血清胸苷激酶1在乳腺癌诊治中的应用

目的:探讨血清胸苷激酶1(TK1)检测在乳腺癌辅助诊断及术后化疗效果评估中的作用。方法:应用免疫印迹-增强化学发光法(ECL)检测20例健康志愿者(健康对照组)和30例乳腺癌患者(乳腺癌组)术前、术后及化疗后血清TK1水平。比较不同疾病分期下TK1水平的差异。分析术前血清TK1水平与雌激素受体(ER)、孕激素受体(PR)的关系。结果:乳腺癌患者血清TK1水平均明显高于健康对照组(P<0.05);乳腺癌患者化疗后TK1水平明显低于术前(P<0.05),但术前术后TK1水平无明显差异(P>0.05),且TK1水平与乳腺癌分期也无明显相关性(P>0.05);同时ER、PR双阳性乳腺癌患者术前血清TK1水平低于ER、PR双阴性患者(P<0.05)。结论:血清TK1水平可反映肿瘤细胞增殖,有望成为乳腺癌预后判断及病情监测的重要指标,但其确切机制及与肿瘤进展间的关系还需深入研究。     

血清胸苷激酶1水平在乳腺癌术后疗效评估中的作用

目的探讨血清胸苷激酶1（TK1）水平对乳腺癌的临床应用价值。方法采用CIS-1型印迹免疫-增强发光检测系统检测100例乳腺癌患者、30例乳腺良性疾病、30例正常对照者血清TK1水平。比较乳腺癌患者不同病理参数下血清TK1水平的差异。分析血清TK1水平与雌激素受体（ER）、孕激素受体（PR）的关系。结果乳腺癌患者血清TK1水平均明显高于乳腺良性疾病组和对照组（P〈0.05）,且血清TK1水平与乳腺癌分期密切相关。在有淋巴结转移或术后2年复发的乳腺癌患者中,TK1水平明显升高（P〈0.05）。ER、PR双阳性的乳腺癌患者术后血清TK1水平高于术前（P〈0.05）,ER、PR双阴性的乳腺癌患者术前和术后1年的TK1水平无差异（P〉0.05）,ER、PR双阳性的乳腺癌患者术前血清TK1水平低于ER、PR双阴性患者（P〈0.05）。结论血清TK1可为乳腺癌预后判断及病情监测提供重要价值。     

Cancer-associated antigen CA 15-3 in the diagnostics of breast tumours

The serum concentration of the new marker CA 15-3 was determined by a kit method, which is based on the use of two different monoclonal antibodies 115D8 and DF3, in a coated tube immunoradiometric technique. The mean CA 15-3 values in breast cancer patients (n = 40) were significantly higher than in patients with benign breast disease (n = 52, p less than 0.001) and in control subjects (n = 32, p less than 0.001). When we used the cut-off level 35 kU/l for CA 15-3, 0/32 of control subjects, 1/52 (2%) of patients with benign breast disease, 8/40 (20%) of all breast cancer patients, 6/19 (32%) of breast cancer patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were above this level. Among the same patients the CEA serum test was positive at a cut-off level of 5 micrograms/l in 7/40 (18%) cancer cases, and in 6/19 (32%) of cancer patients with nodal involvement. When we used the cut-off level 35 kU/l for CA 15-3 and 5 micrograms/l for CEA 1/52 (2%) of patients with benign breast disease, 10/40 (25%) of all breast cancer patients, 7/19 (37%) patients with axillary nodal involvement and 1/1 of breast cancer patients with distant metastases were positive in one or both of the tests. The serum CA 15-3 and CEA values were higher in patients with tumour size above 2 cm in diameter than in patients with smaller tumours (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endoscopic treatment of submucosal lesions of the gastrointestinal tract.

Fourteen of symptomatic submucosal lesions located in the esophagus (n = 4), stomach (n = 4), duodenum (n = 1) and colon (n = 5) were treated by means of endoscopy. Treatment selection criteria for tumours (n = 10) were presence of a pedunculated tumour, or presence of a sessile tumour with a base smaller than 2 cm which originated in the upper wall layers, as judged by the mobility of the lesion. All tumours but one were successfully and completely removed by snare cauterization. The failure was a gastric fibroma which was incompletely resected; bleeding ensued rendering emergency surgery necessary. Mucosal cysts in the esophagus and colon were treated by either snare polypectomy in the case of smaller lesions or drainage in the case of larger cysts. Follow-up for 5 to 12 months (mean 8.7 months) in the 13 cases treated by means of endoscopy alone did not reveal recurrence. These preliminary results show that endoscopic treatment of smaller and superficially originating submucosal tumours may be a feasible alternative to surgery, however meticulous patient selection is necessary to avoid major complications.     

慢性淋巴细胞白血病患者脂蛋白酯酶和血清胸苷激酶水平及其与其他预后因素的相关性研究

目的 探讨慢性淋巴细胞白血病(CLL)患者脂蛋白酯酶(LPL)和血清胸苷激酶(TK)水平及其与其他CLL预后因素的相关性.方法 采用RT-PCR方法 检测58例CLL患者外周血标本中LPL的表达水平;增强化学发光法(ECL)和TK1单克隆抗体检测39例CLL患者外周血血清标本中TK1浓度;多重PCR及序列测定检测IgVH基因突变;流式细胞术检测ZAP-70蛋白及CD38的表达;组合探针荧光原位杂交(FISH)技术检测分子遗传学异常.结果 CLL患者LPL中位表达水平为0.26(0～6.29),而在正常对照中均未检测到LPL表达.LPL表达水平与IgVH基因突变、Binet分期、CD38表达和遗传学异常具有显著相关性,无IgVH突变患者的LPL表达水平明显高于突变患者(P=0.010);Binet A期患者LPL表达水平低于Binet B期和C期患者(P=0.011);CD38高表达组(≥30%)LPL表达水平高于CD38低表达组(<30%)(P=0.001);分子遗传学预后较好组[仅有del(13q14)]LPL表达水平明显低于预后较差组[del(17p13)或del(11q22)](P=0.002).LPL表达水平与患者性别、年龄及ZAP-70蛋白表达水平均无明显相关性(P>0.05).CLL患者血清TK1浓度明显高于正常对照(P<0.05).在外周血淋巴细胞绝对计数(ALC)明显增高组(≥50×109/L)、血清乳酸脱氢酶(LDH)高水平组、无IgVH基因突变组和ZAP-70蛋白高表达组(≥20%)的患者中,血清TK1浓度分别明显高于ALC无明显增高组(<50×109/L)(P=0.018)、血清LDH水平正常组(P=0.018)、具有IgVH基因突变组(P=0.030)和ZAP-70蛋白低表达组(<20%)(P=0.038)的患者.血清TK1浓度与CLL患者性别、年龄、Binet分期、CD38表达水平和遗传学异常无明显相关性(P>0.05).结论 CLL患者LPL和血清TK1表达水平与CLL其他预后因素相关,两者均对IgVH突变情况有一定预示作用,在CLL的预后中具有重要价值.     

血清TK1、TPS、CA15-3联合检测在乳腺癌诊断中的临床价值

目的 探讨血清胸苷激酶1(TK1)、特异性组织多肽抗原(TPS)、糖类抗原15-3(CA15-3)联合检测在乳腺癌诊断中的临床价值.方法 采用免疫印迹-增强化学发光法对乳腺癌组(69例)、乳腺良性疾病组(52例)、健康对照组(48例)血清TK1进行检测,采用酶联免疫吸附试验(ELISA)对血清TPS进行检测,采用化学发光法对血清CA15-3进行检测,并对检验结果进行统计学分析.结果 乳腺癌患者血清TK1、TPS、CA15-3水平均显著高于乳腺良性疾病组与健康对照组(P＜0.01),3项指标联合检测的敏感性显著高于单项检测或2项联合检测(P＜0.05).结论检测血清TK1、TPS、CA15-3水平,对乳腺癌的诊断具有重要的价值,3种标志物联合检测能明显提高乳腺癌诊断的敏感性.     

胰腺癌患者血清细胞质胸腺激酶1及肿瘤标志物水平变化及其临床意义

目的探讨胰腺癌患者血清细胞质胸腺激酶1(TK1)、癌胚抗原(CEA)、糖链抗原19-9(CA19-9)、糖链抗原72-4(CA72-4)水平变化及其临床意义。方法我院诊治的胰腺癌患者75例(胰腺癌组)和40例良性胰腺疾病患者(良性组),同期体检健康志愿者35例(对照组)。检测各组血清TK1、CEA、CA19-9、CA72-4水平,根据血清TK1、CEA、CA19-9、CA72-4检测(串联)结果分为联合检测阳性组(n=49)和联合检测阴性组(n=26),依据患者预后情况分为预后良好组(n=24)、预后不良组(n=51)。比较各组血清TK1、CEA、CA19-9、CA72-4水平,ROC曲线分析四项指标联合检测对胰腺癌患者预后的预测价值。结果与对照组比较,胰腺癌组、良性组血清TK1、CEA、CA19-9、CA72-4水平明显增高,且胰腺癌组高于良性组(P<0.05)。联合检测阳性组临床分期为Ⅳ期、分化程度为低分化的占比高于联合检测阴性组(P<0.05)。预后不良组血清TK1、CEA、CA19-9、CA72-4水平高于预后良好组(P<0.05)。TK1、CEA、CA19-9、CA72-4水平联合检测诊断胰腺癌患者预后的ROC曲线下面积、灵敏度均较四项指标单独检测的高。结论胰腺癌患者血清TK1、CEA、CA19-9、CA72-4水平呈明显升高趋势,且四项指标联合检测对胰腺癌患者预后的预测价值较高,有望为胰腺癌患者预后的改善提供理论参考。     

乳腺癌患者血清TK1、CA153、CEA的变化及临床意义

目的探讨胸苷激酶1(TK1)、糖类抗原(CA)153、癌胚抗原(CEA)在乳腺癌患者血清中的变化情况及临床意义。方法选择92例住院治疗的乳腺癌患者,66例乳腺良性疾病患者和50例健康体检者,分别检测各组血清TK1、CA153、CEA水平,用单因素分析法分析血清TK1、CA153、CEA水平与乳腺癌病理参数的关系。结果乳腺癌组血清TK1、CA153、CEA水平显著高于乳腺良性疾病组和对照组,差异均有统计学意义(P0.05)。血清TK1、CA153、CEA水平与乳腺癌病理分期、淋巴结转移等因素相关(P0.05)。结论 TK1、CA153、CEA水平升高对乳腺癌的诊断、浸润、转移及严重程度具有重要临床意义。     

Plasma angiopoietin-1, angiopoietin-2 and Tie-2 in breast and prostate cancer: a comparison with VEGF and Flt-1

BACKGROUND: Angiogenesis is essential for tumour growth and metastasis, and is coordinated by several classes of growth factors mediating their effect through receptors linked, in turn, to tyrosine kinase. These growth factors include angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF), which act through receptors Flt-1 and Tie-2. MATERIALS AND METHODS: In order to further determine abnormalities in levels of Ang-1, Ang-2, Tie-2, sFlt-1 and VEGF in human cancer (and their interrelationships), these molecules were measured in plasma from 30 patients with breast cancer, 30 patients with prostate cancer and 12 healthy controls per cancer group. RESULTS: In breast cancer, levels of Ang-1 (P=0.0005), Ang-2 (P=0.0173), Tie-2 (P=0.0001), and VEGF (P=0.0001) were all significantly raised, and plasma levels of sFlt-1 (P=0.045) were significantly reduced compared with controls. However, in prostate cancer, only levels of VEGF and Tie-2 were significantly higher (both P=0.001). There were no significant differences between levels of any molecule between the two groups of cancer. The only difference between the healthy control groups was lower Ang-1 in the women compared with men. Significant correlations were found between levels of Ang-1 and Tie-2 both in breast (r=0.498, P=0.005) and prostate cancer (r=0.643, P=<0.001). Angiopoietin-1 was also positively correlated with Ang-2 in both breast (r=0.422, P=0.02) and prostate cancer (r=0.543, P=0.002). CONCLUSIONS: Abnormal levels of Ang-1, Ang-2 and their receptor, Tie-2, are present in breast and prostate cancer, and their interrelationships may be important in the pathophysiology of these conditions.     

Stimulation of human breast cancers by dietary L-arginine.

1. The amino acid L-arginine has been shown to enhance immune mechanisms and inhibit tumour growth in experimental animals, but although many of the immunological effects of arginine have been reproduced in man there have been few studies of its effects on human tumours. In this study the effects of arginine on human breast cancers were determined by measuring tumour protein synthesis and comparing this with immunohistochemical assessments of cell proliferation. 2. Patients with breast cancer were randomized to receive either a standard diet or arginine supplementation. At the time of surgery, the rate of tumour protein synthesis was measured by the incorporation of the stable isotope [1-13C]leucine into tumour protein. Tumours were also assessed histologically and by staining for the presence of the activation antigen Ki67. 3. The median rate of tumour protein synthesis was 10%/day (range 5.5-15.8%/day) in the control patients and 25.6%/day (range 9-37%/day) in the patients receiving arginine supplements (P less than 0.005, Wilcoxon rank sum test). The rates of protein synthesis correlated with Ki67 expression within these tumours (r = 0.78, P less than 0.001). A double-staining technique confirmed that tumour cells, rather than tumour-infiltrating lymphoreticular cells, expressed Ki67. 4. This study demonstrates that, in contrast to animal studies, L-arginine stimulates human tumours in vivo. This represents the first direct evidence that a single amino acid can modulate the behaviour of a human cancer.     

Prolactin response to dopamine and valproate administration in breast cancer patients

There is only indirect evidence available at present to suggest the role of prolactin (PRL) in either the promotion or progression of human breast cancer. In order to determine if dopaminergic and GABAergic regulation of PRL are similar in breast cancer patients, we studied 2 groups of premenopausal women with no evident endocrine alteration: 1) control subjects (C); and 2) breast cancer patients (CA). Basal PRL levels were measured and their response to dopamine (DA) infusion (0.004 micrograms/kg/min) and valproate administration (400 mg/p.o.). The mean of percentage inhibition by DA in C (n = 6) was significantly higher than in CA (n = 11) at 180 min; P less than 0.025. On the other hand, group C (n = 8) responded to valproate with maximal inhibition at 180 min; in the CA group (n = 8) no inhibition was observed; P less than 0.0025.     

直接测试红细胞流变性对老年脑梗死的临床意义探讨

目的　用两种方法做比较 ,探讨老年脑梗死患者治疗前、治疗后以及治愈后又复发时红细胞聚集指数和变形指数的变化 ,确定可靠的诊断依据。方法　分 3组 ,第 1组为实验组 ,确诊前未用过溶栓药和解聚药的初患者 ;第 2组为复发组 ,脑梗死治愈后近期头痛、头晕病情复发的病人 ;第 3组为正常对照组。均空腹抽血肝素抗凝 ,直接测试红细胞聚集指数 (Agg)和变形指数 (DEF) ,同时测试全血粘度高切值 (2 0 0s 1) ,低切值 (1s 1) ,常规法测试红细胞压积和纤维蛋白原 ,计算红细胞聚集指数(RE)和变形指数 (TK) ,实验组和复发组治疗后重复以上实验。结果　实验组和复发组直接测试的红细胞聚集指数 (Agg)明显高于对照组 (P <0 .0 5) ,与治疗后相比 (P <0 .0 5)有显著差异。间接计算的红细胞聚集指数 (RE)和变形指数 (TK)P >0 .0 5,无显著差异。结论　红细胞聚集指数Agg增高 ,红细胞变形指数降低是脑梗塞发生和复发的危险因素 ,Agg和DEF随病情变化 ,RE和TK随血粘度变化     

Measurement of tumour protein synthesis in vivo in human colorectal and breast cancer and its variability in separate biopsies from the same tumour.

1. A method is described for measuring the rates of protein synthesis in vivo in human colorectal and breast tumours by the intravenous injection of L-[1-13C]leucine as a 'flooding dose'. 2. The incorporation of isotope into colorectal tumour protein was measured in six patients, whose tumours were biopsied after the injection. Fractional rates of protein synthesis were calculated from the enrichment of leucine in protein and the average free leucine enrichment in plasma. The range of rates obtained was 17.2-33.9%/day, with a mean rate (+/- SEM) of 22.5 +/- 2.6%/day. 3. Tumour protein synthesis rates were also measured in 15 patients with breast cancer. The range of rates obtained was 5.3-15.9%/day, with a mean rate (+/- SEM) of 10.3 +/- 0.8%/day. These rates are significantly lower than those obtained with colorectal tumours (P less than 0.001). 4. In 9 of the breast cancer patients, protein synthesis was measured in multiple random biopsies taken from the same tumour. The mean (+/- SEM) difference between the highest and lowest rates in biopsies from the same tumour was only 1.1 +/- 0.3%/day. Only 13% of the variation in protein synthesis between separate tumours could be explained by sampling error because of variation within the tumour itself, the remainder being genuine variation between individual tumours.     

3种乳腺癌分子亚型与数字乳腺断层合成显像X线特征的关系:基于BI-RADS

目的探讨乳腺癌分子亚型与数字乳腺断层合成（DBT）X线征象的关系。方法回顾性分析153例乳腺癌患者的DBT影像及病理资料，根据雌激素受体、孕激素受体及人表皮生长因子受体2（HER2）表达水平分为激素受体（HR）阳性组（n=90）、HER2阳性组（n=20）及三阴性组（n=33）。以第5版ACR乳腺X摄影影像报告与数据系统定义的影像征象为标准，比较不同分子分型的临床病理特征及DBT征象。结果HER2+、三阴性组组织学分级、Ki67表达水平高于HR+组，差异有统计学意义（P < 0.05）。3组分子亚型表现为单纯肿块、单纯钙化、肿块伴钙化、不对称致密及结构扭曲等差异无统计学意义（P > 0.05）。HER2+组、三阴性组表现为圆形/卵圆形肿块发生率（50.0%、59.3%）高于HR+组（24.6%），差异有统计学意义（P=0.003）；HR+组、HER2+组表现为分叶征的发生率（93.8%、95%）高于三阴性组（55.6%），差异有统计学意义（P < 0.001）；HR+组表现为毛刺征的发生率（72.3%）高于HER2+、三阴性组（20.0%、30.7%），差异有统计学意义（P < 0.001）。HER2+组表现为细线分支状钙化及线/段样分布特征发生率高于HR+、三阴性组（P < 0.001）。HER2+组、三阴性组周围腺体结构扭曲、小梁增厚发生率高于HR+组（P < 0.05）。结论乳腺癌分子亚型与DBT影像征象有一定关系，认识这些征象有利于预测乳腺癌分子分型。      

血清DKK1、TK1水平预测老年胸段食管癌患者根治术后复发、转移的研究

目的分析血清分泌型蛋白Dikkopf1(DKK1)、细胞质胸苷激酶1(TK1)水平与老年胸段食管癌患者根治术后复发、转移的关系。方法选取2016年6月至2018年6月于该院接受根治术治疗的63例老年胸段食管癌患者为研究对象,全部患者术后均接受为期3年的随访,依据随访期间复发、转移的发生情况分为发生组与未发生组,比较两组一般资料、实验室检测结果,分析根治术前血清DKK1、TK1水平与患者术后复发、转移的关系。结果63例老年胸段食管癌患者发生复发、转移26例,发生率为41.27%;发生组术前血清癌胚抗原(CEA)、鳞状细胞癌抗原(SCC)、DKK1、TK1水平均高于未发生组(P<0.05);相关性分析结果显示,老年胸段食管癌患者血清CEA、SCC、DKK1及TK1之间呈正相关(P<0.05);Logistic回归分析结果显示,老年胸段食管癌患者根治术前血清CEA、SCC、DKK1、TK1异常表达与术后复发、转移有关,各指标异常表达可能是老年胸段食管癌患者术后复发、转移的危险因素(OR>1,P<0.05);绘制受试者工作特征曲线,结果显示,老年胸段食管癌患者根治术前血清CEA、SCC、DKK1、TK1水平预测术后复发、转移风险的曲线下面积均>0.800,预测价值较理想,且根治术前血清DKK1、TK1的最佳截断值分别为3.535 ng/mL、3.470 pmol/L时,预测价值最佳。结论老年胸段食管癌患者根治术前血清DKK1、TK1水平与术后复发、转移有关,二者异常表达可能是患者根治术后复发、转移的危险因素,将二者用于预测患者根治术后的复发、转移风险有一定价值。     

乳腺癌组织中lncRNA PVT1 的表达与患者临床特征及总体生存率的关系

目的　探讨乳腺癌组织中lncRNA PVT1 的表达与患者临床特征及总体生存率的关系。方法　采用实时荧光 定量PCR 法检测乳腺癌组织及其相应癌旁正常组织中lncRNA PVT1 的相对表达量;分析lncRNA PVT1 表达水平与 乳腺癌患者临床特征与总体生存率间的关系。结果　lncRNA PVT1 在乳腺癌组织中的相对表达量显著高于癌旁正常 组织(0.007 5 vs 0.003),其差异具有统计学意义(P=0.0186)。lncRNA PVT1 表达水平与乳腺癌患者的年龄(χ2=5.948, P=0.015)、临床分期(χ2=12.349,P=0.006)、淋巴结转移(χ2=20.942,P<0.001)、远端转移(χ2=5.330,P=0.021) 和 Her2(χ2=5.221,P=0.022) 显著相关。lncRNA PVT1 高表达组患者的总体生存率(overall survival, OS) 显著低于lncRNA PVT1 低表达组,差异具有统计学意义(P=0.036)。结论 　lncRNA PVT1 是一种可预测乳腺癌患者预后的有潜力的生物 学指标。     

改良根治术与保乳手术治疗早期乳腺癌的近远期疗效比较

目的 探讨改良根治术与保乳手术治疗早期乳腺癌的近、远期疗效.方法 回顾性分析住院治疗的120例早期乳腺癌手术患者,其中改良根治术组52例,保乳手术组68例.比较两组患者手术效果、1年和5年生存率、局部复发率、远行转移率以及生活质量.结果 保乳手术组手术时间、术中出血量及住院时间显著少于改良手术组(P<0.05);两组患者1年及5年生存率、局部复发率、远行转移率均无显著差异(P>0.05);术后5年,保乳手术组SF-36各项评分显著高于改良手术组(P<0.05).结论 保乳手术与改良根治术治疗早期乳腺癌疗效确切,但保乳手术对患者损伤小、恢复快,术后患者生活质量高.     

非小细胞肺癌患者血清血管生成素2定量检测及其临床意义

目的 探讨非小细胞肺癌(NSCLC)患者血清血管生成素2(Ang-2)水平及其临床意义.方法 采用酶联免疫吸附试验(ELISA)定量检测98例NSCLC患者和30名健康对照者血清Ang-2水平,比较不同分期、有无转移及术后1年复发与否的患者之间是否存在差异.结果 NSCLC患者血清Ang-2水平[中位数3 230.5 ng/L,范围(1 231.6～4 612.5)ng/L]显著高于健康对照者[中位数831.7 ng/L,范围(592.4～1 701.1)ng/L,U=15,P＜0.01].Ⅲ期患者血清Ang-2水平[中位数2 311.7 ng/L,范围(1 512.9～3 530.7)ng/L]显著高于Ⅰ期患者[1 593.6 ng/L,范围(1 235.2～2 763.1)ng/L,H=27.66,P＜0.01]和Ⅱ期患者[中位数1 581.4 ng/L,范围(1 231.6～2 852.3)ng/L,H=27.66,P＜0.01],但显著低于Ⅳ期患者[中位数3 808.2 ng/L,范围(2 235.8～4 612.5)ng/L,H=65.76,P＜0.01].有转移患者和术后1年内复发患者血清Ang-2水平分别高于无转移患者和无复发患者.结论 NSCLC患者血清Ang-2水平有可能作为肿瘤转移和术后复发的预测指标.