A5065416088- Melanoma and MAPK Pathways
- Advanced Glycation End Products research
- CAR-T cell therapy research
- Skin Protection and Aging
- Natural Antidiabetic Agents Studies
- Animal testing and alternatives
- Hedgehog Signaling Pathway Studies
- Cancer Genomics and Diagnostics
- Cutaneous Melanoma Detection and Management
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Angiogenesis and VEGF in Cancer
- Cancer-related Molecular Pathways
- Effects and risks of endocrine disrupting chemicals
- Biochemical effects in animals
- Cell Adhesion Molecules Research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- melanin and skin pigmentation
- Synthesis and biological activity
- Cancer Research and Treatments
- Immunotoxicology and immune responses
- Epigenetics and DNA Methylation
- Lymphatic System and Diseases
- Ear Surgery and Otitis Media
- Chemokine receptors and signaling
Instituto Butantan
2021
Universidade de São Paulo
2014-2021
Spanish National Cancer Research Centre
2017-2020
Universidad San Pedro
2017
Instituto de Ciências Farmacêuticas
2017
Universidade Federal de Alfenas
2012-2015
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...
The advanced glycation end products (AGEs) of proteins are common factors in the pathophysiology a number disorders related to aging. skin generation AGEs occurs mainly through nonenzymatic reactions extracellular matrix (ECM) dermis. have been touted as one responsible for healing impairment and loss elasticity skin, affecting growth, differentiation, cellular motility, well cytokines response, metalloproteinases expression, vascular hemostasis. In this study, we generated an vitro...
Different models of reconstructed human epidermis (RHE) are currently validated to assess skin irritation in vitro and ultimately the animal replacement Draize test. The development a new RHE model is challenge for many laboratories, representing potential gain autonomy improvement technological knowledge. Organization Economic Co-operation Development (OECD) encourages and, this purpose, offers thorough guideline on quality control parameters (OECD TG 439 performance standards). This work...
Our data suggest that impaired activity of myeloperoxidase (MPO) may play an important role in the dysfunction neutrophils from hyperglycemic rats. Neutrophil biochemical pathways include NADPH oxidase system and MPO enzyme. They both killing function neutrophils. The effect hyperglycemia on these enzymes consequences with regard to Candida albicans phagocytosis microbicidal property rat peritoneal is evaluated here. was measured using chemiluminescence cytochrome C reduction assays. by...
Melanoma is the most aggressive form of skin cancer and until recently, it was extremely resistant to radio-, immuno-, chemotherapy. Despite latest success BRAF V600E-targeted therapies, responses are typically short lived relapse all but certain. Furthermore, a percentage (40%) melanoma cells wild type. Emerging evidence suggests role for normal host in occurrence drug resistance. In current study, we compared variety cell culture models with an organotypic incomplete model (the "dermal...
Abstract Background: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) cervix. However, role MMPs inflammatory process Chlamydia trachomatis infection concomitant carcinogenic driven by HPV has not yet been addressed. In present study, we analyzed state MMP-9–RECK axis carcinogenesis. Methods: The levels MMP-9 and RECK expression were...
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,...
A bioassay-guided study aiming at identifying inhibitors of the glycation process on leaves Ocotea paranapiacabensis afforded four benzylisoquinoline alkaloids (1–4), with 1 and 2 identified as new naturals products, while 3 4 were previously described in literature, being magnocurarine. Purification was performed by column chromatography high-performance liquid chromatography. The structures isolated compounds elucidated spectroscopic methods including UV, NMR, HRMS. skin aging has been...
In melanoma development, oncogenic process is mediated by genetic and epigenetic mutations, few studies have so far explored the role of DNA methylation either as predisposition factor or biomarker. We tested patient samples for germline CDKN2A status found no evidence inactivation promoter hypermethylation. also investigated association clinical characteristics with pattern twelve genes relevant melanomagenesis. Five ( BAP1, MGMT, MITF, PALB2 , POT1 ) presented statistical between blood...
Different Passiflora species have been appointed as a promising herbal medicine due to antioxidant properties; however, their effect on oxidative process induced by diabetes is still controversial. We aimed evaluate effects of hydroethanolic extract 70% from P. edulis leaf biochemical blood markers, collagen glycation, production oxidant and platelet aggregation in diabetic rats. The phytochemical analysis the was performed dereplication using LC coupled Photodiode Array Detector Mass...
Abstract Background Natural killer (NK) cells originate from bone marrow precursors and mediate effective anti-tumor responses. Clinical trials of cytokine-primed memory-like (ML) NK in acute myeloid leukemia (AML) have demonstrated activity without major toxicity, including graft-versus-host disease or cytokine release syndrome. However, broad application non-expanded, non-engineered ML has been hindered by limited availability a single donor, thereby precluding aggressive dose escalation...
Epigenetic dysregulation is an important emerging hallmark of cutaneous melanoma development. The global loss DNA methylation in gene-poor regions and transposable elements cancer cells contributes to increased genomic instability. Long interspersed element-1 (LINE-1) sequences are the most abundant repetitive sequence genome can be evaluated as a surrogate marker level methylation. In this work, LINE-1 levels were melanomas normal melanocyte primary cell cultures investigate their possible...
170 Background: CRC is the 4 th leading cause of global cancer-related deaths, and novel therapeutic strategies for advanced are urgently needed. Adoptive cell therapy (ACT) effective in treating hematological malignancies; however, ACT solid tumors hindered by target antigen identification, restricted migration into tumors, survival tumor microenvironment (TME) due to immunosuppressive signals scarcity nutrients. NK cells central anti-tumor immunity can directly eliminate without prior...
Cutaneous melanoma (CM) is the most aggressive subtype of skin cancer, with increasing incidence over past several decades. DNA methylation a key element biological processes such as genomic imprinting, cell differentiation and senescence, deregulation this mechanism has been implicated in diseases, including cancer. In order to understand relationship CMs, we searched for an epigenetic signature cutaneous melanomas by comparing profiles between tumours benign melanocytes, precursor cells...
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,...
<h3>Background</h3> Tumor-infiltrating lymphocytes (TILs) are immune cells that have migrated from the bloodstream into a tumor. These play crucial role in body's response against cancer and their behavior function influenced by tumor microenvironment (TME), which includes various factors such as cytokines, chemokines, checkpoint (IC) molecules. TIL therapy represents promising avenue oncology for harnessing system to target eliminate cells. It can be combined with other immunotherapies (IO)...
Abstract The impact of advanced glycation end products (AGEs) accumulation is associated with the development and exacerbation many degenerative processes disorders, including aging cancer. AGEs in skin leads to stiffness loss elasticity by building up connective tissue during process. This process has implications extracellular matrix, affecting adhesion, migration, invasiveness potential melanoma cells. Furthermore, tumor correlated mechanical stiffness, contributing high metastatic...