Autophagy Inhibition with Chloroquine Increased Pro-Apoptotic Potential of New Aziridine-Hydrazide Hydrazone Derivatives against Glioblastoma Cells.

Tumor therapy escape due to undesired side effects induced by treatment, such as prosurvival autophagy or cellular senescence, is one of the key mechanisms of resistance that eventually leads to tumor dormancy and recurrence. Glioblastoma is the most frequent and practically incurable neoplasm of the central nervous system; thus, new treatment modalities have been investigated to find a solution more effective than the currently applied standards based on temozolomide. The present study examined the newly synthesized compounds of aziridine-hydrazide hydrazone derivatives to determine their antineoplastic potential against glioblastoma cells in vitro. Although the output of our investigation clearly demonstrates their proapoptotic activity, the cytotoxic effect appeared to be blocked by treatment-induced autophagy, the phenomenon also detected in the case of temozolomide action. The addition of an autophagy inhibitor, chloroquine, resulted in a significant increase in apoptosis triggered by the tested compounds, as well as temozolomide. The new aziridine-hydrazide hydrazone derivatives, which present cytotoxic potential against glioblastoma cells comparable to or even higher than that of temozolomide, show promising results and, thus, should be further investigated as antineoplastic agents. Moreover, our findings suggest that the combination of an apoptosis inducer with an autophagy inhibitor could optimize chemotherapeutic efficiency, and the addition of an autophagy inhibitor should be considered as an optional adjunctive therapy minimizing the risk of tumor escape from treatment.

Association of anxiety sensitivity-physical concerns and FVC with dyspnea severity in sarcoidosis.

OBJECTIVE: The purpose of the study was to evaluate the relationship of an objective functional lung parameter (FVC) and a subjective psychological factor (physical symptom concerns) with dyspnea in sarcoidosis. Dyspnea constitutes one of the most common and burdensome symptoms in sarcoidosis, yet little is known about its mechanisms and, in particular, psychological. METHOD: A total of 107 hospitalized sarcoidosis patients (Female=50, Mage=45.3years) volunteered to take part in the correlational research study. Participants underwent spirometry and completed the MRC Dyspnea Scale and the Anxiety Sensitivity Index-3 (ASI) questionnaire. Linear hierarchical regression analysis was used to determine the relationship between the studied predictors and dyspnea severity. RESULTS: The best fitting model predicted 18% of variance in dyspnea severity. Physical symptom concerns subscale of ASI (ß=0.24) and FVC (ß=-0.23) were significantly related to dyspnea MRC severity, but only physical concerns remained significantly related to dyspnea when both predictors were in the model. CONCLUSIONS: The current results suggest that both psychological and physiological factors should be taken into account when explaining subjective dyspnea severity in sarcoidosis. More specifically, these findings call for including cognitive vulnerability factors related to anxiety (physical symptom concerns) into the diagnostic procedures and management of dyspnea in sarcoidosis.