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
21 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 21
- Hedgehog signaling pathway mediates tongue tumorigenesis in wild-type mice but not in Ga13-deficient mice(2014) SANTOS, Debora de Oliveira; LOYOLA, Adriano Mota; CARDOSO, Sergio Vitorino; CHAMMAS, Roger; LIU, Fu-Tong; FARIA, Paulo Rogerio deOral squamous cell carcinoma (OSCC) is one of the most aggressive cancers of the oral cavity and an important cause of death worldwide. Currently, there are limited clinical tools aiding clinicians to establish its early diagnosis, and genetic and epigenetic events leading to the pathogenesis of OSCC remain unsolved. The use of carcinogen-induced knocked out mouse models would help to improve its early detection and also determine the role of proteins such as galectin-3 (Gal3) in this process. Here we used a mouse model of oral carcinogenesis employing two mouse genotypes: wild-type (Gal3 +/+) and galectin-3-deficient mice (Gal3 -/-) challenged by the carcinogen 4NQO for 16 weeks. After induction, the expression of Wnt1, Wnt3A, Shh and Gli3 proteins in tongue samples was evaluated using an immunohistochemistry approach. All samples of dysplasia and carcinoma were negative for Wnt1. Wnt3A expression was detected in both Gal3 +/+ and Gal3 -/- mice, at similar levels. Wnt3A expression did not predict tongue tumorigenesis in either genotype. Dysplastic- and carcinoma-expressing Shh was statistically significantly higher in Gal3 +/+ mice than Gal3 -/- mice (p < 0.0001), and was associated with tongue tumorigenesis only in the former. Gli3 expression decreased and increased from dysplasia to carcinoma in Gal3 +/+ and Gal3 -/- mice, respectively, although the difference was not significant. The results suggest that activated Wnt signaling is present in both mice, and that the Hh signaling pathway might play a role in tongue carcinoma development in Gal3 +/+ mice.
- Prohibitin Expression Deregulation in Gastric Cancer Is Associated with the 3 ' Untranslated Region 1630 C > T Polymorphism and Copy Number Variation(2014) LEAL, Mariana Ferreira; CIRILO, Priscila Daniele Ramos; MAZZOTTI, Tatiane Katsue Furuya; CALCAGNO, Danielle Queiroz; WISNIESKI, Fernanda; DEMACHKI, Samia; MARTINEZ, Margarita Cortes; ASSUMPCAO, Paulo Pimentel; CHAMMAS, Roger; BURBANO, Rommel Rodriguez; SMITH, Marilia CardosoPHB is a reported oncogene and tumor suppressor in gastric cancer. Here, we evaluated whether the PHB copy number and the rs6917 polymorphism affect its expression in gastric cancer. Down-regulation and up-regulation of PHB were observed in the evaluated tumors. Reduced expression was associated with tumor dedifferentiation and cancer initiation. The T allele of the rs6917 polymorphism was associated with reduced PHB mRNA levels. Moreover, the up-regulation of PHB appeared to be regulated by the gain of additional gene copies. Thus, PHB copy number variation and differential expression of the rs6917 polymorphism may play a role in PHB transcriptional regulation.
- Emerging technologies in extracellular vesicle-based molecular diagnostics(2014) JIA, Shidong; ZOCCO, Davide; SAMUELS, Michael L.; CHOU, Michael F.; CHAMMAS, Roger; SKOG, Johan; ZAROVNI, Natasa; MOMEN-HERAVI, Fatemeh; KUO, Winston PatrickExtracellular vesicles (EVs), including exosomes and microvesicles, have been shown to carry a variety of biomacromolecules including mRNA, microRNA and other non-coding RNAs. Within the past 5 years, EVs have emerged as a promising minimally invasive novel source of material for molecular diagnostics. Although EVs can be easily identified and collected from biological fluids, further research and proper validation is needed in order for them to be useful in the clinical setting. In addition, innovative and more efficient means of nucleic acid profiling are needed to facilitate investigations into the cellular and molecular mechanisms of EV function and to establish their potential as useful clinical biomarkers and therapeutic tools. In this article, we provide an overview of recent technological improvements in both upstream EV isolation and downstream analytical technologies, including digital PCR and next generation sequencing, highlighting future prospects for EV-based molecular diagnostics.
- PAF Receptor and Tumor Growth(2014) JANCAR, Sonia; CHAMMAS, RogerThe receptor for the lipid mediator PAF (PAFR) is a G-protein coupled receptor expressed in several cell types. Besides PAF, a series of oxidized phospholipids can also bind to PAFR. Dying cells also express PAFR-ligands and, in both situations, scavenger receptors are involved as well. There is evidence that the scavenger receptor CD36 and PAFR associate in the macrophages membrane and signal in conjunction to induce a regulatory phenotype. In the tumor microenvironment, apoptotic cells are abundant due to hypoxia, and PAF-like phospholipids are generated. Engagement of PAFR expressed by tumor macrophages and dendritic cells induces a regulatory/tolerogenic phenotype and subverts the innate and adaptive immune response to the tumor. During cancer therapies, PAFR-ligands can be generated, further aggravating the immune suppression. Moreover, some tumor cells express PAFR and its activation by PAFR-ligands generated during chemotherapy induce anti-apoptotic factors, which protect the tumor cells from death induced by these treatments. It is proposed that PAFR antagonists, administered in combination with chemotherapy, may represent a promising strategy for cancer treatment.
- Mesenchymal Stem Cells Do Not Prevent Antibody Responses against Human alpha-L-Iduronidase when Used to Treat Mucopolysaccharidosis Type I(2014) MARTIN, Priscila Keiko Matsumoto; STILHANO, Roberta Sessa; SAMOTO, Vivian Yochiko; TAKIYA, Christina Maeda; PERES, Giovani Bravin; MICHELACCI, Yara Maria Correa da Silva; SILVA, Flavia Helena da; PEREIRA, Vanessa Goncalves; D'ALMEIDA, Vania; MARQUES, Fabio Luiz Navarro; OTAKE, Andreia Hanada; CHAMMAS, Roger; HAN, Sang WonMucopolysaccharidosis type I (MPSI) is an autosomal recessive disease that leads to systemic lysosomal storage, which is caused by the absence of alpha-L-iduronidase (IDUA). Enzyme replacement therapy is recognized as the best therapeutic option for MPSI; however, high titers of anti-IDUA antibody have frequently been observed. Due to the immunosuppressant properties of MSC, we hypothesized that MSC modified with the IDUA gene would be able to produce IDUA for a long period of time. Sleeping Beauty transposon vectors were used to modify MSC because these are basically less-immunogenic plasmids. For cell transplantation, 4x10(6) MSC-KO-IDUA cells (MSC from KO mice modified with IDUA) were injected into the peritoneum of KO-mice three times over intervals of more than one month. The total IDUA activities from MSC-KO-IDUA before cell transplantation were 9.6, 120 and 179 U for the first, second and third injections, respectively. Only after the second cell transplantation, more than one unit of IDUA activity was detected in the blood of 3 mice for 2 days. After the third cell transplantation, a high titer of anti-IDUA antibody was detected in all of the treated mice. Anti-IDUA antibody response was also detected in C57Bl/6 mice treated with MSC-WT-IDUA. The antibody titers were high and comparable to mice that were immunized by electroporation. MSC-transplanted mice had high levels of TNF-alpha and infiltrates in the renal glomeruli. The spreading of the transplanted MSC into the peritoneum of other organs was confirmed after injection of In-111-labeled MSC. In conclusion, the antibody response against IDUA could not be avoided by MSC. On the contrary, these cells worked as an adjuvant that favored IDUA immunization. Therefore, the humoral immunosuppressant property of MSC is questionable and indicates the danger of using MSC as a source for the production of exogenous proteins to treat monogenic diseases.
conferenceObject Synthesis and Preliminary Assessment of (99)m tc-HYNICF-ab's (Rituximab) for Non-Hodgkin Lymphoma Diagnosis(2014) CAMACHO, Ximena; MACHADO, Camila; BANCHERO, Agustina; GARCIA, Maria Fernanda; CALZADA, Victoria; FERNANDEZ, Marcelo; MORENO, Maria; GAMBINI, Juan Pablo; ALONSO, Omar; CHAMMAS, Roger; CABRAL, Pablo; RIVA, Eloisa- Galectin-3 disruption impaired tumoral angiogenesis by reducing VEGF secretion from TGF beta 1-induced macrophages(2014) MACHADO, Camila Maria Longo; ANDRADE, Luciana Nogueira Sousa; TEIXEIRA, Veronica Rodrigues; COSTA, Fabricio Falconi; MELO, Camila Morais; SANTOS, Sofia Nascimento dos; NONOGAKI, Suely; LIU, Fu-Tong; BERNARDES, Emerson Soares; CAMARGO, Anamaria Aranha; CHAMMAS, RogerIn order to study the role of galectin-3 in tumor angiogenesis associated with tumor-associated macrophages (TAM) and tumor parenchyma, the galectin-3 expression was reconstituted in Tm1 melanoma cell line that lacks this protein. Galectin-3-expressing cells (Tm1G3) and mock-vector transfected cells (Tm1N3) were injected into wild-type (WT) and galectin-3 knockout (KO) C57Bl/6 mice. Tumors originated from Tm1G3 were larger in tumor volume with enlarged functional vessels, decreased necrotic areas, and increased vascular endothelial growth factor (VEGF) protein levels. Galectin-3-nonexpressing-cells injected into WT and KO showed increased levels of transforming growth factor beta 1 (TGF beta 1) and, in WT animals this feature was also accompanied by increased VEGFR2 expression and its phosphorylation. In KO animals, tumors derived from galectin-3-expressing cells were infiltrated by CD68(+) -cells, whereas in tumors derived from galectin-3-nonexpressing-cells, CD68(+) cells failed to infiltrate tumors and accumulated in the periphery of the tumor mass. In vitro studies showed that Tm1G3 secreted more VEGF than Tm1N3 cells. In the latter case, TGF beta 1 induced VEGF production. Basal secretion of VEGF was higher in WT-bone marrow-derived macrophages (BMDM) than in KO-BMDM. TGF beta 1 induced secretion of VEGF only in WT-BMDM. Tm1G3-induced tumors had the Arginase I mRNA increased, which upregulated alternative macrophage (M2)/TAM induction. M2 stimuli, such as interleukin-4 (IL4) and TGF beta 1, increased Arginase I protein levels and galectin-3 expression in WTBMDM, but not in cells from KO mice. Hence, we report that galectin-3 disruption in tumor stroma and parenchyma decreases angiogenesis through interfering with the responses of macrophages to the interdependent VEGF and TGF beta 1 signaling pathways.
- Characterization of LGALS3 (galectin-3) as a player in DNA damage response(2014) CARVALHO, Renato S.; FERNANDES, Vanessa C.; NEPOMUCENO, Thales C.; RODRIGUES, Deivid C.; WOODS, Nicholas T.; SUAREZ-KURTZ, Guilherme; CHAMMAS, Roger; MONTEIRO, Alvaro N.; CARVALHO, Marcelo A.DNA damage repair (DDR) is an orchestrated process encompassing the injury detection to its complete resolution. DNA double-strand break lesions are repaired mainly by two distinct mechanisms: the error-free homologous recombination (HR) and the error-prone non-homologous end-joining. Galectin-3 (GAL3) is the unique member of the chimeric galectins subfamily and is reported to be involved in several cancer development and progression related events. Recently our group described a putative protein interaction between GAL3 and BARD1, the main partner of breast and ovarian cancer susceptibility gene product BRCA1, both involved in HR pathway. In this report we characterized GAL3/BARD1 protein interaction and evaluated the role of GAL3 in DDR pathways using GAL3 silenced human cells exposed to different DNA damage agents. In the absence of GAL3 we observed a delayed DDR response activation, as well as a decrease in the G(2)/M cell cycle checkpoint arrest associated with HR pathway. Moreover, using a TAP-MS approach we also determined the protein interaction network of GAL3.
- A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma(2014) PASINI, Fatima Solange; ZILBERSTEIN, Bruno; SNITCOVSKY, Igor; ROELA, Rosimeire Aparecida; MANGONE, Flavia R. Rotea; RIBEIRO JR., Ulysses; NONOGAKI, Suely; BRITO, Glauber Costa; CALLEGARI, Giovanna D.; CECCONELLO, Ivan; ALVES, Venancio Avancini Ferreira; ELUF-NETO, Jose; CHAMMAS, Roger; FEDERICO, Miriam Hatsue HondaThe TNM Classification of Malignant Tumours (TNM) staging system is the primary means of determining a prognosis for gastric adenocarcinoma (GC). However, tumor behavior in the individual patient is unpredictable and in spite of treatment advances, a classification of 'advanced stage' still portends a poor prognosis. Thus, further insights from molecular analyses are needed for better prognostic stratification and determination of new therapeutic targets. A total of fifty-one fresh frozen tumor samples from patients with histopathologically confirmed diagnoses of GC, submitted to surgery with curative intent, were included in the study. Total RNA was extracted from an initial group of fifteen samples matched for known prognostic factors, categorized into two subgroups, according to patient overall survival: poor (< 24 months) or favorable (at or above 24 months), and hybridized to Affymetrix Genechip human genome U133 plus 2.0 for genes associated with prognosis selection. Thirteen genes were selected for qPCR validation using those initial fifteen samples plus additional thirty-six samples. A total of 108 genes were associated with poor prognosis, independent of tumor staging. Using systems biology, we suggest that this panel reflects the dampening of immune/inflammatory response in the tumor microenvironment level and a shift to Th2/M2 activity. A gene trio (OLR1, CXCL11 and ADAMDEC1) was identified as an independent marker of prognosis, being the last two markers validated in an independent patient cohort. We determined a panel of three genes with prognostic value in gastric cancer, which should be further investigated. A gene expression profile suggestive of a dysfunctional inflammatory response was associated with unfavorable prognosis.
conferenceObject Differentially expressed genes in the lungs of fetuses mice exposed to ambient air pollution(2014) MENDES-LOPES, Thais; VERAS, Mariana; COSTA, Natalia; MAZZOTTI, Tatiane; BRITO, Glauber; CHAMMAS, Roger; SALDIVA, Paulo; MAUAD, Thais
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