A5019910604- Melanoma and MAPK Pathways
- Sirtuins and Resveratrol in Medicine
- Computational Drug Discovery Methods
- Histone Deacetylase Inhibitors Research
- Air Quality and Health Impacts
- Redox biology and oxidative stress
- Carcinogens and Genotoxicity Assessment
- Hedgehog Signaling Pathway Studies
- Endoplasmic Reticulum Stress and Disease
- Indoor Air Quality and Microbial Exposure
- Cancer-related Molecular Pathways
- Cutaneous lymphoproliferative disorders research
- Skin Protection and Aging
- Cell death mechanisms and regulation
- Bioactive Natural Diterpenoids Research
- Biochemical effects in animals
- Autophagy in Disease and Therapy
- Genetics, Aging, and Longevity in Model Organisms
- Genomics, phytochemicals, and oxidative stress
- Biological Stains and Phytochemicals
- Cancer Mechanisms and Therapy
- RNA Interference and Gene Delivery
- NF-κB Signaling Pathways
- RNA regulation and disease
- Microbial Natural Products and Biosynthesis
Universidade Federal de São Paulo
2019-2025
Universidade de São Paulo
2014-2020
BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all relapse within a few months. Understanding molecular mechanisms underpinning BRAFi-based therefore an important issue. Here we identified previously unsuspected mechanism of BRAFi resistance driven by elevated Hedgehog (Hh) pathway activation that observed in cohort after vemurafenib treatment. Specifically, demonstrate cell lines, with acquired vitro-induced...
The BRAF(V600E) mutation confers constitutive kinase activity and accounts for >90% of BRAF mutations in melanoma. This genetic alteration is a current therapeutic target; however, the antitumorigenic effects inhibitor vemurafenib are short-lived majority patients present tumor relapse short period after treatment. Characterization resistance has been essential to efficacy next generation strategies. Herein, we found that acute inhibition induced decrease active MMP-2, MT1-MMP MMP-9, but did...
Abstract Tumor recurrence, which can occur many years after therapeutic intervention, represents the main challenge in clinical oncology. Clinically, this period between “cure” of primary tumor and its local or distal metastatic relapse is known as “dormancy state.” dormancy has been linked to resistance a high potential malignant neoplasms. During immunoediting, immune response shapes adapt thrive within an immunocompetent host. Epigenetic modulation important way by cells quickly regulate...
Atmospheric particulate matter (PM) is genotoxic and recently was classified as carcinogenic to humans by the International Agency for Research on Cancer. PM chemical composition varies depending source atmospheric conditions. The Salmonella /microsome assay most used mutagenicity test can identify major classes responsible observed mutagenicity. objective of this work characterize samples from a countryside city, Limeira, Brazil, which influenced heavy traffic sugar cane biomass burning....
Despite the recent advances in clinical management of melanoma, there remains a need for new pharmacological approaches to treat this cancer. 2-methoxyestradiol (2ME) is metabolite estrogen that has shown anti-tumor effects many cancer types. In study we show 2ME treatment leads growth inhibition melanoma cells, an effect associated with entry into senescence, decreased pRb and Cyclin B1 expression, increased p21/Cip1 expression G2/M cell cycle arrest. also inhibits colony formation assay,...
Melanoma is a type of skin cancer with an elevated incidence metastasis and chemoresistance. Such features hamper treatment success these neoplasms, demanding the search for new therapeutic options. Using two-step resin-based approach, we recently demonstrated that cytotoxic prodiginines bind to inhibitor apoptosis protein, survivin. Herein, explore role survivin in melanoma whether its modulation related antimelanoma properties three (prodigiosin, cyclononylprodigiosin, nonylprodigiosin)...
The Salmonella/microsome assay is the most used for evaluation of air particulate matter (PM) mutagenicity and a positive correlation between strain TA98 responses benzo[a]pyrene (B[a]P) levels in PM has been found. However, it seems that major causes this are nitro oxy‐PAHs. Salmonella YG5161, 30‐times more responsive to B[a]P developed. To verify if YG5161 was sufficiently sensitive detect associated with mutagenicity, samples were collected Brazil Sweden, extracted toluene tested...
Deregulation of miRNAs contributes to the development distinct cancer types, including melanoma, an aggressive form skin characterized by high metastatic potential and poor prognosis. The expression a set 580 was investigated in model murine melanoma progression, comprising non-metastatic (4C11-) (4C11+) cells. A significant increase miR-138-5p found 4C11+ cells compared 4C11-, which prompted us investigate its role aggressiveness. Functional assays, anoikis resistance, colony formation,...
Melanoma accounts for only 4% of malignant neoplasms the skin, but is considered most serious because it highly deadly. Mutations in MAPK (Ras-Raf-MEK-ERK) pathway closely linked to lack control cell proliferation. Especially melanoma, this has become a target development oncogene-targeted therapies, such as potent inhibitors v-Raf murine sarcoma viral oncogene homolog B (BRAFi) and mitogen-activated protein kinase (MEKi). Very high rates response have been achieved, patients are relapsed...
Abstract Melanoma represents the deadliest of all skin cancers being responsible for more than 75% cancer-related deaths. Although results with BRAF inhibitors have been very promising, practically patients treated thus far developed resistance to these drugs. The Hedgehog (Hh) signaling pathway has implicated in a variety malignancies, including melanoma. However, there are no reports on activation this setting vemurafenib-resistance. Herein, we first identified that melanoma cell lines,...
NRAS-mutations arise in 15–20% of all melanomas and are associated with aggressive disease poor prognosis. Besides, the treatment for NRAS-mutant melanoma not very efficient is currently limited to immune checkpoints inhibitors or chemotherapy. 4-nerolidylcathecol (4-NC), a natural product extracted from Pothomorphe umbellata, induces apoptosis cells by ROS production, DNA damage increased p53 expression, addition inhibiting invasion reconstructed skin. Moreover, 4-NC showed cytotoxicity...
Oxidation and reduction of thiol proteins are considered the major mechanisms by which reactive oxidants control cellular signaling pathways. Protein disulfide isomerase (PDI) is a member thioredoxin superfamily. PDI multifunctional protein primarily involved in exchanges native ER proteins. Emerging evidence from our group indicates functional association between NADPH oxidase family members (Nox). We have shown that can regulate Nox activation expression multiple cell types. Therefore,...
Abstract Melanoma accounts for only 4% of skin malignancies, but it has a high mortality rate. Though the specific inhibitors MAPK pathway (BRAFi and MEKi) have revolutionized melanoma treatment, most patients are subject to resistance, justifying constant search new therapeutic compounds. Recent data from our laboratory indicated that 4-nerolidylcathecol (4-NC), extracted Pothomorphe umbellata, native Brazilian plant, induces apoptosis in cells by ROS production, DNA damage p53 expression...