A5037639617- Advanced Breast Cancer Therapies
- Pancreatic function and diabetes
- Cancer, Hypoxia, and Metabolism
- Cancer Treatment and Pharmacology
- Endoplasmic Reticulum Stress and Disease
- Diabetes and associated disorders
- Cell Image Analysis Techniques
- Cancer Research and Treatments
- Photodynamic Therapy Research Studies
- bioluminescence and chemiluminescence research
- Nanoplatforms for cancer theranostics
- Computational Drug Discovery Methods
- Cancer, Stress, Anesthesia, and Immune Response
- Cancer Cells and Metastasis
- TGF-β signaling in diseases
- Growth Hormone and Insulin-like Growth Factors
- Genetics and Neurodevelopmental Disorders
- 3D Printing in Biomedical Research
- Enzyme function and inhibition
- Melanoma and MAPK Pathways
- Biological Research and Disease Studies
- Diabetes Management and Research
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Microtubule and mitosis dynamics
Instituto Butantan
2023-2024
Universidade de São Paulo
2012-2023
Universidade Cidade de São Paulo
2022
Abstract Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity such aberrant signaling. Although inhibition signaling has been explored extensively, there is increasing evidence overactivation same can also disrupt cancer cause lethality. We show here protein phosphatase 2A (PP2A) hyperactivates multiple engages responses in colon cells. Genetic compound screens...
Abstract Background Metastasis is the main factor responsible for death in breast cancer patients. Matrix metalloproteinases (MMPs) and their inhibitors, known as tissue inhibitors of MMPs (TIMPs), membrane-associated MMP inhibitor (RECK), are essential metastatic process. We have previously shown a positive correlation between expression during progression; however, molecular mechanisms underlying this coordinate regulation remain unknown. In report, we investigated whether TGF-β1 could be...
Breast cancer is the main cause of mortality among women. The disease presents high recurrence mainly due to incomplete efficacy primary treatment in killing all cells. Photodynamic therapy (PDT), an approach that causes tissue destruction by visible light presence a photosensitizer (Ps) and oxygen, appears as promising alternative could be used adjunct chemotherapy surgery for curing cancer. However, PDT treat breast tumours well molecular mechanisms lead cell death remain unclear. In this...
Abstract Lack of effective treatments for aggressive breast cancer is still a major global health problem. We have previously reported that photodynamic therapy using methylene blue as photosensitizer (MB-PDT) massively kills metastatic human cancer, marginally affecting healthy cells. In this study, we aimed to unveil the molecular mechanisms behind MB-PDT effectiveness and specificity towards tumor Through lipidomics biochemical approaches, demonstrated efficiency rely on polyunsaturated...
Abstract Photodynamic therapy (PDT) appears as a promising alternative in the treatment of breast cancer since it can be highly effective curing while preserving normal tissue. However, predicting outcomes PDT still constitutes great challenge. One parameters that are usually empirically determined is rate photon flux delivered to tissue (light fluence rate). In present study, we intended understand why monolayers human cells derived from mammary adenocarcinomas (MDA‐MB‐231 and MCF‐7)...
Maintaining islet cell viability in vitro, although challenging, appears to be a strategy for improving the outcome of pancreatic transplantation. We have shown that prolactin (PRL) leads beta-cell cytoprotection against apoptosis, an effect mediated by heat shock protein B1 (HSPB1). Since role HSPB1 beta-cells is still unclear and hormone concentration used not compatible with clinical applications because all side effects displayed other tissues, we explored molecular mechanisms which...
<div>Abstract<p>Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress response programs that counteract the inherent toxicity such aberrant signaling. Although inhibition signaling has been explored extensively, there is increasing evidence overactivation same can also disrupt cancer cause lethality. We show here protein phosphatase 2A (PP2A) hyperactivates multiple engages responses in colon cells. Genetic...
During type 1 diabetes mellitus (T1DM) development, beta-cells undergo intense endoplasmic reticulum (ER) stress that could result in apoptosis through the failure of adaptation to unfolded protein response (UPR). Islet transplantation is considered an attractive alternative among beta-cell replacement therapies for T1DM. To avoid loss will jeopardize transplant's outcome, several strategies are being studied. We have previously shown prolactin induces protection against proinflammatory...
ABSTRACT Cancer homeostasis depends on a balance between activated oncogenic pathways driving tumorigenesis and engagement of stress-response programs that counteract the inherent toxicity such aberrant signaling. While inhibition signaling has been explored extensively, there is increasing evidence overactivation same can also disrupt cancer cause lethality. We show here Protein Phosphatase 2A (PP2A) hyperactivates multiple engages stress responses in colon cells. Genetic compound screens...
The success of islet transplantation has improved lately. Unfortunately, it is still compromised by cell loss. We have shown that prolactin (PRL) inhibits beta-cell apoptosis and up-regulates the antiapoptotic Heat Shock Protein B1 (HSPB1) in human islets. Since its function pancreatic islets not been studied, we explored role HSPB1 PRL-induced survival. significant cytoprotection control cells was abrogated silenced cells, overexpression recovered PRL-mediated inhibition cytokine-induced...
In view of the great demand for human beta-cells physiological and medical studies, we generated cell lines derived from insulinomas which secrete insulin, C-peptide express neuroendocrine islet markers. this study, set out to characterize their proteomes, comparing them those primary using DIGE followed by MS. The results were validated Western blotting. An average 1800 spots was detected with less than 1% exhibiting differential abundance. Proteins more abundant in islets, such as...
The nucleolus is sensitive to stress and can orchestrate a chain of cellular events in response signals. Despite being growth factor, FGF2 has antiproliferative tumor-suppressive functions some contexts. In this work, we investigated how the effect modulates chromatin-, nucleolus- rDNA-associated proteins. chromatin nucleolar proteome indicated that stimulation proteins related transcription, rRNA expression chromatin-remodeling global transcriptional rate area increased along with...
Abstract Matrix metalloproteinases (MMPs) and their specific inhibitors, known as tissue inhibitors of MMPs (TIMPs) the membrane-associated MMP inhibitor (RECK), are involved in several steps metastatic process. Previous results from our laboratory showed a positive correlation between high mRNA expression levels upon breast cancer progression, both cellular models tumor samples. However, molecular mechanisms underlying this coordinate regulation MMPs, TIMPs RECK remain unknown. Since...
<p>Figure S9: Single-cell RNAseq identify transcriptional signatures downregulated in CRC cells after acquired resistance to the combination of LB-100 and adavosertib UMAP representations HT-29 (A) SW-480 (B) colored by activity scores for indicated pathways. UMAPs sample origin from both cell lines are present left reference. The boxen plots show pathway parental (red) resistant (blue) cells.</p>
<p>Supplementary table 6: Stress-focused drug screens AUC differences in SW-480 cells Area Under the Curve (AUC) from each compound of stress-focused screen presence or absence LB-100. Compounds are ranked by difference between LB-100-treated and untreated samples.</p>
<p>Supplementary table 3: Full list of genes whose knockout attenuated LB-100 toxicity in SW-480 cells the CRISPR-KO screen FDR smaller or equal to 0.25 and log2 fold change greater 1 treated/untreated comparison were criteria for hit selection.</p>
<p>Supplementary table 1: Cancer cell lines with oncogenic drivers The mutational status of the was compiled from ATCC, Catalogue Somatic Mutations in (COSMIC) and Cell Model Passport, Wellcome Trust Sanger Institute, Depmap portal databases.</p>
<p>Supplementary table 4: The composition of the stress-focused drug library Compounds comprising with their respective targets.</p>
<p>Supplementary table 4: The composition of the stress-focused drug library Compounds comprising with their respective targets.</p>
<p>Figure S7: Normal tissues from the orthotopic CRC PDXs are not affected by LB-100, adavosertib, or combination. Representative Hematoxylin & Eosin (H&E) stainings of heart, liver, lung, and spleen PDOX1 treated as indicated. Original magnifications indicated.</p>