Haptoglobin (Hp) is a blood plasma glycoprotein that plays a critical role in tissue protection and the prevention of oxidative damage. Haptoglobin is an acute-phase protein, its concentration in plasma changes in pathology, and the test for its concentration is part of normal clinical practice. Haptoglobin is a conservative protein and is the subject of research as a potential biomarker of many diseases, including malignant neoplasms. The Human gene is polymorphic and controls the synthesis of three major phenotypes-homozygous Hp1-1 and Hp2-2, and heterozygous Hp2-1, determined by a combination of allelic variants that are inherited. Numerous studies indicate that the phenotype of haptoglobin can be used to judge the individual's predisposition to various diseases. In addition, Hp undergoes various post-translational modifications (PTMs). Glioblastoma multiform (GBM) is the most malignant primary brain tumor. In our study, we have analyzed the state of Hp proteoforms in plasma and cells using 1D (SDS-PAGE) and 2D electrophoresis (2DE) with the following mass spectrometry (LC ES-MS/MS) or Western blotting. We found that the levels of α2- and β-chain proteoforms are up-regulated in the plasma of GBM patients. An unprocessed form of Hp2-2 (PreHp2-2, zonulin) with unusual biophysical parameters (pI/w) was also detected in the plasma of GBM patients and glioblastoma cells. Altogether, this data shows the possibility to use proteoforms of haptoglobin as a potential GBM-specific plasma biomarker.
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http://dx.doi.org/10.3390/ijms22126533 | DOI Listing |
Free Radic Biol Med
December 2024
Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, Seoul, 01897, South Korea. Electronic address:
Glioblastoma (GBM) remains a formidable clinical challenge, with cancer stem cells (CSCs) contributing to treatment resistance and tumor recurrence. Conventional treatments often fail to eradicate these CSCs characterized by enhanced resistance to standard therapies through metabolic plasticity making them key targets for novel treatment approaches. Addressing this challenge, this study introduces a novel combination therapy of dichloroacetate (DCA), a metabolic modulator and nonthermal plasma to induce oxidative stress in glioblastomas.
View Article and Find Full Text PDFCancer Cell Int
December 2024
Sezione di Farmacologia, Dipartimento di Medicina Interna, Università di Genova, Genova, Italy.
Background: Cellular prion protein (PrP) is a widely expressed membrane-anchored glycoprotein, which has been associated with the development and progression of several types of human malignancies, controlling cancer stem cell activity. However, the different molecular mechanisms regulated by PrP in normal and tumor cells have not been characterized yet.
Methods: To assess the role of PrP in patient-derived glioblastoma stem cell (GSC)-enriched cultures, we generated cell lines in which PrP was either overexpressed or down-regulated and investigated, in 2D and 3D cultures, its role in cell proliferation, migration, and invasion.
Cell Death Differ
December 2024
Division of Hematology and Oncology, Department of Pediatrics, Penn State College of Medicine, Hershey, PA, USA.
Disulfidptosis is a recently identified form of cell death characterized by the aberrant accumulation of cellular disulfides. This process primarily occurs in glucose-starved cells expressing higher levels of SLC7A11 and has been proposed as a therapeutic strategy for cancers with hyperactive SCL7A11. However, the potential for inducing disulfidptosis through other mechanisms in cancers remains unclear.
View Article and Find Full Text PDFInt J Gen Med
December 2024
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China.
Purpose: Glioblastoma (GBM) is associated with metabolic disturbances, yet the relationships between metabolites with GBM have not been comprehensively explored. This study aims to fill this gap by integrating Mendelian randomization (MR) analysis with clinical validation.
Patients And Methods: Summary data from genome-wide association study (GWAS) of cerebrospinal fluid (CSF) metabolites, plasma metabolites, and GBM were obtained separately.
Redox Biol
December 2024
Radiation Immuno-Oncology Group, Central Institute for Translational Cancer Research (TranslaTUM), TUM School of Medicine and Health, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany; Department of Radiation Oncology, TUM School of Medicine and Health, Klinikum rechts der Isar, Technical University of Munich (TUM), Munich, Germany. Electronic address:
Despite advances in multimodal therapy approaches such as resection, chemotherapy and radiotherapy, the overall survival of patients with grade 4 glioblastoma (GBM) remains extremely poor (average survival time <2 years). Altered lipid metabolism, which increases fatty acid synthesis and thereby contributes to radioresistance in GBM, is a hallmark of cancer. Therefore, we explored the radiosensitizing effect of the clinically approved, lipid-lowering drug fenofibrate (FF) in different GBM cell lines (U87, LN18).
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