Dataset Information

Cigarette use, comorbidities, and prognosis in a prospective head and neck squamous cell carcinoma population.

ABSTRACT: BACKGROUND:To better understand the associations between a history of tobacco use and survival outcomes, cigarette use was prospectively surveyed in 687 previously untreated patients with cancer of the oral cavity (n = 271), oropharynx (n = 257), larynx (n = 135), or hypopharynx (n = 24). METHODS:Kaplan-Meier and Cox models explored the associations of tobacco use intensity (packs/day), duration (years of use), and timing before diagnosis with overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). RESULTS:Cigarette use duration, timing, and intensity were significant predictors for all outcomes in univariate analysis. Never smoking and pack-years were not significantly associated with outcomes after adjustment for prognostic factors, such as stage, comorbidities, and human papillomavirus (HPV) status, which were strongly associated with clinical outcomes. CONCLUSION:The findings confirm the association between smoking history and survival and the importance of clinical variables in evaluating smoking as a prognostic factor. Timing, intensity, and duration of cigarette use should be considered with other prognostic factors when considering risk stratification for treatment planning. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1810-1820, 2016.

SUBMITTER: Peterson LA

PROVIDER: S-EPMC5391974 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Cigarette use, comorbidities, and prognosis in a prospective head and neck squamous cell carcinoma population.

Peterson Lisa A LA Bellile Emily L EL Wolf Gregory T GT Virani Shama S Shuman Andrew G AG Taylor Jeremy M G JM Rozek Laura S LS

Head & neck 20160719 12

<h4>Background</h4>To better understand the associations between a history of tobacco use and survival outcomes, cigarette use was prospectively surveyed in 687 previously untreated patients with cancer of the oral cavity (n = 271), oropharynx (n = 257), larynx (n = 135), or hypopharynx (n = 24).<h4>Methods</h4>Kaplan-Meier and Cox models explored the associations of tobacco use intensity (packs/day), duration (years of use), and timing before diagnosis with overall survival (OS), disease-specif ...[more]

PMID: 27432208

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Project description:Head and neck squamous cell carcinoma (HNSCC) is comprised of metabolically linked distinct compartments. Cancer-associated fibroblasts (CAF) and nonproliferative carcinoma cells display a glycolytic metabolism, while proliferative carcinoma cells rely on mitochondrial oxidative metabolism fueled by the catabolites provided by the adjacent CAFs. Metabolic coupling between these reprogrammed compartments contributes to HNSCC aggressiveness. In this study, we examined the effects of cigarette smoke-exposed CAFs on metabolic coupling and tumor aggressiveness of HNSCC. Cigarette smoke (CS) extract was generated by dissolving cigarette smoke in growth media. Fibroblasts were cultured in CS or control media. HNSCC cells were cocultured in vitro and coinjected in vivo with CS or control fibroblasts. We found that CS induced oxidative stress, glycolytic flux and MCT4 expression, and senescence in fibroblasts. MCT4 upregulation was critical for fibroblast viability under CS conditions. The effects of CS on fibroblasts were abrogated by antioxidant treatment. Coculture of carcinoma cells with CS fibroblasts induced metabolic coupling with upregulation of the marker of glycolysis MCT4 in fibroblasts and markers of mitochondrial metabolism MCT1 and TOMM20 in carcinoma cells. CS fibroblasts increased CCL2 expression and macrophage migration. Coculture with CS fibroblasts also increased two features of carcinoma cell aggressiveness: resistance to cell death and enhanced cell migration. Coinjection of carcinoma cells with CS fibroblasts generated larger tumors with reduced apoptosis than control coinjections, and upregulation of MCT4 by CS exposure was a driver of these effects. We demonstrate that a tumor microenvironment exposed to CS is sufficient to modulate metabolism and cancer aggressiveness in HNSCC. IMPLICATIONS: CS shifts cancer stroma toward glycolysis and induces head and neck cancer aggressiveness with a mitochondrial profile linked by catabolite transporters and oxidative stress. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/17/9/1893/F1.large.jpg.

Dataset Information

Cigarette use, comorbidities, and prognosis in a prospective head and neck squamous cell carcinoma population.

Publications

Cigarette use, comorbidities, and prognosis in a prospective head and neck squamous cell carcinoma population.

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