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Sacituzumab govitecan in triple-negative breast cancer: from bench to bedside, and back.
Front Immunol
August 2024
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology (IOV)-IRCCS, Padova, Italy.
Triple-negative breast cancer (TNBC) represents a major therapeutic challenge due to its heterogeneous and aggressive phenotype, and limited target-specific treatment options. The trophoblast cell surface antigen (Trop-2), a transmembrane glycoprotein overexpressed in various cancers, has emerged as a promising target for TNBC. Sacituzumab govitecan (SG), an antibody-drug conjugate (ADC) that targets Trop-2, has recently entered treatment algorithms for advanced and metastatic TNBC, independently from Trop-2 expression status, with manageable toxicity.
View Article and Find Full Text PDFDegradation and mineralization of anti-cancer drugs Capecitabine, Bicalutamide and Irinotecan by UV-irradiation and ozone.
Chemosphere
May 2024
Karlsruhe Institute of Technology (KIT), Engler-Bunte-Institut, Water Chemistry and Water Technology, Engler-Bunte-Ring 9, 76131, Karlsruhe, Germany; DVGW Research Laboratories for Water Chemistry and Water Technology, Engler-Bunte-Ring 9, 76131, Karlsruhe, Germany. Electronic address:
The degradation of three anti-cancer drugs (ADs), Capecitabine (CAP), Bicalutamide (BIC) and Irinotecan (IRI), in ultrapure water by ozonation and UV-irradiation was tested in a bench-scale reactor and AD concentrations were measured through ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). A low-pressure mercury UV (LP-UV) lamp was used and degradation by UV (λ = 254 nm) followed pseudo-first order kinetics. Incident radiation in the reactor was measured via chemical actinometry using uridine.
View Article and Find Full Text PDFGeneration and Use of Glycosyl Radicals under Acidic Conditions: Glycosyl Sulfinates as Precursors.
Angew Chem Int Ed Engl
April 2023
Department of Emergency, State Key Laboratory of Biotherapy, West China Hospital, and School of Chemical Engineering, Sichuan University, No. 17 Renmin Nan Road, Chengdu, 610041, China.
We herein report a method that enables the generation of glycosyl radicals under highly acidic conditions. Key to the success is the design and use of glycosyl sulfinates as radical precursors, which are bench-stable solids and can be readily prepared from commercial starting materials. This development allows the installation of glycosyl units onto pyridine rings directly by the Minisci reaction.
View Article and Find Full Text PDFNon-Coding Micro RNAs and Hypoxia-Inducible Factors Are Selenium Targets for Development of a Mechanism-Based Combination Strategy in Clear-Cell Renal Cell Carcinoma-Bench-to-Bedside Therapy.
Int J Mol Sci
October 2018
Roswell Park Comprehensive Cancer Center, Department of Pharmacology & Therapeutics, Buffalo, NY 14263, USA.
Durable response, inherent or acquired resistance, and dose-limiting toxicities continue to represent major barriers in the treatment of patients with advanced clear-cell renal cell carcinoma (ccRCC). The majority of ccRCC tumors are characterized by the loss of Von Hippel⁻Lindau tumor suppressor gene function, a stable expression of hypoxia-inducible factors 1α and 2α (HIFs), an altered expression of tumor-specific oncogenic microRNAs (miRNAs), a clear cytoplasm with dense lipid content, and overexpression of thymidine phosphorylase. The aim of this manuscript was to confirm that the downregulation of specific drug-resistant biomarkers deregulated in tumor cells by a defined dose and schedule of methylselenocysteine (MSC) or seleno-l-methionine (SLM) sensitizes tumor cells to mechanism-based drug combination.
View Article and Find Full Text PDFUltrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay for simultaneous quantifications of CZ48, lactone-stabilized camptothecin, and camptothecin and their pharmacokinetic and biliary evaluations in rats.
J Pharm Biomed Anal
November 2018
Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX, 77204, USA. Electronic address:
CZ48, a prodrug of camptothecin (CPT), has a broad spectrum of antitumor activity against various types of human tumors without severe toxicity in preclinical human tumor-xenografted mouse models, which facilitates further preclinical and clinical pharmacokinetic (PK) evaluations of CZ48. In this study, a UHPLC-MS/MS method was developed and validated to simultaneously quantify CZ48 and CPT in rat plasma and bile. Detection was performed using the API 3200 Q Trap triple quadrupole mass spectrometer in a positive ion mode.
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