Paola Alberti

Università degli Studi di Milano-Bicocca | UNIMIB · School of Medicine and Surgery

Oxaliplatin (OHP)-induced peripheral neurotoxicity (OIPN), one of the major dose-limiting side effects of colorectal cancer treatment, is characterized by both acute and chronic syndromes. Acute exposure to low dose OHP on dorsal root ganglion (DRG) neurons is able to induce an increase in intracellular calcium and proton concentration, thus influe...

Chemotherapy-induced peripheral neurotoxicity is one of the most common dose-limiting toxicities of several widely used anticancer drugs such as platinum derivatives (cisplatin) and taxanes (paclitaxel). Several molecular mechanisms related to the onset of neurotoxicity have already been proposed, most of them having the sensory neurons of the dors...

Peripheral Neuropathies (PN) are common conditions whose treatment is still lacking in most cases. Animal models are crucial, but experimental procedures should be refined in some cases. We performed a detailed characterization of the ventral caudal nerve to contribute to a more effective assessment of axonal damage in future PN studies. PN was ind...

Simple Summary: Cancer survivors can experience neurological complications after exposure to anticancer therapy. Chemotherapy-induced peripheral neurotoxicity (CIPN), mainly consisting of sensory loss and neuropathic pain in hands and feet, is most commonly encountered. Cognitive impairment, although less frequent, is also a severe adverse event, s...

Pharmacogenomics is a powerful tool to predict individual response to treatment, in order to personalize therapy, and it has been explored extensively in oncology practice. Not only efficacy on the malignant disease has been investigated but also the possibility to predict adverse effects due to drug administration. Chemotherapy-induced peripheral...

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 (Na+VOC). This leads to sustained depolarisation which can activate the r...

Neurons are permanent cells whose key feature is information transmission via chemical and electrical signals. Therefore, a finely tuned homeostasis is necessary to maintain function and preserve neuronal lifelong survival. The cytoskeleton, and in particular microtubules, are far from being inert actors in the maintenance of this complex cellular...

Our aim was to assess the significance of measuring serum neurofilament light chain (sNfL) levels as biomarker of paclitaxel‐induced peripheral neurotoxicity (PIPN). We longitudinally measured sNfL in breast cancer patients, scheduled to receive the 12‐weekly paclitaxel‐based regimen. Patients were clinically examined by means of the Total Neuropat...

Chemotherapy-induced peripheral neurotoxicity is a common dose-limiting side effect of several cancer chemotherapeutic agents, and no effective therapies exist. Here we constructed a systems pharmacology model of intracellular signaling in peripheral neurons to identify novel drug targets for preventing peripheral neuropathy associated with proteas...

Pharmacological strategies for chemotherapy-induced peripheral neurotoxicity (CIPN) are very limited. We systematically reviewed data on rehabilitation, exercise, physical therapy, and other physical non-pharmacological interventions and offered evidence-based recommendations for the prevention and treatment of CIPN. A literature search using PubMe...

Introduction Chemotherapy-induced peripheral neurotoxicity (CIPN) remains a significant toxicity in cancer survivors without preventative strategies or rehabilitation. Exercise and physical activity-based interventions have demonstrated promise in reducing existing CIPN symptoms and potentially preventing toxicity, however there is a significant ga...

Proceedings of the 31st National Conference of the Italian Group for the Study of Neuromorphology “Gruppo Italiano per lo Studio della Neuromorfologia” G.I.S.N., Milan, November 26-27, 2021

Internationally known CIPN scientists and clinicians will provide practical tips and clinical demonstrations to guide busy oncology clinicians to incorporate CIPN assessment into daily practice. Presentations: • Mechanisms of Chemotherapy-Induced Peripheral Neuropathy (CIPN) with Dr M Imad Damaj; • Challenges in Accurately Grading CIPN with Availa...

The authors will present a comprehensive account of the neurological aspects of SARS-CoV-2 infection. The aim is to provide a practical clinical book which will serve as a guide for clinicians from all specialties involved in the management of COVID-19 patients. The authors share the extensive clinical experience gained in major hospitals in Lombar...

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a treatment related toxicity that burdens the quality of life of cancer survivors. Unfortunately, no efficacious treatment (symptomatic or preventive) is available for this condition for many reasons. First, a still incomplete pathogenetic knowledge hampers the recognition of a strong biologic...

Background peripheral neuropathy treatment is not always satisfactory. To fill this gap, inferences from bench side are warranted, where morphological and pathogenetic determinations can be performed. Nerve conduction studies (NCS) are ideal to translate results from preclinical to clinical setting. New Methods we propose a comprehensive 8-minute...

OBJECTIVE There is not agreement on the “gold standard” for detection and grading of Chemotherapy Induced Peripheral Neurotoxicity (CIPN) in clinical trials. We performed an observational prospective study to assess and compare both patient-based and physician-based methods. METHODS Consecutive patients, aged 18 years or older, candidates for ne...

This systematic review provides a high-quality synthesis of the empirical evidence regarding chemotherapy-induced peripheral neuropathy (CIPN) characteristics and patterns described in studies of children who received neurotoxic chemotherapy to treat cancer. PubMed, CINAHL, PsycINFO, and Embase were searched for articles published 2009 - 2019, yiel...

Peripheral neuropathies (PNs) are a type of common disease that hampers the quality of life of affected people. Treatment, in most cases, is just symptomatic and often ineffective. To improve drug discovery in this field, preclinical evidence is warranted. In vivo rodent models allow a multiparametric approach to test new therapeutic strategies, si...

The onset of chemotherapy-induced peripheral neurotoxicity (CIPN) is a leading cause of the dose reduction or discontinuation of cancer treatment due to sensory symptoms. Paclitaxel (PTX) can cause painful peripheral neuropathy, with a negative impact on cancer survivors' quality of life. While recent studies have shown that neuroinflammation is in...

Significance Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating “dying back” neuropathy featuring a distal-to-proximal peripheral nerve degeneration seen in cancer patients undergoing chemotherapy. The pathogenenic mechanisms of CIPN are largely unknown. We report that in sensory neurons, the CIPN-inducing drug bortezomib caused ax...

OBJECTIVES: Oxaliplatin (OHP) induced peripheral neurotoxicity (OIPN), a persistent adverse event of chemotherapy, is characterized by a sensory, length-dependent, chronic polyneuropathy that affects cancer survivors; moreover, OIPN is characterized also by an acute neurotoxicity syndrome. Acute OIPN shows hallmark of axonal hyperexcitability. This...

INTRODUCTION. We demonstrated Topiramate (TPM) prevents Oxaliplatin (OHP) Induced Peripheral Neurotoxicity (OIPN; Alberti et al. 2020) in rats. Moreover, being a carbon anhydrase inhibitor, it can reduce neoangiogenesis and prevent chemoresistance. To verify this, we are searching promising findings in vivo and in vitro. METHODS. In vivo we defined...

INTRODUCTION. Taxane-induced Peripheral Neurotoxicity (TIPN) is a relevant late toxicity that, so far, lacks an efficacious treatment. Neurofilament light chain (NfL) serum levels have emerged as a potential biomarker in neurological diseases and have shown promising usefulness in detecting chemotherapy induced peripheral neurotoxicity in animal mo...

Dear Colleagues, Sodium voltage-operated ion channels (NaV) are widely represented in the peripheral nervous system (PNS), being crucial for action potential generation. Modulators of NaV are attracting interest as potential therapeutic strategies for PNS disorders. They represent a valuable strategy for neuropathic pain management, gaining attent...

Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a potentially persistent late toxicity of most common anticancer regimens. There is still a huge lack in CIPN assessment in clinical trials; therefore, biomarkers, both neuroimagery and molecular, could fill this gap. Areas covered In this review the first applications of high-resol...

BACKGROUND: Oxaliplatin (OHP) induced peripheral neurotoxicity (OIPN) is a potentially persistent side effect of cancer treatment that hampers colorectal cancer survivors' quality of life; notably, there is no efficacious treatment for OIPN. OIPN consists of two different conditions: an acute and chronic syndrome. Chronic OIPN is characterized by a...

Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a severe and long-lasting side effect of anticancer therapy, which can severely impair patients’ quality of life. It is a sensory and length-dependent neuropathy, which predominantly affects large myelinated fibers. Easy and reliable monitoring of CIPN in patients is still an unmet clinical ne...

Peripheral neurotoxicity is a debilitating toxicity that afflicts up to 90% of patients with colorectal cancer receiving oxaliplatin-containing therapy. Although emerging evidence has highlighted the importance of various solute carriers to the toxicity of anticancer drugs, the contribution of these proteins to oxaliplatin-induced peripheral neurot...

In children who receive neurotoxic chemotherapy, peripheral neurotoxicity occurs frequently, necessitates dose reduction or treatment cessation, and affects function and long-term quality of life. No treatments exist for peripheral neurotoxicity and few assessment measures are specific to children. We did a systematic review to analyse the publishe...

At the time of this writing, healthcare systems are facing worldwide the pandemic of the coro-navirus severe acute respiratory coronavirus 2 (SARS-COV-2) and its associated disease, named cronavirus disease 19 (COVID-19). This virus is a new human pathogen, and currently, there are no specific treatment options. 1 COVID-19 mostly affects the respir...

Annual meeting organized by SigN (Young Neurologists' section of the Italian Society of Neurology)

Peripheral neuropathy is one of the most common, dose limiting, and long-lasting disabling adverse events of chemotherapy treatment. Unfortunately, no treatment has proven efficacy to prevent this adverse effect in patients or improve the nerve regeneration, once it is established. Experimental models, particularly using rats and mice, are useful t...

Oxaliplatin (OHP) Induced Peripheral Neurotoxicity (OIPN) is one of the dose-limiting toxicities of the drug and these adverse effects limit cancer therapy with L-OHP, used for colorectal cancer treatment. Acute neurotoxicity consists of symptoms that are the hallmarks of a transient axonal hyperexcitability; chronic neurotoxicity has a clinical pi...

Proteasome inhibitors (PIs), especially bortezomib (BTZ), have come to the forefront over the last years because of their unprecedented efficacy mainly against multiple myeloma (MM). Unfortunately, peripheral neuropathy (PN) secondary to treatment of MM with PIs has emerged as a clinically relevant complication, which negatively impacts the quality...

Taxane‐induced peripheral neurotoxicity (TIPN) is the most common non‐hematological side effect of taxane‐based chemotherapy, and may result in dose reductions and discontinuations, having as such a detrimental effect on patients' overall survival. Epothilones share similar mechanism of action with taxanes. The typical TIPN clinical presentation is...

Vinca alkaloids, thalidomide, and eribulin are widely used to treat patients with childhood acute lymphoblastic leukemia (ALL), adults affected by multiple myeloma and locally invasive or metastatic breast cancer, respectively. However, soon after their introduction into clinical practice, chemotherapy‐induced peripheral neurotoxicity (CIPN) emerge...

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a potentially dose-limiting side effect of several commonly used cytotoxic chemotherapy agents. The main pharmacological classes that may cause CIPN include classical anticancer drugs, as well as the recently introduced immune checkpoint inhibitors and antibody drug conjugates. The absence of...

Background: Thus far, there are conflicting results on the causal role of K+ channels in the pathogenesis of acute Oxaliplatin-Induced Peripheral Neurotoxicity (OXAIPN). As such, we tested the hypothesis that the voltage-gated K+ channel KCNN3 repeat polymorphism confers liability to acute OXAIPN. Methods: DNA from 151 oxaliplatin-treated patien...

The pathogenesis of chemotherapy induced peripheral neuropathy (CIPN) is still poorly understood. Herein, we found that the CIPN-causing drug, bortezomib (Bort), induces delta 2 tubulin (D2) while affecting MT stability and dynamics in sensory neurons, and that accumulation of D2 is a hallmark of Bort-induced peripheral neuropathy in humans. Furthe...

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major toxicity of cancer treatment, leading to dose reduction and premature treatment cessation, potentially affecting patient function, and quality of life. The development of accurate and sensitive assessment tools for CIPN is essential to enable clinical monitoring during treatment , foll...

Purpose of review: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and distressing side-effect of many chemotherapy regimens. Currently, aside from symptomatic treatments for neuropathic pain, there are no treatments to prevent CIPN or treat established CIPN. We discuss recent articles addressing clinimetric issues and treatment of C...

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common dose-limiting side effect of several anticancer medications. CIPN may involve multiple areas of the peripheral nervous system from the autonomic and dorsal root ganglia (DRG) to the axon and any peripheral nerve fibre type. Large diameter sensory myelinated (Aβ) fibres are more freque...

INTRODUCTION: Platinum-drugs (Cisplatin, Carboplatin, Oxaliplatin) are widely used in Medical Oncology departments to treat common neoplasms whose survival has greatly increased in the last few years. Thus, there is a growing population of cancer survivors who were treated with them and whose Quality of Life can be impaired by this late toxicity. A...

Objective To test if and how Chemotherapy‐Induced Peripheral Neurotoxicity (CIPN) is perceived differently by patients and physicians, making assessment and interpretation challenging. Methods We performed a secondary analysis of the CI‐PeriNomS study which included 281 patients with stable CIPN. We tested: a) the association between patients’ per...

Purpose: We aimed to verify the predictiveness of dorsal sural nerve neurophysiological monitoring in obtaining risk stratification for oxaliplatin-induced peripheral neurotoxicity (OXAPN). Methods: We conducted a secondary analysis on a cohort of 110 colorectal cancer patients who were evaluated clinically and neurophysiologically before chemot...

Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is often dose-limiting and impacts life quality and survival of cancer patients. Ghrelin agonists have neuroprotectant effects and may have a role in treating or preventing CIPN. We evaluated the CNS-penetrant ghrelin agonist HM01 in three experimental models of CIPN at doses of 3-30mg/kg p.o. da...

Background: Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe adverse effect in patients receiving antitumor agents, and no effective treatment is available. Although the mechanisms responsible for the development of CIPN are poorly understood, recent findings make neuroinflammation an attractive target to be investigated, particula...

[Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I) and gold(I) water-soluble complexes characterized by high anticancer activity in a wide range of solid tumors, often able to overcome drug resistance of platinum-based compounds. For thes...

Backround: The number of cancer survivors is growing steadily and increasingly, clinical trials are being designed to include long-term follow-up to assess not only survival, but also late effects and health-related quality of life (HRQOL). Therefore it is is essential to develop patient-reported outcome measures (PROMs) that capture the full rang...