Publications by authors named "Gabriella Nicolini"

The vacuolar proton-translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism underlying carcinogenesis is mainly based on anaerobic glycolytic reactions. Moreover, neoplastic cells use the V-ATPase to extrude chemotherapy drugs into the extra-cellular compartment as a drug resistance mechanism.

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Chemotherapy-induced peripheral neuropathy (CIPN) commonly arises as a side effect of diverse cancer chemotherapy treatments. This condition presents symptoms such as numbness, tingling, and altered sensation in patients, often accompanied by neuropathic pain. Pathologically, CIPN is characterized by an intensive "dying-back" axonopathy, starting at the intra-epidermal sensory innervations and advancing retrogradely.

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Article Synopsis
  • This study explores the effectiveness of combining immune checkpoint blockade (ICB) with various epigenetic drugs to boost immune responses in melanoma.
  • Different epigenetic inhibitors, like guadecitabine and givinostat, impact gene expression in melanoma cells differently, particularly affecting immune-related genes.
  • Results from patient biopsies show that guadecitabine treatment enhances specific immune gene signatures, indicating its potential effectiveness in ICB therapies compared to other epigenetic drugs.
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5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an enzyme that regulates cellular energy homeostasis, glucose, fatty acid uptake, and oxidation at low cellular ATP levels. AMPK plays an important role in several molecular mechanisms and physiological conditions. It has been shown that AMPK can be dysregulated in different chronic diseases, such as inflammation, diabetes, obesity, and cancer.

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Oxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN) is a frequent adverse event of colorectal cancer treatment. OIPN encompasses a chronic and an acute syndrome. The latter consists of transient axonal hyperexcitability, due to unbalance in Na voltage-operated channels (NaVOC).

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Glioblastoma (GBM, grade IV glioma) represents the most aggressive brain tumor and patients with GBM have a poor prognosis. Until now surgical resection followed by radiotherapy and temozolomide (TMZ) treatment represents the standard strategy for GBM. We showed that the imidazobenzoxazin-5-thione MV1035 is able to significantly reduce GBM U87-MG cells migration and invasiveness through inhibition of the RNA demethylase ALKBH5.

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Purpose: We investigated the dose enhancement and internalization of gold nanoparticles (AuNPs) used as a radiosensitizer agent for rotational radiotherapy of breast cancer using a kilovoltage (kV) X-ray beam.

Methods: Human breast cancer cells MDA-MB-231 were incubated with or without 100 μg/mL (4.87 nM) or 200 μg/mL (9.

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We report the NMR characterization of the molecular interaction between Gastrin Releasing Peptide Receptor (GRP-R) and its natural ligand bombesin (BN). GRP-R is a transmembrane G-protein coupled receptor promoting the stimulation of cancer cell proliferation; in addition, being overexpressed on the surface of different human cancer cell lines, it is ideal for the development of new strategies for the selective targeted delivery of anticancer drugs and diagnostic devices to tumor cells. However, the design of new GRP-R binders requires structural information on receptor interaction with its natural ligands.

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The imidazobenzoxazin-5-thione MV1035, synthesized as a new sodium channel blocker, has been tested on tumoral cells that differ for origin and for expressed Na pool (U87-MG, H460 and A549). In this paper we focus on the effect of MV1035 in reducing U87 glioblastoma cell line migration and invasiveness. Since the effect of this compound on U87-MG cells seemed not dependent on its sodium channel blocking capability, alternative off-target interaction for MV1035 have been identified using SPILLO-PBSS software.

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Multiple myeloma (MM) belongs to hematological cancers and its incidence is increasing worldwide. Despite recent advances in its therapy, MM still causes many deaths every year. In fact, current therapies sometimes fail and are associated with severe adverse effects, including neurotoxicity.

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Despite the different antineoplastic mechanisms of action, peripheral neurotoxicity induced by all chemotherapy drugs (anti-tubulin agents, platinum compounds, proteasome inhibitors, thalidomide) is associated with neuron morphological changes ascribable to cytoskeleton modifications. The "dying back" degeneration of distal terminals (sensory nerves) of dorsal root ganglia sensory neurons, observed in animal models, in in vitro cultures and biopsies of patients is the most evident hallmark of the perturbation of the cytoskeleton. On the other hand, in highly polarized cells like neurons, the cytoskeleton carries out its role not only in axons but also has a fundamental role in dendrite plasticity and in the organization of soma.

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Discovery of new actionable targets and functional networks in melanoma is an urgent need as only a fraction of metastatic patients achieves durable clinical benefit by targeted therapy or immunotherapy approaches. Here we show that NFATc2 expression is associated with an EMT-like transcriptional program and with an invasive melanoma phenotype, as shown by analysis of melanoma cell lines at the mRNA and protein levels, interrogation of the TCGA melanoma dataset and characterization of melanoma lesions by immunohistochemistry. Gene silencing or pharmacological inhibition of NFATc2 downregulated EMT-related genes and AXL, and suppressed c-Myc, FOXM1, and EZH2.

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Objectives: To explore whether facial emotion recognition (FER), impaired in both schizophrenia and alcohol and substance use disorders (AUDs/SUDs), is additionally compromised among comorbid subjects, also considering the role of catechol-O-methyltransferase (COMT) Val158Met.

Methods: We conducted a cross-sectional study, randomly recruiting 67 subjects with a DSM-IV-TR diagnosis of schizophrenia, and rigorously assessing AUDs/SUDs and COMT Val158Met polymorphism. FER was assessed using the Ekman 60 Faces Test- EK-60F.

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Background: A functional polymorphism in the catechol-O-methyltransferase (COMT) gene (Val158Met) appears to influence cognition in people with alcohol/substance use disorders (AUD/SUD) and in those with psychosis.

Methods: To explore the potential moderating effect of these factors, a cross-sectional study was conducted, randomly recruiting subjects with DSM-IV diagnosis of schizophrenia. AUD/SUD was rigorously assessed, as well as COMT Val158Met polymorphism.

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Background: Biological basis of prolapse development and recurrence are still unclear. Aim of this observational and prospective study is to correlate clinical stage of anterior vaginal wall prolapse and anatomical recurrence to histological and metabolic characteristics of vaginal tissue.

Methods: Patients undergoing surgery were divided into two groups according to anterior stage ≤II (group A) and ≥III (group B).

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Cancer is a leading cause of death worldwide. Despite therapeutic improvements, some cancers are still untreatable. Recently there has been an increasing interest in the use of natural substances for cancer prevention and treatment.

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Intrinsic cross-resistance to inhibition of different signaling pathways may hamper development of combinatorial treatments in melanoma, but the relative frequency of this phenotype and the strategies to overcome this hurdle remain poorly understood. Among 49 BRAF-mutant melanoma cell lines from patients not previously treated with target therapy, 21 (42.9%) showed strong primary resistance (IC50 > 1 μM) to a BRAFV600E inhibitor.

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Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a dose-limiting side effect of several antineoplastic drugs which significantly reduces patients' quality of life. Although different molecular mechanisms have been investigated, CIPN pathobiology has not been clarified yet. It has largely been recognized that Dorsal Root Ganglia are the main targets of chemotherapy and that the longest nerves are the most damaged, together with fast axonal transport.

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Dysregulation of receptor tyrosine kinases (RTKs) contributes to several aspects of oncogenesis including drug resistance. In melanoma, distinct RTKs have been involved in BRAF inhibitors (BRAFi) resistance, yet the utility of RTKs expression pattern to identify intrinsically resistant tumors has not been assessed. Transcriptional profiling of RTKs and integration with a previous classification, reveals three robust subtypes in two independent datasets of melanoma cell lines and one cohort of melanoma samples.

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Oral cancer, representing all the malignancies arising in the oral cavity, is the eighth most diffused neoplasm worldwide. Despite therapeutic improvements, its survival rate has not changed significantly over the past few decades, with a 5-year survival rate slightly above 50%. In this context, a search for new therapeutic strategies is mandatory.

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Introduction And Hypothesis: To test in vitro and in vivo the capability of mesh materials to act as scaffolds for rat-derived mesenchymal stem cells (rMSCs) and to compare inflammatory response and collagen characteristics of implant materials, either seeded or not with rMSCs.

Methods: rMSCs isolated from rat bone marrow were seeded and cultured in vitro on four different implant materials. Implants showing the best rMSC proliferation rate were selected for the in vivo experiment.

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Background: Glioblastoma multiforme (GBM) is one of the deadliest cancers characterized by very limited sensitivity to chemo- and/or radiotherapy. The presence of GBM stem-like cells in the tumor might be relevant for GBM treatment resistance.

Aim: To provide a proof-of-concept of the efficacy of photon activation therapy (PAT) using monochromatic synchrotron radiation (SR), in killing GBM stem cells pre-treated with cisplatin.

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In this study the potential anticancer effect of 2 flavonoids, myiricetin (MYR) and naringenin (NAR) has been evaluated on an oral squamous cell carcinoma (OSCC) cell line, SCC-25, and HaCaT cells. Both the flavonoids inhibited SCC-25 cell growth, although NAR selectively affected cancer cells without impairing HaCaT cell growth. The cell proliferation inhibition by MYR and NAR was not related to apoptosis induction, but on cell cycle impairment, because a G0/G1 and a G2/M blockage was highlighted following 24 h of treatment in SCC-25 and HaCaT cells, respectively.

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The anticancer activity of a novel pure 1,4-Diaryl-2-azetidinone (1), endowed with a higher solubility than the well known Combretastatin A4, is tested in mice. We previously reported that Compound (1) showed specific antiproliferative activity against duodenal and colon cancer cells, inducing activation of AMP-activated protein kinase and apoptosis. Here we estimate that the maximum tolerated dose in a mouse model is 40 mg/kg; the drug is well tolerated both in single dose and in repeated administration schedules.

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