Adiponectin receptor agonist AdipoRon induces apoptotic cell death and suppresses proliferation in human ovarian cancer cells.

We tested the hypothesis that stimulation of adiponectin receptors with the synthetic agonist AdipoRon suppresses proliferation and induces apoptotic death in human high grade serous ovarian tumor cell lines and in ex vivo primary tumors, mediated by activation of 5' AMP-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin (mTOR). We determined the effect of AdipoRon on high grade serous ovarian tumor cells lines (OVCAR3, OVCAR4, A2780) and ex vivo primary tumor tissue. Western blotting analysis was performed to examine changes in activation of AMPK and mTOR signaling and flow cytometry was utilized to examine changes in cell cycle progression.

Ovarian Tumor Cell Expression of Claudin-4 Reduces Apoptotic Response to Paclitaxel.

A significant factor contributing to poor survival rates for patients with ovarian cancer is the insensitivity of tumors to standard-of-care chemotherapy. In this study, we investigated the effect of claudin-4 expression on ovarian tumor cell apoptotic response to cisplatin and paclitaxel. We manipulated claudin-4 gene expression by silencing expression [short hairpin RNA (shRNA)] in cells with endogenously expressed claudin-4 or overexpressing claudin-4 in cells that natively do not express claudin-4.

A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells.

Ovarian cancer is a complex disease marked by tumor heterogeneity, which contributes to difficulties in diagnosis and treatment. New molecular targets and better molecular profiles defining subsets of patients are needed. tRNA fragments (tRFs) offer a recently identified group of noncoding RNAs that are often as abundant as microRNAs in cancer cells.

A method for extracting and characterizing RNA from urine: For downstream PCR and RNAseq analysis.

Readily accessible samples such as urine or blood are seemingly ideal for differentiating and stratifying patients; however, it has proven a daunting task to identify reliable biomarkers in such samples. Noncoding RNA holds great promise as a source of biomarkers distinguishing physiologic wellbeing or illness. Current methods to isolate and characterize RNA molecules in urine are limited.

Claudin-4 activity in ovarian tumor cell apoptosis resistance and migration.

Background: Claudin-4 is a transmembrane protein expressed at high levels in the majority of epithelial ovarian tumors, irrespective of subtype, and has been associated with tumor cells that are both chemoresistant and highly mobile. The objective of this study was to determine the functional role that claudin-4 plays in apoptosis resistance and migration as well as the therapeutic utility of targeting claudin-4 activity with a small mimic peptide.

Methods: We examined claudin-4 activity in human ovarian tumor cell lines (SKOV3, OVCAR3, PEO4) using in vitro caspase and scratch assays as well as an in vivo mouse model of ovarian cancer.

Cricothyroid Muscle Botulinum Toxin Injection to Improve Airway for Bilateral Recurrent Laryngeal Nerve Paralysis, A Case Series.

Bilateral vocal fold paralysis most commonly results from iatrogenic trauma to the recurrent laryngeal nerve during surgical procedures in the anterior neck. Patients may require tracheostomy because of acute or gradual onset of dyspnea and airway compromise. The intralaryngeal injection of Botox has been considered as a possible therapy for these airway symptoms of bilateral vocal fold paralysis.

Regulation of trachebronchial tissue-specific stem cell pool size.

Tissue-specific stem cell (TSC) number is tightly regulated in normal individuals but can change following severe injury. We previously showed that tracheobronchial epithelial TSC number increased after severe naphthalene (NA) injury and then returned to normal. This study focused on the fate of the supernumerary TSC and the signals that regulate TSC pool size.

Roles for β-catenin and doxycycline in the regulation of respiratory epithelial cell frequency and function.

The expression of β-catenin-dependent genes can be increased through the Cre recombinase (Cre)-mediated elimination of the exon 3-encoded sequence. This mutant β-catenin is termed DE3, and promotes the expression of β-catenin-dependent genes. Our previous study used the DE3 model to demonstrate that persistent β-catenin activity inhibited bronchiolar Clara-to-ciliated cell differentiation.

β-catenin dosage is a critical determinant of tracheal basal cell fate determination.

The purpose of this study was to determine whether β-catenin regulates basal cell fate determination in the mouse trachea. Analysis of TOPGal transgene reporter activity and Wnt/β-catenin pathway gene expression suggested a role for β-catenin in basal cell proliferation and differentiation after naphthalene-mediated Clara-like and ciliated cell depletion. However, these basal cell activities occurred simultaneously, limiting precise determination of the role(s) played by β-catenin.

Context-dependent differentiation of multipotential keratin 14-expressing tracheal basal cells.

Multipotential (MP) differentiation is one characteristic of a tissue-specific stem cell (TSC). Lineage tracing of tracheobronchial basal cells after naphthalene (NA) injury or in the postnatal period demonstrated that basal cells were MP progenitors for Clara-like and ciliated cells. These studies, as well as reports of spatially restricted, label-retaining basal cells, and MP differentiation by human bronchial cells support the hypothesis that a TSC maintained and repaired the tracheobronchial epithelium.

Ansa cervicalis-to-recurrent laryngeal nerve anastomosis for unilateral vocal fold paralysis: experience of a single institution.

Objectives: One treatment option for unilateral vocal fold paralysis (UVFP) is ansa cervicalis-to-recurrent laryngeal nerve (ansa-RLN) anastomosis to provide reinnervation to the affected vocal fold. The advantages of this treatment approach are that it 1) provides vocal fold tone, bulk, and tension, 2) is technically simple, and 3) does not preclude other medialization procedures. We present all patients who have undergone ansa-RLN anastomosis for UVFP at our institution.

Results of ansa to recurrent laryngeal nerve reinnervation.

Objective: We sought to describe the results of ansa cervicalis to recurrent laryngeal nerve (ansa-RLN) reinnervation for unilateral vocal fold paralysis.

Study Design: A chart review was performed on patients undergoing ansa-RLN reinnervation for unilateral vocal cord paralysis at a tertiary care center. Patient perceptions of preoperative and postoperative voice quality was surveyed.

Vocal outcomes after laser resection of early-stage glottic cancer with adjuvant cryotherapy.

Objective: To evaluate the vocal outcomes of patients with early-stage glottic carcinoma undergoing laser resection with adjuvant cryoablative therapy.

Design: Retrospective review.

Setting: Tertiary care center.

Surgical fundoplication in laryngopharyngeal reflux unresponsive to aggressive acid suppression: a controlled study.

Background & Aims: In patients with persistent laryngeal symptoms despite aggressive proton pump inhibitor therapy, gastroesophageal reflux disease (GERD) continues to be implicated. The role of surgical fundoplication as the definitive therapy for these patients is uncertain.

Methods: In this prospective concurrent controlled study, 72 patients with suspected GERD-related laryngeal symptoms received aggressive acid-suppressive therapy.

Chronic laryngitis associated with gastroesophageal reflux: prospective assessment of differences in practice patterns between gastroenterologists and ENT physicians.

Objectives: Ear, nose, and throat (ENT) physicians often diagnose gastroesophageal reflux disease (GERD)-related laryngitis on the basis of symptoms and laryngeal signs; and may refer patients to gastroenterologists who contend that many such patients do not have reflux. Because of this dichotomy we designed this study to assess the practice pattern differences among ENT physicians and gastroenterologists in relation to the diagnosis and treatment of patients with GERD-related laryngitis.

Methods: Separate surveys were specifically designed for ENT physicians and gastroenterologists to assess the following: the percentage of patients diagnosed with GERD-related laryngitis, dose and duration of therapy, treatment response, and other diagnostic options in nonresponders.

Prevalence of laryngeal irritation signs associated with reflux in asymptomatic volunteers: impact of endoscopic technique (rigid vs. flexible laryngoscope).

Objectives: The objectives of this study were to 1) determine the prevalence of ENT findings in the normal asymptomatic population and 2) to compare findings between flexible and rigid laryngoscopes in an attempt to increase specificity of diagnosis of reflux in endoscopic laryngeal examinations.

Study Design: Prospective study.

Methods: Fifty-two nonsmoker volunteers (24 male, 28 female), mean age of 42.

Correlation between symptoms and laryngeal signs in laryngopharyngeal reflux.

Objective/hypothesis: Laryngopharyngeal reflux (LPR) is diagnosed by the presence of laryngeal signs and symptoms. Some studies have noted that signs and symptoms may be nonspecific and may have poor correlation. However, many such studies were either observational or had short-term follow-up.

Long-term effects of micronized Alloderm injection for unilateral vocal fold paralysis.

Objectives: Micronized Alloderm (Cymetra) is a relatively new product used for vocal fold augmentation. Previous studies evaluating possible long-term effectiveness of this product have shown mixed results. The objective of this present study is to reassess possible long-term results of Cymetra injection laryngoplasty in patients with unilateral true vocal fold paralysis.

Laryngopharyngeal reflux: prospective cohort study evaluating optimal dose of proton-pump inhibitor therapy and pretherapy predictors of response.

Purpose: Laryngopharyngeal reflux (LPR) is frequently treated with empiric proton-pump inhibitors (PPI), but the optimal dosing and duration is unknown. We performed an open label prospective cohort study to evaluate whether twice-daily (BID) PPI is more effective than once-daily (QD) PPI for the treatment of LPR.

Methods: Patients diagnosed with LPR based on ear, nose, and throat (ENT) symptoms and laryngoscopy findings were enrolled.

Laryngeal nerve function after total laryngeal transplantation.

The first successful composite human laryngeal transplantation was performed by a team led by the senior author on January 4, 1998. The recipient was a 40-year-old male who had sustained a crush injury to his larynx 20 years prior, rendering him aphonic. Multiple previous attempts for reconstruction at an outside hospital were unsuccessful.

Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association.

Gastroesophageal reflux disease (GERD) has been associated increasingly with ear, nose, and throat (ENT) signs and symptoms. However, the cause and effect relationship between these two clinical entities are far from established. Many patients diagnosed initially with GERD as the cause of laryngeal signs do not symptomatically or laryngoscopically respond to aggressive acid suppression and do not have abnormal esophageal acid exposure by pH monitoring.

The prevalence of hypopharynx findings associated with gastroesophageal reflux in normal volunteers.

Routine laryngeal examination of patients with otolaryngologic complaints often reveals findings thought to result from gastroesophageal reflux. The direct association between these mucosal findings and uncontrolled reflux is not well established. To begin exploring the specificity of tissue signs, 105 normal, healthy, adult volunteers were examined by routine video fiber-optic endoscopy for the presence of findings attributed to reflux disease.