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1.
Cancer ; 117(13): 2926-38, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21692052

RESUMO

BACKGROUND: Tumor metabolism is an essential contributor to disease progression and response to treatment. An understanding of the metabolic phenotype of head and neck squamous cell carcinoma (HNSCC) will allow the development of appropriate antimetabolic strategies for this tumor type. METHODS: A panel of 15 HNSCC cell lines was assayed for glucose and glutamine dependence and sensitivity to metabolic inhibitors. In addition, broad-spectrum metabolomic analysis using mass spectrometry/liquid chromatography was combined with individual measurements of reducing potential, adenosine triphosphate, and lactate production to characterize cellular metabolic phenotypes. RESULTS: HNSCC energy and reducing potential levels closely mirrored extracellular glucose concentrations. Glucose starvation induced cell death despite the activation of secondary energetic pathways. Conversely, glutamine was not required for HNSCC survival and did not serve as a significant source of energy. 2-deoxyglucose (2-DG) and its fluorinated derivative decreased glycolytic and Krebs cycle activity, cellular energy, and reducing potential and inhibited HNSCC cell proliferation. 2-DG effects were potentiated by the addition of metformin, but not by inhibitors of the pentose phosphate pathway or glutaminolysis. Despite dependence on glucose catabolism, the authors identified a subset of cell lines with relative resistance to starvation. Exploration of 1 such cell line (HN30) suggested that the presence of wild-type p53 can partially protect tumor cells from glucose starvation. CONCLUSIONS: HNSCC tumor cells are dependent on glucose, not glutamine, for energy production and survival, providing a rationale for treatment strategies that target glucose catabolism. However, antimetabolic strategies may need to be tailored to the tumor background, more specifically, p53 status.


Assuntos
Glucose/metabolismo , Glutamina/metabolismo , Trifosfato de Adenosina/metabolismo , Carcinoma/metabolismo , Carcinoma de Células Escamosas , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Cromatografia Líquida , Desoxiglucose/farmacologia , Progressão da Doença , Genes p53 , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Ácido Láctico/metabolismo , Espectrometria de Massas , Metabolômica , Metformina/farmacologia , Neoplasias de Células Escamosas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Resultado do Tratamento , Proteína Supressora de Tumor p53/metabolismo
2.
WMJ ; 107(2): 62-8, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18593080

RESUMO

CONTEXT: Nonmelanoma skin cancer (NMSC) is the most common cancer among humans, yet risk perceptions and preventive health behaviors in those who survive this cancer are relatively unknown. OBJECTIVES: To assess the impact of the disease and its treatment on sun-protective behaviors, general preventive health behaviors, and risk perception in NMSC patients, and to determine factors associated with behavioral change. DESIGN AND SETTING: A prospective study was conducted of 211 consecutive NMSC patients presenting to a dermatologic surgery clinic at a tertiary care university medical center from February 2005 to March 2006. These patients were all adults, were fluent in English, and had NMSC of the head and neck. Of the 211 eligible patients, complete data was obtained for 183 (87%). The most common reasons for dropout were voluntary withdrawal and incompletely answered surveys. INTERVENTION AND OUTCOME MEASURES: Surveys that assessed disease-specific quality of life (QoL), preventive health behaviors, sun-protective behaviors, and risk perception were administered before and after surgical treatment of NMSC. RESULTS: Sun-protective behaviors improved postsurgery even after controlling for seasons (P<0.001). Predictor factors associated with increased sun-protective behavior included poor skin tanning ability, summer season, no employment, less comorbid conditions, and previous NMSC treatment. Baseline QoL was not predictive of behavioral change. As for risk perception, respondents thought they were more likely than someone similar to themselves to develop future NMSCs but thought they had similar risks of developing melanoma or other non-skin cancers (P<0.001). NMSC patients demonstrated disease-specific behavior modifications by selectively improving their sun habits but showed no significant improvement in other preventive health behaviors. This finding is consistent with patients' specific perception of increased risk for future NMSCs, but surprisingly, not for melanoma. Increased patient education of associated cancer risks with NMSC is warranted. CONCLUSIONS: NMSC patients demonstrated disease-specific behavior modifications by selectively improving their sun habits but showed no significant improvement in other preventive health behaviors. This finding is consistent with patients' specific perception of increased risk for future NMSCs, but surprisingly, not for melanoma. Increased patient education of associated cancer risks with NMSC is warranted.


Assuntos
Terapia Comportamental , Carcinoma Basocelular/prevenção & controle , Carcinoma Basocelular/psicologia , Comportamentos Relacionados com a Saúde , Percepção , Risco , Neoplasias Cutâneas/prevenção & controle , Neoplasias Cutâneas/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Queimadura Solar/prevenção & controle
3.
Head Neck ; 37(8): 1116-21, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24764188

RESUMO

BACKGROUND: Sentinel lymph node biopsy remains controversial for cutaneous melanoma of the head and neck (CMHN). Incidence and factors associated with recurrence after negative sentinel lymph node biopsy have not been well delineated. METHODS: Characteristics of 204 patients with head and neck melanoma who had a negative sentinel lymph node biopsy were studied. Main outcomes were overall survival and disease-free survival. RESULTS: Recurrence developed in 45 patients (22%) with a median time to recurrence of 20.1 months. Five-year overall survival was 91.8% for patients without recurrence and 57.0% for those with recurrence. The overall regional recurrence rate was 8.8% (n = 18) and was associated with Breslow thickness >2 mm and scalp location of the primary tumor. The false omission rate was 3.4%. CONCLUSION: For CMHN, regional recurrence after negative sentinel lymph node biopsy occurs at acceptably low rates relative to other sites, although it is associated with adverse survival.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Melanoma/cirurgia , Recidiva Local de Neoplasia/cirurgia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Procedimentos Cirúrgicos Dermatológicos/métodos , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Resultado do Tratamento
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