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
13 resultados
Resultados de Busca
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conferenceObject Stochastic model of contact inhibition and the proliferation of melanoma in situ.(2018) MORAIS, Mauro Cesar C.; STUHL, Izabella; SABINO, Alan U.; LAUTENSCHLAGER, Willian W.; QUEIROGA, Alexandre S.; TORTELLI JR., Tharcisio C.; CHAMMAS, Roger; SUHOV, Yuri; RAMOS, Alexandre F.- Emerging targets for combination therapy in melanomas(2015) SAITO, Renata de Freitas; TORTELLI JR., Tharcisio Citrangulo; JACOMASSI, Mayara D'Auria; OTAKE, Andreia Hanada; CHAMMAS, RogerCutaneous melanomas are often difficult to treat when diagnosed in advanced stages. Melanoma cells adapt to survive in extreme environmental conditions and are among the tumors with larger genomic instability. Here we discuss some intrinsic and extrinsic mechanisms of resistance of melanoma cells to both conventional and target therapies, such as autophagy, adaptation to endoplasmic reticulum stress, metabolic reprogramming, mechanisms of tumor repopulation and the role of extracellular vesicles in this later phenomenon. These biological processes are potentially targetable and thus provide a platform for research and discovery of new drugs for combination therapy to manage melanoma patient treatment.
conferenceObject 7-Ketocholesterol loaded-phosphatidylserine liposome induces cell death, autophagy, and growth inhibition of melanoma and breast adenocarcinoma.(2018) FAVERO, Giovani Marino; TORTELLI JR., Tharcisio Citrangulo; FERNANDES, Daniel; PRESTES, Ana Paula; KMETIUK, Louise N. B.; OTAKE, Andreia Hanada; ANDRADE, Luciana N. S.; FARIA, Daniele de Paula; CARNEIRO, Camila de Godoi; GARCEZ, Alexandre Teles; MARQUES, Fabio L. N.; CHAMMAS, Roger- 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.
- Metformin impairs cisplatin resistance effects in A549 lung cancer cells through mTOR signaling and other metabolic pathways(2021) MORELLI, Ana Paula; TORTELLI, Tharcisio Citrangulo Jr Jr; PAVAN, Isadora Carolina Betim; SILVA, Fernando Riback; GRANATO, Daniela Campos; PERUCA, Guilherme Francisco; PAULETTI, Bianca Alves; DOMINGUES, Romenia Ramos; BEZERRA, Rosangela Maria Neves; MOURA, Leandro Pereira De; LEME, Adriana Franco Paes; CHAMMAS, Roger; SIMABUCO, Fernando MoreiraLung cancer is the leading cause of cancer-associated death worldwide and exhibits intrinsic and acquired therapeutic resistance to cisplatin (CIS). The present study investigated the role of mTOR signaling and other signaling pathways after metformin (MET) treatment in control and cisplatin-resistant A549 cells, mapping pathways and possible targets involved in CIS sensitivity. MTT, flow cytometry, clonogenic assay, western blotting, proteomic analysis using the Stable Isotope Labeling by Amino acids in Cell culture (SILAC) approach and reverse transcription-quantitative PCR were performed. The results revealed that CIS treatment induced mTOR signaling pathway overactivation, and the mTOR status was restored by MET. MET and the mTOR inhibitor rapamycin (RAPA) decreased the viability in control and resistant cells, and decreased the cell size increase induced by CIS. In control cells, MET and RAPA decreased colony formation after 72 h and decreased IC50 values, potentiating the effects of CIS. Proteomics analysis revealed important pathways regulated by MET, including transcription, RNA processing and IL-12-mediated signaling. In CIS-resistant cells, MET regulated the apoptotic process, oxidative stress and G(2)/M transition. Annexin 4 (ANXA4) and superoxide dismutase 2 (SOD2), involved in apoptosis and oxidative stress, respectively, were chosen to validate the SILAC analysis and may represent potential therapeutic targets for lung cancer treatment. In conclusion, the chemosensitizing and antiproliferative effects of MET were associated with mTOR signaling and with potential novel targets, such as ANXA4 and SOD2, in human lung cancer cells.
- 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.
- Accumulation of prohibitin is a common cellular response to different stressing stimuli and protects melanoma cells from ER stress and chemotherapy-induced cell death(2017) TORTELLI JUNIOR, Tharcisio Citrangulo; GODOY, Lyris Martins Franco de; SOUZA, Gustavo Antonio de; BONATTO, Diego; OTAKE, Andreia Hanada; SAITO, Renata de Freitas; ROSA, Jose Cesar; GREENE, Lewis Joel; CHAMMAS, RogerMelanoma is responsible for most deaths among skin cancers and conventional and palliative care chemotherapy are limited due to the development of chemoresistance. We used proteomic analysis to identify cellular responses that lead to chemoresistance of human melanoma cell lines to cisplatin. A systems approach to the proteomic data indicated the participation of specific cellular processes such as oxidative phosphorylation, mitochondrial organization and homeostasis, as well as the unfolded protein response (UPR) to be required for the survival of cells treated with cisplatin. Prohibitin (PHB) was among the proteins consistently accumulated, interacting with the functional clusters associated with resistance to cisplatin. We showed PHB accumulated at different levels in melanoma cell lines under stressing stimuli, such as (i) treatment with temozolomide (TMZ), dacarbazine (DTIC) and cisplatin; (ii) serum deprivation; (iii) tunicamycin, an UPR inducer. Prohibitin accumulated in the mitochondria of melanoma cells after cisplatin and tunicamycin treatment and its de novo accumulation led to chemoresistance melanoma cell lines. In contrast, PHB knockdown sensitized melanoma cells to cisplatin and tunicamycin treatment. We conclude that PHB participates in the survival of cells exposed to different stress stimuli, and can therefore serve as a target for the sensitization of melanoma cells to chemotherapy.
conferenceObject Effects of sulforaphane association to conventional therapy for treating triple-negative breast cancer(2023) COUTINHO, L. L.; CHENG, R.; RIDNOUR, L.; JUNQUEIRA, M. S.; CHAMMAS, R.; WINK, D.; TORTELLI, T. C.; RANGEL, M.- 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.
- Metformin-induced chemosensitization to cisplatin depends on P53 status and is inhibited by Jarid1b overexpression in non-small cell lung cancer cells(2021) TORTELLI JR., Tharcisio Citrangulo; TAMURA, Rodrigo Esaki; JUNQUEIRA, Mara de Souza; MORORO, Janio da Silva; BUSTOS, Silvina Odete; NATALINO, Renato Jose Mendonca; RUSSELL, Shonagh; DESAUBRY, Laurent; STRAUSS, Bryan Eric; CHAMMAS, RogerMetformin has been tested as an anti-cancer therapy with potential to improve conventional chemotherapy. However, in some cases, metformin fails to sensitize tumors to chemotherapy. Here we test if the presence of P53 could predict the activity of metformin as an adjuvant for cisplatin-based therapy in non-small cell lung cancer (NSCLC). A549, HCC 827 (TP53 WT), H1299, and H358 (TP53 null) cell lines were used in this study. A549 cells were pre-treated with a sub-lethal dose of cisplatin to induce chemoresistance. The effects of metformin were tested both in vitro and in vivo and related to the ability of cells to accumulate Jarid1b, a histone demethylase involved in cisplatin resistance in different cancers. Metformin sensitized A549 and HCC 827 cells (but not H1299 and H358 cells) to cisplatin in a P53-dependent manner, changing its subcellular localization to the mitochondria. Treatment with a sub-lethal dose of cisplatin increased Jarid1b expression, yet downregulated P53 levels, protecting A549Res cells from metformin-induced chemosensitization to cisplatin and favored a glycolytic phenotype. Treatment with FL3, a synthetic flavagline, sensitized A549Res cells to cisplatin. In conclusion, metformin could potentially be used as an adjuvant for cisplatin-based therapy in NSCLC cells if wild type P53 is present.