Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 11, 2024
Language: Английский
Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)
Published: March 11, 2024
Abstract Osteosarcoma (OS) is considered a sex steroid hormone-dependent bone tumor. The development and progression of OS are regulated by 17β-estradiol (E2). However, the detailed mechanisms E2-modulated remained to be elucidated. Here, we found that E2-activated mammalian target rapamycin (mTOR) signaling promoted N6-methyladenosine (m 6 A) modification through regulating WTAP. Inhibition mTOR complex 1 (mTORC1) reversed WTAP expression. Meanwhile, inhibition mTORC1 suppressed cell proliferation migration. Deficiency TSC2 activated enhanced migration, while abrogated Rapamycin. Interestingly, mTOMC1 mRNA stability ubiquitin-specific protease 7 (USP7) m A modification. Loss USP7 proliferation, ASC specks, apoptosis cells. interacted with NLRP3 deubiquitinated K48-ubiquitination. was upregulated positive correlation in patients high level E2. via inhibiting inflammasome pathway. Our results demonstrated E2-activtated stability, which migration upregulating expression enhancing These discover novel mechanism E2 provide promising therapeutic for progression.
Language: Английский
Citations
9
BMC Cancer, Journal Year: 2025, Volume and Issue: 25(1)
Published: Feb. 18, 2025
Differences in overall survival (OS) between pediatric and adult patients diagnosed with osteosarcoma are poorly understood. The objective of this study is to compare the OS osteosarcoma, identify prognostic factors associated OS, explore specifically using data gathered from National Cancer Database (NCDB). Patients > = 1 years old 2004 2017 were included study. Multivariable Cox regression analysis adjusted for gender, race, income, education, place living, health insurance status, year diagnosis, stage cancer, surgery, chemotherapy, radiation therapy (RT) was used assess association age patients. 8,458 among whom 3,027 (35.8%) 17 old. In multivariable analysis, had worse compared (HR: 1.84; p < .01). When stratified by treatment type, better several groups. This includes those who received chemotherapy alone 0.58, .01), surgery 0.48, plus 0.56, no 0.31, There significant difference receiving a combination RT 0.81, .42). cancer stage, at each stage. logistic revealed that more likely be non-white, have insurance, present unknown/occult disease, differentiated tumors, receive or surgery. Additionally, identified improved OS: age, diagnosis 2011 2015, private non-metastatic well-differentiated but not RT. Pediatric their counterparts. adults when modality cancer. Further research necessary elucidate underlying reason difference.
Language: Английский
Citations
1
Journal of Molecular Pathology, Journal Year: 2023, Volume and Issue: 4(2), P. 99 - 108
Published: May 16, 2023
Osteosarcoma (OS) is a primary malignant bone tumour that usually occurs in children and adolescents. OS highly aggressive type with propensity for local invasion systemic early metastasis to the lungs or other bones. According World Health Organization, there are different subtypes of OS, including conventional (osteoblastic, chondroblastic, fibroblastic), telangiectatic low-grade small-cell parosteal periosteal high-grade surface OS. In this mini review, we will discuss background histopathological patterns clinical behaviour disease. Understanding their pathogenesis crucial developing more precise effective therapies patients.
Language: Английский
Citations
20
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(5), P. 189171 - 189171
Published: Aug. 9, 2024
Language: Английский
Citations
7
Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15
Published: Feb. 14, 2024
Background and objective: Osteosarcoma is a common primary malignant tumor of bone, doxorubicin one the most widely used therapeutic drugs. While problem resistance limits long-term treatment benefits in osteosarcoma patients. The role miRNAs their target genes have become increasingly prominent. Currently, there no report on miR-506-3p reversing by targeting STAT3 osteosarcoma. purpose this study was to investigate molecular mechanism that overexpression reverses drug-resistant cells. Methods: Doxorubicin-resistant cells (U-2OS/Dox) were constructed intermittent stepwise increasing stoichiometry. predicted bioinformatics approach relationship between detected using dual luciferase reporter assay. U-2OS/Dox treated with silencing respectively. Then Western blot RT-qPCR detect protein mRNA expression levels JAK2/STAT3 signaling pathway, apoptotic associated molecules. migration invasion assessed cell scratch assay transwell proliferative viability apoptosis investigated CCK8 flow cytometry Results: successfully 14.4-fold resistance. MiR-506-3p directly bound 3′-UTR mRNA. Compared U-2OS cells, reduced Overexpression decreased JAK2, STAT3, MDR1/ABCB1, MRP1/ABCC1, Survivin Bcl-2, p-JAK2, conversely increased Bax expression. It also inhibited proliferation, promoted apoptosis. results experiments above indicators consistent overexpression. Conclusion: could inhibit pathway biological behaviors, then further reverse reported new for chemotherapy provided theoretical support solving clinical problems
Language: Английский
Citations
6
British Journal of Pharmacology, Journal Year: 2023, Volume and Issue: 180(24), P. 3175 - 3193
Published: July 28, 2023
Osteosarcoma, a primary malignant bone tumour prevalent among adolescents and young adults, remains considerable challenge despite protracted progress made in enhancing patient survival rates over the last 40 years. Consequently, development of novel therapeutic approaches for osteosarcoma is imperative. Sanguinarine (SNG), compound with demonstrated potent anticancer properties against various malignancies, presents promising avenue exploration. Nevertheless, intricate molecular mechanisms underpinning SNG's actions remain elusive, necessitating further elucidation.Single-stranded DNA-binding protein 1 (SSBP1) was screened out by differential proteomic analysis. Apoptosis, cell cycle, reactive oxygen species (ROS) mitochondrial changes were assessed via flow cytometry. Western blotting quantitative real-time reverse transcription PCR (qRT-PCR) used to determine gene levels. The antitumour mechanism SNG explored at level using chromatin immunoprecipitation (ChIP) dual luciferase reporter plasmids.Our investigation revealed that exerted an up-regulated effect on SSBP1, disrupting function inducing apoptosis. In-depth analysis uncovered whereby hindered JAK/signal transducer activator 3 (STAT3) signalling pathway, relieved inhibitory STAT3 SSBP1 transcription, inhibited downstream PI3K/Akt/mTOR axis, ultimately activating apoptosis.The study delved into elucidating osteosarcoma. Notably, we unravelled previously undisclosed apoptotic potential cells. This finding holds substantial promise advancing drugs identification targets.
Language: Английский
Citations
12
Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13
Published: May 1, 2023
In osteosarcoma patients, metastasis of the primary cancer is leading cause death. At present, management options to prevent are limited and non-curative. this study, we review current state knowledge on molecular mechanisms discuss promising new therapies combat metastasis. Genomic epigenomic changes, metabolic reprogramming, transcription factors, dysregulation physiologic pathways, alterations tumor microenvironment some changes reportedly involved in regulation Key factors within include infiltrating lymphocytes, macrophages, cancer-associated fibroblasts, platelets, extracellular components such as vesicles, proteins, other secreted molecules. We conclude by discussing potential osteosarcoma-limiting agents their clinical studies.
Language: Английский
Citations
11
Biomedical Materials, Journal Year: 2024, Volume and Issue: 19(2), P. 022003 - 022003
Published: Feb. 7, 2024
Abstract Osteosarcoma (OS) is a malignant bone neoplasm plagued by poor prognosis. Major treatment strategies include chemotherapy, radiotherapy, and surgery. Chemotherapy to treat OS has severe adverse effects due systemic toxicity healthy cells. A possible way overcome the limitation utilize nanotechnology. Nanotherapeutics an emerging approach in treating using nanoparticulate drug delivery systems. Surgical resection of leaves critical defect requiring medical intervention. Recently, tissue engineered scaffolds have been reported provide physical support defects aid multimodal OS. These loaded with systems could also actively repress tumor growth new formation. The rapid developments nanotherapeutics engineering paved for improved efficacy OS-related defects. This review focuses on current bifunctional nanomaterials-based (NTE) that use novel approaches such as magnetic hyperthermia, photodynamic therapy, photothermal bioceramic polymeric against With further optimization screening, NTE meet clinical applications patients.
Language: Английский
Citations
4
Oncotarget, Journal Year: 2025, Volume and Issue: 16(1), P. 51 - 62
Published: Feb. 12, 2025
// Elodie Verdier 1 , 2 Nathalie Gaspar Maria Eugenia Marques Da Costa and Antonin Marchais UMR 1015 Tumour Immunology anti-cancer immunotherapy Unit, Gustave Roussy Cancer Campus, Villejuif 94800, France Department of Oncology for Child Adolescent, Université Paris-Saclay, 94805, Correspondence to: Marchais, email: [email protected] Costa, [email protected] Keywords: SETDB1; cancer epigenetics; tumor immunogenicity; mesenchymal differentiation in osteosarcoma Received: August 02, 2024 Accepted: January 15, 2025 Published: February 12, Copyright: © et al. This is an open access article distributed under the terms Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, reproduction any medium, provided original author source are credited. ABSTRACT Epigenetic modifications, reversibly regulate gene expression without altering DNA sequence, increasingly described literature as essential elements processes leading to development. SETDB1 regulates histone 3 (H3) K9 di- trimethylation, promoting heterochromatin formation, plays a key role silencing. deregulation appears be involved different cancers types, particularly aggressive, relapsing or treatment-resistant subtypes. Despite advances research, full range mechanisms through this protein acts remains unclear; however, it evident that has pivotal role, stem cells differentiation, evasion treatment resistance. Its genetically complex sarcomas, such osteosarcoma, not been fully explored, although recent Omics analyses suggest its presence amplification osteosarcoma. Given involvement osteoblastogenesis adipogenesis, we discuss potential target new therapeutic strategies
Language: Английский
Citations
0
Cancer Cell International, Journal Year: 2025, Volume and Issue: 25(1)
Published: Jan. 30, 2025
Osteosarcoma (OS) is a commonly observed malignant tumor in orthopedics that has very poor prognosis. The endosomal sorting complex required for transport (ESCRT) important the development and progression of cancer may be significant target therapy. First, we built prognostic signature using 7 ESCRT-related genes (ERGs) to predict OS patient Analysis internal external datasets revealed ERG good predictive ability reproducibility. Immune analysis demonstrated correlation between immune status score. Moreover, score was found associated with response patients immunotherapy anticancer drugs. Additionally, constructed consisting 10 long noncoding RNAs (ERLs) effectively predicted prognosis patients. Furthermore, two subgroups distinct prognoses (clusters 1 2) were identified. Finally, LMO7-AS1 chosen functional experimental validation. knockdown suppressed cells. transcriptome sequencing performed on cells PI3K-Akt signaling pathway. In conclusion, our ESCRT transcriptome-associated signatures can act as biomarkers OS, novel therapeutic treatment OS.
Language: Английский
Citations
0