ABSTRACT
The effects of anti-angiogenic therapies in guiding tumor angioarchitecture prompted us to examine the modifications in the vascular network of the oral squamous cell carcinoma (SCC) produced by the multitargeted tyrosine kinase inhibitor sunitinib malate. Twelve Syrian hamsters had their right buccal pouches submitted to tumor induction with dimethylbenzanthracene and carbamide peroxide for 55 days. The animals were then divided into two groups of six animals each; group I was treated with sunitinib malate and group II (control) was remained untreated. After 4 weeks, the hamsters had their vascular networks casted by Mercox® resin and analyzed by scanning electron microscopy. The qualitative study of the vascular network of the control tumor-bearing pouches showed images of intussusception and sprouting angiogenesis, flattened blood vessels, abrupt variations in their diameter, and a tortuous course. The samples treated with sunitinib exhibited a qualitative reduction of the signs of vascular proliferation. In addition, these casts presented an attenuation of the morphological features observed in the untreated tumor-bearing pouches. Quantitative analysis demonstrated that the pouches treated with sunitinib did not show a decrease (P > 0.05) in the vascular diameter and intervessel distances when compared with the control group. The results of the present study suggest that sunitinib may act on the vascular network of oral SCC, normalizing the blood vessels. However, further experiments should be performed in order to determine a judicious dose of this anti-angiogenic therapy.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Blood Vessels/drug effects , Carcinoma, Squamous Cell/blood supply , Carcinoma, Squamous Cell/drug therapy , Indoles/administration & dosage , Mouth Neoplasms/blood supply , Mouth Neoplasms/drug therapy , Pyrroles/administration & dosage , Animals , Blood Vessels/ultrastructure , Carcinoma, Squamous Cell/pathology , Cricetinae , Humans , Male , Mesocricetus , Microscopy, Electron, Scanning , Mouth Neoplasms/pathology , Neovascularization, Pathologic , SunitinibABSTRACT
A falta de integração entre a ciência básica e a clinica é considerada como um grande obstáculo para o progresso de novas descobertas cientificas. Atualmente, a rota de uma idéia ate o desenvolvimento de uma nova forma de diagnostico ou tratamento de doenças apresenta diversos obstáculos, por ocorrer através de um processo demorado e muito fragmentado. A medicina translacional visa uma integração racional entre pesquisas básicas e clínicas, acelerando a obtenção de resultados e tendo como objetivo principal a melhora da saúde da população. As barreiras intelectuais, regulatórias e econômicas tem sido apontadas como os principais fatores que contribuem para o atraso nas pesquisas. Esse trabalho tem seu escopo em definir o termo medicina translacional, assim como discorrer sobre suas barreiras e as soluções.
Subject(s)
Biomedical Research , Human ExperimentationABSTRACT
Tumoral angiogenesis has been widely studied by histochemical analysis but little has been done regarding morphology of these new vessels. The objective of this study was to perform a qualitative analysis of the angiogenic response to chemical induction with dimethylbenzanthracene (DMBA) and carbamide peroxide of squamous cell carcinoma in pouches of Syrian hamsters after different periods of treatment. Twenty-four Syrian golden hamsters, divided into three groups of eight animals each, had their right jugal pouches treated with a 5% DMBA solution three times a week and a 10% carbamide peroxide two times a week for 55, 70 and 90 days. The left pouch was considered the control. After tumor induction, five animals in each group had their pouches prepared for analysis under scanning electron microscopy and three animals for analysis under light microscopy. The control pouches showed a vascular system composed by few main vessels running parallel to the longest axis of the pouch with some branches. In the pouches submitted to tumor induction, a well-differentiated squamous cell carcinoma was present since 55 days induction in all samples. The new vascular system showed the presence of many tortuous vessels and the majority of them were veins and capillaries. Terminal loops were extremely sinuous adopting a glomerular or corkscrew shape. These tumor vessels are different from normal vessels, presenting irregular diameters, outpouchings and constrictions. Angiogenesis of sprouting and intussusceptive kind could be identified in the tumor pouches, and they were more frequent as the tumor developed.
