Background: Gastric cancer, one of the leading causes of cancer-related death, is strongly associated with H. pylori infection, although other risk factors have been identified. The sirtuin (Sirt) family is involved in the tumorigenesis of gastric cancer, and sirtuins can have pro- or anti-tumorigenic effects. Methods: After determining the overall survival rate of gastric cancer patients with or without Sirt6 expression, the effect of Sirt6 upregulation was also tested using a xenograft mouse model. The regulation of Sirt6 and Sirt1, leading to the induction of mouse double minute 2 homolog (MDM2) and reactive oxygen species (ROS), was mainly analyzed using Western blotting and immunofluorescence staining, and gastric cancer cell (SNU-638) death associated with these proteins was measured using flow cytometric analysis. Results: Sirt6 overexpression led to Sirt1 suppression in gastric cancer cells, resulting in a higher level of gastric cancer cell death in vitro and a reduced tumor volume. ROS and MDM2 expression levels were upregulated by Sirt6 overexpression and/or Sirt1 suppression according to Western blot analysis. The upregulated ROS ultimately led to gastric cancer cell death as determined via Western blot and flow cytometric analysis. Conclusion: We found that the upregulation of Sirt6 suppressed Sirt1, and Sirt6- and Sirt1-induced gastric cancer cell death was mediated by ROS production. These findings highlight the potential of Sirt6 and Sirt1 as therapeutic targets for treating gastric cancer.
1 January 2016 in Korean Journal of Otorhinolaryngology-Head and Neck Surgery
Background: Tinnitus is often difficult to treat because it is closely related to hearing loss, central nervous system disorders, and emotional problems. Although various drug treatments have been attempted for patients with tinnitus, there is no drug that has been clearly proven to be effective. On the other hand, there are some studies showing the effectiveness of various non-pharmacological treatments for tinnitus.Current Concepts: Tinnitus is classified into subjective and objective tinnitus. Representative non-pharmacological treatments for chronic subjective tinnitus include sound therapy, hearing aids or implantable hearing rehabilitation devices, tinnitus retraining therapy, neuropsychiatric therapy, and neuromodulatory treatment. When objective tinnitus does not improve with conservative treatment, surgical treatment can be selected depending on the cause. Acupuncture treatment for tinnitus is not recommended due to lack of evidence on its effectiveness and safety.Discussion and Conclusion: Despite many studies, the mechanisms of tinnitus remain unknown. Thus, it is difficult to cure the cause of tinnitus. Because subjective responses to tinnitus vary according to the patient’s psychological state, a variety of approaches would be needed for the treatment of tinnitus.
21 December 2021 in Korean Journal of Otorhinolaryngology-Head and Neck Surgery
Background and Objectives To describe and evaluate modified circumferential subannular tympanoplasty (MCST) via endoscopic approach, we compared the results of MCST to those of the underlay technique and the results of previous studies.Subjects and Method A retrospective comparative study was conducted of 31 patients who underwent endoscopic transcanal tympanoplasty. Patients were classified into the MCST group (n=11) and the underlay group (n=20) according to the graft technique. Demographic data, size and location of the perforation, pre- and postoperative hearing, operating time, complication rate, and graft success rate were analyzed in each group.Results No significant differences between the two groups were observed in the demographic data or the locations of the perforations. The sizes of the perforations were 31.4±14.3% and 25.0±18.1%, respectively. The average operating times were 68.6±16.5 min and 64.9±9.3 min, respectively, and canaloplasty was not required in any patient. The postoperative hearing improvement and air-bone gap were not significantly different. No postoperative complications were observed in either group.Conclusion MCST is a feasible and effective technique for endoscopic transcanal tympanoplasty. The postoperative results and operating times of MCST were comparable to those of other graft techniques. MCST showed more stable results in anterior perforation than in underlay graft.
Ototoxicity is traditionally viewed as a local cochlear adverse effect of indispensable therapies such as cisplatin and aminoglycosides. However, emerging evidence suggests that cochlear vulnerability is shaped by systemic physiology, including inflammatory tone, vascular barrier integrity, and metabolic state. In this Review, we propose a Gut–Mito–Ear axis in which gut ecosystem function influences circulating mediator modules that converge on two cochlear mediator nodes: blood–labyrinth barrier (BLB) gating and mitochondrial stress tolerance. We synthesize evidence showing that gut perturbation can alter cochlear outcomes in vivo, that at least one microbiota-derived metabolite signal can directly protect hearing in experimental settings, and that BLB dysfunction and inflammatory trafficking are mechanistically relevant to cisplatin- and aminoglycoside-induced injury. We further organize the literature using an evidence-weighted framework that distinguishes direct cochlear causality from mechanistic plausibility and explicitly retains negative studies as boundary-setting evidence. Finally, we outline a translational roadmap in which microbiome-targeted prevention is pursued through mediator-anchored, non-interference-aware strategies and evaluated across linked state variables spanning exposure context, gut function, defined mediator modules, BLB gating, mitochondrial stress tolerance, and auditory phenotype. The Gut–Mito–Ear axis is not considered an established mechanism. We present it as a falsifiable systems-biology model that organizes the current evidence. Within this model, we define the minimum and ideal standards for A-tier causal evidence, explicit criteria for interpreting boundary-setting negative (A−) studies, and a set of testable predictions for causal validation.
31 March 2024 in Journal of Clinical Otolaryngology