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
- 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, DanieleBackgroundThe 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.
- Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression(2023) TOBIAS, Gabriel C.; GOMES, Joao L. P.; FERNANDES, Larissa G.; VOLTARELLI, Vanessa A.; ALMEIDA, Ney R. de; JANNIG, Paulo R.; SOUZA, Rodrigo W. Alves de; NEGRAO, Carlos E.; OLIVEIRA, Edilamar M.; CHAMMAS, Roger; ALVES, Christiano R. R.; BRUM, Patricia C.Exercise training reduces the incidence of several cancers, but the mechanisms underlying these effects are not fully understood. Exercise training can affect the spleen function, which controls the hematopoiesis and immune response. Analyzing different cancer models, we identified that 4T1, LLC, and CT26 tumor-bearing mice displayed enlarged spleen (splenomegaly), and exercise training reduced spleen mass toward control levels in two of these models (LLC and CT26). Exercise training also slowed tumor growth in melanoma B16F10, colon tumor 26 (CT26), and Lewis lung carcinoma (LLC) tumor-bearing mice, with minor effects in mammary carcinoma 4T1, MDA-MB-231, and MMTV-PyMT mice. In silico analyses using transcriptome profiles derived from these models revealed that platelet factor 4 (Pf4) is one of the main upregulated genes associated with splenomegaly during cancer progression. To understand whether exercise training would modulate the expression of these genes in the tumor and spleen, we investigated particularly the CT26 model, which displayed splenomegaly and had a clear response to the exercise training effects. RT-qPCR analysis confirmed that trained CT26 tumor-bearing mice had decreased Pf4 mRNA levels in both the tumor and spleen when compared to untrained CT26 tumor-bearing mice. Furthermore, exercise training specifically decreased Pf4 mRNA levels in the CT26 tumor cells. Aspirin treatment did not change tumor growth, splenomegaly, and tumor Pf4 mRNA levels, confirming that exercise decreased non-platelet Pf4 mRNA levels. Finally, tumor Pf4 mRNA levels are deregulated in The Cancer Genome Atlas Program (TCGA) samples and predict survival in multiple cancer types. This highlights the potential therapeutic value of exercise as a complementary approach to cancer treatment and underscores the importance of understanding the exercise-induced transcriptional changes in the spleen for the development of novel cancer therapies.
- The PANcreatic Disease ReseArch (PANDoRA) consortium: Ten years' experience of association studies to understand the genetic architecture of pancreatic cancer(2023) CAMPA, Daniele; GENTILUOMO, Manuel; STEIN, Angelika; AOKI, Mateus Nobrega; OLIVERIUS, Martin; VODICKOVA, Ludmila; JAMROZIAK, Krzysztof; THEODOROPOULOS, George; PASQUALI, Claudio; GREENHALF, William; ARCIDIACONO, Paolo Giorgio; UZUNOGLU, Faik; PEZZILLI, Raffaele; LUCHINI, Claudio; PUZZONO, Marta; LOOS, Martin; GIACCHERINI, Matteo; KATZKE, Verena; MAMBRINI, Andrea; KIUDELIENE, Edita; FEDERICO, Kauffmann Emanuele; JOHANSEN, Julia; HUSSEIN, Tamas; MOHELNIKOVA-DUCHONOVA, Beatrice; EIJCK, Casper H. J. van; BRENNER, Hermann; FARINELLA, Riccardo; PEREZ, Juan Sainz; LOVECEK, Martin; BUECHLER, Markus W.; HLAVAC, Viktor; IZBICKI, Jakob R.; HACKERT, Thilo; CHAMMAS, Roger; ZERBI, Alessandro; LAWLOR, Rita; FELICI, Alessio; GOETZ, Mara; CAPURSO, Gabriele; GINOCCHI, Laura; GAZOULI, Maria; KUPCINSKAS, Juozas; CAVESTRO, Giulia Martina; VODICKA, Pavel; MOZ, Stefania; NEOPTOLEMOS, John P.; KUNOVSKY, Lumir; BOJESEN, Stig E.; CARRARA, Silvia; GIOFFREDA, Domenica; MORKUNAS, Egidijus; ABIAN, Olga; BUNDUC, Stefania; BASSO, Daniela; BOGGI, Ugo; WLODARCZYK, Barbara; SZENTESI, Andrea; VANELLA, Giuseppe; CHEN, Inna; BIJLSMA, Maarten F.; KIUDELIS, Vytautas; LANDI, Stefano; Ben Schoettker; CORRADI, Chiara; GIESE, Nathalia; KAAKS, Rudolf; PEDUZZI, Giulia; HEGYI, Peter; MORELLI, Luca; FURBETTA, Niccolo; SOUCEK, Pavel; LATIANO, Anna; TALAR-WOJNAROWSKA, Renata; LINDGAARD, Sidsel C.; DIJK, Frederik; MILANETTOJ, Anna Caterina; TAVANO, Francesca; CERVENA, Klara; EROSS, Balint; TESTONI, Sabrina G.; VERHAGEN-OLDENAMPSEN, Judith H. E.; MALECKA-WOJCIESKO, E.; COSTELLO, Eithne; SALVIA, Roberto; MAIELLO, Evaristo; ERMINI, Stefano; SPERTI, Cosimo; HOLLECZEK, Bernd; PERRI, Francesco; SKIECEVICIENE, Jurgita; ARCHIBUGI, Livia; LUCCHESI, Maurizio; RIZZATO, Cosmeri; CANZIAN, FedericoPancreatic cancer has an incidence that almost matches its mortality. Only a small number of risk factors and 33 susceptibility loci have been identified. so Moreover, the relative rarity of pancreatic cancer poses significant hurdles for research aimed at increasing our knowledge of the genetic mechanisms contributing to the disease. Additionally, the inability to adequately power research questions prevents small monocentric studies from being successful. Several consortia have been established to pursue a better understanding of the genetic architecture of pancreatic cancers. The Pancreatic disease research (PANDoRA) consortium is the largest in Europe. PANDoRA is spread across 12 European countries, Brazil and Japan, bringing together 29 basic and clinical research groups. In the last ten years, PANDoRA has contributed to the discovery of 25 susceptibility loci, a feat that will be instrumental in stratifying the population by risk and optimizing preventive strategies.
- Insights from a Computational-Based Approach for Analyzing Autophagy Genes across Human Cancers(2023) CARRASCO, Alexis German Murillo; GIOVANINI, Guilherme; RAMOS, Alexandre Ferreira; CHAMMAS, Roger; BUSTOS, Silvina OdeteIn the last decade, there has been a boost in autophagy reports due to its role in cancer progression and its association with tumor resistance to treatment. Despite this, many questions remain to be elucidated and explored among the different tumors. Here, we used omics-based cancer datasets to identify autophagy genes as prognostic markers in cancer. We then combined these findings with independent studies to further characterize the clinical significance of these genes in cancer. Our observations highlight the importance of innovative approaches to analyze tumor heterogeneity, potentially affecting the expression of autophagy-related genes with either pro-tumoral or anti-tumoral functions. In silico analysis allowed for identifying three genes (TBC1D12, KERA, and TUBA3D) not previously described as associated with autophagy pathways in cancer. While autophagy-related genes were rarely mutated across human cancers, the expression profiles of these genes allowed the clustering of different cancers into three independent groups. We have also analyzed datasets highlighting the effects of drugs or regulatory RNAs on autophagy. Altogether, these data provide a comprehensive list of targets to further the understanding of autophagy mechanisms in cancer and investigate possible therapeutic targets.
- Extracellular Vesicle-Packaged miR-195-5p Sensitizes Melanoma to Targeted Therapy with Kinase Inhibitors(2023) SANTOS, Nathalia L.; BUSTOS, Silvina O.; REIS, Patricia P.; CHAMMAS, Roger; ANDRADE, Luciana N. S.Management of advanced melanoma remains challenging, with most BRAF (B-Raf proto-oncogene, serine/threonine kinase)-mutated metastatic patients relapsing within a few months upon MAPK inhibitors treatment. Modulation of tumor-derived extracellular vesicle (EVs) cargo with enrichment of antitumoral molecules is a promising strategy to impair tumor progression and increase treatment response. Herein, we report that restored expression of miR-195-5p, down-regulated in melanoma favoring drug resistance, increases the release of EVs enriched in the tumor suppressor miRNAs, miR-195-5p, miR-152-3p, and miR-202-3p. Incorporating these EVs by bystander tumor cells resulted in decreased proliferation and viability, accompanied by a reduction in CCND1 and YAP1 mRNA levels. Upon treatment with MAPK inhibitors, miR-195 EVs significantly decreased BCL2-L1 protein levels and increased cell death ratio and treatment efficacy. Additionally, EVs exogenously loaded with miR-195-5p by electroporation reduced tumor volume in vivo and impaired engraftment and growth of xenografts implanted with melanoma cells exposed to MAPK inhibitors. Our study shows that miR-195-5p antitumoral activity can be spread to bystander cells through EVs, improving melanoma response to targeted therapy and revealing a promising EV-based strategy to increase clinical response in patients harboring BRAF mutations.
- Role of galectin-3 in the elastic response of radial growth phase melanoma cancer cells(2023) HERRERA-REINOZA, Nataly; TORTELLI JUNIOR, Tharcisio Citrangulo; TEIXEIRA, Fernanda de Sa; CHAMMAS, Roger; SALVADORI, Maria CeciliaMelanoma is originated from the malignant transformation of the melanocytes and is characterized by a high rate of invasion, the more serious stage compromising deeper layers of the skin and eventually leading to the metastasis. A high mortality due to melanoma lesion persists because most of melanoma lesions are detected in advanced stages, which decreases the chances of survival. The identification of the principal mechanics implicated in the development and progression of melanoma is essential to devise new early diagnosis strategies. Cell mechanics is related with a lot of cellular functions and processes, for instance motility, differentiation, migration and invasion. In particular, the elastic modulus (Young's modulus) is a very explored parameter to describe the cell mechanical properties; most cancer cells reported in the literature smaller elasticity modulus. In this work, we show that the elastic modulus of melanoma cells lacking galectin-3 is significantly lower than those of melanoma cells expressing galectin-3. More interestingly, the gradient of elastic modulus in cells from the nuclear region towards the cell periphery is more pronounced in shGal3 cells.
- Unraveling the peripheral and local role of inflammatory cytokines in glioblastoma survival(2023) CAVALHEIRO, Vitor J.; CAMPOS, Ana Carolina P.; LIMA, Luiz G. C. A.; ROEA, Cairo Thome; DOCEMA, Marcos Fernando L.; LANCELLOTTI, Carmen Lucia P.; MARTINEZ, Raquel C. R.; PAGANO, Rosana L.; CHAMMAS, Roger; TEIXEIRA, Manoel J.; MALDAUN, Marcos V. C.; NEVILLE, Iuri S.Glioblastoma (GBM) is a life-threatening disease that presents high morbidity and mortality. The standardized treatment protocol results in a global survival of less than three years in the majority of cases. Immunotherapies have gained wide recognition in cancer treatment; however, GBM has an immunosuppressive microenvironment diminishing the possible effectiveness of this therapy. In this sense, investigating the inflammatory settings and the tumoral nature of GBM patients are an important goal to create an individual plan of treatment to improve overall survival rate and quality of life of these patients. Thirty-two patients who underwent surgical resection of GBM were included in this study. Tumor samples and 10 mL of peripheral blood were collected and immediately frozen. TNF-a, IL-1a and IL-4 were evaluated in the tumor and TNF-a, IL-1a and TGF-b in the plasma by Luminex assay. Immunohistochemistry analysis to determine immune celular profile was done, including immunohisto-chemistry for CD20, CD68 and CD3. Three cases were excluded. Tumor topography, tumor nature, and tumor volume reconstructions were accurately analyzed by T1-weighted, T2-weighted, and FLAIR magnetic resonance imaging. We found that GBM patients with below median peripheral levels of TNF-a and IL-1a had a decreased survival rate when compared to above median patients. On the other hand, patients with below median pe-ripheral levels of TGF-b increased overall survival rate. Intratumoral IL-1a above median was associated with higher number of macrophages and fewer with B cells. Furthermore, plasmatic TNF-a levels were correlated with intratumoral TNF-a levels, suggesting that peripheral cytokines are related to the tumoral microenvironment. Even though tumor size has no difference regarding survival rate, we found a negative correlation between intratumoral IL-4 and tumor size, where larger tumors have less IL-4 expression. Nevertheless, the tumoral nature had a significant effect in overall survival rate, considering that infiltrative tumors showed decreased survival rate and intratumoral TNF-a. Moreover, expansive tumors revealed fewer macrophages and higher T cells. In multiple variation analyzes, we demonstrated that infiltrative tumors and below median peripheral IL-1a expression represent 3 times and 5 times hazard ratio, respectively, demonstrating a poor prognosis. Here we found that peripheral cytokines had a critical role as prognostic tools in a small cohort of GBM patients.
conferenceObject Prognostic impact of primary tumor sidedness in stage III colorectal cancer(2023) PROTASIO, Bruno Mendonca; CASTRIA, Tiago Biachi de; SARAGIOTTO, Daniel Fernandes; NATALINO, Renato Jose Mendonca; MANGONE, Flavia Regina Rotea; SABBAGA, Jorge; HOFF, Paulo M.; CHAMMAS, Roger- Deciphering the Functional Status of Breast Cancers through the Analysis of Their Extracellular Vesicles(2023) CARRASCO, Alexis German Murillo; OTAKE, Andreia Hanada; MACEDO-DA-SILVA, Janaina; SANTIAGO, Veronica Feijoli; PALMISANO, Giuseppe; ANDRADE, Luciana Nogueira de Sousa; CHAMMAS, RogerBreast cancer (BC) accounts for the highest incidence of tumor-related mortality among women worldwide, justifying the growing search for molecular tools for the early diagnosis and follow-up of BC patients under treatment. Circulating extracellular vesicles (EVs) are membranous nanocompartments produced by all human cells, including tumor cells. Since minimally invasive methods collect EVs, which represent reservoirs of signals for cell communication, these particles have attracted the interest of many researchers aiming to improve BC screening and treatment. Here, we analyzed the cargoes of BC-derived EVs, both proteins and nucleic acids, which yielded a comprehensive list of potential markers divided into four distinct categories, namely, (i) modulation of aggressiveness and growth; (ii) preparation of the pre-metastatic niche; (iii) epithelial-to-mesenchymal transition; and (iv) drug resistance phenotype, further classified according to their specificity and sensitivity as vesicular BC biomarkers. We discuss the therapeutic potential of and barriers to the clinical implementation of EV-based tests, including the heterogeneity of EVs and the available technologies for analyzing their content, to present a consistent, reproducible, and affordable set of markers for further evaluation.
- deltaXpress (ΔXpress): a tool for mapping differentially correlated genes using single-cell qPCR data(2023) CARRASCO, Alexis German Murillo; FURUYA, Tatiane Katsue; UNO, Miyuki; JR, Tharcisio Citrangulo Tortelli; CHAMMAS, RogerBackgroundHigh-throughput experiments provide deep insight into the molecular biology of different species, but more tools need to be developed to handle this type of data. At the transcriptomics level, quantitative Polymerase Chain Reaction technology (qPCR) can be affordably adapted to produce high-throughput results through a single-cell approach. In addition to comparative expression profiles between groups, single-cell approaches allow us to evaluate and propose new dependency relationships among markers. However, this alternative has not been explored before for large-scale qPCR-based experiments.ResultsHerein, we present deltaXpress (Delta Xpress), a web app for analyzing data from single-cell qPCR experiments using a combination of HTML and R programming languages in a friendly environment. This application uses cycle threshold (Ct) values and categorical information for each sample as input, allowing the best pair of housekeeping genes to be chosen to normalize the expression of target genes. Delta Xpress emulates a bulk analysis by observing differentially expressed genes, but in addition, it allows the discovery of pairwise genes differentially correlated when comparing two experimental conditions. Researchers can download normalized data or use subsequent modules to map differentially correlated genes, perform conventional comparisons between experimental groups, obtain additional information about their genes (gene glossary), and generate ready-to-publication images (600 dots per inch).Conclusions Delta Xpress web app is freely available to non-commercial users at https://alexismurillo.shinyapps.io/dXpress/ and can be used for different experiments in all technologies involving qPCR with at least one housekeeping region.