99mTc(CO)3-labeled 1-(2-Pyridyl)piperazine derivatives as radioligands for 5HT7 receptors DOI Creative Commons
Alireza Mardanshahi,

Samaneh Vaseghi,

Seyed Jalal Hosseinimehr

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 17, 2023

Abstract The 5-hydroxytryptamine receptor (5-HTR) family involves seven classes of receptors. 5-HT 7 R is the newest member this and contributes to different physiological pathological processes. As a pathology, Glioblastoma multiform (GBM) overexpresses R; hence, study aims develop radiolabeled aryl piperazine derivatives as imaging agents. To that end, compounds 6 1-(3-nitropyridin-2-yl)piperazine were with fac -[ 99m Tc(CO) 3 (H 2 O) ] + ( Tc(CO)3-[ ]) obtained high radiochemical purity (RCP>94%). possess affinity toward U-87 MG cell line. calculated K i for them was 26.85±0.78 nM 36.67±0.89 nM. biodistribution in normal mice indicates brain uptake highest at 30 min post-injection (0.8±0.25 0.64±0.18 %ID/g, respectively). data U87-MG xenograft model revealed these radiotracers could accumulate tumor site, observed 60 (3.38±0.65 3.27±0.5 injection pimozide can block tumor’s radiotracer uptake, indicating binding R. also confirms data. acquired images clearly show tumor-to-muscle ratio 3.33 3.88, respectively.

Language: Английский

microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)—Recent Literature Review DOI Open Access
Marianna Makowska, Beata Smolarz, Hanna Romanowicz

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3521 - 3521

Published: Feb. 9, 2023

Glioblastoma multiforme (GBM) is the most common, malignant, poorly promising primary brain tumor. GBM characterized by an infiltrating growth nature, abundant vascularization, and a rapid aggressive clinical course. For many years, standard treatment of gliomas has invariably been surgical supported radio- chemotherapy. Due to location significant resistance conventional therapies, prognosis glioblastoma patients very poor cure rate low. The search for new therapy targets effective therapeutic tools cancer current challenge medicine science. microRNAs (miRNAs) play key role in cellular processes, such as growth, differentiation, cell division, apoptosis, signaling. Their discovery was breakthrough diagnosis diseases. Understanding structure miRNAs may contribute understanding mechanisms regulation dependent on miRNA pathogenesis diseases underlying these short non-coding RNAs, including glial tumors. This paper provides detailed review latest reports relationship between changes expression individual formation development gliomas. use this also discussed.

Language: Английский

Citations

60

Identification of a disulfidptosis-related genes signature for prognostic implication in lung adenocarcinoma DOI Creative Commons
Jiaqi Huang, Jingyuan Zhang,

Fanqin Zhang

et al.

Computers in Biology and Medicine, Journal Year: 2023, Volume and Issue: 165, P. 107402 - 107402

Published: Aug. 28, 2023

Lung adenocarcinoma (LUAD) is the most prevalent subtype of non-small cell lung cancer. Additionally, disulfidptosis, a newly discovered type death, has been found to be closely associated with onset and progression tumors. The study first identified genes related disulfidptosis through correlation analysis. These were then screened using univariate cox regression LASSO regression, prognostic model was constructed multivariate regression. A nomogram also created predict prognosis LUAD. validated in three independent data sets: GSE72094, GSE31210, GSE37745. Next, patients grouped based on their median risk score, differentially expressed between two groups analyzed. Enrichment analysis, immune infiltration drug sensitivity evaluation conducted. In this study, we examined 21 developed gene signature that poorer Our datasets showed AUC values greater than 0.5 at 1, 3, 5 years. analysis revealed disulfidptosis-related had multifaceted impact LUAD, particularly relation tumor development, proliferation, metastasis. Patients high-risk group exhibited higher purity lower stromal ESTIMATE Immune score. This analyzed its disease association microenvironment. findings research provide valuable insights into understanding could potentially lead development new treatment strategies.

Language: Английский

Citations

41

Engineered Salmonella inhibits GPX4 expression and induces ferroptosis to suppress glioma growth in vitro and in vivo DOI
Jiawen Chen, Ting Li, Nan Zhou

et al.

Journal of Neuro-Oncology, Journal Year: 2023, Volume and Issue: 163(3), P. 607 - 622

Published: June 23, 2023

Language: Английский

Citations

13

The dopamine receptor D1 inhibitor, SKF83566, suppresses GBM stemness and invasion through the DRD1-c-Myc-UHRF1 interactions DOI Creative Commons
Zhiyi Xue, Yan Zhang, Ruiqi Zhao

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Jan. 22, 2024

Abstract Background Extensive local invasion of glioblastoma (GBM) cells within the central nervous system (CNS) is one factor that severely limits current treatments. The aim this study was to uncover genes involved in process, which could also serve as therapeutic targets. For isolation invasive GBM from non-invasive cells, we used a three-dimensional organotypic co-culture where glioma stem cell (GSC) spheres were confronted with brain organoids (BOs). Using ultra-low input RNA sequencing (ui-RNA Seq), an gene signature obtained exploited context. Methods GFP-labeled tumor sorted and regions co-cultures. Ui-RNA analysis performed find cluster up-regulated compartment. This further analyzed using Connectivity MAP (CMap) database. led identification SKF83566, antagonist D1 dopamine receptor (DRD1), candidate molecule. Knockdown overexpression experiments molecular pathways responsible for effects SKF83566. Finally, SKF83566 validated orthotopic xenograft models vivo. Results seq three GSC (P3, BG5 BG7) yielded set 27 differentially expressed between cells. CMap analysis, identified selective inhibitor targeting both DRD1 DRD5. In vitro studies demonstrated inhibited proliferation, sphere formation, invasion. SKF83566-treated P3, BG5, BG7, control populations total 32 genes, predicted be regulated by c-Myc. Of these, UHRF1 emerged most downregulated following treatment, ChIP revealed c-Myc binds its promoter region. or stable knockdown, growth (BG5) derived xenografts nude mice. Conclusions contributes progression regulating entry into nucleus affects transcription gene. inhibits transmembrane protein DRD1, such represents small molecule GBMs.

Language: Английский

Citations

4

Metabolomic and Lipidomic Profiling of Gliomas—A New Direction in Personalized Therapies DOI Open Access
Magdalena Gaca-Tabaszewska, Joanna Bogusiewicz, Barbara Bojko

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(20), P. 5041 - 5041

Published: Oct. 14, 2022

In addition to being the most common primary brain tumor, gliomas are also among difficult diagnose and treat. At present, “gold standard” in glioma treatment entails surgical resection of largest possible portion followed by temozolomide therapy radiation. However, this approach does not always yield desired results. Additionally, ability cross blood-brain barrier remains a major challenge for new potential drugs. Thus, researchers continue search targeted therapies that can be individualized based on specific characteristics each case. Metabolic lipidomic research may represent two best ways achieve goal, as they enable detailed insights into changes profile small molecules biological system/specimen. This article reviews approaches analysis alterations biochemical pathways, it provides an overview clinical results support personalized future.

Language: Английский

Citations

17

Impact of Solute Carrier Transporters in Glioma Pathology: A Comprehensive Review DOI Open Access
Filippos Anagnostakis, Michail Kokkorakis,

Mariam Markouli

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9393 - 9393

Published: May 28, 2023

Solute carriers (SLCs) are essential for brain physiology and homeostasis due to their role in transporting necessary substances across cell membranes. There is an increasing need further unravel pathophysiological implications since they have been proposed play a pivotal tumor development, progression, the formation of microenvironment (TME) through upregulation downregulation various amino acid transporters. Due implication malignancy SLCs currently positioned at center novel pharmacological targeting strategies drug development. In this review, we discuss key structural functional characteristics main SLC family members involved glioma pathogenesis, along with potential options provide new opportunities CNS design more effective management.

Language: Английский

Citations

10

Long-Chain Cyclic Arylguanidines as Multifunctional Serotonin Receptor Ligands with Antiproliferative Activity DOI Creative Commons
Przemysław Zaręba, Anna K. Drabczyk, Artur Wnorowski

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: 10(7), P. 6446 - 6469

Published: Feb. 11, 2025

Recent investigations have shown serotonin's stimulatory effect on several types of cancers and carcinoid tumors. Nowadays there has been a significant increase in interest 5-HT7 5-HT5A receptors the context cancer treatment. The possible role 5-HT6R pathogenesis progression glioma remains an interesting relatively unexplored issue. We developed new group long-chain 2-aminoquinazoline sulfonamides as multifunctional serotonin receptor ligands, focused 5-HT6R. chosen was further evaluated for antiproliferative effects 1321N1 astrocytoma cells, along with U87MG, U-251, LN-229 glioblastoma cell lines. Certain compounds were subjected to vitro absorption, distribution, metabolism, excretion, toxicity (ADMET) testing, assessing factors such lipophilicity, plasma protein binding, phospholipid affinity, potential drug–drug interactions (DDI), membrane permeability (PAMPA), metabolic stability, hepatotoxicity. Additionally, vivo testing performed using Danio rerio model. includes selective antagonist PP 15, dual ligand 5-HT1AR/5-HT6R 13, 5-HT5AR/5-HT6R 10. use ligands associated high anticancer activity both against selected lines other (IC50 < 25 μM).

Language: Английский

Citations

0

Identification of therapeutic targets and immune landscape in glioblastoma through crosstalk with glioma-associated mesenchymal stem cells DOI Creative Commons
Haoyang Zheng, Haofei Wang, Duo Zhang

et al.

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 150, P. 114228 - 114228

Published: Feb. 12, 2025

Glioma-associated mesenchymal stem cells (GA-MSCs) are one of the key factors limiting effectiveness glioblastoma (GBM) treatment and contributing to poor patient prognosis, making them a potential therapeutic target for GBM. In-depth research into complex crosstalk between GA-MSCs GBM not only aids in understanding mechanisms progression but also provides valuable insights developing new drugs. We conducted comprehensive bioinformatics analysis aimed at identifying shared dysregulated genes GA-MSCs. Through hub gene enrichment immune infiltration analyses, we explored molecular pathways landscape. Additionally, Cox regression was employed identify influencing overall survival The expression patterns functional roles were validated across various cancer types datasets. Finally, dynamic simulations used assess binding affinity drugs targets, further supporting their as candidates. identified 32 candidate primarily involved 1-kappa-B kinase/NF-kappa-B MAPK signaling pathways, both which played critical tumor survival, proliferation, invasion. Notable included DUSP1, FYN, FLNC, FN1, G3BP1, MYO1B, WLS, each uniquely progression. Among them, FLNC highlighted regulatory factor Molecular dynamics revealed its target, particularly demonstrating high with staurosporine. proportion dendritic contributed formation microenvironment. This study co-expression metabolic GBM, providing Targeting staurosporine presents promising strategy Aditionally, targeting may offer approach treating malignant brain tumors.

Language: Английский

Citations

0

Neuropeptide Signaling in Glioblastoma: A Comprehensive Review of the Current State and Future Direction DOI

Shahid Afridi,

Mohd Muzzammil,

Intezar Ali

et al.

NeuroMolecular Medicine, Journal Year: 2025, Volume and Issue: 27(1)

Published: April 14, 2025

Language: Английский

Citations

0

Neurotransmitter power plays: the synaptic communication nexus shaping brain cancer DOI Creative Commons
Jayanta Mondal, Jason T. Huse

Acta Neuropathologica Communications, Journal Year: 2025, Volume and Issue: 13(1)

Published: April 30, 2025

Gliomas and brain metastases are notorious for their dismal prognosis low survival rates, a challenge exacerbated by our incomplete grasp of the complex dynamics that govern cancers. Recently, groundbreaking paradigm shift has emerged, highlighting crucial role synaptic communication between neurons tumor cells in reshaping neuronal signaling to favor growth. This review delves into pivotal interplay mechanisms, focusing on excitatory glutamatergic inhibitory GABAergic pathways. Glutamatergic synapses utilize glutamate propagate signals, while employ gamma-aminobutyric acid (GABA) inhibit firing. can be broadly classified ionotropic (NMDAR, AMPAR kainite receptors) metabotropic subtypes. The harmonious orchestration these types is essential normal function, dysregulation implicated neurodegenerative disorders such as Alzheimer's disease epilepsy. Emerging evidence reveals glioma metastatic exploit pathways neurotransmitters enhance proliferation survival. In this review, we will first explore intricate mechanisms underlying signaling. Next, summarize recent advancements understanding how cancer hijack advantage. Finally, propose novel therapeutic strategies aimed at disrupting aberrant neuron-tumor communication, offering potential treatment combating otherwise incurable

Language: Английский

Citations

0