Blood-tumor barrier organoids recapitulate glioblastoma microenvironment and enable high-throughput modeling of therapeutic delivery DOI Open Access
Pei Zhuang, Benjamin B. Scott, Shuai Gao

et al.

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

Published: Nov. 12, 2024

The blood-brain barrier (BBB) is a highly specialized system that critical for regulating transport between the blood and central nervous system. In brain tumors, vasculature compromised, referred to as blood-tumor (BTB). ability precisely model unique physiological properties of BTB essential decipher its role in tumor pathophysiology rational design efficacious therapeutics. Here, we introduce robust high-throughput vitro 3D human organoid recapitulates various key features observed vivo clinical GBM samples. organoids are composed patient-derived glioblastoma stem cells (GSCs), endothelial (EC), astrocytes pericytes, which formed through self-assembly. Transcriptomic functional analyses reveal GSCs exhibit enhanced level stemness, mesenchymal signature, invasiveness angiogenesis, this further confirmed studies. We demonstrate therapeutic delivery drug efficacy on cells. Collectively, our findings show has broad utility clinically representative studying evaluating therapies.

Language: Английский

The Role of Mesenchymal Reprogramming in Malignant Clonal Evolution and Intra-Tumoral Heterogeneity in Glioblastoma DOI Creative Commons
Qiong Wu, Anders Berglund, Robert J.B. Macaulay

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(11), P. 942 - 942

Published: May 30, 2024

Glioblastoma (GBM) is the most common yet uniformly fatal adult brain cancer. Intra-tumoral molecular and cellular heterogeneities are major contributory factors to therapeutic refractoriness futility in GBM. Molecular heterogeneity represented through subtype clusters whereby proneural (PN) associated with significantly increased long-term survival compared highly resistant mesenchymal (MES) subtype. Furthermore, it universally recognized that a small subset of GBM cells known as stem (GSCs) serve reservoirs for tumor recurrence progression. The clonal evolution GSC subtypes response therapy drives intra-tumoral remains critical determinant outcomes. In particular, MES reprogramming GSCs using current therapies has emerged leading hypothesis refractoriness. Preventing divergent toward via new treatments would dramatically improve patients have significant impact on this review, we examine challenges role malignant glioblastoma provide future perspectives addressing unmet need overcome resistance

Language: Английский

Citations

5
Microenvironmental regulation of tumor-associated neutrophils in malignant glioma: from mechanism to therapy DOI Creative Commons
Jiayi Wen, Dan Liu, Hongtao Zhu

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Sept. 16, 2024

Glioma is the most common primary intracranial tumor in adults, with high incidence, recurrence, and mortality rates. Tumor-associated neutrophils (TANs) are essential components of microenvironment (TME) glioma play a crucial role cell proliferation, invasion proneural-mesenchymal transition. Besides interactions between TANs cells, multi-dimensional crosstalk other within TME have been reported to participate progression. More importantly, several therapies targeting developed relevant preclinical clinical studies conducted cancer therapy. In this review, we introduce origin functions malignant behaviors glioma, highlighting microenvironmental regulation TANs. Moreover, focus on summarizing TANs-targeted methods therapy, aiming provide insights into mechanisms therapeutic opportunities microenvironment.

Language: Английский

Citations

5
Tumor-Associated Microglia Secrete Extracellular ATP to Support Glioblastoma Progression DOI
Caren Yu-Ju Wu, Yiyun Chen,

Ya-Jui Lin

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(23), P. 4017 - 4030

Published: Dec. 2, 2024

Abstract Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and high recurrence rates. The complex immune microenvironment of GBM infiltrated by tumor-associated microglia macrophages (TAM). TAMs are known to be heterogeneous in their functional metabolic states can transmit either protumoral or antitumoral signals glioma cells. Here, we performed bulk RNA sequencing single-cell on samples from patients GBM, which revealed increased ATP synthase expression oxidative phosphorylation activity located the core relative periphery. Both vitro vivo models displayed similar trends augmented TAM mitochondrial activity, along elevated fission, glucose uptake, membrane potential, extracellular (eATP) production presence Tumor-secreted factors, including GM-CSF, induced increase eATP production. Elevated promoted growth invasion activating P2X purinoceptor 7 (P2X7R) Inhibition eATP–P2X7R axis attenuated cell viability reduced size prolonged survival glioma-bearing mouse models. Overall, this study TAM-derived provided basis for targeting signaling as therapeutic strategy GBM. Significance: Glioblastoma-mediated reprogramming increases secretion that supports cancer proliferation P2X7R, inhibited attenuate growth.

Language: Английский

Citations

4
Sesquiterpene Lactones as Promising Anti-Glioblastoma Drug Candidates Exerting Complex Effects on Glioblastoma Cell Viability and Proneural–Mesenchymal Transition DOI Creative Commons
Andrey V. Markov,

Arseny D. Moralev,

Kirill V. Odarenko

et al.

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 133 - 133

Published: Jan. 8, 2025

Glioblastoma is one of the most aggressive brain cancers, characterized by active infiltrative growth and high resistance to radiotherapy chemotherapy. Sesquiterpene triterpenoids (STLs) their semi-synthetic analogs are considered as a promising source novel anti-tumor agents due low systemic toxicity multi-target pharmacological effects on key processes associated with tumor progression. The current review aims systematize knowledge anti-glioblastoma potential STLs accumulated over last decade identify in glioblastoma cells that susceptible action STLs. An analysis published data clearly demonstrated STLs, which can successfully cross blood-brain barrier, exert complex inhibitory effect through induction "mitochondrial dysfunction-oxidative stress-apoptosis" axis, inhibition glucose metabolism cell cycle phase transition, suppression motility invasion blockade proneural-mesenchymal transition. Taken together, this highlights not only able induce death, but also effectively affect diffusive spread, suggests possible directions for further investigation context better understand mechanism action.

Language: Английский

Citations

0
Exploring the co‐morbid relationship between Alzheimer's disease and lung cancer in the 5xFAD transgenic mouse model DOI Creative Commons
Ming‐Feng Li, Xinghan Wu, Lin Jiang

et al.

Animal Models and Experimental Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Alzheimer's disease (AD) and lung cancer are leading causes of mortality among the older population. Epidemiological evidence suggests an antagonistic relationship between them, whereby patients with AD exhibit a reduced risk developing vice versa. However, precise mechanism by which antagonizes progression warrants further elucidation. To this end, we established co-morbidity model using 5xFAD transgenic mice induced carcinogen urethane. We visualized quantified surface tumor colonies, assessed pathological parameters associated histopathological analysis, employed single-cell sequencing molecular analyses to explore mechanisms confers resistance cancer. Our findings revealed significant reduction in incidence group compared that wild-type (WT) group. The results indicated close association AD-induced inhibition iron homeostasis imbalance increased oxidative stress. Moreover, greater CD8+ T cytotoxic lymphocyte effector natural killer cell infiltration tissues enhanced lymphocyte-mediated killing target cells may be primary factors contributing growth presence AD. This study identified essential through suppresses tumorigenesis, thereby providing targets for potential therapeutic interventions these diseases.

Language: Английский

Citations

0
Single-Molecule Biophysics: Probing Biological Processes at the Nanoscale DOI
Afam Uzorka

Biophysical Reviews and Letters, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 17

Published: March 29, 2025

Single-molecule biophysics has become a ground-breaking field that enables scientists to precisely study biological processes at the nanoscale. This review examines most current developments and uses of single-molecule methods for studying biomolecular interactions, DNA mechanics, protein folding, cellular dynamics, such as fluorescence microscopy force spectroscopy. The behavior functions individual biomolecules within intricate settings are better understood by researchers through biomolecules. Additionally, machines, development molecular motors, creation synthetic have all been made possible intriguing applications in biology. incorporation into these fields creates new opportunities comprehending basic utilizing engineering wide range biotechnology medical applications. More fundamental secrets life will be revealed this subject develops, opening door discoveries across scientific fields.

Language: Английский

Citations

0
CDKN2A promoter methylation enhances self-renewal of glioblastoma stem cells and confers resistance to carmustine DOI Creative Commons
Jing Wang, Yanfeng Xi, Qi Zhao

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: March 5, 2024

Abstract Background Glioblastoma, a highly aggressive form of brain cancer, poses significant challenges due to its resistance therapy and high recurrence rates. This study aimed investigate the expression functional implications CDKN2A, key tumor suppressor gene, in glioblastoma cells, building upon existing background knowledge this field. Method Quantitative reverse transcription PCR (qRT-PCR) analysis was performed evaluate CDKN2A U87 cells compared normal human astrocytes (NHA). levels were manipulated using small interfering RNA (siRNA) overexpression vector. Cell viability assays carmustine sensitivity tests conducted assess impact modulation on cell drug response. Sphere formation western blot role stem (GSC) self-renewal pluripotency marker expression. Additionally, methylation-specific (MSP) demethylation treatment employed elucidate mechanism downregulation cells. Result significantly reduced NHA. resulted decreased enhanced treatment. inhibition promoted capacity increased upregulation led elevated protein p16INK4a, p14ARF, P53, P21, which are involved cycle regulation. associated with promoter methylation, reversed by demethylating agent. Conclusion Our findings demonstrate that is viability, resistance, capacity, altered markers. The observed changes mediated methylation. These results highlight potential as therapeutic target prognostic glioblastoma.

Language: Английский

Citations

3
The impact of hyaluronic acid coating on polyether ether ketone dental implant surface: An in vitro analysis DOI Creative Commons

Mohammed Aso Abdulghafor,

Zanyar Amin

The Saudi Dental Journal, Journal Year: 2024, Volume and Issue: 36(10), P. 1326 - 1332

Published: July 17, 2024

Polyether ether ketone (PEEK), a biocompatible polymer, is being explored as an alternative to metallic alloys for dental implants due its aesthetic and mechanical properties. This study aimed enhance the surface biofunctionality through evaluating human MG-63 osteoblastic cell survival, proliferation, differentiation, mineralization.

Language: Английский

Citations

2
Soloxolone para-methylanilide effectively suppresses aggressive phenotype of glioblastoma cells including TGF-β1-induced glial-mesenchymal transition in vitro and inhibits growth of U87 glioblastoma xenografts in mice DOI Creative Commons
Kirill V. Odarenko,

Aleksandra V. Sen’kova,

Oksana V. Salomatina

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: July 29, 2024

Soloxolone amides are semisynthetic triterpenoids that can cross the blood-brain barrier and inhibit glioblastoma growth both in vitro vivo . Here we investigate impact of these compounds on processes associated with invasiveness therapy resistance. Screening soloxolone against cells revealed ability compound 7 (soloxolone para -methylanilide) to transforming factor-beta 1 (TGF-β1)-induced glial-mesenchymal transition Compound inhibited morphological changes, wound healing, transwell migration, expression mesenchymal markers (N-cadherin, fibronectin, Slug) TGF-β1-induced U87 U118 cells, while restoring their adhesiveness. Confocal microscopy molecular docking showed reduced SMAD2/3 nuclear translocation probably by direct interaction TGF-β type I II receptors (TβRI/II). In addition, suppressed stemness as evidenced inhibition colony forming ability, spheroid growth, aldehyde dehydrogenase (ALDH) activity. Furthermore, exhibited a synergistic effect temozolomide (TMZ) cell viability. Using N-acetyl-L-cysteine (NAC) flow cytometry analysis Annexin V-FITC-, propidium iodide-, DCFDA-stained was found synergize cytotoxicity TMZ inducing ROS-dependent apoptosis. Further studies , alone or combination TMZ, effectively xenograft tumors mice. Thus, demonstrated promising potential component for glioblastoma, reducing its increasing sensitivity chemotherapy.

Language: Английский

Citations

2
Immunogenic cell death mediated TLR3/4-activated MSCs in U87 GBM cell line DOI Creative Commons
Seyed Mahdi Emami Meybodi, Fateme Moradi Moraddahande, Ali Dehghani Firoozabadi

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(9), P. e29858 - e29858

Published: April 22, 2024

Glioblastoma (GBM) is an aggressive primary brain cancer with no promising curative therapies. It has been indicated that MSCs can interact the tumour microenvironment (TME) through secretion of soluble mediators regulating intercellular signalling within TME. TLRs are a multigene family pattern recognition receptors evolutionarily conserved regions and widely expressed in immune other body cells. by recognize molecular components (DAPMPs PAPMPs) activate pathways, which regulate inflammatory responses. may exert immunomodulatory functions interaction their toll-like (TLRs) protective effect against antigens. As emerging approach, we aimed to monitor U87 cell line growth, migration death markers following specific TLR3/4-primed-MSCs-CMs treatment.

Language: Английский

Citations

1