Loperamide is a peripheral opiate agonist that can cause apoptosis and G2/M arrest in human cancer cell lines and may sensitize cells to chemotherapy. The objectives of this study were to investigate the effects of loperamide on viability, apoptosis and cell cycle kinetics in canine cancer cells and to establish whether the drug sensitizes cells to doxorubicin. Cell viability was assessed using Alamar Blue. Cell death and cell cycle were studied using flow cytometry with 7-Aminoactinomycin-D (7-AAD) and propidium iodide (PI), respectively. Loperamide decreased cell viability in a dose-dependent fashion and was most effective against canine osteosarcoma cells. In all cell lines, it induced a dose and time dependent apoptosis and resulted in accumulation in G0/G1. When co-incubated with doxorubicin, loperamide induced a synergistic cell kill in canine carcinoma cells. Investigation is warranted into the role of loperamide in the treatment of canine cancer.
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http://dx.doi.org/10.1292/jvms.13-0537 | DOI Listing |
Heliyon
January 2025
Department of Pulmonary, Vitkovice Hospital, Ostrava, Czech Republic.
Introduction: The use of signal dogs for cancer detection is not yet routinely performed,but dogs and their powerful olfactory system have proven to be a unique and valuable tool for many lineages and are beginning to be incorporated into medical practice. This method has great advantages; the dog can detect a tumour in the human body already in preclinical stages, when the patient has no symptoms yet. The identification of cancer biomarkers to enable early diagnosis is a need for many types of cancer, whose prognosis is strongly dependent on the stage of the disease.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
Research Center of Transport Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand.
: Pinocembrin is a promising drug candidate for treating ischemic stroke. The interaction of pinocembrin with drug transporters and drug-metabolizing enzymes is not fully revealed. The present study aims to evaluate the interaction potential of pinocembrin with cytochrome P450 (CYP450: CYP2B6, CYP2C9, and CYP2C19) and drug transporters including organic anion transporters (OAT1 and OAT3), organic cation transporters (OCT1 and OCT2), multidrug and toxin extrusion (MATE1 and MATE2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP).
View Article and Find Full Text PDFMolecules
January 2025
MBC Pharma Inc., Aurora, CO 80045, USA.
Background: The use of the bone-seeking properties of bisphosphonates (BPs) to target the delivery of therapeutic drugs is a promising approach for the treatment of bone metastases. Currently, the most advanced example of this approach is a gemcitabine-ibandronate conjugate (GEM-IB), where the bone-targeting BP ibandronate (IB) is covalently linked to the antineoplastic agent gemcitabine (GEM) via a spacer phosphate group. In the present study, we describe the development of a new analytical platform to evaluate the metabolism and pharmacokinetics of GEM-IB in mice and dogs and the results of proof-of-concept studies assessing the pharmacokinetics of GEM-IB in dogs and mice.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Biomembrane Group, Tokyo Metropolitan Institute of Medical Science, 6-1-2, Kamikitazawa, Setagaya-Ku, Tokyo 113-8613, Japan.
We previously isolated a cDNA clone for galactosylceramide expression factor 1, which is the rat homologue of hepatocyte-growth-factor-regulated tyrosine kinase substrate (HGS) and induces galactosylceramide expression and morphological changes in COS-7 cells, and reported that overexpression of HGS induced morphological changes in canine kidney epithelial MDCK cells. HGS is a component of the endosomal sorting complexes required for transport machinery that mediates endosomal multivesicle body formation. In this study, the overexpression of HGS induced epithelial-mesenchymal transition and caused transformation in MDCK cells, whereas the overexpression of a coiled-coil domain of HGS inhibited induction of epithelial-mesenchymal transition by HGF stimulation.
View Article and Find Full Text PDFAnimals (Basel)
January 2025
Department of General Pathology, Laboratory of Comparative Pathology, Federal University of Minas Gerais, Belo Horizonte 31270-091, Minas Gerais, Brazil.
In canine mammary neoplasms, greater inflammation is associated with higher histological grade, lymphatic invasion, and metastases. This retrospective study assessed the density of peri- and intratumoral tumor-infiltrating lymphocytes (TILs), tumor-associated neutrophils (TANs), and CD3 and CD79 lymphocytes in canine mammary neoplasms with a solid arrangement, and associated such data with histological types, immunophenotype, prognostic factors, cyclooxygenase-2 (Cox-2) expression and overall and cancer-specific survival. Sixty-one neoplasms with a solid arrangement were classified as malignant myoepitheliomas (6/9.
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