FERNANDA ANTUNES
Índice h a partir de 2011
3
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- Emerging Autophagy Functions Shape the Tumor Microenvironment and Play a Role in Cancer Progression-Implications for Cancer Therapy(2020) BUSTOS, Silvina Odete; ANTUNES, Fernanda; RANGEL, Maria Cristina; CHAMMAS, RogerThe tumor microenvironment (TME) is a complex environment where cancer cells reside and interact with different types of cells, secreted factors, and the extracellular matrix. Additionally, TME is shaped by several processes, such as autophagy. Autophagy has emerged as a conserved intracellular degradation pathway for clearance of damaged organelles or aberrant proteins. With its central role, autophagy maintains the cellular homeostasis and orchestrates stress responses, playing opposite roles in tumorigenesis. During tumor development, autophagy also mediates autophagy-independent functions associated with several hallmarks of cancer, and therefore exerting several effects on tumor suppression and/or tumor promotion mechanisms. Beyond the concept of degradation, new different forms of autophagy have been described as modulators of cancer progression, such as secretory autophagy enabling intercellular communication in the TME by cargo release. In this context, the synthesis of senescence-associated secretory proteins by autophagy lead to a senescent phenotype. Besides disturbing tumor treatment responses, autophagy also participates in innate and adaptive immune signaling. Furthermore, recent studies have indicated intricate crosstalk between autophagy and the epithelial-mesenchymal transition (EMT), by which cancer cells obtain an invasive phenotype and metastatic potential. Thus, autophagy in the cancer context is far broader and complex than just a cell energy sensing mechanism. In this scenario, we will discuss the key roles of autophagy in the TME and surrounding cells, contributing to cancer development and progression/EMT. Finally, the potential intervention in autophagy processes as a strategy for cancer therapy will be addressed.
- Potentiation of combined p19Arf and interferon-beta cancer gene therapy through its association with doxorubicin chemotherapy(2022) V, Ruan F. Medrano; SALLES, Thiago A.; DARIOLLI, Rafael; ANTUNES, Fernanda; FEITOSA, Valker A.; HUNGER, Aline; CATANI, Joao P. P.; MENDONCA, Samir A.; TAMURA, Rodrigo E.; LANA, Marlous G.; RODRIGUES, Elaine G.; STRAUSS, Bryan E.Balancing safety and efficacy is a major consideration for cancer treatments, especially when combining cancer immunotherapy with other treatment modalities such as chemotherapy. Approaches that induce immunogenic cell death (ICD) are expected to eliminate cancer cells by direct cell killing as well as activation of an antitumor immune response. We have developed a gene therapy approach based on p19Arf and interferon-beta gene transfer that, similar to conventional inducers of ICD, results in the release of DAMPS and immune activation. Here, aiming to potentiate this response, we explore whether association between our approach and treatment with doxorubicin (Dox), a known inducer of ICD, could further potentiate treatment efficacy without inducing cardiotoxicity, a critical side effect of Dox. Using central composite rotational design analysis, we show that cooperation between gene transfer and chemotherapy killed MCA205 and B16F10 cells and permitted the application of reduced viral and drug doses. The treatments also cooperated to induce elevated levels of ICD markers in MCA205, which correlated with improved efficacy of immunotherapy in vivo. Treatment of subcutaneous MCA205 tumors associating gene transfer and low dose (10 mg/kg) chemotherapy resulted in inhibition of tumor progression. Moreover, the reduced dose did not cause cardiotoxicity as compared to the therapeutic dose of Dox (20 mg/kg). The association of p19Arf/interferon-beta gene transfer and Dox chemotherapy potentiated antitumor response and minimized cardiotoxicity.
- Protein Disulfide Isomerase overexpression induces mitochondrial reorganization and a differentiated VSMC phenotype: role of mitofusin-2(2023) WOSNIAK JR., Joao; RODRIGUES, Rafael F. G.; KAKIMOTO, Pamela A.; SILVA, Camille C. Caldeira da; ANTUNES, Fernanda; STRAUSS, Bryan E.; KOWALTOWSKI, Alicia; LAURINDO, Francisco R.
- Reporter system controlled by the involucrin promoter as a tool to follow epidermal differentiation(2022) FERNANDES, Myrian Thiago Pruschinski; SANTOS, Jeniffer Farias dos; FREITAS, Bruna Leticia; REIGADO, Gustavo Roncoli; ANTUNES, Fernanda; TESSAROLLO, Nayara Gusmao; CHAMBERGO, Felipe Santiago; STRAUSS, Bryan Eric; NUNES, Viviane AbreuVarious approaches have been explored to study skin biology, including the use of stem cells. Mesen-chymal stem cells (MSCs) from the umbilical cord can be safely and easily obtained; however, a simple strategy to monitor their differentiation is essential. Involucrin is a marker of keratinocyte differentiation, and its promoter (pINV) directs stratum-specific expression of this protein. We designed a reporter system containing EGFP under the control of pINV to assess MSC transdifferentiation into keratinocytes. The functional sequence of pINV was inserted into a lentiviral vector, producing LeGO-GpINV. MSCs were transduced with LeGO-GpINV and induced to transdifferentiate into keratinocytes under cultivation with keratinocyte serum-free medium. MSC transdifferentiation was confirmed by morphological changes and by the expression of epidermal markers by flow cytometry, quantitative PCR, Western blot and the activity of epidermal kallikreins 5, 6 and 7. After 14 days of transdifferentiation, MSCs transduced with LeGO-GpINV showed an increase in EGFP fluorescence and expressed CK10, CK14, involucrin and filag-grin. There was also an increase in kallikrein activity. This reporter system allowed us to temporally assess epidermal differentiation, simultaneously with involucrin expression, opening possibilities for the in vivo study of skin biology and in regenerative medicine.(c) 2022 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.
- Stable expression of shRNA for the control of recombinant adenovirus replication(2023) LANA, M. V. G.; ANTUNES, F.; TESSAROLLO, N. G.; STRAUSS, B. E.Preventing the replication of adenovirus could have practical uses, such as controlling infection with wild-type virus or in applications involving recombinant vectors. Mainly transient methods have been used to inhibit adenovirus replication, including siRNA or drugs. Here, we tested whether stable expression of shRNA designed to target hexon, Iva2, or pol can inhibit the replication of a recombinant adenoviral vector, Ad-LacZ (serotype 5, E1/E3 deleted), in 293T cells. Significant knockdown correlating with reduced Ad-LacZ replication was achieved only when hexon was targeted. Cell sorting and isolation of cellular clones further accentuated knockdown of the hexon transcript, reduced protein levels by more than 90%, and diminished adenovirus production. As visualized by transmission electron microscopy, the cellular clone expressing the hexon-specific shRNA yielded 89.2% fewer particles compared to the parental 293T cells. Full scale production followed by purification revealed a 90.2% reduction in Ad-LacZ biological titer. These results support the notion that stable expression of shRNA can be used as a means to control adenovirus replication.
- Perspectives for Combining Viral Oncolysis With Additional Immunotherapies for the Treatment of Melanoma(2022) CERQUEIRA, Otto Luiz Dutra; ANTUNES, Fernanda; ASSIS, Nadine G.; CARDOSO, Elaine C.; CLAVIJO-SALOMON, Maria A.; DOMINGUES, Ana C.; TESSAROLLO, Nayara G.; STRAUSS, Bryan E.Melanoma is the deadliest type of skin cancer with steadily increasing incidence worldwide during the last few decades. In addition to its tumor associated antigens (TAAs), melanoma has a high mutation rate compared to other tumors, which promotes the appearance of tumor specific antigens (TSAs) as well as increased lymphocytic infiltration, inviting the use of therapeutic tools that evoke new or restore pre-existing immune responses. Innovative therapeutic proposals, such as immune checkpoint inhibitors (ICIs), have emerged as effective options for melanoma. However, a significant portion of these patients relapse and become refractory to treatment. Likewise, strategies using viral vectors, replicative or not, have garnered confidence and approval by different regulatory agencies around the world. It is possible that further success of immune therapies against melanoma will come from synergistic combinations of different approaches. In this review we outline molecular features inherent to melanoma and how this supports the use of viral oncolysis and immunotherapies when used as monotherapies or in combination.
- 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.
- Induction of Immune-Stimulating Factors and Oncolysis Upon p14(ARF) Gene Transfer in Melanoma Cell Lines(2023) MENDONCA, Samir Andrade; ANTUNES, Fernanda; CERQUEIRA, Otto L. D.; VALLE, Paulo Roberto Del; HUNGER, Aline; OLIVEIRA, Percillia V. S. de; BRITO, Barbara; COSTANZI-STRAUSS, Eugenia; STRAUSS, Bryan E.Together with an anti-tumor immune response, oncolysis using a recombinant viral vector promises to eliminate cancer cells by both gene transfer and host-mediated functions. In this study we explore oncolysis induced by nonreplicating adenoviral vectors used for p14(ARF) and interferon-beta (hIFN beta) gene transfer in human melanoma cell lines, revealing an unexpected role for p14(ARF) in promoting cellular responses predictive of immune stimulation. Oncolysis was confirmed when UACC-62 (p53 wild-type) cells succumbed upon p14(ARF) gene transfer in vitro, whereas SK-Mel-29 (p53-mutant) benefitted from its combination with hIFN beta. In the case of UACC-62, in situ gene therapy in nude mice yielded reduced tumor progression in response to the p14(ARF) and hIFN beta combination. Potential for immune stimulation was revealed where p14(ARF) gene transfer in vitro was sufficient to induce emission of immunogenic cell death factors in UACC-62 and upregulate pro-immune genes, including IRF1, IRF7, IRF9, ISG15, TAP-1, and B2M. In SK-Mel-29, p14(ARF) gene transfer induced a subset of these factors. hIFN beta was, as expected, sufficient to induce these immune-stimulating genes in both cell lines. This work is a significant advancement for our melanoma gene therapy strategy because we revealed not only the induction of oncolysis, but also the potential contribution of p14(ARF) to immune stimulation.
- 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.
bookPart Metabolismo da célula tumoral(2022) SILVA, Gabriela Ávila Fernandes; TORTELLI JUNIOR, Tharcisio Citrângulo; ANTUNES, Fernanda