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

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.

Efficacy of Hydroxytyrosol as Chemopreventive Agent on Induced Hamster Buccal Pouch Carcinogenesis

“…More ever, traditional treatment for oral precancerous is total surgical excision that always leads to scar formation for a large precancerous lesion. The consensus is that the reversal of precancerous lesions or protection from malignant transformation would have a great impact on the prevention and treatment of OSCC (13) . Extensive studies highlighted the chemopreventive effects of diverse natural products (14,15) .…”

In-Vivo Nonlinear Optical Microscopy (NLOM) of Epithelial-Connective Tissue Interface (ECTI) Reveals Quantitative Measures of Neoplasia in Hamster Oral Mucosa

“…The hamster model provided the ability for noninvasive in-vivo imaging in a buccal mucosa in which the ECTI is relatively flat ( Fig. 2a , d, and g), similar to the human buccal mucosa, floor of the mouth and the ventral surface of the tongue in human oral cavity [ 34 ], all common sites for neoplastic transformation. Our interest in ECTI shape is based on the potential central role this interface serves in neoplastic transformation.…”

“…There are indications that early pathological events leading to neoplastic transformation of basal epithelium initiate structural alterations in the ECTI [ 56 ]. Neoplastic epithelial cell proliferation leads to non-uniform expansion of the epithelium resulting in focal increases in epithelial thickness and shape changes to the ECTI, including formation of rete ridges [ 4 , 6 , 34 ]. Invasion is initiated when the BM is disrupted and neoplastic epithelial cells migrate into the underlying lamina propria, crossing the BM/ECTI.…”

“…Studies resulting in direct assessment of irregularities in ECTI morphology have been restricted to histological evaluation and in some part electron microscopy [ 1 , 14 , 15 , 23 , 37 , 57 , 58 ]. Studies have been reported in which density [ 34 ] or shape [ 58 ] of rete ridges from histological sections under normal and dysplastic conditions were quantified. Others have demonstrated ECTI irregularities in histology by looking at tissue complexity based on fractal geometry calculations [ 1 , 4 ].…”

Skin graft associated with platelet-rich plasma in correcting extensive injuries resulting from the resection of skin cancer chemically induced in rats

“…For the safety of the team, the procedure was conducted in a laminar flow chamber and with individual protection, because the DMBA is a highly carcinogenic substance. The size of the lesion induced by applying DMBA should be approximately 0.5 mm 20 .…”