Approximately 50% of metastatic melanoma patients harbor BRAF mutations. Several treatment options including the combination of BRAF and MEK inhibitors (BRAF/MEKi) and immunotherapy (mainly anti CTLA-4 and anti PD-1 antibodies), have been shown to improve survival in these patients. Although preclinical data support the synergistic effect of both modalities in combination, data confirming the activity and tolerability of these combinations are not yet available in the clinical setting. Herein, we report the case of a melanoma patient treated with sequential BRAF/MEKi (dabrafenib plus trametinib) followed by the anti CTLA-4 antibody ipilimumab who achieved a pathological complete response. Unfortunately, the patient died due to fatal gastrointestinal (GI) toxicity. Analysis of the BRAFV600E mutation in circulating tumoral DNA (ctDNA) from peripheral blood samples and serial tumor tissue biopsies throughout treatment demonstrated a good correlation with clinical evolution.
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http://dx.doi.org/10.18632/oncotarget.10651 | DOI Listing |
Ann Hematol
January 2025
Department of Biomedicine and Prevention, University Tor Vergata, Rome, Italy.
Myeloid sarcoma (MS) is an extramedullary localization of immature granulocyte cells that can occur in association with acute myeloid leukemia (AML). Gastrointestinal involvement is relatively common in MS, but exclusive colonic localization is a rare occurrence. Here, we report on a 53-year-old male patient affected by AML developing a severe abdominal pain caused by intestinal perforation requiring surgical intervention.
View Article and Find Full Text PDFToxics
December 2024
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 12371, Saudi Arabia.
Methanol is a widely used industrial and household alcohol that poses significant health risks upon exposure. Despite its extensive use, methanol poisoning remains a critical public health concern globally, often resulting from accidental or intentional ingestion and outbreaks linked to contaminated beverages. Methanol toxicity stems from its metabolic conversion to formaldehyde and formic acid, leading to severe metabolic acidosis and multiorgan damage, including profound CNS effects and visual impairments.
View Article and Find Full Text PDFBiology (Basel)
November 2024
Department of Pathology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
The Eurasian lynx (), a widespread wild felid on the Eurasian continent, is currently classified as "critically endangered" in Germany. Understanding the impact of infectious agents is of particular importance for the continued conservation of these animals, especially regarding pathogens with broad host ranges and risk of interspecies transmission. Feline leukemia virus (FeLV) is known to infect wild and domestic felids worldwide, including several species of lynx, but it has not been reported thus far in the Eurasian lynx.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Laboratory of Gastrointestinal Cancer and Liver Disease, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:
Organ fibrosis, such as lung fibrosis and liver fibrosis, is a progressive and fatal disease. Fibroblast growth factor receptors (FGFRs) play an important role in the development and progression of fibrosis. Through scaffold hopping, bioisosteric replacement design, and structure-activity relationship optimization, we developed a series of highly potent FGFRs inhibitors, and the indazole-containing candidate compound A16 showed potent kinase activity comparable to that of AZD4547.
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