A5090058088- Cancer Treatment and Pharmacology
- Glioma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Microtubule and mitosis dynamics
- Pain Mechanisms and Treatments
- Colorectal Cancer Treatments and Studies
- Plant-based Medicinal Research
- Cancer-related cognitive impairment studies
- Brain Metastases and Treatment
- Chemotherapy-related skin toxicity
- Mesoporous Materials and Catalysis
- Peripheral Neuropathies and Disorders
- Cancer therapeutics and mechanisms
- Sphingolipid Metabolism and Signaling
- Protein Interaction Studies and Fluorescence Analysis
- Eicosanoids and Hypertension Pharmacology
- Drug Transport and Resistance Mechanisms
- Traumatic Brain Injury and Neurovascular Disturbances
- Anesthesia and Neurotoxicity Research
- Intracranial Aneurysms: Treatment and Complications
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Gastrointestinal disorders and treatments
- Diet and metabolism studies
- Spaceflight effects on biology
- Nerve injury and regeneration
University of Milano-Bicocca
2017-2024
University of Surrey
2021
University of Milan
2015
University of Turin
2015
Peripheral neurotoxicity is one of the most distressing side effects oxaliplatin therapy for cancer. Indeed, patients that received experience acute and/or chronic severe sensory peripheral neuropathy. However, despite similar co-morbidities, cancer stage, demographics and treatment schedule, develop oxaliplatin-induced with remarkably different severity. This suggests individual genetic variability, which might be used to glean mechanistic insights into neurotoxicity. We characterized...
Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of disability in cancer survivors. CIPN investigations preclinical model systems have focused on either behaviors or acute changes nerve conduction velocity (NCV) and amplitude, but greater understanding the underlying nature axonal injury its long-term processes needed as patients live longer. In this study, we used multiple independent endpoints to systematically characterize recovery mice exposed antitubulin drugs...
Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe adverse effect in patients receiving antitumor agents, and no effective treatment available. Although the mechanisms responsible for development of CIPN are poorly understood, recent findings make neuroinflammation an attractive target to be investigated, particularly when neuropathic pain prominent feature such as after bortezomib administration. The aim our study was evaluate intravenous immunoglobulins (IVIg) delivery...
Abstract Paclitaxel-induced peripheral neurotoxicity (PIPN) is a potentially dose-limiting side effect in anticancer chemotherapy. Several animal models of PIPN exist, but their results are sometimes difficult to be translated into the clinical setting. We compared 2 widely used characterized by marked differences methodologies. Female C57BL/6JOlaHsd mice were used, and they received only paclitaxel vehicle (n = 38) or via intravenous injection 19, 70 mg/kg) once week for 4 weeks (Study 1)...
Oxaliplatin is a cornerstone chemotherapeutic used in the treatment of colorectal cancer, third leading cause death Western countries. Most side effects this platinum-containing drug are adequately managed clinic, although acute and long-term neurotoxicity still severely compromises quality life patients treated with oxaliplatin. We have previously demonstrated that therapeutically relevant concentrations/doses oxaliplatin lead to reduction intracellular pH mouse dorsal root ganglion (DRG)...
Oxaliplatin (OHP) is an antineoplastic compound able to induce peripheral neurotoxicity. Oxidative stress has been suggested be a key factor in the development of OHP-related Mangafodipir, contrast agent possessing mitochondrial superoxide dismutase (MnSOD)-mimetic activity, tested as cytoprotector chemotherapy-induced neurotoxicity (CIPN). Calmangafodipir (PledOx®) even better therapeutic activity. We investigated BALB/c mouse model CIPN and effects pre-treatment calmangafodipir (2.5, 5, or...
Glioblastoma is the most common and aggressive brain tumor, associated with poor prognosis survival, representing a challenging medical issue for neurooncologists. Dysregulation of histone-modifying enzymes (HDACs) commonly identified in many tumors has been linked to cancer proliferation, changes metabolism, drug resistance. These findings led development HDAC inhibitors, which are limited by their narrow therapeutic index. In this work, we provide proof concept delivery system that can...
Oxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN) is a frequent adverse event of colorectal cancer treatment. OIPN encompasses chronic and an acute syndrome. The latter consists transient axonal hyperexcitability, due to unbalance in Na+ voltage-operated channels (Na+VOC). This leads sustained depolarisation which can activate the reverse mode Na+/Ca2+ exchanger 2 (NCX2), resulting toxic Ca2+ accumulation damage (ADa). We explored role NCX2 vitro vivo settings. Embryonic rat Dorsal...
Chemotherapy-induced peripheral neurotoxicity is one of the most common dose-limiting toxicities several widely used anticancer drugs such as platinum derivatives (cisplatin) and taxanes (paclitaxel). Several molecular mechanisms related to onset have already been proposed, them having sensory neurons dorsal root ganglia (DRG) nerve fibers principal targets. In this study we explore chemotherapy-induced beyond neuronocentric view, investigating changes induced by paclitaxel (PTX) cisplatin...
The onset of chemotherapy-induced peripheral neurotoxicity (CIPN) is a leading cause the dose reduction or discontinuation cancer treatment due to sensory symptoms. Paclitaxel (PTX) can painful neuropathy, with negative impact on survivors’ quality life. While recent studies have shown that neuroinflammation involved in PTX-induced (PIPN), pathophysiology this disabling side effect remains largely unclear and no effective therapies are available. Therefore, here we investigated effects human...
The peripheral nervous system can encounter alterations due to exposure some of the most commonly used anticancer drugs (platinum drugs, taxanes, vinca alkaloids, proteasome inhibitors, thalidomide), so-called chemotherapy-induced neurotoxicity (CIPN). CIPN be long-lasting or even permanent, and it is detrimental for quality life cancer survivors, being associated with persistent disturbances such as sensory loss neuropathic pain at limb extremities a mostly axonal...
Chemotherapy-induced peripheral neurotoxicity is a common dose-limiting side effect of several cancer chemotherapeutic agents, and no effective therapies exist. Here we constructed systems pharmacology model intracellular signaling in neurons to identify novel drug targets for preventing neuropathy associated with proteasome inhibitors. Model predictions suggested the combinatorial inhibition TNFα, NMDA receptors, reactive oxygen species should prevent inhibitor-induced neuronal apoptosis....
Peripheral neurotoxicity is a dose-limiting adverse reaction of primary frontline chemotherapeutic agents, including vincristine. Neuropathy can be so disabling that patients drop out potentially curative therapy, negatively impacting cancer prognosis. The hallmark vincristine axonopathy, yet its underpinning mechanisms remain uncertain. We developed comprehensive drug discovery platform to identify neuroprotective agents against vincristine-induced neurotoxicity. Among the hits identified,...
Chemotherapy-induced peripheral neurotoxicity represents one of the most relevant dose-limiting side effects that can affect cancer patients treated with common antineoplastic agents. Since severity often leads to dose reduction or early cessation chemotherapy, investigation molecular mechanisms underlying chemotherapy-induced is an urgent clinical need in order better understand its physiopathology and find effective strategies for neuroprotection. Several vivo preclinical models have been...
Peripheral Neuropathies (PN) are common conditions whose treatment is still lacking in most cases. Animal models crucial, but experimental procedures should be refined some We performed a detailed characterization of the ventral caudal nerve to contribute more effective assessment axonal damage future PN studies. was induced via weekly systemic injection neurotoxic drug (paclitaxel); we compared control and PN-affected rats, performing serial neurophysiological evaluations for its entire...
Abstract Oxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN), one of the major dose-limiting side effects colorectal cancer treatment, is characterized by both acute and chronic syndromes. Acute exposure to low dose OHP on dorsal root ganglion (DRG) neurons able induce an increase in intracellular calcium proton concentration, thus influencing ion channels activity neuronal excitability. The Na + /H exchanger isoform-1 (NHE1) a plasma membrane protein that plays pivotal role pH (pH i )...
Abstract Background and Aims Chemotherapy‐induced peripheral neurotoxicity (CIPN) is a common long‐lasting adverse event of several anticancer compounds, for which treatment has not yet been developed. To fill this gap, preclinical studies are warranted, exploiting highly translational outcome measure(s) to transfer data from bench bedside. Nerve excitability testing (NET) enables test in vivo axonal properties can be used monitor early changes leading damage. Methods We tested NET use two...
Abstract Background and Aims Chemotherapy‐induced peripheral neurotoxicity (CIPN) is one of the most common dose‐limiting side effects paclitaxel (PTX) treatment. Many age‐related changes have been hypothesized to underlie susceptibility damage or impaired regeneration/repair after nerve injury. The results these studies, however, are inconclusive other potential biomarkers impairment need be investigated. Methods Twenty‐four young (2 months) 24 adult (9 Wistar male rats were randomized...