The Role of Sphingolipid Metabolism in Pregnancy-Associated Breast Cancer After Chemotherapy DOI Creative Commons
V. E. Blokhin, Т. М. Заварыкина, Vasily Kotsuba

и другие.

Biomedicines, Год журнала: 2024, Номер 12(12), С. 2843 - 2843

Опубликована: Дек. 13, 2024

Background: The aim of our study was to determine the role sphingolipids, which control proliferation and apoptosis, in placenta pregnant women with pregnancy-associated breast cancer (PABC) after chemotherapy compared healthy patients. Methods: We analyzed (by PCR method) gene expression key sphingolipid metabolism enzymes (sphingomyelinases (SMPD1 SMPD3), acid ceramidase (ASAH1), ceramide synthases (CERS 1–6), sphingosine kinase1 (SPHK1), sphingosine-1-phosphate lyase 1 (SGPL1), receptors (S1PR1, S1PR2, S1PR3)) content subspecies ceramides, sphingosine, seven patients PABC eight as a group. Results: found significant increase genes kinase 1-3, 5, 6) samples during their treatment cytostatic chemotherapy. enzymes’ not accompanied by changes studied sphingolipids. Such controlling level CER, S1P may indicate ability initiate pro-apoptotic anti-apoptotic sphingolipids undergoing order maintain levels typical women. Conclusions: Our results promising mechanism protection for and, consequently, newborn. This protective effect especially newborn has been discovered first time requires more careful study.

Язык: Английский

Lipid dysregulation in triple negative breast cancer: Insights from mass spectrometry-based approaches DOI Creative Commons
Xiaoyue Huang, Ahmed Ali,

Dounia E I Yachioui

и другие.

Progress in Lipid Research, Год журнала: 2025, Номер 98, С. 101330 - 101330

Опубликована: Фев. 4, 2025

Язык: Английский

Процитировано

0
Melanophilin inhibit the growth and lymph node metastasis of triple negative breast cancer via the NONO-SPHK1-S1P axis DOI Creative Commons
Xing Yao,

Tiffany Yuen,

Qingchuan Chen

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 6, 2025

Triple negative breast cancer (TNBC) is the most aggressive subtype with worst prognosis, and there are no targeted treatments available. TNBC patients more likely to develop metastases relapse than other subtypes. Lymph node metastasis first sign of metastatic spread. We aimed characterize mechanism lymph in provide a new strategy for treatment TNBC. Gene Expression Omnibus (GEO) database was utilized screen genes related N staging. Screening downstream target Melanophilin (MLPH) through RNA sequencing (RNA seq) analysis. Protein mass spectrometry analyze protein which interacts MLPH, binding immunoprecipitation quantitative real-time PCR (RIP qPCR) were verify regulation sphingosine kinase 1 (SPHK1) expression by MLPH Non-POU domain-containing octamer-binding (NONO). Cell functional assays vivo models experiments further confirmed effects on proliferation SPHK1-S1P axis. downregulated inhibits tumor growth though MLPH-NONO-SPHK1-S1P pathway. NONO identified as an essential factor involved SPHK1 mRNA splicing. inhibit splicing SPHK1, reduces content S1P, thereby inhibiting This study preliminarily elucidated underlying role axis regulating These findings may help design strategies predicting treating

Язык: Английский

Процитировано

0
A first-in-human phase 1 study of BXQ-350, a first-in-class sphingolipid metabolism regulator, in patients with advanced/recurrent solid tumors or high-grade gliomas DOI

Olivier Rixe,

John L. Villano, Robert Wesolowski

и другие.

Clinical Cancer Research, Год журнала: 2024, Номер 30(22), С. 5053 - 5060

Опубликована: Сен. 12, 2024

Abstract Purpose: BXQ-350, a nanovesicle formulation of saposin C, is an allosteric sphingolipid metabolism regulator that increases proapoptotic ceramide and decreases oncogenic sphingosine-1-phosphate levels. We conducted first-in-human phase I study BXQ-350. Patients Methods: Adults (≥18 years old) with advanced/recurrent, treatment-refractory solid tumors or high-grade gliomas received BXQ-350 intravenously in five dose cohorts (0.7–2.4 mg/kg) 3+3 escalation expansion design. The primary endpoints during were dose-limiting toxicities maximum tolerated dose; the objective parts was assessment antitumor activity (RECIST v1.1/Response Assessment Neuro-Oncology criteria). Results: Eighty-six patients enrolled. Dose-limiting not observed (n = 18), identified. An additional 68 2.4 mg/kg dose. Nine (10%) discontinued due to adverse events. most common treatment-related events nausea (24%) fatigue (23%). Eight had progression-free survival ≥6 months. Two these achieved partial response, six stable disease, among whom three reduction ≥1 target lesion. Of those months, seven remained on for >12 >24 after 7 years, two without disease progression. Conclusions: well-tolerated as monotherapy at doses up mg/kg. It provided some lasting clinical benefit recurrent malignancies across several tumor types, consistent decreased systemic sphingosine-1-phosphate/ceramide metabolic rheostat. warrants further investigation alone combined standard care advanced tumors.

Язык: Английский

Процитировано

2
Integrated Metabolomics and Transcriptomics Analysis of Anacardic Acid Inhibition of Breast Cancer Cell Viability DOI Open Access
Kellianne M. Piell,

Claire C. Poulton,

Christian G. Stanley

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(13), С. 7044 - 7044

Опубликована: Июнь 27, 2024

Anacardic acid (AnAc) inhibits the growth of estrogen receptor α (ERα)-positive MCF-7 breast cancer (BC) cells and MDA-MB-231 triple-negative BC (TNBC) cells, without affecting primary epithelial cells. RNA sequencing (seq) network analysis AnAc-treated suggested that AnAc inhibited lipid biosynthesis increased endoplasmic reticulum stress. To investigate impact on cellular metabolism, a comprehensive untargeted metabolomics was performed in five independent replicates control versus additional TNBC cell lines: MDA-MB-468, BT-20, HCC1806. An global metabolome identified key metabolic differences between within each line lines as well diversity among four lines, reflecting heterogeneity. AnAc-regulated metabolites were involved alanine, aspartate, glutamate, glutathione metabolism; pentose phosphate pathway; citric cycle. Integration transcriptome data for Signal transduction: mTORC1 downstream signaling both cell-specific pathways. Together, these suggest treatment differentially alters multiple pools building blocks, nutrients, transcripts resulting reduced viability.

Язык: Английский

Процитировано

1
Explore the Role of the Sphingosine-1-Phosphate Signalling as a Novel Promising Therapeutic Target for the Management of Parkinson's Disease DOI
Manoj Kumar Bisht, Jai Parkash Kadian, Tanuj Hooda

и другие.

Drug Research, Год журнала: 2024, Номер 74(08), С. 365 - 378

Опубликована: Окт. 1, 2024

Abstract Sphingosine-1-phosphate (S1P) is a cellular signalling molecule derived from sphingosine, which pro-apoptotic sphingolipid. Sphingolipids control various actions like growth, homeostasis, and stress-related responses. The main sources of S1P in our body are erythrocytes. controls both mediators other second messengers intracellularly. receptor also helps inflammatory neuroprotective effects (required to manage Parkinsonʼs). A large number anti-Parkinson drugs available, but still, there need for more effective safer drugs. its receptors could be targeted as novel due their involvement neuro-inflammation Parkinsonʼs. present review effort explore the biological role related receptors, possible PD; furthermore. Overall, metabolizing enzymes have significant therapeutic opportunities Parkinsonʼs disease along with neurological disorders.

Язык: Английский

Процитировано

0
The Role of Sphingolipid Metabolism in Pregnancy-Associated Breast Cancer After Chemotherapy DOI Creative Commons
V. E. Blokhin, Т. М. Заварыкина, Vasily Kotsuba

и другие.

Biomedicines, Год журнала: 2024, Номер 12(12), С. 2843 - 2843

Опубликована: Дек. 13, 2024

Background: The aim of our study was to determine the role sphingolipids, which control proliferation and apoptosis, in placenta pregnant women with pregnancy-associated breast cancer (PABC) after chemotherapy compared healthy patients. Methods: We analyzed (by PCR method) gene expression key sphingolipid metabolism enzymes (sphingomyelinases (SMPD1 SMPD3), acid ceramidase (ASAH1), ceramide synthases (CERS 1–6), sphingosine kinase1 (SPHK1), sphingosine-1-phosphate lyase 1 (SGPL1), receptors (S1PR1, S1PR2, S1PR3)) content subspecies ceramides, sphingosine, seven patients PABC eight as a group. Results: found significant increase genes kinase 1-3, 5, 6) samples during their treatment cytostatic chemotherapy. enzymes’ not accompanied by changes studied sphingolipids. Such controlling level CER, S1P may indicate ability initiate pro-apoptotic anti-apoptotic sphingolipids undergoing order maintain levels typical women. Conclusions: Our results promising mechanism protection for and, consequently, newborn. This protective effect especially newborn has been discovered first time requires more careful study.

Язык: Английский

Процитировано

0