【作者】 盛大平；

【导师】 吴宜灿； 王欣；

【作者基本信息】 中国科学技术大学 ， 核能科学与工程， 2014， 博士

【摘要】 白血病是最常见的恶性血液疾病,在我国白血病年发病率为2.76/10万,在恶性肿瘤的死亡率中,白血病居男性第六位和女性第八位。胃癌是人体常见的恶性肿瘤,在全球范围内病死率居第二位,在每年新诊断的癌症病例中它仅次于肺癌、乳腺癌与肠癌,全球平均每年新增约80万例胃癌患者而75万胃癌患者死亡。白血病与胃癌严重危害人类健康,因此如何提高它们的早期诊断水平是临床医学的重要任务之一。红外光谱是近些年发展的一种从分子水平研究肿瘤的新方法,它包含丰富的分子结构信息,具有灵敏度高、制样简单和无损检测等优点。因为红外光谱可以从分子层面对肿瘤细胞或组织等复杂体系进行分析,所以从20世纪80年代应用红外光谱研究白血病以来,它已经广泛应用于生物医学领域的研究。在本博士论文中,以红外光谱为研究工具对白血病与胃癌进行分析,开展了以下工作：1、对白血病患者与健康者血清/指甲进行对比,得出它们之间的差异；2、对胃癌患者与健康者血清进行对比,同时对术前与术后胃癌患者的血清进行比较,发现它们之间的差异；3、对胃癌患者术前与术后的血红细胞分别进行比较,发现它们之间的差异；4、对胃癌细胞株与正常细胞株进行焦平面阵列成像分析,从分子水平了解胃癌的发病机理。本论文取得了以下结果：(1)白血病患者与健康者血清的红外光谱比较后发现二者的H2959/H2931(甲基/亚甲基)与A1115/A1028(RNA/DNA)差异明显,可用于白血病患者与健康者鉴别。(2)白血病患者与健康者指甲的红外光谱比较后发现白血病患者指甲的角蛋白含量发生变化,同时指甲中核酸含量逐渐升高,表明白血病的发生可导致患者指甲核酸分子内磷酸二酯键骨架的结构改变。(3)胃癌患者与健康者血清的红外光谱比较后发现二者的H2959/H2931(甲基／亚甲基)值具有显著性差异,这说明健康者血清比胃癌患者血清含有较短和／或较多支链的脂质；通过曲线拟合,得到RNA/DNA值,胃癌患者的血清较健康者的血清的RNA/DNA值低,且存在明显差异。(4)胃癌患者的术前与术后血清的红外光谱进行对比,发现术前与术后血清的相应成分比值有变化,说明红外光谱可能对胃癌患者的手术治疗效果进行监测。(5)胃癌患者的术前与术后的血红细胞的红外光谱进行对比,发现胃癌患者术前的血红细胞的A1543/A1085值较胃癌患者术后的A1543/A1085值高,表明胃癌患者肿瘤切除后红细胞中核糖体或核酸的相对含量较术前血红细胞中的核糖体或核酸的相对含量增加。(6)应用焦平面阵列成像系统对胃癌与正常细胞株进行对比研究,发现SGC7901与BGC823细胞的H1121/H1020(RNA/DNA)值比GES1细胞的值高,这三种细胞中的DNA、蛋白质与脂类分布相似,其最强吸收频率位于细胞核区域。上述研究结果说明红外光谱与成像技术在生物医学领域中有重要的作用,这些研究有助于阐明肿瘤的早期诊断及发病机理研究,这为红外光谱与成像技术在肿瘤的早期诊断与治疗监测方面的应用提供了实践基础。更多还原

【Abstract】 Leukemia is the most common malignant blood disease, and its morbidity was2.76/100000in China while its mortality ranked the sixth among men and the eighth among women in all malignant tumors. Gastric cancer is one of the most common tumors and its mortality ranked the second among all tumors worldwide. Gastric cancer ranked the fourth in all newly diagnosed cancer cases each year, which was second to lung cancer, breast cancer and colon cancer. About800000persons were diagnosed as gastric cancer while750000patients were died from it annually.As leukemia and gastric cancer do serious harm to human beings’ health, it is of great importance to diagnose them at early stage. In recent years, IR spectroscopy has been developed as a new method to investigate diseases at molecular level. IR spectroscopy contains abundant information about molecular structures and can probe structural changes sensitively. Since IR spectroscopy has advantages such as high sensitivity, preparing specimens easily and testing samples non-destructively, it can study cancer cells and tissues at the molecular level. Since the first application of IR spectroscopy on medical research in the1980s, it has been widely used in biomedical field.In this doctoral dissertation, the leukemia and gastric cancer were investigated by IR spectroscopy and the following studies were carried out:1Comparing the serum and fingernails of leukemia patients with those of healthy persons to explore the differences between them;2Comparing serum of①gastric cancer patients with that of healthy persons,②pre-operative and post-operative gastric cancer patients to explore the differences between them;3. Comparing erythrocyte of pre-operative and post-operative gastric cancer patients to explore the differences between them;4Analyzing the gastric cancer cell lines and normal gastric cell lines by focal plane array (FPA) to understand the gastric cancer pathogenesis further. The following results were obtained:(1) The ratios of H2959/H2931(methyl/methylene) and A1115/A1028(RNA/DNA) were different between leukemia patients and healthy persons, which could be used to identify the leukemia patients from healthy persons.(2) IR spectra of fingernails showed’the keratin and nucleic acid contents of leukemia patients increased gradually, indicating that leukemia could lead to the changes of the phosphodiester structures,(3) The ratios of H2959/H2931and RNA/DNA were different between serum of gastric cancer patients and healthy persons, which indicated that the serum of healthy persons contained shorter and/or more branched chains of lipids than that of gastric cancer patients.(4) The corresponding components of gastric cancer patients’serum were changed after surgery, which suggested that IR spectroscopy might be used to monitor the curative effect of operation for gastric cancer patients.(5) The ratios of A1543/A1085of red blood cells decreased after operation, which indicated that the relative content of ribosomal/nucleic acids of RBCs were higher in post-operative gastric cancer patients.(6) The FPA results showed:①the ratios of H1121/H1020(RNA/DNA) of SGC7901and BGC823cells were higher than that of GES1cells with tumor becoming malignant,②the strongest absorption of DNA, protein and lipids were all found in in the nucleus of gastric cells.The above studies showed that IR spectroscopy and imaging may play an important role in biomedical field. Those studies might be helpful to elucidate cancer pathogenesis and be useful for cancer diagnosis, which would provide basis for the application of IR spectroscopy and imaging in cancer research.更多还原