Background & Objectives: The clinical study showed that the P-glycoprotein(P-gp) expression was closely associated with the chemotherapeutic effect, response rate, prognosis, and survival time. Until now, few clinical papers have reported about metastatic sites and its response to chemotherapy with P-gp expression in metastatic breast carcinoma. The current study was designed to investigate the role of P-gp expression and its clinical value of chemotherapy for the patients with different metastatic sites of this carcinoma.
Methods: P-gp expression in 46 postoperative patients with metastatic breast carcinoma was detected by SABC immunohistochemical method. 43 cases treated with combination regimen: Cyclophosphamide 600 mg/m2 i.v. on day 1, Pirarubicin 60 mg/m2 i.v. on day 1, 5-Fluorouracil 600 mg/m2 i.v. on days 1 and 8. Repeat the cycle every 3 weeks for at least 2 cycles. The correlation between P-gp expression and chemotherapeutic response was analyzed.
Results: 1) P-gp expression positive rate was 56.5%, the P-gp expression in the patients with lung or liver viscera metastasis was higher than that in skin or lymph node metastasis (P = 0.049). 2) The overall response rate was 58.1% in 43 patients. The response rate of the P-gp negative group was higher than the P-gp positive group(P < 0.01). 3) The response rate in the patients with skin and lymph node metastasis was higher than the patients with lung and liver metastasis (P < 0.05). 4) The postoperative patients who had received CAF(cyclophosphamide + adriamycin + 5-fluorouracil) or CMF(cyclophosphamide + methotrexate + 5-fluorouracil) regimen adjuvant chemotherapy previously, the response rate of metastatic diseases to chemotherapy had no significant difference (P > 0.05).
Conclusions: P-gp expression may be considered as an index for evaluating multidrug resistance, guiding drug use, and judging prognosis of the patients with metastatic breast carcinoma.
Download full-text PDF |
Source |
---|
Technol Cancer Res Treat
January 2025
Cell Therapy Center, The University of Jordan, Amman, Jordan.
Background: Doxorubicin (DOX) is a potent chemotherapeutic agent for breast cancer, but its effectiveness is often diminished by resistance mechanisms, particularly through p-glycoprotein (P-gp) mediated drug efflux. Clarithromycin (CAM), a macrolide antibiotic, inhibits multiple metabolic pathways including CYP3A and P-gp, potentially countering DOX resistance.
Objective: This study aimed to evaluate the potentiation of DOX and its effectiveness against the MCF-7 breast cancer cell line by encapsulating both DOX and CAM in PEGylated liposomes.
Eur J Pharm Sci
January 2025
Preclinical Sciences & Translational Safety, Janssen R&D, Turnhoutseweg 30, 2340, Beerse, Belgium. Electronic address:
The purpose of this study was to evaluate EpiColon, a novel human organotypic 3D colon microtissue prototype, developed to assess colonic drug disposition, with a particular focus on permeability ranking, and compare its performance to Caco-2 monolayers. EpiColon was characterized for barrier function using transepithelial electrical resistance (TEER), morphology via histology and immunohistochemistry, and functionality through drug transport studies measuring apparent permeability (P). Cutoff thresholds for the permeability of FITC-dextran 4 kDa (FD4), FITC-dextran 10 kDa (FD10S), and [C]mannitol were established to monitor microtissue integrity.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address:
Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
January 2025
Université Clermont Auvergne, Institut Universitaire de Technologie, UMR INSERM-UCA, U1240, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), 5 Avenue Blaise Pascal, 63000 Clermont-Ferrand, France.
A method using high-performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) was developed and validated to quantify the innovative tool LightSpot®-FL-1, a selective permeability-glycoprotein (P-gp)-targeted fluorescent conjugate used to measure P-gp expression in cell samples. Quantifying P-gp is a major challenge in oncology as its overexpression in many cancer cells results in Multidrug Resistance (MDR) associated with chemotherapy failure. To develop the method reported herein, both sample preparation and analysis parameters were investigated.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Mechanistic Toxicology Branch, Division of Translational Toxicology, National Institutes of Environmental Health Sciences (NIH), Research Triangle Park, Durham, NC 27709, USA.
Acquired resistance to chemotherapeutic drugs is the primary cause of treatment failure in the clinic. While multiple factors contribute to this resistance, increased expression of ABC transporters-such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance proteins-play significant roles in the development of resistance to various chemotherapeutics. We found that Erastin, a ferroptosis inducer, was significantly cytotoxic to NCI/ADR-RES, a P-gp-expressing human ovarian cancer cell line.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!