RESUMO
Radiation therapy for head and neck cancer causes damage to the surrounding salivary glands, resulting in salivary gland hypofunction and xerostomia. Current treatments do not provide lasting restoration of salivary gland function following radiation; therefore, a new mechanistic understanding of the radiation-induced damage response is necessary for identifying therapeutic targets. The purpose of the present study was to investigate the metabolic phenotype of radiation-induced damage in parotid salivary glands by integrating transcriptomic and metabolomic data. Integrated data were then analyzed to identify significant gene-metabolite interactions. Mice received a single 5 Gy dose of targeted head and neck radiation. Parotid tissue samples were collected 5 days following treatment for RNA sequencing and metabolomics analysis. Altered metabolites and transcripts significantly converged on a specific region in the metabolic reaction network. Both integrative pathway enrichment using rank-based statistics and network analysis highlighted significantly coordinated changes in glutathione metabolism, energy metabolism (TCA cycle and thermogenesis), peroxisomal lipid metabolism, and bile acid production with radiation. Integrated changes observed in energy metabolism suggest that radiation induces a mitochondrial dysfunction phenotype. These findings validated previous pathways involved in the radiation-damage response, such as altered energy metabolism, and identified robust signatures in salivary glands, such as reduced glutathione metabolism, that may be driving salivary gland dysfunction.
Assuntos
Perfilação da Expressão Gênica/métodos , Neoplasias de Cabeça e Pescoço/radioterapia , Metabolômica/métodos , Lesões Experimentais por Radiação/genética , Glândulas Salivares/efeitos da radiação , Animais , Redes Reguladoras de Genes/efeitos da radiação , Humanos , Camundongos , Mapas de Interação de Proteínas/genética , Mapas de Interação de Proteínas/efeitos da radiação , Lesões Experimentais por Radiação/metabolismo , Glândulas Salivares/metabolismo , Glândulas Salivares/fisiopatologia , Transdução de Sinais/genética , Transdução de Sinais/efeitos da radiação , Xerostomia/genética , Xerostomia/metabolismo , Xerostomia/fisiopatologiaRESUMO
Purpose: The goals of this article are to explore the use of textured thin liquids for dysphagic patients who require thickened liquids and to illustrate their impact on hydration and patient satisfaction. Method: A retrospective evaluation of textured thin liquids was completed using patient data looking at laboratory values relevant to the detection of dehydration (blood urea nitrogen, creatinine, sodium) and patient satisfaction (using a clinician-generated questionnaire) on different modified liquid textures. In addition, the viscosity for all liquids was tested using a rheometer. Results: Measurements show that the viscosity of the textured thin liquids examined in this pilot study are significantly lower than the viscosity of nectar-thick liquids and fall within the "thin" category as defined by the National Dysphagia Diet guidelines. Patients on honey- and nectar-thick liquids had laboratory values signifying dehydration, whereas those receiving the textured thin liquid consistency were within the normal range for all laboratory values. Importantly, when consuming textured thin liquids, patients reported significant improvement in their satisfaction related to their thirst. Conclusion: The results of this pilot study highlight the consequences of common thickened liquid dietary recommendations and of the potentially beneficial clinical application of textured thin liquids for patients with dysphagia as well as the need for future prospective research.