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Purine Synthesis Inhibitor L-Alanosine Impairs Mitochondrial Function and Stemness of Brain Tumor Initiating Cells.
Biomedicines
March 2022
The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA.
Article Synopsis
- Glioblastoma (GBM) is a deadly brain cancer that has a high resistance to treatments, partly due to the presence of cancer stem cells.
- Recent studies show that a genetic change known as homozygous deletion, common in GBM, enhances the stem-like properties of the tumor cells.
- Treatment with L-Alanosine (ALA) reduces these stem-like properties by impairing mitochondrial function and also makes GBM cells more sensitive to the standard chemotherapy drug temozolomide (TMZ), suggesting that targeting purine synthesis could improve treatment outcomes with less toxicity.
Downregulated MTAP expression in myxofibrosarcoma: A characterization of inactivating mechanisms, tumor suppressive function, and therapeutic relevance.
Oncotarget
November 2014
Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Myxofibrosarcomas are genetically complex and involve recurrently deleted chromosome 9p, for which we characterized the pathogenically relevant target(s) using genomic profiling. In 12 of the 15 samples, we detected complete or partial losses of 9p. The only aggressiveness-associated, differentially lost region was 9p21.
View Article and Find Full Text PDFPersonalized cancer medicine: from molecular diagnostics to targeted therapy with natural products.
Planta Med
August 2010
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Mainz, Germany.
Personalized cancer medicine aims to develop individualized treatment options adapted to factors relevant for the prognosis of each patient. Molecular biomarkers are required to predict the likelihood of an individual tumor's responsiveness or of toxicity in normal organs and to advise optimized treatments with improved efficacy at reduced side effects for each cancer patient. In the present review, we present a concept, which takes advantage of methods of molecular diagnostics to identify predictive markers at the DNA, mRNA, and protein levels.
View Article and Find Full Text PDFA phase II multicenter study of L-alanosine, a potent inhibitor of adenine biosynthesis, in patients with MTAP-deficient cancer.
Invest New Drugs
February 2009
University of Chicago, 5841 South Maryland Avenue, MC2115, Chicago, IL, 60637-1460, USA.
Objective: Methylthioadenosine phosphorylase (MTAP)-deficient tumors are dependent on the de novo purine synthesis pathway. These cancers are potential targets for selective chemotherapy with inhibitors of de novo adenine synthesis such as L-alanosine [L-2-amino-3-(N-hydroxy-N-nitrosamino) propionic acid]. This phase II study was designed to evaluate the efficacy and safety of L-alanosine in patients with MTAP-deficient solid tumors.
View Article and Find Full Text PDFGenome-scale analysis of anti-metabolite directed strain engineering.
Metab Eng
March 2008
Department of Chemical and Biological Engineering, University of Colorado, UCB 424 Boulder, CO 80309, USA.
Classic strain engineering methods have previously been limited by the low-throughput of conventional sequencing technology. Here, we applied a new genomics technology, scalar analysis of library enrichments (SCALEs), to measure >3 million Escherichia coli genomic library clone enrichment patterns resulting from growth selections employing three aspartic-acid anti-metabolites. Our objective was to assess the extent to which access to genome-scale enrichment patterns would provide strain-engineering insights not reasonably accessible through the use of conventional sequencing.
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