Telomerase is known to contribute to telomere maintenance and to provide cancer cell immortality. However, numerous reports are showing that the function of the enzyme goes far beyond chromosome ends. The study aimed to explore how telomerase downregulation in MCF7 and MDA-MB-231 breast cancer cells affects their ability to survive. Consequently, sensitivity to drug resistance, proliferation, and adhesion were assessed. The lentiviral-mediated human telomerase reverse transcriptase (hTERT) downregulation efficiency was performed at gene expression and protein level using qPCR and Western blot, respectively. Telomerase activity was evaluated using the Telomeric Repeat Amplification Protocol (TRAP) assay. The study revealed that hTERT downregulation led to an increased sensitivity of breast cancer cells to doxorubicin which was demonstrated in MTT and clonogenic assays. During a long-term doubling time assessment, a decreased population doubling level was observed. Interestingly, it did not dramatically affect cell cycle distribution. hTERT downregulation was accompanied by an alteration in β1-integrin- and by focal adhesion kinase (FAK)-driven pathways together with the reduction of target proteins phosphorylation, i.e., paxillin and c-Src. Additionally, autophagy activation was observed in MDA-MB-231 cells manifested by alternations in Atg5, Beclin 1, LC3II/I ratio, and p62. These results provide new evidence supporting the possible therapeutic potential of telomerase downregulation leading to induction of autophagy and cancer cells elimination.
Remote monitoring (RM) of cardiac implantable electronic devices for adults offers improved treatment efficacy and, consequently, better patient clinical outcomes. There is scant data on the value and prognosis of RM in the pediatric population. The goal of this study was to determine the efficacy of RM by analyzing the connectivity of bedside transmitters, adherence to planned automatic follow-ups, and occurrence of alert-based events. We evaluated the pediatric population with implanted pacemakers for congenital AV block or after surgically corrected congenital heart diseases. A total of 69 patients were included in our study. The median (Q1-Q3) patient age was 6.0 (2.0-11.0) years. All patients received bedside transmitters and were enrolled in the RM system. Among them, 95.7% of patients had their first scheduled follow-up successfully sent. Patients were followed up remotely over a median time of 33.0 (13-45) months. Only 42% of patients were continuously monitored, and all scheduled transmissions were delivered on time. Further analysis revealed that 34.8% of patients missed transmissions between June and September (holiday season). Alert-based events were observed in 40.6% patients, mainly related to epicardial lead malfunction and arrhythmic events. Overall compliance was also compromised by socioeconomic factors. Our findings are in concordance with recently published results by PACES regarding a high level of compliance in patient enrollment to RM and time to initial transmission. However, a lower level of adherence was observed during the holiday season due to interrupted connectivity of bedside transmitters. Importantly, a relatively low occurrence of alert transmissions was observed, mainly related to epicardial lead malfunction and arrhythmic events.
Due to distressing statistics concerning cardiovascular diseases, remote monitoring of cardiac implantable electronic devices (CIED) has received a priority recommendation in daily patient care. However, most bedside systems available so far are not optimal due to limited patient adherence. We report that smartphone app technology communicating with CIED improved the patient’s engagement and adherence, as well as the accuracy of atrial and ventricular arrhythmias diagnosis, thus offering more efficient treatment and, consequently, better patient clinical outcomes. Our findings are in concordance with previously published results for implantable loop recorders and pacemakers, and provide new insight for heart failure patients with an implanted cardiac resynchronization therapy defibrillator.
Background/Objectives: Remote monitoring (RM) cardiac implantable electronic devices for adults delivers improved patient outcomes. However, previously used bedside transmitters are not optimal due to deficient patient adherence. The goal of this study was to evaluate the efficacy of RM regarding the connectivity of smartphone app-based solutions, adherence to scheduled automatic follow-ups, and prevalence of alert-based events. Methods: We evaluated the adult heart failure (HF) population with an implanted cardiac resynchronization therapy defibrillator (CRT-D) divided into two arms: with app-based RM (abRM) and without app-based RM (control). Results: A total of 81 patients (median age of 69.0) were included in our study. Sixty-five patients received a CRT-D with abRM functionality, and sixteen did not. Twelve patients had no smartphone, and two provided no consent, resulting in their transfer to the control group. Finally, the abRM arm consisted of 51 patients, while 30 patients were in the control group. The median period of follow-up lasted 12 months. Among abRM patients, 98.0% successfully transmitted their first scheduled follow-up, and 80.4% were continuously monitored. Alert-based events were mainly related to arrhythmic events and device functionality with significantly shorter median times to notification (1 day vs. 101 days; p < 0.0001) in the abRM group. Conclusions: Our study showed a high level of compliance with timely initial transmission and adherence to scheduled remote follow-ups. Patient enrollment eligibility was a major challenge due to the limited accessibility of smartphones in the population. App-based RM demonstrated an accurate notification of events and patient-initiated transmissions in emergencies, regardless of location.
Background/Objectives: Remote monitoring (RM) of cardiac implantable electronic devices for adults offers improved patient outcomes. However, bedside transmitters utilized so far are not optimal due to limited patient adherence. The goal of this study was to evaluate the efficacy of RM regarding the connectivity of smartphone app-based solutions, adherence to planned automatic follow-ups, and occurrence of alert-based events. Methods: We evaluated the adult heart failure (HF) population with implanted cardiac resynchronization therapy defibrillator (CRT-D) divided into two arms: with app-based RM (abRM) and without app-based RM (control). Results: A total of 81 patients (median age of 69.0) were included in our study. 65 patients received a CRT-D with abRM functionality, and 16 did not. 12 patients had no smartphone, and 2 provided no consent, resulting in their transfer to the control group. Finally abRM arm consisted of 51 patients, while 30 patients were in the control group. Median period of follow-up lasted 12 months. Among abRM patients, 98.0% successfully transmitted their first scheduled follow-up, and 80.4% were continuously monitored. Alert-based events were mainly related to arrhythmic events and device functionality with significantly shorter median time to notification (1 day vs. 101 days; p<0.0001) in the abRM group. Conclusions: Our study showed a high level of compliance with timely initial transmission and adherence to scheduled remote follow-ups. Patient enrollment eligibility was a major challenge due to the limited accessibility of smartphones in the population. App-based RM demonstrated an accurate notification of events and patient-initiated transmissions in emergencies, regardless of location.