JOAQUIM MAURICIO DA MOTTA LEAL FILHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
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- Imaging response predictors following drug eluting beads chemoembolization in the neoadjuvant liver transplant treatment of hepatocellular carcinoma(2020) GALASTRI, Francisco Leonardo; NASSER, Felipe; AFFONSO, Breno Boueri; VALLE, Leonardo Guedes Moreira; ODISIO, Bruno Calazans; MOTTA-LEAL FILHO, Joaquim Mauricio; SALVALAGGIO, Paolo Rogerio; GARCIA, Rodrigo Gobbo; ALMEIDA, Marcio Dias de; BARONI, Ronaldo Hueb; WOLOSKER, NelsonBACKGROUND Drug-eluting bead transarterial chemoembolization (DEB-TACE) is an endovascular treatment to release chemotherapeutic agents within a target lesion, minimizing systemic exposure and adverse effects to chemotherapeutics. Therefore, identifying which patient characteristics may predict imaging response to DEB-TACE can improve treatment results while selecting the best candidates. Predictors of the response after DEB-TACE still have not been fully elucidated. This is the first prospective study performed with standardized DEB-TACE technique that aim to identify predictors of radiological response, assessing patients clinical and laboratory characteristics, diagnostic imaging and intraprocedure data of the hepatocellular carcinoma treated in the neoadjuvant context for liver transplantation. AIM To identify pre- and intraoperative clinical and imaging predictors of the radiological response of drug-eluting bead transarterial chemoembolization (DEB-TACE) for the neoadjuvant treatment of hepatocellular carcinoma (HCC). METHODS This is prospective, cohort study, performed in a single transplant center, from 2011 to 2014. Consecutive patients with HCC considered for liver transplant who underwent DEB-TACE in the first session for downstaging or bridging purposes were recruited. Pre and post-chemoembolization imaging studies were performed by computed tomography or magnetic resonance. The radiological response of each individual HCC was evaluated by objective response using mRECIST and the percentage of necrosis. RESULTS Two hundred patients with 380 HCCs were examined. Analysis of the objective response (nodule-based analysis) demonstrated that HCC with pseudocapsules had a 2.01 times greater chance of being responders than those without pseudocapsules (P = 0.01), and the addition of every 1mg of chemoembolic agent increased the chance of therapeutic response in 4% (P < 0.001). Analysis of the percentage of necrosis through multiple linear regression revealed that the addition of each 1mg of the chemoembolic agent caused an average increase of 0.65% (P < 0.001) in necrosis in the treated lesion, whereas the hepatocellular carcinoma with pseudocapsules presented 18.27% (P < 0.001) increased necrosis compared to those without pseudocapsules. CONCLUSION The presence of a pseudocapsule and the addition of the amount of chemoembolic agent increases the chance of an objective response in hepatocellular carcinoma and increases the percentage of tumor necrosis following drug-eluting bead chemoembolization in the neoadjuvant treatment, prior to liver transplantation.
- Vascular smooth muscle cells exhibit a progressive loss of rigidity with serial culture passaging(2012) DINARDO, Carla Luana; VENTURINI, Gabriela; OMAE, Samantha Vieira; ZHOU, Enhua H.; MOTTA-LEAL-FILHO, Joaquim Maurcio da; DARIOLLI, Rafael; KRIEGER, Jose Eduardo; ALENCAR, Adriano Mesquita; PEREIRA, Alexandre CostaOne drawback of in vitro cell culturing is the dedifferentiation process that cells experience. Smooth muscle cells (SMC) also change molecularly and morphologically with long term culture. The main objective of this study was to evaluate if culture passages interfere in vascular SMC mechanical behavior. SMC were obtained from five different porcine arterial beds. Optical magnetic twisting cytometry (OMTC) was used to characterize mechanically vascular SMC from different cultures in distinct passages and confocal microscopy/western blotting, to evaluate cytoskeleton and extracellular matrix proteins. We found that vascular SMC rigidity or viscoelastic complex modulus (G) decreases with progression of passages. A statistically significant negative correlation between G and passage was found in four of our five cultures studied. Phalloidin-stained SMC from higher passages exhibited lower mean signal intensity per cell (confocal microscopy) and quantitative western blotting analysis showed a decrease in collagen I content throughout passages. We concluded that vascular SMC progressively lose their stiffness with serial culture passaging. Thus, limiting the number of passages is essential for any experiment measuring viscoelastic properties of SMC in culture.
- Variation of mechanical properties and quantitative proteomics of VSMC along the arterial tree(2014) DINARDO, Carla Luana; VENTURINI, Gabriela; ZHOU, Enhua H.; WATANABE, Ii Sei; CAMPOS, Luciene Cristina Gastalho; DARIOLLI, Rafael; MOTTA-LEAL-FILHO, Joaquim Mauricio da; CARVALHO, Valdemir Melechco; CARDOZO, Karina Helena Morais; KRIEGER, Jose Eduardo; ALENCAR, Adriano Mesquita; PEREIRA, Alexandre CostaVascular smooth muscle cells (VSMCs) are thought to assume a quiescent and homogeneous mechanical behavior after arterial tree development phase. However, VSMCs are known to be molecularly heterogeneous in other aspects and their mechanics may play a role in pathological situations. Our aim was to evaluate VSMCs from different arterial beds in terms of mechanics and proteomics, as well as investigate factors that may influence this phenotype. VSMCs obtained from seven arteries were studied using optical magnetic twisting cytometry (both in static state and after stretching) and shotgun proteomics. VSMC mechanical data were correlated with anatomical parameters and ultrastructural images of their vessels of origin. Femoral, renal, abdominal aorta, carotid, mammary, and thoracic aorta exhibited descending order of stiffness (G, P < 0.001). VSMC mechanical data correlated with the vessel percentage of elastin and amount of surrounding extracellular matrix (ECM), which decreased with the distance from the heart. After 48 h of stretching simulating regional blood flow of elastic arteries, VSMCs exhibited a reduction in basal rigidity. VSMCs from the thoracic aorta expressed a significantly higher amount of proteins related to cytoskeleton structure and organization vs. VSMCs from the femoral artery. VSMCs are heterogeneous in terms of mechanical properties and expression/organization of cytoskeleton proteins along the arterial tree. The mechanical phenotype correlates with the composition of ECM and can be modulated by cyclic stretching imposed on VSMCs by blood flow circumferential stress.