ABSTRACT
BACKGROUND AND OBJECTIVES: Non-small cell lung cancer (NSCLC) is a global health concern. NSCLC treatment outcomes are generally poor due to treatment resistance or toxicity. Ferroptosis is a novel cell death triggered by iron accumulation, reactive oxygen species (ROS), and lipid peroxidation. Ferroptosis may kill cancer cells, particularly those resistant to apoptosis. MATERIALS AND METHODS: The Cell Counting Kit-8 assay assessed NSCLC cell viability after trabectedin treatment. Flow cytometry with Annexin V-FITC staining evaluated cell death. ROS, iron, lipid peroxidation, and GSH levels were measured using commercial kits. qRT-PCR and western blots evaluated messenger RNA and protein levels. Proteins were inhibited using short interfering RNA transfection and specific inhibitors. RESULTS: Trabectedin was cytotoxic to NSCLC cells regardless of p53 status. Trabectedin upregulated iron, ROS, and lipid peroxidation in NSCLC cells, causing ferroptosis. Trabectedin increases iron and ROS levels by upregulating transferrin receptor 1 and the HIF-1/IRP1 axis. In NSCLC cells, trabectedin suppresses glutathione peroxidase 4, followed by the Keap1/Nrf2 axis. CONCLUSIONS: Our findings imply that trabectedin may treat NSCLC effectively.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Ferroptosis , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Trabectedin/pharmacology , NF-E2-Related Factor 2/metabolism , Reactive Oxygen Species/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Lung Neoplasms/drug therapy , Iron/metabolismABSTRACT
Background: Sedation and analgesia use in percutaneous radiofrequency ablation (RFPA) for liver cancer is a necessary part of the procedure; however, the optimal medicine for sedation and analgesia for PRFA remains controversial. The aim of this study was to compare the perioperative pain management, haemodynamic stability and side effects between oxycodone (OXY) and fentanyl (FEN) use in patients under dexmedetomidine sedation. Methods: Two hundred and five adults with an American Society of Anaesthesiologists physical status score of I to II were included in this study. Patients were assigned to the OXY (n=101) or FEN (n=104) group. Radiofrequency ablation was performed under spontaneous breathing and with painless anaesthesia administered intravenously. The outcomes included fluctuations in mean arterial pressure, heart rate, side effects and the perioperative numerical rating scale (NRS). Results: Radiofrequency ablation was successfully performed in 205 patients. No significant differences were observed in mean blood pressure fluctuations between the two groups despite the longer durations of ablation and total sedation time in the OXY group. The highest NRS score during the surgery and 1 hour and 2 hours after the surgery were significantly lower in the OXY group than in the FEN group. Heart rate fluctuations were significantly lower in the OXY group than in FEN group throughout the surgery. More patients in the FEN group displayed unwanted body movement and respiratory depression. Conclusions: Both oxycodone and fentanyl can be applied for liver cancer percutaneous radiofrequency ablation; however, oxycodone provides a better patient experience, lower postoperative pain, less respiratory depression and stable haemodynamic fluctuations.
Subject(s)
Analgesia/methods , Analgesics, Opioid/administration & dosage , Conscious Sedation/methods , Liver Neoplasms/surgery , Radiofrequency Ablation/adverse effects , Aged , Analgesia/adverse effects , Analgesics, Opioid/adverse effects , Blood Pressure/drug effects , Blood Pressure Determination , Conscious Sedation/adverse effects , Dexmedetomidine/administration & dosage , Dexmedetomidine/adverse effects , Female , Fentanyl/administration & dosage , Fentanyl/adverse effects , Humans , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/adverse effects , Male , Middle Aged , Oxycodone/administration & dosage , Oxycodone/adverse effects , Pain Measurement/statistics & numerical data , Pain, Postoperative/diagnosis , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Pain, Postoperative/psychology , Pain, Procedural/diagnosis , Pain, Procedural/etiology , Pain, Procedural/prevention & control , Pain, Procedural/psychology , Radiofrequency Ablation/psychology , Respiration/drug effects , Treatment OutcomeABSTRACT
The aim of this prospective observational study was to screen for risk factors of intraoperative atrial fibrillation (AF) during noncardiac thoracic surgery. The study was conducted as a single-institution study in Zhejiang Cancer Hospital, Hangzhou, China. All the participants were patients with cancer scheduled for thoracotomy.This study was conducted from July 2013 to August 2016 and included 144 patients scheduled for thoracotomy under general anesthesia. We collected the patients' demographic and perioperative medical data in our hospital. AF was diagnosed using electrocardiography (ECG), on the basis of the presence of characteristic ECG features of AF by one or more ECG leads for at least 30âseconds.Of the participants, 144 completed the study and 18 developed intraoperative AF. Higher percentages of subjects in the AF group than in the non-AF group had histories of chemotherapy (Pâ=â.014) and alcohol consumption (Pâ=â.034) before surgery. The AF group had a lower mean body mass index (Pâ=â.019), significantly higher mean heart rate (Pâ<â.001), and lower tidal volume (Pâ=â.01) than the non-AF group. After the logistic regression analysis, only alcohol consumption (odds ratio [OR]â=â5.279; 95% confidence interval [CI]: 1.432-19.467), history of chemotherapy (ORâ=â4.019; 95% CI: 1.504-15.334), and high heart rate (ORâ=â1.093; 95% CI: 1.033-1.156) during 1-lung ventilation were identified as the risk factors of AF during lung and esophageal surgeries.The incidence of intraoperative AF during noncardiac thoracic surgery was 12.5%. Alcohol consumption, history of chemotherapy, and high heart rate during 1-lung ventilation were the risk factors related to intraoperative AF.
