Knockdown of iPLA2γ enhances cisplatin-induced apoptosis by increasing ROS-dependent peroxidation of mitochondrial phospholipids in bladder cancer cells.

Cisplatin (CDDP) is a platinum-based drug with anti-cancer activity and is widely used as a standard therapy for bladder cancer. It is well known that CDDP causes cell death by increasing the generation of reactive oxygen species (ROS) and lipid peroxidation, but the mechanism of its anti-cancer effects has not been fully elucidated. There are still some problems such as chemoresistance in CDDP therapy. In the present study, we found the expression of Ca2+-independent phospholipase A2γ (iPLA2γ), which has been reported to regulate cellular redox homeostasis by inhibiting lipid peroxide accumulation, in human bladder cancer tissues. Thus, we investigated the effect of iPLA2γ knockdown on CDDP-induced bladder cancer cell death. As a result, we found that iPLA2γ knockdown significantly enhanced CDDP-induced apoptosis, intracellular and mitochondrial ROS production, cytochrome c release and caspase activation in bladder cancer cells. Moreover, mitochondrial membrane potential was decreased and peroxidation of mitochondrial phospholipids was increased by iPLA2γ knockdown. It was also shown that co-treatment of bromoenol lactone, an iPLA2 inhibitor, increased CDDP-induced apoptosis. These results indicated that iPLA2γ plays an important role in protecting bladder cancer cells from CDDP-induced apoptosis, and that iPLA2γ inhibitors might represent a novel strategy in CDDP-based multi-drug therapy.

Cardiac arrest during hemodialysis: a survey of five Japanese hospitals.

AIM: Intraprocedural cardiac arrest is a serious complication among patients receiving hemodialysis. However, the frequency and reaction to these events remain unclear. This study aimed to explore the clinical picture of cardiac arrest during hemodialysis. METHODS: Ten cardiac arrests that had occurred during 217,984 hemodialysis treatments in five Japanese hospitals, between 2008 and 2017, were reviewed. We investigated the underlying disease, vital signs, emergency responses, and outcomes using patient medical records. RESULTS: The cardiac arrest rate ranged from 1.1 to 7.5 per 100,000 hemodialysis sessions. All included cases of cardiac arrest occurred in a hemodialysis unit and had been witnessed and reported by supervising clinicians. The initial rhythm was ventricular fibrillation/ventricular tachycardia in six patients (60%) and pulseless electrical activity/asystole in four patients (40%). Seven (70%) patients showed a return of spontaneous circulation (ROSC), and two (20%) patients were discharged with a cerebral performance category score of 1. There was a statistically significant difference in the ROSC rate (P = 0.048) only in the event of an emergency call. The SpO2 and respiratory rates had not been recorded in six patients. There was no significant difference in ROSC between initial rhythms of ventricular fibrillation/ventricular tachycardia and pulseless electrical activity/asystole. CONCLUSION: We evaluated the frequency of cardiac arrest during hemodialysis. Overall assessment including respiratory status is needed at initiation of hemodialysis. In case of a sudden change in a patient's status, high-quality resuscitation treatment that includes an emergency call can improve prognosis.

A retrospective study of in-hospital cardiac arrest.

Aim: In-hospital cardiac arrest is an important issue in health care today. Data regarding in-hospital cardiac arrest in Japan is limited. In Australia and the USA, the Rapid Response System has been implemented in many institutions and data regarding in-hospital cardiac arrest are collected to evaluate the efficacy of the Rapid Response System. This is a multicenter retrospective survey of in-hospital cardiac arrest, providing data before implementing a Rapid Response System. Methods: Ten institutions planning to introduce a Rapid Response System were recruited to collect in-hospital cardiac arrest data. The Institutional Review Board at each participating institution approved this study. Data for patients admitted at each institution from April 1, 2011 until March 31, 2012 were extracted using the three keywords "closed-chest compression", "epinephrine", and "defibrillation". Patients under 18 years old, or who suffered cardiac arrest in the emergency room or the intensive care unit were excluded. Results: A total of 228 patients in 10 institutions were identified. The average age was 73 ± 13 years. Males represented 64% of the patients (82/146). Overall survival after in-hospital cardiac arrest was 7% (16/228). Possibly preventable cardiac arrests represented 15% (33/228) of patients, with medical safety issues identified in 8% (19/228). Vital sign abnormalities before cardiac arrest were observed in 63% (138/216) of patients. Conclusions: Approximately 60% of patients had abnormal vital signs before cardiac arrest. These patients may have an improved clinical outcome by implementing a Rapid Response System.