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.

Background: Epilepsy is a common disease in the pediatric population; accounting for most referrals to the Neurology Department. In Honduras there are few recent publications on the subject. Objective: To describe the clinical and sociodemographic characteristics of the patients with epilepsy in a national paediatric reference centre. Methods: retrospective descriptive study. Medical files of patients from the Pediatric Neurology outpatient clinic of the Hospital María, Especialidades Pediatricas (HMEP), Tegucigalpa, Honduras during May 2015 – March 2019 were used. Data analysis was done through descriptive statistics. Results: 334 patients were studied, with male population being the most frequently affected 55.7% (186), patients mostly came from an urban zone 69.5% (232), and median age was 7.3 years. A high proportion of patients 81.1% (271) were children of an unemployed mother and in 26.3% (88) of the total cases, the father was absent. Epilepsy etiology was unknown in 54.4% (182) of cases. In 26.3% (88) of patients, a family history of epilepsy was present. For patients with history of any perinatal event 50.6% (174/344), 24.7% (43/174) suffered birth asphyxia. Malnutrition was found in 32.7% (108/330) of subjects. Focal seizures were the most common type; crises were triggered mainly by treatment dropout. Some kind of disability was present in 36.6% (126) of patients, being cognitive disability the most relevant. Discussion: There is a need to strengthen public health strategies aimed at prenatal, natal and postnatal prevention of epilepsy, provide support to single-parent families and ensure continued access to health services.

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.