156 research outputs found
Publisher Correction: The dual role of curcumin and ferulic acid in counteracting chemoresistance and cisplatin-induced ototoxicity (Scientific Reports, (2020), 10, 1, (1063), 10.1038/s41598-020-57965-0)
No full textIn the original version of this Article, the author Anna Rita Fetoni was incorrectly indexed. This error has now been corrected
Cisplatin Chemotherapy and Cochlear Damage: Otoprotective and Chemosensitization Properties of Polyphenols
No full textSignificance: Cisplatin is an important component of treatment regimens for different cancers. Notwithstanding that therapeutic success often results from partial efficacy or stabilizing the disease, chemotherapy failure is driven by resistance to drug treatment and occurrence of side effects, such as progressive irreversible ototoxicity. Cisplatin's side effects, including ototoxicity, are often dose limiting. Recent Advances: Cisplatin ototoxicity results from several mechanisms, including redox imbalance caused by reactive oxygen species production and lipid peroxidation, activation of inflammation, and p53 and its downstream pathways that culminate in apoptosis. Considerable efforts in research have targeted development of molecular interventions that can be concurrently administered with cisplatin or other chemotherapies to reduce side effect toxicities while preserving or enhancing the antineoplastic effects. Evidence from studies has indicated some polyphenols, such as curcumin, can help to regulate redox signaling and inflammatory effects. Furthermore, polyphenols can exert opposing effects in different types of tissues, that is, normal cells undergoing stressful conditions versus cancer cells. Critical Issues: This review article summarizes evidence of curcumin antioxidant effect against cisplatin-induced ototoxicity that is converted to a pro-oxidant activity in cisplatin-treated cancer cells, thus providing an ideal chemosensitivity combined with otoprotection. Polyphenols can modulate the adaptive responses to stress in the cisplatin-exposed cochlea. These adaptive effects can result from the interaction/cross talk between the cell's defenses, inflammatory molecules, and the key signaling molecules of signal transducers and activators of transcription 3 (STAT-3), nuclear factor κ-B (NF-κB), p53, and nuclear factor erythroid 2-related factor 2 (Nrf-2). Future Directions: We provide molecular evidence for alternative strategies for chemotherapy with cisplatin addressing the otoprotection and chemosensitization properties of polyphenols
Il contributo della ricerca di base e la gestione clinica dell'ototossicità da cisplatino e irradiazione: dai protocolli di sorveglianza al trattamento
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An Src-protein tyrosine kinase inhibitor to reduce cisplatin ototoxicity while preserving its antitumor effect
No full textOtotoxicity remains a major dose-limiting side effect of cisplatin. The current studies were carried out to evaluate the effectiveness of a novel Src-protein tyrosine kinase inhibitor in protecting the ear from cisplatin ototoxicity without compromising cisplatin's antitumor effects. The Src inhibitor has been shown to be effective in protecting the ear from noise-induced hearing loss. Three studies were carried out to determine whether this compound has otoprotective activity in rats treated with cisplatin. The first two studies used the Src inhibitor as a cotreatment with single doses of cisplatin in Fischer 344/NHsd rats and nude rats, respectively. Cochlear damage was assessed by auditory brainstem response threshold shifts and outer hair cell loss. The third study was carried out in nude rats with implanted HT-29 tumors, and the Src inhibitor was administered as a cotreatment with a lower dose of cisplatin. Cochlear damage and changes in tumor volume were assessed in the third study. In the first two studies, cotreatment with the Src inhibitor reduced cisplatin-induced hearing loss significantly. In the third study, little hearing loss was induced because of the use of a lower dose of cisplatin. However, cotreatment with the Src inhibitor did not exert a negative effect on cisplatin's slowing of tumor growth in the treated rats. The findings suggest that the Src inhibitor may provide an effective cotreatment with cisplatin to reduce cisplatin's ototoxicity, without compromising its antitumor capability
Study of Angiogenic, Pro-Apoptotic, and Pro-Inflammatory Factors in Congenital and Acquired Cholesteatomas
No full textObjectives. Despite recent advances in biomolecular research that have improved our knowledge of cholesteatoma pathogenesis, the reasons behind its highly variable clinical course are still not clarified. It has been proposed that biological signaling between peri-matrix and matrix cells could play a critical role in disease homeostasis. The aim of our study was to analyze the expression of inflammatory (IL-1 beta), hyper-proliferative (STAT-3, TGF- beta), and angiogenic (VEGF-C, PDGFr) factors in congenital and acquired cholesteatomas (both in adults and children), which might correlate with the clinical features observed. We performed an experimental study on 37 patients (29 males and 8 females, ranging from 4 to 66 years of age) who were diagnosed with cholesteatoma between 2020 and 2021 in our institution. All patients underwent clinical, audiologic, and radiologic assessments. Bone erosion grading and staging of cholesteatoma growth were assessed through preoperative evaluation and intraoperative middle ear findings, according to the PTAM System proposed by the Japan Otological Society (2016). Retro-auricular skin specimens were intraoperatively collected in all patients. Skin and cholesteatoma samples were analyzed through histopathological, western blot, and immunohistochemical evaluations. The expression rate was measured to find out the differences between congenital and acquired cholesteatomas as well as between the adult and pediatric populations. Expression of angiogenic, inflammatory, and proliferative biomarkers is significantly increased in acquired cholesteatomas in children as compared to congenital and acquired forms in adults, in accordance with the higher stage of disease shown by imaging, surgical, and histological features. Our data suggest that pathways already supposed to be involved in the pathogenesis of cholesteatomas could be differently activated in more destructive forms, typically found in children. The identification of potential biomarkers of cholesteatoma aggressiveness could lead to more personalized management (timing of intervention, recurrence prevention) and the future identification of anti-growth/anti-proliferative agents as non-surgery therapeutic options
The New Semisynthetic TORP: A Prosthesis for Ossicular Reconstruction Both with the Absence and the Presence of the Stapes Superstructure
No full textObjectives To describe the new semisynthetic total ossicular replacement prosthesis (New-SSTORP) and to evaluate the New-SSTORP ossiculoplasty results both with the presence and absence of the stapes superstructure. Study Design Prospective study. Setting Tertiary referral center. Methods From April 2023 to May 2023, 18 New-SSTORP ossiculoplasties were performed by the first author. In all patients, the New-SSTORP was interposed between the footplate and the eardrum. The study group was divided into two groups (group A and group B). Group A included 13 patients with the absence of stapes superstructure. Group B included five patients with the presence of stapes superstructure. A successful reconstruction was defined as a postoperative air-bone gap ABG ≤20 dB. For all patients of groups A and B, the last audiometric control considered was performed in January 2024. The mean follow-up was 81⁄2 months. The χ2 test was used to compare results. p < 0.05 was considered significant. Main Outcome Measures Mean postoperative ABG ≤20 dB Results At the end of follow-up, the overall success rate (ABG ≤20 dB) of New-SSTORP ossiculoplasty was obtained in 88.8% (n = 16 of 18) of cases. In group A, the success rate of New-SSTORP ossiculoplasty occurred in 84.6% (n = 11 of 13) of cases, and in group B, the success rate of New-SSTORP ossiculoplasty occurred in 100% (n = 5 of 5) of cases. There was no audiological statistically significant difference between groups A and B (Fisher value is 1; p < 0.05). In all cases, the time for positioning of New-SSTORP was about 5 minutes Conclusion The New-SSTORP has a minimal technical challenge for building and placement. The New-SSTORP ossiculoplasty results are very good both with the presence and absence of SS
Protective effects of N-acetylcysteine on noise-induced hearing loss in guinea pigs
No full textIncreasing evidence suggests the involvement of oxidative stress in noise-induced hearing loss. The present study analysed, in an animal experimental model, the time course of the pathogenic mechanisms of noise-induced cochlear damage and the efficacy of the antioxidant drug N-acetylcysteine in reducing noise ototoxicity. Animals were divided into two groups, exposed to noise one treated with N-acetylcysteine for 3 days and one (the control group) with saline. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 minutes. Electrocochleographic recordings were made from an implanted round window electrode and the compound action potentials were measured daily at 2-16 kHz for 7 days. Morphological changes were analysed by scanning electron microscopy. The acoustic threshold measured 1 hour after acoustic trauma was elevated in the control group to 70-90 dB in the higher frequencies of the compound action potential audiogram, with a maximum threshold elevation ranging between 12 and 16 kHz. During the first 24 h, following acoustic trauma, there was a partial recovery of compound action potential thresholds of about 20 dB to reach a final threshold elevation of about 50-70 dB; there was no further improvement over the remaining experimental week. Animals treated with N-acetylcysteine showed a similar temporary threshold shift but a clear improvement in the recovery of compound action potential thresholds, with significantly reduced permanent threshold shift and hair cell loss. These data suggest that N-acetylcysteine is able to attenuate the toxic effect of acoustic trauma and could represent an interesting molecule for preventing inner ear injuries
Pathogenesis of presbycusis in animal models: A review
No full textPresbycusis is the most common cause of hearing loss in aged subjects, reducing individual's communicative skills. Age related hearing loss can be defined as a progressive, bilateral, symmetrical hearing loss due to age related degeneration and it can be considered a multifactorial complex disorder, with both environmental and genetic factors contributing to the aetiology of the disease. The decline in hearing sensitivity caused by ageing is related to the damage at different levels of the auditory system (central and peripheral). Histologically, the aged cochlea shows degeneration of the stria vascularis, the sensorineural epithelium, and neurons of the central auditory pathways. The mechanisms responsible for age-associated hearing loss are still incompletely characterized. This work aims to give a broad overview of the scientific findings related to presbycusis, focusing mainly on experimental studies in animal model
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