DRG2 as a Biomarker to Enhance the Predictive Efficacy of PD-L1 Immunohistochemistry Assays.

PD-L1 immunohistochemistry (IHC) assays are used as a companion diagnostic for immunotherapy with immune checkpoint inhibitors (ICIs). However, despite the association between PD-L1 expression and clinical benefit from ICIs, the PD-L1 IHC assay is not sufficiently accurate in predicting response to ICIs; some patients with high PD-L1 expression do not respond to ICIs. Recently, researchers provided insights into why some patients with high PD-L1 expression fail to respond to ICIs.

Extrinsic Laryngeal Muscle Activity and Vocal Economy in Professionally Trained Voices During Vocal Vibrato.

Purpose: The purpose of the present study was to determine the extrinsic laryngeal muscle activity and vocal economy during two different singing conditions (straight-tone- vs vibrato singing) over a physiologically relevant singing range.

Methods: Thirty professional singers or voice coaches participated in the study. The participants sang a sustained /a:/ vowel for approximately 5seconds, once in straight-tone singing conditions and once more in vibrato.

DRG2 is required for surface localization of PD-L1 and the efficacy of anti-PD-1 therapy.

More than half of tumor patients with high PD-L1 expression do not respond to anti-PD-1/PD-L1 therapy, and the underlying mechanisms are yet to be clarified. Here we show that developmentally regulated GTP-binding protein 2 (DRG2) is required for response of PD-L1-expressing tumors to anti-PD-1 therapy. DRG2 depletion enhanced IFN-γ signaling and increased the PD-L1 level in melanoma cells.

Extrinsic Laryngeal Muscle Activity With Different Diameters and Water Depths in a Semi-Occluded Vocal Tract Exercise.

Purpose: Surface electromyography (sEMG) has been used to evaluate extrinsic laryngeal muscle activity during swallowing and phonation. In the current study, sEMG amplitudes were measured from the infrahyoid and suprahyoid muscles during phonation through a tube submerged in water.

Method: The sEMG amplitude values measured from the extrinsic laryngeal muscles and the electroglottographic contact quotient (CQ) were obtained simultaneously from 62 healthy participants (31 men, 31 women) during phonation through a tube at six different depths (2, 4, 7, 10, 15, and 20 cm) while using two tubes with different diameters (1 and 0.

Clinical Practice Guidelines for Oropharyngeal Dysphagia.

Objective: Dysphagia is a common clinical condition characterized by difficulty in swallowing. It is sub-classified into oropharyngeal dysphagia, which refers to problems in the mouth and pharynx, and esophageal dysphagia, which refers to problems in the esophageal body and esophagogastric junction. Dysphagia can have a significant negative impact one's physical health and quality of life as its severity increases.

FOXO1 Is a Key Mediator of Glucocorticoid-Induced Expression of Tristetraprolin in MDA-MB-231 Breast Cancer Cells.

The mRNA destabilizing factor tristetraprolin (TTP) functions as a tumor suppressor by down-regulating cancer-associated genes. expression is significantly reduced in various cancers, which contributes to cancer processes. Enforced expression of impairs tumorigenesis and abolishes maintenance of the malignant state, emphasizing the need to identify a inducer in cancer cells.

Depletion Promotes Endothelial Cell Senescence and Vascular Endothelial Dysfunction.

Endothelial cell senescence is involved in endothelial dysfunction and vascular diseases. However, the detailed mechanisms of endothelial senescence are not fully understood. Here, we demonstrated that deficiency of developmentally regulated GTP-binding protein 2 () induces senescence and dysfunction of endothelial cells.

Clinical Usefulness of the Korean Version of the Dysphagia Handicap Index: Reliability, Validity, and Role as a Screening Test.

This study aimed to measure the validity and reliability of the Korean version of the Dysphagia Handicap Index (K-DHI) and evaluate its diagnostic efficacy for predicting aspiration. We enrolled 104 patients with dysphagia symptoms (D group) and 88 controls (ND group). Among controls, there were 43 patients without dysphagia symptoms (ND patient group).

Doxorubicin inhibits PD-L1 expression by enhancing TTP-mediated decay of PD-L1 mRNA in cancer cells.

Recent research revealed that doxorubicin (DOX) decreased expression of programmed death-ligand 1 (PD-L1) in cancer cells. However, the detailed mechanisms underlying this effect are not well established. Here, we demonstrate that doxorubicin down-regulates PD-L1 expression through induction of AU-rich element (ARE) binding protein tristetraprolin (TTP) in cancer cells.

DRG2 supports the growth of primary tumors and metastases of melanoma by enhancing VEGF-A expression.

Malignant metastatic melanoma (MM) is the most lethal of all skin cancers, but detailed mechanisms for regulation of melanoma metastasis are not fully understood. Here, we demonstrated that developmentally regulated GTP-binding protein 2 (DRG2) is required for the growth of primary tumors and for metastasis. DRG2 expression was significantly increased in MM compared with primary melanoma (PM) and dysplastic nevi.

Tristetraprolin posttranscriptionally downregulates PFKFB3 in cancer cells.

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases 3 (PFKFB3) catalyzes the first committed rate-limiting step of glycolysis and is upregulated in cancer cells. The mechanism of PFKFB3 expression upregulation in cancer cells has not been fully elucidated. The PFKFB3 3'-UTR is reported to contain AU-rich elements (AREs) that are important for regulating PFKFB3 mRNA stability.

Tristetraprolin-mediated hexokinase 2 expression regulation contributes to glycolysis in cancer cells.

Hexokinase 2 (HK2) catalyzes the first step of glycolysis and is up-regulated in cancer cells. The mechanism has not been fully elucidated. Tristetraprolin (TTP) is an AU-rich element (ARE)-binding protein that inhibits the expression of ARE-containing genes by enhancing mRNA degradation.

Tristetraprolin inhibits mitochondrial function through suppression of α-Synuclein expression in cancer cells.

Mitochondrial dynamics play critical roles in maintaining mitochondrial functions. Here, we report a novel mechanism for regulation of mitochondrial dynamics mediated by tristetraprolin (TTP), an AU-rich element (ARE)-binding protein. Overexpression of TTP resulted in elongated mitochondria, down-regulation of mitochondrial oxidative phosphorylation, reduced membrane potential, cytochrome c release, and increased apoptotic cell death in cancer cells.

Epidemiologic Study of Human Epidermal Growth Factor Receptor 2 Expression in Advanced/Metastatic Gastric Cancer: an Assessment of Human Epidermal Growth Factor Receptor 2 Status in Tumor Tissue Samples of Gastric and Gastro-Esophageal Junction Cancer.

Purpose: The Trastuzumab for gastric cancer (GC) trial identified human epidermal growth factor receptor 2 (HER2) as a predictor of successful treatment with trastuzumab (HER2 receptor targeting agent) among patients with advanced/metastatic GC. To date, the prevalence of HER2 overexpression in the Korean population is unknown. The present study aimed to assess the incidence of HER2 positivity among GC and gastroesophageal (GE) junction cancer samples and the relationship between HER2 overexpression and clinicopathological characteristics in Korean patients.

Noise-Induced Neural Degeneration and Therapeutic Effect of Antioxidant Drugs.

The primary site of lesion induced by noise exposure is the hair cells in the organ of Corti and the primary neural degeneration occurs in synaptic terminals of cochlear nerve fibers and spiral ganglion cells. The cellular basis of noise-induced hearing loss is oxidative stress, which refers to a severe disruption in the balance between the production of free radicals and antioxidant defense system in the cochlea by excessive production of free radicals induced by noise exposure. Oxidative stress has been identified by a variety of biomarkers to label free radical activity which include four-hydroxy-2-nonenal, nitrotyrosine, and malondialdehyde, and inducible nitric oxide synthase, cytochrome-C, and cascade-3, 8, 9.

Speech Recognition in Real-Life Background Noise by Young and Middle-Aged Adults with Normal Hearing.

Background And Objectives: People usually converse in real-life background noise. They experience more difficulty understanding speech in noise than in a quiet environment. The present study investigated how speech recognition in real-life background noise is affected by the type of noise, signal-to-noise ratio (SNR), and age.

Effect of TBT and PAHs on CYP1A, AhR and Vitellogenin Gene Expression in the Japanese Eel, Anguilla japonica.

Gene expressions of cytochrome P4501A (CYP1A), aryl hydrocarbon receptor (AhR) and vitellogenin (Vg) by endocrine disruptors, benzo[α]pyrene (B[a]P) and tributyltin (TBT) were examined in cultured eel hepatocytes which were isolated from eels treated previously with B[a]P (10 mg/kg) or estradiol-17β (20 mg/kg) in vivo, and the relationship between CYP1A, AhR and Vg genes were studied. When the cultured eel hepatocytes were treated with B[a]P (10(-6)-10(-5) M) the gene expressions of CYP1A and AhR were enhanced in a concentration-dependent manner. However, when treated with TBT (10(-9)-10(-5) M) the gene expressions of CYP1A and AhR were suppressed at high concentrations (10(-6)-10(-5) M), while having no effects at low concentrations (10(-9)-10(-7) M).

Reliability and validity of the Korean version of Pediatric Voice Handicap Index: in school age children.

Objective: The aim of this study was to assess the reliability and validity of the Pediatric Voice Handicap Index (pVHI) for cross-cultural adaptation of the Korean version with school age children.

Methods: The questionnaire was translated into Korean and was completed by 101 Korean parents who have children with or without disordered voice. The Korean version-pVHI scores were obtained with 60 parents of normal children and 41 parents who have children with voice problems.

Effect of vocal fold injury location on vibratory parameters in excised canine larynges.

Objective: To investigate the effect of vocal fold injury location on vibratory amplitude and lateral phase difference.

Study Design: Repeated measures with each excised canine larynx serving as own control.

Setting: Basic science study conducted in university laboratory.

Opuntia humifusa supplementation increased bone density by regulating parathyroid hormone and osteocalcin in male growing rats.

We investigated the effect of Opuntia humifusa (O. humifusa) supplementation on bone density and related hormone secretion in growing male rats. Sixteen six-week-old male Sprague-Dawley rats were randomly divided into two groups; control diet group (CG, n = 8), and experimental diet group (EG, n = 8).

Nonlinear dynamic-based analysis of severe dysphonia in patients with vocal fold scar and sulcus vocalis.

Objective: The primary goal of this study was to evaluate a nonlinear dynamic approach to the acoustic analysis of dysphonia associated with vocal fold scar and sulcus vocalis.

Study Design: Case-control study.

Methods: Acoustic voice samples from scar/sulcus patients and age-/sex-matched controls were analyzed using correlation dimension (D2) and phase plots, time-domain based perturbation indices (jitter, shimmer, signal-to-noise ratio [SNR]), and an auditory-perceptual rating scheme.

The effect of segment selection on acoustic analysis.

Objective/hypothesis: Acoustic analysis is a commonly used method for quantitatively measuring vocal fold function. Voice signals are analyzed by selecting a waveform segment and using various algorithms to arrive at parameters such as jitter, shimmer, and signal-to-noise ratio (SNR). Accurate and reliable methods for selecting a representative vowel segment have not been established.

Prospective multi-arm evaluation of surgical treatments for vocal fold scar and pathologic sulcus vocalis.

Objectives/hypothesis: The purpose of this study was to compare the clinical effectiveness of type I thyroplasty, injection laryngoplasty, and graft implantation for the treatment of vocal fold scar and pathologic sulcus vocalis.

Study Design: Prospective, multi-arm, quasi-experimental research design.

Methods: Twenty-eight patients with newly diagnosed vocal fold scar and/or pathologic sulcus vocalis were assigned to one of three treatment modalities: type I thyroplasty (n = 9), injection laryngoplasty (n = 9), and graft implantation (n = 10).

Cross-sample validation provides enhanced proteome coverage in rat vocal fold mucosa.

The vocal fold mucosa is a biomechanically unique tissue comprised of a densely cellular epithelium, superficial to an extracellular matrix (ECM)-rich lamina propria. Such ECM-rich tissues are challenging to analyze using proteomic assays, primarily due to extensive crosslinking and glycosylation of the majority of high M(r) ECM proteins. In this study, we implemented an LC-MS/MS-based strategy to characterize the rat vocal fold mucosa proteome.

Stapling technique for performing Billroth II anastomosis after distal gastrectomy.

The circular stapling technique has been widely applied for gastrointestinal anastomosis in gastrectomies (open or laparoscopic) for distal gastric cancers. We describe this method for use in performing Billroth II anastomosis in distal gastrectomies. From 2002-2009, we report the results following the use of the circular stapling technique performed in 520 patients at a single institution.