Caspase-3-like activity determines the type of cell death following ionizing radiation in MOLT-4 human leukaemia cells

Caspases, a family of cysteine proteases, play a central role in the pathways leading to apoptosis. Recently, it has been reported that a broad spectrum inhibitor of caspases, the tripeptide Z-VAD-fmk, induced a switch from apoptosis to necrosis in dexamethasone-treated B lymphocytes and thymocytes. As such a cell death conversion could increase the efficiency of radiation therapy and in order to identify the caspases involved in this cell death transition, we investigated the effects of caspase-3-related proteases inhibition in irradiated MOLT-4 cells. Cells were pretreated with Ac-DEVD-CHO, an inhibitor of caspase-3-like activity, and submitted to X-rays at doses ranging from 1 to 4 Gy. Our results show that the inhibition of caspase-3-like activity prevents completely the appearance of the classical hallmarks of apoptosis such as internucleosomal DNA fragmentation or hypodiploid particles formation and partially the externalization of phosphatidylserine. However, this was not accompanied by any persistent increase in cell survival. Instead, irradiated cells treated by this inhibitor exhibited characteristics of a necrotic cell death. Therefore, functional caspase-3-subfamily not only appears as key proteases in the execution of the apoptotic process, but their activity may also influence the type of cell death following an exposure to ionizing radiation. © 2000 Cancer Research Campaig

IPEM Topical Report: an international IPEM survey of MRI use for external beam radiotherapy treatment planning

Introduction/Background: Despite growing interest in magnetic resonance imaging (MRI), integration in external beam radiotherapy (EBRT) treatment planning uptake varies globally. In order to understand the current international landscape of MRI in EBRT a survey has been performed in 11 countries. This work reports on differences and common themes identified. Methods: A multi-disciplinary Institute of Physics and Engineering in Medicine working party modified a survey previously used in the UK to understand current practice using MRI for EBRT treatment planning, investigate how MRI is currently used and managed as well as identify knowledge gaps. It was distributed electronically within 11 countries: Australia, Belgium, Denmark, Finland, France, Italy, the Netherlands, New Zealand, Sweden, the UK and the USA. Results: The survey response rate within the USA was <1% and hence these results omitted from the analysis. In the other 10 countries the survey had a median response rate of 77% per country. Direct MRI access, defined as either having a dedicated MRI scanner for radiotherapy (RT) or access to a radiology MRI scanner, varied between countries. France, Italy and the UK reported the lowest direct MRI access rates and all other countries reported direct access in ≥82% of centres. Whilst ≥83% of centres in Denmark and Sweden reported having dedicated MRI scanners for EBRT, all other countries reported ≤29%. Anatomical sites receiving MRI for EBRT varied between countries with brain, prostate, head and neck being most common. Commissioning and QA of image registration and MRI scanners varied greatly, as did MRI sequences performed, staffing models and training given to different staff groups. The lack of financial reimbursement for MR was a consistent barrier for MRI implementation for RT for all countries and MR access was a reported important barrier for all countries except Sweden and Denmark. Conclusion: No country has a comprehensive approach for MR in EBRT adoption and financial barriers are present worldwide. Variations between countries in practice, equipment, staffing models, training, QA and MRI sequences have been identified, and are likely to be due to differences in funding as well as a lack of consensus or guidelines in the literature. Access to dedicated MR for EBRT is limited in all but Sweden and Denmark, but in all countries there are financial challenges with ongoing per patient costs. Despite these challenges, significant interest exists in increasing MR guided EBRT planning over the next 5 years

Radiotherapy treatment planning of prostate cancer using magnetic resonance imaging

Purpose.-Magnetic resonance imaging (MRI) plays an increasing role in radiotherapy dose planning. Indeed, MRI offers superior soft tissue contrast compared to computerized tomography (CT) and therefore could provide a better delineation of target volumes and organs at risk than CT for radiotherapy. Furthermore, an MRI-only radiotherapy workflow would suppress registration errors inherent to the registration of MRI with CT. However, the estimation of the electronic density of tissues using MRI images is still a challenging issue. The purpose of this work was to design and evaluate a pseudo-CT generation method for prostate cancer treatments. Materials and methods.-A pseudo-CT was generated for ten prostate cancer patients using an elastic deformation based method. For each patient, dose delivered to the patient was calculated using both the planning CT and the pseudo-CT. Dose differences between CT and pseudo-CT were investigated. Results.-Mean dose relative difference in the planning target volume is 0.9% on average and ranges from 0.1% to 1.7%. In organs at risks, this value is 1.8%, 0.8%, 0.8% and 1% on average in the rectum, the right and left femoral heads, and the bladder respectively. Conclusio.-The dose calculated using the pseudo-CT is very close to the dose calculated using the CT for both organs at risk and PTV. These results confirm that pseudo-CT images generated using the proposed method could be used to calculate radiotherapy treatment doses on MRI images. (C) 2019 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.Peer reviewe