MARCELO LUIZ BALANCIN
Projetos de Pesquisa
Unidades Organizacionais
10 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 10
- Pulmonary Neuroendocrine Neoplasms Overexpressing Epithelial-Mesenchymal Transition Mechanical Barriers Genes Lack Immune-Suppressive Response and Present an Increased Risk of Metastasis(2021) PRIETO, Tabatha Gutierrez; BALDAVIRA, Camila Machado; MACHADO-RUGOLO, Juliana; FARHAT, Cecilia; OLIVIERI, Eloisa Helena Ribeiro; SA, Vanessa Karen de; SILVA, Eduardo Caetano Abilio da; BALANCIN, Marcelo Luiz; SABER, Alexandre Muxfeldt Ab; TAKAGAKI, Teresa Yae; LIMA, Vladmir Claudio Cordeiro de; CAPELOZZI, Vera LuizaTypical carcinoids (TC), atypical carcinoids (AC), large cell neuroendocrine carcinomas (LCNEC), and small cell lung carcinomas (SCLC) encompass a bimodal spectrum of metastatic tumors with morphological, histological and histogenesis differences, The hierarchical structure reveals high cohesiveness between neoplastic cells by mechanical desmosomes barrier assembly in carcinoid tumors and LCNEC, while SCLC does not present an organoid arrangement in morphology, the neoplastic cells are less cohesive. However, the molecular mechanisms that lead to PNENs metastasis remain largely unknown and require further study. In this work, epithelial to mesenchymal transition (EMT) transcription factors were evaluated using a set of twenty-four patients with surgically resected PNENs, including carcinomas. Twelve EMT transcription factors (BMP1, BMP7, CALD1, CDH1, COL3A1, COL5A2, EGFR, ERBB3, PLEK2, SNAI2, STEAP1, and TCF4) proved to be highly expressed among carcinomas and downregulated in carcinoid tumors, whereas upregulation of BMP1, CDH2, KRT14 and downregulation of CAV2, DSC2, IL1RN occurred in both histological subtypes. These EMT transcription factors identified were involved in proliferative signals, epithelium desmosomes assembly, and cell motility sequential steps that support PNENs invasion and metastasis in localized surgically resected primary tumor. We used a two-stage design where we first examined the candidate EMT transcription factors using a whole-genome screen, and subsequently, confirmed EMT-like changes by transmission electron microscopy and then, the EMT-related genes that were differentially expressed among PNENs subtypes were predicted through a Metascape analysis by in silico approach. A high expression of these EMT transcription factors was significantly associated with lymph node and distant metastasis. The sequential steps for invasion and metastasis were completed by an inverse association between functional barrier created by PD-L1 immunosuppressive molecule and EMT transcriptional factors. Our study implicates upregulation of EMT transcription factors to high proliferation rates, mechanical molecular barriers disassembly and increased cancer cell motility, as a critical molecular event leading to metastasis risk in PNENs thus emerging as a promising tool to select and customize therapy.
conferenceObject Pleckstrin Homology-Like (PHLDA) Domain Family Members Immunoexpression as Prognostic Marker in Lung Cancer and Mesothelioma(2021) BALDAVIRA, C. Machado; PRIETO, T.; BALANCIN, M.; EHER, E.; FERNEZLIAN, S.; SOUZA, P.; NAGAI, M.; CAPELOZZI, V.- 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.
- Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group(2020) AMGAD, Mohamed; STOVGAARD, Elisabeth Specht; BALSLEV, Eva; THAGAARD, Jeppe; CHEN, Weijie; DUDGEON, Sarah; SHARMA, Ashish; KERNER, Jennifer K.; DENKERT, Carsten; YUAN, Yinyin; ABDULJABBAR, Khalid; WIENERT, Stephan; SAVAS, Peter; VOORWERK, Leonie; BECK, Andrew H.; MADABHUSHI, Anant; HARTMAN, Johan; SEBASTIAN, Manu M.; HORLINGS, Hugo M.; HUDECEK, Jan; CIOMPI, Francesco; MOORE, David A.; SINGH, Rajendra; ROBLIN, Elvire; BALANCIN, Marcelo Luiz; MATHIEU, Marie-Christine; LENNERZ, Jochen K.; KIRTANI, Pawan; CHEN, I-Chun; BRAYBROOKE, Jeremy P.; PRUNERI, Giancarlo; DEMARIA, Sandra; ADAMS, Sylvia; SCHNITT, Stuart J.; LAKHANI, Sunil R.; ROJO, Federico; COMERMA, Laura; BADVE, Sunil S.; KHOJASTEH, Mehrnoush; SYMMANS, W. Fraser; SOTIRIOU, Christos; GONZALEZ-ERICSSON, Paula; POGUE-GEILE, Katherine L.; KIM, Rim S.; RIMM, David L.; VIALE, Giuseppe; HEWITT, Stephen M.; BARTLETT, John M. S.; PENAULT-LLORCA, Frederique; GOEL, Shom; LIEN, Huang-Chun; LOIBL, Sibylle; KOS, Zuzana; LOI, Sherene; HANNA, Matthew G.; MICHIELS, Stefan; KOK, Marleen; NIELSEN, Torsten O.; LAZAR, Alexander J.; BAGO-HORVATH, Zsuzsanna; KOOREMAN, Loes F. S.; LAAK, Jeroen A. W. M. van der; SALTZ, Joel; GALLAS, Brandon D.; KURKURE, Uday; BARNES, Michael; SALGADO, Roberto; COOPER, Lee A. D.Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.
- The path to a better biomarker: application of a risk management framework for the implementation of PD-L1 and TILs as immuno-oncology biomarkers in breast cancer clinical trials and daily practice(2020) I, Paula Gonzalez-Ericsson; STOVGAARD, Elisabeth S.; SUA, Luz F.; REISENBICHLER, Emily; KOS, Zuzana; CARTER, Jodi M.; MICHIELS, Stefan; QUESNE, John Le; NIELSEN, Torsten O.; LAENKHOLM, Anne-Vibeke; FOX, Stephen B.; ADAM, Julien; BARTLETT, John M. S.; RIMM, David L.; QUINN, Cecily; PEETERS, Dieter; V, Maria Dieci; VINCENT-SALOMON, Anne; CREE, Ian; I, Akira Hida; BALKO, Justin M.; HAYNES, Harry R.; FRAHM, Isabel; ACOSTA-HAAB, Gabriela; BALANCIN, Marcelo; BELLOLIO, Enrique; YANG, Wentao; KIRTANI, Pawan; SUGIE, Tomoharu; EHINGER, Anna; CASTANEDA, Carlos A.; KOK, Marleen; MCARTHUR, Heather; SIZIOPIKOU, Kalliopi; BADVE, Sunil; FINEBERG, Susan; GOWN, Allen; VIALE, Giuseppe; SCHNITT, Stuart J.; PRUNERI, Giancarlo; PENAULT-LLORCA, Frederique; HEWITT, Stephen; THOMPSON, E. Aubrey; ALLISON, Kimberly H.; SYMMANS, William F.; BELLIZZI, Andrew M.; BROGI, Edi; MOORE, David A.; LARSIMONT, Denis; DILLON, Deborah A.; LAZAR, Alexander; LIEN, Huangchun; GOETZ, Matthew P.; BROECKX, Glenn; BAIRI, Khalid El; HARBECK, Nadia; CIMINO-MATHEWS, Ashley; SOTIRIOU, Christos; ADAMS, Sylvia; LIU, Shi-Wei; LOIBL, Sibylle; CHEN, I-Chun; LAKHANI, Sunil R.; JUCO, Jonathan W.; DENKERT, Carsten; BLACKLEY, Elizabeth F.; DEMARIA, Sandra; LEON-FERRE, Roberto; GLUZ, Oleg; ZARDAVAS, Dimitrios; EMANCIPATOR, Kenneth; ELY, Scott; LOI, Sherene; SALGADO, Roberto; SANDERS, MelindaImmune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying >= 1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. (c) 2020 Pathological Society of Great Britain and Ireland.
- COVID-19 bimodal clinical and pathological phenotypes(2022) BATAH, Sabrina S.; BENATTI, Maira N.; SIYUAN, Li; TELINI, Wagner M.; BARBOZA, Jamile O.; MENEZES, Marcelo B.; NADAI, Tales R.; SA, Keyla S. G.; VASWANI, Chirag M.; GUPTA, Sahil; ZAMBONI, Dario S.; WADA, Danilo T.; CALADO, Rodrigo T.; OLIVEIRA, Rene D. R.; LOUZADA-JUNIOR, Paulo; AUXILIADORA-MARTINS, Maria; VERAS, Flavio P.; CUNHA, Larissa D.; CUNHA, Thiago M.; LUPPINO-ASSAD, Rodrigo; BALANCIN, Marcelo L.; MORAIS, Sirlei S.; MARTINS, Ronaldo B.; ARRUDA, Eurico; CHAHUD, Fernando; SANTOS, Marcel Koenigkam; CETLIN, Andrea A.; CUNHA, Fernando Q.; SANTOS, Claudia dos; CAPELOZZI, Vera L.; FUKUOKA, Junya; ACHCAR, Rosane Duarte; FABRO, Alexandre T.
- The Immunological Landscape of M1 and M2 Macrophages and Their Spatial Distribution in Patients with Malignant Pleural Mesothelioma(2023) LABERIANO-FERNANDEZ, Caddie; BALDAVIRA, Camila Machado; MACHADO-RUGOLO, Juliana; TAMEGNON, Auriole; PANDURENGAN, Renganayaki Krishna; AB'SABER, Alexandre Muxfeldt; BALANCIN, Marcelo Luiz; TAKAGAKI, Teresa Yae; NAGAI, Maria Aparecida; CAPELOZZI, Vera Luiza; PARRA, Edwin RogerSimple Summary Identifying biomarkers to guide immunotherapy regimens remains an unmet clinical need in malignant pleural mesothelioma. A potential source of such markers is tumor-associated macrophages (TAMs), which contribute to the immunosuppressive microenvironment of mesothelioma. By examining distinct subsets of pleural macrophages to identify their gene signatures and protein expression, we found that TAMs preferentially contribute to M2a and M2b phenotypes, and M2a, M2b, and M2c more specifically contributed to immune tolerance. CD206, ARG1, CD274, CD163, and MRP8-14 are potential therapeutic targets in this disease.Abstract Background: Several tumor-associated macrophages (TAMs) have shown promise as prognosticators in cancer. Our aim was to validate the importance of TAMs in malignant pleural mesothelioma (MPM) using a two-stage design. Methods: We explored The Cancer Genome Atlas (TCGA-MESO) to select immune-relevant macrophage genes in MPM, including M1/M2 markers, as a discovery cohort. This computational cohort was used to create a multiplex immunofluorescence panel. Moreover, a cohort of 68 samples of MPM in paraffin blocks was used to validate the macrophage phenotypes and the co-localization and spatial distribution of these immune cells within the TME and the stromal or tumor compartments. Results: The discovery cohort revealed six immune-relevant macrophage genes (CD68, CD86, CD163, CD206, ARG1, CD274), and complementary genes were differentially expressed by M1 and M2 phenotypes with distinct roles in the tumor microenvironment and were associated with the prognosis. In addition, immune-suppressed MPMs with increased enrichment of CD68, CD86, and CD163 genes and high densities of M2 macrophages expressing CD163 and CD206 proteins were associated with worse overall survival (OS). Interestingly, below-median distances from malignant cells to specific M2a and M2c macrophages were associated with worse OS, suggesting an M2 macrophage-driven suppressive component in these tumors. Conclusions: The interactions between TAMs in situ and, particularly, CD206+ macrophages are highly relevant to patient outcomes. High-resolution technology is important for identifying the roles of macrophage populations in tissue specimens and identifying potential therapeutic candidates in MPM.
- The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group(2021) BAIRI, Khalid El; HAYNES, Harry R.; BLACKLEY, Elizabeth; FINEBERG, Susan; SHEAR, Jeffrey; TURNER, Sophia; FREITAS, Juliana Ribeiro de; SUR, Daniel; AMENDOLA, Luis Claudio; GHARIB, Masoumeh; KALLALA, Amine; ARUN, Indu; AZMOUDEH-ARDALAN, Farid; FUJIMOTO, Luciana; SUA, Luz F.; LIU, Shi-Wei; LIEN, Huang-Chun; KIRTANI, Pawan; BALANCIN, Marcelo; ATTAR, Hicham El; GULERIA, Prerna; YANG, Wenxian; SHASH, Emad; CHEN, I-Chun; BAUTISTA, Veronica; MOURA, Jose Fernando Do Prado; RAPOPORT, Bernardo L.; CASTANEDA, Carlos; SPENGLER, Eunice; ACOSTA-HAAB, Gabriela; FRAHM, Isabel; SANCHEZ, Joselyn; CASTILLO, Miluska; BOUCHMAA, Najat; ZIN, Reena R. Md; SHUI, Ruohong; ONYUMA, Timothy; YANG, Wentao; HUSAIN, Zaheed; WILLARD-GALLO, Karen; COOSEMANS, An; PEREZ, Edith A.; PROVENZANO, Elena; ERICSSON, Paula Gonzalez; RICHARDET, Eduardo; MEHROTRA, Ravi; SARANCONE, Sandra; EHINGER, Anna; RIMM, David L.; BARTLETT, John M. S.; VIALE, Giuseppe; DENKERT, Carsten; HIDA, Akira I.; SOTIRIOU, Christos; LOIBL, Sibylle; HEWITT, Stephen M.; BADVE, Sunil; SYMMANS, William Fraser; KIM, Rim S.; PRUNERI, Giancarlo; GOEL, Shom; FRANCIS, Prudence A.; INURRIGARRO, Gloria; YAMAGUCHI, Rin; GARCIA-RIVELLO, Hernan; HORLINGS, Hugo; AFQIR, Said; SALGADO, Roberto; ADAMS, Sylvia; KOK, Marleen; DIECI, Maria Vittoria; MICHIELS, Stefan; DEMARIA, Sandra; LOI, ShereneThe advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.
- 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.
- Association of Functional Polymorphism in CTLA-4 Gene with Survival in Non-Small Cell Lung Cancer: A Brazilian Study(2018) MACHADO-RUGOLO, J.; FABRO, A.; CUENTAS, E.; SA, V. De; RAINHO, C.; NAGAI, M.; CAPELOZZI, V.; BALANCIN, M.