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
15 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 15
- [(99)mTc(CO)(3)]- Radiolabeled Bevacizumab: In vitro and in vivo Evaluation in a Melanoma Model(2013) CAMACHO, Ximena; GARCIA, Maria Fernanda; CALZADA, Victoria; FERNANDEZ, Marcelo; CHABALGOITY, Jose A.; MORENO, Maria; AGUIAR, Rodrigo Barbosa de; ALONSO, Omar; GAMBINI, Juan Pablo; CHAMMAS, Roger; CABRAL, PabloIntroduction: Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several tumor types, including melanoma. Bevacizumab, a monoclonal antibody against VEGF, could be used as an imaging tool in preclinical studies. Objective: To radiolabel bevacizumab with [Tc-99m(CO)(3)(OH2)(3)]+ and evaluate it in vivo and in vitro for melanoma imaging properties. Methods: Bevacizumab was radiolabeled with [Tc-99m(CO)(3)(OH2)(3)]+ ion in saline. The radiochemical stability of the labeled antibody was assessed. The biodistribution and scintigraphy imaging of the radiolabeled antibody were evaluated in normal C57BL/6J mice and in C57BL/6J mice bearing murine B16F1 melanoma tumors. Immunoreactivity of bevacizumab to murine tumors was determined from direct immunofluorescence and immunoblotting assays. Results: We demonstrate that Tc-99m(CO)(3) -bevacizumab was stable. In vivo biodistribution studies revealed that tumor uptake of Tc-99m(CO)(3)-bevacizumab was 2.64 and 2.51 %ID/g at 4 and 24 h postinjection. Scintigraphy image studies showed tumor selective uptake of Tc-99m(CO)(3)-bevacizumab in the tumor-bearing mice. This affinity was confirmed by immunoassays performed on B16F10 tumor samples. Conclusions: Tc-99m(CO)(3)-bevacizumab could be used as an approach for tumor nuclear imaging in preclinical studies. This should be useful to provide insights into the angiogenic stimulus before and after chemotherapy, which might help improve current antitumor therapy.
- Endoplasmic reticulum stress conditioned melanoma cell lines to chemotherapy-induced cell death.(2013) SAITO, Renata F.; OTAKE, Andreia H.; CORTES, Margarita M.; CHAMMAS, Roger
bookPart Biologia molecular dos melanomas(2013) FRANCISCO, Guilherme; OTAKE, Andréia Hanada; SAITO, Renata de Freitas; CHAMMAS, Roger- Neutrophils LL-37 migrate to the nucleus during overwhelming infection(2013) SILVA, Fabiano Pinheiro da; MEDEIROS, Maria Cristina Rodrigues; SANTOS, Angela Batista Gomes dos; FERREIRA, Marcelo Alves; GARIPPO, Ana Lucia; CHAMMAS, Roger; CALDINI, Elia; VELASCO, Irineu Tadeu; SOUZA, Heraldo Possolo de; MACHADO, Marcel Cerqueira CesarLL-37 is the only cathelicidin produced by human cells. It is secreted by a variety of cell types, including monocyte/macrophages, neutrophils, mast cells, keratinocytes and epithelial cells, acting on the extracellular milieu by directly killing bacteria or boosting innate immunity. Here, we show that LL-37 translocates to the nucleus following overwhelming infection, putting in evidence that its role may be even broader, with new potential important implications to cell biology. Future studies are necessary to address if LL-37 is able to induce or affect transcription, since it can lead to a novel cell signaling pathway that probably will contribute to the understanding of complex diseases.
- Galectin-3 negatively regulates the frequency and function of CD4(+)CD25(+)Foxp3(+) regulatory T cells and influences the course of Leishmania major infection(2013) FERMINO, Marise L.; DIAS, Fabricio C.; LOPES, Carla D.; SOUZA, Maria A.; CRUZ, Angela K.; LIU, Fu-Tong; CHAMMAS, Roger; ROQUE-BARREIRA, Maria Cristina; RABINOVICH, Gabriel A.; BERNARDES, Emerson S.Galectin-3, an endogenous glycan-binding protein, plays essential roles during microbial infection by modulating innate and adaptive immunity. However, the role of galectin-3 within the CD4(+)CD25(+)Foxp3(+) T regulatory (T-REG) cell compartment has not yet been explored. Here, we found, in a model of Leishmania major infection, that galectin-3 deficiency increases the frequency of peripheral T-REG cells both in draining lymph nodes (LNs) and sites of infection. These observations correlated with an increased severity of the disease, as shown by increased footpad swelling and parasite burden. Galectin-3-deficient (Lgals3(-/-)) T-REG cells displayed higher CD103 expression, showed greater suppressive capacity, and synthesized higher amounts of IL-10 compared with their wild-type (WT) counterpart. Furthermore, both T-REG cells and T effector (T-EFF) cells from Lgals3(-/-) mice showed higher expression of Notch1 and the Notch target gene Hes-1. Interestingly, Notch signaling components were also altered in both T-REG and T-EFF cells from uninfected Lgals3(-/-) mice. Thus, endogenous galectin-3 regulates the frequency and function of CD4(+)CD25(+)Foxp3(+) T-REG cells and alters the course of L. major infection.
- Polymorphisms in the p27(kip-1) and prohibitin genes denote novel genes associated with melanoma risk in Brazil, a high ultraviolet index region(2013) FRANCISCO, Guilherme; GONCALVES, Fernanda T.; LUIZ, Olinda C.; SAITO, Renata F.; TOLEDO, Rodrigo A.; SEKIYA, Tomoko; TORTELLI JR., Tharcisio C.; VIOLLA, Esther D. V. B.; MAZZOTTI, Tatiane K. Furuya; CIRILO, Priscila D. R.; FESTA-NETO, Cyro; SANCHES, Jose A.; GATTAS, Gilka J. F.; ELUF-NETO, Jose; CHAMMAS, RogerUltraviolet (UV) radiation is a major environmental risk factor to the development of cutaneous melanoma as it induces pyrimidine dimers in DNA. Genes that exert their function by arresting the cell cycle are critical to avoid carcinogenic mutations, allowing the processing of DNA repair systems. This study was carried out to evaluate the role of polymorphisms in cell cycle genes such as TP53, p27(kip-1), CDKN2A, prohibitin, and GADD153 in melanoma risk as well as their influence on known risk factors in a high UV index region. A hospital-based case-control study was carried out in Brazil to evaluate the contribution of polymorphisms in cell cycle genes toward melanoma risk. The study comprised 202 melanoma patients and 210 controls. The polymorphisms analyzed were TP53 Arg72Pro, p27(kip-1) Val109Gly, GADD153 Phe10Phe (rs697221), CDKN2A 3 ' UTR C540G, and prohibitin 3 ' UTR C1703T. As regards, p27(kip-1) Val109Gly, both heterozygous and homozygous Gly genotypes were shown to be protective genotypes on calculating both crude and adjusted odds ratios (ORs) for age, sex, and educational level [OR 0.37; 95% confidence interval (CI) 0.16-0.87; P < 0.05]. Similarly, the prohibitin TT genotype increased melanoma risk in the crude and adjusted analyses (OR 2.40; 95% CI 1.10-5.26; P < 0.05). The p27(kip-1) Gly protective genotype decreased the risk for melanoma in a stratified analysis of the known risk factors such as hair and eye color, sunburns, pigmented lesions, and European ancestry. The prohibitin TT genotype increased the risk of melanoma by such host factors. Our results showed for the first time that polymorphisms in p27(kip-1) Val109Gly and in prohibitin 3 ' UTR C1703T genotypes modulate the risk to melanoma in a high UV index region. Melanoma Res 23: 231-236 (C) 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
- A novel proteasome inhibitor acting in mitochondrial dysfunction, ER stress and ROS production(2013) MARIA, Durvanei Augusto; SOUZA, Jean Gabriel de; MORAIS, Katia L. P.; BERRA, Carolina Maria; ZAMPOLLI, Hamilton de Campos; DEMASI, Marilene; SIMONS, Simone Michaela; SAITO, Renata de Freitas; CHAMMAS, Roger; CHUDZINSKI-TAVASSI, Ana MarisaIn cancer-treatment, potentially therapeutic drugs trigger their effects through apoptotic mechanisms. Generally, cell response is manifested by Bcl-2 family protein regulation, the impairment of mitochondrial functions, and ROS production. Notwithstanding, several drugs operate through proteasome inhibition, which, by inducing the accumulation and aggregation of misfolded or unfolded proteins, can lead to endoplasmic reticulum (ER) stress. Accordingly, it was shown that Amblyomin-X, a Kunitz-type inhibitor identified in the transcriptome of the Amblyomma cajennense tick by ESTs sequence analysis of a cDNA library, obtained in recombinant protein form, induces apoptosis in murine renal adenocarcinoma (RENCA) cells by: inducing imbalance between pro- and anti-apoptotic Bcl-2 family proteins, dysfunction/mitochondrial damage, production of reactive oxygen species (ROS), caspase cascade activation, and proteasome inhibition, all ER-stress inductive. Moreover, there was no manifest action on normal mouse-fibroblast cells (NHI3T3), suggesting an Amblyomin-X tumor-cell selectivity. Taken together, these evidences indicate that Amblyomin-X could be a promising candidate for cancer therapy.
- Implications on glycobiological aspects of tumor hypoxia in breast ductal carcinoma in situ(2013) REGO, Moacyr Jesus Barreto de Melo; MELLO, Gabriela Souto Vieira de; SANTOS, Carlos Andre da Silva; CHAMMAS, Roger; BELTRAO, Eduardo Isidoro CarneiroBreast carcinoma is one of the most common neoplasia and the first cause of women cancer related deaths worldwide. In the past few years with diagnostic increment, the number of patients diagnosed with ductal carcinoma in situ (DCIS) increased considerably and opened up new ways in research and new dilemmas in diagnostic and clinical practice. This work aimed to evaluate differences in Galectin-1 and Galectin-3 expression and lectins ligands profile on DCIS cells in hypoxic microenvironment. Lectin histochemistry and immunohistochemistry were performed with Concanavalin A, Wheat Germ Agglutinin, Peanut Agglutinin and Ulex europaeus Agglutinin lectins and with anti-Galectin-1 and anti-Galectin-3 antibodies. Lectin ligands were more recognized in hypoxic lesions by Concanavalin A (p = 0.0019), Wheat Germ Agglutinin (p < 0.001) and Ulex europaeus Agglutinin (p = 0.0014), but not by Peanut Agglutinin (p = 0.5779) when compared to non-hypoxic. Galectin-1 was not observed in all cases analyzed on both groups, differing from Galectin-3 that was overexpressed on cytoplasm of DCIS hypoxic group in relation to control group (p = 0.031). As far as we are concerned, this is the first paper that describes glycobiological alterations in breast cancer hypoxic environment in vivo that could be used to validate in vitro models on this aspect. Moreover, comedogenic/necrotic carcinomas were usually associated with poor-prognostic than others, and our results show that glycosylation may play an important role in this event.
- Vascular endothelial growth factor as a biomarker for endostatin gene therapy(2013) BRAGA, Marina Souza; TURACA, Thiago Lauro; FOGUER, Karen; CHAVES, Karen Cristina Barbosa; PESQUERO, Joao Bosco; CHAMMAS, Roger; SCHOR, Nestor; BELLINI, Maria HelenaRenal cell carcinoma (RCC) is characterized by high vascular endothelial growth factor (VEGF) production and, consequently, excessive angiogenesis. Several strategies have been developed to target angiogenesis as a method for treating metastatic RCC (mRCC). Endostatin (ES) is a C-terminal fragment of collagen XVIII that has antiangiogenic activity. The aim of this study was to investigate the predictive value of circulating VEGF-A in a murine model of mRCC after ES gene therapy. ES therapy did not affect the levels of collagen XVIII/ES or ES in the tissue. The circulating level of ES was increased in the control and ES-treated groups (normal vs. control, P < 0.05 and ES-treated vs. control, P < 0.001), and the intratumoral vessels were significantly decreased (ES-treated vs. control, P < 0.05). ES therapy decreased the VEGF mRNA levels. The tissue and circulating levels of VEGF in the control group were significantly higher than normal (P < 0.01 and P < 0.05, respectively). Treatment with ES significantly reduced the VEGF concentrations in both compartments (P < 0.001 for tissue and P < 0.05 for plasma). Our findings indicate that in addition to the directly targeted tumor vessels, ES exerts its antitumor effect by down-regulating VEGF gene expression in renal tumor cells. Additionally, our findings point to the predictive value of VEGF for ES therapy.
- Characterization of risk factors in breast cancer young adult patients(2013) ENCINAS, G.; DIZ, M. D. P. E.; LYRA, E. C.; KATAYAMA, M. L. H.; PASINI, F. S.; BRENTANI, M. M.; CHAMMAS, R.; GOES, J. C. G. S.; FOLGUEIRA, M. A. A. K.