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: cancer ×

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  • 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 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 45 Citação(ões) na Scopus
    Emerging Autophagy Functions Shape the Tumor Microenvironment and Play a Role in Cancer Progression-Implications for Cancer Therapy
    (2020) BUSTOS, Silvina Odete; ANTUNES, Fernanda; RANGEL, Maria Cristina; CHAMMAS, Roger
    The tumor microenvironment (TME) is a complex environment where cancer cells reside and interact with different types of cells, secreted factors, and the extracellular matrix. Additionally, TME is shaped by several processes, such as autophagy. Autophagy has emerged as a conserved intracellular degradation pathway for clearance of damaged organelles or aberrant proteins. With its central role, autophagy maintains the cellular homeostasis and orchestrates stress responses, playing opposite roles in tumorigenesis. During tumor development, autophagy also mediates autophagy-independent functions associated with several hallmarks of cancer, and therefore exerting several effects on tumor suppression and/or tumor promotion mechanisms. Beyond the concept of degradation, new different forms of autophagy have been described as modulators of cancer progression, such as secretory autophagy enabling intercellular communication in the TME by cargo release. In this context, the synthesis of senescence-associated secretory proteins by autophagy lead to a senescent phenotype. Besides disturbing tumor treatment responses, autophagy also participates in innate and adaptive immune signaling. Furthermore, recent studies have indicated intricate crosstalk between autophagy and the epithelial-mesenchymal transition (EMT), by which cancer cells obtain an invasive phenotype and metastatic potential. Thus, autophagy in the cancer context is far broader and complex than just a cell energy sensing mechanism. In this scenario, we will discuss the key roles of autophagy in the TME and surrounding cells, contributing to cancer development and progression/EMT. Finally, the potential intervention in autophagy processes as a strategy for cancer therapy will be addressed.
  • article 15 Citação(ões) na Scopus
    Amblyomin-X induces ER stress, mitochondrial dysfunction, and caspase activation in human melanoma and pancreatic tumor cell
    (2016) MORAIS, Katia L. P.; PACHECO, Mario Thiego Fernandes; BERRA, Carolina Maria; BOSCH, Rosemary V.; SCIANI, Juliana Mozer; CHAMMAS, Roger; SAITO, Renata de Freitas; IQBAL, Asif; CHUDZINSKI-TAVASSI, Ana Marisa
    During the last two decades, new insights into proteasome function and its role in several human diseases made it a potential therapeutic target. In this context, Amblyomin-X is a Kunitz-type FXa inhibitor similar to endogenous tissue factor pathway inhibitor (TFPI) and is a novel proteasome inhibitor. Herein, we have demonstrated Amblyomin-X cytotoxicity to different tumor cells lines such as pancreatic (Panc1, AsPC1BxPC3) and melanoma (SK-MEL-5 and SK-MEL-28). Of note, Amblyomin-X was not cytotoxic to normal human fibroblast cells. In addition, Amblyomin-X promoted accumulation of ER stress markers (GRP78 and GADD153) in sensitive (SK-MEL-28) and bortezomib-resistant (Mia-PaCa-2) tumor cells. The intracellular calcium concentration [Ca2+] (i) was slightly modulated in human tumor cells (SK-MEL-28 and Mia-PaCa-2) after 24 h of Amblyomin-X treatment. Furthermore, Amblyomin-X induced mitochondrial dysfunction, cytochrome-c release, PARP cleavage, and activation of caspase cascade in both human tumor (SK-MEL-28 and Mia-PaCa-2) cells. These investigations might help in further understanding of the antitumor properties of Amblyomin-X.
  • article 0 Citação(ões) na Scopus
    Exploring the Neandertal legacy of pancreatic ductal adenocarcinoma risk in Eurasians
    (2023) PICCARDI, Margherita; GENTILUOMO, Manuel; BERTONCINI, Stefania; PEZZILLI, Raffaele; EROSS, Balint; BUNDUC, Stefania; UZUNOGLU, Faik G.; TALAR-WOJNAROWSKA, Renata; VANAGAS, Tomas; SPERTI, Cosimo; OLIVERIUS, Martin; AOKI, Mateus Nobrega; ERMINI, Stefano; HUSSEIN, Tamas; BOGGI, Ugo; JAMROZIAK, Krzysztof; MAIELLO, Evaristo; MORELLI, Luca; VODICKOVA, Ludmila; FRANCO, Gregorio Di; LANDI, Stefano; SZENTESI, Andrea; LOVECEK, Martin; PUZZONO, Marta; TAVANO, Francesca; LAARHOVEN, Hanneke W. M. van; ZERBI, Alessandro; MOHELNIKOVA-DUCHONOVA, Beatrice; STOCKER, Hannah; COSTELLO, Eithne; CAPURSO, Gabriele; GINOCCHI, Laura; LAWLOR, Rita T.; VANELLA, Giuseppe; BAZZOCCHI, Francesca; IZBICKI, Jakob R.; LATIANO, Anna; BUENO-DE-MESQUITA, Bas; PISANI, Ruggero Ponz de Leon; SCHOETTKER, Ben; SOUCEK, Pavel; HEGYI, Peter; GAZOULI, Maria; HACKERT, Thilo; KUPCINSKAS, Juozas; POSKIENE, Lina; TACELLI, Matteo; ROTH, Susanne; CARRARA, Silvia; PERRI, Francesco; HLAVAC, Viktor; THEODOROPOULOS, George E.; BUSCH, Olivier R.; MAMBRINI, Andrea; EIJCK, Casper H. J. van; ARCIDIACONO, Paolo; SCARPA, Aldo; PASQUALI, Claudio; BASSO, Daniela; LUCCHESI, Maurizio; MILANETTO, Anna Caterina; NEOPTOLEMOS, John P.; CAVESTRO, Giulia Martina; JANCIAUSKAS, Dainius; CHEN, Xuechen; CHAMMAS, Roger; GOETZ, Mara; BRENNER, Hermann; ARCHIBUGI, Livia; DANNEMANN, Michael; CANZIAN, Federico; TOFANELLI, Sergio; CAMPA, Daniele
    BackgroundThe genomes of present-day non-Africans are composed of 1-3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50-60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations.ResultsThe high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19-1.54, P = 3.59 x 10(-6)), with a P-value close to a threshold that takes into account multiple testing.ConclusionsOur results show only a minimal contribution of Neandertal SNPs to PDAC risk.
  • article 41 Citação(ões) na Scopus
    Preclinical anticancer effectiveness of a fraction from Casearia sylvestris and its component Casearin X: in vivo and ex vivo methods and microscopy examinations
    (2016) FERREIRA, Paulo Michel Pinheiro; BEZERRA, Daniel Pereira; SILVA, Jurandy do Nascimento; COSTA, Marcilia Pinheiro da; FERREIRA, Jose Roberto de Oliveira; ALENCAR, Nylane Maria Nunes; FIGUEIREDO, Ingrid Samantha Tavares de; CAVALHEIRO, Alberto Jose; MACHADO, Camila Maria Longo; CHAMMAS, Roger; ALVES, Ana Paula Negreiros Nunes; MORAES, Manoel Odorico de; PESSOA, Claudia
    Ethnopharmacological relevance: Casearia sylvestris (Salicaceae) is found in South America and presents antiulcerogenic, cytotoxic, antimicrobial, anti-inflammatory and antihypertensive activities. Aim of the study: To assess the in vivo and ex vivo antitumor action of a fraction with casearins (FC) and its main component- Casearin X-isolated from C sylvestris leaves. Materials and methods: Firstly, Sarcoma 180 bearing Swiss mice were treated with FC and Cas X for 7 days. Secondly, BALB/c nude animals received hollow fibers with colon carcinoma (HCT-116) or glioblastoma (SF-295) cells and were treated with FC for 4 days. On 5th day, proliferation was determined by MIT assay. Results: FC 10 and 25 mg/kg/day i.p. and 50 mg/kg/day oral and Cas X 25 mg/kg/day i.p. and 50 mg/kg/ day oral revealed tumor growth inhibition rates of 35.8, 86.2, 53.7, 90.0 and 65.5% and such tumors demonstrated rare mitoses and coagulation necrosis areas. Similarly, FC reduced multiplying of HCT-116 and SF-295 cells when evaluated by the Hollow Fiber Assay (2.5 and 5 mg/kg/day i.p. and 25 and 50 mg/ kg/day oral), with cell growth inhibition rates ranging from 33.3 to 67.4% (p < 0.05). Flow cytometry experiments revealed that FC reduced membrane integrity and induced DNA fragmentation and mitochondrial depolarization (p < 0.05). Conclusions: FC and Cas X were efficient antitumor substances against murine and human cancer cells and caused reversible morphological changes in liver, kidneys and spleens, emphasizing clerodane diterpenes as an emerging class of anticancer molecules.
  • 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 49 Citação(ões) na Scopus
    Malignant transformation in melanocytes is associated with increased production of procoagulant microvesicles
    (2011) LIMA, Luize G.; OLIVEIRA, Andreia S.; CAMPOS, Luiza C.; BONAMINO, Martin; CHAMMAS, Roger; WERNECK, Claudio C.; VICENTE, Cristina P.; BARCINSKI, Marcello A.; PETERSEN, Lars C.; MONTEIRO, Robson Q.
    Shedding of microvesicles (MVs) by cancer cells is implicated in a variety of biological effects, including the establishment of cancer-associated hypercoagulable states. However, the mechanisms underlying malignant transformation and the acquisition of procoagulant properties by tumour-derived MVs are poorly understood. Here we investigated the procoagulant and prothrombotic properties of MVs produced by a melanocyte-derived cell line (melan-a) as compared to its tumourigenic melanoma counterpart Tm1. Tumour cells exhibit a two-fold higher rate of MVs production as compared to melan-a. Melanoma MVs display greater procoagulant activity and elevated levels of the clotting initiator protein tissue factor (TF). On the other hand, tumour- and melanocyte-derived MVs expose similar levels of the procoagulant lipid phosphatidylserine, displaying identical abilities to support thrombin generation by the prothrombinase complex. By using an arterial thrombosis model, we observed that melanoma-but not melanocyte-derived MVs strongly accelerate thrombus formation in a IF-dependent manner, and accumulate at the site of vascular injury. Analysis of plasma obtained from melanoma-bearing mice showed the presence of MVs with a similar procoagulant pattern as compared to Tm1 MVs produced in vitro. Remarkably, flow-cytometric analysis demonstrated that 60% of ex vivo MVs are IF-positive and carry the melanoma-associated antigen, demonstrating its tumour origin. Altogether our data suggest that malignant transformation in melanocytes increases the production of procoagulant MVs, which may contribute for a variety of coagulation-related protumoural responses.
  • article 3 Citação(ões) na Scopus
    Tocilizumab Labeling with (99m)Technetium via HYNIC as a Molecular Diagnostic Agent for Multiple Myeloma
    (2017) CAMACHO, Ximena; MACHADO, Camila Longo; GARCIA, Maria Fernanda; FERNANDEZ, Marcelo; ODDONE, Natalia; BENECH, Juan; GAMBINI, Juan Pablo; CERECETTO, Hugo; CHAMMAS, Roger; CABRALA, Pablo; RIVA, Eloisa
    Background: Multiple myeloma is the second most common hematological malignancy. Interleukin-6 (IL-6) is one of the key molecules related to growth, survival and proliferation of myeloma cells. Tocilizumab is a humanized monoclonal antibody directed against receptor of IL-6. Objective: To radiolabel Tocilizumab with (99m)Technetium as a potential imaging agents for MM. Methods: IL-6R expression was studied by laser confocal microscopy in MM cell lines (U266, NCI-H929 and MM1S). Tocilizumab was derivatized with NHS-HYNIC-Tfa and radiolabeling with Tc-99m. Radiochemical stability was determined. In-vitro binding and immunoreactive fraction assays were performed. Biodistribution and SPECT/CT imaging were evaluated in healthy BALB/c and MM-bearing BALB/c nude mice. Results: LCM studies allowed us to demonstrate that U266, NCI-H929 and MM1S cells present high expression of IL-6R in cell membrane. Radiolabeling was carried out in a fast, reproducible, easy and stable way having high radiochemical purity and did not interfere with epitope recognition. The immunoreactive fraction of (TcHYNIC)-Tc-99m-Tocilizumab was 86.35%. Biodistribution showed a high uptake in liver, spleen, gastrointestinal tract and kidneys. SPECT/CT imaging of MM-bearing BALB/c nude mice showed liver uptake and a high tumor selective uptake at 24 hours. Conclusions: Our results support the potential role of 99mTc-HYNIC-Tocilizumb as a novel MM radiotracer for targeting IL-6 expression in-vivo. We describe the development of a formulation kit to radiolabeling monoclonal antibodies in a clinical setting. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for MM disease.
  • 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.