One of the mechanisms by which multidrug resistance is mediated, is the mdr1 gene product, P-glycooprotein. Immunohistochemistry was performed for 63 osteosarcomas of 54 patients to investigate P-glycoprotein expression using the monoclonal antibody JSB-1. Most of the patients were children or adolescents who had received treatment under the framework of the Cooperative Osteosarcoma Study Group. In addition P-glycoprotein expression was assayed in five growth plates. Of all cases 68.5% stained positive for P-glycoprotein. Cases that had received chemotherapy showed a higher incidence (80.9%) of positive P-glycoprotein immunostaining than cases that had not received chemotherapy (66.6%). No relation could be established between P-glycoprotein expression and the response to chemotherapy, since the majority of P-glycoprotein positive biopsies showed a good response in the surgical specimen after chemotherapy. Furthermore, 42.9% of P-glycoprotein negative biopsies were classified as non-responders in the later surgical specimen. In addition to P-glycoprotein expression in osteosarcomas positive immunostaining was also detected in osteoblasts, osteocytes, osteoclasts as well as in some chondroblasts. The results indicate that P-glycoprotein expression in osteosarcomas also exists prior to chemotherapy and resembles the phenotype of normal bone tissue. However, the determination of P-glycoprotein by using immunohistochemistry in biopsies of osteosarcomas cannot predict the response to chemotherapy.
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http://dx.doi.org/10.1007/s002920050134 | DOI Listing |
Int J Biol Macromol
January 2025
College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, PR China. Electronic address:
Multidrug resistance (MDR) has become a major challenge in tumor chemotherapy, primarily associated with the overexpression of P-glycoprotein (P-gp). Inhibiting P-gp expression and function through redox dyshomeostasis has shown great potential for reversing MDR. Here, a nanometer system of copper-based metal-organic framework (HA-CuMOF@DOX) modified with hyaluronic acid (HA) was constructed to overcome MDR via two-way regulation of redox homeostasis under hypoxia.
View Article and Find Full Text PDFFront Pharmacol
January 2025
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin, China.
Introduction: Deglycosylated azithromycin (Deg-AZM), a new transgelin agonist with positive therapeutic effects on slow transit constipation, has been approved for clinical trials in 2024. This work investigated the drug metabolism and transport of Deg-AZM to provide research data for further development of Deg-AZM.
Methods: A combination of UPLC-QTOF-MS was used to obtain metabolite spectra of Deg-AZM in plasma, urine, feces and bile.
Exp Mol Med
January 2025
Department of Pharmacy at The Second Affiliated Hospital, and Department of Pharmacology at College of Pharmacy (The Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), Harbin Medical University, Harbin, P. R. China.
Doxorubicin (DOX) is a first-line chemotherapy agent known for its cardiac toxicity. DOX-induced cardiotoxicity (DIC) severely limits the use for treating malignant tumors and is associated with a poor prognosis. The sensitivity to DIC varies among patients, but the precise mechanisms remain elusive.
View Article and Find Full Text PDFRegarding flotillin knockdown, drug resistance is reversed in colorectal cancer (CRC) cell lines; this is associated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, as our previous experimental results indicated. However, the exact mechanism underlying this pathway remains unclear. PI3K inhibitor and activator were added separately to clarify the role of the PI3K pathway in reversing drug resistance.
View Article and Find Full Text PDFFront Pharmacol
January 2025
The Marine Biomedical Research Institute, Guangdong Medical University, Zhanjiang, China.
Objectives: The purpose of this study was to investigate the effect of intestinal dysbiosis on the bioavailability of voriconazole and to explore any underlying mechanisms.
Method: Sprague-Dawley rats were randomly divided into two groups: a normal control group and a ceftriaxone-associated dysbiotic group. The composition of the intestinal flora was examined using 16S rRNA sequencing analysis.
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