Kinesin superfamily proteins: roles in osteosarcoma

Lu, Yao; Song, Tao; Xue, Xue; Cao, Gaolu; Huang, Panpan

doi:10.52586/4950

Cited by 8 publications

(4 citation statements)

References 87 publications

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“…Currently, osteosarcoma accounts for approximately 2.4% of malignancies in children and adolescents worldwide [ 3 ]. Osteosarcoma is characterized by the presence of spindle-shaped stromal cells and osteoid [ 4 ]. And the typical symptoms of patients are local swelling, pain and functional limitation.…”

Section: Introductionmentioning

confidence: 99%

Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

XIAO,

CAI

et al. 2024

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Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis. Immunotherapy has shown great potential in the treatment of osteosarcoma. However, the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment. The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment. Here, we prepared a dual pH-sensitive nanocarrier, loaded with the photosensitizer Chlorin e6 (Ce6) and CD47 monoclonal antibodies (aCD47), to deliver synergistic photodynamic and immunotherapy of osteosarcoma. On laser irradiation, Ce6 can generate reactive oxygen species (ROS) to kill cancer cells directly and induces immunogenic tumor cell death (ICD), which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47. Moreover, both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages, promote antigen presentation, and eventually induce T lymphocyte-mediated antitumor immunity. Overall, the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma, which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.

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Section: Introductionmentioning

confidence: 99%

Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

XIAO,

CAI

et al. 2024

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“…Osteosarcoma (OS) is the number one primary malignant bone tumor among orthopedic tumors, and those who are susceptible to this disease are children and adolescents, whose 5-year survival rate is less than 20% if it metastasizes 1 , 2 . It has been shown that immune dysregulation in the body is associated with the development of osteosarcoma, and improving the survival of patients with osteosarcoma has long been considered challenging, although treatment of this disease has also improved in recent years, and immune checkpoint inhibition may enhance the therapeutic effect on OS by improving immunosuppression as well as the tumor microenvironment 3 .…”

Section: Introductionmentioning

confidence: 99%

Artificial intelligence reveals dysregulation of osteosarcoma and cuproptosis-related biomarkers, PDHA1, CDKN2A and neutrophils

Zhan

Wei

et al. 2023

Sci Rep

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At present, the impact of cuproptosis-related genes in the study of osteosarcoma is largely unknown. Genome-wide data of osteosarcoma and controls were downloaded from 3 different databases, and specific diagnostic models associated with cuproptosis in osteosarcoma were constructed by support vector machines with artificial intelligence, random forest trees and LASSO regression. Differential analysis of immune cell infiltration was examined using routine blood data from 25,665 cases. Differential expression was examined using immunohistochemistry and PCR. PDHA1 and CDKN2A were obtained as specific cuproptosis-related biomarkers for osteosarcoma after artificial intelligence analysis. PDHA1, CDKN2A and neutrophils were differentially expressed in OS and control groups. PDHA1 and CDKN2A are significantly dysregulated in OS and are able to serve as biomarkers of OS.

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“…Moreover, OS is prone to local invasion and early metastasis, mainly affecting the lung and skeleton. Additionally, local recurrence, metastasis, and chemotherapy resistance are associated with poor prognosis (3,4). Despite signi cant improvements in treatment strategies in recent years, treatment outcomes for patients with metastatic or recurrent OS remain pessimistic, with a rather grim prognosis and greatly reduced 5-year overall survival rate of only 20-30% (5,6).…”

Section: Introductionmentioning

confidence: 99%

The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression

Lu¹,

Huang²,

Li³

et al. 2023

ABBS

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Background: Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents.In clinical treatments, the insensitivity of OS to conventional radiotherapy regimens signi cantly contributes to poor patient prognosis and survival. EXO1 is responsible for DNA repair pathways and telomere maintenance. Meanwhile, ATM and ATR are considered switches as they can regulate the expression of EXO1. However, their expression and interaction in OS cells under irradiation (IR) remains unclear. This study aimed to investigate the roles of FBXO32, ATM, ATR and EXO1 in OS radiotherapy insensitivity and poor patient prognosis and explore potential pathogenic mechanisms. Methods: Bioinformaticsmethods were employed to analyze differential gene expression and the correlations with prognosis in OS. Cell counting kit 8 assays, clone formation assays, and ow cytometry were used to evaluate cell survivaland apopotosisunder IR. Co-IP assays detected protein-protein interactions. Results: Bioinformatics analysis revealed that EXO1 is closely related to the survival, apoptosis and poorer prognosis in OS. The silencingof EXO1 suppressed cell proliferation and increased the sensitivity of OS cells. Molecular biological experiments showed that the ATMand ATR acted as the switch to regulate EXO1 expression under IR. Conclusion: Higher expression of EXO1, which was closely correlated with IR insensitivity and poorer prognosis, might be used as a prognostic indicator for OS. Phosphorylated-ATM enhanced the expression of EXO1, and phosphorylated-ATR induced the degradation of EXO1. More importantly, FBXO32 degraded ATR via ubiquitination in time dependent. Our data may provide a reference for future research on mechanisms, clinical diagnosis, and treatment of OS.

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Kinesin superfamily proteins: roles in osteosarcoma

Cited by 8 publications

References 87 publications

Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

Codelivery of anti-CD47 antibody and chlorin e6 using a dual pH-sensitive nanodrug for photodynamic immunotherapy of osteosarcoma

Artificial intelligence reveals dysregulation of osteosarcoma and cuproptosis-related biomarkers, PDHA1, CDKN2A and neutrophils

The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression

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