Perturbation of Copper Homeostasis Sensitizes Cancer Cells to Elevated Temperature.

Temporary elevation of tumor temperature, also known as hyperthermia, is a safe and well-tolerated treatment modality. The efficacy of hyperthermia can be improved by efficient thermosensitizers, and various candidate drugs, including inhibitors of the heat stress response, have been explored in vitro and in animal models, but clinically relevant thermosensitizers are lacking. Here, we employ unbiased in silico approaches to uncover new mechanisms and compounds that could be leveraged to increase the thermosensitivity of cancer cells. We then focus on elesclomol, a well-performing compound, which amplifies cell killing by hyperthermia by 5- to 20-fold in cell lines and outperforms clinically applied chemotherapy when combined with hyperthermia in vitro. Surprisingly, our findings suggest that the thermosensitizing effects of elesclomol are independent of its previously reported modes of action but depend on copper shuttling. Importantly, we show that, like elesclomol, multiple other copper shuttlers can thermosensitize, suggesting that disturbing copper homeostasis could be a general strategy for improving the efficacy of hyperthermia.

Signatures of cochlear processing in neuronal coding of auditory information.

The vertebrate ear is endowed with remarkable perceptual capabilities. The faintest sounds produce vibrations of magnitudes comparable to those generated by thermal noise and can nonetheless be detected through efficient amplification of small acoustic stimuli. Two mechanisms have been proposed to underlie such sound amplification in the mammalian cochlea: somatic electromotility and active hair-bundle motility. These biomechanical mechanisms may work in concert to tune auditory sensitivity. In addition to amplitude sensitivity, the hearing system shows exceptional frequency discrimination allowing mammals to distinguish complex sounds with great accuracy. For instance, although the wide hearing range of humans encompasses frequencies from 20 Hz to 20 kHz, our frequency resolution extends to one-thirtieth of the interval between successive keys on a piano. In this article, we review the different cochlear mechanisms underlying sound encoding in the auditory system, with a particular focus on the frequency decomposition of sounds. The relation between peak frequency of activation and location along the cochlea - known as tonotopy - arises from multiple gradients in biophysical properties of the sensory epithelium. Tonotopic mapping represents a major organizational principle both in the peripheral hearing system and in higher processing levels and permits the spectral decomposition of complex tones. The ribbon synapses connecting sensory hair cells to auditory afferents and the downstream spiral ganglion neurons are also tuned to process periodic stimuli according to their preferred frequency. Though sensory hair cells and neurons necessarily filter signals beyond a few kHz, many animals can hear well beyond this range. We finally describe how the cochlear structure shapes the neural code for further processing in order to send meaningful information to the brain. Both the phase-locked response of auditory nerve fibers and tonotopy are key to decode sound frequency information and place specific constraints on the downstream neuronal network.

The Effects of Heat Stress on the Transcriptome of Human Cancer Cells: A Meta-Analysis.

Hyperthermia is clinically applied cancer treatment in conjunction with radio- and/or chemotherapy, in which the tumor volume is exposed to supraphysiological temperatures. Since cells can effectively counteract the effects of hyperthermia by protective measures that are commonly known as the heat stress response, the identification of cellular processes that are essential for surviving hyperthermia could lead to novel treatment strategies that improve its therapeutic effects. Here, we apply a meta-analytic approach to 18 datasets that capture hyperthermia-induced transcriptome alterations in nine different human cancer cell lines. We find, in line with previous reports, that hyperthermia affects multiple processes, including protein folding, cell cycle, mitosis, and cell death, and additionally uncover expression changes of genes involved in KRAS signaling, inflammatory responses, TNF-a signaling and epithelial-to-mesenchymal transition (EMT). Interestingly, however, we also find a considerable inter-study variability, and an apparent absence of a 'universal' heat stress response signature, which is likely caused by the differences in experimental conditions. Our results suggest that gene expression alterations after heat stress are driven, to a large extent, by the experimental context, and call for a more extensive, controlled study that examines the effects of key experimental parameters on global gene expression patterns.

Estado nutricional de pacientes diagnosticados con cáncer, Hospital General San Felipe, Honduras / Nutritional assessment of cancer patients at Hospital General San Felipe, Honduras

Los pacientes diagnosticados con cáncer están en riesgo de malnutrición debido al efecto físico o metabólico de la enfermedad y a las terapias utilizadas en su manejo. La pérdida de peso y la malnutrición, son problemas frecuentes que afectan del 40% al 80% de los pacientes con cáncer, prolongando la estadía hospitalaria, disminuyendo la tolerancia y respuesta a la terapia, encareciendo los costos, afectando la calidad y sobrevida global. Objetivo: evaluar el estado nutricional y el riesgo de desnutrirse en pacientes diagnosticados con cáncer en el Hospital General San Felipe. Material y Métodos: estudio descriptivo, transversal, no aleatorizado, en 100 pacientes oncológicos adultos en los que se determinó los datos generales, sintomatología, hábitos tóxicos, comorbilidades, medidas antropométricas, índice de masa corporal y rendimiento físico. Se aplicó el instrumento de la Valoración Global Subjetiva Generada por el Paciente. Resultados: de los 100 casos estudiados 80 fueron mujeres y 20 hombres, los tipos de cáncer más frecuentes fueron: de mama, genital femenino, esófago-gástrico y colo-rectal; la mayoría presentaron síntomas de impacto nutricional. El uso de alcohol y tabaco fue 18% y 11% respectivamente. La hipertensión arterial y la diabetes mellitus fueron las comorbilidades más frecuentes; 48% presentaron índice de masa corporal en rango normal, 14% bajo peso y 38% sobrepeso. Según la Escala del Grupo Oncológico Cooperativo del Este 47% presentaron estado funcional normal y el 53% se encontró cierto grado de afectación. Al aplicarse el instrumento para Valoración Global Subjetiva, 55% de los 100 casos perdieron peso en los últimos 6 meses y 63% en el último mes. De acuerdo a la escala de reconocimiento físico global 59 pacientes mostraron déficit de peso, la evaluación del tejido graso y muscular mostró déficit en más de la mitad de los casos, 60% de los pacientes estaban moderada a severamente malnutridos y el riesgo de desnutrirse fue del 90%. Conclusión: la condición nutricional está afectada en más de la mitad de los casos y el riesgo de desnutrirse está presente en la mayoría de los pacientes oncológicos.

Caracterización de los factores de riesgo cardiovascular para infarto agudo de miocardio en población Garífuna / Characterization of cardiovascular risk factors for myocardial acute infarction in a Garifuna Population

RESUMEN Introducción. La enfermedad cardiovascular se caracteriza por una etiología multifactorial, siendo los factores de riesgos generalmente potenciados entre sí y con frecuencia asociados. Se tuvo como objetivo, caracterizar los factores de riesgo cardiovascular para infarto agudo de miocardio en una población de raza Garifuna, tomando en cuenta factores de riesgo modificables y no modificables. Los resultados de este estudio, facilitarán la creación de programas de intervención para prevención de enfermedades cardiovasculares y la disminución de factores de riesgo en la población de Ciriboya y/o poblaciones similares. Métodos. Se realizó una investigación cuantitativa de tipo observacional, descriptivo, de corte transversal. La muestra fue conformada por 139 personas, calculada con un nivel de confianza del 95%, seleccionadas mediante un muestreo de tipo probabilístico aleatorio. Se utilizó la Encuesta de la Asociación Colombiana de Cardiología como instrumento de recolección de datos, la cual asigna puntaje a los factores de riesgo según su magnitud; se aplicó casa por casa a los miembros del hogar en el rango etario estudiado. Resultados. Se encontró que 67% de los encuestados presenta riesgo cardiovascular; de las mujeres encuestadas, 64% presenta riesgo, mientras que 71% de los hombres presenta riesgo. Los factores de riesgo con mayor prevalencia son sobrepeso (58%), antecedente familiar de hipertensión arterial (43%), antecedente familiar de diabetes mellitus (35%) e hipertensión arterial diagnosticada (32%). Conclusiones. En la población estudiada los hombres poseen mayor riesgo cardiovascular que las mujeres. Entre los factores de riesgo el más significativo fue sobrepeso.

ABSTRACT Introduction. Cardiovascular disease is characterized by a multifactorial etiology, with risk factors generally being strengthened among themselves and frequently associated. The objective of this study was to characterize cardiovascular risk factors for acute myocardial infarction in a Garifuna population, taking into account modifiable and non-modifiable risk factors. The results of this study will facilitate the creation of intervention programs for the prevention of cardiovascular diseases and the reduction of risk factors in the population of Ciriboya and / or similar populations. Methods. A quantitative observational, descriptive, cross - sectional study was performed. The sample consisted of 139 individuals, calculated with a confidence level of 95%, selected by random probabilistic sampling. The Colombian Cardiology Association Survey was used as a data collection instrument, which assigns scores to the risk factors according to their magnitude; Was applied house to house to the members of the household in the studied age range. Results. It was found that 67% of the respondents presented cardiovascular risk; Of the women surveyed, 64% are at risk, while 71% of men are at risk. The most prevalent risk factors were overweight (58%), family history of hypertension (43%), family history of diabetes mellitus (35%) and diagnosed hypertension (32%). Conclusions. In the studied population, men have a higher cardiovascular risk than women. Among the risk factors the most significant was overweight.