Journal of Bone Oncology最新文献

{"title":"From bimodal to unimodal: The transformed incidence of osteosarcoma in the United States","authors":"Emma Kar ,&nbsp;Amrit Ammanamanchi ,&nbsp;Miranda Yousif ,&nbsp;Saroja Devi Geetha ,&nbsp;Kendall Schwartz ,&nbsp;Arya Suman Mishra ,&nbsp;Jiali Ling ,&nbsp;Kristie Nneoma Nonyelu ,&nbsp;Bijun Sai Kannadath","doi":"10.1016/j.jbo.2024.100613","DOIUrl":"https://doi.org/10.1016/j.jbo.2024.100613","url":null,"abstract":"<div><h3>Background</h3><p>Osteosarcoma is the most common primary bone malignancy. It has classically been described as having a bimodal incidence by age. We sought to identify whether the bimodal incidence distribution still exists for osteosarcoma using the SEER and NIS databases.</p></div><div><h3>Methods</h3><p>Incidence rates of primary osteosarcoma between 2000–2021 were analyzed by age at diagnosis, year of occurrence, sex, and tumor site from the SEER Research Data, 17 Registries, Nov 2023 Sub (2000–2021). The incidence of cases in 35–64 year-olds and 65 and above was compared statistically to determine if there is an increased incidence in the later ages. Incidence of tumors of the long bones of the lower limbs from the NIS discharge database 2012–2019 was also analyzed for comparison.</p></div><div><h3>Results</h3><p>Overall, 5,129 cases of osteosarcoma were reported in the SEER database. Across the 22 calendar year span, a consistent first peak appeared in the second decade of life. There was no consistent second peak in the 35+ age group. There were 86,100 discharges with long bone tumors analyzed in the NIS data which exhibited nearly identical patterns.</p></div><div><h3>Conclusions</h3><p>Our analysis shows that the incidence of osteosarcoma is no longer bimodally distributed but rather unimodally distributed.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"47 ","pages":"Article 100613"},"PeriodicalIF":3.4,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000939/pdfft?md5=52d2c1b2b6b14a31cc4ff7f26044de3a&pid=1-s2.0-S2212137424000939-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141325682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adipocytes and metabolism: Contributions to multiple myeloma","authors":"Heather Fairfield ,&nbsp;Michelle Karam ,&nbsp;Allyson Schimelman ,&nbsp;Ya-Wei Qiang ,&nbsp;Michaela R. Reagan","doi":"10.1016/j.jbo.2024.100609","DOIUrl":"10.1016/j.jbo.2024.100609","url":null,"abstract":"<div><p>Obesity contributes to many cancers, including breast cancer and multiple myeloma, two cancers that often colonize the bone marrow (BM). Obesity often causes metabolic disease, but at the cellular level, there is uncertainty regarding how these shifts affect cellular phenotypes. Evidence is building that different types of fuel affect tumor cell metabolism, mitochondrial function, and signaling pathways differently, but tumor cells are also flexible and adapt to less-than ideal metabolic conditions, suggesting that single-pronged attacks on tumor metabolism may not be efficacious enough to be effective clinically. In this review, we describe the newest research at the pre-clinical level on how tumor metabolic pathways and energy sources affect cancer cells, with a special focus on multiple myeloma (MM). We also describe the known forward-feedback loops between bone marrow adipocytes (BMAds) and local tumor cells that support tumor growth. We describe how metabolic targets and transcription factors related to fatty acid (FA) oxidation, FA biosynthesis, glycolysis, oxidative phosphorylation (OXPHOS), and other pathways hold great promise as new vulnerabilities in myeloma cells. Specifically, we describe the importance of the acetyl-CoA synthetase (ACSS) and the acyl-CoA synthetase long chain (ACSL) families, which are both involved in FA metabolism. We also describe new data on the importance of lactate metabolism and lactate transporters in supporting the growth of tumor cells in a hypoxic BM microenvironment. We highlight new data showing the dependency of myeloma cells on the mitochondrial pyruvate carrier (MPC), which transports pyruvate to the mitochondria to fuel the tricarboxylic acid (TCA) cycle and electron transport chain (ETC), boosting OXPHOS. Inhibiting the MPC affects myeloma cell mitochondrial metabolism and growth, and synergizes with proteosome inhibitors in killing myeloma cells. We also describe how metabolic signaling pathways intersect established survival and proliferation pathways; for example, the fatty acid binding proteins (FABPs) affect MYC signaling and support growth, survival, and metabolism of myeloma cells. Our goal is to review the current the field so that novel, metabolic-focused therapeutic interventions and treatments can be imagined, developed and tested to decrease the burden of MM and related cancers.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"46 ","pages":"Article 100609"},"PeriodicalIF":3.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000897/pdfft?md5=58e857e7b31825db0b4bbaa32df22153&pid=1-s2.0-S2212137424000897-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141139250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging roles for stromal cells in bone metastasis","authors":"Karl J. Nyman ,&nbsp;Jeremy S. Frieling ,&nbsp;Conor C. Lynch","doi":"10.1016/j.jbo.2024.100610","DOIUrl":"10.1016/j.jbo.2024.100610","url":null,"abstract":"<div><p>The skeleton is a common site of cancer metastasis and malignancy with the resultant lesions often being incurable. Interactions between metastatic cancer cells and the bone microenvironment are critical for cancer cell survival, outgrowth, and progression. Mesenchymal Stem Cells (MSCs) are an essential stromal cell type in bone that are appreciated for their impacts on cancer-induced bone disease, however, newer evidence suggests that MSCs possess extensive roles in cancer-bone crosstalk, including cancer cell dormancy, metabolic demands, and immune-oncology. Emerging evidence has also identified the importance of MSC tissue source and the influence of ageing when studying MSC biology. Combining these considerations together with developing technologies such as spatial transcriptomics will contribute to defining the molecular mechanisms underlying complex stroma-cancer interactions in bone and assist with identification of therapeutically tractable targets.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"47 ","pages":"Article 100610"},"PeriodicalIF":3.4,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000903/pdfft?md5=ae412111d0019fe7a11e98e9ecb3f4a3&pid=1-s2.0-S2212137424000903-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141054790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of IL-1B in breast cancer bone metastasis","authors":"Jiabao Zhou,&nbsp;Penelope D. Ottewell","doi":"10.1016/j.jbo.2024.100608","DOIUrl":"https://doi.org/10.1016/j.jbo.2024.100608","url":null,"abstract":"<div><p>Interleukin-1B (IL-1B) is a potent pro-inflammatory cytokine that plays multiple, pivotal roles, in the complex interplay between breast cancer cells and the bone microenvironment. IL-1B is involved in the growth of the primary tumours, regulation of inflammation within the tumour microenvironment, promotion of epithelial to mesenchymal transition (EMT), migration and invasion. Moreover, when breast cancer cells arrive in the bone microenvironment there is an upregulation of IL-1B which promotes the creation of a conducive niche for metastatic breast cancer cells as well as stimulating initiation of the vicious cycle of bone metastasis. Pre-clinical studies have demonstrated that inhibition of IL-1 signalling reduces bone metastasis from oestrogen receptor positive/triple-negative breast cancers in various mouse models. However, effects on primary tumours and soft tissue metastasis remain controversial with some studies showing increased tumour growth in these sites, whilst others show no effects. Notably, combining anti-IL-1 therapy with standard-of-care treatments, such as chemotherapy and immunotherapy, has been demonstrated to reduce the growth of primary tumours, bone metastasis, as well as metastatic outgrowth in other organs. This review focuses on the mechanisms by which IL-1B promotes breast cancer bone metastasis.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"46 ","pages":"Article 100608"},"PeriodicalIF":3.4,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000885/pdfft?md5=126c4bf642c1927ff4d4f37687864167&pid=1-s2.0-S2212137424000885-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140951615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automatic classification of spinal osteosarcoma and giant cell tumor of bone using optimized DenseNet","authors":"Jingteng He,&nbsp;Xiaojun Bi","doi":"10.1016/j.jbo.2024.100606","DOIUrl":"https://doi.org/10.1016/j.jbo.2024.100606","url":null,"abstract":"<div><h3>Objective</h3><p>This study aims to explore an optimized deep-learning model for automatically classifying spinal osteosarcoma and giant cell tumors. In particular, it aims to provide a reliable method for distinguishing between these challenging diagnoses in medical imaging.</p></div><div><h3>Methods</h3><p>This research employs an optimized DenseNet model with a self-attention mechanism to enhance feature extraction capabilities and reduce misclassification in differentiating spinal osteosarcoma and giant cell tumors. The model utilizes multi-scale feature map extraction for improved classification accuracy. The paper delves into the practical use of Gradient-weighted Class Activation Mapping (Grad-CAM) for enhancing medical image classification, specifically focusing on its application in diagnosing spinal osteosarcoma and giant cell tumors. The results demonstrate that the implementation of Grad-CAM visualization techniques has improved the performance of the deep learning model, resulting in an overall accuracy of 85.61%. Visualizations of images for these medical conditions using Grad-CAM, with corresponding class activation maps that indicate the tumor regions where the model focuses during predictions.</p></div><div><h3>Results</h3><p>The model achieves an overall accuracy of 80% or higher, with sensitivity exceeding 80% and specificity surpassing 80%. The average area under the curve AUC for spinal osteosarcoma and giant cell tumors is 0.814 and 0.882, respectively. The model significantly supports orthopedics physicians in developing treatment and care plans.</p></div><div><h3>Conclusion</h3><p>The DenseNet-based automatic classification model accurately distinguishes spinal osteosarcoma from giant cell tumors. This study contributes to medical image analysis, providing a valuable tool for clinicians in accurate diagnostic classification. Future efforts will focus on expanding the dataset and refining the algorithm to enhance the model's applicability in diverse clinical settings.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"46 ","pages":"Article 100606"},"PeriodicalIF":3.4,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000861/pdfft?md5=f86097750f579a86e14b7f108120273b&pid=1-s2.0-S2212137424000861-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140917777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trends in primary malignant bone cancer incidence and mortality in the United States, 2000–2017: A population-based study","authors":"Jie Yang ,&nbsp;Suo Lou ,&nbsp;Teng Yao","doi":"10.1016/j.jbo.2024.100607","DOIUrl":"https://doi.org/10.1016/j.jbo.2024.100607","url":null,"abstract":"<div><h3>Background</h3><p>Primary malignant bone cancers have extremely low incidence, resulting in poor evaluation of their epidemiological characteristics. The objective of this study was to investigate trends in the incidence of primary malignant bone cancers and related mortality.</p></div><div><h3>Materials and methods</h3><p>Data from patients diagnosed with malignant bone cancers from 2000 to 2017 in the Surveillance Epidemiology and End Results database were retrospectively analyzed. Annual age-adjusted incidence and mortality were calculated, and the annual percentage change analyzed. Further, characteristics including patient age and sex, as well as the primary site and stage of different tumor types, were analyzed.</p></div><div><h3>Results</h3><p>The overall age-adjusted incidence rate of primary malignant bone cancers was 7.70 per million people per year, and incidence rates had increased in patients between 60 and 79 years old, or with tumor size ≥ 8 cm. The incidence of chordoma increased significantly (annual percentage change (APC), 3.0 % per year), while those of WHO grade I and II primary bone cancers decreased. During 2000–2017, the mortality rate attributable to malignant bone cancers across the entire United States was 4.41 per million people per year. A positive mortality trend was observed during the study period (APC = 0.7 %, 95 % confidence interval: 0.0 %–1.5 %). Patients with osteosarcoma, and those who were female or of white ethnicity showed significant increasing trends in mortality rate.</p></div><div><h3>Conclusions</h3><p>Different tumor types have variable epidemiological manifestations, in terms of incidence and mortality, and exhibited altered trends over recent years. These variables can provide guidance to inform allocation of medical resources.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"46 ","pages":"Article 100607"},"PeriodicalIF":3.4,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000873/pdfft?md5=7b1c6dba9a37e8be4c48aecf4c621b1e&pid=1-s2.0-S2212137424000873-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140914088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptional profiling in osteosarcoma and the effect of neoadjuvant chemotherapy on the tumor microenvironment","authors":"Xiao-yu He ,&nbsp;Liu-yi Que ,&nbsp;Fan Yang ,&nbsp;Yi Feng ,&nbsp;Dong Ren ,&nbsp;Xiang Song","doi":"10.1016/j.jbo.2024.100604","DOIUrl":"https://doi.org/10.1016/j.jbo.2024.100604","url":null,"abstract":"<div><p>Osteosarcoma (OS), a malignant tumor, originates from the bone marrow. Currently, treatment for OS remains limited, making it urgent to understand the immune response in the tumor microenvironment of patients with OS. A comprehensive bioinformatics analysis was performed, including cell clustering subgroups, differential expression genes screening, proposed temporal order, and genomic variant analysis on single-cell RNA-sequencing data, from ten pre-chemotherapy patients and eleven post-chemotherapy patients. Subsequently, we analyzed the differentiation trajectories of osteoblasts, osteoclasts, fibroblasts, myeloid cells, and tumor-infiltrating lymphocytes (TILs) in detail to compare the changes in cell proportions and differential genes pre- and post-chemotherapy. The nine cell types were identified, including fibroblasts, myeloid cells, osteoblasts, TILs, osteoclasts, proliferative osteoblasts, pericytes, endothelial cells, and B cells. Post-chemotherapy treatment, the proportions of myeloid cells and TILs in OS were declined, while the number of osteoblasts was elevated. Besides, a decrease was observed in CD74, FTL, FTH1, MT1X and MT2A, and an increase in PTN, COL3A1, COL1A1, IGFBP7 and FN1. Meanwhile, EMT, DNA repair, G2M checkpoint, and E2F targets were highly enriched post-chemotherapy. Furthermore, there was a down-regulation in the proportions of CD14 monocytes, Tregs, NK cells and CD1C-/CD141-DCs, while an up-regulation was observed in the proportions of SELENOP macrophages, IL7R macrophages, COL1A1 macrophages, CD1C DCs, CD4+ T cells and CD8+ T cells. Overall, these findings revealed changes in the tumor microenvironment of OS post-chemotherapy treatment, providing a new direction for investigating OS treatment.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"46 ","pages":"Article 100604"},"PeriodicalIF":3.4,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000848/pdfft?md5=435ec41b8170ff8ca7ceda4cccbac000&pid=1-s2.0-S2212137424000848-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FBXO22 is a potential therapeutic target for recurrent chondrosarcoma","authors":"Baoquan Xin ,&nbsp;Hui Chen ,&nbsp;Zhi Zhu ,&nbsp;Qiujing Guan ,&nbsp;Guangjian Bai ,&nbsp;Cheng Yang ,&nbsp;WeiWei Zou ,&nbsp;Xin Gao ,&nbsp;Lei Li ,&nbsp;Tielong Liu","doi":"10.1016/j.jbo.2024.100605","DOIUrl":"https://doi.org/10.1016/j.jbo.2024.100605","url":null,"abstract":"<div><p>Chondrosarcoma (CHS) is a malignant bone tumor with insensitivity to both radiotherapy and chemotherapy, and a high recurrence rate. However, the latent mechanism of recurrent CHS (Re-CHS) remains elusive. Here, we discovered that FBXO22 was highly expressed in clinical samples of Re-CHS. FBXO22 played a significant role in various cancers. However, the role of FBXO22 in Re-CHS remained unclear. Our research demonstrated that suppressing FBXO22 abated the proliferation and migration of CHS cells and facilitated their apoptosis. In addition, suppressing FBXO22 raised the expression of PD-L1 in Re-CHS. All these findings provide new evidence for using FBXO22 and PD-L1 as combined targets to prevent and treat Re-CHS, which may prove to be a novel strategy for immunotherapy of CHS, especially Re-CHS.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"46 ","pages":"Article 100605"},"PeriodicalIF":3.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221213742400085X/pdfft?md5=4748719c82c02d032574b97af535fd09&pid=1-s2.0-S221213742400085X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidence, Risk Factors, and Survival of Bone Metastases and Skeletal-Related Events in Melanoma Patients: A Systematic Review and Quality Assessment of 29 Studies","authors":"Michelle R. Shimizu ,&nbsp;Olaf N. van de Langerijt ,&nbsp;Daniel Torres ,&nbsp;Tom de Groot ,&nbsp;Olivier Q. Groot","doi":"10.1016/j.jbo.2024.100603","DOIUrl":"10.1016/j.jbo.2024.100603","url":null,"abstract":"<div><h3>Background</h3><p>Skeletal metastases make up 17% of all metastases from advanced-stage melanoma. Bone metastases are associated with increased morbidity and mortality and decreased quality of life due to their association with skeletal-related events (SREs), including pathological fracture, spinal cord compression, hypercalcemia, radiotherapy, and surgery. The study aimed to determine the incidence of bone metastases and SREs in melanoma, identify possible risk factors for the development of bone metastases and SREs, and investigate survival rates in this patient population.</p></div><div><h3>Methods</h3><p>A computer-based literature search was conducted using Pubmed, Embase, and Cochrane Central Register of Controlled Trials up to July 2023. The Newcastle-Ottawa Quality Assessment Scale (NOS) was utilized for quality assessment. Study characteristics, patient information, risk factors for developing bone metastases and SREs, and characteristics for survival were recorded.</p></div><div><h3>Results</h3><p>We included 29 studies. The average bone metastasis-free interval ranged from four to 72 months. Incidence of bone metastases varied from 2 % to 49 % across 14 studies. 69 % (20/29) of studies described the location of bone metastases, with 24 % (7/29) focusing solely on spinal metastases. In one study, 129 SREs were recorded in 71 % (59/83) of the patient cohort, with various manifestations. The use of bone-directed agents was independently associated with lower risk of SREs. Survival after detection of bone metastasis ranged from three to 13 months. Factors associated with survival included clinical, tumor-related, and treatment features.</p></div><div><h3>Conclusion</h3><p>This review highlights the notable prevalence and risk factors of developing bone metastases and subsequent SREs in patients with melanoma. The surge in bone metastases poses a challenge in complication management, given the high prevalence of SREs. While this study offers a comprehensive overview of the incidence, risk factors, and outcomes associated with bone metastases and SREs in melanoma patients that may guide patient and physician decision-making, a notable gap lies in the limited availability of high-quality data and the heterogeneous design of the existing literature. Future research should address predictive factors for bone metastases and SREs in melanoma to facilitate patient and physician decision-making and ultimately improve outcomes in this patient population.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"46 ","pages":"Article 100603"},"PeriodicalIF":3.4,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000836/pdfft?md5=41f31a2ffea4ebb37db7f3d04deceb85&pid=1-s2.0-S2212137424000836-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140769005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversine inhibits proliferation and induces apoptosis of human osteosarcoma cells through targeting MEK1","authors":"Xianlong Chen ,&nbsp;Yeyin Zhong ,&nbsp;Simiao Wang ,&nbsp;Shujie Xu ,&nbsp;Junyuan Chen ,&nbsp;Xin Cheng ,&nbsp;Xuesong Yang","doi":"10.1016/j.jbo.2024.100601","DOIUrl":"https://doi.org/10.1016/j.jbo.2024.100601","url":null,"abstract":"<div><p>Reversine, or 2-(4-morpholinoanilino)-6-cyclohexylaminopurine, is a 2,6-disubstituted purine derivative. This small molecule shows anti-tumor potential by playing a central role in the inhibition of several kinases related to cell cycle regulation and cytokinesis. In this study, systematic review demonstrated the feasibility and pharmacological mechanism of anti-tumor effect of reversine. Firstly, we grafted MNNG/HOS, U-2 OS, MG-63 osteosarcoma cell aggregates onto chicken embryonic chorioallantoic membrane (CAM) to examine the tumor volume of these grafts after reversine treatment. Following culture, reversine inhibited the growth of osteosarcoma cell aggregates on CAM significantly. <em>In vitro</em> experiment, reversine suppressed osteosarcoma cell viability, colony formation, proliferation, and induced apoptosis and cell cycle arrest at G₀-G₁ phase. Scratch wound assay demonstrated that reversine restrained cell migration. Reversine increased the protein expression of E-cadherin. The mRNA expression of Rac1, RhoA, CDC42, PTK2, PXN, N-cadherin, Vimentin in MNNG/HOS, U-2 OS and MG-63 cells were suppressed and PTEN increased after reversine treatment. Network pharmacology prediction, molecular docking and systematic review revealed MEK1 can be used as an effective target for reversine to inhibit osteosarcoma. Western blot results show the regulation of MEK1 and ERK1/2 by reversine was not consistent in different osteosarcoma cell lines, but we found that reversine significantly inhibited the protein expression of MEK1 in MNNG/HOS, U-2 OS and MG-63. All these suggested that reversine can exert its anti-tumor effect by targeting the expression of MEK1.</p></div>","PeriodicalId":48806,"journal":{"name":"Journal of Bone Oncology","volume":"46 ","pages":"Article 100601"},"PeriodicalIF":3.4,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2212137424000812/pdfft?md5=17b197984c69eab329554364783ee9b3&pid=1-s2.0-S2212137424000812-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}