A5071970617- DNA Repair Mechanisms
- Glioma Diagnosis and Treatment
- Chromium effects and bioremediation
- Light effects on plants
- Circadian rhythm and melatonin
- Cancer Research and Treatments
- Radiation Therapy and Dosimetry
- Plant Molecular Biology Research
- Biomedical Text Mining and Ontologies
- Mitochondrial Function and Pathology
- ATP Synthase and ATPases Research
- Genetics, Aging, and Longevity in Model Organisms
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- Microtubule and mitosis dynamics
- Sirtuins and Resveratrol in Medicine
- Drug Transport and Resistance Mechanisms
- RNA regulation and disease
- Autophagy in Disease and Therapy
- Cancer, Hypoxia, and Metabolism
- Semantic Web and Ontologies
- Carcinogens and Genotoxicity Assessment
- RNA modifications and cancer
- Nematode management and characterization studies
- RNA Interference and Gene Delivery
Italian Institute of Technology
2019-2023
Ospedale Policlinico San Martino
2012-2019
Molecular Medicine Research Institute
2019
University of Genoa
2009-2019
Istituti di Ricovero e Cura a Carattere Scientifico
2012-2014
University of Pisa
2009-2010
We have previously shown that pharmacological inhibition of ataxia telangiectasia mutated (ATM) protein sensitizes glioblastoma-initiating cells (GICs) to ionizing radiation (IR). Herein, we report the experimental conditions overcome GIC radioresistance in vitro using specific ATM inhibitor KU-60019, two major determinants tumor response this drug and absence toxicity treatment vivo. Repeated treatments with KU-60019 followed by IR substantially delayed proliferation even eradicated...
We have recently reported that glioblastoma (GB)-initiating cells (GIC) with low expression and/or mutation of TP53 and high PI3K ("responder" genetic profile) can be effectively safely radiosensitized by the ATM inhibitor KU60019. report here on drug's diffusion elimination from animal body brain, its effects orthotopic GB efficacy toward pediatric GIC. Healthy mice were infused convection enhanced delivery (CED) KU60019 drug kinetics followed performance liquid chromatography-mass...
Abstract Background High grade gliomas are one of the most difficult cancers to treat and despite surgery, radiotherapy temozolomide-based chemotherapy, prognosis glioma patients is poor. Resistance temozolomide major barrier effective therapy. Alternative therapeutic approaches have been shown be ineffective for treatment genetically unselected patients. Thus, novel therapies needed. Mitochondria-directed chemotherapy an emerging tool combat cancer, inner mitochondrial permeability...
Previous studies have shown that tumor-driving glioma stem cells (GSC) may promote radio-resistance by constitutive activation of the DNA damage response started ataxia telangiectasia mutated (ATM) protein. We investigated whether GSC be specifically sensitized to ionizing radiation inhibiting response. Two grade IV cell lines (BORRU and DR177) were characterized for a number immunocytochemical, karyotypic, proliferative differentiative parameters. In particular, expression panel nine...
Adenine nucleotide translocases (ANTs) are multitask proteins involved in several aspects of cell metabolism, as well the regulation death/survival processes. We investigated role played by ANT isoforms 1 and 2 growth a human glioblastoma line (ADF cells). The silencing ANT2 isoform, small interfering RNA, did not produce significant changes ADF viability. By contrast, ANT1 isoform strongly reduced viability inducing non-apoptotic death process resembling paraptosis. demonstrated that...
The circadian transcriptional network is based on a competition between activator and repressor complexes regulating the rhythmic expression of clock-controlled genes. We show here that MYC-associated factor X, MAX, plays repressive role in this operates through MYC-independent binding to E-box-containing regulatory regions within promoters BMAL1 targets. further “clock” function MAX required for maintaining proper rhythm contribute two temporally alternating clock-regulated promoters. also...
Cigarette smoke (CS) is associated to a number of pathologies including lung cancer. Its mutagenic and carcinogenic effects are partially linked the presence reactive oxygen species polycyclic aromatic hydrocarbons (PAH) inducing DNA damage. The bacterial repair enzyme formamidopyrimidine glycosylase (FPG) repairs both oxidized bases different types bulky adducts. We investigated in vitro whether FPG expression may enhance CS-damaged counteract CS human cells. NCI-H727 non small cell...
Abstract It has been reported that the ATM kinase inhibitor KU60019 preferentially radiosensitizes orthotopic high grade gliomas (HGG) driven by established U87 and U1242 cell lines bearing specific TP53 mutations. We wished to determine whether those results could be extended tumors primary glioma initiating cells (GIC) closely mimic clinical tumors. Orthotopic HGG were developed in immunodeficient non-obese diabetic-severe combined (NOD-SCID) mice intracranial injection of GIC isolated...
The autophagy process appears as a promising target for anticancer interventions. Chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) are the only FDA-approved flux inhibitors. Although diverse clinical trials providing encouraging results, several limitations associated with need of high dosage long-term administration these inhibitors also emerging. We showed that inhibition REV-ERB, nuclear receptor regulating circadian rhythm metabolism, enhances CQ-mediated cancer cell death...
Summary The circadian transcriptional network is based on a competition between activator and repressor complexes regulating the rhythmic expression of clock-controlled genes. We show here that MYC-Associated factor X, MAX, plays repressive role in this operates through its MYC-independent binding to E-box-containing regulatory regions within promoters BMAL1 targets. This clock function MAX essential for maintaining proper rhythm but separated by as partner MYC controlling cell...
The circadian transcriptional network is based on a competition between activator and repressor complexes regulating the rhythmic expression of clock-controlled genes. We show here that MYC-Associated factor X, MAX, plays repressive role in this operates through its MYC-independent binding to E-box-containing regulatory regions within promoters BMAL1 targets. This clock function MAX essential for maintaining proper rhythm but separated by as partner MYC controlling cell proliferation. also...