ROGER CHAMMAS

(Fonte: Lattes)
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Lattes
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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

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Assunto: expression ×

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Agora exibindo 1 - 10 de 35
  • article 4 Citação(ões) na Scopus
    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 de
    Oral 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.
  • article 5 Citação(ões) na Scopus
    Melatonin Regulates the Daily Levels of Plasma Amino Acids, Acylcarnitines, Biogenic Amines, Sphingomyelins, and Hexoses in a Xenograft Model of Triple Negative Breast Cancer
    (2022) JUNIOR, Rubens Paula; CHUFFA, Luiz Gustavo de Almeida; SIMAO, Vinicius Augusto; SONEHARA, Nathalia Martins; CHAMMAS, Roger; REITER, Russel J.; ZUCCARI, Debora Aparecida Pires de Campos
    Metabolic dysregulation as a reflection of specific metabolite production and its utilization is a common feature of many human neoplasms. Melatonin, an indoleamine that is highly available during darkness, has a variety of metabolic functions in solid tumors. Because plasma metabolites undergo circadian changes, we investigated the role of melatonin on the profile of amino acids (AAs), biogenic amines, carnitines, sphingolipids, and hexoses present in the plasma of mice bearing xenograft triple negative breast cancer (MDA-MB-231 cells) over 24 h. Plasma concentrations of nine AAs were reduced by melatonin, especially during the light phase, with a profile closer to that of non-breast cancer (BC) animals. With respect to acylcarnitine levels, melatonin reduced 12 out of 24 molecules in BC-bearing animals compared to their controls, especially at 06:00 h and 15:00 h. Importantly, melatonin reduced the concentrations of asymmetric dimethylarginine, carnosine, histamine, kynurenine, methionine sulfoxide, putrescine, spermidine, spermine, and symmetric dimethylarginine, which are associated with the BC metabolite sets. Melatonin also led to reduced levels of sphingomyelins and hexoses, which showed distinct daily variations over 24 h. These results highlight the role of melatonin in controlling the levels of plasma metabolites in human BC xenografts, which may impact cancer bioenergetics, in addition to emphasizing the need for a more accurate examination of its metabolomic changes at different time points.
  • article 15 Citação(ões) na Scopus
    Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model
    (2012) CHAVES, K. C. B.; PERON, J. P. S.; CHAMMAS, R.; TURACA, L. T.; PESQUERO, J. B.; BRAGA, M. S.; FOGUER, K.; SCHOR, N.; BELLINI, M. H.
    One of the greatest challenges in urological oncology is renal cell carcinoma (RCC), which is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and respond positively to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of ES-based antiangiogenic therapy to activate tumor-associated endothelial cells in metastatic RCC (mRCC). Balb/c-bearing Renca cells were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. The T-cell subsets and lymphocyte populations of tumors, mediastinal lymph nodes and the spleen were assessed by flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed by real-time PCR, flow cytometry and immunohistochemistry analysis. ES gene therapy led to an increase in the percentage of infiltrating CD4-interferon (IFN)-gamma cells (P<0.05), CD8-IFN-gamma cells (P<0.01) and CD49b-tumor necrosis factor-alpha cells (P<0.01). In addition, ES therapy caused an increase at the mRNA level of ICAM-1 (1.4-fold; P<0.01) and VCAM-1 (1.5-fold) (control vs treated group; P<0.001). Through flow cytometry, we found a significant increase in the CD34/ICAM-1 cells (8.1-fold; P<0.001) and CD34/VCAM-1 cells (1.6-fold; P<0.05). ES gene therapy induced a significant increase in both T CD4 and CD8 cells in the lymph nodes and the spleen, suggesting that ES therapy may facilitate cell survival or clonal expansion. CD49b cells were also present in increased quantities in all of these organs. In this study, we demonstrate an antitumor inflammatory effect of ES in an mRCC model, and this effect is mediated by an increase in ICAM-1 and VCAM-1 expression in tumor-associated endothelial cells.
  • article 16 Citação(ões) na Scopus
    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, Roger
    Expression 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.
  • article 15 Citação(ões) na Scopus
    Plasma Exosome-Derived microRNAs as Potential Diagnostic and Prognostic Biomarkers in Brazilian Pancreatic Cancer Patients
    (2022) MARIN, Anelis Maria; MATTAR, Sibelle Botogosque; AMATUZZI, Rafaela Ferreira; CHAMMAS, Roger; UNO, Miyuki; ZANETTE, Dalila Luciola; AOKI, Mateus Nobrega
    Pancreatic cancer represents one of the leading causes of oncological death worldwide. A combination of pancreatic cancer aggressiveness and late diagnosis are key factors leading to a low survival rate and treatment inefficiency, and early diagnosis is pursued as a critical factor for pancreatic cancer. In this context, plasma microRNAs are emerging as promising players due to their non-invasive and practical usage in oncological diagnosis and prognosis. Recent studies have showed some miRNAs associated with pancreatic cancer subtypes, or with stages of the disease. Here we demonstrate plasma exosome-derived microRNA expression in pancreatic cancer patients and healthy individuals from Brazilian patients. Using plasma of 65 pancreatic cancer patients and 78 healthy controls, plasma exosomes were isolated and miRNAs miR-27b, miR-125b-3p, miR-122-5p, miR-21-5p, miR-221-3p, miR-19b, and miR-205-5p were quantified by RT-qPCR. We found that miR-125b-3p, miR-122-5p, and miR-205-5p were statistically overexpressed in the plasma exosomes of pancreatic cancer patients compared to healthy controls. Moreover, miR-205-5p was significantly overexpressed in European descendants, in patients with tumor progression and in those who died from the disease, and diagnostic ability by ROC curve was 0.86. Therefore, we demonstrate that these three microRNAs are potential plasma exosome-derived non-invasive biomarkers for the diagnosis and prognosis of Brazilian pancreatic cancer, demonstrating the importance of different populations and epidemiological bias.
  • article 33 Citação(ões) na Scopus
    Platelet-activating factor (PAF) receptor as a promising target for cancer cell repopulation after radiotherapy
    (2017) SILVA JR., I. A. da; CHAMMAS, R.; LEPIQUE, A. P.; JANCAR, S.
    A major drawback of radiotherapy is the accelerated growth of the surviving tumor cells. Radiotherapy generates a variety of lipids that bind to the receptor for platelet-activating factor, expressed by cells in the tumor microenvironment. In the present study, using the TC-1 tumor cell line, we found that irradiation induced a twofold increase in receptor expression and generated agonists of receptor. Irradiated cells induced a 20-fold increase in live TC-1 proliferation in vitro. Furthermore, subcutaneous co-injection of irradiated TC-1 cells with TC-1 expressing luciferase (TC-1 fluc(+)) markedly increased TC-1 fluc(+) proliferation in a receptor-dependent way. Moreover we used a human carcinoma cell line not expressing the PAF receptor (KBM) and the same cell transfected with the receptor gene (KBP). Following co-injection of live KBP cells with irradiated KBM in RAG mice, the tumor growth was significantly increased compared with tumor formed following co-injection of live KBM with irradiated KBM. This tumor cell repopulation correlated with increased infiltration of tumor-promoting macrophages (CD206+). We propose that receptor represents a possible target for improving the efficacy of radiotherapy through inhibition of tumor repopulation.
  • article 0 Citação(ões) na Scopus
    Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk
    (2024) UENAL, Pelin; LU, Ye; BUENO-DE-MESQUITA, Bas; EIJCK, Casper H. J. van; TALAR-WOJNAROWSKA, Renata; SZENTESI, Andrea; GAZOULI, Maria; KREIVENAITE, Edita; TAVANO, Francesca; MALECKA-WOJCIESKO, Ewa; EROSS, Balint; OLIVERIUS, Martin; BUNDUC, Stefania; AOKI, Mateus Nobrega; VODICKOVA, Ludmila; BOGGI, Ugo; GIACCHERINI, Matteo; KONDRACKIENE, Jurate; CHAMMAS, Roger; PALMIERI, Orazio; THEODOROPOULOS, George E.; BIJLSMA, Maarten F.; BASSO, Daniela; MOHELNIKOVA-DUCHONOVA, Beatrice; SOUCEK, Pavel; IZBICKI, Jakob R.; KIUDELIS, Vytautas; VANELLA, Giuseppe; ARCIDIACONO, Paolo Giorgio; WLODARCZYK, Barbara; HACKERT, Thilo; SCHOETTKER, Ben; UZUNOGLU, Faik G.; BAMBI, Franco; GOETZ, Mara; HLAVAC, Viktor; BRENNER, Hermann; PERRI, Francesco; CARRARA, Silvia; LANDI, Stefano; HEGYI, Peter; DIJK, Frederike; MAIELLO, Evaristo; CAPRETTI, Giovanni; TESTONI, Sabrina Gloria Giulia; PETRONE, Maria Chiara; STOCKER, Hannah; ERMINI, Stefano; ARCHIBUGI, Livia; GENTILUOMO, Manuel; CAVESTRO, Giulia Martina; PEZZILLI, Raffaele; FRANCO, Gregorio Di; MILANETTO, Anna Caterina; SPERTI, Cosimo; NEOPTOLEMOS, John P.; MORELLI, Luca; VOKACOVA, Klara; PASQUALI, Claudio; LAWLOR, Rita T.; BAZZOCCHI, Francesca; KUPCINSKAS, Juozas; CAPURSO, Gabriele; CAMPA, Daniele; CANZIAN, Federico
    Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 x 10-8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 x 10-7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 x 10-6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 x 10-5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.
  • article 23 Citação(ões) na Scopus
    Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout
    (2016) BALBO, Bruno E.; AMARAL, Andressa G.; FONSECA, Jonathan M.; CASTRO, Isac de; SALEMI, Vera M.; SOUZA, Leandro E.; SANTOS, Fernando dos; IRIGOYEN, Maria C.; QIAN, Feng; CHAMMAS, Roger; ONUCHIC, Luiz F.
    Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1(cond/cond) Nestin(cre) (CYG+) cystic mice exposed to increased blood pressure, at 5 to 6 and 20 to 24 weeks of age, and Pkd1(+/-) (HTG+) noncystic mice at 5-6 and 10-13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1(cond/cond) and Pkd1(+/+) controls. Hearts from CYG+ and HTG+ mice presented reduced polycystin-1 expression, increased apoptosis, and mild fibrosis. Since galectin-3 has been associated with heart dysfunction, we studied it as a potential modifier of the ADPKD cardiac phenotype. Double-mutant Pkd1(cond/cond):Nestin(cre);Lgals(3-/-) (CYG-) and Pkd1(+/-);Lgals(3-/-) (HTG-) mice displayed improved cardiac deformability and systolic parameters compared to single -mutants, not differing from the controls. CYG- and HTG- showed decreased apoptosis and fibrosis. Analysis of a severe cystic model (Pkd1(v/v); VVG+) showed that Pkd1(v/v);Lgals(3-/-) (VVG-) mice have longer survival, decreased cardiac apoptosis and improved heart function compared to VVG+. CYG- and VVG- animals showed no difference in renal cystic burden compared to CYG+ and VVG+ mice. Thus, myocardial dysfunction occurs in different Pkdl-deficient models and suppression of galectin-3 expression rescues this phenotype.
  • article 12 Citação(ões) na Scopus
    The inactive form of glycogen synthase kinase-3 beta is associated with the development of carcinomas in galectin-3 wild-type mice, but not in galectin-3-deficient mice
    (2012) MENDONCA, Daniella Fernandes; CHAMMAS, Roger; LIU, Fu-Tong; NONOGAKI, Suely; CARDOSO, Sergio Vitorino; LOYOLA, Adriano Mota; FARIA, Paulo Rogerio de
    Galectin-3 has been implicated in the tumor development via its mediation of the Wnt signaling pathway. Likewise, glycogen synthase kinase-3beta (GSK3 beta) also plays a role in the Wnt signaling pathway by controlling the levels of cytoplasmic beta-catenin. Altered GSK3 beta expression has been described in various tumors, but to date, there are no studies evaluating its expression in models of oral carcinogenesis. Additionally, it is unknown whether the absence of galectin-3 regulates the expression of GSK3 beta. To this end, Gal3-deficient (Gal3(-/-)) and wild-type (Gal3(+/+)) male mice were treated with 4NQO for 16 weeks and sacrificed at week 16 and 32. The tongues were removed, processed, and stained with H&E to detect dysplasias and carcinomas. An immunohistochemical assay was performed to determine the level of P-GSK3 beta-Ser9 expression in both groups. Carcinomas were more prevalent in Gal3(+/+) than Gal3(-/-) mice (55.5% vs. 28.5%), but no statistical difference was reached. In the dysplasias, the proportion of cells positive for P-GSK3 beta-Ser9 was slightly higher in Gal3(+/+) than Gal3(-/-) mice (63% vs. 61%). In the carcinomas, a significant difference between Gal3(+/+) and Gal3(-/-) mice was found (74% vs. 59%; p=0.02). P-GSK3 beta-Ser9-positive cells slightly decreased from the progression of dysplasias to carcinomas in Gal3(-/-) mice (61% vs. 59%; p>0.05). However, a significant increase in P-GSK3 beta-Ser9 expression was observed from dysplasias to carcinomas in Gal3(+/+) mice (63% vs. 74%; p=0.01). In conclusion, these findings suggest that fully malignant transformation of the tongue epithelium is associated with increased P-GSK3 beta-Ser9 expression in Gal3(+/+) mice, but not in Gal3(-/-) mice.
  • article 20 Citação(ões) na Scopus
    Lack of Galectin-3 Disturbs Mesenteric Lymph Node Homeostasis and B Cell Niches in the Course of Schistosoma mansoni Infection
    (2011) OLIVEIRA, Felipe L.; BRAND, Camila; PAULA, Adelzon A.; ARCANJO, Katia D.; HSU, Daniel K.; LIU, Fu-Tong; TAKIYA, Christina M.; BOROJEVIC, Radovan; CHAMMAS, Roger; EL-CHEIKH, Marcia C.
    Galectin-3 is a beta-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs) during chronic schistosomiasis, using WT and galectin-3(-/-) mice. Schistosoma mansoni synthesizes GalNAc beta 1-4(Fuc alpha 1-3) GlcNAc(Lac-DiNAc) structures (N-acetylgalactosamine beta 1-4 N-acetylglucosamine), which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/-) mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+)/PI(-) cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in nonlymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S. mansoni.