Because a subpopulation of cancer stem cells (tumor-initiating cells, TICs) is believed to be responsible for the development, progression, and recurrence of many tumors, we evaluated the in vitro sensitivity of human glioma TICs to epidermal growth factor receptor (EGFR) kinase inhibitors (erlotinib and gefitinib) and possible molecular determinants for their effects. Cells isolated from seven glioblastomas (GBM 1-7) and grown using neural stem cell permissive conditions were characterized for in vivo tumorigenicity, expression of tumor stem cell markers (CD133, nestin), and multilineage differentiation properties, confirming that these cultures are enriched in TICs. TIC cultures were challenged with increasing concentrations of erlotinib and gefitinib, and their survival was evaluated after 1-4 days. In most cases, a time- and concentration-dependent cell death was observed, although GBM 2 was completely insensitive to both drugs, and GBM 7 was responsive only to the highest concentrations tested. Using a radioligand binding assay, we show that all GBM TICs express EGFR. Erlotinib and gefitinib inhibited EGFR and ERK1/2 phosphorylation/activation in all GBMs, irrespective of the antiproliferative response observed. However, under basal conditions GBM 2 showed a high Akt phosphorylation that was completely insensitive to both drugs, whereas GBM 7 was completely insensitive to gefitinib, and Akt inactivation occurred only for the highest erlotinib concentration tested, showing a precise relationship with the antiproliferative effects of the drug. Interestingly, in GBM 2, phosphatase and tensin homolog expression was significantly down-regulated, possibly accounting for the insensitivity to the drugs. In conclusion, glioma TICs are responsive to anti-EGFR drugs, but phosphatase and tensin homolog expression and Akt inhibition seem to be necessary for such effect.
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http://dx.doi.org/10.1074/jbc.M807111200 | DOI Listing |
Int J Mol Sci
December 2024
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Five phenolic Schiff bases (-) incorporating a fragment of methanesulfonamide were synthesized and evaluated for their efficacy as antitumor agents. Compounds and demonstrated the most potent antitumor action, with a positive cytotoxic effect (PCE) of 54/59 and 59/59 and a mean growth percentage (MG%) of 67.3% and 19.
View Article and Find Full Text PDFCancers (Basel)
December 2024
Department of Chest Medicine, Taichung Veterans General Hospital, No. 1650, Sect. 4, Taiwan Boulevard, Taichung 407, Taiwan.
Background/objectives: Osimertinib is a standard sequential therapy for advanced and recurrent Epidermal Growth Factor Receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients with the T790M mutation, following treatment with first- or second-generation EGFR Tyrosine Kinase Inhibitors (TKIs). This study aims to investigate the differences in clinical outcomes between osimertinib as a 2nd-line treatment and as a ≥3rd-line treatment in this patient population.
Methods: Between September 2014 and March 2023, we enrolled advanced and recurrent T790M + NSCLC patients who had received osimertinib as sequential treatment for analysis.
RSC Adv
January 2025
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University P.O. Box 2457 Riyadh 11451 Saudi Arabia
We tested newly synthesized compounds 1-13 on 59 cancer cell lines and found that acylhydrazones 5, 6, 7, 9, and 12 showed the best cytotoxic activity. They stopped the mean growth percentage (MG%) by an average of 23.5, 55.
View Article and Find Full Text PDFCancer Diagn Progn
January 2025
Department of Respiratory Medicine, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan.
Background/aim: The albumin-bilirubin (ALBI) grade is an assessment tool for hepatic function and prognosis in patients with hepatocellular carcinoma (HCC). However, its significance in patients with non-small cell lung cancer (NSCLC) treated with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) remains unclear. We retrospectively investigated the relationship between pre-treatment ALBI grade and hepatotoxicity and treatment efficacy in patients with NSCLC receiving EGFR-TKIs.
View Article and Find Full Text PDFJ Food Drug Anal
December 2024
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Non-small cell lung cancer (NSCLC) is commonly treated with tyrosine kinase inhibitors (TKIs). However, adverse events from such treatment can lead to treatment discontinuation and additional medical expenditures. Ambulatory care from oncology pharmacists in patient education and symptom management can benefit patients with NSCLC.
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