Les Malformations Artérioveineuses sont des lésions vasculaires évolutives. Elles peuvent avoir des conséquences neurologiques lourdes liées au risque hémorragique élevé qui est leur mode de révélation le plus fréquent. Le développement de meilleurs outils d’imagerie a beaucoup amélioré le diagnostic de ces lésions et a permis une meilleure compréhension de leur interaction avec le tissu cérébral. Néanmoins, Leur 4eme dimension et leur évolution restent encore obscures.Par ailleurs, les traitements actuels (embolisation, microchirurgie, chirurgie stéréotaxique) sont associés à des risques de morbidité et mortalité importants.Pour ces raisons, nous avons travaillé sur un traitement potentiel peu invasif: des agents antiangiogéniques. Un modèle porcin simplifié a été élaboré consistant en l’occlusion unilatérale de l’artère carotide primitive et externe par voie endovasculaire. Ce modèle a présenté des preuves d’angiogénèse et des modifications anatomopathologiques proches de celles des MAVc humaines. Le Bevacizumab, un anticorps monoclonal pour le VEGF, a été administré in situ sur ce modèle. Les résultats ont montré que l’agent antiangiogénique altère l’angiogénèse sur les specimens histologiques. L’épaisseur de la paroi des vaissaux a été stabilisée après l’injection de Bevacizumab mais le volume des retia est demeuré identique montrant que le volume dépend de l’angiogénèse mais probablement également du flux / Brain arteriovenous malformations are dynamic, evolving vascular lesions. They present high morbidity rates due to hemorrhagic presentation that is the most frequent symptom at onset and potentially high mortality rates .Up to date imaging techniques has greatly facilitated the diagnosis of these lesions and the better understanding of their relation to adjacent brain tissue. However, it remains still a challenge to define their four dimensional nature and its consequences, a fact that can actually optimize their treatment. Embolization, surgery and stereotactic radiosurgery that are currently used in the treatment of AVMs carry also significant morbi-mortality risks. For this reason, a potential minimally invasive treatment with antiangiogenic agents was tested. A swine model was firstly created using the animal’s rete mirabile and performing an endovascular occlusion of one common and external carotid artery. This simplified model presented evidence of angiogenesis and histologic findings that are also observed in human AVMs compared to a control group. Secondly, Bevacizumab that is a monoclonal antibody to vascular endothelial growth factor, was in situ administered on this model. The results showed that the antiangiogenic agent tampered angiogenesis on histologic samples by stabilizing the wall thickness of the arteries but it did not have any effect on volume that is probably depending on flow and not only on angiogenesis.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / Os mÃtodos tradicionais de tratamento do cÃncer, como a quimioterapia e a radioterapia, embora sejam eficazes em vÃrios tipos de tumores, encontram freqÃentemente populaÃÃes de cÃlulas neoplÃsicas resistentes, alÃm de apresentarem uma baixa margem de seguranÃa para os pacientes. A utilizaÃÃo da hipertermia associada à quimioterapia e/ou radioterapia jà se encontra fartamente relatada como vantajosa na literatura especializada, principalmente em pacientes portadores de cÃncer em estÃdio avanÃado, submetidos previamente aos mÃtodos clÃssicos de tratamento. A aplicaÃÃo de calor nos tecidos atravÃs de ultrassom contÃnuo torna mais Ãgil Ãste procedimento e com eficÃcia comprovada. O uso dos antiangiogÃnicos tambÃm vem sendo relatado como eficaz na literatura especializada e atualmente, a lista destas substÃncias vem aumentando consideravelmente. O estudo da aÃÃo da hipertermia associada a alguns agentes antiangiogÃnicos tem sido sugerida uma vez que os vasos tumorais ao encontrarem-se dilatados, nÃo promoverÃo a diminuiÃÃo da temperatura no tecido tumoral e, consequentemente, os efeitos desta associaÃÃo serÃo mais intensos do que no tecido normal devendo contribuir para a morte celular. Objetiva-se neste trabalho, avaliar o efeito antitumoral e antiangiogÃnico da hipertermia induzida por US isolada e combinada com etoricoxibe e pegaptanibe,no carcinossarcoma de Walker 256 implantado na tela subcutÃnea do dorso de ratos por meio de utilizaÃÃo do modelo experimental de hipertermoterapia por US assim como o estudo dos efeitos da hipertermia por US isolada e em combinaÃÃo com etoricoxibe e pegaptanibe,na angiogÃnese tumoral.O mÃtodo utilizado para o estudo teve inÃcio com o implante de cÃlulas de tumor de Walker 256 no dorso de ratos Wistar machos. Os animais foram tratados com hipertermia aplicada atravÃs de aparelho de ultrassom, mantida a nÃvel de 45o C durante cinco minutos no terceiro dia apÃs a inoculaÃÃo e tambÃm tratados com etoricoxibe e pegaptanibe por via oral e intraperitoneal respectivamente a partir do dia da inoculaÃÃo. Cada grupo de animais foi submetido a medidas do crescimento tumoral durante o perÃodo de 30 dias, assim como tambÃm à avaliaÃÃo da microdensidade vascular atravÃs de estudo mesoscÃpico fotogrÃfico, validado pelo estudo microscÃpico. A aplicaÃÃo do calor atravÃs de aparelho de ultrasom demonstrou eficiÃncia e agilidade A hipertermia, o etoricoxibe e o pegaptanibe, apresentaram capacidade antiangiogÃnica, expressada tanto pela curva de sobrevida, como pela avaliaÃÃo da microdensidade vascular. Particularmente, a hipertermia isoladamente apresentou um efeito antiangiogÃnico significativo tanto na curva de crescimento tumoral como na diminuiÃÃo da densidade microvascular. A associaÃÃo da hipertermia com o pegaptanibe, demonstrou uma eficiÃncia na diminuiÃÃo da densidade microvascular significativamente maior do que os demais grupos. O modelo de aplicaÃÃo de hipertermia gerada por um aparelho de ultrassom na modalidade contÃnua foi satisfatÃria, demonstrando ter sido efetiva tanto na diminuiÃÃo do crescimento tumoral, como na diminuiÃÃo da densidade microvascular. / The traditional methods of cancer treatment, like the chemotherapy and radiotherapy, even though they are effective in many types of tumours, they find frequently resistant neoplasic cellsâ population, beyond presenting a low security margin to the patients. The hyperthermia use associated to the chemotherapy and radiotherapy are plenty mentioned as profitable in the specialist literature, especially in patients with cancer in advanced stage, submitted previously to the classic methods of the treatment. The tissuesâ heat insertion through the continuous ultrasound becomes the procedure faster and with proved efficacy. The antiangiogenic use also is being related like effective in the specialist literature and, at this moment, the substancesâ list has grown vastly. The study of the hyperthermia action associated to antiangiogenic agents has been suggested, once the tumour vessels are dilated, would not promote the temperature reduction in the tumour vessels and, therefore, the effects of this association would be more intense than in the normal tissue, what might contribute to the death cell. The study objective is to evaluate the antitumor and antiangiogenic effect of the hyperthermia induced by isolated ultrasound and combined with etoricoxibe and pegaptanibe in the 256 Walker carcinossarcoma implanted in the subcutaneous back screen of mouse by using the hyperthermia experimental model by ultrasound, like the hyperthermia effects study by isolated ultrasound and linked with etoricoxibe and pegaptanibe, in the tumour angiogenesis. The method used describes the insertion of 256 Walker Tumour cells in the back of male Wistar mouse. The animals were treated with hyperthermia applied through the ultrasound equipment, kept to a 45 C level during five minutes in the third day after the inoculation and also treated with etoricoxibe and pegaptanibe by oral and intraperitoneal respectively since the inoculation day. Each animal group was submitted to a tumour growth measurement during a period of 30 days, as well as also a vascular microdensity evaluation through a photographic mesoscopic study, validated by the microscopic study. The heat application through the ultrasound equipment demonstrated efficiency and agility. The hyperthermia, the etoricoxibe and the pegaptanibe showed antiangiogenic capacity, expressed by the over life curve, and also by the vascular microdensity evaluation. Particularly, the isolated hyperthermia showed a significative antiangiogenic effect in the tumour growth curve and also in the decreasing of the micro vascular density. The association between the hyperthermia and the pegaptanibe demonstrated a greater efficiency in the reducing of the micro vascular density than the other groups. The hyperthermia application model generated by the ultrasound equipment in the continuous modality was satisfactory, demonstrating by being effective as much in the reducing of the tumour growth as in the decreasing of the micro vascular density.