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Glioblastoma is the most common and aggressive primary malignant brain tumor. Temozolomide (TMZ), a chemotherapeutic agent combined with radiation therapy, is used as a standard treatment. The infiltrative nature of glioblastoma, however, interrupts effective treatment with TMZ and increases the tendency to relapse. Voltage-gated chloride channels have been identified as crucial regulators of glioma cell migration and invasion by mediating cell shape and volume change. Accordingly, chloride current inhibition by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), a chloride channel blocker, suppresses cell movement by diminishing the osmotic cell volume regulation. In this study, we developed a novel compound, TMZ conjugated with NPPB (TMZ-NPPB), as a potential anticancer drug. TMZ-NPPB blocked chloride currents in U373MG, a severely invasive human glioma cell line, and suppressed migration and invasion of U373MG cells. Moreover, TMZ-NPPB exhibited DNA modification activity similar to that of TMZ, and surprisingly showed remarkably enhanced cytotoxicity relative to TMZ by inducing apoptotic cell death via DNA damage. These findings indicate that TMZ-NPPB has a dual function in blocking both proliferation and migration of human glioma cells, thereby suggesting its potential to overcome challenges in current glioblastoma therapy.
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http://dx.doi.org/10.1021/acschemneuro.5b00178 | DOI Listing |
Cureus
November 2024
Pathology, University of Pittsburgh Medical Center, Pittsburgh, USA.
Glioma-associated oncogene (-altered mesenchymal tumors are a newly described entity of neoplasms with very few case reports published in the literature. -altered neoplasms have a moderate degree of variability as they are seen in a broad range of anatomic sites and amongst people of all ages. A common feature that most -altered tumors share is the histologic makeup of monomorphic ovoid cells organized in distinct nests and an arborizing vascular blood supply.
View Article and Find Full Text PDFCancer Cell Int
December 2024
Institute for Excellence in Clinical Medicine of Kunshan First People's Hospital, Soochow University, Suzhou, China.
Gliomas are the most common tumors of the central nervous system, with glioblastoma (GBM) being particularly aggressive and fatal. Current treatments for GBM, including surgery and chemotherapy, are limited by tumor aggressiveness and the blood-brain barrier. Therefore, understanding the molecular mechanisms driving GBM growth is essential.
View Article and Find Full Text PDFMol Med
December 2024
Department of Neurobiology and Anatomy, Key Laboratory of Neurobiology, Xuzhou Medical University, 209, Tongshan Road, Xuzhou, 221004, China.
Doublecortin (DCX) is a microtubule-associated protein known to be a key regulator of neuronal migration and differentiation during brain development. However, the role of DCX, particularly in regulating the survival and growth of glioma cells, remains unclear. In this study, we utilized CRISPR/Cas9 technology to knock down DCX in the human glioma cell line (U251).
View Article and Find Full Text PDFSensitive detection of incident acoustic waves over a broad frequency band offers a faithful representation of photoacoustic pressure transients of biological microstructures. Here, we propose a plasmon waveguide resonance sensor for responding to the photoacoustic impulses. By sequentially depositing Au, MgF, and SiO films on a coverslip, a composite waveguide layer produces a tightly confined optical evanescent field at the SiO-water interface with extremely strong electric field intensity, enabling the retrieval of photoacoustic signals with an estimated noise-equivalent-pressure (NEP) sensitivity of ∼92 Pa and a -6-dB bandwidth of ∼208 MHz.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Background: Glioblastoma (GB) is the stage IV of glioma and mesenchymal GB represents the most common and malignant subtype characterized with elevated expression of a mesenchymal marker YKL-40 and resistance to immune drug therapy. Here, we determined if YKL-40 regulates kynurenine (Kyn) pathway (KP) metabolism that contributes to establishing an immune suppressive microenvironment in GB.
Methods: Tumor cells expressing YKL-40 from GB patients were isolated and activated cellular metabolisms were identified via gene microarray analysis.
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