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Gene amplification is a common mechanism that contributes to the drug resistance. To explore the molecular genetic background related to the MTX resistance in the mouse MTX-resistant cells, differential PCR was used to determine the amplification and overexpression of DHFR gene. In addition, the correlations between c-myc, p53 status and dhfr amplification were studied. Amplification and overexpression of dhfr suggested its role in MTX-resistant cells. However, no amplification and overexpression of c-myc were detected. On the other hand, no alteration of p53 copy number was found. The increased mRNA level of p53 suggested the normal function of p53. These results implicated the status of c-myc and p53 had no correlation with dhfr amplification, therefore some other molecular genetic alterations may exist to permit the dhfr amplification in MTX-resistant cells.
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Bioorg Chem
July 2025
Cancer center, Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518000, PR China. Electronic address:
Background: Osteosarcoma (OS) is a malignant primary tumor in bone tissues, and Methotrexate (MTX) is widely used as a chemotherapeutic drug for OS in clinical treatment. However, MTX resistance is a major challenge for OS patients. Polydatin (PD) is an extract derived from Reynoutria japonica Houtt and has been identified as a potential agent for reversing chemotherapy resistance in cancer.
View Article and Find Full Text PDFBMC Rheumatol
April 2025
Department of Rheumatology and Immunology, Lishui District Traditional Hospital of Chinese Medicine, Nanjing, China.
Background: Effective biological markers able to monitor the response of Janus kinase inhibitor (JAKi) are lacking. Exosomal microRNAs (exomiRNAs) can alter their expression during treatment and are ideal biomarkers for therapeutic interventions. In this study, we explored potential biomarkers for monitoring tofacitinib treatment response in patients with RA.
View Article and Find Full Text PDFDiscov Oncol
March 2025
Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Breast cancer is a potentially fatal illness that affects millions of women worldwide. Methotrexate (MTX) may be beneficial for treating breast cancer; however, high doses and prolonged use can cause drug resistance. Although certain citrus flavonoids-nobiletin, sinensetin, tangeretin, hesperidin, hesperetin, and naringenin-may overcome resistance to chemotherapy, no study has investigated MTX resistance.
View Article and Find Full Text PDFAnticancer Res
March 2025
AntiCancer Inc, San Diego, CA, U.S.A.;
Background/aim: Drug-resistance in osteosarcoma results in a very poor clinical prognosis and has been a recalcitrant problem over many decades. We have previously reported the development of super methotrexate (MTX)-resistant osteosarcoma cells (143B-MTX), selected from parental 143B osteosarcoma cells (143B-P) 143B-MTX cells were previously selected by culturing the cells with increasing concentrations of MTX, resulting in osteosarcoma cells which are 5,500 times more MTX-resistant than the parental cells, due to extreme over-expression of dihydrofolate reductase (DHFR). In the present study, the potential therapeutic efficacy of methionine restriction, using recombinant methioninase (rMETase), was explored to overcome super MTX-resistant osteosarcoma cells.
View Article and Find Full Text PDFAnticancer Res
October 2024
AntiCancer Inc., San Diego, CA, U.S.A.;
Background/aim: Methotrexate (MTX) resistance in osteosarcoma results in a very poor patient prognosis. We previously reported that super MTX-resistant osteosarcoma (143B-MTX) cells, selected from parental 143B osteosarcoma (143B-P) cells by culturing them with increasing concentrations of MTX, exhibited reduced malignancy, despite the over-expression of oncogenes. The present study explored the mechanism of reduced malignancy in the super MTX-resistant osteosarcoma cells.
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