MARCELO LUIZ BALANCIN
Projetos de Pesquisa
Unidades Organizacionais
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
- Combining Immunoprofile, Immunogenic Collagen and Mismatch Repair Proteins Predicts Risk of Death and Target Therapy in Malignant Mesothelioma(2019) MACHADO-RUGOLO, J.; BALANCIN, M.; MARTINS, V.; MIRANDA, J.; ASSATO, A.; SOUZA, N.; VELOSA, A. P.; FALZONI, R.; AB'SABER, A.; TEODORO, W.; CAPELOZZI, V.
conferenceObject Immune-profilling depends on immunogenic collagen and mismatch proteins to predict death and therapy in malignant mesothelioma(2019) MORGANTETTI, G.; BALANCIN, M.; MARTINS, V.; MIRANDA, J. T. De; ASSATO, A. K.; SOUZA, N. A. de; VELOSA, A. P. Pereira; TEODORO, W. Rosolia; MEDEIROS, G. A. de; FALZONI, R.; AB'SABER, A. M.; CAPELOZZI, V.- In situ evidence of collagen V and signaling pathway of found inflammatory zone 1 (FIZZ1) is associated with silicotic granuloma in lung mice(2020) MARTINS, Vanessa; SILVA, Adriana Lopes da; TEODORO, Walcy Rosolia; VELOSA, Ana Paula Pereira; BALANCIN, Marcelo Luiz; CRUZ, Fernanda Ferreira; SILVA, Pedro Leme; ROCCO, Patricia Rieken Macedo; CAPELOZZI, Vera LuizaInhalation of silica particles causes silicosis: an occupational lung disease characterized by persistent inflammation with granuloma formation that leads to tissue remodeling and impairment of lung function. Although silicosis has been studied intensely, little is known about the crucial cellular mechanisms that initiate and drive the process of inflammation and fibrosis. Recently, found in inflammatory zone 1 (FIZZ1) protein, produced by alveolar macrophages and fibroblasts have been shown to induce the proliferation of myofibroblasts and their transdifferentiation, causing tissue fibrosis. Moreover, autoimmunogenic collagen V, produced by alveolar epithelial cells and fibroblasts, is involved in the pathophysiology of interstitial pulmonary fibrosis and bleomycin-induced lung fibrosis. Based on the aforementioned we hypothesized that FIZZ1 and collagen V may be involved in the silicotic granuloma process in mice lungs. Male C57BL/6 mice (N = 20) received intratracheal administration of silica particles (Silica; 20 mg in 50 mu L saline) or saline (Control; 50 mu L). After 15 days, the lung histology was performed through immunohistochemistry and morphometric analysis. Within silicotic granulomas, collagen V and FIZZ1 increased, while peroxisome proliferator-activated receptor gamma (PPAR gamma) positive cells decreased. In addition, the expression of proteins Notch-1, alpha smooth muscle actin (alpha-SMA) and macrophages163 (CD163) were higher in silicotic granulomas than control lungs. A significant positive correlation was found between collagen V and FIZZ1 (r = 0.70; p < 0.05), collagen V and Notch-1 (r = 0.72; p < 0.05), whereas Collagen V was inversely associated with peroxisome proliferator-activated receptor gamma (r=-0.69; p < 0.05). These findings suggested that collagen V association with FIZZ1, Notch-1 and PPAR gamma might be a key pathogenic mechanism for silicotic granulomas in mice lungs.
- In situ Evidence of Collagen V and Interleukin-6/Interleukin-17 Activation in Vascular Remodeling of Experimental Pulmonary Hypertension(2020) BATAH, Sabrina Setembre; ALDA, Maiara Almeida; FIGUEIRA, Rebeca Rodrigues Lopes Roslindo; CRUVINEL, Heloisa R.; SILVA, Luis Perdona Rodrigues da; MACHADO-RUGOLO, Juliana; VELOSA, Ana Paula; TEODORO, Walcy Rosolia; BALANCIN, Marcelo; SILVA, Pedro Leme; CAPELOZZI, Vera Luiza; FABRO, Alexandre TodorovicSeveral studies have reported the pathophysiologic and molecular mechanisms responsible for pulmonary arterial hypertension (PAH). However, the in situ evidence of collagen V (Col V) and interleukin-17 (IL-17)/interleukin-6 (IL-6) activation in PAH has not been fully elucidated. We analyzed the effects of collagen I (Col I), Col V, IL-6, and IL-17 on vascular remodeling and hemodynamics and its possible mechanisms of action in monocrotaline (MCT)-induced PAH. Twenty male Wistar rats were randomly divided into two groups. In the PAH group, animals received MCT 60 mg/kg intraperitoneally, whereas the control group (CTRL) received saline. On day 21, the pulmonary blood pressure (PAP) and right ventricular systolic pressure (RVSP) were determined. Lung histology (smooth muscle cell proliferation [alpha-smooth muscle actin; alpha-SMA] and periadventitial fibrosis), immunofluorescence (Col I, Col V, and alpha-SMA), immunohistochemistry (IL-6, IL-17, and transforming growth factor-beta [TGF-beta]), and transmission electron microscopy to detect fibronexus were evaluated. The RVSP (40 +/- 2 vs. 24 +/- 1 mm Hg, respectively; p < 0.0001), right ventricle hypertrophy index (65 +/- 9 and 25 +/- 5%, respectively; p < 0.0001), vascular periadventitial Col I and Col V, smooth muscle cell alpha-SMA+, fibronexus, IL-6, IL-17, and TGF-beta were higher in the MCT group than in the CTRL group. In conclusion, our findings indicate in situ evidence of Col V and IL-6/IL-17 activation in vascular remodeling and suggest that increase of Col V may yield potential therapeutic targets for treating patients with PAH.
conferenceObject Collagen V Expression Pattern as a Proposed Surrogate Marker for the Diagnosis of Malignant Mesothelioma(2020) BALANCIN, Marcelo; CLEMENTE, Leticia; REIS, Lucas; MARQUES-PIUBELLI, Mario; AB'SABER, Alexandre; CONTINI, Vitoria; VELOSA, Ana Paula Pereira; TEODORO, Walcy; SOUZA, Paola Da; CAPELOZZI, Vera LuizaconferenceObject Collagen V Expression Pattern as a Proposed Surrogate Marker for the Diagnosis of Malignant Mesothelioma(2020) BALANCIN, Marcelo; CLEMENTE, Leticia; REIS, Lucas; MARQUES-PIUBELLI, Mario; AB'SABER, Alexandre; CONTINI, Vitoria; VELOSA, Ana Paula Pereira; TEODORO, Walcy; SOUZA, Paola Da; CAPELOZZI, Vera Luiza- An integrative histopathologic clustering model based on immuno-matrix elements to predict the risk of death in malignant mesothelioma(2020) BALANCIN, Marcelo Luiz; TEODORO, Walcy Rosolia; FARHAT, Cecilia; MIRANDA, Tomas Jurandir de; ASSATO, Aline Kawassaki; SILVA, Neila Aparecida de Souza; VELOSA, Ana Paula; FALZONI, Roberto; AB'SABER, Alexandre Muxfeldt; RODEN, Anja C.; CAPELOZZI, Vera LuizaObjective Previous studies have reported a close relationship between malignant mesothelioma (MM) and the immune matricial microenvironment (IMM). One of the major problems in these studies is the lack of adequate adjustment for potential confounders. Therefore, the aim of this study was to identify and quantify risk factors such as IMM and various tumor characteristics and their association with the subtype of MM and survival. Methods We examined IMM and other tumor markers in tumor tissues from 82 patients with MM. These markers were evaluated by histochemistry, immunohistochemistry, immunofluorescence, and morphometry. Logistic regression analysis, cluster analysis, and Cox regression analysis were performed. Results Hierarchical cluster analysis revealed two clusters of MM that were independent of clinicopathologic features. The high-risk cluster included MM with high tumor cellularity, high type V collagen (Col V) fiber density, and low CD8(+) T lymphocyte density in the IMM. Our results showed that the risk of death was increased for patients with MM with high tumor cellularity (OR = 1.63, 95% CI = 1.29-2.89, P = .02), overexpression of Col V (OR = 2.60, 95% CI = 0.98-6.84, P = .04), and decreased CD8 T lymphocytes (OR = 1.001, 95% CI = 0.995-1.007, P = .008). The hazard ratio for the high-risk cluster was 2.19 (95% CI = 0.54-3.03, P < .01) for mortality from MM at 40 months. Conclusion Morphometric analysis of Col V, CD8(+) T lymphocytes, and tumor cellularity can be used to identify patients with high risk of death from MM.
- Dissecting and Reconstructing Matrix in Malignant Mesothelioma Through Histocell-Histochemistry Gradients for Clinical Applications(2022) BALANCIN, Marcelo Luiz; BALDAVIRA, Camila Machado; PRIETO, Tabatha Gutierrez; MACHADO-RUGOLO, Juliana; FARHAT, Cecilia; ASSATO, Aline Kawassaki; VELOSA, Ana Paula Pereira; TEODORO, Walcy Rosolia; AB'SABER, Alexandre Muxfeldt; TAKAGAKI, Teresa Yae; CAPELOZZI, Vera LuizaBackgroundMalignant pleural mesotheliomas (MM) are known for their heterogenous histology and clinical behavior. MM histology reveals three major tumor cell populations: epithelioid, sarcomatoid, and biphasic. Using a dissecting approach, we showed that histochemical gradients help us better understand tumor heterogeneity and reconsider its histologic classifications. We also showed that this method to characterize MM tumor cell populations provides a better understanding of the underlying mechanisms for invasion and disease progression. MethodsIn a cohort of 87 patients with surgically excised MM, we used hematoxylin and eosin to characterize tumor cell populations and Movat's pentachrome staining to dissect the ECM matrisome. Next, we developed a computerized semi-assisted protocol to quantify and reconstruct the ECM in 3D and examined the clinical association between the matricellular factors and patient outcome. ResultsEpithelioid cells had a higher matrix composition of elastin and fibrin, whereas, in the sarcomatoid type, hyaluronic acid and total collagen were most prevalent. The 3D reconstruction exposed the collagen I and III that form channels surrounding the neoplastic cell blocks. The estimated volume of the two collagen fractions was 14% of the total volume, consistent with the median estimated area of total collagen (12.05 mm(2)) for epithelioid MM. ConclusionDifferential patterns in matricellular phenotypes in MM could be used in translational studies to improve patient outcome. More importantly, our data raise the possibility that cancer cells can use the matrisome for disease expansion and could be effectively targeted by anti-collagen, anti-elastin, and/or anti-hyaluronic acid therapies.
- Different histological patterns of type-V collagen levels confer a matrices-privileged tissue microenvironment for invasion in malignant tumors with prognostic value(2020) BALANCIN, Marcelo Luiz; TEODORO, Walcy Rosolia; BALDAVIRA, Camila Machado; PRIETO, Tabatha Gutierrez; FARHAT, Cecilia; VELOSA, Ana Paula; SOUZA, Paola da Costa; YAEGASHI, Lygia Bertalha; AB'SABER, Alexandre Muxfeldt; TAKAGAKI, Teresa Yae; CAPELOZZI, Vera LuizaPrevious studies have reported a close relationship between type V collagen (Col V) and tumor invasion and motility in both breast cancer (BC) and lung cancer (LC). The present work aims to determine whether the extracellular-matrix (ECM)-defined microenvironment influences patient clinical outcome and investigate to which extent histological patterns of Col V expression in malignant cells have a prognostic effect in patients. To that end, we examined the expression of Col V in the tissues of 174 primary tumors (MM, N = 82; LC, N = 41; and BC, N = 46) by immunohistochemistry. We found: (1) diffuse strong green birefringence in membrane and cytoplasm individualizing malignant cells in MM; (2) a focal and weak birefringence mainly in cytoplasmic membrane involving groups of malignant cells in LC and BC; (3) higher average H-score of Col V in MM than in LC and BC samples; (4) a direct correlation between Col V histologic pattern and TNM stage IV, status and median overall survival; (5) patients with LC in TNM stage I, and Col V <= 41.7 IOD/mm2 had a low risk of death and a median survival time more than 20 months; (6) patients with MM in TNM stage IV and Col V > 41.7 IOD/mm2 presented a high risk of death and a median survival time of just 20 months. These findings suggest that high levels of Col V individualizing malignant cells, as observed in MM, and low levels grouping malignant cells, as observed in LC and BC, confers different immune-privileged tissue microenvironment for tumor invasion with impact on prognosis of the patients.