PABPC1在NK/T细胞淋巴瘤发生发展中的作用及机制研究
发布时间：2021-11-09 10:11
研究背景及目的NK/T 细胞淋巴瘤（natural killer/T-cell lymphoma,NKTCL）是一种源于成熟NK细胞或细胞毒T细胞的高度侵袭性非霍奇金淋巴瘤,具有预后差、生存期短等临床特点。该疾病成年男性发病率高于女性,在亚洲和中南美洲多见,与EB病毒（Epstein-Barr virus,EBV）的感染有很强的关系。NKTCL经常发生在鼻腔、鼻窦、鼻咽等上呼吸道,偶尔也会发生在皮肤、消化道、睾丸等。目前对于NKTCL尚无标准的一线治疗方案,初期常使用蒽环类药物为基础的治疗方案,但由于肿瘤细胞高表达P-糖蛋白而易产生耐药。现常用的治疗手段为以左旋门冬酰胺酶或培门冬酶为基础的化疗或联合放疗方案,但是由于该疾病高度的侵袭性以及易产生多药耐药（multiple drug resistance,MDR）,其完全缓解（complete remission,CR）率仅为 50-60%,5 年总生存（overall survival,OS）率在50%左右。因此,了解该病的发病机制,探索更为安全有效的靶向治疗方案,对提高治愈率、延长患者的生存期尤为重要。NKTCL的发病机制不明,近年来...
【文章来源】：郑州大学河南省 211工程院校
【文章页数】：128 页
【学位级别】：博士
【部分图文】：
图１．３?ＮＫ／Ｔ细胞淋巴瘤细胞株和正常人ＮＫ细胞中ＰＡＢＰＣ１蛋白的表达及量化
?第一部分?ＰＡＢＰＣ１在ＮＫ／Ｔ细胞淋巴瘤中的表达和临床意义???Ｕｎｓｔａｉｎｅｄ?ＣＤ５６?ａｎｄ?ＣＤ３??＿?Ｑ１?Ｑ２?Ｑ１?Ｑ２??〇?０６６?０?＇?９６?５?３．３５??ｓ?????Ｑ４?Ｑ３?；?Ｑ４?Ｑ３??．－ｊ?９９?９?０?４?０?１６?０???１????＂■—ｉ????１??￣￣￣ｘ￣??１?■??????■—ｔ????ｉ?■?■??ＣＤ３－ＦＩＴＣ??图１．１磁珠分选正常人ＰＢＭＣ后流式细胞术测定ＮＫ细胞纯度，其纯度超过９５％。??Ａ?Ｂ?Ｃ??４－１?１．５－１?１．５－１??ｉｌｌ．１?－ｄ?，．—■■■■?Ｊ＼〇ＬＩ１０??图１．２?ＮＫ／Ｔ细胞淋巴瘤细胞株和正常人ＮＫ细胞中ＰＡＢＰＣ１、ＰＡＢＰＣ３和ＰＡＢＰＣ４?ｍＲＮＡ??相对表达量。Ａ．与正常ＮＫ细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ１表达均升高；Ｂ．与??正常ＮＫ细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ３表达无明显变化；Ｃ．与正常ＮＫ细胞??相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ４表达无明显变化。ＴＣＯ．ＯＳ，?＊Ｖ＜０．０１，?ＷＰ＜０．００１。??０．８ｎ??〇???ｃ?＊＊＊?＊＊★??ＰＡＢＰＣ１?．．?Ｉｆ。６．?？?Ｐ???１１０４?Ａ?Ｓ１８??＿Ｈ?參，＿?Ｍ?ｐ。２．?Ｉ?｜?｜?＿??Ｖ?ｗ?／??图１．３?ＮＫ／Ｔ细胞淋巴瘤细胞株和正常人ＮＫ细胞中ＰＡＢＰＣ１蛋白的表达及量化。与正常ＮＫ??细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株在ＰＡＢＰＣ１蛋白表达均升高。＊ＰＣ０．０５，?＊＊Ｐ＜０
?第一部分?ＰＡＢＰＣ１在ＮＫ／Ｔ细胞淋巴瘤中的表达和临床意义???Ｕｎｓｔａｉｎｅｄ?ＣＤ５６?ａｎｄ?ＣＤ３??＿?Ｑ１?Ｑ２?Ｑ１?Ｑ２??〇?０６６?０?＇?９６?５?３．３５??ｓ?????Ｑ４?Ｑ３?；?Ｑ４?Ｑ３??．－ｊ?９９?９?０?４?０?１６?０???１????＂■—ｉ????１??￣￣￣ｘ￣??１?■??????■—ｔ????ｉ?■?■??ＣＤ３－ＦＩＴＣ??图１．１磁珠分选正常人ＰＢＭＣ后流式细胞术测定ＮＫ细胞纯度，其纯度超过９５％。??Ａ?Ｂ?Ｃ??４－１?１．５－１?１．５－１??ｉｌｌ．１?－ｄ?，．—■■■■?Ｊ＼〇ＬＩ１０??图１．２?ＮＫ／Ｔ细胞淋巴瘤细胞株和正常人ＮＫ细胞中ＰＡＢＰＣ１、ＰＡＢＰＣ３和ＰＡＢＰＣ４?ｍＲＮＡ??相对表达量。Ａ．与正常ＮＫ细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ１表达均升高；Ｂ．与??正常ＮＫ细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ３表达无明显变化；Ｃ．与正常ＮＫ细胞??相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ４表达无明显变化。ＴＣＯ．ＯＳ，?＊Ｖ＜０．０１，?ＷＰ＜０．００１。??０．８ｎ??〇???ｃ?＊＊＊?＊＊★??ＰＡＢＰＣ１?．．?Ｉｆ。６．?？?Ｐ???１１０４?Ａ?Ｓ１８??＿Ｈ?參，＿?Ｍ?ｐ。２．?Ｉ?｜?｜?＿??Ｖ?ｗ?／??图１．３?ＮＫ／Ｔ细胞淋巴瘤细胞株和正常人ＮＫ细胞中ＰＡＢＰＣ１蛋白的表达及量化。与正常ＮＫ??细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株在ＰＡＢＰＣ１蛋白表达均升高。＊ＰＣ０．０５，?＊＊Ｐ＜０
【参考文献】：
期刊论文
[1]Cytoplasmic Poly（A） Binding Protein 4 Is Highly Expressed in Human Colorectal Cancer and Correlates with Better Prognosis[J]. Dan Liu~(a,b),Bin Yin~c,Qiang Wang~d,Wenyi Ju~c,Yuanjia Chen~a,Huizhong Qiu~e,Ji Li~f, Xiaozhong Peng~(c,*),Chongmei Lu~(a,*) a Department of Gastroenterology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences, Beijing 100730,China b Department of Gastroenterology,The Second Affiliated Hospital of Harbin Medical University,Harbin 150086,China c National Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100005,China d Department of Internal Medicine,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences, Beijing 100730,China e Department of Surgery,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China f Department of Pathology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China. 遗传学报. 2012(08)
[2]Current development of the second generation of mTOR inhibitors as anticancer agents[J]. Hong-Yu Zhou1 and Shi-Le Huang1,2 1Department of Biochemistry and Molecular Biology, 2Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.. 癌症. 2012(01)
[3]EB病毒活化对鼻咽癌基因表达模式的影响[J]. 陈霞,马文丽,梁爽,廖之君,商涛,郑文岭. 癌症. 2008(01)
本文编号：3485133
【文章来源】：郑州大学河南省 211工程院校
【文章页数】：128 页
【学位级别】：博士
【部分图文】：
图１．３?ＮＫ／Ｔ细胞淋巴瘤细胞株和正常人ＮＫ细胞中ＰＡＢＰＣ１蛋白的表达及量化
?第一部分?ＰＡＢＰＣ１在ＮＫ／Ｔ细胞淋巴瘤中的表达和临床意义???Ｕｎｓｔａｉｎｅｄ?ＣＤ５６?ａｎｄ?ＣＤ３??＿?Ｑ１?Ｑ２?Ｑ１?Ｑ２??〇?０６６?０?＇?９６?５?３．３５??ｓ?????Ｑ４?Ｑ３?；?Ｑ４?Ｑ３??．－ｊ?９９?９?０?４?０?１６?０???１????＂■—ｉ????１??￣￣￣ｘ￣??１?■??????■—ｔ????ｉ?■?■??ＣＤ３－ＦＩＴＣ??图１．１磁珠分选正常人ＰＢＭＣ后流式细胞术测定ＮＫ细胞纯度，其纯度超过９５％。??Ａ?Ｂ?Ｃ??４－１?１．５－１?１．５－１??ｉｌｌ．１?－ｄ?，．—■■■■?Ｊ＼〇ＬＩ１０??图１．２?ＮＫ／Ｔ细胞淋巴瘤细胞株和正常人ＮＫ细胞中ＰＡＢＰＣ１、ＰＡＢＰＣ３和ＰＡＢＰＣ４?ｍＲＮＡ??相对表达量。Ａ．与正常ＮＫ细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ１表达均升高；Ｂ．与??正常ＮＫ细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ３表达无明显变化；Ｃ．与正常ＮＫ细胞??相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ４表达无明显变化。ＴＣＯ．ＯＳ，?＊Ｖ＜０．０１，?ＷＰ＜０．００１。??０．８ｎ??〇???ｃ?＊＊＊?＊＊★??ＰＡＢＰＣ１?．．?Ｉｆ。６．?？?Ｐ???１１０４?Ａ?Ｓ１８??＿Ｈ?參，＿?Ｍ?ｐ。２．?Ｉ?｜?｜?＿??Ｖ?ｗ?／??图１．３?ＮＫ／Ｔ细胞淋巴瘤细胞株和正常人ＮＫ细胞中ＰＡＢＰＣ１蛋白的表达及量化。与正常ＮＫ??细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株在ＰＡＢＰＣ１蛋白表达均升高。＊ＰＣ０．０５，?＊＊Ｐ＜０
?第一部分?ＰＡＢＰＣ１在ＮＫ／Ｔ细胞淋巴瘤中的表达和临床意义???Ｕｎｓｔａｉｎｅｄ?ＣＤ５６?ａｎｄ?ＣＤ３??＿?Ｑ１?Ｑ２?Ｑ１?Ｑ２??〇?０６６?０?＇?９６?５?３．３５??ｓ?????Ｑ４?Ｑ３?；?Ｑ４?Ｑ３??．－ｊ?９９?９?０?４?０?１６?０???１????＂■—ｉ????１??￣￣￣ｘ￣??１?■??????■—ｔ????ｉ?■?■??ＣＤ３－ＦＩＴＣ??图１．１磁珠分选正常人ＰＢＭＣ后流式细胞术测定ＮＫ细胞纯度，其纯度超过９５％。??Ａ?Ｂ?Ｃ??４－１?１．５－１?１．５－１??ｉｌｌ．１?－ｄ?，．—■■■■?Ｊ＼〇ＬＩ１０??图１．２?ＮＫ／Ｔ细胞淋巴瘤细胞株和正常人ＮＫ细胞中ＰＡＢＰＣ１、ＰＡＢＰＣ３和ＰＡＢＰＣ４?ｍＲＮＡ??相对表达量。Ａ．与正常ＮＫ细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ１表达均升高；Ｂ．与??正常ＮＫ细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ３表达无明显变化；Ｃ．与正常ＮＫ细胞??相比，ＮＫ／Ｔ细胞淋巴瘤细胞株ＰＡＢＰＣ４表达无明显变化。ＴＣＯ．ＯＳ，?＊Ｖ＜０．０１，?ＷＰ＜０．００１。??０．８ｎ??〇???ｃ?＊＊＊?＊＊★??ＰＡＢＰＣ１?．．?Ｉｆ。６．?？?Ｐ???１１０４?Ａ?Ｓ１８??＿Ｈ?參，＿?Ｍ?ｐ。２．?Ｉ?｜?｜?＿??Ｖ?ｗ?／??图１．３?ＮＫ／Ｔ细胞淋巴瘤细胞株和正常人ＮＫ细胞中ＰＡＢＰＣ１蛋白的表达及量化。与正常ＮＫ??细胞相比，ＮＫ／Ｔ细胞淋巴瘤细胞株在ＰＡＢＰＣ１蛋白表达均升高。＊ＰＣ０．０５，?＊＊Ｐ＜０
【参考文献】：
期刊论文
[1]Cytoplasmic Poly（A） Binding Protein 4 Is Highly Expressed in Human Colorectal Cancer and Correlates with Better Prognosis[J]. Dan Liu~(a,b),Bin Yin~c,Qiang Wang~d,Wenyi Ju~c,Yuanjia Chen~a,Huizhong Qiu~e,Ji Li~f, Xiaozhong Peng~(c,*),Chongmei Lu~(a,*) a Department of Gastroenterology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences, Beijing 100730,China b Department of Gastroenterology,The Second Affiliated Hospital of Harbin Medical University,Harbin 150086,China c National Laboratory of Medical Molecular Biology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100005,China d Department of Internal Medicine,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences, Beijing 100730,China e Department of Surgery,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China f Department of Pathology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China. 遗传学报. 2012(08)
[2]Current development of the second generation of mTOR inhibitors as anticancer agents[J]. Hong-Yu Zhou1 and Shi-Le Huang1,2 1Department of Biochemistry and Molecular Biology, 2Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.. 癌症. 2012(01)
[3]EB病毒活化对鼻咽癌基因表达模式的影响[J]. 陈霞,马文丽,梁爽,廖之君,商涛,郑文岭. 癌症. 2008(01)
本文编号：3485133
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