Publications by authors named "Andrea Gherli"
Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5-10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4-7 years). The mechanisms underlying this neoplastic disease still remain uncovered.
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- The EVI1 gene is linked to a particularly aggressive form of acute myeloid leukemia (AML) characterized by abnormalities on chromosome 3q26.
- Selective and pan-histone deacetylase inhibitors (HDACis) have been identified as effective treatments for this type of leukemia by repressing EVI1 expression.
- The study suggests that the PA2G4 protein plays a key role in EVI1-related leukemia, and targeting PA2G4 could enhance the effects of HDACis, highlighting the potential for combination therapies in patients with 3q26 AML.
Article Synopsis
- PEST domain mutations are commonly found in various hematopoietic malignancies, like T-ALL and CLL, and they contribute to tumor development by enhancing Notch signaling, which leads to increased cell growth and survival.* -
- Currently, there is no specific treatment for cancers linked to PEST domain mutations, but several Notch inhibitors, including CAD204520, are under investigation, showing promise in combating T-ALL and increasing sensitivity in CLL and MCL cases with these mutations.* -
- The study demonstrates that CAD204520, especially when combined with existing treatments like venetoclax and ibrutinib, enhances therapeutic efficacy in cancers with PEST mutations, highlighting its potential as a novel treatment strategy for
Unlabelled: The mechanisms underlying the success of propranolol in the treatment of infantile hemangioma (IH) remain elusive and do not fully explain the rapid regression of hemangiomatous lesions following drug administration. As autophagy is critically implicated in vascular homeostasis, we determined whether β-blockers trigger the autophagic flux on infantile hemangioma-derived endothelial cells (Hem-ECs) in vitro.
Material And Methods: Fresh tissue specimens, surgically removed for therapeutic purpose to seven children affected by proliferative IH, were subjected to enzymatic digestion.
Article Synopsis
- - Genomic studies on acute lymphoblastic leukemia (ALL) have uncovered recurring genetic changes related to DNA methylation and histone modifications, pointing to potential new treatment options.
- - The study identified G9a/EHMT2 as a promising target for T-ALL therapy by combining epigenetic screens with chemical analysis and confirmed its role through various targeted experiments.
- - Findings suggest that inhibiting G9a leads to increased lysosomal activity and autophagy, affecting key metabolic pathways in T-ALL cells, thereby proposing G9a as a viable strategy to disrupt the metabolism of these cancer cells.
The identification of SERCA (sarco/endoplasmic reticulum calcium ATPase) as a target for modulating gain-of-function NOTCH1 mutations in Notch-dependent cancers has spurred the development of this compound class for cancer therapeutics. Despite the innate toxicity challenge associated with SERCA inhibition, we identified CAD204520, a small molecule with better drug-like properties and reduced off-target Ca toxicity compared with the SERCA inhibitor thapsigargin. In this work, we describe the properties and complex structure of CAD204520 and show that CAD204520 preferentially targets mutated over wild-type NOTCH1 proteins in T cell acute lymphoblastic leukemia (T-ALL) and mantle cell lymphoma (MCL).
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