Rational design of poly-L-glutamic acid-palbociclib conjugates for pediatric glioma treatment

Melnyk, Tetiana; Masiá, Esther; Zagorodko, Oleksandr; Conejos‐Sánchez, Inmaculada; Vicent, María J.

doi:10.1016/j.jconrel.2023.01.079

Cited by 7 publications

(3 citation statements)

References 31 publications

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“…A previous study showed that both AQB (HOTAIR-EZH2 inhibitor AC1Q3QWB) and palbociclib inhibited Wnt/β-linked protein signaling, and that the combination of both inhibitors had a stronger inhibitory effect on glioma metastasis ( 35 ). Another study showed that the use of low doses of poly-L-glutamate-paboxinib couples in pediatric gliomas improved the ability of paboxinib alone to killing diffuse pontine glioma cells ( 36 ). LDK-378, also known as Ceritinib, is a small molecule inhibitor of mesenchymal lymphoma kinase, insulin-like growth factor 1 receptor, and focal adhesion kinase, and is highly expressed in glioblastomas and many brain metastases, and has anti-tumor activity in central nervous system malignancies ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Machine learning approach to screen new diagnostic features of adamantinomatous craniopharyngioma and explore personalised treatment strategies

Wu¹,

Qin²,

Fang³

et al. 2023

Transl Pediatr

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Background Adamantinoma craniopharyngioma (ACP) is a non-malignant tumour of unknown pathogenesis that frequently occurs in children and has malignant potential. The main treatment options are currently surgical resection and radiotherapy. These treatments can lead to serious complications that greatly affect the overall survival and quality of life of patients. It is therefore important to use bioinformatics to explore the mechanisms of ACP development and progression and to identify new molecules. Methods Sequencing data of ACP was downloaded from the comprehensive gene expression database for differentially expressed gene identification and visualized by Gene Ontology, Kyoto Gene, and gene set enrichment analyses (GSEAs). Weighted correlation network analysis was used to identify the genes most strongly associated with ACP. GSE94349 was used as the training set and five diagnostic markers were screened using machine learning algorithms to assess diagnostic accuracy using receiver operating characteristic (ROC) curves, while GSE68015 was used as the validation set for verification. Results Type I cytoskeletal 15 (KRT15), Follicular dendritic cell secreted peptide (FDCSP), Rho-related GTP-binding protein RhoC (RHOC), Modulates negatively TGFB1 signaling in keratinocytes (CD109), and type II cytoskeletal 6A (KRT6A) (area under their receiver operating characteristic curves is 1 for both the training and validation sets), Nomograms constructed using these five markers can predict progression of ACP patients. Whereas ACP tissues with activated T-cell surface glycoprotein CD4, Gamma delta T cells, eosinophils and regulatory T cells were expressed at higher levels than in normal tissues, which may contribute to the pathogenesis of ACP. According to the analysis of the CellMiner database (Tumor cell and drug related database tools), high CD109 levels showed significant drug sensitivity to Dexrazoxane, which has the potential to be a therapeutic agent for ACP. Conclusions Our findings extend understandings of the molecular immune mechanisms of ACP and suggest possible biomarkers for the targeted and precise treatment of ACP.

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Section: Discussionmentioning

confidence: 99%

Machine learning approach to screen new diagnostic features of adamantinomatous craniopharyngioma and explore personalised treatment strategies

Wu¹,

Qin²,

Fang³

et al. 2023

Transl Pediatr

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“…Malignant brain and central nervous system (CNS) tumors account for ~21% of tumors in children and represent the second leading cause of pediatric cancer deaths after leukemia [ 57 , 58 ]. Pediatric glioma, a common central nervous system tumor in children, is classified into low-grade and high-grade categories.…”

Section: Lncrnas In Gliomasmentioning

confidence: 99%

Insights into the Role of LncRNAs and miRNAs in Glioma Progression and Their Potential as Novel Therapeutic Targets

Kciuk

Yahya

Mohamed

et al. 2023

Cancers

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Accumulating evidence supports that both long non-coding and micro RNAs (lncRNAs and miRNAs) are implicated in glioma tumorigenesis and progression. Poor outcome of gliomas has been linked to late-stage diagnosis and mostly ineffectiveness of conventional treatment due to low knowledge about the early stage of gliomas, which are not possible to observe with conventional diagnostic approaches. The past few years witnessed a revolutionary advance in biotechnology and neuroscience with the understanding of tumor-related molecules, including non-coding RNAs that are involved in the angiogenesis and progression of glioma cells and thus are used as prognostic biomarkers as well as novel therapeutic targets. The emerging research on lncRNAs and miRNAs highlights their crucial role in glioma progression, offering new insights into the disease. These non-coding RNAs hold significant potential as novel therapeutic targets, paving the way for innovative treatment approaches against glioma. This review encompasses a comprehensive discussion about the role of lncRNAs and miRNAs in gene regulation that is responsible for the promotion or the inhibition of glioma progression and collects the existing links between these key cancer-related molecules.

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“…Polymeric micelles represent probably one of the most studied nanocarriers for anticancer drug delivery owing to their notable advantages. − However, compromised micelle stability in the blood circulation upon intravenous injection due to massive dilution by body fluids and blood and interactions with a variety of biomolecules and extraneous factors leads to leakage and premature diffusion of encapsulated therapeutics resulting in toxicity to normal tissues and significantly compromised therapeutic efficiency at the focal site. , Polymers with advanced topologies, including star-shaped, , (hyper)branched, dendritic, bottlebrush, and cyclic structures, , have been reported to endow the resulting polymeric self-assemblies with enhanced colloidal stability for long blood circulation in vivo. Among these reported advanced topological architectures, cyclic and its derived topologies have attracted considerable interest in the past decade because of the endless chain structure-associated unique properties that are quite different from those of linear counterparts .…”

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confidence: 99%

UV Irradiation-Induced Cyclic-to-Linear Topological Changes of a Light/pH Dual-Sensitive Cyclic Copolymer for Enhanced Drug Delivery

Liu

Zheng

et al. 2023

ACS Macro Lett.

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Cyclic polymers with cleavable backbones triggered by either external or internal stimuli can realize simultaneous extracellular stability and intracellular destabilization of cyclic polymer-based nanocarriers but remain seldom reported. To this end, we prepared herein cyclic-ONB-P(OEGMA-st-DMAEMA) (c-ONB-P(OEGMA-st-DMAEMA)) with a light-cleavable junction in the polymer backbone based on oligo (ethylene glycol) monomethyl ether methacrylate (OEGMA) and N,N-dimethylaminoethyl methacrylate (DMAEMA) using a light-cleavable atom transfer radical polymerization (ATRP) initiator containing an o-nitrobenzyl (ONB) ester group. Together with the pH-sensitivity of DMAEMA, c-ONB-P(OEGMA-st-DMAEMA) shows a light-cleavable mainchain and pH-sensitive side chains. Notably, doxorubicin (DOX)-loaded c-ONB-P(OEGMA4-st-DMAEMA38) (C2) micelles mediated an IC50 value of 2.28 μg/mL in Bel-7402 cells, which is 1.7-fold lower than that acquired without UV irradiation. This study thus reported the synthesis of a cyclic copolymer with a UV-cleavable backbone and uncovered the effects of topological modulation on the in vitro controlled release properties of cyclic polymers.

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Rational design of poly-L-glutamic acid-palbociclib conjugates for pediatric glioma treatment

Cited by 7 publications

References 31 publications

Machine learning approach to screen new diagnostic features of adamantinomatous craniopharyngioma and explore personalised treatment strategies

Machine learning approach to screen new diagnostic features of adamantinomatous craniopharyngioma and explore personalised treatment strategies

Insights into the Role of LncRNAs and miRNAs in Glioma Progression and Their Potential as Novel Therapeutic Targets

UV Irradiation-Induced Cyclic-to-Linear Topological Changes of a Light/pH Dual-Sensitive Cyclic Copolymer for Enhanced Drug Delivery

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