Introduction: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance.
Methods And Analysis: The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival.
Ethics And Dissemination: Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden.
Trial Registration Number: EudraCT number: 2021-001257-31.
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http://dx.doi.org/10.1136/bmjopen-2022-065839 | DOI Listing |
Angew Chem Int Ed Engl
January 2025
Research Center for Energy and Environmental Materials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki, 305-0044, Japan.
Unveiling the key influencing factors towards electrode/electrolyte interface control is a long-standing challenge for a better understanding of microscopic electrode kinetics, which is indispensable to building up guiding principles for designer electrocatalysts with desirable functionality. Herein, we exemplify the oxygen evolution reaction (OER) via water molecule oxidation with the iridium dioxide electrocatalyst and uncovered the significant mismatching effect of pH between local electrode surface and bulk electrolyte: the intrinsic OER activity under acidic or near-neutral condition was deciphered to be identical by adjusting this pH mismatching. This result indicates that the local pH effect at the electrified solid-liquid interface plays the main role in the "fake" OER performance.
View Article and Find Full Text PDFPhytother Res
January 2025
Laboratory of Immunology and Inflammation, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.
Renal fibrosis is the most common pathway for the development of end-stage renal disease (ESRD) in various kidney diseases. Currently, the treatment options for renal fibrosis are limited. Ferroptosis is iron-mediated lipid peroxidation, triggered mainly by iron deposition and ROS generation.
View Article and Find Full Text PDFPublic Health Nutr
January 2025
Department of Nutrition and Food Studies, Steinhardt School of Culture, Education, and Human Development, New York University, 411 Lafayette St, 5th floor, New York, NY 10003.
Objective: The Supplemental Nutrition Assistance Program (SNAP) Online Purchasing Pilot (OPP) authorized the use of SNAP benefits online in Maryland in May 2020. We assessed shopping behavior and intentions associated with uptake and intended future use of online grocery shopping during and after COVID-19 among SNAP-eligible households.
Design: In this mixed-methods study, participants completed a survey on online grocery shopping, and a purposefully sampled subset participated in focus groups or in-depth interviews between November 2020 and March 2021.
Folia Morphol (Warsz)
January 2025
Tekirdağ Namık Kemal University School of MedicineTekirdağ, Türkiye.
Background: Distance education emerged as a potential solution to enhance access, standardize content, and facilitate updates. However, student perceptions varied widely. The COVID-19 pandemic prompted a rapid shift towards distance education in anatomy, presenting challenges and opportunities for medical students globally.
View Article and Find Full Text PDFMicrosc Res Tech
January 2025
School of Electrical & Control Engineering, Shenyang Jianzhu University, Shenyang, China.
The atomic force microscope (AFM) image will be inclined and bent due to the tilt angle between the probe and the sample surface. When the least squares fitting method is used to correct the horizontal distortion of the AFM image, the shape structure that is lower or higher than the sample base will affect the final fitting correction result. In view of the limitations of existing methods and the diversity of AFM images, an AFM image level distortion correction method based on automatic feature marking is proposed.
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