Investigation of YAP-1, OTX-2, and nestin protein expressions in neuroblastoma: a preliminary study.

OBJECTIVES: Neuroblastoma is the most common extracranial solid tumor in childhood. YAP (Yes-associated protein) is a highly expressed protein in NB. Nestin is an important marker of neuronal differentiation in NB. Orthodenticle homeobox (OTX) is a transcription factor and is overexpressed in blastoma-derived tumors. The aim of this study was to examine the potential roles of YAP-1, Nestin, and OTX-2 proteins in prognosis and risk stratification in neuroblastoma METHODS: Tumor sections of 56 patients with different NB risk groups were analyzed. YAP-1, Nestin, and OTX-2 protein expression levels were evaluated by immunohistochemical staining in NB patient tissue samples. RESULTS: YAP-1, Nestin, and OTX-2 protein expression levels were evaluated together with the clinical findings of NB patients. YAP-1 was expressed in 18% of all tissues, while Nestin was expressed in 20.4%. OTX-2 protein expression was found in 41.1% of the NB patients. YAP-1 was expressed in 26.9% of high-risk and 11.5% of low-risk patients. Nestin was expressed in 24.4% high-risk and 33.3% low-risk patients. OTX-2 was expressed in 68.2% high-risk and 60% low-risk patients.YAP-1 was shown to provide survival advantages among risk groups. INTERPRETATION: The findings of this study support that YAP-1 may be a potential prognostic biomarker for staging and risk-group assignment of NB patients. YAP-1 expression in neuroblastoma is associated with significantly poorer survival probabilities and should be considered as a potential therapeutic target. OTX-2 is a promising predictive biomarker candidate, but its mechanisms need further investigation in neuroblastoma, as nestin expression is not significantly linked to patient survival.

Infantile Hemangiomas of the Head and Neck: A Single-Center Experience.

Background: Infantile hemangiomas (IHs) are the most common benign vascular tumors of infancy. Methods: We report our experiences with 248 patients with head and neck IHs. Results: The median admission age was 4 months, and the female/male ratio was 2.18. Among the cases, 45% were followed by no treatment. No local complications were observed in any of these patients. Propranolol was provided to all patients who received medical treatment. The median duration of treatment was 12 months (1-30 months), and the median follow-up period of all patients was 14 months (0-118 months). The treatment response was 98%. The complication rate was 17%, and children aged between 3 and 9 months accounted for 60% of the patients who developed complications. Most of the complications were local complications, such as ulceration and bleeding. Conclusions: Although most IHs regress spontaneously, complications may occur. Propranolol alone is an effective treatment option, and early treatment initiation increases the success rate.

Pediatric paravertebral tumors: analysis of 96 patients.

PURPOSE: The most important complication of paravertebral tumors is cord compression (CC), which is an oncologic emergency. Early and appropriate intervention is important in terms of reducing morbidity and mortality. Here, we report our clinical experience with paravertebral tumors. METHODS: The files of patients who were followed up for benign/malignant paravertebral tumors between 1988 and 2022 were evaluated retrospectively. RESULTS: There were 96 patients with paravertebral tumors. The median age at diagnosis was 5 years (1 month-17 years). The male/female ratio was 1.13. The median time to diagnosis was 4 weeks (0-28 weeks). The most common presenting complaint was pain (62.5%). The diagnosis distribution was as follows: sympathetic nervous system (SNS) tumors (n: 38), soft tissue sarcomas (STS) (n: 23), Langerhans cell histiocytosis (LCH) (n: 12), central nervous system (CNS) tumors (n: 9), germ cell tumor (n: 6), lymphomas (n: 4), and benign tumors (n: 4). Sixty-five patients (67.7%) had CC, 40% of whom received chemotherapy as first-line treatment. Decompression surgery was performed in 58.5% of the patients. For patients with CC, 26 patients had advanced disease at admission. Serious neurologic sequelae were observed in seventeen (17.7%) patients. CONCLUSION: Pain and neurological findings in childhood are warning signs for paravertebral tumors and CC. A detailed neurologic examination and radiodiagnostic imaging should be performed, and a definitive diagnosis should be made quickly. Anticancer treatment should be planned multidisciplinary. Decompression surgery should be discussed for patients with severe neurological deficits. Childhood cancers are chemosensitive; if possible, treatment should be initiated with chemotherapy to avoid neurological sequelae.

S-100 and MATH-1 Protein Expressions Can Be Useful for the Prediction of Clinical Outcome in Neuroblastoma Patients.

Neuroblastoma (NB) is the most frequent extracranial solid tumor of childhood, remarkable for its broad spectrum of clinical behavior. This diversity in behavior correlates closely with defined clinical and biological features and combinations of prognostic variables are used for risk-group assignment. S-100 proteins have roles in differentiation and were shown to be frequently dysregulated in NB. MATH-1 protein plays role in neuronal cell differentiation through development. However, up to date, there are no studies evaluating the relationship between MATH-1 and NB. Grb2-associated binding (Gab) proteins have roles in the regulation of cell growth and differentiation. Gab1 was reported to be related to poor survival of high-risk NB patients. The aim of this study was to investigate the relationship between differentiation-related S-100, MATH-1, and Gab1 proteins and risk group and/or stages of NB. A significant relation was found between S-100 and early stages of NB. This study also revealed a significant association between MATH-1 and low-risk groups. S-100 and MATH-1 were also shown to provide survival advantages among stages and risk groups. The findings of this study support the assumption that S-100 and MATH-1 can be potential prognostic biomarkers for staging and risk-group assignment of NB patients. These proteins can be useful tools for clinicians to guide through treatment options, especially for the evaluation of tumor differentiation.

Comparing Tribbles Homolog 3 (TRIB3) Protein Expression Levels with Clinicopathological Characteristics and Survival Among Neuroblastoma Patients.

Background: Tribbles Homolog 3 (TRIB3) is a member of the pseudokinase family of tribbles and acts as an adaptor protein to regulate different cellular processes. Upregulation of TRIB3 expression was shown either as a favorable or an adverse prognostic factor in various adult malignancies. However, TRIB3 expression has not been examined in pediatric cancers. Neuroblastoma is the most common malignant solid tumor of childhood, which affects mostly children under 5 years old. Risk stratification of patients defined by International Neuroblastoma Risk Group was used to determine prognosis and treatment of the disease. This study aimed to examine the relationship between TRIB3 protein expression levels and clinicopathological features and survival of patients. Methods: TRIB3 protein expression was analyzed using immunohistochemical staining on formalin-fixed paraffin-embedded tissue samples of neuroblastoma patients (n = 56). Survival analyses were performed with Kaplan-Meier method and log-rank tests. Association between TRIB3 expression and clinicopathological characteristics were analyzed with Spearman's correlation. Results: Of the patients, 32.1% were in the low-risk group, 21.4% in the medium-risk group, and 46.4% in the high-risk group. Survival analysis was performed in the entire neuroblastoma patient group and sub-risk groups of neuroblastoma patients. In the entire patient group, there was no significant difference in overall survival (P = .202) and event-free survival (P = .172) between TRIB3-positive and -negative patients. However, when survival analyses were performed in each risk group, TRIB3 expression was significantly associated with higher overall survival (P = .034) and event-free survival (P = .032) in low-risk group neuroblastoma patients. Nevertheless, no association was found between TRIB3 expression and overall survival (P = .799) and event-free survival (P = .448) in high-risk neuroblastoma patients. Furthermore, a significant correlation was identified between 1p36 loss-of-heterozygosity and TRIB3 expression (P = .030). However, TRIB3 expression did not correlate with other clinicopathological features. Conclusion: TRIB3 expression is a potential predictive biomarker for low-risk neuroblastoma patients.

Unraveling the Mystery: Next Generation Sequencing Sheds Light on Neuroblastoma Pathogenesis and Targeted Therapies.

BACKGROUND: There is considerable interest in the molecular evaluation of solid tumors in pediatric cases. Although clinical trials are in progress for targeted therapies against neuroblastoma (NB), novel therapeutic strategies are needed for high-risk cases that are resistant to therapy. The aim of the present study was to document the specific gene mutations related to targeted therapy in relapsed or refractory NB patients by using next generation sequencing (NGS). METHODS: The study included 57 NB patients from amongst 1965 neuroblastic cases in Turkey who experienced a recurrence after multi-model therapy. The cases were diagnosed, risk-stratified, and treated according to the classification system from the International Neuroblastoma Risk Group. Single nucleotide variations in 60 genes were investigated using the Pillar Onco/Reveal Multicancer v4 panel and Pillar RNA fusion panel on the Illumina Miniseq platform. RESULTS: ERBB2 I655V was the most frequent mutation and was found in 39.65% of cases. Anaplastic Lymphoma Kinase (ALK) mutations (F1174L, R1275Q, and rare mutations in the tyrosine kinase domain) were detected in 29.3% of cases. Fusion mutations in NTRK1, NTRK3, ROS1, RET, FGFR3, ALK and BRAF were observed in 19.6% of cases. CONCLUSIONS: This study presents valuable mutation data for relapsed and refractory NB patients. The high frequency of the ERBB2 I655V mutation may allow further exploration of this mutation as a potential therapeutic target. Rare BRAF mutations may also provide opportunities for targeted therapy. The role of ABL1 mutations in NB should also be explored further.

Whole-exome sequencing reveals genetic variants in low-risk and high-risk neuroblastoma.

This study aimed to investigate the genetic aberrations in neuroblastoma (NB) by comparing high and low-risk NB patients by whole-exome sequencing (WES) and to reveal the heterogeneity and association between somatic variants and clinical features. Seven NB patients with available clinical data were included in the study (4 in the low-risk group and 3 in the high-risk group). WES was performed and somatic variants associated with NB genes in the COSMIC database were selected through bioinformatics pipeline analysis. Variants were determined using the Integrative Genomics Viewer (IGV). Some gene variations were found in both groups, including variations in oncogene and tumor suppressor genes. In general, candidate gene variations were associated with chromatin remodeling complexes, the RAS pathway, cell proliferation, and DNA repair mechanism. Some variations in CSF1R, MSH6, PTPN11, SOX9, RET, TSC1, and DNMT1 genes were detected only in high-risk patients, while EP300, TET2, MYCN, PRDM1, and ARID2 gene variations were detected only in low-risk patients. When high-risk gene variants were compared with the cBioportal cancer genomic database, two common gene variants (ARID1A and NCOR2) were identified. However, when low-risk gene variants were compared with the cBioportal cancer genomic database, no common genes were found. GO/KEGG enrichment analysis was performed to find relevant biological processes and molecular pathways related to gene variants, which will help to decipher the molecular mechanisms of NB tumorigenesis and the phenotypic differences between high-risk and low-risk patients.

In-silico molecular interactions among the secondary metabolites of Caulerpa spp. and colorectal cancer targets.

Caulerpa spp. secrete more than thirty different bioactive chemicals which have already been used in cancer treatment research since they play a pivotal role in cancer metabolism. Colorectal cancer is one of the most common cancer types, thus using novel and effective chemicals for colorectal cancer treatment is crucial. In the cheminformatics pipeline of this study, ADME-Tox and drug-likeness tests were performed for filtering the secondary metabolites of Caulerpa spp. The ligands which were selected from the ADME test were used for in silico molecular docking studies against the enzymes of the oxidative branch of the pentose phosphate pathway (glucose-6-phosphate dehydrogenase and 6-phosphoglutarate dehydrogenase), which is of great importance for colorectal cancer, by using AutoDock Vina. Pharmacophore modeling was carried out to align the molecules. Molecular dynamic simulations were performed for each target to validate the molecular docking studies and binding free energies were calculated. According to the ADME test results, 13 different secondary metabolites were selected as potential ligands. Molecular docking studies revealed that vina scores of caulerpin and monomethyl caulerpinate for G6PDH were found as -10.6 kcal mol-1, -10.5 kcal mol-1, respectively. Also, the vina score of caulersin for 6PGD was found as -10.7 kcal mol-1. The highest and the lowest binding free energies were calculated for monomethyl caulerpinate and caulersin, respectively. This in silico study showed that caulerpin, monomethyl caulerpinate, and caulersin could be evaluated as promising marine phytochemicals against pentose phosphate pathway enzymes and further studies are recommended to investigate the detailed activity of these secondary metabolites on these targets.

An Efficient and Quick Analytical Method for the Quantification of an Algal Alkaloid Caulerpin Showed In-Vitro Anticancer Activity against Colorectal Cancer.

Biological invasion is the successful spread and establishment of a species in a novel environment that adversely affects the biodiversity, ecology, and economy. Both invasive and non-invasive species of the Caulerpa genus secrete more than thirty different secondary metabolites. Caulerpin is one of the most common secondary metabolites in genus Caulerpa. In this study, caulerpin found in invasive Caulerpa cylindracea and non-invasive Caulerpa lentillifera extracts were analyzed, quantified, and compared using high-performance thin layer chromatography (HPTLC) for the first time. The anticancer activities of caulerpin against HCT-116 and HT-29 colorectal cancer (CRC) cell lines were also tested. Caulerpin levels were found higher in the invasive form (108.83 ± 5.07 µg mL-1 and 96.49 ± 4.54 µg mL-1). Furthermore, caulerpin isolated from invasive Caulerpa decreased cell viability in a concentration-dependent manner (IC50 values were found between 119 and 179 µM), inhibited invasion-migration, and induced apoptosis in CRC cells. In comparison, no cytotoxic effects on the normal cell lines (HDF and NIH-3T3) were observed. In conclusion, HPTLC is a quick and novel method to investigate the caulerpin levels found in Caulerpa extracts, and this paper proposes an alternative utilization method for invasive C. cylindracea due to significant caulerpin content compared to non-invasive C. lentillifera.

Comparison of Cytotoxic and Ototoxic Effects of Lipoplatin and Cisplatin in Neuroblastoma In Vivo Tumor Model.

BACKGROUND: This study aimed to compare the cytotoxic, cytostatic, and ototoxic effects of lipoplatin compared to cisplatin application in the subcutaneous xenograft nude mouse neuroblastoma tumor model. METHODS: In this study, C1300 neuroblastoma cells were administered subcutaneously to 21 male nude mice. When the tumor reached 150 mm3 diameter, mice were randomized into 3 groups. Saline, cisplatin, and lipoplatin were given intraperitoneally. The auditory function tests were performed before administration and 72 hours after administration. Mice were sacrificed and the tumor and cochlea were removed after 72 hours. Histopathologic evaluation of necrosis and apoptosis was determined by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Cyclooxygenase 2, superoxide dismutase 2, and inducible nitric oxide synthase levels were determined by immunohistochemistry in tissue samples. RESULTS: Apoptosis and necrosis rates were higher in lipoplatin group than in cisplatin group (P=.035 and P=.010, respectively) in tumor tissue. In the spiral ganglion, apoptosis and necrosis were lower in the lipoplatin group than in cisplatin group (P=.002 and P=.002, respectively). Cyclooxygenase 2 pattern in the cochlea was positive in both control and lipoplatin group and negative in cisplatin group (P=.001). Superoxide dismutase 2 and inducible nitric oxide synthase 2 protein expressions showed no difference between groups. The auditory functions were similar to baseline values and had a better threshold value in lipoplatin group than cisplatin group. CONCLUSION: For the treatment of neuroblastoma, the use of lipoplatin seems to be beneficial in reducing side effects of cisplatin. We recommend that the mechanism of these properties of lipoplatin should be evaluated in further studies.

Expression Profile of Selected Antitumor Immune Response Genes in Pediatric Classic Hodgkin Lymphoma.

Classic Hodgkin lymphoma (cHL) is one of the most common pediatric solid tumors and is responsible for cancer-related deaths in children. Therefore, to modulate the active antitumor T-cell immune response in cHL can be a treatment strategy. In the present study, we aimed to investigate the expression profiles of selected antitumor immune response genes in pediatric cHL and their relationships with clinical and prognostic parameters to determine their significance in precision medicine. Thirty-nine pediatric nodal cHL patients were enrolled in the study. We analyzed mRNA expression of selected immune response regulatory genes such as PD-L1, CSF2, CTLA4, CXCL5, IDO1, CXCL8, MIF, NOS2, PDCD1, PTGS2, and TGFß1 using real-time quantitative polymerase chain reaction. Only PD-L1 overexpression was statistically related to bulky disease, advanced tumor stage, and high-risk disease category and seen significantly in Epstein-Barr virus-negative pediatric cHL. No expression profiles were correlated with relapse or survival. We conclude that PD-L1 overexpression in pediatric cHL cases is a strong predictor of high-risk categorization. In addition to being a prognostic biomarker, PD-L1 blockade is also a druggable marker for the targeted therapy in Epstein-Barr virus-negative pediatric Hodgkin lymphoma.

The effect of text message reminders on nausea, vomiting and quality of life in children with cancer receiving cisplatin.

PURPOSE: This study was conducted to examine the effect of text message reminders on nausea, vomiting, and quality of life in children with cancer receiving cisplatin. METHODS: The study was conducted with a pretest-posttest unpaired group model design. The study included 80 children with cancer and their parents (40 controls and 40 experiments) aged between 8 and 18 years, who were on cisplatin treatment, who did not have cognitive disability as a clinical diagnosis, who received chemotherapy during their stay in the clinic, who were literate in Turkish and who volunteered to participate in the study. The educational contents prepared by the researchers to reduce nausea and vomiting were sent to the parents in the experimental group in the form of a text message every day for three weeks. Descriptive statistics, correlation analysis, and regression analysis were used to evaluate the data. RESULTS: While NVTS, ARINVc, ARINVp, Quality of Life Scale pretest and posttest mean scores of both 8-12 and 13-18 age control group children were similar, it was determined that the experimental group's posttest mean scores were higher than the pretest mean scores, and there was a statistically significant difference between the experimental group's pretest and posttest mean scores in terms of the group, time and group*time. In this study, the education program explains 42%, 15%, 16%, 43%, and 43% of the increase in the mean scores of NVTS, ARINVc, ARINVp, Quality of Life Scale Child and Parent Form, respectively, in children aged 8-12. Also, the education program explains 10%, 27%, 28%, 38%, and 39% of the increase in the mean scores of NVTS, ARINVc, ARINVp, Quality of Life Scale Adolescent and Parent Form, respectively, in children aged 13-18. CONCLUSIONS: It has been observed that text message reminders effectively reduce the level of nausea and vomiting and increase the quality of life. PRACTICE IMPLICATIONS: The results of this study, text message reminders can be applied as an alternative intervention method, and including technology-based practices in the care of children with cancer is important in increasing the quality of care.

PD-L1 and PD-L2 Mutations in Pediatric Hodgkin Lymphoma: Do They Have Any Prognostic Significance?

Background: Reed-Sternberg cells can escape from the immune system by enhancement of the expression of PD-L1 and PD-L2. Objectives: The aim of the present study was to investigate the significance PD-L1 and PD-L2 gene mutations in childhood Hodgkin Lymphoma's (HL). Methods: The study included 39 pediatric classical HL cases. PD-L1 and PD-L2 mutations were determined by Sanger sequencing. Clinicopathological parameters were obtained from patients' records. Results: Eight cases (20.5%) showed p.R260C mutations, and three (7.7%) p.R234L in the exome 5 of PD-L1 gene. None of the cases had PD-L2 mutations. p.R260C mutation exhibited a significant relationship with older age and nodular sclerosing (NS) histology and was associated with longer event free survival. Conclusions: Although PD-L1 mutational status did not show statistically significance with well-established prognostic factors, our preliminary data indicate that p.R260C mutation of PD-L1 gene may be associated with longer event free survival in older patients and NS histology in pediatric HL.

Gene-Specific DNA Methylation Profiles in Pediatric Medulloblastomas.

INTRODUCTION: Medulloblastoma is the most common pediatric central nervous tumor of high malignancy that has been classified into both histological subtypes and molecular subgroups by the 2016 World Health Organization classification. However, there is a still need to understand the genomic characteristics and predict the clinical course. The aim of the study is to investigate the significance of the methylation profiles in molecular subclassification and precision medicine of the disease. METHODS: The study enrolled 47 pediatric medulloblastoma patients. DNA methylation levels of KLF4, SPINT2, RASSF1A, EZH2, ZIC2, and PTCH1 genes were analyzed using methylation-specific pyrosequencing. The significance of the statistical relationship between methylation profiles and clinicopathological parameters including molecular subgroups and histological subtypes, the status of metastasis, and event-free survival were analyzed. RESULTS: DNA methylation analysis demonstrated that KLF4, PTCH1, and ZIC2 hypermethylation were associated with the SHH-activated subgroup, whereas both SPINT2 and RASSF1A hypermethylation were associated with metastatic disease. EZH2 gene was not methylated in any of the samples. CONCLUSION: We think that customized DNA methylation profiling may be a useful tool in the molecular subclassification of pediatric medulloblastoma and a potential technical approach in precision medicine.

The Significance of Histopathologic Assessment in Bone Marrow Disease in Neuroblastoma.

OBJECTIVE: Neuroblastoma (NB) is the most common extracranial solid tumor in children and is responsible for 12% of cancer-related deaths. The status of metastatic disease in the bone marrow (BM) is a predictor of poor outcome. The purpose of this study was to investigate the predictive significance of histopathological examination of BM in NB. MATERIAL AND METHOD: The study included 61 cases with archival bone marrow biopsy tissues. The cases were evaluated regarding the percentage of metastatic tissue and its differentiation. Primary tumor slides were also reviewed to perform the Shimada classification based on the differentiation status and mitosis-karyorrhexis index. The patients' age, gender, NMYC amplification, clinical risk group, and disease outcome were also noted. RESULTS: Of the 61 cases, 17 had BM involvement. Of those, eight cases (47.1%) were refractory NB showing disease relapse. Based on BM examination, five cases (29.4%) were categorized as complete response, seven (41.2%) as progressive disease, three (17.6%) as minimal disease, and two (11.8%) as stable disease. The progressive disease category was significantly related with refractory disease and NMYC amplification along with the high-risk category (p =0.002 and p= 0.003 respectively). Undifferentiated histology and presence of more than 20% of tumor tissue in the BM biopsy at diagnosis were significantly associated with the progressive disease category (p=0.01 and p < 0.001, respectively). CONCLUSION: We conclude that evaluating the percentage of metastatic tumor tissue and tumor differentiation in BM biopsies is of clinical importance in the management of neuroblastoma patients.

Dinutuximab beta plus conventional chemotherapy for relapsed/refractory high-risk neuroblastoma: A single-center experience.

Background: Relapsed/refractory high-risk neuroblastoma has a dismal prognosis. Anti-GD2-mediated chemo-immunotherapy has a notable anti-tumor activity in patients with relapsed/refractory high-risk neuroblastoma. The purpose of this study was to analyze the efficacy and safety of the combination of immunotherapy with dinutuximab beta (DB) and chemotherapy in patients with relapsed/refractory high-risk neuroblastoma. Methods: All patients received the Turkish Pediatric Oncology Group NB 2009 national protocol for HR-NB treatment at the time of diagnosis. Salvage treatments were administered after progression or relapse. The patients who could not achieve remission in primary or metastatic sites were included in the study. The most common chemotherapy scheme was irinotecan and temozolomide. DB was administered intravenously for 10 days through continuous infusion with 10 mg/m2 per day. The patients received 2 to 14 successive cycles with duration of 28 days each. Disease assessment was performed after cycles 2, 4, and 6 and every 2 to 3 cycles thereafter. Results: Between January 2020 and March 2022, nineteen patients received a total of 125 cycles of DB and chemotherapy. Objective responses were achieved in 12/19 (63%) patients, including complete remission in 6/19 and partial response in 6/19. Stable disease was observed in two patients. The remaining five patients developed bone/bone marrow and soft tissue progression after 2-4 cycles of treatment. The most common Grade ≥3 toxicities were leukopenia, thrombocytopenia, hypertransaminasemia, fever, rash/itching and capillary leak syndrome, respectively. Conclusion: Our study results suggest that DB-based chemo-immunotherapy seems to be suitable with encouraging response rates in patients with relapsed/refractory high-risk neuroblastoma.

Evaluation of Risk Factors Causing Ototoxicity in Childhood Cancers Located in the Head and Neck Region Treated With Platinum-based Chemotherapy.

The aim of this study is to evaluate risk factors contributing to the development of ototoxicity in children who received platinum-based chemotherapy for malignancies located in the head and neck region. Eighty-four children who received platinum-based chemotherapy were included. Audiologic evaluations were performed before and after each chemotherapy session through pure tone audiometry, distortion product otoacoustic emissions, and auditory brainstem response tests. Ototoxicity was evaluated using Brock, Muenster, and Chang classifications. Factors such as cranial irradiation, cumulative doses of cisplatin, age, sex, cotreatment with aminoglycosides, schedule of platinum, and type of chemotherapeutic agent were analyzed. Using χ2 tests, all risk factors were matched with the 3 ototoxicity classifications, and multivariate analyses were conducted using statistically significant risk factors. In univariate analyses, being between 5 and 12 years of age, cranial irradiation and being treated with both cisplatin and carboplatin were found to be related to ototoxicity in all 3 classifications. Logistic regression modeling analyses with these 3 risk factors showed that being between 5 and 12 years of age and being treated with both cisplatin and carboplatin significantly increased the risk of ototoxicity.

Safety of Eicosapentaenoic Acid in Cancer Treatment: Effect on Cancer Cells and Chemotherapy in Vitro.

Eicosapentaenoic acid (EPA) is a long-chain polyunsaturated fatty acid that has been used to treat cachectic cancer. However, its efficacy and safety with regard to cancer cells remain unclear. The present study comprised an In Vitro investigation of the effects of EPA on cancers. The effects of 0.01-300 µg/mL of EPA on the proliferation and death of cells after 24, 48, and 72 h were explored. The study included cell lines representing neuroblastoma (Kelly, SH-SY5Y, C1300); acute lymphoblastic leukemia (ALL); Burkitt's lymphoma; acute myeloid leukemia (AML); adult cancer cell lines of the pancreas, colon, and prostate; and a fibroblast cell line. EPA caused 4.4%-7% proliferation of fibroblasts, but did not protect them from the toxic effect of cisplatin. It did not induce proliferation in the neuroblastoma cells, and did not reduce the cytotoxic effect of cisplatin. EPA also did not cause proliferation in ALL, Burkitt's lymphoma, and AML cells, and did not alter the cytotoxic effects of L-asparaginase, cyclophosphamide, and cytosine arabinoside, respectively. Our results were similar in the adult cancer cell lines. EPA is safe because it has no effects on the proliferation of cancer cells or on chemotherapy In Vitro.

The effect of virtual reality on pain, fear, and anxiety during access of a port with huber needle in pediatric hematology-oncology patients: Randomized controlled trial.

PURPOSE: Port needle insertions are painful and distressing for Pediatric Hematology-Oncology patients. Virtual Reality (VR) can be used during needle-related procedures in these patients. This study aimed to investigate the effect of VR distraction during access to the venous port with a Huber needle in reducing needle-related pain, fear, and anxiety of children and adolescents with cancer. METHODS: This randomized controlled study used a parallel trial design guided by the CONSORT checklist. The sample of children (n = 42) was allocated to the VR group (n = 21) and the control group (n = 21). Port needle-related pain was assessed using the Wong-Baker Faces Pain Rating Scale after the procedure. Before and after the port needle insertion procedure, anxiety and fear assessed using self- and parent-report using the Children's Anxiety Meter and Child Fear Scale. The primary outcome was the patient-reported pain scores after the procedure and fear and anxiety scores before and after the procedure. Pain, anxiety, and fear scores of the two groups and within groups were analyzed and also Spearman correlation analysis was used. RESULTS: Self-reported pain scores of patients in the VR and control group were 2.4 ± 1.8 and 5.3 ± 1.8, respectively. This study found a statistically significant difference between groups in pain scores (p < .001). A statistically significant difference was found between groups according to the self- and parent-reported fear and anxiety scores after the procedure. Self-reported fear scores in the VR and control group were 0.8 ± 0.9, 2.0 ± 1.0, self-reported anxiety scores were 2.9 ± 2.0, 5.4 ± 2.0, respectively (p < .001). CONCLUSION: Virtual reality is an effective distraction method in reducing port needle-related pain, fear, and anxiety in Pediatric Hematology-Oncology patients. ClinicalTrials.gov NCT04093154.

Antioxidant effect of acetyl-l-carnitine against cisplatin-induced cardiotoxicity.

OBJECTIVE: Cisplatin (CDDP) toxicity is a dose-limiting clinical problem in clinical practice, mainly because of nephrotoxicity or ototoxicity. However, the mechanism of CDDP-induced cardiotoxicity is poorly understood. Acetyl-l-carnitine (ALCAR) is an antioxidant agent with protective effects against the side effects of various chemotherapeutics. CDDP-induced cardiotoxicity and the protective role of ALCAR were evaluated in this study. METHODS: Morphological changes were evaluated in hematoxylin and eosin-stained sections, and immunohistochemistry for caspase-3, superoxide dismutase-2 (SOD-2), inducible nitrite oxide synthase (iNOS), cyclooxygenase-2, and Bcl-2 was performed using the hearts of athymic nude mice carrying xenograft neuroblastoma tumors. Mice were randomized (six/group) to the control, CDDP (16 mg/kg), and ALCAR (200 mg/kg)+CDDP (16 mg/kg) groups. Results were analyzed using nonparametric tests. RESULTS: No difference was observed in the rates of cardiac necrosis, dilated/congested blood vessels, hemorrhage, polymorphonuclear leukocyte infiltration, edema, and pyknotic nuclei among the groups. SOD-2 expression was increased in the CDDP group but not in the ALCAR+CDDP group. iNOS, Bcl-2, and caspase-3 levels were not significantly different among the groups. CONCLUSIONS: ALCAR might be a candidate protective agent for CDDP-induced cardiotoxicity. SOD-2, as a member of the oxidant system, should be evaluated in further studies as a biomarker of cardiotoxicity.