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
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- 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 MarisaDuring 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.
- Phosphatidylcholine-Derived Lipid Mediators: The Crosstalk Between Cancer Cells and Immune Cells(2022) SAITO, Renata de Freitas; ANDRADE, Luciana Nogueira de Sousa; BUSTOS, Silvina Odete; CHAMMAS, RogerTo become resistant, cancer cells need to activate and maintain molecular defense mechanisms that depend on an energy trade-off between resistance and essential functions. Metabolic reprogramming has been shown to fuel cell growth and contribute to cancer drug resistance. Recently, changes in lipid metabolism have emerged as an important driver of resistance to anticancer agents. In this review, we highlight the role of choline metabolism with a focus on the phosphatidylcholine cycle in the regulation of resistance to therapy. We analyze the contribution of phosphatidylcholine and its metabolites to intracellular processes of cancer cells, both as the major cell membrane constituents and source of energy. We further extended our discussion about the role of phosphatidylcholine-derived lipid mediators in cellular communication between cancer and immune cells within the tumor microenvironment, as well as their pivotal role in the immune regulation of therapeutic failure. Changes in phosphatidylcholine metabolism are part of an adaptive program activated in response to stress conditions that contribute to cancer therapy resistance and open therapeutic opportunities for treating drug-resistant cancers.
- 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.
- Eeyarestatin I sensitizes melanoma cells to cisplatin-induced cell death(2018) SAITO, Renata de Freitas; OTAKE, Andreia Hanada; CORTEZ, Margarita M.; GILLIES, Robbert J.; CHAMMAS, Roger
bookPart Biologia molecular dos melanomas(2013) FRANCISCO, Guilherme; OTAKE, Andréia Hanada; SAITO, Renata de Freitas; CHAMMAS, Roger- 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.
bookPart O metabolismo da célula tumoral(2015) SAITO, Renata de Freitas; COLQUHOUN, Alison; CHAMMAS, Roger- A novel proteasome inhibitor acting in mitochondrial dysfunction, ER stress and ROS production(2013) MARIA, Durvanei Augusto; SOUZA, Jean Gabriel de; MORAIS, Katia L. P.; BERRA, Carolina Maria; ZAMPOLLI, Hamilton de Campos; DEMASI, Marilene; SIMONS, Simone Michaela; SAITO, Renata de Freitas; CHAMMAS, Roger; CHUDZINSKI-TAVASSI, Ana MarisaIn cancer-treatment, potentially therapeutic drugs trigger their effects through apoptotic mechanisms. Generally, cell response is manifested by Bcl-2 family protein regulation, the impairment of mitochondrial functions, and ROS production. Notwithstanding, several drugs operate through proteasome inhibition, which, by inducing the accumulation and aggregation of misfolded or unfolded proteins, can lead to endoplasmic reticulum (ER) stress. Accordingly, it was shown that Amblyomin-X, a Kunitz-type inhibitor identified in the transcriptome of the Amblyomma cajennense tick by ESTs sequence analysis of a cDNA library, obtained in recombinant protein form, induces apoptosis in murine renal adenocarcinoma (RENCA) cells by: inducing imbalance between pro- and anti-apoptotic Bcl-2 family proteins, dysfunction/mitochondrial damage, production of reactive oxygen species (ROS), caspase cascade activation, and proteasome inhibition, all ER-stress inductive. Moreover, there was no manifest action on normal mouse-fibroblast cells (NHI3T3), suggesting an Amblyomin-X tumor-cell selectivity. Taken together, these evidences indicate that Amblyomin-X could be a promising candidate for cancer therapy.
bookPart Introdução ao câncer(2015) DIAZ, Ema Elissen Flores; SAITO, Renata de Freitas; CHAMMAS, RogerconferenceObject Jarid1b protects from metformin-induced chemosensitization to cisplatin through p53 downregulation in NSCLC(2018) TORTELLI JR., Tharcisio Citrangulo; TAMURA, Rodrigo Esaki; TOMITAO, Michele Tatiana Pereira; BUSTOS, Silvina Odete; SAITO, Renata de Freitas; LEANDRINI, Sarah Milani de Moraes; JACOMASSI, Mayara D'Aurea; RIBEIRO JR., Ulysses; STRAUSS, Bryan Erik; CHAMMAS, Roger