Pokorná Markéta, Kútna Viera, Ovsepian Saak V, Matěj Radoslav, Černá Marie, O'Leary Valerie Bríd
Department of Medical Genetics, Third Faculty of Medicine, Charles University, Ruská 87, Vinohrady, 10000 Prague, Czech Republic.
Department of Experimental Neurobiology, National Institute of Mental Health, Topolová 748, 25067 Klecany, Czech Republic.
Pharmaceutics. 2024 Jan 18;16(1):123. doi: 10.3390/pharmaceutics16010123.
The heterogeneity of the glioma subtype glioblastoma multiforme (GBM) challenges effective neuropathological treatment. The reliance on in vitro studies and xenografted animal models to simulate human GBM has proven ineffective. Currently, a dearth of knowledge exists regarding the applicability of cell line biomolecules to the realm of GBM pathogenesis. Our study's objectives were to address this preclinical issue and assess prominin-1, ICAM-1, and as potential GBM diagnostic targets. The methodologies included haemoxylin and eosin staining, immunofluorescence, in situ hybridization and quantitative PCR. The findings identified that morphology correlates with malignancy in GBM patient pathology. Immunofluorescence confocal microscopy revealed prominin-1 in pseudo-palisades adjacent to necrotic foci in both animal and human GBM. Evidence is presented for an ICAM-1 association with degenerating vasculature. Significantly elevated nuclear expression from in situ hybridization and quantitative PCR reflected its role as a tumor activator. identified within necrotic GBM validated this potential prognostic biomolecule with extended survival. Here we present evidence for the stem cell marker prominin-1 and the chemotherapeutic target ICAM-1 in a glioma animal model and GBM pathology sections from patients that elicited alternative responses to adjuvant chemotherapy. This foremost study introduces the long non-coding RNA into the context of human GBM pathogenesis while substantiating the role of as a tumor suppressor. The validation of GBM biomarkers from cellular models contributes to the advancement towards superior detection, therapeutic responders and the ultimate attainment of promising prognoses for this currently incurable brain cancer.
多形性胶质母细胞瘤（GBM）这种胶质瘤亚型的异质性对有效的神经病理学治疗构成挑战。依靠体外研究和异种移植动物模型来模拟人类GBM已被证明是无效的。目前，关于细胞系生物分子在GBM发病机制领域的适用性，我们所知甚少。我们研究的目的是解决这一临床前问题，并评估prominin-1、ICAM-1等作为GBM潜在诊断靶点的情况。所采用的方法包括苏木精和伊红染色、免疫荧光、原位杂交和定量PCR。研究结果表明，在GBM患者病理中，形态与恶性程度相关。免疫荧光共聚焦显微镜显示，在动物和人类GBM中，坏死灶附近的假栅栏组织中有prominin-1。有证据表明ICAM-1与退化的血管有关。原位杂交和定量PCR显示核表达显著升高，这反映了它作为肿瘤激活剂的作用。在坏死性GBM中发现的[未提及的物质]通过延长生存期验证了其作为潜在预后生物分子的作用。在这里，我们展示了在胶质瘤动物模型和患者的GBM病理切片中，干细胞标志物prominin-1和化疗靶点ICAM-1的证据，这些证据引发了对辅助化疗的不同反应。这项首要研究将长链非编码RNA引入人类GBM发病机制的背景中，同时证实了[未提及的物质]作为肿瘤抑制因子的作用。从细胞模型验证GBM生物标志物有助于在更好的检测、治疗反应以及最终为这种目前无法治愈的脑癌实现有希望的预后方面取得进展。
