Mitotic Spindle Apparatus Abnormalities in Chronic Obstructive Pulmonary Disease Cells: A Potential Pathway to Lung Cancer.

Chronic obstructive pulmonary disease (COPD) is a long-term lung disease characterized by irreversible lung damage resulting in airflow limitation, abnormal permanent air-space enlargement, and emphysema. Cigarette smoking is the major cause of COPD with 15% to 30% of smokers developing either disease. About 50% to 80% of patients with lung cancer have preexisting COPD and smokers who have COPD are at an increased risk for developing lung cancer. Therefore, COPD is considered an independent risk for lung cancer, even after adjusting for smoking. A crucial early event in carcinogenesis is the induction of the genomic instability through alterations in the mitotic spindle apparatus. To date, the underlying mechanism by which COPD contributes to lung cancer risk is unclear. We hypothesized that tobacco smoke carcinogens induce mitotic spindle apparatus abnormalities and alter expression of crucial genes leading to increased genomic instability and ultimately tumorigenesis. To test our hypothesis, we assessed the genotoxic effects of a potent tobacco-smoke carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, (NNK)] on bronchial epithelial cells from patients with COPD and normal bronchial epithelial cells and identified genes associated with mitotic spindle defects and chromosome missegregation that also overlap with lung cancer. Our results indicate that exposure to NNK leads to a significantly altered spindle orientation, centrosome amplification, and chromosome misalignment in COPD cells as compared with normal epithelial cells. In addition, we identified several genes (such as AURKA, AURKB, and MAD2L2) that were upregulated and overlap with lung cancer suggesting a potential common pathway in the transition from COPD to lung cancer.

[Clinical profile of pediatric patients diagnosed with food allergy in Northwestern Mexico]. / Perfil clínico de pacientes pediátricos con diagnóstico de alergia alimentaria en el noroeste de México.

BACKGROUND: Food allergy is an adverse reaction secondary to a specific immune response after exposure to a food. Knowing the natural course of food allergies is essential for opportune diagnosis and treatment. OBJECTIVE: To know the clinical profile of children diagnosed with food allergy attended to at the pediatric allergology department of a secondary care hospital. METHODS: Cross-sectional study of medical records of children with a confirmed diagnosis of food allergy. The type of food allergy, initial clinical presentation, history of familial atopy, time of breastfeeding, ablactation age and positive food allergens per patient, among others, were assessed. Descriptive analysis was performed and association was searched with the chi-square test. RESULTS: Females were predominant among 95 patients. Milk, soy, wheat and egg were the foods with more allergic responses. Predominant clinical manifestations were gastrointestinal. The time from symptoms' onset to definitive diagnosis was 3.2 years. Food allergy was associated with an ablactation age ≥ 6 months, milk and soy with respiratory and gastrointestinal symptoms, egg with respiratory and dermatological symptoms, and wheat with gastrointestinal symptoms. CONCLUSIONS: Food allergies in our population appeared mainly as gastrointestinal symptoms and there was an association between clinical presentation and allergenic foods.

Antecedentes: La alergia alimentaria es una reacción adversa secundaria a una respuesta inmune específica tras la exposición a un alimento. Conocer el curso natural de las alergias alimentarias es esencial para el diagnóstico y tratamiento oportunos. Objetivo: Conocer el perfil clínico de niños con diagnóstico de alergia alimentaria, atendidos en el servicio de alergología pediátrica de un hospital de segundo nivel. Métodos: Estudio transversal de expedientes de niños con diagnóstico confirmado de alergia alimentaria. Se estudió tipo de alergia alimentaria, cuadro clínico inicial, antecedentes de atopia familiar, tiempo de alimentación al seno materno, edad de ablactación, alimentos alérgenos positivos por paciente, entre otros. Se realizó análisis descriptivo y búsqueda de asociación con chi cuadrada. Resultados: De 95 pacientes estudiados, predominaron las mujeres. Leche, soya, trigo y huevo fueron los alimentos con más respuestas alérgicas. Las manifestaciones clínicas más comunes fueron gastrointestinales. El tiempo de inicio de los síntomas al diagnóstico definitivo fue de 3.2 años. La alergia alimentaria se asoció con edad de ablactación ≥ 6 meses; leche y soya con sintomatología respiratoria y gastrointestinal, huevo con respiratoria y dermatológica y trigo con gastrointestinal. Conclusiones: Las alergias alimentarias se manifestaron principalmente con síntomas gastrointestinales y existió asociación entre cuadro clínico y alimentos alérgenos.

Glutamine Transporters Are Targets of Multiple Oncogenic Signaling Pathways in Prostate Cancer.

Despite the known importance of androgen receptor (AR) signaling in prostate cancer, the processes downstream of AR that drive disease development and progression remain poorly understood. This knowledge gap has thus limited the ability to treat cancer. Here, it is demonstrated that androgens increase the metabolism of glutamine in prostate cancer cells. This metabolism was required for maximal cell growth under conditions of serum starvation. Mechanistically, AR signaling promoted glutamine metabolism by increasing the expression of the glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in prostate cancer. Correspondingly, gene expression signatures of AR activity correlated with SLC1A4 and SLC1A5 mRNA levels in clinical cohorts. Interestingly, MYC, a canonical oncogene in prostate cancer and previously described master regulator of glutamine metabolism, was only a context-dependent regulator of SLC1A4 and SLC1A5 levels, being unable to regulate either transporter in PTEN wild-type cells. In contrast, rapamycin was able to decrease the androgen-mediated expression of SLC1A4 and SLC1A5 independent of PTEN status, indicating that mTOR complex 1 (mTORC1) was needed for maximal AR-mediated glutamine uptake and prostate cancer cell growth. Taken together, these data indicate that three well-established oncogenic drivers (AR, MYC, and mTOR) function by converging to collectively increase the expression of glutamine transporters, thereby promoting glutamine uptake and subsequent prostate cancer cell growth.Implications: AR, MYC, and mTOR converge to increase glutamine uptake and metabolism in prostate cancer through increasing the levels of glutamine transporters. Mol Cancer Res; 15(8); 1017-28. ©2017 AACR.