Mallery Susan R, Tong Meng, Shumway Brian S, Curran Alice E, Larsen Peter E, Ness Gregory M, Kennedy Kelly S, Blakey George H, Kushner George M, Vickers Aaron M, Han Brian, Pei Ping, Stoner Gary D
Authors' Affiliations: Divisions of Oral Maxillofacial Pathology & Radiology and Oral Maxillofacial Surgery & Anesthesiology, College of Dentistry, The Ohio State University; The Ohio State University Comprehensive Cancer, Columbus, Ohio; Departments of Oral & Maxillofacial Pathology and Oral & Maxillofacial Surgery, School of Dentistry, University of Louisville, Kentucky; Departments of Diagnostic Sciences and Oral and Maxillofacial Surgery, University of North Carolina at Chapel Hill School of Dentistry, Chapel Hill, North Carolina; and Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
Clin Cancer Res. 2014 Apr 1;20(7):1910-24. doi: 10.1158/1078-0432.CCR-13-3159. Epub 2014 Jan 31.
Approximately 30% higher grade premalignant oral intraepithelial neoplasia (OIN) lesions will progress to oral cancer. Although surgery is the OIN treatment mainstay, many OIN lesions recur, which is highly problematic for both surgeons and patients. This clinical trial assessed the chemopreventive efficacy of a natural product-based bioadhesive gel on OIN lesions.
This placebo-controlled multicenter study investigated the effects of topical application of bioadhesive gels that contained either 10% w/w freeze-dried black raspberries (BRB) or an identical formulation devoid of BRB placebo to biopsy-confirmed OIN lesions (0.5 g × q.i.d., 12 weeks). Baseline evaluative parameters (size, histologic grade, LOH events) were comparable in the randomly assigned BRB (n = 22) and placebo (n = 18) gel cohorts. Evaluative parameters were: histologic grade, clinical size, and LOH.
Topical application of the BRB gel to OIN lesions resulted in statistically significant reductions in lesional sizes, histologic grades, and LOH events. In contrast, placebo gel lesions demonstrated a significant increase in lesional size and no significant effects on histologic grade or LOH events. Collectively, these data strongly support BRB's chemopreventive impact. A cohort of very BRB-responsive patients, as demonstrated by high therapeutic efficacy, was identified. Corresponding protein profiling studies, which demonstrated higher pretreatment levels of BRB metabolic and keratinocyte differentiation enzymes in BRB-responsive lesions, reinforce the importance of local metabolism and differentiation competency.
Results from this trial substantiate the LOH reductions identified in the pilot BRB gel study and extend therapeutic effects to significant improvements in histologic grade and lesional size.
约30%的高级别口腔上皮内瘤变（OIN）癌前病变会进展为口腔癌。尽管手术是OIN的主要治疗方法，但许多OIN病变会复发，这给外科医生和患者都带来了很大问题。本临床试验评估了一种基于天然产物的生物黏附凝胶对OIN病变的化学预防效果。
这项安慰剂对照的多中心研究调查了局部应用含有10% w/w冻干黑莓（BRB）的生物黏附凝胶或不含BRB的相同配方安慰剂对活检确诊的OIN病变（0.5 g×每日4次，共12周）的影响。在随机分配的BRB（n = 22）和安慰剂（n = 18）凝胶队列中，基线评估参数（大小、组织学分级、杂合性缺失事件）具有可比性。评估参数包括：组织学分级、临床大小和杂合性缺失。
将BRB凝胶局部应用于OIN病变导致病变大小、组织学分级和杂合性缺失事件在统计学上显著降低。相比之下，安慰剂凝胶病变的大小显著增加，对组织学分级或杂合性缺失事件无显著影响。总体而言，这些数据有力地支持了BRB的化学预防作用。确定了一组对BRB反应非常敏感的患者，其治疗效果很高。相应的蛋白质谱研究表明，在对BRB反应的病变中，BRB代谢和角质形成细胞分化酶的预处理水平较高，这强化了局部代谢和分化能力的重要性。
该试验结果证实了在BRB凝胶先导研究中发现的杂合性缺失减少，并将治疗效果扩展到组织学分级和病变大小的显著改善。
