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Factors Influencing the Duration of Maintenance Therapy in Metastatic Colorectal Cancer.
Cancers (Basel)
December 2024
Cancer Biology Transfer Platform, Georges François Leclerc Cancer Center, UNICANCER, 21000 Dijon, France.
Background/objectives: Metastatic colorectal cancer (mCRC) is mainly treated with 5-Fluoro-Uracil (5-FU), Oxaliplatin and Irinotecan chemotherapies and anti-Epidermal Growth Factor Receptor (EGFR) or anti-Vascular Endothelial Growth Factor (VEGF) targeted therapies. Due to chemotherapy-related toxicity, patients receive induction treatment to achieve tumour response followed by maintenance therapy with less cytotoxic molecules or a chemotherapy-free interval to reduce chemotherapy-related toxicity. In this study, the aim was to determine the patient, cancer and treatment factors that influence the duration of maintenance therapy (DMT).
View Article and Find Full Text PDFPreclinical model for evaluating human TCRs against chimeric syngeneic tumors.
J Immunother Cancer
December 2024
Swiss Institute of Bioinformatics, Lausanne, Switzerland
Background: The adoptive cell transfer (ACT) of T cell receptor (TCR)-engineered T cells targeting the HLA-A2-restricted epitope NY-ESO-1 (A2/NY) has yielded important clinical responses against several cancers. A variety of approaches are being taken to augment tumor control by ACT including TCR affinity-optimization and T-cell coengineering strategies to address the suppressive tumor microenvironment (TME). Most TCRs of clinical interest are evaluated in immunocompromised mice to enable human T-cell engraftment and do not recapitulate the dynamic interplay that occurs with endogenous immunity in a treated patient.
View Article and Find Full Text PDFA first-in-human phase 1/2 dose-escalation study of MAK683 (EED inhibitor) in patients with advanced malignancies.
Eur J Cancer
November 2024
David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Purpose: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.
Methods: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles.
Sucralose uses reward pathways to promote acute caloric intake.
Neuropeptides
January 2025
The Dr. John and Anne Chong Laboratory for Functional Genomics, Charles Perkins Centre and School of Life & Environmental Sciences, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address:
Non-nutritive sweeteners (NNSs) are used to reduce caloric intake by replacing sugar with compounds that are sweet but contain little or no calories. In this study, we investigate how non-nutritive sweetener sucralose to promote acute food intake in the fruit fly Drosophila melanogaster. Our results showed that acute exposure to NNSs sweetness induces a robust hyperphagic response in flies.
View Article and Find Full Text PDFApplication of a quantitative uncertainty assessment to develop ranges of plausible toxicity values when using observational data in risk assessment: a case study examining associations between PFOA and PFOS exposures and vaccine response.
Toxicol Sci
January 2025
ToxStrategies LLC, Austin, Texas, USA.
Traditional approaches for quantitatively characterizing uncertainty in risk assessment require adaptation to accommodate increased reliance on observational (vs. experimental) studies in developing toxicity values. Herein, a case study with PFOA and PFOS and vaccine response explores approaches for qualitative and-where possible-quantitative assessments of uncertainty at each step in the toxicity value development process when using observational data, including review and appraisal of individual studies, candidate study selection, dose-response modeling, and application of uncertainty factors.
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