BRYAN ERIC STRAUSS
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
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
87 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 87
- TP53 Regulated Inhibitor of Apoptosis 1 (TRIAP1) stable silencing increases late apoptosis by upregulation of caspase 9 and APAF1 in RPMI8226 multiple myeloma cell line(2016) FOOK-ALVES, Veruska L.; OLIVEIRA, Mariana Bleker de; ZANATTA, Daniela B.; STRAUSS, Bryan E.; COLLEONI, Gisele W. B.Background: TP53 Regulated Inhibitor of Apoptosis 1 (TRIAP1) modulates apoptotic pathways preventing the formation of the apoptosome complex. Our group previous study showed that 90% of patients' multiple myeloma (MM) marrow-derived plasma cells present TRIAP1 overexpression as compared to normal plasma cells. Due to high prevalence and lack of information on TRIAP1's role in MM biology, we decided to explore the impact of TRAIP1 through stable gene silencing in MM cell lines and its effect on cell cycle and apoptosis. Methods: TRIAP1 expression was examined in MM cell lines by quantitative real time PCR. Cell lines were submitted to transduction with lentiviral vector encoding a TRIAP1-specific short hairpin RNA (shRNA) and, as control, encoding a non-targeting shRNA (scramble). Apoptosis was assessed by flow cytometry with annexin V and propidium iodide staining (the later also used for cell cycle), APAF1 and Caspase 9 apoptosome related genes expression and Caspase 9 and Caspase 3/7 activity. Results: RPMI8226 and U266 cell lines were chosen for transduction experiments since they present higher levels of TRIAP1 expression. Inhibition of TRIAP1 in RPMI8226 cells increased the percentage of apoptotic cells, accompanied by increased expression of APAF1 and Caspase 9, and Caspase 9 and Caspase 3/7 activity. Transduced U266 cell line did not show sustained inhibition of TRIAP1 expression nor apoptosis induction. Conclusion: Stable silencing of TRIAP1 induces late apoptosis through APAF1/Caspase 9 pathway at least in RPMI8226 cell line, suggesting that it could be exploited as a potential target at least for a subgroup of MM patients. General significance: In the present study, we demonstrated effects of TRIAP1 silencing on RPMI8226 MM cell line and established its mechanism mediated through APAF1 and Caspase 9. No relevant effect was found after gene silencing in U266 cell line.
bookPart O ciclo celular como alvo da terapia gênica do câncer(2013) COSTANZI-STRAUSS, Eugenia; STRAUSS, Bryan EricconferenceObject Anti-tumor Effect of P19Arf and Interferon-beta Gene Transference to Mouse Melanoma and Mouse Lung Carcinoma Cells is Revealed by a Strong Bystander Activity and a Potential Immune Response(2012) RIBEIRO, A. H.; MEDRANO, R. F. V.; CATANI, J. P. P.; STRAUSS, B. E.Introduction: Two hallmarks of tumor progression are resistance to cell death and lack of an effective anti-tumor immune response. Loss of p53 function, by genetic mutation or alterations in its pathway, such as p19Arf loss and/or mdm2 over-expression, inhibits one of the primary coordinators of cell death. Interferon-beta (IFN), a stimulator of the immune response with anti-neoplastic functions, is also frequently lost in some tumor types. We propose that p19Arf and IFN gene transfer would be an effective strategy, especially in wild-type p53 tumor cells, since cell death and immune activation would be combined to combat the tumor at primary treatment site and metastasis. Material and Methods: Recombinant adenoviral vectors with RGD-modified fiber (rAdRGD) and a p53-responsive promoter (PG) were constructed containing genes of p19Arf, IFN or the combination of both. Evaluation of in vitro antiproliferative effect of transgenes in B16F10 cells (B16, mouse melanoma, p53 wt) was done by annexin/PI staining and MTT assays. Bystander effect was revealed by cell cycle analysis of populations transduced with different proportions of the viruses. Antitumor effect in vivo was observed by treatment of established LLC1 tumors (mouse lung carcinoma, p53 wt) with intratumoral injection of rAdRGD in C57BL/6 mice. Involvement of immune response was revealed by second tumor challenge at contralateral flank of mice with a developed and treated first tumor. Results and Discussion: Cell death was resulted from the p19Arf and IFN combined transference (74% subG0), yet single gene transfer yielded only half the number of subG0 cells. A similar result was seen by measurement of cell viability with MTT. Evidence on a bystander effect was revealed when approximately 50% subG0 cells were observed, even though only 10% of the cells had been transduced with IFN. In a population of cells transduced with p19Arf, when 10% of them also expressed IFN, the number of subG0 cells increased to 68%, compared to transduction of p19Arf alone, which results in 45% subG0 cells. This indicates that p19Arf can sensitize cells to death by IFN bystander effect. In vivo assays with the LLC1 model have shown that in situ gene therapy of p19Arf and IFN combination was more effective to inhibit tumor progression and increase survival than application of a single gene. These animals were then challenged with the implantation of a second tumor, revealing greater retardation of growth at the secondary tumor site in mice treated with the combined gene therapy at the primary tumor locus as compared to animals that received single gene treatment. Conclusion: The use of p53-responsive vectors to express p19Arf and IFN represents a potential strategy for melanoma and lung carcinoma tumor suppression. We have shown that complementation of the p53/Arf and interferon pathways in the primary tumor may generate a strong bystander effect as well as immune stimulation.- Consensus guidelines for the definition, detection and interpretation of immunogenic cell death(2020) GALLUZZI, Lorenzo; VITALE, Ilio; WARREN, Sarah; ADJEMIAN, Sandy; AGOSTINIS, Patrizia; MARTINEZ, Aitziber Buque; CHAN, Timothy A.; COUKOS, George; DEMARIA, Sandra; DEUTSCH, Eric; DRAGANOV, Dobrin; EDELSON, Richard L.; FORMENTI, Silvia C.; FUCIKOVA, Jitka; GABRIELE, Lucia; GAIPL, Udo S.; GAMEIRO, Sofia R.; GARG, Abhishek D.; GOLDEN, Encouse; HAN, Jian; HARRINGTON, Kevin J.; HEMMINKI, Akseli; HODGE, James W.; HOSSAIN, Dewan Md Sakib; ILLIDGE, Tim; KARIN, Michael; KAUFMAN, Howard L.; KEPP, Oliver; KROEMER, Guido; LASARTE, Juan Jose; LOI, Sherene; LOTZE, Michael T.; MANIC, Gwenola; MERGHOUB, Taha; MELCHER, Alan A.; MOSSMAN, Karen L.; PROSPER, Felipe; REKDAL, Oystein; RESCIGNO, Maria; RIGANTI, Chiara; SISTIGU, Antonella; SMYTH, Mark J.; SPISEK, Radek; STAGG, John; STRAUSS, Bryan E.; TANG, Daolin; TATSUNO, Kazuki; GOOL, Stefaan W. van; VANDENABEELE, Peter; YAMAZAKI, Takahiro; ZAMARIN, Dmitriy; ZITVOGEL, Laurence; CESANO, Alessandra; MARINCOLA, Francesco M.Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.
bookPart Terapias alvo dirigidas, gênicas e oncolíticas(2022) RODRIGUES, Otavio Augusto; STRAUSS, Bryan EricconferenceObject Heat Shock Protein 70 Inhibitor, Alone or in Combination with Bortezomib, Prevented Plasmacytoma Development in Immunodeficient Mice Transplanted with Myeloma Cell Lines(2016) OLIVEIRA, Mariana Bleker de; EUGENIO, Angela Isabel; ALVES, Veruska Lia Fook; ZANATTA, Daniela; YAMAMOTO, Mihoko; STRAUSS, Bryan Eric; COLLEONI, Gisele W. B.- Modifications of adenoviral structure and genome improves transduction efficiency and transgene expression(2015) VALLE, Paulo Roberto Del; ZANATTA, Daniela B.; STRAUSS, Bryan E.
- Overhauling CAR T Cells to Improve Efficacy, Safety and Cost(2020) CHICAYBAM, Leonardo; BONAMINO, Martin H.; INVITTI, Adriana Luckow; ROZENCHAN, Patricia Bortman; VIEIRA, Igor de Luna; STRAUSS, Bryan E.Gene therapy is now surpassing 30 years of clinical experience and in that time a variety of approaches has been applied for the treatment of a wide range of pathologies. While the promise of gene therapy was over-stated in the 1990's, the following decades were met with polar extremes between demonstrable success and devastating setbacks. Currently, the field of gene therapy is enjoying the rewards of overcoming the hurdles that come with turning new ideas into safe and reliable treatments, including for cancer. Among these modalities, the modification of T cells with chimeric antigen receptors (CAR-T cells) has met with clear success and holds great promise for the future treatment of cancer. We detail a series of considerations for the improvement of the CAR-T cell approach, including the design of the CAR, routes of gene transfer, introduction of CARs in natural killer and other cell types, combining the CAR approach with checkpoint blockade or oncolytic viruses, improving pre-clinical models as well as means for reducing cost and, thus, making this technology more widely available. While CAR-T cells serve as a prime example of translating novel ideas into effective treatments, certainly the lessons learned will serve to accelerate the current and future development of gene therapy drugs.
conferenceObject Induction of immunogenic cell death in canine melanoma model in response to combined p14ARF and interferon-beta gene transfer(2021) RODRIGUES, O. A.; STRAUSS, B. E.- A quantitative sequencing based method for the monitoring of clonal expansion(2012) STRAUSS, Bryan E.; ZANATTA, Daniela; AGUIAR, Rodrigo B. de