318 research outputs found

    A lean neck mass clinic model: Adding value to care

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/115945/1/lary25535.pd

    Does drugā€induced sleep endoscopy predict surgical success in transoral robotic multilevel surgery in obstructive sleep apnea?

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136419/1/lary26255_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136419/2/lary26255.pd

    The molecular landscape of the University of Michigan laryngeal squamous cell carcinoma cell line panel

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    BackgroundLaryngeal squamous cell carcinomas (LSCCs) have a high risk of recurrence and poor prognosis. Patientā€derived cancer cell lines remain important preclinical models for advancement of new therapeutic strategies, and comprehensive characterization of these models is vital in the precision medicine era.MethodsWe performed exome and transcriptome sequencing as well as copy number analysis of a panel of LSCCā€derived cell lines that were established at the University of Michigan and are used in laboratories worldwide.ResultsWe observed a complex array of alterations consistent with those reported in The Cancer Genome Atlas head and neck squamous cell carcinoma project, including aberrations in PIK3CA, EGFR, CDKN2A, TP53, and NOTCH family and FAT1 genes. A detailed analysis of FAT family genes and associated pathways showed disruptions to these genes in most cell lines.ConclusionsThe molecular profiles we have generated indicate that as a whole, this panel recapitulates the molecular diversity observed in patients and will serve as useful guides in selecting cell lines for preclinical modeling.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151290/1/hed25803.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151290/2/hed25803_am.pd

    Human papillomavirusā€“related oropharyngeal cancer: HPV and p16 status in the recurrent versus parent tumor

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    Background Although typically associated with a favorable prognosis, a minority of human papillomavirus (HPV)ā€related (+) oropharyngeal cancers recur after chemoradiation. We postulated that a minor HPVā€negative tumor subfraction may be responsible for recurrences of HPV+ oropharyngeal cancer. Methods Paired untreated primary and recurrent tumor specimens were identified for 37 patients with oropharyngeal cancer who received definitive chemoradiotherapy at our institution. Concordance in HPV/p16 expression between primary and recurrent tumors was assessed. Results Among 31 patients with HPV+/p16+ primary tumors, 30 (97%) retained evidence of both HPV and p16 expression at recurrence (27 HPV+/p16+; 3 HPV+/p16ā€partial). One (3%) initially HPV+/p16+ patient developed an HPVā€negative/p16ā€negative lung squamous cell carcinoma (SCC), representing either a discordant oropharyngeal cancer metastasis or second primary tumor. Conclusion HPVā€related oropharyngeal cancers retain HPV+/p16+ expression at recurrence. Our results fail to provide evidence that a minor HPVā€negative tumor subfraction is responsible for biologically aggressive behavior of HPV+ oropharyngeal cancer that recurs after chemoradiation. Ā© 2014 Wiley Periodicals, Inc. Head Neck 37 : 8ā€“11, 2015Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109811/1/hed23548.pd

    Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma

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    BackgroundCancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.MethodsWound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44high and aldehyde dehydrogenase [ALDH]+) and assess mobility, tumorigenesis, and metastasis. A prospective collection of 40 patientā€derived primary HNSCC specimens were analyzed for CSCā€proportion compared to clinical variables.ResultsCSCs exhibited significantly faster wound closure and greater tumorigenesis and regional metastasis in vivo than nonā€CSCs. In primary patient tumors, size and advanced stage were correlated with elevated proportion of CSCs, however, not with survival.ConclusionHNSCC stem cells mediate tumorigenesis and regional metastasis in vivo. In primary patient tumors, CSCā€proportion was associated with tumor size and stage, but not with metastatic spread or survival. CSC burden alone may only represent a minor variable in understanding CSCs and metastasis. Ā© 2014 Wiley Periodicals, Inc. Head Neck 37: 317ā€“326, 2015Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110728/1/hed23600.pd

    Individualized outcome prognostication for patients with laryngeal cancer

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142424/1/cncr31087.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142424/2/cncr31087_am.pd

    Signatures of early frailty in the gut microbiota

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    Background: Frailty is arguably the biggest problem associated with population ageing, and associates with gut microbiome composition in elderly and care-dependent individuals. Here we characterize frailty associations with the gut microbiota in a younger community dwelling population, to identify targets for intervention to encourage healthy ageing. Method: We analysed 16S rRNA gene sequence data derived from faecal samples obtained from 728 female twins. Frailty was quantified using a frailty index (FI). Mixed effects models were used to identify associations with diversity, operational taxonomic units (OTUs) and taxa. OTU associations were replicated in the Eldermet cohort. Phenotypes were correlated with modules of OTUs collapsed by co-occurrence. Results: Frailty negatively associated with alpha diversity of the gut microbiota. Models considering a number of covariates identified 637 OTUs associated with FI. Twenty-two OTU associations were significant independent of alpha diversity. Species more abundant with frailty included Eubacterium dolichum and Eggerthella lenta. A Faecalibacterium prausnitzii OTU was less abundant in frailer individuals, and retained significance in discordant twin analysis. Sixty OTU associations were replicated in the Eldermet cohort. OTU co-occurrence modules had mutually exclusive associations between frailty and alpha diversity. Conclusions: There was a striking negative association between frailty and gut microbiota diversity, underpinned by specific taxonomic associations. Whether these relationships are causal or consequential is unknown. Nevertheless, they represent targets for diagnostic surveillance, or for intervention studies to improve vitality in ageing

    COVID- 19 pandemic and health care disparities in head and neck cancer: Scanning the horizon

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    The COVID- 19 pandemic has profoundly disrupted head and neck cancer (HNC) care delivery in ways that will likely persist long term. As we scan the horizon, this crisis has the potential to amplify preexisting racial/ethnic disparities for patients with HNC. Potential drivers of disparate HNC survival resulting from the pandemic include (a) differential access to telemedicine, timely diagnosis, and treatment; (b) implicit bias in initiatives to triage, prioritize, and schedule HNC- directed therapy; and (c) the marked changes in employment, health insurance, and dependent care. We present four strategies to mitigate these disparities: (a) collect detailed data on access to care by race/ethnicity, income, education, and community; (b) raise awareness of HNC disparities; (c) engage stakeholders in developing culturally appropriate solutions; and (d) ensure that surgical prioritization protocols minimize risk of racial/ethnic bias. Collectively, these measures address social determinants of health and the moral imperative to provide equitable, high- quality HNC care.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156210/2/hed26345.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156210/1/hed26345_am.pd
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