57.6％（19/33）（P＜0.01）.KLF6mRNA在胃癌及癌旁组织中表达水平（与GAPDH吸光度比值）分别为0.1586±0.1071、0.8899±0.0638 （P＜0.01）.结论 KLF6蛋白与mRNA在胃癌组织中呈低表达,且在低分化胃癌中低于高-中分化胃癌,表明KLF6与胃癌的发生、发展及分化关系密切,可作为判断胃癌生物学行为的重要指标.     

TNF-A基因多态性及其单体型与新疆维、汉民族胃癌的关系

目的:探讨新疆维吾尔族(维族)和汉族胃癌患者肿瘤坏死因子-α基因(TNF-A)rs1800629和rs361525位点多态性及其单体型与胃癌易感性的关系。方法:采用Snapshot技术分析322例胃癌患者(其中维族93例,汉族229例)和作为对照的487例非胃癌患者(其中维族231例,汉族256例)TNF-A基因rs1800629和rs361525位点基因型的分布;利用SHEsis软件分析其构成的单体型在病例组和对照组中的分布频率,比较基因型和单体型在病例组和对照组间的分布差异。结果:在维族人群中,TNF-A基因rs1800629和rs361.525位点不论是等位基因位点、基因型还是单体型在病例组和对照组中的分布频率差异均无统计学意义(P>0.05)。在汉族人群中,TNF-A基因rs361525位点AA+GA基因型在病例组和对照组之间的分布差异有统计学意义(χ=4.56,P=0.03),即携带A等位基因者发生胃癌的风险增加(OR=2.41,95%CI:1.06～5.49);rs1800629位点基因型与胃癌之间未发现明显关联;A-A单体型在病例组及对照组分布频率分别为0.92%和0.86%,差异有统计学意义(χ~2=7.03,P=0.01)。结论:TNF-A基因单核苷酸多态性与汉族人群胃癌发病风险相关,这种相关性具有民族差异。     

Close correlation between restriction fragment length polymorphism of L-myc gene and susceptibility to gastric cancer

AIM: A common inherited RFLP of the L-myc proto-oncogene has been reported to correlate with cancer susceptibility. Our aim was to test the hypothesis that there was association between L-myc S allele in gastric cancer and predisposition to the disease. METHODS: The distribution of L-myc polymorphism in 25 patients with gastric cancer was determined by polymerase chain reaction-based restriction fragment length polymorphism and compared with that of 83 healthy control subjects. RESULTS: We found a significant difference, both in the distribution of the LL, LS and SS genotypes and in the allelic frequencies, between the control group and the patient group; that is, the frequencies of L-myc alleles were, L and S, 0.52 and 0.48, 0.64 and 0.36, respectively. This difference was primarily the result of a high frequency of the S allele among gastric cancer patients compared to controls. There was a significant difference in the distribution of both genotypes (P = 0.004) and allele frequencies (P = 0.005) between patients with gastric cancer and control groups. CONCLUSIONS: Our results suggested that L-myc polymorphism may be significant in an individual's susceptibility to gastric cancer in Turkey and may be useful for identifying patients at high risk of developing gastric cancer.     

Analysis of serum ErbB-2 protein and HLA-DRB1 in Japanese patients with lung cancer

We investigated the relationship between ErbB-2 and HLA in order to clarify the clinical and genetic factors related to Japanese patients with lung cancer. Thirty-nine of the 73 lung cancer patients (53.4%) had elevated levels of ErbB-2. Only seven of 23 (30. 4%) patients with small cell carcinoma had elevated ErbB-2 levels. The prevalence of ErbB-2 positivity was highest (23 of 32; 71.8%) in patients with adenocarcinoma, while that in patients with squamous cell carcinoma was 50% (9 of 18). The frequencies of HLA A33, B44, B62, and B75 were lower in the lung cancer patients than in the control group. HLA-DR9 was higher in frequency in lung cancer patients than in the healthy controls (P<0.05), but HLA-DR6 was lower in frequency in lung cancer patients than in controls (P<0.01). DRB1*0901 was significantly higher in frequency in lung cancer patients than in controls (P<0.05). On the other hand, DRB1*0802, DRB1*1302 and the DRB1*14 group (*1401, *1403, *1405, *1406, and *1407) were completely absent in lung cancer patients. The frequencies of HLA B35, B52, B62, DRB1*0404, and DRB1*0406 were higher in the ErbB-2-positive lung cancer patients than in the ErbB-2-negative lung cancer patients. However, these types of HLA were not included in significant frequencies in our group of lung cancers. Our results suggest that some HLA-antigens/alleles participate in the pathogenesis of lung cancer in Japanese patients. In addition, the relationship between HLA-associated genetic factors and ErbB-2 seems to be weak. These findings suggest that ErbB-2 is correlated with prognostic factors for lung cancer independently of HLA-associated genetic factors.     

高压氧联合化疗治疗转移性胃癌的临床分析

目的：观察高压氧联合顺铂（DDP）、氟尿嘧啶（5-FU）、甲酰四氢叶酸（CF）组成的FLP方案治疗转移性胃癌的临床疗效及其毒副反应。方法：40例转移性胃癌患者随机分为治疗组和对照组，治疗组采用高压氧联合FLP方案治疗，对照组单用FLP化疗方案，并进行疗效和毒副反应评价。结果：治疗组有效率为55％，对照组有效率为50％，两者比较无显著性差异（P〉0．05）；生存时间：治疗组（8．35±3．91）个月，对照组为（6．83±3．20）个月，两者比较有显著性差异（P〈0．05）；白细胞减少分级评分：治疗组为1．00±0.79，对照组为1．65±0．59，两者比较有显著性差异（P〈0．05）；恶心、呕吐分级评分：治疗组为1．05±0．76，对照组为3．3±0．73，两组比较有显著性差异（P〈0．05）。结论：高压氧联合FLP方案治疗转移性胃癌有效率较高，生存时间延长，患者耐受性较好。     

奥沙利铂联合羟基喜树碱、亚叶酸钙/5-氟尿嘧啶治疗晚期胃癌

目的 :观察奥沙利铂 (L OHP)联合羟基喜树碱 (HCPT)、亚叶酸钙 (CF)和 5 氟尿嘧啶 (5 FU)组成的HLFO方案治疗晚期胃癌的临床疗效和毒副反应 ,并与后三种药物与顺铂 (PDD)组成的HLFP方案进行比较。方法 :采用随机分组的方法将 4 2例晚期胃癌患者分为L OHP +HCPT +CF +5 FU方案组 (治疗组 ) 2 2例与HCPT +CF +5 FU +DDP方案组 (对照组 ) 2 0例 ,观察两组的临床疗效和患者的耐受性。结果 :治疗组 2 2例有效率 5 9 1% (13 2 2 ) ,对照组 2 0例有效率 4 5 % (9 2 0 ) ,治疗组有效率高于对照组 ,但两组差异无统计学意义 (P >0 0 5 )。治疗组KPS评分的改善率为 72 7% ,对照组KPS评分的改善率为 4 0 % ,两组差异有统计学意义 (P <0 0 5 )。治疗组的中位生存期及 1年生存率均优于对照组 ,但生存期比较差异无统计学意义 (P >0 0 5 )。治疗组的周围神经毒性较对照组高 ,差异有统计学意义 (P <0 0 5 ) ;对照组的恶心呕吐反应较治疗组高 ,差异有统计学意义 ;其余不良反应均相似。结论 :与HLFP方案相比 ,HLFO方案能明显改善晚期胃癌患者的生活质量 ,消化道毒副反应较轻 ,值得进一步扩大样本量进行临床随机对照研究     

The prognostic significance of gastric juice CA 19-9 and CEA levels in gastric carcinoma patients

AIM: The usefulness of gastric juice CA 19-9 and carcinoembryonic antigen (CEA) levels in the diagnosis of gastric carcinoma is controversial. There is only one study related with their prognostic value. In this study the clinical significance of gastric juice CA 19-9 and CEA levels in patients with gastric carcinoma was investigated. METHODS: Preoperative serum and gastric juice CA 19-9 and CEA concentrations were measured in 139 patients with gastric carcinoma, 54 patients with benign gastroduodenal disease and as the 'healthy' control group 46 patients with inguinal hernia and with no other pathology. RESULTS: In all groups the mean gastric juice levels of CA 19-9 and CEA were significantly higher than the serum levels. The gastric juice CA 19-9 levels were not different between groups. Gastric juice CEA levels of the gastric carcinoma group were significantly higher than those of the benign gastroduodenal disease group (P=0.007) and had a tendency to increase when compared to those of the control group (P=0.064) whereas there was no significant difference between the benign gastroduodenal disease and the control group. The cut-off values of gastric juice CA 19-9 and CEA were 440U/ml and 320ng/ml and the positivity ratios of these markers in gastric carcinoma patients were 16.5 and 27.3%, respectively. There was no significant relationship between the histopathological features and the gastric juice CA 19-9 or CEA positivities. Neither univariate analysis nor the multivariate Cox proportional hazards model analysis showed prognostic value for gastric juice CA 19-9 and CEA positivities. CONCLUSIONS: The gastric juice CA 19-9 and CEA levels have no diagnostic and prognostic significance in gastric carcinoma patients.     

Association between CagA+ Helicobacter pylori infection and p53, bax and transforming growth factor-beta-RII gene mutations in gastric cancer patients

We assessed the possible association between CagA+ Helicobacter pylori infection and gastric carcinogenesis in gastric cancer patients. Gastric biopsy specimens were obtained from 64 patients with gastric cancer and were histologically classified into intestinal and diffuse types. H. pylori infection was determined by cultivation, flaA-PCR and serum antibody against CagA. p53, BAX and transforming growth factor-beta-RII (TGFbeta-RII) gene mutations were analyzed by PCR-SSCP and direct sequencing. Intestinal and diffuse types of cancer were detected in 45 and 19 patients, respectively. H. pylori infection was found in 55 (85.9%) of 64 patients. There was no significant difference in H. pylori positivity between intestinal and diffuse types. However, the CagA antibody was positive in 15 (78.9%) of 19 patients with the diffuse type and in 22 (48.9%) of 45 patients with the intestinal type (p = 0.030). Among the 55 H. pylori-positive cases, 11 (29.7%) of the 37 patients in the CagA+ group were found to have p53 alterations, compared with 2 (11.1%) in the 18 CagA- group (p = 0.182). Moreover, among the 64 gastric cancer patients, p53 alterations were more frequently found in the CagA+ group (29.7%) than in the H. pylori-positive CagA- and H. pylori-negative groups (7.4%; p = 0.033). BAX gene mutations were found in 19 (29.7%) of 64 patients and there was no relationship among CagA seropositivity, cancer stages and histopathological phenotypes. In contrast, the TGFbeta-RII gene mutation was only detected in one CagA- patient. The results suggest that CagA+ H. pylori infection may have an important role in the development of gastric cancer patients with p53 mutations Copyright 2001 Wiley-Liss, Inc.     

晚期胃癌血清长链非编码RNA H19水平与含紫杉醇方案化疗敏感性的关系

目的 探讨晚期胃癌血清长链非编码RNA（lncRNA） H19水平与含紫杉醇方案化疗敏感性的关系。方法 收集本院2014年6月至2016年6月接受含紫杉醇方案化疗的73例晚期胃癌患者,收集其血清标本并采用实时定量PCR（QPCR）法检测H19水平,分析胃癌患者血清H19水平与临床病理特征（性别、年龄、ECOG评分、肿瘤部位、分化程度及病理类型）的关系,采用RECIST 1.1版评价近期疗效并随访无进展生存期（PFS）和总生存期（OS）,分析胃癌患者血清H19水平与近期疗效及预后的关系。选取81例健康体检者的血清标本作对照。采用受试者工作特征曲线（ROC）评价血清H19水平在胃癌对紫杉醇方案化疗反应的预测价值。结果QPCR检测发现,73例胃癌患者的血清H19水平为3.022±0.210,高于81例健康体检者的1.193±0.082,差异有统计学意义（P<0.05）。血清 H19水平与性别、年龄、ECOG评分、肿瘤部位及病理类型均无关,但与分化程度有关,其中低分化者的H19水平为3.923±0.254,高于高、中分化的1.732±0.188,差异有统计学意义（P<0.05）。73例均完成2个周期以上的化疗,可评价近期疗效,化疗敏感27例的血清H19水平为1.683±0.166,低于化疗抵抗46例的3.809±0.256,差异有统计学意义（P<0.05）;ROC曲线分析显示血清H19水平在不同紫杉醇方案化疗反应胃癌预测中的曲线下面积为0.982（95%CI：0.966～0.998）。至随访截止日期,73例晚期胃癌患者的中位PFS为6.2个月,中位OS为10.6个月。以血清H19水平的中位值将患者分为高水平组（＞2.550）和低水平组（≤2.550）,其中低水平组的中位PFS为7.2个月,高于高水平组的5.3个月（P<0.05）;H19不同水平组中位OS的差异无统计学意义（P＞0.05）。结论 晚期胃癌血清H19水平升高,与含紫杉醇方案化疗敏感性及PFS均有关,其中低水平者的疗效较好且PFS较长。