A5001119506- Cancer Treatment and Pharmacology
- Multiple Myeloma Research and Treatments
- Pain Mechanisms and Treatments
- Glioma Diagnosis and Treatment
- Microtubule and mitosis dynamics
- Peripheral Neuropathies and Disorders
- Brain Metastases and Treatment
- Plant-based Medicinal Research
- Cancer-related cognitive impairment studies
- Colorectal Cancer Treatments and Studies
- Pancreatic function and diabetes
- Nerve injury and regeneration
- Chemotherapy-related skin toxicity
- Nanoparticle-Based Drug Delivery
- Drug Transport and Resistance Mechanisms
- Chemotherapy-induced organ toxicity mitigation
- HER2/EGFR in Cancer Research
- Pharmacological Receptor Mechanisms and Effects
- Cancer therapeutics and mechanisms
- Atherosclerosis and Cardiovascular Diseases
- Regulation of Appetite and Obesity
- Neurological Disorders and Treatments
- Pharmacological Effects and Toxicity Studies
- Cholinesterase and Neurodegenerative Diseases
- Neuroblastoma Research and Treatments
University of Milano-Bicocca
2015-2024
University of Surrey
2021
University of Milan
2009-2018
National Institute of Nursing Research
2018
National Institutes of Health
2018
Bortezomib is the first proteasome inhibitor with significant antineoplastic activity for treatment of relapsed/refractory multiple myeloma as well other hematological and solid neoplasms. Peripheral neurological complications manifesting paresthesias, burning sensations, dysesthesias, numbness, sensory loss, reduced proprioception vibratory sensitivity are among major limiting side effects associated bortezomib therapy. Although bortezomib-induced painful peripheral neuropathy clinically...
ABSTRACT Bortezomib is a proteasome inhibitor showing strong antitumor activity against many tumors, primarily multiple myeloma. Bortezomib‐induced neuropathic pain the main side effect and dose‐limiting factor of drug in clinical practice. In order to obtain pre‐clinical model reproduce characteristic symptoms bortezomib‐treated patients, we developed an animal bortezomib‐induced nociceptive sensory neuropathy. this study, bortezomib (0.15 or 0.20mg/kg) was administered Wistar rats three...
1-Deoxysphingolipids (1-deoxySLs) are atypical neurotoxic sphingolipids that formed by the serine-palmitoyltransferase (SPT). Pathologically elevated 1-deoxySL concentrations cause hereditary sensory and autonomic neuropathy type 1 (HSAN1), an axonal associated with several missense mutations in SPT. Oral L-serine supplementation suppressed formation of 1-deoxySLs patients HSAN1 preserved nerve function mouse model. Because also 2 diabetes mellitus, could be a therapeutic option for diabetic...
Paclitaxel is among the most widely used anticancer drugs and known to cause a dose-limiting peripheral neurotoxicity, initiating mechanisms of which remain unknown. Here, we identified murine solute carrier organic anion–transporting polypeptide B2 (OATP1B2) as mediator paclitaxel-induced neurotoxicity. Additionally, using established tests assess acute chronic found that genetic or pharmacologic knockout OATP1B2 protected mice from mechanically induced allodynia, thermal hyperalgesia,...
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...
Peripheral neurotoxicity is a debilitating condition that afflicts up to 90% of patients with colorectal cancer receiving oxaliplatin-containing therapy. Although emerging evidence has highlighted the importance various solute carriers toxicity anticancer drugs, contribution these proteins oxaliplatin-induced peripheral remains controversial. Among candidate transporters investigated in genetically engineered mouse models, we provide for critical role organic cation transporter 2 (OCT2)...
Bortezomib (BTZ) is the first proteasome inhibitor entered in clinical practice. Peripheral neuropathy likely to be a class side effect of these drugs, although its severity largely variable, and it deserves further investigated, since mechanisms BTZ-induced peripheral neurotoxicity (BiPN) are still unknown. In our study, we investigated vivo vitro possible pathogenic events relevant BiPN using well-established rat model, with particular reference extent inhibition effects on α-tubulin...
To investigate neurochemical changes associated with bortezomib-induced painful peripheral neuropathy (PN), we examined the effects of a single-dose intravenous administration bortezomib and well-established "chronic" schedule in rat model PN. The TRPV1 channel sensory neuropeptides CGRP substance P (SP) were studied L4-L5 dorsal root ganglia (DRGs), spinal cord, sciatic nerve. Behavioral measures, performed at end chronic treatment, confirmed reduction mechanical nociceptive threshold,...
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)...
Abstract: Although bortezomib (BTZ) is the frontline treatment for multiple myeloma, its clinical use limited by occurrence of painful peripheral neuropathy, whose still an unmet need. Previous studies have shown chronic BTZ administration (0.20 mg/kg intravenously three times a week 8 weeks) to female Wistar rats induced neuropathy similar that observed in humans. In this animal model BTZ-induced neurotoxicity, present authors evaluated efficacy CR4056, novel I2 ligand endowed with...
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...