OBJECTIVE: Cisplatin (CDDP) is an anti-neoplastic agent that has been used in treatments of both pediatric and adult cancers. It has many side effects, such as ototoxicity, nephrotoxicity, and neurotoxicity. Lipoplatin (LIPO) is a nanomolecule with 110 nm diameter and composed of lipids and CDDP. In this study, we aimed to compare the toxic effects of LIPO with CDDP in the cochlear cells with anti-tumoral doses determined in neuroblastoma cells. MATERIALS and METHODS: House Ear Institute Organ Corti 1 (HEI-OC1), MYC-N amplified KELLY, and MYC-N non-amplified SH-SY5Y human neuroblastoma cells were used in this study. Firstly, anti-tumoral lethal dose 50 (LD50) of LIPO and CDDP were determined using the WST-1 assay in both neuroblastoma cells. Then anti-tumoral doses of CDDP and LIPO were applied on HEI-OC1 cells for evaluating the toxic effects. The apoptotic cell death was measured using flow cytometric analysis of annexin-V/7-amino-actinomycin (7-AAD) and cell cycle tests. RESULTS: LIPO or CDDP inhibited cell viability in a dose- and time-dependent manner in both neuroblastoma and HEI-OC1 cells. LD50 values were selected as 20 mM for CDDP and 750 mM for LIPO in neuroblastoma cells. After the 48-hour incubation, KELLY cells treated with 20 mM CDDP and 750 mM LIPO had a 53% viability; SH-SY5Y cells treated 20 mM CDDP and 750 mM LIPO had a 45% and 58% viability, respectively; and HEI-OC1 cells treated with 20 mM CDDP and 750 mM LIPO had a 65% and 82% viability, respectively. CONCLUSION: LIPO showed less toxic effects in the HEI-OC1 cells compared to CDDP at anti-tumoral doses. Cite this article as: Serinan E, Atun Z, Aktaş S, Çeçen E, Olgun N. Comparison of Cisplatin with Lipoplatin in Terms of Ototoxicity. J Int Adv Otol 2018; 14(2): 211-5.

Noise-induced hearing loss (NIHL) is one of the most important problems affecting both social and professional life of patients. There is no treatment method considered to be successful on the hearing loss that has become a permanent nature. Aim of this study is to evaluate protective effect of Korean Red Ginseng (KRG) against NIHL in an animal model. Twenty-eight rats were separated into four groups [control saline (group I), control KRG (group II), saline + noise (group III), KRG + noise (group IV)]. Rats in the saline and KRG groups were fed via oral gavage with a dose of 200 mg/kg/day throughout for 10 days. Fourteen rats (group III and IV) were exposed to 4 kHz octave band noise at 120 dB SPL for 5 hours. Hearing levels of rats were evaluated by distortion product otoacoustic emissions (DPOAE) and auditory brainstem responses (ABR) at 4, 8, 12, 16 and 32 kHz frequencies prior to and on days 1, 7 and 10 after the noise exposure. Rats were sacrificed on 10th day, after the last audiological test. Cochlea and spiral ganglion tissues were evaluated by light microscopy. Audiological and histological results demonstrated that after noise the group IV showed better results than group III. In the noise exposed groups, the most prominent damage was seen at the 8 kHz frequency region than other regions. After the noise exposure, DPOAE responses were lost in 1st, 7th and 10th measurements in both group III and IV. Thus, we were not able to perform any statistical analyses for DPOAE results. Our findings suggest that KRG seems to be an efficient agent against NIHL. There is need for additional research to find out about the mechanisms of KRG’s protective effect.

Neuroblastic tumours exhibit heterogeneity, which results in different therapeutic outcomes. Neuroblastoma is categorized into three major risk groups (low, intermediate, high risk). Recent identification of new genes raised the possibility of new biomarkers to identify sub-risk groups. In this retrospective cross-sectional study, we aimed to assess new biomarkers defining the ultra-high-risk subgroup within the high-risk group that differ in clinical situation with very bad prognosis. Twenty-five low- and 29 high-risk groups of patients were analysed for their expression of ALK , ATRX , HIF1a , HIF2a ( EPAS ), H2AFX , and ETV5 genes at the RNA level. Immunohistochemistry was performed to confirm the protein expression level of ALK. The risk group of patients was determined according to the International Neuroblastoma Risk Group Stratification System. Spearman correlation analysis and Mann-Whitney-U nonparametric test were used to assess the importance of expression levels among the groups. P < 0.05 was considered as significant. Sensitivity of the results was checked by ROC curve analysis. All analysed genes were found to be highly expressed in the high-risk group compared to the low-risk group, except for ETV5 . When the ultra-high-risk and highrisk groups were compared, ALK was found to be highly expressed in the ultra-high-risk group. Our results show that ALK may be a candidate gene whose mRNA expression levels can distinguish the ultrahigh- risk subgroup of patients in the high-risk group of patients with non-familial neuroblastoma.

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.

Liposomal cancer treatment strategies are useful in removing the side effects that were the main concern in recent years. In this study, we prepared microbubble (MBs) conjugated with DOX-loaded liposomes (DOX-loaded MBs) and investigated their effectiveness in in vitro breast cancer cells in two dimensions (2D) and three dimensions (3D). With this aim, breast cancer cells with different features (4T1, MDA-MB231, MCF-7) were growth in 2D and 3D dimensions. The cytotoxic and cell death effects under different conditions, durations and doses were evaluated with WST-1, trypan-blue, colony counts. Apoptotic effects were investigated with flow cytometric Annexin-V-PI and immunohistochemical (Ki-67, caspase 3, 8, 9) methods. After free DOX and LipoDOX were applied, the proliferation index of three cell lines reduced. Intrinsic and extrinsic apoptotic pathways were activated in both 2D and 3D models. However, this effect was observed at lower levels in the 3D model due to the difficulty of diffusion of DOX into the spheroids. Additionally, the suitability of the 3D model for breast cancer cells was supported by formation of ductus-like structures and spheroids. Cell deaths were not observed significantly with the DOX-loaded microbubbles due to rising of MBs to the surface and not reaching spheroids held in matrigel of 3D model. DOX and LipoDOX showed anti-proliferative and apoptosis-inducing effects in breast cancer cells. However, these effects indicated variability depending on the cell lines and 2D or 3D model types.

Background and Aim: In neuroblastoma, anaplastic lymphoma kinase mutations have recently received attention as molecular targets for the treatment of neuroblastoma, as 6% to 10% of patients with neuroblastoma have anaplastic lymphoma kinase mutations. There are little data from the cases in Turkey. We aimed to detect anaplastic lymphoma kinase mutations and molecular heterogeneity in neuroblastoma using next-generation sequencing. This study is the first one with this many cases in Turkey. Methods: Next-generation sequencing analysis was performed using an Illumina MiniSeq custom gene panel. Clinically important mutations were selected for the analysis. We also gathered clinical data of the patients from Turkish Pediatric Oncology Group cohorts to associate them with anaplastic lymphoma kinase mutations. This study is a retrospective cross-sectional study. We followed STROBE guideline ( https://www.equator-network.org/reporting-guidelines/strobe/ ) on this study. Results: We analyzed anaplastic lymphoma kinase in 108 patients with neuroblastoma, with a mean age of 43.76 months. Pathogenic anaplastic lymphoma kinase mutations were detected in 13 patients (12.04%). We noted that anaplastic lymphoma kinase mutations were primarily observed in intermediate- and high-risk patients ( P = .028). R1275Q and F1174-related mutations were predominant; I1171T, L1226F, S1189F, V1135A, and G1125S mutations were rare. Duplicate samples did not exhibit any heterogeneity. Conclusions: We found that F1174 and R1275Q-related anaplastic lymphoma kinase mutations are the most common pathogenic mutations in neuroblastoma. Anaplastic lymphoma kinase mutation status did not show any heterogeneity, and the mutations were correlated with intermediate- or high-risk groups.