林贞花
肿瘤分子病理学
个性化签名
- 姓名:林贞花
- 目前身份:
- 担任导师情况:
- 学位:
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学术头衔:
教育部“新世纪优秀人才支持计划”入选者, 博士生导师
- 职称:-
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学科领域:
病理学
- 研究兴趣:肿瘤分子病理学
林贞花,女,1969年7月生,延边大学基础医学院病理学与法医学教研部教授、病理学与病理生理学科博士生导师。1993年毕业于延边大学医学院医疗系本科,1996年获延边大学医学院病理学专业硕士学位,2003年2月获韩国高丽大学医科大学病理学专业医学博士学位,毕业后在韩国高丽大学医科大学病理学室从事了一年的博士后研究员工作。2006.5-2007.9期间以延边大学公派访问学者的身份赴美国约翰.霍普金斯大学医学院病理学系从事博士后研究工作。 研究方向:肿瘤分子病理学 科研成果:近年来,在《Clin Cancer Res》和《Am J Pathol》等国际刊物上发表SCI论文18篇,在《中华病理学杂志》等国家级核心刊物上发表论文12篇。 近5年主持承担的部分主要科研课题有:(1)国家教育部重点项目“新世纪优秀人才支持计划”(2008-2010,50.0万元);(2)国家自然科学基金(2006-2008,22.0万元);(3)国家自然科学基金(2010-2012,27.0万元);(4)教育部留学回国人员科研启动基金(2005-2007,3.0万元);(5)吉林省科技厅社会发展重点项目(2009-2011,6.0万元);(6)吉林省科技厅杰出青年基金(2005-2007,10.0万元)。
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1467
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成果阅读
286
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成果数
6
【期刊论文】人乳头状瘤病毒阴性的宫颈癌及其癌前病变中p16INK4A蛋白表达和DNA倍体分析
林贞花, 柳明洙, 赵稀玮, 吴群英, 刘双平, 金仁仙
中华病理学杂志,2006,35(7):412~416,-0001,():
-1年11月30日
目的探讨人乳头状瘤病毒(HPV)感染阴性的宫颈癌及其癌前病变中p16INK4A蛋白表 达和DNA倍体分析的临床病理学意义。方法应用PcR方法筛查出HPV感染阴性的20例慢性宫 颈炎、20例宫颈上皮内瘤变(CIN)、3例宫颈腺上皮内瘤变(CGIN)、38例浸润性鳞状细胞癌(鳞癌)和15例浸润性腺癌作为研究对象。应用免疫组织化学(LSAB)染色方法检测p16INK4A蛋白在这些病变 组织中的表达,并结合流式细胞仪DNA倍体分析探讨HPV阴性的宫颈癌的早期诊断和预后判定。 结果p16INK4A蛋白特异性地表达在CIN和cGIN病变、鳞癌以及腺癌细胞的胞核和胞质中,而在正常 鳞状上皮和腺上皮中没有任何阳性表达信号。另外,DNA异倍体在浸润性鳞癌和腺癌中的表达率明 显高于CIN病变组(P<0.01)。在有淋巴结转移的浸润癌中DNA异倍体存在的百分率高于无淋巴 结转移组,但尚未发现差异有统计学意义。在8例p16INK4A表达阴性的浸润性鳞癌中有2例表现为DNA异倍体。结论p16INK4蛋白检测可以作为HPV感染阴性的宫颈鳞癌及腺癌的早期诊断指标,结合DNA倍体分析将对宫颈恶性肿瘤的诊断有重要的辅助意义。
宫颈肿瘤, 乳头状瘤病毒, 人, 蛋白质p16
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【期刊论文】子宫颈癌中Hedgehog信号通路蛋白表达与人乳头状瘤病毒16型感染的关系
林贞花 , 玄延花, 李贵铃, 姜宏宇
中华病理学杂志,2009,38(3):178~182,-0001,():
-1年11月30日
目的探讨Hedgehog(Hh)信号通路蛋白在宫颈癌及其癌前病变中的临床病理学意义,并分析其与人乳头状瘤病毒(HPV)16型感染的关系。方法32例正常宫颈上皮、7l例宫颈上皮 舟瘤变(CIN;CINⅠ28例,Cl援Ⅱ18例,CINⅢ25例)和80例宫颈鳞状细胞癌共183例选自延边大学医 院、延边妇幼保健院和延边肿瘤医院病理科存档蜡块。应用PCR技术检测上述组织中HPV16型的 感染情况,并应用Shh、1hh、Ptch和Smo4种Hh信号通路蛋白抗体、组织芯片和免疫组织化学En Vision法检测Hh信号通路蛋白在上述病变组织中的表达情况。结果Shh、1hh、Ptch和Smo在正常宫颈黏膜上皮中为弱阳性,而在宫颈癌和CINⅢ中呈强阳性,其表达率均显著高于正常宫颈黏膜上皮(P均<0.05)。80例宫颈癌标本中珏PVl6阳性率是77.5%(62/80),而且Shh蛋白的强阳性率 在HPVl6型阳性的宫颈癌组织中显著高于HPV16阴性组(P<0.05)。结论Hh信号通路蛋白过表 达可以作为宫颈癌及其癌前病变的早期辅助诊断指标并有望成为宫颈癌靶向治疗的新靶点,而且Shh蛋白的过表达与HPV16型感染密切相关。
子宫肿瘤, 乳头状瘤病毒感染, 宫颈上皮内瘤样病变
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【期刊论文】Combination of Proteasome and HDAC Inhibitors forUterine Cervical Cancer Treatment
林贞花, Zhenhua Lin, , Martina Bazzaro, Mei-Cheng Wang, Kwun C. Chan, Shiwen Peng, and Richard B.S. Roden
Clin Cancer Res 2009; 15(2) January 15, 2009,-0001,():
-1年11月30日
Purpose: Cervical cancer cells are addicted to the expression of the human papillomavirus (HPV)oncoproteins E6 and E7. The oncogencity of E6 is mediated in part by targeting p53a nd PDZfamilytumor suppressor proteins for rapid proteasomal degradation, whereas the E7 oncoproteinacts in part by coopting histone deacetylases (HDAC)1/2. Here, we examine the hypothesis thatinhibition of proteasome function andHDAC activity would synergistically and specifically triggercervical cancer cell death by the interruption of E6 and E7 signaling.Experimental Design: The sensitivity and molecular responses of keratinocytes and HPVpositiveand HPV-negative cervical cancer cells and xenografts to combinations of proteasomeand HDAC inhibitors were tested.The expression of HDAC1/HDAC2 in situ was examined in cervicalcancer, its precursors, and normal epithelium.Results: Cervical cancer cell lines exhibit greater sensitivity to proteasome inhibitors than doHPV-negative cervical cancers or primary human keratinocytes.Treatment of cervical cancer cellswith bortezomib elevated the level of p53b ut not hDlg, hScribble or hMAGI. Immunohistochemicalanalysis revealed elevated HDAC1/HDAC2 expression in cervical dysplasia and cervical carcinomaversus normal cervical epithelium. The combination of bortezomib and HDAC inhibitortrichostatin A or vorinostat shows synergistic killing of HPV-positive, but not HPV-negative, cervicalcancer cell lines. Similarly, treatment ofHeLa xenograftswith the combination of bortezomiband trichostatin A retarded tumor growth significantly more effectively than either agent alone.Conclusions: A combination of proteasome andHDACinhibitors, including bortezomib and vorinostat,respectively, warrants exploration for the treatment of cervical cancer.
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【期刊论文】Expression Pattern and Subcellular Localization ofHuman Papillomavirus Minor Capsid Protein L2
林贞花, Zhenhua Lin, *†‡ Anna V. Yemelyanova, *Ratish Gambhira, * Subhashini Jagu, *Craig Meyers, § Reinhard Kirnbauer, ¶Brigitte M. Ronnett, * Patti E. Gravitt, _**and Richard B.S. Roden*
The American Journal of Pathology, Vol. 174, No.1, January 2009,-0001,():
-1年11月30日
The expression pattern of human papillomavirus (HPV) capsid antigen L2 is poorly described, and the significance of its localization with both promyelocytic leukemia protein (PML) and Daxx in a subnuclear domain, nuclear domain 10 (ND-10), when ectopically expressed in tissue culture cells is controversial. To address whether ND-10 localization of L2 occurs in natural cervical lesions, we used a HPV16 and HPV18 L2-specific monoclonal antibody (RG-1), in addition to rabbit antiserum to HPV6 L2, to localize L2. Immunohistochemical staining with RG-1 produced diffuse staining in the nuclei of some cells located within the superficial epithelial layers in eight of nine cases of HPV16/18 cervical intraepithelial neoplasia grade 1 (CIN1); however, no staining was observed in HPV16/18 high-grade CIN (0 of 8 cases), normal cervical epithelium (0 of 20 cases), cervical squamous cell carcinoma (0 of 102 cases), adenocarcinoma (0 of 51 cases), or adenosquamous carcinoma (0 of 6 cases). HPV16/18 cervical lesions that express L2 exhibit higher HPV16/18 genome copies per cell compared with those that do not positively stain with RG-1 (P<0.04). RG-1 staining of HeLa cells transfected with L2 expression constructs was frequently concentrated in the ND-10, particularly in cells expressing high levels of L2, and co-localized with the cellular markers of ND-10, PML, and Daxx. In contrast, L2 was primarily diffuse within the nucleus and distinct from ND-10 as defined by PML immunofluorescent staining in CIN lesions, condylomata, and HPV16-transduced organotypic cultures.
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【期刊论文】△Np63 protein expression in uterine cervicaland endometrial cancers
林贞花, Zhenhua Lin • Mingzhu Liu • Zhuhu Li •Changheon Kim • Eungseok Lee • Insun Kim
J Cancer Res Clin Oncol (2006) 132: 811-816,-0001,():
-1年11月30日
Purpose To investigate the signiWcance of p63 expressionin uterine cervical and endometrial cancers.Materials and methods _Np63 protein expression wasstudied in a variety of 127 cases of uterine cervicallesions (20 non-neoplastic cervices, 43 cervical intraepithelialneoplasia [CIN], 54 squamous cell carcinomas(SCCs), 40 adenocarcinomas, and 13 otherhistologic types) and 30 endometrioid type of endometrialadenocarcinomas by using immunohistochemistry.One SCC cell line (ME-180) and one adenocarcinomacell line (HeLa) were also included.Results In uterine cervix, the expression of _Np63 wasincreased with progression of CIN, and positive in allSCCs, transitional cell carcinomas, and adenoid basalcarcinoma, but negative in all adenocarcinomas. Adenosquamouscell carcinoma and mixed neuroendocrineand squamous cell carcinoma were positive in squamouscomponent, but not in adenocarcinoma and neuroendocrinecarcinoma components. ME-180 cell linewas positive, whereas HeLa cell line was negative.Endometrioid type of endometrial adenocarcinomasshowed a positive staining in glandular (26.7%) andsquamous component.Conclusions Immunohistochemical staining for △Np63is a powerful marker for squamous diVerentiation anduseful in exclusion of glandular and neuroendocrinediVerentiation in uterine cervical cancers, but notalways in endometrial cancers.
△Np63 • Uterine cervical cancer •Endometrial cancer
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