Search

Mitochondria are critical to the governance of metabolism and bioenergetics in cancer cells1. The mitochondria form highly organized networks, in which their outer and inner membrane structures define their bioenergetic capacity2,3. However, in vivo studies delineating the relationship between the structural organization of mitochondrial networks and their bioenergetic activity have been limited. Here we present an in vivo structural and functional analysis of mitochondrial networks and bioenergetic phenotypes in non-small cell lung cancer (NSCLC) using an integrated platform consisting of positron emission tomography imaging, respirometry and three-dimensional scanning block-face electron microscopy. The diverse bioenergetic phenotypes and metabolic dependencies we identified in NSCLC tumours align with distinct structural organization of mitochondrial networks present. Further, we discovered that mitochondrial networks are organized into distinct compartments within tumour cells. In tumours with high rates of oxidative phosphorylation (OXPHOSHI) and fatty acid oxidation, we identified peri-droplet mitochondrial networks wherein mitochondria contact and surround lipid droplets. By contrast, we discovered that in tumours with low rates of OXPHOS (OXPHOSLO), high glucose flux regulated perinuclear localization of mitochondria, structural remodelling of cristae and mitochondrial respiratory capacity. Our findings suggest that in NSCLC, mitochondrial networks are compartmentalized into distinct subpopulations that govern the bioenergetic capacity of tumours.

BackgroundThe cyclooxygenase 2 (COX-2) pathway has been implicated in the molecular pathogenesis of many malignancies, including lung cancer. Apricoxib, a selective COX-2 inhibitor, has been described to inhibit epithelial-mesenchymal transition (EMT) in human malignancies. The mechanism by which apricoxib may alter the tumor microenvironment by affecting EMT through other important signaling pathways is poorly defined. IL-27 has been shown to have anti-tumor activity and our recent study showed that IL-27 inhibited EMT through a STAT1 dominant pathway.ObjectiveThe purpose of this study is to investigate the role of apricoxib combined with IL-27 in inhibiting lung carcinogenesis by modulation of EMT through STAT signaling.Methods and resultsWestern blot analysis revealed that IL-27 stimulation of human non-small cell lung cancer (NSCLC) cell lines results in STAT1 and STAT3 activation, decreased Snail protein and mesenchymal markers (N-cadherin and vimentin) and a concomitant increase in expression of epithelial markers (E-cadherin, β-and γ-catenins), and inhibition of cell migration. The combination of apricoxib and IL-27 resulted in augmentation of STAT1 activation. However, IL-27 mediated STAT3 activation was decreased by the addition of apricoxib. STAT1 siRNA was used to determine the involvement of STAT1 pathway in the enhanced inhibition of EMT and cell migration by the combined IL-27 and apricoxib treatment. Pretreatment of cells with STAT1 siRNA inhibited the effect of combined IL-27 and apricoxib in the activation of STAT1 and STAT3. In addition, the augmented expression of epithelial markers, decreased expression mesenchymal markers, and inhibited cell migration by the combination treatment were also inhibited by STAT1 siRNA, suggesting that the STAT1 pathway is important in the enhanced effect from the combination treatment.ConclusionCombined apricoxib and IL-27 has an enhanced effect in inhibition of epithelial-mesenchymal transition and cell migration in human lung cancer cells through a STAT1 dominant pathway.

IntroductionThe classification of malignant sweat gland lesions is complex. Traditionally, cutaneous sweat gland tumors have been classified by either eccrine or apocrine features.MethodsA case report of a 33-year-old Hispanic man with a left scalp mass diagnosed as a malignancy of adnexal origin preoperatively is discussed. After presentation at our multidisciplinary tumor board, excision with ipsilateral neck dissection was undertaken.ResultsFinal pathology revealed an apocrine hidradenocarcinoma. The classification and behavior of this entity are discussed in this report.ConclusionApocrine hidradenocarcinoma can be viewed as an aggressive malignant lesion of cutaneous sweat glands on a spectrum that involves both eccrine and apoeccrine lesions.

The variable location and indistinct features of parathyroid glands can make their intraoperative identification challenging. Currently, there exists no routine use of localization methods during surgery. Dynamic optical contrast imaging (DOCI) leverages a novel realization of temporally dependent measurements of tissue autofluorescence that allows the acquisition of specific tissue properties. A prospective series of patients with primary hyperparathyroidism was examined. Parathyroid lesions and surrounding tissues were collected; fluorescence decay images were acquired via DOCI. Ex vivo samples (81 patients) were processed for histologic assessment. DOCI extracts relative fluorescence decay information in a surgically relevant field of view with a clinically accessible acquisition time <2 minutes. Analysis of DOCI revealed microscopic characterization sufficient for tissue type identification consistent with histology ( P < .05). DOCI is capable of efficiently distinguishing parathyroid tissue from adjacent tissues. Such an intraoperative tool would be transformative, helping surgeons to identify lesions, preserve healthy tissue, and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objectives To profile the clinical presentation and treatment results of esthesioneuroblastomas at the University of California, Los Angeles (UCLA), from 2002 to 2013. Design Retrospective review. Setting Tertiary academic institution. Participants Forty-one patients with esthesioneuroblastomas treated at UCLA. Main Outcome Measures Overall survival (OS) and recurrence-free survival (RFS). Results Thirty-six patients were included with a mean age of 50.1 years and a median duration of follow-up of 33 months. The 5-year RFS and OS were 54% and 82%, respectively. Modified Kadish stage was the only factor identified to affect OS. Multivariate analysis demonstrated that tumor grade was the only factor that had an independent impact on RFS. There was no statistical difference in survival among the surgical approaches chosen. Conclusions The updated data on the UCLA experience reveals that all three surgical approaches chosen provide comparable survival, although longer follow-up will be needed to ascertain if these findings hold true. The endoscopic approach had a statistically significant decrease in length of hospital stay and a trend toward reduced blood loss, intensive care unit admission, and complications. The modified Kadish staging was the only factor identified to predict OS. Multivariate analysis revealed that tumor grade was an independent predictor of recurrence; therefore, its importance should be emphasized in future staging systems. [ABSTRACT FROM AUTHOR]

Cancer, a major health problem, affects 12 million people worldwide every year. With surgery and chemo-radiation the long term survival rate for the majority of cancer patients is dismal. Thus novel treatments are urgently needed. Immunotherapy, the harnessing of the immune system to destroy cancer cells is an attractive option with potential for long term anti-tumor benefit. Cytokines are biological response modifiers that stimulate anti-tumor immune responses. In this review, we discuss the anti-tumor efficacy of the chemotactic cytokine CCL21 and its pre-clinical and clinical application in cancer. [ABSTRACT FROM AUTHOR]

Objectives: Pediatric laryngeal trauma is an uncommon event. The purpose of this study was to identify outcomes following surgical procedures for pediatric laryngeal trauma, and to provide an in-depth review of the literature. Methods: The National Trauma Data Bank was utilized to identify pediatric laryngeal trauma incidents with admission years 2002 through 2006. Patient demographics, injury type, surgical procedures, hospital and intensive care unit durations, ventilator duration, and discharge disposition were abstracted. Results: There were 69 laryngeal trauma incidents identified, with a median patient age of 12.8 years and an overall mortality rate of 8.7%. Laryngeal injury was frequently blunt-force in nature (82.8%) and often occurred in conjunction with trauma to multiple organ systems (76.8%). Tracheotomy (16 procedures), laryngeal suturing (13 procedures), and laryngeal fracture repair (10 procedures) were the most frequent procedures identified. Laryngeal fracture repair was noted to increase the overall hospital duration (p - 0.040). The communication scores were affected only by tracheotomy (p = 0.013). Surgical intervention did not significantly affect the frequency of home discharge. Conclusions: Pediatric laryngeal trauma is an uncommon event that can be evaluated with the National Trauma Data Bank. Although patients who undergo laryngeal fracture repair appear to have an increased duration of hospitalization, patients who undergo tracheotomy or laryngeal suturing do not have increased durations of ventilator dependence, stay in an intensive care unit, or hospitalization. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate a single-institutional experience with the use of re-irradiation for recurrent and new primary cancers of the head and neck.Methods: The medical charts of 80 consecutive patients who underwent re-irradiation for local-regionally recurrent or second primary head and neck cancer between November 1998 and December 2015 were analyzed. Multivariate analysis was performed using Cox proportional hazard and logistic regression to determine predictors of clinical outcomes.Results: Seventy-six of the 80 patients were evaluable. The median age was 57.5 (range 26.6-84.9); Intensity-modulated radiotherapy (IMRT) was used in 71 (93.4%) patients with a median dose of 60Gy. Thirty-one patients (40.8%) underwent salvage surgery before re-irradiation and 47 (61.8%) received concurrent systemic therapy. The median time interval between radiation courses was 25.3months (range 2-322months). The 2-year estimates of overall survival, progression free survival, locoregional control, and distant control were 51.0%, 31.3%, 36.8% and 68.3%, respectively. Patients who underwent salvage surgery prior to re-irradiation had significantly improved locoregional control, progression free survival, and overall survival (p<0.05, for all). On multivariate analysis, gross tumor volume (GTV) at re-irradiation and interval between radiation courses were associated with improved overall survival. Severe (grade⩾3) late complications were observed in 25 patients (32.8%).Conclusions: Re-irradiation for recurrent or second primary head and neck cancer is feasible and effective in select patients with head and neck cancer. The high observed rate of treatment-related morbidity highlights the continue challenges that accompany this approach. [ABSTRACT FROM AUTHOR]

Objective: To investigate the state and trajectory of gender, racial, and academic authorship diversity in the otolaryngology clinical trial literature over the past 2 decades., Study Design: Bibliometric analysis., Setting: Otolaryngology clinical trial literature., Methods: Clinical trials published in the 9 major otolaryngology journals between 2000 and 2020 were included. The gender, race, and academic seniority of the first, senior, and corresponding authors were recorded for each trial. Multivariable regression models assessed the temporal trajectory of authorship diversity over time and the disparity in citations across author characteristics. Models adjusted for relevant confounders pertaining to publication environment and study design., Results: Among 2117 trials, first, senior, and corresponding authors have been predominantly White (60%-64%), male (76%-80%), and attending physicians (63%-69%). Trials led by Black (<1%) and Hispanic (<5%) authors were severely underrepresented. Over time, the representation of female (adj. β 0.8%, 95% CI [0.5%, 1.1%] per year), Asian (1.0% [0.7%, 1.3%] per year), and MD resident (0.4% [0.1%, 0.7%] per year) first authorship increased, but representation of female (0.2% [-0.1%, 0.5%] per year), Black (0% [-0.03%, 0.02%] per year), Hispanic (-0.2% [-0.33%, -0.02%] per year) senior authorship remained persistently low. Asian-led trials were cited significantly less compared to White-led trials even after adjusting for study design and publication year (aIRR 0.82 [0.73, 0.92])., Conclusions: Despite promising signs of improving authorship diversity over time, persistent underrepresentation of female, Black, Hispanic senior authorship underscore the need for additional efforts to diversify the otolaryngology clinical science workforce., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)