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
15 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 15
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.- Cochlea cell-specific marker expression upon in vitro Hes1 knockdown(2021) BATISSOCO, A. C.; LEZIROVITZ, K.; ZANATTA, D. B.; HEMZA, C. R. M. L.; VASQUES, L. R.; STRAUSS, B. E.; MINGRONI-NETTO, R. C.; HADDAD, L. A.; BENTO, R. F.; OITICICA, J.NOTCH pathway proteins, including the transcriptional factor HES1, play crucial roles in the development of the inner ear by means of the lateral inhibition mechanism, in which supporting cells have their phenotype preserved while they are prevented from becoming hair cells. Genetic manipulation of this pathway has been demonstrated to increase hair cell number. The present study aimed to investigate gene expression effects in hair cells and supporting cells after Hes1-shRNA lentivirus transduction in organotypic cultures of the organ of Corti from postnatal-day-3 mice. Forty-eight hours after in vitro knockdown, Hes1 gene expression was reduced at both mRNA and protein levels. Myo7a (hair cell marker) and Sox2 (progenitor cell marker) mRNA levels also significantly increased. The modulation of gene expression in the organ of Corti upon Hes1 knockdown is consistent with cell phenotypes related to lateral inhibition mechanism interference in the inner ear. The lentivirus-based expression of Hes1-sh RNA is a valuable strategy for genetic interference in the organ of Corti and for future evaluation of its efficacy in protocols aiming at the regeneration of hair cells in vivo.
- PDIA1 acts as master organizer of NOX1/NOX4 balance and phenotype response in vascular smooth muscle(2021) FERNANDES, Denise C.; JR, Joao Wosniak; GONCALVES, Renata C.; TANAKA, Leonardo Y.; FERNANDES, Carolina G.; ZANATTA, Daniela B.; MATTOS, Ana Barbosa M. de; STRAUSS, Bryan E.; LAURINDO, Francisco R. M.Changes in vascular smooth muscle cell (VSMC) phenotype underlie disease pathophysiology and are strongly regulated by NOX NADPH oxidases, with NOX1 favoring synthetic proliferative phenotype and NOX4 supporting differentiation. Growth factor-triggered NOX1 expression/activity strictly depends on the chaperone oxidoreductase protein disulfide isomerase-A1 (PDIA1). Intracellular PDIA1 is required for VSMC migration and cytoskeleton organization, while extracellular PDIA1 fine-tunes cytoskeletal mechanoadaptation and vascular remodeling. We hypothesized that PDIA1 orchestrates NOX1/NOX4 balance and VSMC phenotype. Using an inducible PDIA1 overexpression model in VSMC, we showed that early PDIA1 overexpression (for 24-48 h) increased NOX1 expression, hydrogen peroxide steady-state levels and spontaneous VSMC migration distances. Sustained PDIA1 overexpression for 72 h and 96 h supported high NOX1 levels while also increasing NOX4 expression and, remarkably, switched VSMC phenotype to differentiation. Differentiation was preceded by increased nuclear myocardin and serum response factor-response element activation, with no change in cell viability. Both NOX1 and hydrogen peroxide were necessary for later PDIA1-induced VSMC differentiation. In primary VSMC, PDIA1 knockdown decreased nuclear myocardin and increased the proliferating cell nuclear antigen expression. Newly-developed PDIA1 -overexpressing mice (TgPDIA1) exhibited normal general and cardiovascular baseline phenotypes. However, in TgPDIA1 carotids, NOX1 was decreased while NOX4 and calponin expressions were enhanced, indicating overdifferentiation vs. normal carotids. Moreover, in a rabbit overdistension injury model during late vascular repair, PDIA1 silencing impaired VSMC redifferentiation and NOX1/NOX4 balance. Our results suggest a model in which PDIA1 acts as an upstream organizer of NOX1/NOX4 balance and related VSMC phenotype, accounting for baseline differentiation setpoint.
conferenceObject Membrane coating for nonreplicating adenoviral vectors aids gene delivery in a murine model of melanoma(2021) TESSAROLLO, N. G.; DOMINGUES, A. C. M.; STRAUSS, B. E.conferenceObject ONCOLYSIS MEDIATED BY INFB AND ARF GENE TRANSFER ACTIVATES KEY COMPONENTS OF THE IMMUNE SYSTEM(2021) CERQUEIRA, O. L. D.; STRAUSS, B. E.conferenceObject DEVELOPMENT OF ADENOVIRAL VECTOR-MEDIATED GENE THERAPY AGAINST CANINE MELANOMA CELL LINES(2021) RODRIGUES, O. A.; STRAUSS, B. E.- miR-138-5p induces aggressive traits by targeting Trp53 expression in murine melanoma cells, and correlates with poor prognosis of melanoma patients(2021) CRUZ, A. T. da; HUNGER, A.; MELO, F. H. M. de; MONTEIRO, A. C.; Paré G. C.; LAI, D.; ALVES-FERNANDES, D. K.; AYUB, A. L. P.; CORDERO, E. M.; FILHO, J. F. D. S.; SCHNEIDER-STOCK, R.; STRAUSS, B. E.; TRON, V.; JASIULIONIS, M. G.Deregulation of miRNAs contributes to the development of distinct cancer types, including melanoma, an aggressive form of skin cancer characterized by high metastatic potential and poor prognosis. The expression of a set of 580 miRNAs was investigated in a model of murine melanoma progression, comprising non-metastatic (4C11-) and metastatic melanoma (4C11+) cells. A significant increase in miR-138-5p expression was found in the metastatic 4C11+ melanoma cells compared to 4C11-, which prompted us to investigate its role in melanoma aggressiveness. Functional assays, including anoikis resistance, colony formation, collective migration, serum-deprived growth capacity, as well as in vivo tumor growth and experimental metastasis were performed in 4C11- cells stably overexpressing miR-138-5p. miR-138-5p induced an aggressive phenotype in mouse melanoma cell lines leading to increased proliferation, migration and cell viability under stress conditions. Moreover, by overexpressing miR-138-5p, low-growing and non-metastatic 4C11- cells became highly proliferative and metastatic in vivo, similar to the metastatic 4C11+ cells. Luciferase reporter analysis identified the tumor suppressor Trp53 as a direct target of miR-138-5p. Using data sets from independent melanoma cohorts, miR-138-5p and P53 expression were also found deregulated in human melanoma samples, with their levels negatively and positively correlated with prognosis, respectively. Our data shows that the overexpression of miR-138-5p contributes to melanoma metastasis through the direct suppression of Trp53. © 2021
- Current Status of Canine Melanoma Diagnosis and Therapy: Report From a Colloquium on Canine Melanoma Organized by ABROVET (Brazilian Association of Veterinary Oncology)(2021) FONSECA-ALVES, Carlos Eduardo; FERREIRA, Enio; MASSOCO, Cristina de Oliveira; STRAUSS, Bryan Eric; FAVARO, Wagner Jose; DURAN, Nelson; CRUZ, Natalia Oyafuso da; CUNHA, Simone Carvalho dos Santos; CASTRO, Jorge Luiz Costa; RANGEL, Marcelo Monte Mor; BRUNNER, Carlos Henrique Maciel; TELLADO, Matias; ANJOS, Denner Santos dos; FERNANDES, Simone Crestoni; NARDI, Andrigo Barbosa de; BIONDI, Luiz Roberto; DAGLI, Maria Lucia Zaidan
- Exploration of p53 plus interferon-beta gene transfer for the sensitization of human colorectal cancer cell lines to cell death(2021) VALLE, Paulo Roberto Del; MENDONCA, Samir Andrade; ANTUNES, Fernanda; HUNGER, Aline; TAMURA, Rodrigo E.; ZANATTA, Daniela Bertolini; STRAUSS, Bryan E.While treatments for colorectal cancer continue to improve, some 50% of patients succumb within 5 years, pointing to the need for additional therapeutic options. We have developed a modified non-replicating adenoviral vector for gene transfer, called AdRGD-PG, which offers improved levels of transduction and transgene expression. Here, we employ the p53-responsive PG promoter to drive expression of p53 or human interferon-beta (hIFN beta) in human colorectal cancer cell lines HCT116(wt) (wtp53), HCT116(-/-) (p53 deficient) and HT29 (mutant p53). The HCT116 cell lines were both easily killed with p53 gene transfer, while combined p53 and hIFN beta cooperated for the induction of HT29 cell death and emission of immunogenic cell death (ICD) markers. Elevated annexinV staining and caspase 3/7 activity point to cell death by a mechanism consistent with apoptosis. P53 gene transfer alone or in combination with hIFN beta sensitized all cell lines to chemotherapy, permitting the application of low drug doses while still achieving significant loss of viability. While endogenous p53 status was not sufficient to predict response to treatment, combined p53 and hIFN beta provided an additive effect in HT29 cells. We propose that this approach may prove effective for the treatment of colorectal cancer, permitting the use of limited drug doses.
- Clinical Applications and Immunological Aspects of Electroporation-Based Therapies(2021) LUZ, Jean Carlos dos Santos da; ANTUNES, Fernanda; CLAVIJO-SALOMON, Maria Alejandra; SIGNORI, Emanuela; TESSAROLLO, Nayara Gusmao; STRAUSS, Bryan E.Reversible electropermeabilization (RE) is an ultrastructural phenomenon that transiently increases the permeability of the cell membrane upon application of electrical pulses. The technique was described in 1972 by Neumann and Rosenheck and is currently used in a variety of applications, from medicine to food processing. In oncology, RE is applied for the intracellular transport of chemotherapeutic drugs as well as the delivery of genetic material in gene therapies and vaccinations. This review summarizes the physical changes of the membrane, the particularities of bleomycin, and the immunological aspects involved in electrochemotherapy and gene electrotransfer, two important EP-based cancer therapies in human and veterinary oncology.