A5068808226- Cancer-related gene regulation
- Nutrition and Health in Aging
- Wnt/β-catenin signaling in development and cancer
- Macrophage Migration Inhibitory Factor
- Hedgehog Signaling Pathway Studies
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- GDF15 and Related Biomarkers
- Biochemical and Molecular Research
- Hippo pathway signaling and YAP/TAZ
- 14-3-3 protein interactions
- Mast cells and histamine
- Sirtuins and Resveratrol in Medicine
- Diet and metabolism studies
- Gut microbiota and health
- Genomics and Chromatin Dynamics
- Cancer-related Molecular Pathways
- HER2/EGFR in Cancer Research
- Chromatin Remodeling and Cancer
- Liver physiology and pathology
- Epigenetics and DNA Methylation
- Biochemical Acid Research Studies
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
McMaster University
2022-2025
Istituto Pasteur
2019-2023
Sapienza University of Rome
2018-2023
Type 2 diabetes and obesity increase the risk of developing colorectal cancer. Metformin may reduce cancer but mechanisms mediating this effect remain unclear. In mice humans, a high-fat diet (HFD), metformin are known to alter gut microbiome whether is important for influencing tumor growth not known. Mice with syngeneic MC38 colon adenocarcinomas were treated or feces obtained from control mice. We find that compared chow-fed controls, increased when fed HFD acceleration can be partially...
Highlights•Therapeutic doses of phenformin suppress Hedgehog-dependent tumor growth•Phenformin inhibits mGPD in cancer cells but does not affect complex I activity•Inhibition mimics and increases redox state/NADH content•Elevated NADH promotes Gli1/CtBP2 formation inhibition growthSummaryThe antidiabetic drug displays potent anticancer activity different tumors, its mechanism action remains elusive. Using Shh medulloblastoma as model, we show here that at clinically relevant concentrations,...
The aberrant activation of hedgehog (HH) signaling is a leading cause the development medulloblastoma, pediatric tumor cerebellum. FDA‑approved HH inhibitor, Vismodegib, which targets transmembrane transducer SMO, has shown limited efficacy in patients with due to compensatory mechanisms that maintain an active HH‑GLI status. Thus, identification novel actionable mechanisms, directly affecting activity HH‑regulated GLI transcription factors important goal for these malignancies. In this...
Targeted approaches aiming at modulating NHERF1 activity, rather than its overall expression, would be preferred to preserve the normal functions of this versatile protein. We focused our attention on NHERF1/PDZ1 domain that governs membrane recruitment/displacement through a transient phosphorylation switch. herein report design and synthesis novel PDZ1 inhibitors. These compounds have potential therapeutic value when used in combination with antagonists β-catenin augment apoptotic death...
Growth differentiation factor 15 (GDF15) is a cytokine of the TGFβ family. Here, we analyzed GDF15 levels in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who participated OCOG-ALMERA (NCT02115464), phase II randomized clinical trial, that investigated metformin combination standard care concurrent chemoradiotherapy (cCRT). was not able to demonstrate benefit arm. Therefore, biomarker studies are needed better define stratification parameters for future trials.
The Wnt/β-catenin pathway is often found deregulated in cancer. aberrant accumulation of β-catenin the cell nucleus results development various malignancies. Specific drugs against this signaling for clinical treatments have not been approved yet. Herein we report inhibitors potential therapeutic value as anticancer agents. Ethyl 4-((4-(trifluoromethyl)phenyl)sulfonamido)benzoate (compound 14) inhibits effect on Wnt reporter with an IC50 7.0 μM, significantly reduces c-MYC levels, HCT116...
Despite intensive efforts, no inhibitors of the Wnt/β-catenin signaling pathway have been approved so far for clinical treatment cancer. We synthesized novel N-(heterocyclylphenyl)benzenesulfonamides as β-catenin inhibitors. Compounds 5–10 showed strong inhibition luciferase activity. 5 and 6 inhibited MDA-MB-231, HCC1806, HCC1937 TNBC cells. Compound 9 induced in vitro cell death SW480 HCT116 cells vivo tumorigenicity a human colorectal cancer line HCT116. In co-immunoprecipitation study...
<title>Abstract</title> Growth differentiation factor 15 (GDF15) is a cytokine of the TGFβ family. Here, we analyzed GDF15 levels in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who participated OCOG-ALMERA (NCT02115464), phase II randomized clinical trial, that investigated metformin combination standard-of-care concurrent chemoradiotherapy (cCRT). <bold>Methods</bold>: Patients were to treatment platinum-based chemotherapy and chest radiotherapy (60-66Gy), or...