Phase II study of amonafide in patients with recurrent glioma

Levitt, Ralph; Buckner, Jan C.; Cascino, Terrence L.; Burch, Patrick A.; Morton, Roscoe F.; Westberg, Mark; Goldberg, Richard M.; Gallagher, James; O’Fallon, Judith R.; Scheithauer, Bernd W.

doi:10.1007/bf01058464

Cited by 9 publications

(1 citation statement)

References 15 publications

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“…Of the 22 eligible and evaluable patients treated, tumour regression persisted for more than 1 year in 2 (9%). The remaining patients did not experience tumour regression; one case had stable disease for more than 6 months ( 41 ). However, the study used a small study sample and a larger clinical trial should be conducted or could be combined with temozolomide.To demonstrate the anti-glioma activity of Amonafide at the cellular level, we examined the proliferation of U251 and A172 cells by means of a CCK-8 assay and a plate-clone formation assay.…”

Section: Discussionmentioning

confidence: 99%

Novel prognostic features and personalized treatment strategies for mitochondria-related genes in glioma patients

Zhou

Chai

et al. 2023

Front. Endocrinol.

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BackgroundGliomas are the most common intracranial nervous system tumours that are highly malignant and aggressive, and mitochondria are an important marker of metabolic reprogramming of tumour cells, the prognosis of which cannot be accurately predicted by current histopathology. Therefore, Identify a mitochondrial gene with immune-related features that could be used to predict the prognosis of glioma patients.MethodsGliomas data were downloaded from the TCGA database and mitochondrial-associated genes were obtained from the MITOCARTA 3.0 dataset. The CGGA, kamoun and gravendeel databases were used as external datasets. LASSO(Least absolute shrinkage and selection operator) regression was applied to identify prognostic features, and area and nomograms under the ROC(Receiver Operating Characteristic) curve were used to assess the robustness of the model. Single sample genomic enrichment analysis (ssGSEA) was employed to explore the relationship between model genes and immune infiltration, and drug sensitivity was used to identify targeting drugs. Cellular studies were then performed to demonstrate drug killing against tumours.ResultsCOX assembly mitochondrial protein homolog (CMC1), Cytochrome c oxidase protein 20 homolog (COX20) and Cytochrome b-c1 complex subunit 7 (UQCRB) were identified as prognostic key genes in glioma, with UQCRB, CMC1 progressively increasing and COX20 progressively decreasing with decreasing risk scores. ROC curve analysis of the TCGA training set model yielded AUC (Area Under The Curve) values >0.8 for 1-, 2- and 3-year survival, and the model was associated with both CD8+ T cells and immune checkpoints. Finally, using cellMiner database and molecular docking, it was confirmed that UQCRB binds covalently to Amonafide via lysine at position 78 and threonine at position 82, while cellular assays showed that Amonafide inhibits glioma migration and invasion.ConclusionOur three mitochondrial genomic composition-related features accurately predict Survival in glioma patients, and we also provide glioma chemotherapeutic agents that may be mitochondria-related targets.

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Section: Discussionmentioning

confidence: 99%