The Evaluation of Glyceryl C3‐Azolyl‐Thiogalactosides as Galectin‐1 and Galectin‐3 Ligands DOI Creative Commons
Vít Prouza, Jakub Zýka, Jaroslav Kozák

et al.

ChemMedChem, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 14, 2024

Abstract Galectins are a family of galactoside‐binding proteins involved in various pathophysiological processes, which makes them attractive targets for drug discovery. The derivatization d ‐galactose at C3 and C1 positions has been shown to increase the affinity synthetic galectin antagonists. In this study, two small libraries derivatives have designed synthesized. first series development novel aromatic 3‐azolyl‐3‐deoxy‐ ‐galactopyranoses. second consisted epimeric analogs glyceryl β‐ S ‐ ‐galactopyranosides, were also derivatized. Binding‐affinity evaluations galectin‐1 galectin‐3 revealed that galactose from both potential further optimization. Notably, combination modifications position ring on aglycone led identification promising inhibitors, specifically compounds 29R 32S .

Language: Английский

Metastatic brain tumors: from development to cutting‐edge treatment DOI Creative Commons
Guilong Tanzhu,

Liu Chen,

Jiaoyang Ning

et al.

MedComm, Journal Year: 2024, Volume and Issue: 6(1)

Published: Dec. 20, 2024

Abstract Metastatic brain tumors, also called metastasis (BM), represent a challenging complication of advanced tumors. Tumors that commonly metastasize to the include lung cancer and breast cancer. In recent years, prognosis for BM patients has improved, significant advancements have been made in both clinical preclinical research. This review focuses on originating from We briefly overview history epidemiology BM, as well current diagnostic treatment paradigms. Additionally, we summarize multiomics evidence mechanisms tumor occurrence development era artificial intelligence discuss role microenvironment. Preclinically, introduce establishment models, detailed molecular mechanisms, cutting‐edge methods. is primarily treated with comprehensive approach, including local treatments such surgery radiotherapy. For cancer, targeted therapy immunotherapy shown efficacy, while monoclonal antibodies, tyrosine kinase inhibitors, antibody–drug conjugates are effective BM. Multiomics approaches assist diagnosis treatment, revealing complex Moreover, agents often need cross blood–brain barrier achieve high intracranial concentrations, small‐molecule nanoparticles, peptide drugs. Addressing imperative.

Language: Английский

Citations

1
Hypoxic stress dysregulates functions of glioma-associated myeloid cells through epigenomic and transcriptional programs DOI Creative Commons
Monika Dźwigońska, Patrycja Rosa, Beata Kaza

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 16, 2024

ABSTRACT Hypoxia rapidly alters gene expression to allow cellular adaptation challenging conditions and support tumour growth. also affects the chromatin structure by modifications of histones DNA methylation. Glioblastoma (GBM) is an aggressive, deadly primary brain for which there no effective treatment. The microenvironment GBM highly heterogeneous, with infiltration glioma-associated microglia macrophages (GAMs) presence necrotic, hypoxic regions. mechanisms through hypoxia regulates functions infiltrating immune cells remain poorly understood. Here, we show that modulates myeloid markers in distinct ways: upregulates monocytic marker Lgals3 downregulates microglial P2ry12 Tmem119 GAMs vitro vivo , as shown using human mouse single-cell transcriptomics datasets. genome-wide hypoxia-dependent transcriptomic changes were determined microglia-glioma co-cultures. Numerous GAM subtype dysregulated response stress due associated accessibility, ATACseq. While alone drives a decrease overall accessibility at promoters, exposure glioma under leads both increases decreases promoter regions cells. enriched motifs transcription factors regarded master regulators cell identity function, including SPI1 or IRF8 . Overall, our data highlights importance strong intratumoral regulator functions, adds complexity characterisation particular subpopulations.

Language: Английский

Citations

0
Systems immunology insights into brain metastasis DOI Creative Commons

Wenjuan Dong,

Jianting Sheng,

Jianxiong Cui

et al.

Trends in Immunology, Journal Year: 2024, Volume and Issue: 45(11), P. 903 - 916

Published: Oct. 22, 2024

Brain metastasis poses formidable clinical challenges due to its intricate interactions with the brain's unique immune environment, often resulting in poor prognoses. This review delves into systems immunology's role uncovering dynamic interplay between metastatic cancer cells and brain immunity. Leveraging spatial single-cell technologies, along advanced computational modeling, immunology offers unprecedented insights mechanisms of evasion tumor proliferation. Recent studies highlight potential immunotherapeutic targets, suggesting strategies boost antitumor immunity counteract cell brain. Despite substantial progress, persist, particularly accurately simulating human conditions. underscores need for interdisciplinary collaboration harness full potential, aiming dramatically improve outcomes patients metastasis.

Language: Английский

Citations

0
The Evaluation of Glyceryl C3‐Azolyl‐Thiogalactosides as Galectin‐1 and Galectin‐3 Ligands DOI Creative Commons
Vít Prouza, Jakub Zýka, Jaroslav Kozák

et al.

ChemMedChem, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 14, 2024

Abstract Galectins are a family of galactoside‐binding proteins involved in various pathophysiological processes, which makes them attractive targets for drug discovery. The derivatization d ‐galactose at C3 and C1 positions has been shown to increase the affinity synthetic galectin antagonists. In this study, two small libraries derivatives have designed synthesized. first series development novel aromatic 3‐azolyl‐3‐deoxy‐ ‐galactopyranoses. second consisted epimeric analogs glyceryl β‐ S ‐ ‐galactopyranosides, were also derivatized. Binding‐affinity evaluations galectin‐1 galectin‐3 revealed that galactose from both potential further optimization. Notably, combination modifications position ring on aglycone led identification promising inhibitors, specifically compounds 29R 32S .

Language: Английский

Citations

0