On 21 patients with T1b-T3b tumours subjected to external radiotherapy and brachytherapy, the expression of P53 and glutathione S-transferase pi [GST-pi], immunohistochemically detected, the S-phase cells fraction (H-3-thymidine labeling index, TLI) and DNA content evaluated by image analysis were determined on biopsies before and after the first 10 Gy. P53 accumulation was reduced in 60% of P53-overexpressing tumours and not induced in P53-negative tumours, GST-pi was induced in about 40% of pretreatment GST-pi-negative cases, TLI was reduced in 70% of the cases regardless of pretreatment values, and DNA profiles remained unchanged in two-thirds of the cases. P53 accumulation was a predictor of 3-year relapse-free survival after radiotherapy, followed by GST-pi expression, whereas TLI did not influence prognosis.
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http://dx.doi.org/10.3892/ijo.10.1.41 | DOI Listing |
Int J Mol Sci
December 2024
Beijing Key Laboratory of Gene Resource and Molecular Development, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Cells meticulously regulate free calcium ion (Ca) concentrations, with the endoplasmic reticulum (ER) being crucial for Ca homeostasis. Disruptions in ER Ca balance can contribute to various diseases, including cancer. Although considerable research has focused on the direct mechanisms of ER Ca regulation, the role of microRNAs (miRNAs) in this process remains underexplored.
View Article and Find Full Text PDFMolecules
January 2025
Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA.
MDM2 and MDM4 are major negative regulators of tumor suppressor p53. Beyond regulating p53, MDM2 possesses p53-independent activity in promoting cell cycle progression and tumorigenesis via its RING domain ubiquitin E3 ligase activity. MDM2 and MDM4 form heterodimer polyubiquitin E3 ligases via their RING domain interaction.
View Article and Find Full Text PDFCancer Chemother Pharmacol
January 2025
Institute of Medicine, Chung-Shan Medical University, Taichung, 40201, Taiwan.
Objective: Based on our previous research, which demonstrated that elevated plasma endoglin (ENG) levels in lung cancer patients were associated with a better prognosis, increased sensitivity to pemetrexed, and enhanced tumor suppression, this study aims to validate these findings at the cellular level. The focus is on membrane and extracellular ENG and their influence on drug response and tumor cell behavior in non-small cell lung cancer (NSCLC) cells.
Methods: The correlation between ENG expression and pemetrexed-induced cytotoxicity in eight human non-squamous subtype NSCLC cell lines was analyzed.
Nat Cell Biol
January 2025
Department of Biochemistry, University of Oxford, Oxford, UK.
Delays in mitosis trigger p53-dependent arrest in G1 of the next cell cycle, thus preventing repeated cycles of chromosome instability and aneuploidy. Here we show that MDM2, the p53 ubiquitin ligase, is a key component of the timer mechanism triggering G1 arrest in response to prolonged mitosis. This timer function arises due to the attenuation of protein synthesis in mitosis.
View Article and Find Full Text PDFAgeing Res Rev
January 2025
Center for Global Health Research, Saveetha Medical College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:
Cellular senescence, a complex biological process resulting in permanent cell-cycle arrest, is central to aging and age-related diseases. A key concept in understanding cellular senescence is the Hayflick Limit, which refers to the limited capacity of normal human cells to divide, after which they become senescent. Senescent cells (SC) accumulate with age, releasing pro-inflammatory and tissue-remodeling factors collectively known as the senescence-associated secretory phenotype (SASP).
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