P-glycoprotein (P-gp/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) expression are frequently related to multidrug resistance (MDR) in neoplastic cells. Canine inflammatory and grade III noninflammatory mammary carcinomas (IMC and non-IMC) are aggressive tumors that could benefit from chemotherapy. This study describes the immunohistochemical detection of P-gp and BCRP in 20 IMCs and 18 non-IMCs from dogs that had not received chemotherapy. Our aim was to determine if P-gp and BCRP expression was related to the "inflammatory" phenotype, to establish a basis for future studies analyzing the response to chemotherapy in dogs with highly malignant mammary cancer. Immunolabeling was primarily membranous for P-gp with a more intense labeling in emboli, and immunolabeling was membranous and cytoplasmic for BCRP. P-gp was expressed in 17 of 20 (85%) IMCs compared to 7 of 18 (39%) non-IMCs ( = 0.006). BCRP was expressed within emboli in 15 of 19 (79%) emboli in IMC, 12 of 15 (80%) primary IMCs, and 12 of 18 (67%) non-IMCs, without statistically significant differences ( > .05). All IMCs and 67% of non-IMCs expressed at least 1 of the 2 transporters, and 63% (12/19) of IMCs and 39% (7/18) of non-IMCs expressed both P-gp and BCRP. P-gp and BCRP evaluation might help select patients for chemotherapy. P-gp, expressed in a significantly higher percentage of IMCs vs non-IMCs, might play a specific role in the chemoresistance of IMC.
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http://dx.doi.org/10.1177/0300985819868647 | DOI Listing |
Front Pharmacol
December 2024
Department of Biochemistry, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia.
Background: Multidrug resistance (MDR), mainly caused by ATP-binding cassette transporters (ABCTs) efflux, makes it difficult for many anticancer drugs to treat breast cancer (BC). Phytochemicals can reverse cancer's MDR by modifying ABC transporter expression and function, as well as working synergistically with anticancer drugs to target other molecules. The reversal effect of the isoquinoline alkaloid coptisine (COP) was assessed on four breast cell lines; Two sensitive MCF-7 cell lines with positive estrogen, androgen, progesterone, and glucocorticoid receptors, as well as MDB-MB-231 cells with negative estrogen, progesterone, and HER2 receptors, and two doxorubicin-resistant cell lines, MCF-7/ADR and MDB-MB-231/ADR.
View Article and Find Full Text PDFPLoS One
December 2024
Therapeutic Development Branch, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institute of Health, Rockville, Maryland, United States of America.
R-VK4-116 is currently being developed as a medication to treat opioid use disorder (OUD). To characterize in vitro safety properties of R-VK4-116, metabolic stability in hepatocytes or liver microsomes, metabolite identification, metabolism/transporter-mediated drug interactions, lysosomal perturbation, mitochondrial toxicity, off-target enzyme effects, cellular and nuclear receptor functional assays, electrophysiological assays, CiPA, KINOMEscanTM, plasma protein binding, phospholipidosis and steatosis assays were performed. Overall, R-VK4-116 was metabolically stable in hepatocytes and microsomes.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
December 2024
Department of Pharmacy, Hebei General Hospital, Shijiazhuang, China; Hebei Key Laboratory of Clinical Pharmacy, Shijiazhuang, China. Electronic address:
Eur J Med Chem
January 2025
School of Pharmacy, Fudan University, Shanghai, 201203, China. Electronic address:
Clin Pharmacol Ther
November 2024
Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
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