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Molecular Biomarker Profiling and Translational Evidence-Based Dentistry in Oral Lichen Planus and Oral Squamous Cell Carcinoma.

机译:口腔扁平苔藓和口腔鳞状细胞癌的分子生物学标志物分析和基于翻译证据的牙科。

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摘要

Oral lichen planus-(OLP) is a T cell mediated disease with controversy about its transformation to oral squamous cell carcinoma-(SCCA). Caution in classifying OLP to be one of the Oral premalignant lesions-(OPM) such as epithelial dysplasia-(EpD) exists. Despite this caution, cases of OLP transforming to SCCA exists, and the incidence of SCCA is increasing. Molecular insights to complement histopathology/management of OLP and SCCA are needed.;Using immunohistochemistry on tissue microarray-(TMA) and evidence-based methods, this work demonstrated:-validity of translational evidence-based dentistry-(T-EBD) through the link of molecular biomarker profiling and evidence-based science. Lck, PI-3K and Survivin, a cancer specific anti-apoptotic protein were assessed on patient biopsy samples with OLP, Chronic interface mucosities-(CIM), EpD and SCCA. Lck expression was high in 78.6 % of OLP patients compared to 3.7% in SCCA; PI-3K was high in 63% of SCCA, 100% of EpD, and 35.7% OLP cases. Survivin was high in 64.3% of OLP cases, 96.3% of SCCA, and 100% of EpD. Biomarker protein voting among markers isolated four high risks OLP cases. This result was supported through a data mining study.;The proteomic signatures of individual patient biopsies and the usage of such information for the best-available treatment intervention for each patient serve as a link for molecular profiling and evidence-based analysis.;Evidence-based analysis revealed no superior management for OLP with limited literatures on Lck inhibitors/Pl-3K inhibitors. Most published reports were studies on animal/cell lines and were difficult to analyze with the Wong scale. The Oluwadara-Kossan (OK) scale was developed and validated to assess literatures based on animal/cell lines studies and it provides basis for numbers of samples needed to conduct a clinical trial (NNCCT).;Taken together, biomarker protein voting can be used to isolate high-risk OLP cases. It is better to treat OLP as OPM, to adopt aggressive treatment for SCCA cases, to monitor diseases molecularly using individualized auto-proteomic approach. Lck inhibitors/PI-3K inhibitors might be useful in the future management of OLP, OPM and SCCA.;The findings presented in this study validate a model of tailored personalized medicine- (PM). In the future, PM will depend on correlating information from molecular spatial segments and T-EBD.
机译:口腔扁平苔藓(OLP)是一种T细胞介导的疾病,关于其向口腔鳞状细胞癌(SCCA)的转化尚存争议。存在将OLP分类为口腔恶性病变(OPM)例如上皮发育不良(EpD)之一的警告。尽管有这种谨慎,但仍存在OLP转化为SCCA的情况,并且SCCA的发生率正在增加。需要分子生物学的见解来补充OLP和SCCA的组织病理学/管理。;在组织微阵列(TMA)和基于证据的方法上使用免疫组织化学,这项工作证明:通过翻译的基于证据的牙科(T-EBD)的有效性。分子生物标志物分析与循证科学的联系。对Lck,PI-3K和Survivin(一种癌症特异性抗凋亡蛋白)进行了OLP,慢性界面粘膜(CIM),EpD和SCCA活检样本的评估。 Lck表达在78.6%的OLP患者中较高,而在SCCA中为3.7%; PI-3K在63%的SCCA,100%的EpD和35.7%的OLP病例中较高。 Survivin在OLP病例中占64.3%,在SCCA中占96.3%,在EpD中占100%。标记之间的生物标记蛋白投票分离了四个高风险OLP病例。该结果得到了数据挖掘研究的支持。个体患者活组织检查的蛋白质组学特征以及此类信息在每位患者的最佳可用治疗干预中的使用,为分子谱分析和循证分析提供了联系。基于分析的结果表明,关于Lck抑制剂/ Pl-3K抑制剂的文献有限,没有对OLP进行更好的处理。大多数发表的报告是关于动物/细胞系的研究,很难用Wong量表进行分析。开发并验证了Oluwadara-Kossan(OK)量表,以评估基于动物/细胞系研究的文献,并为进行临床试验(NNCCT)所需的样本数量提供了基础。总而言之,可以使用生物标记蛋白投票隔离高风险的OLP案件。最好将OLP视为OPM,对SCCA病例采取积极治疗,使用个体化自身蛋白质组学方法从分子上监测疾病。 Lck抑制剂/ PI-3K抑制剂可能在OLP,OPM和SCCA的未来管理中有用。该研究提出的发现验证了量身定制的个性化药物(PM)模型。将来,PM将依赖于分子空间部分和T-EBD的相关信息。

著录项

  • 作者单位

    University of California, Los Angeles.;

  • 授予单位 University of California, Los Angeles.;
  • 学科 Health Sciences Dentistry.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 125 p.
  • 总页数 125
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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