Imaging Modalities: Neuropathology

Weis, Serge; Sonnberger, Michael; Dunzinger, Andreas; Voglmayr, Eva; Aichholzer, Martin; Kleiser, Raimund; Strasser, Peter

doi:10.1007/978-3-7091-1544-2_3

Cited by 1 publication

(1 citation statement)

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“…One of the most common and one of the most malicious CNS tumors is glioblastoma multiforme (GBM), a primary brain cancer that accounts in US for 50.1% of all primary malignant brain and other CNS neoplasms cases with an age-adjusted annual incidence rate of 3.26 per 100,000 population [ 1 ]. GBM is astrocytoma lesion classified as grade IV by the WHO and characterized by a high variability of pathological features, including pleomorphic cells with anaplastic nature, high mitotic activity, invasive growth, microvascular hyperplasia, and presence of necrotic centers due to the hypoxic environment [ 2 , 3 ]. Standard treatment involves the safest surgical removal of tumor mass to the greatest extent possible, followed by radiotherapy at a total dose of 60 Gy delivered in 2 Gy doses over 30 sessions across 6 weeks and concomitant daily 75 mg/m 2 temozolomide (TMZ) administration.…”

Section: Introductionmentioning

confidence: 99%

Repurposed Drugs Celecoxib and Fmoc-L-Leucine Alone and in Combination as Temozolomide-Resistant Antiglioma Agents—Comparative Studies on Normal and Immortalized Cell Lines, and on C. elegans

Uram,

Pieńkowska,

Misiorek

et al. 2024

IJMS

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Glioblastoma multiforme therapy remains a significant challenge since there is a lack of effective treatment for this cancer. As most of the examined gliomas express or overexpress cyclooxygenase-2 (COX-2) and peroxisome proliferator-activated receptors γ (PPARγ), we decided to use these proteins as therapeutic targets. Toxicity, antiproliferative, proapoptotic, and antimigratory activity of COX-2 inhibitor (celecoxib—CXB) and/or PPARγ agonist (Fmoc-L-Leucine—FL) was examined in vitro on temozolomide resistant U-118 MG glioma cell line and comparatively on BJ normal fibroblasts and immortalized HaCaT keratinocytes. The in vivo activity of both agents was studied on C. elegans nematode. Both drugs effectively destroyed U-118 MG glioma cells via antiproliferative, pro-apoptotic, and anti-migratory effects in a concentration range 50–100 µM. The mechanism of action of CXB and FL against glioma was COX-2 and PPARγ dependent and resulted in up-regulation of these factors. Unlike reports by other authors, we did not observe the expected synergistic or additive effect of both drugs. Comparative studies on normal BJ fibroblast cells and immortalized HaCaT keratinocytes showed that the tested drugs did not have a selective effect on glioma cells and their mechanism of action differs significantly from that observed in the case of glioma. HaCaTs did not react with concomitant changes in the expression of COX-2 and PPARγ and were resistant to FL. Safety tests of repurposing drugs used in cancer therapy tested on C. elegans nematode indicated that CXB, FL, or their mixture at a concentration of up to 100 µM had no significant effect on the entire nematode organism up to 4th day of incubation. After a 7-day treatment, CXB significantly shortened the lifespan of C. elegans at 25–400 µM concentration and body length at 50–400 µM concentration.

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Section: Introductionmentioning

confidence: 99%