Background/Objectives: This study aimed to demonstrate the higher efficacy of cryotherapy in temperature reduction in the upper compared to the lower extremity when used for prevention of chemotherapy-induced peripheral neuropathy (CIPN). Methods: This study was conducted between May 2020 and January 2023 at the Department of Obstetrics and Gynecology at the Medical University of Innsbruck. The analysis included all patients from the CROPSI study who received cryotherapy on their upper (UEX) and lower extremity (LEX) and had completed all assessments from start to end of chemotherapy as well as follow-up. The assessments included temperature measurements and neurological tests during CT and at follow-up after completion of CT. Results: Of the 97 patients recruited in the study, 50 completed all assessments and were therefore included in this analysis. Cryotherapy was more effective when cooling was applied to the upper extremity compared to the lower. On the upper extremity, cryotherapy achieved a cooling effect of 12.5 °C compared to 9.6 °C on the lower extremity (p < 0.001). Patients scored better in both neurological tests on their upper extremity compared to lower. Regarding side effects, there was no significant difference between upper and lower extremities. No severe side effects were reported for either location. Conclusions: Our study suggests that currently available devices for continuous cooling for cryotherapy are significantly more effective on the upper extremity.

Peripheral neuropathy requires early detection and intervention.

This study aimed to examine the association between immunomodulatory medications (IMiDs; thalidomide, lenalidomide, and pomalidomide) and peripheral neuropathy.

OpenVigil 2.1 was used to retrieve data associated with IMiDs and peripheral neuropathy from the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis was performed using the reporting odds ratio (ROR) and information components (IC) with a 95% credibility interval. Peripheral neuropathy signals were further prioritized using a rating scale.

We found 645 cases of peripheral neuropathy in 19,622 adverse event reports for thalidomide, 4849 cases in 197,866 adverse event reports for lenalidomide, and 933 cases in 40,582 adverse event reports for pomalidomide. Based on the clinical priority assessment, peripheral neuropathy was identified as having moderate clinical priority for the three immunomodulatory drugs (priority score = 6). In plasma cell myelomas, more peripheral neuropathy was reported for thalidomide [4.24% vs. 2.51%; ROR = 1.72 (1.42, 2.08); IC = 0.23 (0.05, 0.41)] and lenalidomide [2.71% vs. 1.06%, ROR = 2.59 (2.29, 2.91); IC = 0.14 (0.08, 0.20)] than in non-plasma cell myelomas. Peripheral neuropathy signals were detected in age groups 51-74, 63-74, and 51-62 for lenalidomide, thalidomide, and pomalidomide, respectively. No disproportionate gender differences were detected.

Our study indicated that the risk of peripheral neuropathy varied among patients with different indications and age subgroups for the same IMiD. Further investigation is required to verify these risk signals.

Numerous studies have explored the role of acupuncture-related treatments in alleviating chemotherapy-induced peripheral neuropathy (CIPN) and improving the quality of life for patients with cancer, resulting in mixed findings. This umbrella review aimed to synthesize existing systematic reviews (SRs) to deliver an updated assessment of the certainty of evidence concerning the effects of acupuncture-related treatments on CIPN and quality of life among a diverse group of patients with cancer.

This umbrella review considered eligible SRs published on one of nine electronic databases between inception and August 2024. It included adult patients with cancer of any stage who were undergoing chemotherapy. Interventions encompassed acupuncture, either alone or with electrical stimulation or moxibustion, and transcutaneous electrical acupoint/nerve stimulation (TEAS). The outcomes analyzed were changes in CIPN, nerve conduction velocity (NCV), and quality of life.

The outcomes were evaluated using data obtained from 14 SRs that demonstrated moderate to high methodological and reporting quality. The findings showed that acupuncture (either alone or combined with electrical stimulation) and TEAS effectively alleviated CIPN symptoms, reduced CIPN pain, improved NCV, and enhanced quality of life.

The findings of this umbrella review indicate that these benefits were usually noticeable by the second week of treatment, persisted until the sixth week, and then gradually declined. Sensory nerve recovery occurred more rapidly than motor nerve recovery, often within 1.5 weeks. Although acupuncture combined with moxibustion or acupressure also enhanced patient outcomes, there was insufficient information available for further study analysis.

There is justification for optimism about the potential contribution of alternative medicines to cancer management, which now ranks as the second leading cause of death globally. Primary carcinogens arise from several sources, including agriculture, industry, and dietary intake. Gastric cancer (GC) significantly affects an individual's health due to its classification as a malignant tumor associated with elevated mortality and morbidity rates. Chemotherapy is now widely regarded as the gold standard for treating GC. Chemotherapy, however, exerts significant detrimental effects on human health, including irreversible damage to multiple organs. Consequently, it is essential to employ innovative strategies for cancer prevention. Natural products are now the focus of intensive study due to their efficacy against cancer and low toxicity levels. Natural compounds have shown a diverse range of anti-cancer properties. This review aims to emphasize studies on natural compounds that inhibit metastasis, induce apoptosis in GC, and decrease cellular proliferation. All the natural compounds from different sources were incorporated in this review not only medicinal plants derived compounds. This review aims to examine a comprehensive array of natural therapies that may enhance human health and facilitate GC prevention without inducing discernible negative effects. Moreover, this review aims to discuss the toxic side effects of phytochemicals and shed light on mechanisms underlying the action of potential natural products against GC. This review offers a novel perspective by integrating a broad spectrum of natural compounds from diverse sources, not limited to medicinal plants, to explore their anti-cancer properties against gastric cancer.

The present study evaluated the effect of chelidonic acid on paclitaxel-induced neuropathy in male Wistar rats. Neuropathy was induced by administering paclitaxel (2 mg/kg, i.p.) on 0, 2, 4, and 6 days of the protocol. Chelidonic acid treatment (at doses of 10, 20, and 40 mg/kg orally, for 21 days) was initiated simultaneously with paclitaxel administration. After completion of the protocol, mechanical allodynia, hyperalgesia, and thermal hyperalgesia were measured. Additionally, nerve conduction velocity was assessed. The study investigated inflammatory cytokines, oxidative stress, and histological changes in the sciatic nerve. Furthermore, the Nrf2 was measured, and the protein expression of pAMPK and HIF-1α was assessed using western blotting. The results showed that chelidonic acid significantly normalized mechanical allodynia, hyperalgesia, and thermal hyperalgesia. It also led to a significant improvement in motor and sensory nerve conduction velocity and reduced oxidative stress compared with paclitaxel alone. Inflammatory markers such as TNF-alpha, IL-6, and IL-1β concentrations, as well as nitric oxide and C-reactive protein, were significantly decreased in the chelidonic acid-treated group. Histopathological examination revealed reduced neuronal damage, demyelination, and leukocyte infiltration with chelidonic acid treatment. Chelidonic acid treatment also resulted in a considerable rise in Nrf2 levels (p < 0.001) and increased protein expression of pAMPK in the sciatic nerve. Conversely, HIF-1α expression was significantly declined in the chelidonic acid treatment. Overall, the findings suggest that chelidonic acid treatment attenuates paclitaxel-induced neuropathic pain.

Paclitaxel-induced neuropathy stands out as the primary, dose-limiting side effect of this extensively used chemotherapy agent. Prolonged hypersensitivity and pain represent the most severe clinical manifestations. Effective preventive and therapeutic strategies are currently lacking.

Our study aimed to assess the impact of early oral administration of pharmaceutical-grade formulations containing the phytocannabinoids THC and CBD in a rat model of paclitaxel-induced neuropathy.

The experimental design involved the co-administration of paclitaxel and cannabinoid formulations with different THC to CBD ratios (THC:CBD 1:1 and THC:CBD 1:20) to adult male rats. Mechanical and thermal sensitivity, locomotor activity, vertical exploratory behaviors, anxiety-related parameters, weight gain, food and water consumption, and liver functionality were assessed.

Daily administration of THC:CBD 1:1 successfully prevented paclitaxel-induced cold allodynia, while THC:CBD 1:20 effectively prevented both thermal and mechanical hypersensitivities. Additionally, THC:CBD 1:1 formulation restored rearing behavior, significantly reduced by paclitaxel. Conversely, neither cannabinoid formulation was able to counteract paclitaxel-induced hypo-locomotion, reduced vertical exploratory activity, increased anxiety-like behaviors, attenuated weight gain, or decreased food and water intakes. However, the formulations employed did not induce further alterations or toxicity in animals receiving paclitaxel, and no signs of liver damage were detected.

Our results suggest a differential therapeutic effect of two THC:CBD formulations on pain-related behaviors and spontaneous activities, particularly in the context of peripheral neuropathy. These formulations represent a promising therapeutic strategy not only to managing pain but also for enhancing daily activities and improving the quality of life for cancer patients.

Advances in cancer treatment have led to a steady increase in the rate of disease remission. However, while many treatment-related adverse effects gradually resolve after therapy, chemotherapy-induced peripheral neuropathy (CIPN) often persists, with no means of prevention or direct treatment available. Herein, we present Carba1, a novel bi-functional carbazole that mitigates neuropathy through two distinct mechanisms. First, by interacting with tubulin, Carba1 reduces the required dose of taxanes, widely used chemotherapy drugs notorious for their toxic side effects, including CIPN. Second, Carba1 activates nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD salvage pathway, triggering a metabolic rewiring that enhances the resilience of neurons and Schwann cells against chemotherapy-induced toxicity. We demonstrate the neuroprotective efficacy of Carba1 both in vitro, against neurotoxicity induced by paclitaxel (PTX), cisplatin, and bortezomib, and in vivo in a rat model of PTX-induced neuropathy. Importantly, we establish that Carba1 does not compromise the therapeutic efficacy of PTX nor promotes tumor growth. Comparative analyses of Carba1 derivatives further suggest the potential of designing compounds with either dual synergistic and neuroprotective activity or exclusive neuroprotective properties. Altogether, our findings position Carba1 as a promising therapeutic candidate for preventing CIPN, with the potential, if successfully translated to clinical settings, to improve both the quality of life and treatment outcome for cancer patients.

High-grade chemotherapy-induced peripheral neuropathy (CIPN) represents a dreaded toxicity of cancer treatments. In some cases, it may limit activities of daily living and become permanent. Because many prior studies of CIPN were conducted in breast cancer populations, less is known about CIPN in men. We therefore determined the incidence and correlates of high-grade CIPN in a large cohort of patients with lung cancer.

We collected data from the ECOG-ACRIN E1594 (comparison of 4 chemotherapy regimens: cisplatin-paclitaxel, cisplatin-gemcitabine, cisplatin-docetaxel, carboplatin-paclitaxel) and E4599 (carboplatin-paclitaxel ± concurrent and maintenance bevacizumab) clinical trials. We identified cases with grade ≥3 CIPN. Multivariable logistic regression modeling was performed to estimate adjusted odds ratios according to patient characteristics.

Among 1,998 patients included in the study, 167 (8%) developed grade ≥3 CIPN. Grade ≥3 CIPN was associated with higher body mass index (BMI) (P = .01), sex (7% for men vs 10% for women; P = .005), age (11% for ≥65 years vs 7% for <65 years; P < .001), chemotherapy regimen (P = .01), and greater number treatment cycles (P < .001). In a multivariate model, regimens featuring higher doses of paclitaxel or cisplatin, greater number of chemotherapy cycles, female sex, greater age, and higher BMI remained independently associated with grade ≥3 CIPN.

High-grade CIPN is associated with chemotherapy type and exposure, female sex, greater age, and elevated BMI. Given the ongoing use of cytotoxic agents in established and new (eg, antibody-drug conjugates) treatment regimens, these findings have implications for patient monitoring and treatment selection.

Paclitaxel, a chemotherapeutic drug, induces sensorimotor peripheral neuropathy. Carvedilol, a nonselective β-adrenoreceptor blocker, has been shown to exert antioxidant activity. Platelet-rich plasma (PRP) has supra-physiological levels of growth factors (GFs), enhances biosynthesis of antioxidant enzymes, and suppresses oxidative stress. This study compared the ameliorative effects of carvedilol and PRP on paclitaxel-induced femoral neuropathy. Eighty-eight adult male albino rats were equally randomized into four groups: group I served as the control; group II received paclitaxel (16 mg/kg intraperitoneally, weekly); group III received carvedilol (10 mg/kg daily, orally) concomitant with paclitaxel; and group IV received PRP (0.5 mL/kg subcutaneously, twice weekly) concomitant with paclitaxel. After 5 weeks, femoral nerve conduction velocity was measured, and blood samples were collected to assess catalase and superoxide dismutase levels. All animals were sacrificed, and gene expression of miR-21 was quantified. Tissue sections were stained with hematoxylin and eosin and toluidine blue. Then, the ultrathin sections were examined by transmission electron microscopy. Both carvedilol and PRP reversed paclitaxel-induced changes in the peripheral nerve, but PRP demonstrated a stronger antioxidant effect and a more pronounced presence of GFs, as evidenced by electron microscopy. PRP may represent a promising therapeutic approach for paclitaxel-induced neuropathy.

One of the most common adverse side effects of chemotherapeutics is chemotherapy-induced peripheral neuropathy (CIPN). Paclitaxel, a highly effective chemotherapeutic, is associated with a high incidence of paclitaxel-induced peripheral neuropathy (PIPN) that persists for over a year in 64% of patients and worsens with cumulative PTX dose. Patients experiencing PIPN may reduce the dosage of chemotherapy or halt treatment due to this pain. Current preclinical models have improved our understanding of PIPN but have been ineffective in generating translational therapeutic options. These models administer a single cycle of PTX to induce a PIPN phenotype of mechanical and cold hypersensitivity that resolves within 28 days. However, this does not mirror the clinical dosing regimen or the patient experience of CIPN. In this study, we conduct a comprehensive and longitudinal behavioral profile of our novel model of PIPN in mice where three consecutive cycles of PTX (4 mg/kg, 4 doses/cycle) are given to mimic the clinical administration. Repeated cycles of PTX caused long-lasting mechanical and cold hypersensitivity in male and female C57Bl/6J mice that mirrors clinical observations of persistent CIPN without causing detrimental effects to rodent overall health, normal rodent behavior, or motor function. Our findings support the use of this translational model to facilitate a better understanding of PIPN and the development of effective treatment options. Improved pain management will enable the completion of cancer treatment, decrease health care expenditure, decrease mortality, and improve the quality of life for cancer patients and survivors.

Minocycline suppresses chemotherapy-induced neuroinflammation in preclinical models, but its effects in cancer survivors are unknown. This study evaluated the longitudinal effects of minocycline on affective behaviors, cognitive functions, and inflammation in women with breast cancer (BC) undergoing chemotherapy.

This is a pilot, double-blind, randomized controlled trial of oral minocycline (100 mg BID) versus placebo for chemotherapy-induced affective disorders in women initiating chemotherapy for stage I-III BC. Participants received minocycline or placebo up to one week before chemotherapy, continuing through cycle 4 (C4). Epidemiologic Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI) were assessed at baseline, each cycle of chemotherapy (C1-C4), 2-3-week post-chemotherapy (end of chemotherapy), and 6-month post-chemotherapy (6 M) as the primary outcomes. Sub-group analysis of CES-D and STAI based on the severity of symptoms was also performed. Changes in self-reported cognition and serum inflammatory markers were also evaluated.

Fifty-seven women enrolled and 55 completed the study. Except for Interleukin-8 (p ≤ 0.03), changes in inflammatory markers, cognitive function, CES-D, and STAI were not significantly different between groups from baseline to any cycle or post-chemotherapy time point (all p > 0.05), adjusting for baseline scores. Increases in serum Interleukin-8 from baseline to C4 and 6 M were ameliorated by minocycline (p < 0.05). The sub-group symptomatic for depression (CES-D > = 16 at baseline) treated with minocycline had a greater reduction in CES-D score compared to placebo from baseline to 6 M (p = 0.01).

Despite attenuation of IL-8, minocycline did not alter self-reported affective symptoms or cognition in this cohort of BC survivors undergoing chemotherapy. The effect of minocycline on BC survivors symptomatic for depression before chemotherapy warrants further investigation.

A microphysiological system (MPS) is an in vitro culture technology that reproduces the physiological microenvironment and functionality of humans and is expected to be applied for drug screening. In this study, we developed an MPS for the structured culture of human iPSC-derived sensory neurons and then predicted drug-induced neurotoxicity by morphological deep learning. Using human iPSC-derived sensory neurons, after the administration of representative anti-cancer drugs, the toxic effects on soma and axons were evaluated by an AI model with neurite images. Significant toxicity was detected in positive drugs and could be classified by different effects on soma or axons, suggesting that the current method provides an effective evaluation of chemotherapy-induced peripheral neuropathy. The results of neurofilament light chain expression changes in the MPS device also agreed with clinical reports. Therefore, the present MPS combined with morphological deep learning is a useful platform for in vitro peripheral neurotoxicity assessment.

Chemodynamic therapy (CDT) is a new method for cancer treatment that produces highly toxic reactive oxygen species (ROS) in the tumor microenvironment to induce cancer cell apoptosis or necrosis. However, the therapeutic effect of CDT is often hindered by intracellular H2O2deficiency and the activity of antioxidants such as glutathione (GSH). In this study, a nano-catalyst HCM was developed using a self-assembled Cu/Mn-doped metal-organic framework, and its surface was modified with hyaluronic acid to construct a tumor-targeting CDT therapeutic agent with improved the efficiency and specificity. Three substances HHTP (2, 3, 6, 7, 10, 11-hexahydroxybenzophenanthrene), Cu2+, and Mn2+were shown to be decomposed and released under weakly acidic conditions in tumor cells. HHTP produces exogenous H2O2in the presence of oxygen to increase the H2O2content in tumors, Cu2+reduces GSH content and generates Cu+in the tumor, and Cu+and Mn2+catalyze H2O2to produce ∙OH in a Fenton-like reaction. Together, these three factors change the tumor microenvironment and improve the efficiency of ROS production. HCM showed selective and efficient cytotoxicity to cancer cells, and could effectively inhibit tumor growthin vivo, indicating a good CDT effect.

Colorectal cancer (CRC) is a global health challenge necessitating innovative therapeutic strategies. There is an increasing trend toward the clinical application of integrative Chinese medicine (CM) and Western medicine approaches. Chinese herbal monomers and formulations exert enhanced antitumor effects by modulating multiple signaling pathways in tumor cells, including inhibiting cell proliferation, inducing apoptosis, suppressing angiogenesis, reversing multidrug resistance, inhibiting metastasis, and regulating immunity. The synergistic effects of CM with chemotherapy, targeted therapy, immunotherapy, and nanovectors provide a comprehensive framework for CRC treatment. CM can mitigate drug toxicity, improve immune function, control tumor progression, alleviate clinical symptoms, and improve patients' survival and quality of life. This review summarizes the key mechanisms and therapeutic strategies of CM in CRC, highlighting its clinical significance. The potential for CM and combination with conventional treatment modalities is emphasized, providing valuable insights for future research and clinical practice.

Chemodynamic therapy (CDT) has emerged as a transformative paradigm in the realm of reactive oxygen species -mediated cancer therapies, exhibiting its potential as a sophisticated strategy for precise and effective tumor treatment. CDT primarily relies on metal ions and hydrogen peroxide to initiate Fenton or Fenton-like reactions, generating cytotoxic hydroxyl radicals. Its notable advantages in cancer treatment are demonstrated, including tumor specificity, autonomy from external triggers, and a favorable side-effect profile. Recent advancements in nanomedicine are devoted to enhancing CDT, promising a comprehensive optimization of CDT efficacy. This review systematically elucidates cutting-edge achievements in chemodynamic nanotherapeutics, exploring strategies for enhanced Fenton or Fenton-like reactions, improved tumor microenvironment modulation, and precise regulation in energy metabolism. Moreover, a detailed analysis of diverse CDT-mediated combination therapies is provided. Finally, the review concludes with a comprehensive discussion of the prospects and intrinsic challenges to the application of chemodynamic nanotherapeutics in the domain of cancer treatment.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major long-lasting side effect of some chemotherapy drugs, which threatens cancer survival rate. CIPN mostly affects sensory neurons and occasionally motor neurons, causing numbness, tingling, discomfort, and burning pain in the upper and lower extremities. The pathophysiology of CIPN is not completely understood; however, it is believed that chemotherapies induce peripheral neuropathy via directly damaging mitochondria, impairing the function of ion channels, triggering immunological mechanisms, and disrupting microtubules. The treatment of CIPN is a medical challenge, and there are no approved pharmacological options. Currently, duloxetine and other antidepressants, antioxidant, anti-inflammatory, and ion-channel targeted therapies are commonly used in clinics to relieve the symptoms of CIPN. Several other types of drugs, such as cannabinoids, sigma-1 receptor antagonists, and nicotinamides ribose, are being evaluated in preclinical and clinical studies. This paper summarizes the information related to the physiology of CIPN and medicines that could be used for treating this condition.

Calcitriol as a biologically active form of vitamin D3 has beneficial effects on all body systems. This vitamin has a potent neuroprotective effect via several independent mechanisms against brain insults induced by anticancer drugs. The present study was designed to examine the neuroprotective effects of calcitriol against neurotoxicity induced by cisplatin. Induction of neurotoxicity was done with cisplatin administration (5 mg/kg/week) for 5 successive weeks in male Wistar rats. The neuroprotective influence of calcitriol supplementation (100ng/kg/day for 5 weeks) was assessed through behavioral, electrophysiological, and molecular experiments. Cisplatin administration impaired spatial learning and memory and decreased prefrontal brain-derived neurotrophic factor (BDNF). Peripheral sensory neuropathy was induced through cisplatin administration. Cisplatin also reduced the amplitudes of the compound action potential of sensory nerves in electrophysiological studies. Cisplatin treatment elevated MDA levels and reduced anti-oxidant (SOD and GPx) enzymes. Pro-inflammatory cytokines (IL-1β and TNF-α) and metalloproteinase-2 and 9 (MMP-2/9) were augmented through treatment with cisplatin. Learning and memory impairments along with BDNF changes caused by cisplatin were amended with calcitriol supplementation. Reduced sensory nerve conduction velocity in the cisplatin-treated group was improved by calcitriol. Calcitriol partially improved redox imbalance and diminished the pro-inflammatory cytokines and MMP-2/9 levels. Our findings showed that calcitriol supplementation can relieve cisplatin-induced peripheral neurotoxicity. Calcitriol can be regarded as a promising new neuroprotective agent.

This study aimed to demonstrate the superiority of cryocompression over cryotherapy alone in the prevention of chemotherapy-induced peripheral neuropathy (CIPN) grade 2 or above.

This prospective randomized study was conducted between May 2020 and January 2023 in Innsbruck. Eligible patients had a diagnosis of gynecological cancer and received a minimum of 3 cycles of taxane-based CT (neoadjuvant, adjuvant or palliative therapy). Patients were randomized 1:1 to receive either cryotherapy or cryocompression on their upper extremities during chemotherapy (CT). We performed temperature measurements, two QoL questionnaires and neurological tests during CT and at follow-up 3 and 6-9 months after the completion of CT. CIPN was assessed using the CTCAE score.

Of 200 patients recruited, both groups showed a lower prevalence of CIPN in this study compared to recent literature. In the group receiving cryotherapy, the prevalence of grade 1 CIPN was 30.1 %, and that of grade 2 CIPN or above was 13.7 %; in the group treated with cryocompression, the prevalence of grade 1 CIPN was 32.8 %, and that of grade 2 or above CIPN was 17.2 %. We found a significant reduction in temperature in the cryotherapy and cryocompression groups. Regarding the two QOL questionnaires as well as the neurological tests no significant differences were found between the two groups.

Our study suggests that cryotherapy as well as cryocompression is a safe and effective way to cool patients' extremities to lower the prevalence of CIPN. Cryocompression was not more effective than cryotherapy alone in the prevention of CIPN.

The study investigates cryotherapy's efficacy in mitigating Chemotherapy-induced peripheral neuropathy (CIPN), an adverse effect of chemotherapy that often leads to dosage reduction or treatment discontinuation.

The study was registered with PROSPERO (CRD42023428936). A literature search was conducted using the PubMed, Embase, and Cochrane Library databases. Randomized and nonrandomized controlled trials that investigated the effects of cryotherapy on CIPN were included for systematic review and meta-analysis. The primary outcome for prevention was the incidence of CIPN.

We identified 17 trials involving 2,851 patients. In total, 11 trials compared the incidence of CIPN between cryotherapy and control groups. Significant differences in the incidence of CIPN at the midpoint and end of chemotherapy were observed, with risk ratios (RRs) of 0.23 (95% confidence interval [CI] = 0.13 to 0.43) and 0.54 (95% CI = 0.33 to 0.88), respectively. Cryotherapy also significantly reduced the incidence of sensory CIPN, with an RR of 0.67 (95% CI = 0.49 to 0.92). Additionally, cryotherapy demonstrated a significant reduction in the incidence of CIPN in patients with gynecological cancers (RR = 0.24, 95% CI = 0.14 to 0.41). Significantly favorable global quality of life scores following chemotherapy (standardized mean difference = 1.43; 95% CI = 0.50 to 2.36) and relieved neuropathic symptoms were found with cryotherapy.

Cryotherapy demonstrates a pronounced preventive effect against the development of CIPN, providing substantial symptomatic relief and quality of life improvements for patients undergoing chemotherapy. The administration of cryotherapy through the use of frozen gloves and socks, or continuous-flow cooling systems, optimally initiated 15 min prior to and concluded 15 min following chemotherapy, is recommended for achieving maximum therapeutic efficacy.

Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect with ineffective preventative and curative treatment. Currently, only Duloxetine has been recommended as effective treatment for CIPN, which has shown individual-dependent, short-term analgesic effects, with limiting adverse effects and poor bioavailability. The neuropeptide, oxytocin, may offer significant analgesic and anxiolytic potential, as it exerts central and peripheral attenuating effects on nociception. However, it is unknown whether the intervention administered in a model of CIPN is an effective therapeutic alternative or adjuvant. Materials and Methods The intervention was divided into two phases. Phase 1 aimed to induce CIPN in adult Wistar rats using the chemotherapeutic agent Paclitaxel. Mechanical (electronic von Frey filament) and thermal (acetone evaporation test and Hargreaves test) hypersensitivity testing were used to evaluate changes due to the neuropathic induction. Phase 2 consisted of a 14-day intervention period with saline (o.g.), duloextine (o.g.), or oxytocin (i.n.) administered as treatment. Following the intervention, anxiety-like behaviour was assessed using the elevated plus maze (EPM) and light-dark box protocols. Analysis of peripheral plasma corticosterone, peripheral plasma oxytocin, and hypothalamic oxytocin concentrations were assessed using ELISA assays. Results The findings showed that we were able to successfully establish a model of chemotherapy-induced peripheral neuropathy during Phase 1, determined by the increase in mechanical and thermal nociceptive responses following Paclitaxel administration. Furthermore, the animals treated with oxytocin displayed a significant improvement in mechanical sensitivity over the intervention phase, indicative of an improvement in nociceptive sensitivity in the presence of neuropathic pain. Animals that received Paclitaxel and treated with oxytocin also displayed significantly greater explorative behaviour during the EPM, indicative of a reduced presence of anxiety-like behaviour. Conclusion Our results support the hypothesis that intranasally administered oxytocin may augment the analgesic and anxiolytic effects of duloxetine in a chemotherapy induced peripheral neuropathy model in a Wistar rat. Future studies should consider administering the treatments in combination to observe the potential synergistic effects.

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of cancer treatment, often linked with pain complaints. Patients report mechanical and thermal hypersensitivity that may emerge during chemotherapy treatment and may persist after cancer remission. Whereas the latter situation disturbs the quality of life, life itself may be endangered by the appearance of CIPN during cancer treatment. The causes of CIPN have almost entirely been ascribed to the neurotoxicity of chemotherapeutic drugs in the peripheral nervous system. However, the central consequences of peripheral neuropathy are starting to be unraveled, namely in the supraspinal pain modulatory system. Based on our interests and experience in the field, we undertook a review of the brain-centered alterations that may underpin pain in CIPN. The changes in the descending pain modulation in CIPN models along with the functional and connectivity abnormalities in the brain of CIPN patients are analyzed. A translational analysis of preclinical findings about descending pain regulation during CIPN is reviewed considering the main neurochemical systems (serotoninergic and noradrenergic) targeted in CIPN management in patients, namely by antidepressants. In conclusion, this review highlights the importance of studying supraspinal areas involved in descending pain modulation to understand the pathophysiology of CIPN, which will probably allow a more personalized and effective CIPN treatment in the future.

Chemotherapy-induced peripheral neuropathy (CIPN) is still an unresolved problem in cisplatin (CIS) use.

This study investigates possible anti-neuropathic effect of chlorogenic acid (CGA) against CIS-induced CIPN in rats while also investigating the contribution of nitric oxide (NO) to this phenomenon.

Initially, CGA (250-1000 μM) was tested by MTT assay on primary DRG neurons. Subsequently, CIPN was induced in Sprague-Dawley rats by 3 mg/kg intraperitoneal injections of CIS once/week for 5 weeks. CGA (100 mg/kg) was co-administered with CIS, both alone and in combination with l-arginine (LARG) or l-nitro-arginine-methyl-ester (LNAME), to elucidate the contribution of nitrergic system to anti-neuropathic effects. Mechanical allodynia, thermal hyperalgesia, and cold plate tests were performed to test CIPN. Rotarod, footprint analysis, and activitymeter were used to evaluate motor coordination and performance. Tumor necrosis factor alpha (TNF-α) was measured as a marker of inflammation. Histological evaluations of DRG and sciatic nerves (SNs) were performed utilizing toluidine blue staining. Two-way analysis of variance and Kruskal-Wallis following Tukey's test were used as statistical analysis.

Higher concentration of CGA (1000 μM) exhibited protective effect against in vitro neurotoxicity. Neither LARG nor LNAME exerted significant change in this effect. Co-administration of CGA alleviated histological abnormalities and neuropathic effects induced by CIS. Ameliorative effect of CGA was not changed in mechanical allodynia but attenuated in cold allodynia, and motor activity/coordination tests by LARG and LNAME. Neuropathic effects of CIS remained unchanged with LARG and LNAME in behavioral experiments.

The study identified CGA as candidate agent in mitigating CIPN. NO seems to play a modulatory role in this effect.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant cancer treatment side effect that can influence both quality of life and treatment course. Melissa Officinalis (MO), due to its high content of flavonoids, has antioxidant, anti-inflammatory, and neuroprotective properties.  Materials and Methods: The cancer patients diagnosed with CIPN attended a referral center in Sari (Iran). The hydroalcoholic extract of MO leaves was extracted by the maceration method. The control group received a placebo along with gabapentin as the standard treatment, and the intervention group received 500 mg Melissa officinalis 2 times daily for 3 months plus gabapentin. Patients were evaluated at the baseline and 3 months later, according to Common Terminology Criteria for Adverse Effects (CTCAE) and EORTC QLQ-C30 (Integrated System for Quality of Life Assessment).  Results: A total of 40 patients were considered as group D (intervention group), and 35 patients completed the study. Out of 40 subjects in the placebo group (P), 3 patients could not tolerate the drug due to gastrointestinal disturbances. The final values of CTCAE showed a statistically significant difference (p=0.010). Indicators related to the quality of life in both groups showed a significant improvement. In the intervention group, the pain perception and diarrhea experience were significantly reduced. Conclusion: Quality of life indicators were improved by prescribing gabapentin with and without Melissa officinalis. The addition of Melissa officinalis to the chemotherapy regimen may improve diarrhea and pain perception.

This study investigated the clinical risk factors for peripheral neuropathy induced by docetaxel and albumin-bound paclitaxel (AP) in patients with breast cancer.

This prospective observational study recruited 268 patients between March 2019 and December 2020. Patient information was obtained through the query system for laboratory test results, patient consultations, and scale evaluations. Neuropathic symptoms were followed up throughout and until 3 months after taxane chemotherapy. Univariate and multivariate analyses were used to find the risk factors for overall and moderate-severe taxane-induced peripheral neuropathy (TIPN).

Cumulative dose (odds ratio [OR] = 3.533, 95% confidence interval [CI]: 1.797-6.944, p < 0.001), body mass index (BMI) (OR = 2.926, 95% CI: 1.621-5.281, p < 0.001), body surface area (BSA) (OR = 1.724, 95% CI: 1.011-2.941, p = 0.045), and hypocalcemia (OR = 4.899, 95% CI: 1.518-15.811, p = 0.008) all increased the risk of TIPN. Only cumulative dose (OR = 2.577, 95% CI: 1.161-5.719, p = 0.020) and BSA (OR = 2.040, 95% CI: 1.073-3.877, p = 0.030) were independent risk factors for moderate-severe TIPN.

Cumulative dose, BMI, BSA, and hypocalcemia are all risk factors for overall TIPN, whereas cumulative dose and BSA are risk factors for moderate-severe TIPN. Patients with breast cancer who have high BMI, large BSA, hypocalcemia, and large cumulative dose may be at risk of TIPN, and intervention measures must be actively carried out for them.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and severe adverse reaction in taxane-based chemotherapy. This study aimed to analyze the risk factors of peripheral neuropathy in patients with breast cancer receiving paclitaxel chemotherapy to provide a reference for the early prevention of CIPN.

We included 350 patients with breast cancer who received chemotherapy for the first time at the Tangshan People's Hospital between August 2022 and June 2023 and were followed for at least 3 months after the end of chemotherapy. The incidence of CIPN in patients with breast cancer was calculated, and risk factors for CIPN were analyzed using logistic regression analysis.

The incidence rate of CIPN was 79.1%. Multifactor logistic regression analysis indicated that age ≥45 years [odds ratio (OR)=5.119, 95% confidence interval (CI)=1.395-18.780] and ≥60 years (OR=9.366, 95% CI=1.228-71.421), history of hypertension (OR=3.475, 95% CI=1.073-11.250), cumulative dose of chemotherapy drugs >900 mg (OR=4.842, 95% CI=1.961-5.946), vitamin D deficiency (OR=6.214, 95% CI=2.308-16.729), abnormal alanine aminotransferase (OR=3.154, 95% CI=1.010-9.844), anemia before chemotherapy (OR=2.770, 95% CI=1.093-7.019), infusion duration of chemotherapy drugs >30 min (OR=3.673, 95% CI=1.414-9.539), body mass index ≥24 kg/m2 (OR=8.139, 95% CI=1.157-57.240), mild depression (OR=4.546, 95% CI=1.358-15.223), and major depression (OR=4.455, 95% CI=1.237-16.037) increased the risk of CIPN. Having a regular caregiver (OR=0.223, 95% CI=0.087-0.573), high levels of physical activity (OR=0.071, 95% CI=0.008-0.647), and strong social support (OR=0.048, 95% CI=0.003-0.682) were protective factors against CIPN.

Clinical attention should be paid to patients with these risk factors, and active and effective preventive measures should be taken to reduce the occurrence of CIPN and improve the quality of life.

Bortezomib (BTZ) is a commonly used antitumor drug, but its peripheral neuropathy side effect poses a limitation on its dosage. Evodiamine (EVO) exhibits various biological activities, including antioxidant, anti-inflammatory, and anticancer effects. The purpose of this investigation is to confirm the impact of EVO on BTZ-induced peripheral neurotoxicity.

GeneCards and HERB were applied to analyze the targets of peripheral neurotoxicity and EVO. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis of the hub genes were identified by DAVID. Rat dorsal root ganglion neurons (DRGs) and rat RSC96 Schwann cells (SCs) were treated with BTZ to simulate peripheral neurotoxicity. BTZ-induced peripheral neurotoxicity was assessed by detecting cell viability, proliferation, oxidative stress, and ferroptosis in DRGs and SCs. The mitogen-activated protein kinase (MAPK) signaling was scrutinized by Western blot assay.

The Venn diagram for the overlapping targets of EVO and peripheral neurotoxicity showed that EVO might regulate peripheral neurotoxicity by influencing cell oxidative stress, ferroptosis, and MAPK signaling pathway. EVO attenuated BTZ-induced toxicity in DRGs and SCs. EVO attenuated BTZ-induced oxidative stress damage in DRGs and SCs by reducing reactive oxygen species and malondialdehyde levels and enhancing glutathione level. EVO attenuated BTZ-induced ferroptosis in DRGs and SCs. EVO inhibited BTZ-induced activation of the MAPK signaling in DRGs and SCs. Activation of the MAPK signaling reversed the neuroprotective effect of EVO on BTZ-induced oxidative stress injury and ferroptosis.

EVO attenuated oxidative stress and ferroptosis by inhibiting the MAPK signaling to improve BTZ-induced peripheral neurotoxicity.

Cisplatin is a platinum-based chemotherapy drug widely used to treat various solid tumours. Although it is effective in anti-cancer therapy, many patients develop peripheral neuropathy during and after cisplatin treatment. Peripheral neuropathy results from lesions or diseases in the peripheral somatosensory nervous system and is a significant cause of debilitation and suffering in patients. In recent years, preclinical studies have been conducted to elucidate the mechanisms involved in chemotherapy-induced peripheral neuropathic pain, as well as to promote new therapeutic targets since current treatments are ineffective and are associated with adverse effects. G-protein coupled receptors and ion channels play a significant role in pain processing and may represent promising targets for improving the management of cisplatin-induced neuropathic pain. This review describes the role of G protein-coupled receptors and ion channels in cisplatin-induced pain, analysing preclinical experimental studies that investigated the role of each receptor subtype in the modulation of cisplatin-induced pain.

Objective: Development of chemotherapy-induced peripheral neuropathy (CIPN) poses significant challenges in cancer treatment, often leading to dose reductions or treatment discontinuation. Goshajinkigan (GJG), a traditional Japanese medicine, has shown promise for alleviating CIPN symptoms. This multicenter, randomized controlled trial aimed to prospectively examine the efficacy of GJG in preventing paclitaxel-induced peripheral neuropathy. Methods: This study enrolled 55 patients with ovarian cancer undergoing first-line chemotherapy using paclitaxel and carboplatin. The participants were randomized into Groups A (GJG initiation after onset of grade 2 neuropathy) and B (prophylactic administration of GJG from 1 week before chemotherapy). The primary endpoints were the proportion with a maximum sensory neuropathy grade and visual analog scale (VAS) scores. The secondary endpoints were the rate of chemotherapy completion and paclitaxel dose reduction due to neurotoxicity. Results: Prophylactic GJG administration (Group B) resulted in significant benefits. While both groups had a similar incidence of grade 2 sensory neuropathy, all patients in Group B with grade 2 neuropathy completed treatment without requiring additional analgesics. Group B exhibited lower VAS scores by the end of the study, reduced reliance on adjuvant analgesics (27.3% vs 66.7% in Group A), and significantly less frequent persistent CIPN 6 months post-chemotherapy (18.2% vs 55.6% in Group A). No differences were observed in the chemotherapy completion rates or CIPN-related changes between the groups. Conclusion: GJG, when administered prophylactically, showed potential for mitigating CIPN symptoms during paclitaxel chemotherapy. While promising, further research with placebo controls and objective measures is essential to comprehensively validate these findings.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a major adverse event of anti-cancer drugs, which still lack standardized measurement and treatment methods. In the present study, we attempted to evaluate neuronal dysfunctions in cultured rodent primary peripheral neurons using a microelectrode array system. After exposure to typical anti-cancer drugs (i.e., paclitaxel, vincristine, oxaliplatin, and bortezomib), we successfully detected neurotoxicity in dorsal root ganglia neurons by measuring electrical activities, including impedance value and spontaneous activity. The impedance value decreased significantly for all compounds, even at low concentrations, which indicated cell loss and/or neurite degeneration. The spontaneous activity was also suppressed after exposure, which suggested neurotoxicity again. However, an acute response was observed for paclitaxel and bortezomib before toxicity, which showed different mechanisms based on compounds. Therefore, MEA measurement of impedance value could provide a simple assessment method for CIPN, combined with neuronal morphological changes.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of several antitumor agents resulting in progressive and often irreversible damage of peripheral nerves. In addition to their known anticancer effects, taxanes, including paclitaxel, can also induce peripheral neuropathy by activating microglia and astrocytes, which release pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 1-beta (IL-1β), and chemokine (C-C motif) ligand 2 (CCL-2). All these events contribute to the maintenance of neuropathic or inflammatory response. Complement component 5a (C5a)/C5a receptor 1 (C5aR1) signaling was very recently shown to play a crucial role in paclitaxel-induced peripheral neuropathy. Our recent findings highlighted that taxanes have the previously unreported property of binding and activating C5aR1, and that C5aR1 inhibition by DF3966A is effective in preventing paclitaxel-induced peripheral neuropathy (PIPN) in animal models. Here, we investigated if C5aR1 inhibition maintains efficacy in reducing PIPN in a therapeutic setting. Furthermore, we characterized the role of C5aR1 activation by paclitaxel and the CIPN-associated activation of nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome. Our results clearly show that administration of the C5aR1 inhibitor strongly reduced cold and mechanical allodynia in mice when given both during the onset of PIPN and when neuropathy is well established. C5aR1 activation by paclitaxel was found to be a key event in the induction of inflammatory factors in spinal cord, such as TNF-α, ionized calcium-binding adapter molecule 1 (Iba-1), and glial fibrillary acidic protein (GFAP). In addition, C5aR1 inhibition significantly mitigated paclitaxel-induced inflammation and inflammasome activation by reducing IL-1β and NLRP3 expression at both sciatic and dorsal root ganglia level, confirming the involvement of inflammasome in PIPN. Moreover, paclitaxel-induced upregulation of C5aR1 was significantly reduced by DF3966A treatment in central nervous system. Lastly, the antinociceptive effect of C5aR1 inhibition was confirmed in an in vitro model of sensory neurons in which we focused on receptor channels usually activated upon neuropathy. In conclusion, C5aR1 inhibition is proposed as a therapeutic option with the potential to exert long-term protective effect on PIPN-associated neuropathic pain and inflammation.

Since the successful approval of gemtuzumab ozogamicin, antibody-drug conjugates (ADCs) have emerged as a pivotal category of targeted therapies for cancer. Among these ADCs, the use of monomethyl auristatin E (MMAE) as a payload is prevalent in the development of ADC drugs, which has significantly improved overall therapeutic efficacy against various malignancies. However, increasing clinical observations have raised concerns regarding the potential nervous system toxicity associated with MMAE-based ADCs. Specifically, a higher incidence of peripheral neuropathy has been reported in ADCs incorporating MMAE as payloads. Considering the increasing global use of MMAE-based ADCs, it is imperative to provide an inclusive overview of diagnostic and management strategies for this adverse event. In this review, we examine current information and what future research directions are required to better understand and manage this type of clinical challenge.

Paclitaxel is associated with an acute pain syndrome (P-APS- and chronic chemotherapy-induced peripheral neuropathy (CIPN). P-APS is associated with higher risk of CIPN. Omega-3 fatty acids have well-established anti-inflammatory and neuroprotective properties. The primary purpose of this pilot study was to assess whether omega-3 fatty acids could decrease P-APS and thus CIPN.

Patients scheduled to receive weekly paclitaxel for breast cancer were randomized to receive 4 g of omega-3 acid ethyl esters (Lovaza) or placebo, beginning 1 week prior and continued until paclitaxel was stopped. Patients completed acute pain questionnaires at baseline, daily after each treatment, and 1 month after completion of therapy.

Sixty patients (49 evaluable) were randomized to treatment versus placebo. Seventeen (68.0%) patients receiving the omega-3 fatty acids intervention experienced P-APS, compared to 15 (62.5%) of those receiving placebo during the first week of treatment (p = 0.77). Over the full 12-week study, 21 (84.0%) patients receiving the omega-3 fatty acid intervention experienced P-APS, compared to 21 (87.5%) of those receiving placebo (p = 1.0). Secondary outcomes suggested that those in the intervention arm used more over-the-counter analgesics (OR: 1.65, 95% CI: 0.72-3.78, p = 0.23), used more opiates (OR: 2.06, 95% CI: 0.55-7.75, p = 0.28), and experienced higher levels of CIPN (12.8, 95% CI: 7.6-19.4 vs. 8.4, 95% CI: 4.6-13.2, p = 0.21).

The results of this pilot study do not support further study of the use of omega-3 fatty acids for the prevention of the P-APS and CIPN.

Number: NCT01821833.

Several anticancer drugs used in cancer therapy induce chemotherapy-induced peripheral neuropathy (CIPN), leading to dose reduction or therapy cessation. Consequently, there is a demand for an in vitro assessment method to predict CIPN and mechanisms of action (MoA) in drug candidate compounds. In this study, a method assessing the toxic effects of anticancer drugs on soma and axons using deep learning image analysis is developed, culturing primary rat dorsal root ganglion neurons with a microphysiological system (MPS) that separates soma from neural processes and training two artificial intelligence (AI) models on soma and axonal area images. Exposing the control compound DMSO, negative compound sucrose, and known CIPN-causing drugs (paclitaxel, vincristine, oxaliplatin, suramin, bortezomib) for 24 h, results show the somatic area-learning AI detected significant cytotoxicity for paclitaxel (* p < 0.05) and oxaliplatin (* p < 0.05). In addition, axonal area-learning AI detected significant axonopathy with paclitaxel (* p < 0.05) and vincristine (* p < 0.05). Combining these models, we detected significant toxicity in all CIPN-causing drugs (** p < 0.01) and could classify anticancer drugs based on their different MoA on neurons, suggesting that the combination of MPS-based culture segregating soma and axonal areas and AI image analysis of each area provides an effective evaluation method to predict CIPN from low concentrations and infer the MoA.

Oxaliplatin-based chemotherapy is a major first-line conventional therapy for advanced and metastatic colorectal cancer (CRC). However, oxaliplatin causes chemotherapy-induced peripheral neuropathy (CIPN). Acupuncture has long been used to alleviate limb numbness in Chinese medicine practice.

The aim of this study was to examine the efficacy and safety of electroacupuncture (EA) for the alleviation of CIPN in CRC patients.

This was a pilot single-blinded, randomized, sham-controlled trial.

Sixty eligible patients, who had been diagnosed with CRC and were undergoing oxaliplatin-based chemotherapy, were randomized in a ratio of 1:1 to the EA intervention group or sham acupuncture (SA) control group. During a 12-week treatment period, patients in the EA group received EA once a week, while patients in the SA group received SA; both groups were followed up for 12 weeks.

Compared with the SA group, the EA group exhibited significant alleviation of CIPN severity during chemotherapy. Moreover, EA also improved the physical function, role function, and social function of CRC patients. However, there were no significant differences in tests of vibration or light touch sensation. In addition, EA appeared to be a safe treatment for CIPN and was both feasible and acceptable to CRC patients during chemotherapy.

This study showed preliminary evidence for the efficacy and safety of EA in acute CIPN among CRC patients, although further studies are needed to verify these effects and to further explore the potential role of EA in chronic CIPN (effects on which remain unclear).

NCT03582423 (ClinicalTrials.gov).

5-fluorouracil (5-FU) is an antineoplastic drug used to treat colorectal cancer, but it causes, among other adverse effects, diarrhea and mucositis, as well as enteric neuropathy, as shown in experimental animals. It might also cause neuropathic pain and alterations in visceral sensitivity, but this has not been studied in either patients or experimental animals. Cannabinoids have antimotility and analgesic effects and may alleviate 5-FU-induced adverse effects. Our aim was to evaluate the effects of the cannabinoid agonist WIN 55,212-2 on neuropathic and visceral pain induced by a non-diarrheagenic dose of 5-FU. Male Wistar rats received a dose of 5-FU (150 mg/kg, ip) and gastrointestinal motility, colonic sensitivity, gut wall structure and tactile sensitivity were evaluated. WIN 55,212-2 (WIN) was administered to evaluate its effect on somatic (50-100 µg ipl; 1 mg/kg, ip) and visceral (1 mg/kg, ip) sensitivity. The cannabinoid tetrad was used to assess the central effects of WIN (1 mg/kg, ip). 5-FU decreased food intake and body weight gain, produced mucositis and thermal hyperalgesia, but these effects were reduced afterwards, and were not accompanied by diarrhea. Tactile mechanical allodynia was also evident and persisted for 15 days. Interestingly, it was alleviated by WIN. 5-FU tended to increase colonic sensitivity whereas WIN reduced the abdominal contractions induced by increasing intracolonic pressure in both control and 5-FU-treated animals. Importantly, the alleviating effects of WIN against those induced by 5-FU were not accompanied by any effect in the cannabinoid tetrad. The activation of the peripheral cannabinoid system may be useful to alleviate neuropathic and visceral pain associated with antitumoral treatment.

Rhenium disulfide (ReS2) with distinct physicochemical properties has shown promising potential in disease theranostics, such as drug delivery, computed tomography (CT), radiotherapy, and photothermal therapy (PTT). However, the synthesis and post-modification of ReS2 agents for different application scenarios are time- and energy-consuming, which seriously hinders the clinical translation of ReS2. Herein, we proposed three facile excipient strategies for different theranostic applications of ReS2 just through the flexible use of commercial ReS2 powder. Three excipients, including sodium alginate (ALG), xanthan gum (XG), and ultraviolet-cured resin (UCR), were used to prepare different dosage forms of commercial ReS2 powder, like hydrogel, suspension, and capsule, respectively. These dosage forms of ReS2 with distinct characteristics showed great potential for second near-infrared window PTT against tumours, gastric spectral CT imaging, and functional evaluation of the digestive tract in vivo. In addition, these ReS2 formulations exhibited good biocompatibility both in vitro and in vivo, showing a promising prospect for clinical transformation. More importantly, the facile excipient strategies for commercial agents pave a bridge to the development and wide bioapplication of many other theranostic biomaterials.

Background: Taxane-induced peripheral neuropathy (TIPN) is an important cause of premature treatment cessation and dose-limitation in cancer therapy. It also reduces quality of life and survivorship in affected patients. Genetic polymorphisms in the CYP3A family have been investigated but the findings have been inconsistent and contradictory. Methods: A systematic review identified 12 pharmacogenetic studies investigating genetic variation in CYP3A4*22 and CYP3A5*3 and TIPN. In our candidate gene study, 288 eligible participants (211 taxane participants receiving docetaxel or paclitaxel, and 77 control participants receiving oxaliplatin) were successfully genotyped for CYP3A4*22 and CYP3A5*3. Genotyping data was transformed into a combined CYP3A metaboliser phenotype: Poor metabolisers, intermediate metabolisers and extensive metabolisers. Individual genotypes and combined CYP3A metaboliser phenotypes were assessed in relation to neurotoxicity, including by meta-analysis where possible. Results: In the systematic review, no significant association was found between CYP3A5*3 and TIPN in seven studies, with one study reporting a protective association. For CYP3A4*22, one study has reported an association with TIPN, while four other studies failed to show an association. Evaluation of our patient cohort showed that paclitaxel was found to be more neurotoxic than docetaxel (p < 0.001). Diabetes was also significantly associated with the development of TIPN. The candidate gene analysis showed no significant association between either SNP (CYP3A5*3 and CYP3A4*22) and the development of TIPN overall, or severe TIPN. Meta-analysis showed no association between these two variants and TIPN. Transformed into combined CYP3A metaboliser phenotypes, 30 taxane recipients were poor metabolisers, 159 were intermediate metabolisers, and 22 were extensive metabolisers. No significant association was observed between metaboliser status and case-control status. Summary: We have shown that the risk of peripheral neuropathy during taxane chemotherapy is greater in patients who have diabetes. CYP3A genotype or phenotype was not identified as a risk factor in either the candidate gene analysis or the systematic review/meta-analysis, although we cannot exclude the possibility of a minor contribution, which would require a larger sample size.

Chemotherapy-induced peripheral neuropathy is a severe clinical problem frequently associated with cisplatin use. Although its pathophysiology is poorly understood, it is known that kinin receptors and the transient receptor potential ankyrin 1 (TRPA1) channel play a significant role in the peripheral neuropathy induced by cisplatin in rodents. However, the role of signalling pathways downstream from B₂ kinin receptors activation and sensitisation of the TRPA1 channel remains unknown in this model. The cisplatin-induced neuropathy model caused mechanical and cold allodynia in male Swiss mice. Antagonists for kinin B₂ and B₁ receptors and the TRPA1 channel attenuated the painful parameters. Local sub-nociceptive doses of kinin B₂ receptor (bradykinin) and TRPA1 channel (allyl isothiocyanate; AITC) agonists enhanced the painful parameters in cisplatin-treated mice, which their respective antagonists attenuated. Furthermore, we demonstrated the interaction between the kinin B₂ receptor and the TRPA1 channel in cisplatin-induced peripheral neuropathy since phospholipase C (PLC) and protein kinase C epsilon (PKCε) inhibitors attenuated the increase in mechanical and cold allodynia evoked by bradykinin and AITC in cisplatin-treated mice. Therefore, regulating the activation of signalling pathways downstream from the kinin B₂ receptors activation and TRPA1 channel sensitisation can mitigate the painful peripheral neuropathy decurrent of the oncology treatment with cisplatin.

Alterations in calcium (Ca²⁺) signaling is a major mechanism in the development of chemotherapy-induced peripheral neuropathy (CIPN), a side effect caused by multiple chemotherapy regimens. CIPN is associated with numbness and incessant tingling in hands and feet which diminishes quality of life during treatment. In up to 50% of survivors, CIPN is essentially irreversible. There are no approved, disease-modifying treatments for CIPN. The only recourse for oncologists is to modify the chemotherapy dose, a situation that can compromise optimal chemotherapy and impact patient outcomes. Here we focus on taxanes and other chemotherapeutic agents that work by altering microtubule assemblies to kill cancer cells, but also have off-target toxicities. There have been many molecular mechanisms proposed to explain the effects of microtubule-disrupting drugs. In neurons, an initiating step in the off-target effects of treatment by taxane is binding to neuronal calcium sensor 1 (NCS1), a sensitive Ca²⁺ sensor protein that maintains the resting Ca²⁺ concentration and dynamically enhances responses to cellular stimuli. The taxane/NCS1 interaction causes a Ca²⁺ surge that starts a pathophysiological cascade of consequences. This same mechanism contributes to other conditions including chemotherapy-induced cognitive impairment. Strategies to prevent the Ca²⁺ surge are the foundation of current work.

Paclitaxel, a widely used cancer chemotherapeutic agent, has high incidence of neurotoxicity associated with the production of neuropathic pain, for which only duloxetine has shown significant but moderate analgesic effect. Since statins, classically used to reduce hypercholesterolemia, have shown antinociceptive effect in preclinical studies on neuropathic pain, we studied whether the antinociceptive efficacy of duloxetine could be synergistically potentiated by rosuvastatin in a model of paclitaxel-induced neuropathy in mice. The astrocytic and microglial responses in the spinal cord of paclitaxel-treated mice were also assessed by measuring GFAP and CD11b proteins, respectively. Paclitaxel treatment did not impair motor coordination and balance in rotarod testing. Rosuvastatin, duloxetine, and the rosuvastatin/duloxetine combination (combined at equieffective doses) dose-dependently decreased mechanical allodynia (ED₃₀, von Frey testing) and thermal hyperalgesia (ED₅₀, hot plate testing) in paclitaxel-treated mice. Isobolographic analysis showed a superadditive interaction for rosuvastatin and duloxetine, as both the ED₃₀ and ED₅₀ for the rosuvastatin/duloxetine combination contained only a quarter of each drug compared to the individual drugs. The rosuvastatin/duloxetine combination reversed paclitaxel-induced GFAP overexpression, indicating that such effects might depend in part on astrocyte inactivation. Results suggest that statins could be useful in synergistically enhancing the efficacy of duloxetine in some chemotherapy-induced neuropathic conditions.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of several anticancer agents including paclitaxel, a chemotherapeutic drug widely used in cancer treatment. CIPN deteriorates patients' quality of life and compromises cancer treatment. Dysfunction or injury of mitochondria has been suggested to be involved in the induction of this neuropathy. SS-20 is a tetrapeptide that targets mitochondria and restores mitochondrial bioenergetics. This study was aimed to examine the protective effect of SS-20 against paclitaxel-induced peripheral neuropathy using a murine model. Repeated administration of paclitaxel to mice induced peripheral neuropathy as demonstrated by the presence of mechanical allodynia and the loss of intraepidermal nerve fibers in the hind paw. Concomitant administration of SS-20 protected against the development of the neuropathy. Our results suggest that SS-20 may be a drug candidate for the prevention of CIPN.

The aim of this study was to quantitatively evaluate the efficacy of a self-monitoring intervention for the management of persistent chemotherapy-induced peripheral neuropathy (CIPN).

A randomized controlled clinical trial was conducted on 65 outpatients receiving taxane or platinum-based anticancer drugs. Participants were assigned to the control group (CG; n ​= ​32) or the self-monitoring group (SMG; n ​= ​33) and followed for 6 weeks. Non-interveners were blinded. Participants in the intervention group self-monitored and recorded. The researchers provided feedback on the recorded symptoms and coping strategies once every 3 weeks. The efficacy of the 6-week self-monitoring intervention was assessed, using various measures, at baseline (T0), 3 weeks (T1), and 6 weeks (T2). Scores of CIPN, Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity, Distress and Impact Thermometer, Self-Efficacy Scale for Advanced Cancer, and Functional Assessment of Cancer Therapy-General of both groups were compared. Safety behavior in daily life was also compared. The study was conducted from August 9, 2017 to March 30, 2020 in outpatient clinics at three hospitals. Analysis was conducted using the t-test, Mann-Whitney U test, χ² test, and two-way repeated-measures analysis of variance (two-way RMANOVA).

No significant differences were noted between the two groups in the CIPN score, the Distress and Impact Thermometer score, and in safety behavior in daily life. The mean Self-Efficacy Scale for Advanced Cancer score at T1 differed between the two groups (CG mean ​± ​SD: 358.44 ​± ​109.90; SMG mean ​± ​SD: 421.21 ​± ​85.54), which was significantly higher in the SMG (P ​= ​0.012). Two-way RMANOVA revealed an interaction between the CG and SMG (F ​= ​5.689, P ​= ​0.004). Quality of life scores were higher in the SMG than in the CG at T0, T1, and T2. Two-way RMANOVA analysis showed an effect of the intervention (F ​= ​7.914, P ​= ​0.007).

The self-monitoring intervention maintained the participants' quality of life. This finding suggests its effectiveness in patients with peripheral neuropathy.