肺癌、肠癌多肿瘤标志物联合检测及菜菔硫烷预防化学性致癌的效果初探

发布时间：2018-09-16 20:27

【摘要】：目的：研究巨噬细胞抑制因子-1(MIC-1)在较大样本的早期肺癌和肺癌中的辅助诊断价值,并评价多肿瘤标志物联合应用相关数据的临床意义。方法：应用本实验室自主研制的MIC-1定量检测试剂盒及Roche Cobas 601电化学发光免疫分析仪分别检测663例不同临床分期的未治疗肺癌患者和488例正常人群血清样本中的MIC-1、CEA、CA125、NSE、SCC和Cyfra21-1水平和分布,分析患者血清MIC-1水平与肺癌临床分期、病理分型和细胞分化程度的关系,并研究多标志联合检测的价值。结果：肺癌患者血清MIC-1水平显著高于正常人群(p0.001)；MIC-1水平随临床分期显著上升(p0.001),且与肿瘤浸润(p0.001)、淋巴结转移(p=0.037)、远端转移(p0.001)和肿瘤分化程度(p0.001)显著相关。MIC-1肺癌诊断的敏感性高于其它五种肺癌标志物的联合应用(76.6% vs 72.2%),在腺癌诊断中更为突出(腺癌：74.7% vs68.9%；鳞癌：81.6% vs 82.8%；小细胞癌：84.9% vs 83.0%)。尤为显著的是,MIC-1诊断Ⅰ期和ⅡI期肺癌的敏感性可达70.2%和69.9%,显著优于五种常用标志物中敏感性最高的Cyfra21-1(Ⅰ期20.7%,Ⅱ期52.1%)；MIC-1联合上述五种标志物诊断Ⅰ期和Ⅱ期肺癌的灵敏度可达79.8%和87.7%。结论：MIC-1是肺癌尤其是早期肺癌有价值的血清肿瘤标志物,MIC-1和CEA、 CA125、NSE、SCC、Cyfra21-1联合检测用于普通人群体检和肺癌早期诊断具有重要的临床意义和价值。目的：研究巨噬细胞抑制因子-1(MIC-1)在较大样本的早期肠癌和肠癌中的辅助诊断价值,并评价多肿瘤标志物联合应用相关数据的临床意义。方法：应用本实验室自主研制的MIC-1定量检测试剂盒及Roche Cobas 601电化学发光免疫分析仪分别检测441例不同临床分期的未治疗肠癌患者、179例治疗患者和617例正常人群血清样本中的MIC-1、CA19-9和CEA水平和分布,分析患者血清MIC-1水平与肠癌临床分期、病理分型和细胞分化程度的关系,并研究多标志物联合检测的价值。结果：肠癌患者血清MIC-1水平均极显著高于正常人群(p0.001),肠癌水平随临床分期进展而显著上升(p0.001),与肿瘤浸润(p=0.01)、淋巴结转移(p=0.017)、远端转移(p0.001)及发病部位(p0.05)有关。MIC-1的诊断敏感性高于CA19-9和CEA(52.4% vs 14.5%、36.3%),尤其在早期诊断时具有更高的敏感性(Ⅰ期43.4%,Ⅱ期55.0%),而MIC-1、CA19-9、CEA联合诊断时敏感性高达69.6%,Ⅰ期肠癌诊断敏感性高达52.8%,Ⅱ期肠癌诊断敏感性高达70.7%。结论：MIC-1是肠癌尤其是早期肠癌有价值的血清肿瘤标志物,MIC-1和CA19-9、CEA联合检测用于普通人群体检和肠癌早期诊断具有重要的临床意义和价值。目的：探讨莱菔硫烷在小鼠3,4-苯并芘诱导前胃癌过程中的化学预防作用。方法：小鼠以10g/L 3,4-苯并芘灌胃诱导前胃癌,实验组小鼠从第一次灌胃前2周持续到第四次灌胃后2周的时间内饲喂不同浓度的莱菔硫烷特殊小鼠饲料,分别为每千克饲料500mg、250mg莱菔硫烷,第四次灌胃后每隔5周处死一批小鼠,对前胃组织进行病理组织学观察。结果：小鼠饲喂第16周前胃组织出现肿瘤,且随时间增长,肿瘤数量增多,直径增大。不同浓度莱菔硫烷对小鼠前胃肿瘤出现有抑制作用,并呈现剂量依赖效应。第26周时,高剂量莱菔硫烷对小鼠平均荷瘤数的抑制率为30.7%,低剂量莱菔硫烷抑制率为18.2%。HE染色切片显示26周时,高剂量莱菔硫烷对小鼠3,4-苯并芘诱导出现增生性病变、癌前病变、原位癌和浸润癌的抑制率分别为14.0%、28.1%、56.1%和100%,低剂量组抑制率分别为7.4%、29.1%、34.1%和16.7%。结论：莱菔硫烷能够抑制小鼠3,4-苯并芘诱导小鼠前胃癌出现过程中增生性病变、癌前病变、原位癌和浸润癌的病灶数,对小鼠前胃癌的诱发有明确的预防效果。
[Abstract]:Objective: To study the diagnostic value of macrophage inhibitory factor-1 (MIC-1) in large sample of early lung cancer and lung cancer, and to evaluate the clinical significance of combined application of multiple tumor markers. The levels and distribution of MIC-1, CEA, CA125, NSE, SCC and Cyfra21-1 in serum samples of 663 patients with untreated lung cancer at different clinical stages and 488 normal persons were detected, and the relationship between the levels of MIC-1 and clinical stage, pathological classification and cell differentiation of lung cancer was analyzed. The serum level of MIC-1 was significantly higher than that of the normal population (p0.001); the level of MIC-1 increased significantly with clinical stage (p0.001), and was significantly correlated with tumor infiltration (p0.001), lymph node metastasis (p = 0.037), distal metastasis (p0.001) and tumor differentiation (p0.001). The diagnostic sensitivity of MIC-1 lung cancer was higher than that of other five lung cancer markers (76.6%). Vs 72.2% (adenocarcinoma: 74.7% vs 68.9%; squamous carcinoma: 81.6% vs 82.8%; small cell carcinoma: 84.9% vs 83.0%). Conclusion: MIC-1 is a valuable serum tumor marker for lung cancer, especially for early stage lung cancer. The combined detection of MIC-1 and CEA, CA125, NSE, SCC, Cyfra21-1 has important clinical significance and value in the physical examination of general population and early diagnosis of lung cancer. Objective: To study the diagnostic value of macrophage inhibitory factor-1 (MIC-1) in large samples of early colorectal cancer and colorectal cancer, and to evaluate the clinical significance of combined application of multiple tumor markers and related data. The serum levels of MIC-1, CA19-9 and CEA were measured in 441 untreated, 179 untreated and 617 normal subjects. The relationship between serum levels of MIC-1 and clinical stage, pathological classification and cell differentiation of colorectal cancer was analyzed. The serum level of MIC-1 in cancer patients was significantly higher than that in normal people (p0.001). The level of intestinal cancer increased significantly with clinical stage (p0.001). It was associated with tumor invasion (p = 0.01), lymph node metastasis (p = 0.017), distal metastasis (p0.001) and site of disease (p0.05). The diagnostic sensitivity of MIC-1 was higher than that of CA19-9 and CEA (52.4% vs 14.5%, 36.3%) especially in early stage. The sensitivity of combined diagnosis of MIC-1, CA19-9 and CEA was 69.6%, 52.8% for stage I and 70.7% for stage II. Conclusion: MIC-1 is a valuable serum tumor marker for colorectal cancer, especially for early stage colorectal cancer. Objective: To investigate the chemopreventive effect of sulforaphane on 3,4-benzopyrene-induced precancerous carcinoma in mice. Methods: The precancerous carcinoma was induced by intragastric administration of 10 g/L 3,4-benzopyrene in mice, and the precancerous carcinoma lasted from 2 weeks before the first gastric administration to 4 times in the experimental group. The mice were fed with different concentrations of sulforaphane (500 mg/kg, 250 mg/kg) for 2 weeks after gastric administration. A batch of mice were sacrificed every 5 weeks after the fourth gastric administration. The histopathological changes of the forestomach tissues were observed. At the 26th week, the inhibition rate of high dose of sulforaphane was 30.7% and that of low dose of sulforaphane was 18.2%. HE staining showed that at the 26th week, high dose of sulforaphane inhibited 3,4-in mice. The inhibition rates of benzopyrene-induced proliferative lesions, precancerous lesions, carcinoma in situ and invasive carcinoma were 14.0%, 28.1%, 56.1% and 100%, respectively. The inhibition rates of low dose group were 7.4%, 29.1%, 34.1% and 16.7% respectively. Conclusion: Raphane can inhibit the proliferative lesions, precancerous lesions and carcinoma in situ in mice with 3,4-benzopyrene-induced precancerous lesions. And the number of infiltrating cancer has a definite preventive effect on the induction of gastric cancer in mice.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R730

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