MIRIAN GALLIOTE MORALE
Projetos de Pesquisa
Unidades Organizacionais
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- p53 and metabolism: From mechanism to therapeutics(2018) SIMABUCO, F. M.; MORALE, M. G.; PAVAN, I. C. B.; MORELLI, A. P.; SILVA, F. R.; TAMURA, R. E.The tumor cell changes itself and its microenvironment to adapt to different situations, including action of drugs and other agents targeting tumor control. Therefore, metabolism plays an important role in the activation of survival mechanisms to keep the cell proliferative potential. The Warburg effect directs the cellular metabolism towards an aerobic glycolytic pathway, despite the fact that it generates less adenosine triphosphate than oxidative phosphorylation; because it creates the building blocks necessary for cell proliferation. The transcription factor p53 is the master tumor suppressor; it binds to more than 4,000 sites in the genome and regulates the expression of more than 500 genes. Among these genes are important regulators of metabolism, affecting glucose, lipids and amino acids metabolism, oxidative phosphorylation, reactive oxygen species (ROS) generation and growth factors signaling. Wild-type and mutant p53 may have opposing effects in the expression of these metabolic genes. Therefore, depending on the p53 status of the cell, drugs that target metabolism may have different outcomes and metabolism may modulate drug resistance. Conversely, induction of p53 expression may regulate differently the tumor cell metabolism, inducing senescence, autophagy and apoptosis, which are dependent on the regulation of the PI3K/AKT/mTOR pathway and/or ROS induction. The interplay between p53 and metabolism is essential in the decision of cell fate and for cancer therapeutics. © Simabuco et al.
conferenceObject HPV-positive tumor cell lines exhibit major alterations in Toll-like receptor pathways and depend on HMGB1 expression(2018) MORALE, Mirian Galliote; ABJAUDE, Walason da Silva; SILVA, Aline Montenegro da; VILLA, Luisa Lina; BOCCARDO, Enrique- Innate immunity and HPV: friends or foes(2018) NUNES, Rafaella Almeida Lima; MORALE, Mirian Galliote; SILVA, Gabriela Avila Fernandes; VILLA, Luisa Lina; TERMINI, LaraMost human papillomavirus infections are readily cleared by the host immune response. However, in some individuals, human papillomavirus can establish a persistent infection. The persistence of high-risk human papillomavirus infection is the major risk factor for cervical cancer development. These viruses have developed mechanisms to evade the host immune system, which is an important step in persistence and, ultimately, in tumor development. Several cell types, receptors, transcription factors and inflammatory mediators involved in the antiviral immune response are viral targets and contribute to tumorigenesis. These targets include antigen-presenting cells, macrophages, natural killer cells, Toll-like receptors, nuclear factor kappa B and several cytokines and chemokines, such as interleukins, interferon and tumor necrosis factor. In the present review, we address both the main innate immune response mechanisms involved in HPV infection clearance and the viral strategies that promote viral persistence and may contribute to cancer development. Finally, we discuss the possibility of exploiting this knowledge to develop effective therapeutic strategies.
- Oxidative stress: therapeutic approaches for cervical cancer treatment(2018) SILVA, Gabriela Avila Fernandes; NUNES, Rafaella Almeida Lima; MORALE, Mirian Galliote; BOCCARDO, Enrique; AGUAYO, Francisco; TERMINI, LaraOBJECTIVES: Oxidative stress results from an imbalance between the generation and elimination of oxidant species. This condition may result in DNA, RNA and protein damage, leading to the accumulation of genetic alterations that can favor malignant transformation. Persistent infection with high-risk human papillomavirus types is associated with inflammatory responses and reactive oxygen species production. In this context, oxidative stress, chronic inflammation and high-risk human papillomavirus can act in a synergistic manner. To counteract the harmful effects of oxidant species, protective molecules, known as antioxidant defenses, are produced by cells to maintain redox homeostasis. In recent years, the use of natural antioxidants as therapeutic strategies for cancer treatment has attracted the attention of the scientific community. This review discusses specific molecules and mechanisms that can act against or together with oxidative stress, presenting alternatives for cervical cancer prevention and treatment.
- HPV-transformed cells exhibit altered HMGB1-TLR4/MyD88-SARM1 signaling axis(2018) MORALE, Mirian Galliote; ABJAUDE, Walason da Silva; SILVA, Aline Montenegro; VILLA, Luisa Lina; BOCCARDO, EnriqueCervical cancer is one of the leading causes of cancer death in women worldwide. Persistent infection with high-risk human papillomavirus (HPV) types is the main risk factor for the development of cervical cancer precursor lesions. HPV persistence and tumor development is usually characterized by innate immune system evasion. Alterations in Toll-like receptors (TLR) expression and activation may be important for the control of HPV infections and could play a role in the progression of lesions and tumors. In the present study, we analyzed the mRNA expression of 84 genes involved in TLR signaling pathways. We observed that 80% of the differentially expressed genes were downregulated in cervical cancer cell lines relative to normal keratinocytes. Major alterations were detected in genes coding for several proteins of the TLR signaling axis, including TLR adaptor molecules and genes associated with MAPK pathway, NF kappa B activation and antiviral immune response. In particular, we observed major alterations in the HMGB1-TLR4 signaling axis. Functional analysis also showed that HMGB1 expression is important for the proliferative and tumorigenic potential of cervical cancer cell lines. Taken together, these data indicate that alterations in TLR signaling pathways may play a role in the oncogenic potential of cells expressing HPV oncogenes.