Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy

Yamamoto, Seigo; Egashira, Nobuaki

doi:10.3390/ijms22020888

Cited by 78 publications

(67 citation statements)

References 88 publications

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“…The differences among groups observed in the behavioral tests for evaluating mood disorders are not biased by changes in locomotor activity in fact no alterations are detected at the static rod test between BTZ and CTR mice. We and others previously [ 28 , 34 , 38 ] demonstrated that neuroinflammation plays an important role in the development of BTZ-induced neuropathic pain. The damage due to BTZ cytotoxicity in the PNS promotes the recruitment of CD68 positive cells with consequent release of immunomodulatory molecules, such as cytokines and chemokines, that are important in the sensitization process.…”

Section: Discussionmentioning

confidence: 96%

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations

Amodeo

Verduci

Sartori

et al. 2021

IJMS

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The development of neuropathy and of mood alterations is frequent after chemotherapy. These complications, independent from the antitumoral mechanism, are interconnected due to an overlapping in their processing pathways and a common neuroinflammatory condition. This study aims to verify whether in mice the treatment with the proteasome inhibitor bortezomib (BTZ), at a protocol capable of inducing painful neuropathy, is associated with anxiety, depression and supraspinal neuroinflammation. We also verify if the therapeutic treatment with the antagonist of the prokineticin (PK) system PC1, which is known to contrast pain and neuroinflammation, can prevent mood alterations. Mice were treated with BTZ (0.4 mg/kg three times/week for 4 weeks); mechanical allodynia and locomotor activity were evaluated over time while anxiety (dark light and marble burying test), depression (sucrose preference and swimming test) and supraspinal neuroinflammation were checked at the end of the protocol. BTZ treated neuropathic mice develop anxiety and depression. The presence of mood alterations is related to the presence of neuroinflammation and PK system activation in prefrontal cortex, hippocampus and hypothalamus with high levels of PK2 and PKR2 receptor, IL-6 and TNF-α, TLR4 and an upregulation of glial markers. PC1 treatment, counteracting pain, prevented the development of supraspinal inflammation and depression-like behavior in BTZ mice.

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Section: Discussionmentioning

confidence: 96%

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations

Amodeo

Verduci

Sartori

et al. 2021

IJMS

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“…Even when treatment is successful, however, a narrow therapeutic window exists along with a high degree of toxicity [ 11 ]. Individuals with relapsed or resistant multiple myeloma experience peripheral neuropathy after taking BTZ, which greatly affects the quality of life for patients [ 12 ]. Other obstacles faced by currently FDA approved proteasome inhibitors are poor bioavailability in solid tumors, solubility, developed or acquired resistance, or adverse side effects such as anemia, hepatic toxicity, and adverse cardiovascular events [ 11 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

26S Proteasome Non-ATPase Regulatory Subunits 1 (PSMD1) and 3 (PSMD3) as Putative Targets for Cancer Prognosis and Therapy

Rubio

Bencomo‐Alvarez

Young

et al. 2021

Cells

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Ever since the ubiquitin proteasome system was characterized, efforts have been made to manipulate its function to abrogate the progression of cancer. As a result, the anti-cancer drugs bortezomib, carfilzomib, and ixazomib targeting the 26S proteasome were developed to treat multiple myeloma, mantle cell lymphoma, and diffuse large B-cell lymphoma, among others. Despite success, adverse side effects and drug resistance are prominent, raising the need for alternative therapeutic options. We recently demonstrated that knockdown of the 19S regulatory components, 26S proteasome non-ATPase subunits 1 (PSMD1) and 3 (PSMD3), resulted in increased apoptosis of chronic myeloid leukemia (CML) cells, but had no effect on normal controls, suggesting they may be good targets for therapy. Therefore, we hypothesized that PSMD1 and PSMD3 are potential targets for anti-cancer therapeutics and that their relevance stretches beyond CML to other types of cancers. In the present study, we analyzed PSMD1 and PSMD3 mRNA and protein expression in cancerous tissue versus normal controls using data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC), comparing expression with overall survival. Altogether, our data suggest that PSMD1 and PSMD3 may be novel putative targets for cancer prognosis and therapy that are worthy of future investigation.

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“…Finally, other studies have associated CIPN by bortezomib with interference with transcription, nuclear processing, and cytoplasmic translation of mRNAs in dorsal root ganglia neurons, with further damage of large and C-fibers [25,46]. Damage to dorsal root ganglia has also been associated with infiltration by inducible nitric oxide synthase (iNOS)-expressing inflammatory macrophages [47].…”

Section: Cipn By Bortezomibmentioning

confidence: 99%

“…Moreover, a high dose of O 3 promotes inflammation by the activation of the NF-κB pathway [64]. Additionally, the inhibition of the NF-κB pathway could potentially downregulate iNOS [68] because, for bortezomib treatment, it has been described that most of the infiltrating macrophages in the dorsal root ganglia are iNOS-expressing inflammatory macrophages [47].…”

Section: Modulation Of Oxidative Stress By Ozone Therapymentioning

confidence: 99%

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial

Clavo

Martı́nez-Sánchez²,

Rodrı́guez-Esparragón

et al. 2021

IJMS

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(1) Background: Chemotherapy-induced peripheral neuropathy (CIPN) decreases the quality of life of patients and can lead to a dose reduction and/or the interruption of chemotherapy treatment, limiting its effectiveness. Potential pathophysiological mechanisms involved in the pathogenesis of CIPN include chronic oxidative stress and subsequent increase in free radicals and proinflammatory cytokines. Approaches for the treatment of CIPN are highly limited in their number and efficacy, although several antioxidant-based therapies have been tried. On the other hand, ozone therapy can induce an adaptive antioxidant and anti-inflammatory response, which could be potentially useful in the management of CIPN. (2) Methods: The aims of this works are: (a) to summarize the potential mechanisms that could induce CIPN by the most relevant drugs (platinum, taxanes, vinca alkaloids, and bortezomib), with particular focus on the role of oxidative stress; (b) to summarize the current situation of prophylactic and treatment approaches; (c) to describe the action mechanisms of ozone therapy to modify oxidative stress and inflammation with its potential repercussions for CIPN; (d) to describe related experimental and clinical reports with ozone therapy in chemo-induced neurologic symptoms and CIPN; and (e) to show the main details about an ongoing focused clinical trial. (3) Results: A wide background relating to the mechanisms of action and a small number of experimental and clinical reports suggest that ozone therapy could be useful to prevent or improve CIPN. (4) Conclusions: Currently, there are no clinically relevant approaches for the prevention and treatment of stablished CIPN. The potential role of ozone therapy in this syndrome merits further research. Randomized controlled trials are ongoing.

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Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy

Cited by 78 publications

References 88 publications

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations

The Antagonism of the Prokineticin System Counteracts Bortezomib Induced Side Effects: Focus on Mood Alterations

26S Proteasome Non-ATPase Regulatory Subunits 1 (PSMD1) and 3 (PSMD3) as Putative Targets for Cancer Prognosis and Therapy

Modulation by Ozone Therapy of Oxidative Stress in Chemotherapy-Induced Peripheral Neuropathy: The Background for a Randomized Clinical Trial

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