Reactivity of gastric cancer patients in leucocyte migration inhibition tests to 3M KCl extracts from gastric tumor

Leucocytes from patients with gastric cancer and other malignant and non-malignant diseases of the gastrointestinal tract as well as from healthy controls were tested for leucocyte migration inhibition test (LMI) using five different, allogeneic 3M KCl soluble extracts from gastric cancer tissues. The normal range of migration index (MI) was considered to be between. 0.77 and 1.18 by calculating the mean MI±2SD of ten healthy controls with cancer extracts. MIs out of this range were considered to be pathologic. In LMI test with a single tumor extract, pathologic MI was found in 48% of 79 gastric cancer patients, such being significantly higher than in those (4–21%) of three other groups of patients. In the panel model of LMI, i.e., testing each blood sample with five different tumor extracts, 79% (62/79) of patients with gastric cancer were reactive, while 25% (5/20) of colorectal cancer patients showed “positive” reaction and no “positive” reactivity was observed in two other groups of patients. thus, the “positive” reactivity in patients with gastric cancer was observed significantly higher than those in the other 3 groups of patients. Gastric cancer extracts had a wide range of cross-reactivity when compared with colorectal tumor extracts which showed a relatively restricted corss-reactivity. Thus, the LMI test, particularly when tested by a panel mode, seems to express cell-mediated immunity against tumor associated antigens of gastric cancer.     

E-钙黏附素基因甲基化与结直肠癌临床病理特征的关系

目的探讨E-钙黏附素（E-cadherin）基因甲基化与结直肠癌临床病理特征的关系。方法采用甲基化特异性巢式PCR技术（nMSP法）研究100例结直肠癌组织及100例癌旁组织E-eadherin基因甲基化与临床病理特征的关系。结果100例结直肠癌组织中有33例呈E-cad基因甲基化阳性（阳性率33.0％），相应的癌旁组织无甲基化。Dukes分期中C、D期组织E-cad基因甲基化阳性率（72.7％）明显高于A、B期（27.3％）（P〈0.05）；伴肝转移的结直肠癌组织甲基化阳性率（81．8％）明显高于无肝转移者（18．2％）（P〈0．01）；在肿瘤细胞分化程度、大体类型、年龄、性别和肿瘤部位等其他病理特征，E-cad基因甲基化阳性组与阴性组差异无统计学意义（P〉0．05）。结论结直肠癌组织E-cad基因甲基化与淋巴结转移、肝转移和Dukes分期明显相关，E-cad基因甲基化可能是结直肠癌侵袭性增强的原因之一。     

组织蛋白酶 B在结直肠癌中的表达及临床意义

目的探讨组织蛋白酶 B( CatB)的表达与结直肠癌浸润和转移的关系及临床意义.方法采用免疫组织化学(免疫组化)法检测 83例患者的结直肠癌原发灶、正常结肠黏膜、转移淋巴结和肝转移灶中 CatB表达,用酶联免疫吸附法检测患者外周静脉血 CatB水平.结果结直肠癌原发灶、正常结肠黏膜、转移淋巴结和肝转移灶中 CatB表达阳性率分别为 56.6%、 31.3%、 88.4%和 85.0%,癌原发灶、肝转移灶和转移淋巴结中 CatB表达阳性率高于正常肠黏膜组织(χ 2=45.6124, P< 0.01);转移淋巴结和肝转移灶中 CatB表达阳性率高于癌原发灶(χ 2=11.5982、 4.3747, P< 0.05). Dukes C、 D期 CatB表达阳性率高于 Dukes A、 B期(χ 2=16.9385, P< 0.01),低分化腺癌和黏液腺癌 CatB表达阳性率高于高、中分化腺癌(χ 2=14.2338, P< 0.01). 83例结直肠癌患者外周静脉血 CatB平均水平为( 5.9± 2.9) ng/ml, 30例健康志愿者 CatB平均水平为( 2.3± 1.1) ng/ml,两者差异有统计学意义( t=6.6975,P< 0.01). Dukes C、 D期结直肠癌患者外周血 CatB水平高于 Dukes A、 B期患者.结论 CatB增强表达与结直肠癌浸润转移有关,检测外周静脉血 CatB水平对临床预测和判断淋巴结和肝转移有重要意义,有助于评价和观察临床治疗效果.     

环氧合酶-2及血管生成素-2在大肠癌中的表达及临床意义

目的 研究环氧合酶-2（cyclooxygenase-2，Cox-2）及血管生成素-2（angiopoietin-2，Ang-2）在大肠癌组织、癌旁组织及正常大肠组织中的表达及其与大肠癌临床病理特征之间的关系。方法 采用免疫组化SP法检测45例大肠癌组织、45例癌旁组织及15例正常大肠组织中Cox-2和Ang2的表达情况。结果 大肠癌组织中的Cox-2和Ang-2的表达阳性率（80.0％，66.7％）均分别高于癌旁组织（35．6％，11．1％）及正常大肠组织（0，0），P均〈0.01。在大肠癌组织中Cox-2和Ang-2蛋白表达与淋巴结转移及Dukes分期有关（P〈0．05），且二者的表达具有相关性（P〈0．01）。结论 Cox-2和Ang-2在大肠癌发生、发展中起重要作用，二者在表达上密切相关。     

利用组织芯片研究VEGF-C和MMP-9在大肠癌中的表达及其意义

目的:探讨VEGF-C和MMP-9在大肠癌中的表达及其意义。方法:利用免疫组化技术检测组织芯片(包括110例大肠癌组织和20例癌旁正常组织)中VEGF-C及MMP-9的表达。结果:VEGF-C和MMP-9在大肠癌中表达的阳性率分别为82.7%和80.0%,明显高于两者在癌旁正常组织中的表达(5.0%,10.0%)(P<0.05)。VEGF-C和MMP-9在Dukes C/D期大肠癌中表达的阳性率分别为90.7%和88.9%,明显高于两者在Dukes A/B期大肠癌中的表达(73.2%,69.6%)(P<0.05)。在大肠癌组织中,VEGF-C与MMP-9的阳性表达呈低度正相关(r=0.253,P<0.05)。结论:VEGF-C和MMP-9的表达与大肠癌的发生发展及浸润转移密切相关,两者的高表达提示大肠癌恶性程度较高。     

CD4+、CD8+和NK在结直肠癌中的表达及其与淋巴结微转移的关系

目的 检测不同Dukes分期结直肠癌患者淋巴结细胞角蛋白20(CK20)mRNA的表达及外周血CD4+、CD8+、CD4+/CD8+与NK细胞活性表达,探讨两者间关系.方法 采用常规苏木素.伊红(HE)染色病理切片检测21例结直肠癌患者281枚淋巴结转移癌灶及逆转录-聚合酶链反应(RT-PCR)方法检测患者淋巴结CK20 mRNA表达;采用流式细胞仪检测患者外周血CD4+、CD8+、CD4+/CD8+及NK细胞活性表达.结果 HE染色法检出有淋巴结转移者为16枚(6%,16/281),RT-PCR法检出有淋巴结转移者140枚(50%,140/281);按有淋巴结微转移重新Dukes分期后,手术前,A、B期患者血CD4+、CD4+/CD8+高于c期(P<0.05);A期患者血CD8+低于C期(P<0.05);B期患者血NK细胞活性高于C期(P<0.05).新Dukes分期与血CD4+呈负相关(r=-0.497,P<0.01);与CD4+/CD8+呈负相关(r=-0.714,P<0.01);与CD8+呈正相关(r=0.945,P<0.01).结论 RT-PCR方法对淋巴结微转移的检出率明显优于HE染色切片法,结直肠癌淋巴结微转移的发生与患者免疫功能明显低下密切相关.     

Are screen detected colorectal cancers asymptomatic?

Objective Colorectal cancer (CRC) screening aims to detect asymptomatic disease and thus provide the opportunity for early diagnosis and treatment. This study assesses the prevalence of significant symptoms in patients found to have CRC detected through the NHS National Bowel Cancer Screening Programme (NHS NBCSP) pilots. Method All patients in the NHS NBCSP pilots with a positive faecal occult blood completed a standardized symptomatology questionnaire before colonoscopy. This data was entered into the NHS BCS pilot database, data from the English arm has been analysed retrospectively. Results There were 200 patients diagnosed with colorectal cancer. Of these, 28.5% were Dukes A, 35% Dukes B, 31% Dukes C1 and 5.5% Dukes C2. Some 81.5% reported experiencing GI symptoms. Symptoms considered significant included rectal bleeding, change in bowel habit, tenesmus and peri‐anal discomfort, reported in 47.7%, 24%%, 36.5% and 15.5% of patients respectively. In addition to this, 27% reported urgency, 20.5% reported abdominal pain and 29% reported upper GI symptoms. Discussion This data suggests a high prevalence of significant symptoms amongst patients with screening‐detected CRC. It is possible that these patients would have presented via routine colorectal services if the awareness of symptoms of colorectal cancer were increased.     

Anchor Attachment蛋白在结直肠癌中的表达及临床意义

目的 探讨Anchor Attachment蛋白(AAP)的表达与结直肠癌浸润和转移的关系及临床意义.方法 采用免疫组织化学方法检测83例结直肠癌患者的正常肠黏膜、癌原发灶、转移淋巴结及肝转移灶中AAP的表达,并分析AAP表达水平与肿瘤临床病理特征之间的关系.结果 结直肠正常肠黏膜、癌原发灶、淋巴结和肝转移灶中AAP的表达阳性率分别为20.5%、53.0%、69.8%和80.0%;癌原发灶、转移淋巴结和肝转移灶中AAP表达阳性率均显著高于正常肠黏膜组织(x2=42.349,P<0.01),转移淋巴结和肝转移灶中AAP阳性率又高于癌原发灶(x2=6.666,P<0.05);淋巴结转移患者和肝转移患者的原发灶AAP阳性率显著高于无转移者(x2=10.056,7.705,P<0.01);Dukes分期A、B、c、D期患者AAP阳性率逐渐增高,各分期之间差异有统计学意义(x2=12.313,P<0.01).83例结直肠癌患者血清AAP水平为(6.3±2.8)ng/ml,30例志愿者AAP水平为(2.2±0.9)ng/m1,两者差异有统计学意义(t=6.97,P<0.01);Dukes分期A、B期患者血清AAP水平为(5 2±2.6)ng/ml,C、D期患者AAP水平为(7.1±2.9)ng/ml,两者差异有统计学意义(t=2.028,P<0.05).结论 AAP增强表达与结直肠癌浸润和转移密切相关,检测外周静脉血AAP水平对预测和判断结直肠癌局部复发和肝转移有重要意义.     

Leukocyte migration inhibition assay in patients with prostate adenocarcinoma

The leukocyte migration inhibition (LMI) assay was used to determine the cell-mediated immune reactivity of prostate cancer patients to putative tumor antigens present in potassium chloride extracts of surgically removed prostate tumor tissue. Using an extract prepared from prostate tumor tissue, inhibition of leukocyte migration was found more frequently in prostate tumor patients (61%) than in patients with benign prostate hyperplasia (37%), patients with nonprostate cancers (26%), or normal donors (10%). Control extracts prepared from normal prostate tissue, benign prostate hyperplasia tissue, and unrelated tumor tissue were statistically less reactive in the LMI assay than the prostate tumor extract when reacted against leukocytes from prostate tumor patients. These results suggest that the LMI assay might be potentially useful for measuring the tumor-directed, cell-mediated immune responses in patients with prostate cancer.     

结直肠癌患者骨髓微小转移的免疫组化研究

为研究直肠癌的骨髓微小转移,自１９９４年４月至１９９６年４月作者采用抗ＥＭＡ单抗检测直、结肠癌患者骨髓血中的微小转移灶。全组共５７例,３４例结肠癌患者检出１４例阳性病例（阳性率为４１％）,２３例直肠癌发现９例阳性病例（阳性率为３９．１％）,经统计学分析发现阳性细胞检出率与患者年龄、癌肿病理类型及改良Ｄｕｋｅｓ分期有关,而与癌的原发灶部位无关。作者认为该法可准确判断直、结肠癌的病变范围,指导临床治疗有重要意义。     

癌基因Stat3与结直肠癌临床病理特征的关系

目的探讨转录信号传导子与激活子 3(Stat3)在结直肠癌中的表达情况 ,分析Stat3的表达与结直肠癌临床病理特征的关系。方法应用Westernblot检测 4 5例结直肠癌组织及其邻近正常肠粘膜中Stat3蛋白的表达。结果结直肠癌组织中Stat3蛋白表达水平明显高于正常肠粘膜(P <0 0 5 ) ,平均为正常肠粘膜的 2 4 5倍 ;Stat3表达水平与Dukes分期、分化及淋巴结转移有关 (P <0 0 5 ) ;Stat3表达水平与肿瘤大小、远处转移、年龄、性别以及是否浸润浆膜无关 (P >0 0 5 )。结论Stat3的过量表达可能在结直肠癌的发生、发展过程中起重要作用。     

血管内皮细胞生长因子与增殖细胞核抗原联合检测用于大肠癌临床预后判定

目的　探讨大肠癌血管内皮细胞生长因子 (VEGF)及增殖细胞核抗原 (PCNA)与大肠癌术后有无潜在性转移及复发的关系。方法　对 5 9例已获确诊的大肠癌石蜡标本作免疫组化SP法染色 ,检测其VEGF及PCNA的表达 ,并与 12例正常大肠组织和 16例大肠腺瘤进行比较。结果　大肠癌VEGF的表达明显高于大肠腺瘤 (P<0 .0 5 ) ;DukesA +B期大肠癌VEGF的表达与DukesC +D期比较 ,差异有显著性 (P<0 .0 5 ) ;术后复发组VEGF的表达明显高于无复发组 (P<0 .0 5 )。增殖活性表达提示 ,大肠癌分化程度越低 ,有淋巴结或肝转移时 ,其PCNA指数增高 ;术后有、无复发者之间 ,其PCNA指数差异有显著性 (P<0 .0 5 )。结论　大肠癌VEGF与PCNA的表达与肿瘤的浸润、转移密切相关。手术时虽然无明显转移灶 ,VEGF阳性及PCNA活性增强时仍可能有潜在的转移存在。     

核不均一性核糖核蛋白A1在大肠癌中的表达

目的检测大肠癌组织中核不均一性核糖核蛋白（hnRNPA1）及其基因的表达情况，探讨hnRNPA1与大肠癌临床各项指标的相关性。方法收集60例大肠癌患者手术切除标本，制备快速冰冻病理切片，免疫组织化学链霉菌抗生素蛋白-过氧化酶连接（SP）法检测hnRNPA1蛋白的表达；同时应用半定量聚合酶链反应（PCR）法检测组织hnRNPA1基因表达情况，分析基因表达量与临床指标的关系。结果免疫组织化学检测可见hnRNPA1蛋白着色主要位于细胞浆和细胞核；60例大肠癌标本中有35例阳性表达，表达率明显高于正常大肠黏膜组织（P〈0．05），与肿瘤的分化程度、临床Dukes分期和淋巴结转移密切相关（P〈0．05）。逆转录（RT）-PCR可见hnRNPA1阳性标本占96．7％，平均比值显著高于正常大肠黏膜的平均比值，不同分化程度及不同临床分期的大肠癌中hnRNPA1基因的表达差异有统计学意义（P〈0．05）。结论hnRNPA1在大肠癌中高表达。在晚期伴淋巴结转移的大肠癌中其蛋白和基因的表达明显高于早期大肠癌。表达强度随分化程度的降低而递增。     

结直肠癌患者血清可溶性CD26增高及其意义

目的评价血清可溶性CD2(6sCD26)对结直肠癌的诊断价值。方法收集我院59例结直肠癌患者、51例结直肠良性疾病患者和41例健康对照患者的血清,采用ELISA法检测血清中sCD26浓度。采用受试者工作曲线(ROC)法评价血清sCD26对结直肠癌的诊断价值,并采用logistic回归分析其对结直肠癌的关系是否独立于癌胚抗原(CEA)。结果结直肠癌患者血清sCD26水平较健康对照组和结直肠良性疾病组患者增高(P<0.01),但sCD26在Dukes不同分期间的差异无统计学意义(P=0.78)。sCD26诊断结直肠癌的曲线下面积为0.72〔95%可信区间(CI)为0.63～0.82,P<0.01〕,最佳诊断界值为526μg/L。sCD26的诊断敏感度和特异度分别为0.59(95%CI为0.48～0.72)和0.80(95%CI为0.67～0.90)。在包含了CEA的logistic回归模型中,sCD26阳性(≥526μg/L)的优势比为5.17(95%CI为1.72～15.53,P<0.01)。DukesA期结直肠癌患者sCD26较CEA具有更高的阳性率(P=0.03),但Dukes B、C和D期结直肠癌患者sCD26的阳性率均低于CEA(P<0.05)。结论sCD26对结直肠癌具有较高且独立于CEA的诊断价值。与CEA相比,sCD26更具有成为结直肠癌早期标志物的潜质。     

Results of long-term follow-up after curative resection of Dukes A colorectal cancer

Patients with Dukes A (UICC I) colorectal cancer have a good prognosis after curative resection. It is not known, however, if the outcome is significantly different for UICC Ia and Ib patients or if patients with reduced risks of recurrences can be identified early after surgery. This is of interest, as it would permit a more cost-effective, patient-oriented, and tumor stage-oriented follow-up program. To study these questions, a prospective follow-up database, including 1375 patients after curative resection of colorectal cancer, was analyzed. A total of 296 patients with Dukes A colorectal cancer with a median follow-up of 44 months were studied. Perioperative and follow-up mortality rates were 3% and 14%, respectively. Recurrent disease developed in 10% of Dukes A patients after a disease-free interval of 16 months. Significantly more patients suffering from pT2 (UICC Ib) cancer had recurrent disease than patients with pT1 (UICC Ia) cancer (13% vs. 4%; p <0.05). Preoperative CEA levels in patients with recurrent disease were significantly higher than in long-term disease-free patients (5.3 +/- 1.8 vs. 3.5 +/- 0.6 ng/ml; p <0.05). Curative resection of recurrent disease was achieved in 38% of the patients with recurrences (4% of all patients). Survival analysis showed significantly better survival in patients with Dukes A cancer than in those at higher tumor stages (log rank, <0.0001), and only 39% of all Dukes A patients who died during follow-up had recurrent disease. Dukes A (UICC Ia and Ib) colorectal cancer was diagnosed in 22% of our patients treated for cure, and long-term survival was 86%. There were significantly fewer cases of recurrent disease after curative resection of UICC Ia (pT1N0M0) cancer, so we propose a novel, less intensive follow-up regimen for these patients, leading to a more cost-effective, patient-oriented, and tumor stage-oriented follow-up program.     

大肠癌鸟氨酸脱羧酶基因表达及临床意义研究

目的:研究鸟氨酸脱羧酶(ODC)基因在结直肠癌中的表达,探讨其在大肠癌形成中的作用.方法:建立测定ODC基因mRNA表达的逆转录多聚酶链反应(RT-PCR)最适条件,在半定量水平测定31例结直肠癌的癌旁正常组织和癌组织中的ODC mRNA表达的相对水平,观察其与临床病理学指标的关系.结果:31例结直肠癌中ODC基因表达较癌旁正常组织高,差异显著(P＜0.01),ODC基因表达在性别、病理类型之间差异无显著意义(P＞0.05),在Dukes分期之间差异有显著意义(P=0.012).结论:ODC在大肠癌组织中表达增高并与恶性程度呈正相关,提示ODC表达增加与大肠癌发生、浸润及转移有关,为大肠癌病因及诊断和治疗方法研究提供了实验依据.     

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目的 观察大肠癌病人血循环中肿瘤细胞的存在与大肠癌的分期以及术后发生肝转移之间的关系。方法 以CEAmRNA为肿瘤细胞的标志物，利用RT-PCR检测了38例大肠癌病人的术前外周血、术中门静脉血和术后外周血中微转移的肿瘤细胞。结果 血循环中CEAmRNA的阳性检出率与大肠癌的Dukes分期密切相关，即使在Dukes A期的病人中也有术前外周血和术中门静脉血中CEAmRNA的表达阳性者（33.3%）。随访发现，血循环中尤其术后外周血中CEAmRNA呈阳性的大肠癌病人日后发生肝转移的机率大大高于CEAmRNA呈阴性的病人[5/9（55.6%)vs3/26(11.5%),P=0.024]。结论 检测大肠癌病人血循环中的肿瘤细胞对于准确评估大肠癌预后具有较为重要的临床意义。     

淋巴结微转移及相关蛋白检测在大肠癌患者Dukes分期、治疗和预后中的意义

目的 探讨淋巴结微转移（LNMM）和nm23-H1、基质金属蛋白酶9（MMP9）、金属蛋白酶2组织抑制因子（TIMP2）蛋白检测及其相关性在大肠癌患者Dukes分期、治疗和预后中的意义。方法 应用免疫组化SABC法检测30例DukesB期大肠癌淋巴结细胞角蛋白20（CK20）和癌组织nm23-H1、MMP9、TIMP2蛋白表达,另对同期30例DukesC和D期大肠癌患者检测nm23-H1、MMP9和TIMP2;随访、记录患者的临床病理参数和生存资料,分析其相关性。结果 （1）26．7％DukesB期大肠癌患者、7．8％DukesB期大肠癌淋巴结存在CK20阳性。（2）DukesB期大肠癌nm23-H1、MMP9表达与DukesC和D期差异显著（P〈0．05）;nm23-H,表达下降和（或）MMP9表达增强与LNMM相关（P〈0．05）,两者预测大肠癌LNMM敏感性和特异性分别为62．5％和81．8％、75．0％和69．8％,联合检测特异性则达90．9％;而TIMP2与Dukes分期、LNMM无关。（3）DukesB期LNMM（＋）患者癌复发转移率明显高于同期LNMM（-）组（P〈0．05）,而生存率则降低（P〈0．05）;nm23-H1（-）LNMM（＋）、MMP9（＋）LNMM（＋）患者生存期明显短于nm23-H1（＋）LNMM（-）、MMPq（＋）LNMM（-）组（P〈0．05）。结论 CK20免疫组化可检出大肠癌LNMM;DukesB期大肠癌nm23-H1、MMP9表达与LNMM相关,且表达异常LNMM患者预后差;联合检测淋巴结CK20和癌组织rim23-H1、MMP9表达,对大肠癌Dukes分期、术后辅助化疗和预后判断有重要意义。     

VEGF和CK20mRNA联合检测在大肠癌病人中的意义

目的探讨大肠癌病人外周血细胞角蛋白(CK20 mRNA)和肿瘤组织VEGF蛋白作为大肠癌肿瘤细胞血行播散标志的临床意义。方法应用逆转录聚合酶链反应(RT-PCR)技术和免疫组织化学方法检测63例大肠癌术中抽取的外周血CK20 mRNA和手术切除肿瘤组织中VEGF蛋白的表达,并对所测结果进行分析和比较。结果高、中分化和低、未分化大肠癌病人的CK20 mRNA和VEGF的阳性率分别为30.0%、50.0%和84.6%、92.3%,均有非常显著性差异(P<0.01)。DukesA、B期和C、D期大肠癌病人CK20 mRNA和VEGF的阳性率分别为32.4%、56.8%和53.8%、61.6%,无显著性差异(P>0.05)。CK20 mRNA与VEGF作为单项指标测定的阳性率分别为41.3%和58.3%,联合检测时阳性率升至69.8%,有非常显著性差异(P<0.01)。结论大肠癌病人外周血CK20 mRNA和肿瘤组织VEGF可作为衡量术后复发转移的有效指标;两者联合检测时,敏感性显著提高。