Oncology Division, Department of Surgery, Dr. Cipto Mangunkusumo National Central General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, 10430, Indonesia.
Department of Urology, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
J Egypt Natl Canc Inst. 2020 Feb 28;32(1):12. doi: 10.1186/s43046-020-0021-0.
Squamous cell carcinoma of the oral cavity (OSCC) is the sixth most common malignancy. Surgery is mainstay treatment for oral cancers. Surgery in locally advanced OSCC presents many challenges primarily because the head and neck have critical structures that can be damaged by tumor or treatment. It is thought that neoadjuvant chemotherapy (NC) in locally advanced OSCC is able to shrink tumor size. Chemoresistancy is a problem due to hypoxic microenvironment characterized by increased expression of HIF-1α. It is also regulated by miR-210 as well as increased expression of CD44 and CD133. Melatonin has a powerful antioxidant and oncostatic effects that are expected to improve tumor hypoxia and clinical response. Fifty patients with OSCC were included and randomized. miR-210 and CD44 expression were measured before and after intervention using qRT-PCR absolute quantification, and clinical response was evaluated according to RECIST 1.1 criteria. This study aims to determine the effect of melatonin in improving the clinical response of patients with locally advanced oral squamous cell carcinoma (OSCC) after neoadjuvant chemotherapy to miR-210 and CD44 expression.
Melatonin administration reduced miR-210 levels but not significant (p = 0.767). CD44 expression also decreased in the melatonin group compared with placebo yet was not significant (p = 0.103). There was a decrease in the expression of miR-210 and CD44 followed by a decrease in the percentage of residual tumor but not significant (p = 0.114).
In OSCC, the addition of 20-mg melatonin to neoadjuvant chemotherapy (NC) reduced the expression of miR-210 and CD44 and decreased the percentage of tumor residue; however, no statistically significant result was observed.
This study is registered to ClinicalTrials.gov under trial registration number: NCT04137627 with date of registration on October 22, 2019-retrospectively registered, accessible from: https://clinicaltrials.gov/ct2/show/NCT04137627.
口腔鳞状细胞癌（OSCC）是第六大常见恶性肿瘤。手术是口腔癌的主要治疗方法。局部晚期 OSCC 的手术存在许多挑战，主要是因为头颈部有重要结构，这些结构可能会因肿瘤或治疗而受损。人们认为，局部晚期 OSCC 中的新辅助化疗（NC）能够缩小肿瘤大小。由于缺氧微环境导致缺氧诱导因子 1α（HIF-1α）表达增加，出现化疗耐药是一个问题。miR-210 的表达以及 CD44 和 CD133 的表达增加也调节了化疗耐药。褪黑素具有强大的抗氧化和抗肿瘤作用，有望改善肿瘤缺氧和临床反应。纳入 50 例 OSCC 患者并进行随机分组。采用 qRT-PCR 绝对定量法检测干预前后 miR-210 和 CD44 的表达，根据 RECIST1.1 标准评估临床反应。本研究旨在确定褪黑素对改善新辅助化疗后局部晚期口腔鳞状细胞癌（OSCC）患者临床反应的作用及其对 miR-210 和 CD44 表达的影响。
褪黑素给药降低了 miR-210 水平，但无统计学意义（p = 0.767）。与安慰剂组相比，褪黑素组 CD44 表达也降低，但无统计学意义（p = 0.103）。miR-210 和 CD44 表达降低后，肿瘤残留百分比降低，但无统计学意义（p = 0.114）。
在 OSCC 中，将 20mg 褪黑素加入新辅助化疗（NC）中可降低 miR-210 和 CD44 的表达，并降低肿瘤残留百分比；但未观察到统计学显著结果。
本研究在 ClinicalTrials.gov 注册，注册号为 NCT04137627，注册日期为 2019 年 10 月 22 日-回顾性注册，可从以下网址获取：https://clinicaltrials.gov/ct2/show/NCT04137627。
