Osteosarcoma mechanobiology and therapeutic targets

British Journal of Pharmacology, Год журнала: 2021, Номер 179(2), С. 201 - 217

Опубликована: Окт. 22, 2021

Osteosarcoma is one of the most common primary tumours bone, with a 5-year survival rate less than 20% after development metastases. highly predisposed in Paget's disease and both have characteristic skeletal features due to rapid bone remodelling. prognosis location dependent, which further emphasizes likely contribution microenvironment its pathogenesis. Mechanobiology describes processes involved when mechanical cues from changing physical are transduced biological pathways through mechanosensitive cellular components. Mechanobiology-driven therapies been used curb tumour progression by direct alteration or inhibition metastasis-associated proteins. This review mechanobiology osteosarcoma sheds light on current mechanobiology-based potential new targets for improving management. Additionally, many different 3D models currently study summarized.

Язык: Английский

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Post‐translational modifications of histones: Mechanisms, biological functions, and therapeutic targets

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Май 20, 2023

Abstract Histones are DNA‐binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute “histone code.” The relationship between their combination biological function can be used an important epigenetic marker. Methylation demethylation of same residue, acetylation deacetylation, phosphorylation dephosphorylation, even methylation different residues cooperate or antagonize with each other, forming a complex network. Histone‐modifying enzymes, cause numerous codes, have become hot topic research on cancer therapeutic targets. Therefore, thorough understanding role post‐translational modifications (PTMs) cell life activities is very for preventing treating human diseases. In this review, several most thoroughly studied newly discovered PTMs introduced. Furthermore, we focus histone‐modifying enzymes carcinogenic potential, abnormal modification sites tumors, multiple essential molecular regulation mechanism. Finally, summarize missing areas current point out direction future research. We hope to provide comprehensive promote further field.

Язык: Английский

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Active targeting schemes for nano-drug delivery systems in osteosarcoma therapeutics

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Март 22, 2023

Abstract Osteosarcoma, the most common malignant tumor of bone, seriously influences people’s lives and increases their economic burden. Conventional chemotherapy drugs achieve limited therapeutic effects owing to poor targeting severe systemic toxicity. Nanocarrier-based drug delivery systems can significantly enhance utilization efficiency chemotherapeutic through ligand modifications reduce occurrence adverse effects. A variety ligand-modified nano-drug have been developed for different schemes. Here we review biological characteristics main challenges current therapy OS, further elaborate on schemes selection osteosarcoma, which may provide new horizons development advanced targeted in future.

Язык: Английский

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Advances in Osteosarcoma

Current Osteoporosis Reports, Год журнала: 2023, Номер 21(4), С. 330 - 343

Опубликована: Июнь 17, 2023

Abstract Purpose of Review This article gives a brief overview the most recent developments in osteosarcoma treatment, including targeting signaling pathways, immune checkpoint inhibitors, drug delivery strategies as single or combined approaches, and identification new therapeutic targets to face this highly heterogeneous disease. Recent Findings Osteosarcoma is one common primary malignant bone tumors children young adults, with high risk lung metastases 5-year survival rate around 70% absence 30% if are detected at time diagnosis. Despite novel advances neoadjuvant chemotherapy, effective treatment for has not improved last 4 decades. The emergence immunotherapy transformed paradigm focusing on potential inhibitors. However, clinical trials show slight improvement over conventional polychemotherapy scheme. Summary tumor microenvironment plays crucial role pathogenesis by controlling growth, metastatic process resistance paved way options that must be validated accurate pre-clinical studies trials.

Язык: Английский

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Tantalum–Zirconium Co‐Doped Metal–Organic Frameworks Sequentially Sensitize Radio–Radiodynamic–Immunotherapy for Metastatic Osteosarcoma

Advanced Science, Год журнала: 2023, Номер 10(10)

Опубликована: Фев. 5, 2023

Due to radiation resistance and the immunosuppressive microenvironment of metastatic osteosarcoma, novel radiosensitizers that can sensitize radiotherapy (RT) antitumor immunity synchronously urgently needed. Here, authors developed a nanoscale metal-organic framework (MOF, named TZM) by co-doping high-atomic elements Ta Zr as metal nodes porphyrinic molecules (tetrakis(4-carboxyphenyl)porphyrin (TCPP)) photosensitizing ligand. Given 3D arrays ultra-small heavy metals, porous TZM serves an efficient attenuator absorbing X-ray energy sensitizing hydroxyl radical generation for RT. Ta-Zr narrowed highest occupied molecular orbital-lowest unoccupied orbital (HOMO-LUMO) gap exhibited close levels between singlet triplet photoexcited states, facilitating transfer photosensitizer TCPP oxygen (

Язык: Английский

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Nanoparticles and bone microenvironment: a comprehensive review for malignant bone tumor diagnosis and treatment

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Ноя. 1, 2024

Malignant bone tumors, which are difficult to treat with current clinical strategies, originate from tissues and can be classified into primary secondary types. Due the specificity of microenvironment, results traditional means treating tumors often unsatisfactory, so there is an urgent need develop new treatments for malignant tumors. Recently, nanoparticle-based approaches have shown great potential in diagnosis treatment. Nanoparticles (NPs) gained significant attention due their versatility, making them highly suitable applications tissue engineering, advanced imaging techniques, targeted drug delivery. For diagnosis, NPs enhance contrast sensitivity by integrating targeting ligands, significantly improve specific recognition localization tumor cells early detection. treatment, enable delivery, increasing accumulation at sites while reducing systemic toxicity. In conclusion, understanding microenvironment using unique properties holds promise improving disease management, enhancing treatment outcomes, ultimately quality life patients Further research development will undoubtedly contribute advancement personalized medicine field oncology.

Язык: Английский

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Circ‐CTNNB1 drives aerobic glycolysis and osteosarcoma progression via m6A modification through interacting with RBM15

Cell Proliferation, Год журнала: 2022, Номер 56(1)

Опубликована: Окт. 1, 2022

Circular RNAs (circRNAs) are a subclass of noncoding RNAs, playing essential roles in tumorigenesis and aggressiveness. Recent studies have revealed the pivotal functions circ-CTNNB1 (a circular RNA derived from CTNNB1) cancer progression. However, little is known about role osteosarcoma (OS), highly malignant bone tumour children adolescents.Circ-CTNNB1 was analysed by qRT-PCR, results were confirmed Sanger sequencing. The interaction effects between binding motif protein 15 (RBM15) through biotin-labelled pull-down mass spectrometry, vitro binding, electrophoretic mobility shift assays. In vivo experiments performed to evaluate biological underlying mechanisms RBM15 OS cells.Circ-CTNNB1 expressed tissues predominantly detected nucleus cells. Ectopic expression promoted growth, invasion, metastasis cells vivo. Mechanistically, interacted with subsequently hexokinase 2 (HK2), glucose-6-phosphate isomerase (GPI) phosphoglycerate kinase 1 (PGK1) N6-methyladenosine (m6A) modification facilitate glycolysis process activate progression.Circ-CTNNB1 drives aerobic progression facilitating RBM15-mediated m6A modification.

Язык: Английский

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Role of WTAP in Cancer: From Mechanisms to the Therapeutic Potential

Biomolecules, Год журнала: 2022, Номер 12(9), С. 1224 - 1224

Опубликована: Сен. 2, 2022

Wilms’ tumor 1-associating protein (WTAP) is required for N6-methyladenosine (m6A) RNA methylation modifications, which regulate biological processes such as splicing, cell proliferation, cycle, and embryonic development. m6A the predominant form of mRNA modification in eukaryotes. WTAP exerts by binding to methyltransferase-like 3 (METTL3) nucleus METTL3-methyltransferase-like 14 (METTL14)-WTAP (MMW) complex, a core component methyltransferase complex (MTC), localizing nuclear patches. Studies have demonstrated that plays critical role various cancers, both dependent independent its methyltransferases. Here, we describe recent findings on structural features WTAP, mechanisms regulates functions, molecular functions cancers. By summarizing latest research, expect provide new directions insights oncology research discover targets cancer treatment.

Язык: Английский

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Anti-Invasive and Anti-Migratory Effects of Ononin on Human Osteosarcoma Cells by Limiting the MMP2/9 and EGFR-Erk1/2 Pathway

Cancers, Год журнала: 2023, Номер 15(3), С. 758 - 758

Опубликована: Янв. 26, 2023

Osteosarcoma is a common malignancy of the bone. Due to its high metastatic properties, osteosarcoma becomes leading cause cancer death worldwide. Ononin an isoflavone glycoside known have various pharmacological including antioxidant and anti-inflammatory activities. In present study, we aimed investigate efficacy ononin on cell migration, invasion, underlying mechanisms. The in vitro anti-tumorigenic anti-migratory properties were determined by MTT, colony formation, migration MG-63 U2OS lines. results compared with standard chemotherapeutic drug, doxorubicin (DOX), as positive control. dose-dependent manners treatment increased expression apoptosis inhibition proliferation through EGFR-Erk1/2 signaling pathways. Additionally, significantly inhibited invasion human cells. For consistency, used MG-63-xenograft mice model confirm vivo inhibiting protein expressions MMP2/9. According histological had no adverse effect liver kidney. Overall, our findings suggested that could be potentially effective agent against development metastasis osteosarcoma.

Язык: Английский

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Hypoxia inducible factor-1ɑ as a potential therapeutic target for osteosarcoma metastasis

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Янв. 24, 2024

Osteosarcoma (OS) is a malignant tumor originating from mesenchymal tissue. Pulmonary metastasis usually present upon initial diagnosis, and the primary factor affecting poor prognosis of patients with OS. Current research shows that ability to regulate cellular microenvironment essential for preventing distant OS, anoxic microenvironments are important features solid tumors. During hypoxia, hypoxia-inducible factor-1α (HIF-1α) expression levels stability increase. Increased HIF-1α promotes vascular remodeling, epithelial-mesenchymal transformation (EMT), OS cells invasiveness; this leads cells. plays an role in mechanisms metastasis. In order develop precise prognostic indicators potential therapeutic targets treatment, review examines molecular cells; signal transduction pathways mediated by also discussed.

Язык: Английский

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