A5013987297- Cancer Treatment and Pharmacology
- Glioma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Pain Mechanisms and Treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- Microtubule and mitosis dynamics
- Acute Ischemic Stroke Management
- Cancer-related cognitive impairment studies
- Brain Metastases and Treatment
- Chemotherapy-related skin toxicity
- Peripheral Neuropathies and Disorders
- Photoacoustic and Ultrasonic Imaging
- Intracerebral and Subarachnoid Hemorrhage Research
- Stroke Rehabilitation and Recovery
- Colorectal Cancer Treatments and Studies
- Mesoporous Materials and Catalysis
- Botulinum Toxin and Related Neurological Disorders
- Drug-Induced Ocular Toxicity
- Synthetic Organic Chemistry Methods
- Peripheral Nerve Disorders
- Neurological Disease Mechanisms and Treatments
- HER2/EGFR in Cancer Research
- Eicosanoids and Hypertension Pharmacology
- Mitochondrial Function and Pathology
- Brain Tumor Detection and Classification
University of Milano-Bicocca
2015-2024
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...
Significance Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating “dying back” featuring distal-to-proximal nerve degeneration seen in cancer patients undergoing chemotherapy. The pathogenenic mechanisms of CIPN are largely unknown. We report that sensory neurons, the CIPN-inducing drug bortezomib caused axonopathy and disrupted mitochondria motility by increasing delta 2 tubulin (D2), only irreversible posttranslational modification marker hyper-stable microtubules. These...
Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy safety of four pathophysiologically distinct strategies for modulation collateral flow (collateral therapeutics) rat stroke model transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) receive phenylephrine (induced hypertension), polygeline (intravascular volume load),...
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...
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....
High variability in infarct size is common experimental stroke models and affects statistical power validity of neuroprotection trials. The aim this study was to explore cerebral collateral flow as a stratification factor for the prediction ischemic outcome. Transient intraluminal occlusion middle artery induced 90 min 18 Wistar rats. Cerebral assessed intra-procedurally using multi-site laser Doppler flowmetry monitoring both lateral territory borderzone between anterior artery. Multi-modal...
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...
Cerebral collaterals are recruited after arterial occlusion with a protective effect on tissue outcome in acute ischemic stroke. Head down tilt 15° (HDT15) is simple, low cost and accessible procedure that could be applied as an emergency treatment, before recanalization therapies, the aim to increase cerebral collateral flow. Spontaneously hypertensive rats have been shown display anatomical differences morphology function of collaterals, compared other rat strains, resulting overall poor...
Peripheral neuropathies (PNs) are a type of common disease that hampers the quality life affected people. Treatment, in most cases, is just symptomatic and often ineffective. To improve drug discovery this field, preclinical evidence warranted. In vivo rodent models allow multiparametric approach to test new therapeutic strategies, since they can pathogenetic morphological studies different from clinical setting. However, human readouts warranted promptly translate data bench bedside. A...