Molecular Oncology, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 26, 2025
Language: Английский
Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(23)
Published: May 28, 2024
The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, Huashan Hospital, Shanghai. infiltrative nature gliomas makes rapid necessary to guide extent surgical resection central nervous system (CNS) tumors. combination tissue biopsy MS analysis used here satisfies this requirement. key feature both described methods use tandem measure oncometabolite 2-hydroxyglutarate (2HG) relative endogenous glutamate (Glu) characterize presence mutant tumor. experiments i) provide IDH mutation status individual patients ii) demonstrate a strong correlation 2HG signals with tumor infiltration. measured ratio Glu correlates IDH-mutant (IDH-mut) ( P < 0.0001) core data teams. Despite using different ionization spectrometers, comparable determining from biopsies was achieved sensitivities, specificities, accuracies all 100%. None 31 Clinic or 74 Hospital were misclassified when analyzing biopsies. Robustness methodology evaluated postoperative re-examination samples. Both noted high concentrations margins, supporting future monitor clean margins. power diagnostics shown resolving contradictory clinical features, e.g., distinguishing gliosis IDH-mut glioma.
Language: Английский
Citations
8
Pharmaceutics, Journal Year: 2022, Volume and Issue: 15(1), P. 59 - 59
Published: Dec. 24, 2022
Glioblastoma multiforme (GBM) is an aggressive brain tumor with high mortality rates. Due to its invasiveness, heterogeneity, and incomplete resection, the treatment very challenging. Targeted therapies such as tyrosine kinase inhibitors (TKIs) have great potential for GBM treatment, however, their efficacy primarily limited by poor distribution due presence of blood–brain barrier (BBB). This review focuses on TKIs in therapy provides insight into reasons behind unsuccessful clinical trials despite success treating other cancer types. The main section dedicated use promising drug delivery strategies targeted tumors. Use can help enhance GBM. Among various approaches used bypass or cross BBB, utilizing nanocarriers a strategy augment pharmacokinetic properties overcome limitations. because advantages ability chemical stabilization circulation, passive active targeting tumor, modulation release from carrier, possibility be delivered via non-invasive intranasal route.
Language: Английский
Citations
30
Biomedicines, Journal Year: 2022, Volume and Issue: 10(3), P. 728 - 728
Published: March 21, 2022
This article reviews the existing approaches to determining
Language: Английский
Citations
29
Nature Nanotechnology, Journal Year: 2023, Volume and Issue: 18(4), P. 336 - 342
Published: April 1, 2023
Expansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited systems1. However, optimal performance is usually reached laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only light-emitting diode (LED)-based widefield systems. As a possible alternative, computational method for image enhancement, namely, super-resolution radial fluctuations (SRRF)2,3, has recently been developed. this not explored pathology date, because on own, it does sufficient routine use. Here, we report expansion-enhanced (ExSRRF), simple, robust, scalable and accessible workflow that provides of up 25 nm LED-based microscopy. ExSRRF enables molecular profiling subcellular structures from archival formalin-fixed paraffin-embedded tissues complex experimental specimens, including ischaemic, degenerative, neoplastic, genetic immune-mediated disorders. Furthermore, examples potential application show can be used identify quantify classical features endoplasmic reticulum stress the murine ischaemic kidney diagnostic ultrastructural human biopsies.
Language: Английский
Citations
20
Cancers, Journal Year: 2023, Volume and Issue: 15(12), P. 3158 - 3158
Published: June 12, 2023
The most aggressive primary malignant brain tumor in adults is glioblastoma (GBM), which has poor overall survival (OS). There a high relapse rate among patients with GBM despite maximally safe surgery, radiation therapy, temozolomide (TMZ), and treatment. Hence, there an urgent unmet clinical need for new approaches to managing GBM. current study identified modules (MYC, EGFR, PIK3CA, SUZ12, SPRK2) involved disease through the NeDRex plugin. Furthermore, hub genes were comprehensive interaction network containing 7560 proteins related 3860 associated signaling pathways By integrating results of analyses mentioned above again performing centrality analysis, eleven key identified. ProteomicsDB Gliovis databases used determining gene expression normal tissue. NetworkAnalyst mGWAS-Explorer tools miRNAs, SNPs, metabolites these 11 genes. Moreover, literature review recent studies revealed other lists disease. enrichment analysis genes, was performed using ExpressAnalyst, miEAA, MetaboAnalyst tools. Further investigation metabolite roles pathway, joint analyses. this allowed us identify (UBC, HDAC1, CTNNB1, TRIM28, CSNK2A1, RBBP4, TP53, APP, DAB1, PINK1, RELN), five miRNAs (hsa-mir-221-3p, hsa-mir-30a-5p, hsa-mir-15a-5p, hsa-mir-130a-3p, hsa-let-7b-5p), six (HDL, N6-acetyl-L-lysine, cholesterol, formate, N, N-dimethylglycine/xylose, X2. piperidinone) 15 distinct that play indispensable role development. top signatures can be targeted establish early diagnostic methods plan personalized treatment strategies.
Language: Английский
Citations
19
Trends in Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(4), P. 282 - 296
Published: Feb. 15, 2023
Language: Английский
Citations
17
Small, Journal Year: 2023, Volume and Issue: 19(52)
Published: Aug. 30, 2023
Abstract Glioblastoma (GBM) is the most common primary malignant brain cancer in adults with a dismal prognosis. Temozolomide (TMZ) first‐in‐line chemotherapeutic; however, resistance frequent and multifactorial. While many molecular genetic factors have been linked to TMZ resistance, role of solid tumor morphology microenvironment, particularly blood‐brain barrier (BBB), unknown. Here, authors investigate these using complex vitro model for GBM its surrounding BBB. The recapitulates important clinical features such as dense core cells that invade along perivascular space; perfusable BBB physiological permeability altered presence spheroid. It demonstrated sensitivity decreases increasing cell spatial organization, can contribute resistance. Proteomic analysis next‐generation low volume sample workflows cultured microtissues revealed potential clinically relevant proteins involved aggressiveness demonstrating utility models interrogating microenvironment therapy validation.
Language: Английский
Citations
17
Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 397 - 397
Published: Jan. 17, 2024
GBM accounts for most of the fatal brain cancer cases, making it one deadliest tumor types. is characterized by severe progression and poor prognosis with a short survival upon conventional chemo- radiotherapy. In order to improve therapeutic efficiency, considerable efforts have been made target various features GBM. One targetable rewired lipid metabolism that contributes tumor’s aggressive growth penetration into surrounding tissue. Lipid reprogramming allows acquire survival, proliferation, invasion benefits as well supportive modulation microenvironment. Several attempts find novel approaches exploiting metabolic in recent studies, components de novo lipogenesis, fatty acid oxidation, uptake, prostaglandin synthesis considered promising targets Emerging data also suggest significant role hence potential endocannabinoid pathway Here we review lipid-related characteristics detail highlight specific their use antitumor approaches.
Language: Английский
Citations
7
Current Oncology Reports, Journal Year: 2024, Volume and Issue: 26(4), P. 377 - 390
Published: March 15, 2024
Language: Английский
Citations
6
Clinical and Translational Medicine, Journal Year: 2021, Volume and Issue: 11(5)
Published: May 1, 2021
Abstract Abnormal energy metabolism, including enhanced aerobic glycolysis and lipid synthesis, is a well‐established feature of glioblastoma (GBM) cells. Thus, targeting the cellular glycolipid metabolism can be feasible therapeutic strategy for GBM. This study aimed to evaluate roles MSI2, SNORD12B, ZBTB4 in regulating proliferation GBM MSI2 SNORD12B expression was significantly upregulated low tissues Knockdown or overexpression inhibited cell proliferation. may improve by increasing its stability. Importantly, increased utilization mRNA transcript distal polyadenylation signal alternative processing competitively combining with FIP1L1, which decreased because proportion 3′ untranslated region long transcript. transcriptionally suppressed HK2 ACLY binding directly promoter regions. Additionally, bound MSI suppress expression, thereby forming an MSI2/SNORD12B/FIP1L1/ZBTB4 feedback loop regulate In conclusion, stability regulated FIP1L1. positive plays crucial role cells provides potential drug target glioma treatment.
Language: Английский
Citations
33