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1.
Clin Otolaryngol ; 46(6): 1205-1212, 2021 11.
Article in English | MEDLINE | ID: mdl-34075701

ABSTRACT

INTRODUCTION: Several independent studies report an alarming increase in patients younger than 40 being diagnosed with squamous cell carcinoma. There is currently a lack of available data clearly tracking changes in the age distribution of head and neck cancer (HNC) within the United States. This study attempts to elucidate any trends in oral cavity, oropharynx, larynx and hypopharynx cancer age distribution in the United States population from 1975 to 2016. Unlike previous studies, this paper does not track incidence but rather reports proportional changes of prevalence within age cohorts over time. METHODS: This is a retrospective chart review centred on data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). Each decade interval from 1975 to 2016 displays the proportion of HNC patients, classified by primary tumour subsite, within each age cohort. RESULTS: Mean age at diagnosis increased for all subsites except oropharynx. Oropharyngeal cancer was the only subsite to show a decrease in the mean age at diagnosis. In addition, oropharyngeal cancer was the only subsite to demonstrate an overall increase in proportional prevalence, largely due to increased incidence in middle-age (40-59 years) patients. Cancers of the oral cavity were the only subset to show a true increase in the proportion of young (0-39 years) patients, but its mean age at diagnosis still increased. When stratifying by gender, the proportion of young patients in female HNC cases is higher than the young male proportion. CONCLUSION: Overall, this study demonstrates an increased proportion of older HNC patients that is consistent with the ageing population. Oral cavity cancer demonstrated a true increase in the proportion of young patients, likely due to the increased incidence of young women diagnosed with this cancer. Oropharyngeal cancer was the only subsite to show a decrease in the mean age at diagnosis. The increased proportion of middle-age patients with oropharyngeal cancer likely reflects the increase in HPV-related cancers.


Subject(s)
Head and Neck Neoplasms/epidemiology , Age Distribution , Aged , Female , Humans , Male , Middle Aged , Prevalence , Retrospective Studies , United States/epidemiology
2.
Int Forum Allergy Rhinol ; 11(8): 1152-1161, 2021 08.
Article in English | MEDLINE | ID: mdl-33527730

ABSTRACT

BACKGROUND: Asthma and some chronic rhinosinusitis (CRS) subtypes are mediated by similar pathophysiologic mechanisms. The purpose of this study was to evaluate the effects of biologic therapy for asthma on co-existent CRS in the "real-world" setting. METHODS: A review of electronic health records (2016-2019) at Mayo Clinic was conducted to identify asthma patients treated with biologics who had co-existent CRS. Matched-pair analyses compared pretherapy and posttherapy Lund-Mackay computed tomography (CT) scores and 22-item Sino-Nasal Outcome Test (SNOT-22) scores. Performance of endoscopic sinus surgery (ESS) after initiating biologics was studied. RESULTS: We identified 247 patients who received anti-asthma biologic therapy and had co-existent CRS. Of these, 181 patients (73.3%) had CRS with nasal polyposis (CRSwNP) and 66 (26.7%) had CRS without nasal polyposis (CRSsNP). The biologics utilized were omalizumab (51.0%), mepolizumab (46.6%), benralizumab (10.5%), reslizumab (1.6%), and dupilumab (2.4%). Anti-interleukin-5 (anti-IL-5) intervention was associated with significant improvement in CT scores (CRS overall, CRSwNP subgroup, CRSsNP subgroup) and SNOT-22 scores (CRS overall, CRSwNP subgroup). Patients on omalizumab had a decrease in CT scores, but not SNOT-22 scores. ESS was performed in 206 patients (84.1%); 55 (22.3%) underwent surgery post-biologic intervention (anti-IL-5: 16.5%; omalizumab 27.8% of patients). CONCLUSION: Anti-IL-5 agents were associated with improved CT and SNOT-22 scores in the overall CRS group and in CRSwNP subgroup; CRSsNP patients showed improved CT scores only. Omalizumab improved CT but not SNOT-22 scores. ESS was performed in 22% of patients after initiating biologics. These real-world results may influence future trial designs and clinical applications of biologics for CRS. ©2021 ARSAAOA, LLC.


Subject(s)
Asthma , Nasal Polyps , Rhinitis , Sinusitis , Asthma/drug therapy , Biological Therapy , Chronic Disease , Humans , Nasal Polyps/drug therapy , Nasal Polyps/surgery , Rhinitis/drug therapy , Rhinitis/surgery , Sinusitis/drug therapy , Sinusitis/surgery
3.
J Biol Chem ; 294(46): 17301-17313, 2019 11 15.
Article in English | MEDLINE | ID: mdl-31591264

ABSTRACT

A successful pregnancy is critically dependent upon proper placental development and function. During human placentation, villous cytotrophoblast (CTB) progenitors differentiate to form syncytiotrophoblasts (SynTBs), which provide the exchange surface between the mother and fetus and secrete hormones to ensure proper progression of pregnancy. However, epigenetic mechanisms that regulate SynTB differentiation from CTB progenitors are incompletely understood. Here, we show that lysine-specific demethylase 1 (LSD1; also known as KDM1A), a histone demethylase, is essential to this process. LSD1 is expressed both in CTB progenitors and differentiated SynTBs in first-trimester placental villi; accordingly, expression in SynTBs is maintained throughout gestation. Impairment of LSD1 function in trophoblast progenitors inhibits induction of endogenous retrovirally encoded genes SYNCYTIN1/endogenous retrovirus group W member 1, envelope (ERVW1) and SYNCYTIN2/endogenous retrovirus group FRD member 1, envelope (ERVFRD1), encoding fusogenic proteins critical to human trophoblast syncytialization. Loss of LSD1 also impairs induction of chorionic gonadotropin α (CGA) and chorionic gonadotropin ß (CGB) genes, which encode α and ß subunits of human chorionic gonadotrophin (hCG), a hormone essential to modulate maternal physiology during pregnancy. Mechanistic analyses at the endogenous ERVW1, CGA, and CGB loci revealed a regulatory axis in which LSD1 induces demethylation of repressive histone H3 lysine 9 dimethylation (H3K9Me2) and interacts with transcription factor GATA2 to promote RNA polymerase II (RNA-POL-II) recruitment and activate gene transcription. Our study reveals a novel LSD1-GATA2 axis, which regulates human trophoblast syncytialization.


Subject(s)
Cell Differentiation/genetics , GATA2 Transcription Factor/genetics , Histone Demethylases/genetics , Trophoblasts/metabolism , Chorionic Villi/growth & development , Chorionic Villi/metabolism , Epigenesis, Genetic/genetics , Female , Gene Expression Regulation, Developmental/genetics , Gene Products, env/genetics , Humans , Mother-Child Relations , Placentation/genetics , Pregnancy , Pregnancy Proteins/genetics , RNA Polymerase II/genetics , Signal Transduction/genetics
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