Advances in the treatment of Ewing's sarcoma (EWS) are desperately needed, particularly in the case of metastatic disease. A deeper understanding of collateral sensitivity, where the evolution of therapeutic resistance to one drug aligns with sensitivity to another drug, may improve our ability to effectively target this disease. For the first time in a solid tumor, we produced a temporal collateral sensitivity map that demonstrates the evolution of collateral sensitivity and resistance in EWS. We found that the evolution of collateral resistance was predictable with some drugs but had significant variation in response to other drugs. Using this map of temporal collateral sensitivity in EWS, we can see that the path toward collateral sensitivity is not always repeatable, nor is there always a clear trajectory toward resistance or sensitivity. Identifying transcriptomic changes that accompany these states of transient collateral sensitivity could improve treatment planning for patients with EWS.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334607 | PMC |
http://dx.doi.org/10.1016/j.isci.2020.101293 | DOI Listing |
ACS Synth Biol
January 2025
Department of Chemical and Biomolecular Engineering (BK21 Four), Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.
We herein developed an ultrasensitive and rapid strategy to identify genomic nucleic acids by integrating a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 13a (Cas13a) into our recently developed isothermal technique, nicking and extension chain reaction system-based amplification (NESBA) reaction. In this technique, named CESBA, the NESBA reaction isothermally produces a large amount of RNA amplicons from the initial target genomic RNA (gRNA). The RNA amplicons bind to the crispr RNA (crRNA) and activate the collateral cleavage activity of Cas13a, which would then cleave the reporter probe nearby, consequently producing the final signals.
View Article and Find Full Text PDFACS Infect Dis
January 2025
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, United States.
Half the world's population is at risk of developing a malaria infection, which is caused by parasites of the genus . Currently, resistance has been identified to all clinically available antimalarials, highlighting an urgent need to develop novel compounds and better understand common mechanisms of resistance. We previously identified a novel tetrahydro-β-carboline compound, PRC1590, which potently kills the malaria parasite.
View Article and Find Full Text PDFAJNR Am J Neuroradiol
January 2025
From the Department of Radiology, Medical Physics (MML, TJC), Department of Interventional Radiology (NS, GAC), Department of Surgery and Large Animal Studies (MAN), and the Department of Statistics (MG), University of Chicago, Chicago, IL, USA; Department of Anesthesiology (SPR), University of Illinois, Chicago, IL, USA; Department of Radiology (MSS), University of Massachusetts Chan Medical School, Worcester, MA, USA; Department of Radiology, Biomedical Engineering and Imaging Institute (Current affiliation MML), Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mount Carmel Health Systems (Current affiliation GAC), Columbus, OH, USA.
Background And Purpose: In acute ischemic stroke, the amount of "local" CBF distal to the occlusion, i.e. all blood flow within a region whether supplied antegrade or delayed and dispersed through the collateral network, may contain valuable information regarding infarct growth rate and treatment response.
View Article and Find Full Text PDFPLoS Biol
January 2025
Department of Biophysics, University of Michigan, Ann Arbor, Michigan, United States of America.
As failure rates for traditional antimicrobial therapies escalate, recent focus has shifted to evolution-based therapies to slow resistance. Collateral sensitivity-the increased susceptibility to one drug associated with evolved resistance to a different drug-offers a potentially exploitable evolutionary constraint, but the manner in which collateral effects emerge over time is not well understood. Here, we use laboratory evolution in the opportunistic pathogen Enterococcus faecalis to phenotypically characterize collateral profiles through evolutionary time.
View Article and Find Full Text PDFBMC Med Inform Decis Mak
January 2025
Department of Vascular and Wound Center, Jinshan Hospital, Fudan University, Shanghai, 201508, China.
Background: To construct a nomogram combining CT varices vein evaluation and clinical laboratory tests for predicting the risk of esophageal gastric variceal bleeding (EGVB) in patients with noncirrhotic portal hypertension (NCPH).
Methods: A total of 315 NCPH patients with non-EGVB and EGVB were retrospectively enrolled and randomly divided into training and testing cohorts. Thirteen collateral vessels were identified and evaluated after CT portal vein system reconstruction.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!