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肺癌、腸癌多腫瘤標(biāo)志物聯(lián)合檢測(cè)及菜菔硫烷預(yù)防化學(xué)性致癌的效果初探

發(fā)布時(shí)間:2018-09-16 20:27
【摘要】:目的:研究巨噬細(xì)胞抑制因子-1(MIC-1)在較大樣本的早期肺癌和肺癌中的輔助診斷價(jià)值,并評(píng)價(jià)多腫瘤標(biāo)志物聯(lián)合應(yīng)用相關(guān)數(shù)據(jù)的臨床意義。方法:應(yīng)用本實(shí)驗(yàn)室自主研制的MIC-1定量檢測(cè)試劑盒及Roche Cobas 601電化學(xué)發(fā)光免疫分析儀分別檢測(cè)663例不同臨床分期的未治療肺癌患者和488例正常人群血清樣本中的MIC-1、CEA、CA125、NSE、SCC和Cyfra21-1水平和分布,分析患者血清MIC-1水平與肺癌臨床分期、病理分型和細(xì)胞分化程度的關(guān)系,并研究多標(biāo)志聯(lián)合檢測(cè)的價(jià)值。結(jié)果:肺癌患者血清MIC-1水平顯著高于正常人群(p0.001);MIC-1水平隨臨床分期顯著上升(p0.001),且與腫瘤浸潤(rùn)(p0.001)、淋巴結(jié)轉(zhuǎn)移(p=0.037)、遠(yuǎn)端轉(zhuǎn)移(p0.001)和腫瘤分化程度(p0.001)顯著相關(guān)。MIC-1肺癌診斷的敏感性高于其它五種肺癌標(biāo)志物的聯(lián)合應(yīng)用(76.6% vs 72.2%),在腺癌診斷中更為突出(腺癌:74.7% vs68.9%;鱗癌:81.6% vs 82.8%;小細(xì)胞癌:84.9% vs 83.0%)。尤為顯著的是,MIC-1診斷Ⅰ期和ⅡI期肺癌的敏感性可達(dá)70.2%和69.9%,顯著優(yōu)于五種常用標(biāo)志物中敏感性最高的Cyfra21-1(Ⅰ期20.7%,Ⅱ期52.1%);MIC-1聯(lián)合上述五種標(biāo)志物診斷Ⅰ期和Ⅱ期肺癌的靈敏度可達(dá)79.8%和87.7%。結(jié)論:MIC-1是肺癌尤其是早期肺癌有價(jià)值的血清腫瘤標(biāo)志物,MIC-1和CEA、 CA125、NSE、SCC、Cyfra21-1聯(lián)合檢測(cè)用于普通人群體檢和肺癌早期診斷具有重要的臨床意義和價(jià)值。目的:研究巨噬細(xì)胞抑制因子-1(MIC-1)在較大樣本的早期腸癌和腸癌中的輔助診斷價(jià)值,并評(píng)價(jià)多腫瘤標(biāo)志物聯(lián)合應(yīng)用相關(guān)數(shù)據(jù)的臨床意義。方法:應(yīng)用本實(shí)驗(yàn)室自主研制的MIC-1定量檢測(cè)試劑盒及Roche Cobas 601電化學(xué)發(fā)光免疫分析儀分別檢測(cè)441例不同臨床分期的未治療腸癌患者、179例治療患者和617例正常人群血清樣本中的MIC-1、CA19-9和CEA水平和分布,分析患者血清MIC-1水平與腸癌臨床分期、病理分型和細(xì)胞分化程度的關(guān)系,并研究多標(biāo)志物聯(lián)合檢測(cè)的價(jià)值。結(jié)果:腸癌患者血清MIC-1水平均極顯著高于正常人群(p0.001),腸癌水平隨臨床分期進(jìn)展而顯著上升(p0.001),與腫瘤浸潤(rùn)(p=0.01)、淋巴結(jié)轉(zhuǎn)移(p=0.017)、遠(yuǎn)端轉(zhuǎn)移(p0.001)及發(fā)病部位(p0.05)有關(guān)。MIC-1的診斷敏感性高于CA19-9和CEA(52.4% vs 14.5%、36.3%),尤其在早期診斷時(shí)具有更高的敏感性(Ⅰ期43.4%,Ⅱ期55.0%),而MIC-1、CA19-9、CEA聯(lián)合診斷時(shí)敏感性高達(dá)69.6%,Ⅰ期腸癌診斷敏感性高達(dá)52.8%,Ⅱ期腸癌診斷敏感性高達(dá)70.7%。結(jié)論:MIC-1是腸癌尤其是早期腸癌有價(jià)值的血清腫瘤標(biāo)志物,MIC-1和CA19-9、CEA聯(lián)合檢測(cè)用于普通人群體檢和腸癌早期診斷具有重要的臨床意義和價(jià)值。目的:探討萊菔硫烷在小鼠3,4-苯并芘誘導(dǎo)前胃癌過(guò)程中的化學(xué)預(yù)防作用。方法:小鼠以10g/L 3,4-苯并芘灌胃誘導(dǎo)前胃癌,實(shí)驗(yàn)組小鼠從第一次灌胃前2周持續(xù)到第四次灌胃后2周的時(shí)間內(nèi)飼喂不同濃度的萊菔硫烷特殊小鼠飼料,分別為每千克飼料500mg、250mg萊菔硫烷,第四次灌胃后每隔5周處死一批小鼠,對(duì)前胃組織進(jìn)行病理組織學(xué)觀(guān)察。結(jié)果:小鼠飼喂第16周前胃組織出現(xiàn)腫瘤,且隨時(shí)間增長(zhǎng),腫瘤數(shù)量增多,直徑增大。不同濃度萊菔硫烷對(duì)小鼠前胃腫瘤出現(xiàn)有抑制作用,并呈現(xiàn)劑量依賴(lài)效應(yīng)。第26周時(shí),高劑量萊菔硫烷對(duì)小鼠平均荷瘤數(shù)的抑制率為30.7%,低劑量萊菔硫烷抑制率為18.2%。HE染色切片顯示26周時(shí),高劑量萊菔硫烷對(duì)小鼠3,4-苯并芘誘導(dǎo)出現(xiàn)增生性病變、癌前病變、原位癌和浸潤(rùn)癌的抑制率分別為14.0%、28.1%、56.1%和100%,低劑量組抑制率分別為7.4%、29.1%、34.1%和16.7%。結(jié)論:萊菔硫烷能夠抑制小鼠3,4-苯并芘誘導(dǎo)小鼠前胃癌出現(xiàn)過(guò)程中增生性病變、癌前病變、原位癌和浸潤(rùn)癌的病灶數(shù),對(duì)小鼠前胃癌的誘發(fā)有明確的預(yù)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.
【學(xué)位授予單位】:北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2015
【分類(lèi)號(hào)】:R730

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