Sunitinib Improves Some Clinical Aspects and Reverts DMBA-Induced Hyperplasic Lesions in Hamster Buccal Pouch

Fernanda Lopes De Souza,Luisa Maria G De M Braga,Mariana Oliveira,Maria Antonieta Lopes De Souza,Alan Arrieira Azambuja,Marianne Brochado Nunes,Lisiani Saur,Léder Leal Xavier,Lucas Horstmann Serafim

doi:10.1155/2014/859621

Fernanda Lopes De Souza, Luisa Maria G De M Braga + Show 7 more

Open Access

https://doi.org/10.1155/2014/859621

Copy DOI

Abstract

Oral squamous cell carcinoma (OSCC) is a public health problem. The hamster buccal pouch model is ideal for analyzing the development of OSCC. This research analysed the effects of sunitinib (tyrosine kinase inhibitor) in precancerous lesions induced by 7,12-dimethylbenz(a)anthracene (DMBA) in this model. Thirty-four male hamsters, divided into six groups: control—C (n = 7), acetone—A (n = 12), carbamide peroxide—CP (n = 5 ), acetone and CP—A+CP (n = 8), 1% DMBA in acetone and CP—DA+CP (n = 6), and 1% DMBA in acetone and CP and 4-week treatment with sunitinib—DA+CP+S (n = 7). The aspects evaluated were anatomopathological features (peribuccal area, paws, nose, and fur), histological sections of the hamster buccal pouches (qualitatively analyzed), epithelium thickness, and the rete ridge density (estimated). Sunitinib was unable to attenuate the decrease in weight gain induced by DMBA; no increase in volume was detected in the pouch and/or ulceration, observed in 43% of the animals in the DA+CP group. DA+CP groups presented a significant increase in rete ridge density compared to the control groups (P < 0.01) which was reverted by sunitinib in the DA+CP+S group. Sunitinib seems to have important benefits in early stage carcinogenesis and may be useful in chemoprevention.

Highlights

Oral squamous cell carcinoma is a global public health problem with about 300,000 new cases diagnosed per year representing 5% of all cancers for men and 2% for women [1], twothirds of which are from developing countries [2]
We observed that, during the 83 experimental days, there was a statistically significant lower weight gain in the DA+carbamide Peroxide (CP) and DMBA in acetone + carbamide Peroxide (DA+CP)+S groups when compared to the control groups (Figure 1)
We observed that DMBA treatment induced a significant reduction in weight gain in the DA+CP and DA+CP+S groups (Figure 1)

Summary

Introduction

Oral squamous cell carcinoma is a global public health problem with about 300,000 new cases diagnosed per year representing 5% of all cancers for men and 2% for women [1], twothirds of which are from developing countries [2]. Squamous cell carcinoma of the upper aerodigestive tract has a high risk of primary-treatment failure and death. Some patients will be at risk for malnutrition, infection [3], severe depression, or suicide. Oral squamous cell carcinoma (OSCC) is caused by DNA mutation, often spontaneous but increased by the exposure to a range of mutagens [8]—one of them being chemical. The changes in the DNA can progress from a normal keratinocyte to a premalignant or a potentially malignant keratinocyte that is characterized by the ability to proliferate in a lesscontrolled way than normal. The cells become autonomous and cancer results (characterized by invasion through the epithelial basement membrane) [9]

Objectives

Methods

Results

Conclusion