Colorectal cancer (CRC) is one of the leading cancers and causes of death in patients. 5-fluorouracil (5-FU) is the therapy of choice for CRC, but it exhibits high toxicity and drug resistance. Tumorigenesis is characterized by a deregulated metabolism, which promotes cancer cell growth and survival. The pentose phosphate pathway (PPP) is required for the synthesis of ribonucleotides and the regulation of reactive oxygen species and is upregulated in CRC. Mannose was recently reported to halt tumor growth and impair the PPP. Mannose inhibitory effects on tumor growth are inversely related to the levels of phosphomannose isomerase (PMI). An in silico analysis showed low PMI levels in human CRC tissues. We, therefore, investigated the effect of mannose alone or in combination with 5-FU in human CRC cell lines with different p53 and 5-FU resistance statuses. Mannose resulted in a dose-dependent inhibition of cell growth and synergized with 5-FU treatment in all tested cancer cell lines. Mannose alone or in combination with 5-FU reduced the total dehydrogenase activity of key PPP enzymes, enhanced oxidative stress, and induced DNA damage in CRC cells. Importantly, single mannose or combination treatments with 5-FU were well tolerated and reduced tumor volumes in a mouse xenograft model. In summary, mannose alone or in combination with 5-FU may represent a novel therapeutic strategy in CRC.
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http://dx.doi.org/10.3390/cancers15082268 | DOI Listing |
Stem Cell Reports
December 2024
Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, 150 Harrison Avenue, Boston, MA 02111, USA. Electronic address:
It is widely recognized that the glycocalyx has significant implications in regulating the self-renewal and differentiation of adult stem cells; however, its composition remains poorly understood. Here, we show that the fucose-binding Aleuria aurantia lectin (AAL) binds differentially to basal cells in the stratified epithelium of the human limbus, hair follicle epithelium, and meibomian gland duct. Using fluorescence-activated cell sorting in combination with single-cell transcriptomics, we find that most epithelial progenitor cells and melanocytes in the limbus display low AAL staining (AAL) on their cell surface, an attribute that is gradually lost in epithelial cells as they differentiate into mature corneal cells.
View Article and Find Full Text PDFMater Today Bio
December 2024
Immunology & Immuno-bioengineering, School of Life Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, NG7 2RD, United Kingdom.
Dendritic cells (DCs) have emerged as a promising target for drug delivery and immune modulation due to their pivotal role in initiating the adaptive immune response. Gold nanoparticles (AuNPs) have garnered interest as a platform for targeted drug delivery due to their biocompatibility, low toxicity and precise control over size, morphology and surface functionalization. Our investigation aimed to elucidate the intracellular uptake and trafficking of AuNPs coated with different combinations of monosaccharides (mannose, galactose, and fucose) in DCs.
View Article and Find Full Text PDFPolymers (Basel)
December 2024
Faculty of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1/3, 119991 Moscow, Russia.
Bronchial asthma remains a serious medical problem, as approximately 10% of patients fail to achieve adequate symptom control with available treatment options. Macrophages play a pivotal role in the pathophysiology of asthma, as well as in some other respiratory disorders. Typically, they are classified into two major classes, M1 and M2; however, recent findings have indicated that in fact there is a whole range of macrophage polarization and functional diversity beyond this bimodal division.
View Article and Find Full Text PDFChemSusChem
December 2024
Université Clermont Auvergne, Institut de Chimie de Clermont-Ferrand (ICCF), 24 avenue Blaise Pascal, 63177, AUBIERE, FRANCE.
Commun Med (Lond)
December 2024
Medical University of South Carolina, Department of Cell and Molecular Pharmacology, Charleston, SC, 29425, USA.
Background: Worldwide, hepatocellular carcinoma (HCC) is the second most lethal cancer, although early-stage HCC is amenable to curative treatment and can facilitate long-term survival. Early detection has proved difficult, as proteomics, transcriptomics, and genomics have been unable to discover suitable biomarkers.
Methods: To find new biomarkers of HCC, we utilized a spatial omics N-glycan imaging method to identify altered glycosylation in cancer tissue (n = 53) and in paired serum of individuals with HCC (n = 23).
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