Mechanisms, Characteristics, and Treatment of Neuropathic Pain and Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients

Rivetti, Serena; Triarico, Silvia; Romano, Alberto; Attinà, Giorgio; Maurizi, Palma; Ruggiero, Antonio

doi:10.3390/ijms222312648

Cited by 13 publications

(12 citation statements)

References 67 publications

(102 reference statements)

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“…From the known biological activities of the identified compounds in the non-polar fraction of the extract, we can speculate that the observed immunomodulatory properties are due to the azithromycin (84) and betulin (111), compounds that have been formerly stated to possess such properties [31][32][33]. Other compounds with biological activities that could affect the immunomodulation are autumnolide (6), phomoarcherin B (17), nahuoic acid A (29), 3-hydroxyechinenone (40), nootkatone (59), oligomycin C (78), plakevulin A (101), and anhydroretinol (112). Here, we discuss only the compounds with reported biological activities.…”

Section: Discussionmentioning

confidence: 99%

“…Nahuoic acid A (29), oleamide (37), erucamide (52), oligomycin C (78), and plakevulin A (101) are known as inhibitors of different enzymes [52][53][54][55]. Some of identified compounds (17,18,34,37,41,59, and 111) are characterized by anti-inflammatory or antimalarial properties [42,43,49,[56][57][58].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, other compounds in P. papyraceum extract have been used for treatment of neuropathic pain (gabapentin, 1) [59] or for preparation of liposomes of mixed lipid composition such as 1-(9Z-octadecenoyl)-2-hexadecanoyl-3-beta-D-galactosyl-sn-glycerol (104) [60].…”

Section: Discussionmentioning

confidence: 99%

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A Novel Approach for Fast Screening of a Complex Cyanobacterial Extract for Immunomodulatory Properties and Antibacterial Activity

Teneva

Batsalova

Bardarov³

et al. 2022

Applied Sciences

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The filamentous cyanobacteria from genus Phormidium are rich natural sources of bioactive compounds that could be exploited as pharmaceuticals or nutraceuticals. In this study, we suggest a novel approach for assessing the immunomodulatory properties of the products derived from cyanobacteria. The influence of Phormidium papyraceum extract on the human leukocyte immunophenotype was evaluated by attempting to link this activity to certain putative compounds identified in the extract. By using three staining panels and flow cytometry, we found that the cyanobacterial extract affected mainly CD4+ T cells upregulating activated CD4+CD152+ T cells (15.75 ± 1.93% treated vs. 4.65 ± 1.41% control) and regulatory CD4+CD25+ T cells (5.36 ± 0.64% treated vs. 1.03 ± 0.08% control). Furthermore, P. papyraceum extract can modulate T cell subpopulations with a CD4+ effector/memory phenotype. Extract-treated cells showed increased production of IL-2 (55 ± 12 pg/mL) and IL-6 (493 ± 64 pg/mL) compared to the untreated, 21 ± 7 pg/mL and 250 ± 39 pg/mL, respectively. No significant changes were observed in the secretion of TNF-α. In addition, P. papyraceum extract displayed antibacterial activity against both Gram-negative (inhibition zone from 18.25 ± 0.50 mm to 20.28 ± 1.50 mm) and Gram-positive (inhibition zone from 10.86 ± 0.85 mm to 17.00 ± 0.82 mm) bacteria. The chemical profile of the cyanobacterial extract was determined using LC–ESI–MS/MS analysis, where at least 112 putative compounds were detected. Many of these compounds have proven different biological activities. We speculated that compounds such as betulin and the macrolide azithromycin (or their analogues) could be responsible for the immunomodulatory potential of the investigated extract. More studies are needed to determine and validate the biological activities of the determined putative compounds.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Approach for Fast Screening of a Complex Cyanobacterial Extract for Immunomodulatory Properties and Antibacterial Activity

Teneva

Batsalova

Bardarov³

et al. 2022

Applied Sciences

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“…Dinutuximab beta is a chimeric monoclonal immunoglobulin (Ig) G1 antibody that is specifically targeted against the carbohydrate moiety of GD2, which is present on the suface of NB cells [ 13 ]. The complex antigen GD2 antibody activates the antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity, which cause apoptosis of NB cells [ 14 ]. In the presence of human effector cells, including peripheral blood nuclear cells and granulocytes from healthy human donors, dinutuximab beta was found to mediate the lysis of human NB and melanoma cell lines in a dose-dependent manner (Fig.…”

Section: Dinutuximab Betamentioning

confidence: 99%

Recent Evidence-Based Clinical Guide for the Use of Dinutuximab Beta in Pediatric Patients with Neuroblastoma

et al. 2022

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The anti-GD2 antibody dinutuximab beta (Qarziba ® ) has been added to the present standard of care for patients with highrisk neuroblastoma in Europe based on the positive results obtained in different studies. In both the first-line and relapsed/ refractory settings, treatment with dinutuximab beta attains objective clinical responses in children with high-risk neuroblastoma. Its incorporation has changed the outcome for these patients and optimized management should be guaranteed to minimize possible adverse effects. Most prevalent adverse events include pain, allergic reactions, fever and capillary leak syndrome. There are still no evidence-based clinical guidelines that include the latest published evidence to optimize its use, as it depends on the experience gained in each referral center. Topics such as the mode of preparation and administration, the concomitant use of interleukin-2, the recommended pediatric age and dose for its use, or the adequate management of possible toxicities are important aspects to review. The objective of this article was to update the clinical guide to management with dinutuximab beta of children with neuroblastoma based on the most recent published evidence and our own experience in clinical practice.

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“…Treatment of NB depends on the individual involved, and accuracy in clinical staging and risk stratification is extremely vital for planning therapeutic methods and prognosis. The therapy for the low-risk group is safe and feasible, while the treatment of high-risk NB includes surgery, chemotherapy, radiation, hematopoietic stem cell transplantation, immunotherapy, and targeted therapy [14,15]. Even after multimodal therapy, the 5-year OS for high-risk NB is still below 50% [16].…”

Section: Introductionmentioning

confidence: 99%

Increased D-dimer level was a poor predictor of neuroblastoma, especially in the high-risk group

Li²,

Zhao³

et al. 2023

World J Surg Onc

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Purpose D-dimer levels are associated with tumor progression and prognosis in various cancers. However, there are few research about the relationship between D-dimer and neuroblastoma (NB). This study assessed the relationships of D-dimer levels with clinical features and overall survival (OS) in patients with NB. Methods Information about the clinical features of 365 patients and the prognosis of 301 patients was collected. The relationship between D-dimer levels and clinical features or OS was analyzed. We constructed the risk score based on Cox regression analysis and verified the predictive efficacy of the model through ROC curve and calibration curve. Results The results showed that D-dimer levels were significantly increased in patients with nonmediastinal tumor, tumor larger than 10 cm, stage 3–4 disease, bone marrow metastasis, unfavorable histology, bone metastasis, NMYC amplification, and the high-risk group (all P < 0.05). The Kaplan–Meier survival analysis showed that there were significant differences in 3- and 5-year OS (87.4% vs. 32.3%, 79.3% vs. 32.3%, P < 0.0001) between the low D-dimer and high D-dimer groups. In the high-risk group, the OS of high D-dimer was significantly lower than that of low D-dimer (P < 0.0001). All cases were divided into the training cohort (N = 211) and the validation cohort (N = 90). Multivariate analysis further suggested that D-dimer level, bone metastasis, and NMYC status were independent prognostic factors for OS (all P < 0.05). Based on the above three factors, we constructed the risk score in the training cohort. Survival analysis showed that compared with the other groups, the group with 11 scores had the worst prognosis (3-year OS 0%, P < 0.0001). The time-dependent ROC analysis and calibration curve indicated that the risk score had good accuracy. Conclusions Patients with high D-dimer levels tended to have unfavorable clinical characteristics and poor prognosis.

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Mechanisms, Characteristics, and Treatment of Neuropathic Pain and Peripheral Neuropathy Associated with Dinutuximab in Neuroblastoma Patients

Cited by 13 publications

References 67 publications

A Novel Approach for Fast Screening of a Complex Cyanobacterial Extract for Immunomodulatory Properties and Antibacterial Activity

A Novel Approach for Fast Screening of a Complex Cyanobacterial Extract for Immunomodulatory Properties and Antibacterial Activity

Recent Evidence-Based Clinical Guide for the Use of Dinutuximab Beta in Pediatric Patients with Neuroblastoma

Increased D-dimer level was a poor predictor of neuroblastoma, especially in the high-risk group

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