ROGER CHAMMAS
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Radiologia, Faculdade de Medicina - Docente
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/05 - Laboratório de Poluição Atmosférica Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
14 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 14
- The Promigratory Activity of the Matricellular Protein Galectin-3 Depends on the Activation of PI-3 Kinase(2011) MELO, Fabiana H. M.; BUTERA, Diego; JUNQUEIRA, Mara de Souza; HSU, Daniel K.; SILVA, Ana Maria Moura da; LIU, Fu-Tong; SANTOS, Marinilice F.; CHAMMAS, RogerExpression of galectin-3 is associated with sarcoma progression, invasion and metastasis. Here we determined the role of extracellular galectin-3 on migration of sarcoma cells on laminin-111. Cell lines from methylcholanthrene-induced sarcomas from both wild type and galectin-3(-/-) mice were established. Despite the presence of similar levels of laminin-binding integrins on the cell surface, galectin-3(-/-) sarcoma cells were more adherent and less migratory than galectin-3+/+ sarcoma cells on laminin-111. When galectin-3 was transiently expressed in galectin-3(-/-) sarcoma cells, it inhibited cell adhesion and stimulated the migratory response to laminin in a carbohydrate-dependent manner. Extracellular galectin-3 led to the recruitment of SHP-2 phosphatase to focal adhesion plaques, followed by a decrease in the amount of phosphorylated FAK and phospho-paxillin in the lamellipodia of migrating cells. The promigratory activity of extracellular galectin-3 was inhibitable by wortmannin, implicating the activation of a PI-3 kinase dependent pathway in the galectin-3 triggered disruption of adhesion plaques, leading to sarcoma cell migration on laminin-111.
- O-glycan sialylation alters galectin-3 subcellular localization and decreases chemotherapy sensitivity in gastric cancer(2016) SANTOS, Sofia N.; JUNQUEIRA, Mara S.; FRANCISCO, Guilherme; VILANOVA, Manuel; MAGALHAES, Ana; BARUFFI, Marcelo Dias; CHAMMAS, Roger; HARRIS, Adrian L.; REIS, Celso A.; BERNARDES, Emerson S.ST6GalNAc-I, the sialyltransferase responsible for sialyl-Tn (sTn) synthesis, has been previously reported to be positively associated with cancer aggressiveness. Here we describe a novel sTn-dependent mechanism for chemotherapeutic resistance. We show that sTn protects cancer cells against chemotherapeutic-induced cell death by decreasing the interaction of cell surface glycan receptors with galectin-3 and increasing its intracellular accumulation. Moreover, exogenously added galectin-3 potentiated the chemotherapeutics-induced cytotoxicity in sTn non-expressing cells, while sTn overexpressing cells were protected. We also found that the expression of sTn was associated with a reduction in galectin-3-binding sites in human gastric samples tumors. ST6GalNAc-I knockdown restored galectin-3-binding sites on the cell surface and chemotherapeutics sensibility. Our results clearly demonstrate that an interruption of O-glycans extension caused by ST6GalNAc-I enzymatic activity leads to tumor cells resistance to chemotherapeutic drugs, highlighting the need for the development of novel strategies to target galectin-3 and/or ST6GalNAc-I.
conferenceObject Near Infrared Fluorescence In-Vivo Imaging of Non-Hodgkin Lymphoma Using Cy7-Bevacizumab(2017) CAMACHO, Ximena; PERRONI, Carolina; JUNQUEIRA, Mara de Souza; FERNANDEZ, Marcelo; BUSTOS, Silvina; BUCHPIGUEL, Carlos; CHAMMAS, Roger; GAMBINI, Juan Pablo; CABRAL, Pablo; RIVA, Eloisa- Potential of [C-11](R)-PK11195 PET Imaging for Evaluating Tumor Inflammation: A Murine Mammary Tumor Model(2022) SOUZA, Aline Morais de; REAL, Caroline Cristiano; JUNQUEIRA, Mara de Souza; SOUZA, Larissa Estessi de; MARQUES, Fabio Luiz Navarro; BUCHPIGUEL, Carlos Alberto; CHAMMAS, Roger; SAPIENZA, Marcelo Tatit; FARIA, Daniele de PaulaBackground: Breast tumor inflammation is an immunological process that occurs mainly by mediation of Tumor-Associated Macrophages (TAM). Aiming for a specific measurement of tumor inflammation, the current study evaluated the potential of Positron Emission Tomography (PET) imaging with [C-11](R)-PK11195 to evaluate tumor inflammation in a mammary tumor animal model. Methods: Female Balb/C mice were inoculated with 4T1 cells. The PET imaging with [C-11](R)-PK11195 and [F-18]FDG was acquired 3 days, 1 week, and 2 weeks after cell inoculation. Results: The [C-11](R)-PK11195 tumor uptake increased from 3 days to 1 week, and decreased at 2 weeks after cell inoculation, as opposed to the [F-18]FDG uptake, which showed a slight decrease in uptake at 1 week and increased uptake at 2 weeks. In the control group, no significant differences occurred in tracer uptake over time. Tumor uptake of both radiopharmaceuticals is more expressed in tumor edge regions, with greater intensity at 2 weeks, as demonstrated by [C-11](R)-PK11195 autoradiography and immunofluorescence with TSPO antibodies and CD86 pro-inflammatory phenotype. Conclusion: The [C-11](R)-PK11195 was able to identify heterogeneous tumor inflammation in a murine model of breast cancer and the uptake varied according to tumor size. Together with the glycolytic marker [F-18]FDG, molecular imaging with [C-11](R)-PK11195 may provide a better characterization of inflammatory responses in cancer.
conferenceObject Radioactive and near-infrared fluorescence in vivo imaging of Non-Hodgkin Lymphoma using 99mTc/Cy7-Fab(Bevacizumab)(2021) CAMACHO, X.; PERRONI, C.; CARNEIRO, C.; JUNQUEIRA, M.; FARIA, D.; GARCIA, M.; FERNANDEZ, M.; BUCHPIGUEL, C.; CERECETTO, H.; CHAMMAS, R.; RIVA, E.; CABRAL, P.; GAMBINI, J.- Radio- and Fluorescent-Labeling of Rituximab Based on the Inverse Electron Demand Diels-Alder Reaction(2021) GARCIA, Maria Fernanda; JUNQUEIRA, Mara de Souza; MORORO, Janio da Silva; CAMACHO, Ximena; FARIA, Daniele de Paula; CARNEIRO, Camila de Godoi; GALLAZZI, Fabio; CHAMMAS, Roger; QUINN, Thomas; CABRAL, Pablo; CERECETTO, HugoThe bioorthogonal reaction between([1,2,4,5])tetrazines with trans-cyclooctene through the inverse electron demand Diels-Alder (IEDDA) has been described as powerful bioconjugation tool. In this work, we explore the IEDDA as a modular conjugation strategy for in vitro and in vivo labeling of Rituximab for the generation of radioactive and fluorescently label immunoconjugates. The strategy allowed the generation, in vitro and in vivo, of conjugated Rituximab with cyanine 5 and 7 and the gamma emmiter technetium-99m.
- Transient increase of tumor perfusion using hypertonic saline(2018) PATINO, Angelica M.; JUNQUEIRA, Mara S.; ZHANG, Xiaomeng; BAILEY, Kate; IBRAHIM-HASHIM, Arig; GILLIES, Robert J.; CHAMMAS, Roger
- 99mTechnetium-or Cy7-Labeled Fab(Tocilizumab) as Potential Multiple Myeloma Imaging Agents(2021) CAMACHO, Ximena; PERRONI, Carolina; MACHADO, Camila L.; CARNEIRO, Camila de Godoi; JUNQUEIRA, Mara de Souza; FARIA, Daniele; GARCIA, Maria F.; FERNANDEZ, Marcelo; ODDONE, Natalia; BENECH, Juan; BUCHPIGUEL, Carlos A.; CERECETTO, Hugo; CHAMMAS, Roger; RIVA, Eloisa; CABRAL, Pablo; GAMBINI, Juan P.Background: Multiple Myeloma (MM) is a malignant hematologic disorder and the second most common blood cancer. Interleukin-6 (IL-6) has been identified as a crucial factor for the proliferation and survival of MM cells and the overexpression of IL-6 receptor is being studied as a molecular target for therapeutic and diagnostic use in myelomas and other comorbidities. Tocilizumab is a humanized monoclonal antibody that binds IL-6R. Objective: We aim to label and evaluate Fab(Tocilizumab) with 99mTechnetium or Cy7 as potential MM imaging agents. Methods: IL-6R distribution was analyzed by Laser Confocal Microscopy (LCM) in MM cell lines. Fab(Tocilizumab) was produced by the digestion of Tocilizumab with papain for 24h at 37 degrees C, derivatized with NHS-HYNIC-Tfa and radiolabeled with Tc-99m. Radiochemical stability and in vitro cell assays were evaluated. Biodistribution and SPECT/CT were performed. Also, Fab(Tocilizumab) was labeled with Cy7 for in vivo fluorescence imaging up to 72h. Results: LCM analysis demonstrates IL-6R distribution on MM cell lines. Incubation with papain resulted in complete digestion of Tocilizumab and exhibited a good purity and homogeneity. Radiolabeling with Tc-99m via NHS-HYNIC-Tfa was found to be fast, easy, reproducible and stable, revealing high radiochemical purity and without interfering with IL-6R recognition. Biodistribution and SPECT/CT studies showed a quick blood clearance and significant kidney and MM engrafted tumor uptake. Cy7-Fab(Tocilizumab) fluorescent imaging allowed MM1S tumor identification up to 72h p.i. Conclusion: These new molecular imaging agents could potentially be used in the clinical setting for staging and follow-up of MM through radioactive whole-body IL-6R expression visualization in vivo. The fluorescent version could be used for tissue sample evaluation and to guide surgical excision, if necessary.
- Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo(2022) KE, W.; CHANDLER, M.; CEDRONE, E.; SAITO, R. F.; RANGEL, M. C.; JUNQUEIRA, M. De Souza; WANG, J.; SHI, D.; TRUONG, N.; RICHARDSON, M.; ROLBAND, L. A.; DRéAU, D.; BEDOCS, P.; CHAMMAS, R.; DOKHOLYAN, N. V.; DOBROVOLSKAIA, M. A.; AFONIN, K. A.The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. We introduce a user-friendly biomolecular platform based on modular RNA-DNA anticoagulant fibers programmed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a ""kill-switch""mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, we designed and tested a set of anticoagulant fibers that carry different thrombin-binding aptamers. All fibers are immunoquiescent, as confirmed in freshly collected human peripheral blood mononuclear cells. To assess interindividual variability, the anticoagulation is confirmed in the blood of human donors from the U.S. and Brazil. The anticoagulant fibers reveal superior anticoagulant activity and prolonged renal clearance in vivo in comparison to free aptamers. Finally, we confirm the efficacy of the ""kill-switch""mechanism in vivo in murine and porcine models.
conferenceObject Effects of sulforaphane association to conventional therapy for treating triple-negative breast cancer(2023) COUTINHO, L. L.; CHENG, R.; RIDNOUR, L.; JUNQUEIRA, M. S.; CHAMMAS, R.; WINK, D.; TORTELLI, T. C.; RANGEL, M.