Effect of melatonin supplementation in combination with neoadjuvant chemotherapy to miR-210 and CD44 expression and clinical response improvement in locally advanced oral squamous cell carcinoma: a randomized controlled trial.


Journal

Journal of the Egyptian National Cancer Institute
ISSN: 2589-0409
Titre abrégé: J Egypt Natl Canc Inst
Pays: England
ID NLM: 9424566

Informations de publication

Date de publication:
28 Feb 2020
Historique:
received: 04 11 2019
accepted: 31 01 2020
entrez: 7 5 2020
pubmed: 7 5 2020
medline: 9 2 2021
Statut: epublish

Résumé

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.

Sections du résumé

BACKGROUND BACKGROUND
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.
RESULTS RESULTS
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).
CONCLUSION CONCLUSIONS
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.
TRIAL REGISTRATION BACKGROUND
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.

Identifiants

pubmed: 32372215
doi: 10.1186/s43046-020-0021-0
pii: 10.1186/s43046-020-0021-0
doi:

Substances chimiques

CD44 protein, human 0
Hyaluronan Receptors 0
MIRN210 microRNA, human 0
MicroRNAs 0
Melatonin JL5DK93RCL

Banques de données

ClinicalTrials.gov
['NCT04137627']

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

12

Auteurs

Diani Kartini (D)

Oncology Division, Department of Surgery, Dr. Cipto Mangunkusumo National Central General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, 10430, Indonesia. d.kartini@gmail.com.

Akmal Taher (A)

Department of Urology, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Sonar Soni Panigoro (SS)

Oncology Division, Department of Surgery, Dr. Cipto Mangunkusumo National Central General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, 10430, Indonesia.

Rianto Setiabudy (R)

Department of Pharmacology and Therapeutics, Dr. Cipto Mangunkusumo National Central General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

Sri Widia Jusman (SW)

Department of Biochemistry and Molecular Genetics, Dr. Cipto Mangunkusumo National Central General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

Sofia Mubarika Haryana (SM)

Department of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

Murdani Abdullah (M)

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia.

Primariadewi Rustamadji (P)

Department of Pathological Anatomy, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Denni Joko Purwanto (DJ)

Department of Surgical Oncology, Dharmais Hospital, National Cancer Center, Jakarta, Indonesia.

Noorwati Sutandyo (N)

Department of Hematology and Medical Oncology, Dharmais Hospital, National Cancer Center, Jakarta, Indonesia.

Indrati Suroyo (I)

Department of Radiology, Dr. Cipto Mangunkusumo National Central General Hospital, Jakarta, Indonesia.

Budi Harapan Siregar (BH)

Oncology Division, Department of Surgery, Persahabatan General Hospital, Jakarta, Indonesia.

Haris Maruli (H)

Oncology Division, Department of Surgery, Persahabatan General Hospital, Jakarta, Indonesia.

Saleha Sungkar (S)

Department of Parasitology, Dr. Cipto Mangunkusumo National Central General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

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Classifications MeSH