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Whole body technetium bone scan of the patient in Fig. 5, demonstrating osteosarcoma skip lesions within the left femur
Source publication
Osteosarcoma is a malignant tumor that primarily affects the long bones but can also involve other bones in the body. It has a bimodal distribution with peaks in the second decade of life and late adulthood. This chapter will highlight the clinical presentation, diagnosis, and treatment of osteosarcoma.
Context in source publication
Context 1
... final technique of routine work-up in osteosarcoma patients is a whole body technetium bone scan (Fig. 6). This test provides a reliable means of imaging the entire body to look for other sites of osseous and nonosseous disease. The bone scan demonstrates areas of high bone turnover and given the osteoblastic nature of most osteosarcomas, the majority show increased uptake at sites of disease. The bone scan may show distant sites of uptake ...
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Objectives:
Osteosarcoma (OS) is one of the two most common malignant bone tumors among children and teens but it is still a rare disorder. Semaphorin 4D (Sema4D) has been reported to play a specific role in human cancers. The aim of this study was to explore the function of Sema4D in the tumorigenesis and development of OS.
Methods:
10 pairs of...
Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant bone tumors. Neoadjuvant chemotherapy combined with limb-preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases and OS cells' resistance to chemotherapeutic agents are pressing challen...
Background:
Osteosarcoma is the most common pediatric malignant bone tumor, frequently surgically managed with limb salvage rather than amputation. Local recurrences are seen in up to 9% of osteosarcoma patients, with CT and MRI imaging often limited by metal artifacts.
Objective:
To describe the [F-18]2-fluoro-2-deoxyglucose (FDG) PET/CT appear...
Osteosarcoma is one of the most common bone tumors in teenagers. We hope to provide a reliable method to predict the prognosis of osteosarcoma and find potential targets for early diagnosis and precise treatment. To address this issue, we performed a detailed bioinformatics analysis based on the Cancer Genome Atlas (TCGA). A total of 85 osteosarcom...
Periosteal osteosarcoma is an uncommon primary malignant bone tumor in dogs and humans. This type of tumor is one of the four variants of osteosarcoma. The main feature is a superficial lesion without evidence of bone marrow involvement. The treatment usually performed is limb amputation. There is insufficient data on long-term disease-free time, s...
Citations
... Osteosarcoma is a frequently aggressive neoplasm affecting children and adolescents, with a low rate of survival [16]. The GA has a crucial role in tumor microenvironment, malignant progression, and pharmacotherapy [9,17,18]. ...
Background:
The Golgi apparatus (GA) is crucial for protein synthesis and modification, and regulates various cellular processes. Dysregulation of GA can lead to pathological conditions like neoplastic growth. GA-related genes (GARGs) mutations are commonly found in cancer, contributing to tumor metastasis. However, the expression and prognostic significance of GARGs in osteosarcoma are yet to be understood.
Methods:
Gene expression and clinical data of osteosarcoma patients were obtained from the TARGET and GEO databases. A consensus clustering analysis identified distinct molecular subtypes based on GARGs. Discrepancies in biological processes and immunological features among the subtypes were explored using GSVA, ssGSEA, and Metascape analysis. A GARGs signature was constructed using Cox regression. The prognostic value of the GARGs signature in osteosarcoma was evaluated using Kaplan-Meier curves and a nomogram.
Results:
Two GARG subtypes were identified, with Cluster A showing better prognosis, immunogenicity, and immune cell infiltration than Cluster B. A novel risk model of 3 GARGs was established using the TARGET dataset and validated with independent datasets. High-risk patients had poorer overall survival, and the GARGs signature independently predicted osteosarcoma prognosis. Combining risk scores and clinical characteristics in a nomogram improved prediction performance. Additionally, we discovered Stanniocalcin-2 (STC2) as a significant prognostic gene highly expressed in osteosarcoma and potential disease biomarker.
Conclusions:
Our study revealed that patients with osteosarcoma can be divided into two GARGs subgroups. Furthermore, we have developed a GARGs prognostic signature that can accurately forecast the prognosis of osteosarcoma patients.
... Osteosarcoma is an aggressive malignancy of the skeletal system [1,2]. It develops rapidly and has a poor prognosis and is associated with high mortality rates in children and adolescents [3,4]. The prognosis of osteosarcoma patients has greatly improved over the last few decades, due to advances in chemotherapy and surgical resection [5,6]. ...
Mitochondria play a vital role in osteosarcoma. Therefore, the purpose of this study was to investigate the potential role of mitochondrial-related genes (MRGs) in osteosarcoma. Based on 92 differentially expressed MRGs, osteosarcoma samples were divided into two subtypes using the nonnegative matrix factorization (NMF). Ultimately, a univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analysis were performed to construct a prognostic risk model. The single-sample gene set enrichment analysis assessed the immune infiltration characteristics of osteosarcoma patients. Finally, we identified an osteosarcoma biomarker, malonyl-CoA decarboxylase (MLYCD), which showed downregulation. Osteosarcoma cells proliferation, migration, and invasion were effectively inhibited by the overexpression of MLYCD. Our findings will help us to further understand the molecular mechanisms of osteosarcoma and contribute to the discovery of new diagnostic biomarkers and therapeutic targets.
... Osteosarcoma, a term first proposed in 1805 by the French surgeon Alexis Boyer, refers to a tumor derived from primitive osteogenic mesenchymal cells and describes the production of bone by osteosarcoma cells [1]. As the most common and aggressive type of bone neoplasm in children and adolescents, osteosarcoma frequently occurs in the epiphyses of long bones; therefore, osteosarcoma is characterized by rapid growth and fast progression [2]. ...
As one of the most ubiquitous types of posttranscriptional modification, N6-methyladenosine (m6A) is extensively implicated in almost all types of cancers, including osteosarcoma. Our previous research partially uncovered the role of Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) in osteosarcoma. However, the relationships between methyltransferase-like 3 (METTL3) and noncoding RNAs modified by METTL3, especially MALAT1, in osteosarcoma remain obscure.
The expression of METTL3 in osteosarcoma was evaluated by online bioinformatics analysis, immunohistochemical (IHC) staining, western blotting (WB), and reverse transcription–quantitative PCR (RT‒qPCR). Cell Counting Kit 8 (CCK-8) and Transwell assays were used to evaluate the cell proliferation and invasion abilities. The expression of MALAT1 in osteosarcoma was evaluated by online bioinformatics analysis and RT‒qPCR analysis. m6A methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) was used to detect m6A modification changes in MALAT1. An actinomycin D assay was used to study changes in the stability of MALAT1.
METTL3 was upregulated in osteosarcoma tissues and cell lines. Functionally, METTL3 promoted the proliferation and migration of osteosarcoma cells. Moreover, a clear positive correlation was found between METTL3 and MALAT1 expression, and MALAT1 was upregulated in osteosarcoma tissues and cells. Mechanistically, the presence of m6A modification sites in MALAT1 and METTL3-mediated m6A modification increased the stability of MALAT1 in osteosarcoma cells and promoted their proliferation and migration.
In this study, it was concluded that in osteosarcoma cells, METTL3, acting as an oncogene, promoted m6A modification of MALAT1, increased the stability of MALAT, and enhanced MALAT1-mediated oncogenic function.
... Nevertheless, other bones can also be affected. Although OS is more prevalent in children and adolescents, it can also occur in people over the age of 50, resulting in a second peak incidence [1,2]. OS affects 2-3 individuals per million each year in the general population. ...
... The majority of cancer hospitals currently use neoadjuvant chemotherapy, extensive tumor resection, and further adjuvant chemotherapy to treat high-grade OS. Low-grade OS is usually treated only with surgical excision [1]. Localized disease in children and young adults boasts a five-year survival rate of 78 %. ...
Objective
To study pyroptosis-related biomarkers that are associated with the prognosis and immune microenvironment characteristics of osteosarcoma (OS). The goal is to establish a foundation for the prognosis and treatment of OS.
Methods
We retrieved transcriptome and clinical data from The Cancer Genome Atlas (TCGA) database for 88 OS patients. Using this data, we constructed a prognostic model to identify pyroptosis-related genes (PRGs) associated with OS prognosis. To further explore the biological function of these PRGs, we performed enrichment analysis. To identify pyroptosis-related long non-coding RNAs (PRLncs) associated with the prognosis of OS, we performed co-expression analysis. Subsequently, a risk prognostic model was constructed using these PRLncs to generate a risk score, termed as PRLncs-score, thereby obtaining PRLncs associated with the prognosis of OS. The accuracy of the prognostic model was verified through survival analysis, risk curve, independent prognostic analysis, receiver operating characteristic (ROC) curve, difference analysis between high- and low-risk groups, and clinical correlation analysis. And to determine whether PRLncs-score is independent prognostic factor for OS. In addition, we further conducted external and internal validation for the risk prognosis model. Further analyses of immune cell infiltration and tumor microenvironment were performed. A pyroptosis-related competitive endogenous RNA (PRceRNA) network was constructed to obtain PRceRNAs associated with the prognosis of OS and performed gene set enrichment analysis (GSEA) on PRceRNA genes.
Results
We obtained five PRGs (CHMP4C, BAK1, GSDMA, CASP1, and CASP6) that predicted OS prognosis and seven PRLncs (AC090559.1, AP003119.2, CARD8-AS1, AL390728.4, SATB2-AS1, AL133215.2, and AC009495.3) and one PRceRNA (CARD8-AS1-hsa-miR-21-5p-IL1B) that predicted OS prognosis and indicated characteristics of the OS immune microenvironment. The PRLncs-score, in combination with other clinical features, was established as an independent prognostic factor for OS patients. Subsequent scrutiny of the tumor microenvironment and immune infiltration indicated that patients with low-PRLncs-scores were associated with reduced metastatic risk, improved survival rates, heightened levels of immune cells and stroma, and increased immune activity compared to those with high-PRLncs-scores.
Conclusion
The study's findings offer insight into the prognosis of OS and its immune microenvironment, and hold promise for improving early diagnosis and immunotherapy.
... The most prevalent primary bone tumor in children and adolescents is OS ("Osteosarcoma"), which is defined by the local invasion of bone and soft tissues and by the relatively poor response of these tissues to chemotherapy and radiation. 242 Drugs that target the PI3K/Akt pathway may be utilized to treat OS invasion and migration since PI3K ("Phosphatidylinositol 3-Kinase") and Akt are abnormally active in OS. 243 There is evidence that supports that the EMT ("Epithelial-Mesenchymal Transition") serves a significant role in metastasis initiation. EMT contributes to the invasion and metastasis of cancer cells. ...
Metformin has been designated as one of the most crucial first-line therapeutic agents in the management of type 2 diabetes mellitus. Primarily being an antihyperglycemic agent, metformin also has a plethora of pleiotropic effects on various systems and processes. It acts majorly by activating AMPK (Adenosine Monophosphate-Activated Protein Kinase) in the cells and reducing glucose output from the liver. It also decreases advanced glycation end products and reactive oxygen species production in the endothelium apart from regulating the glucose and lipid metabolism in the cardiomyocytes, hence minimizing the cardiovascular risks. Its anticancer, antiproliferative and apoptosis-inducing effects on malignant cells might prove instrumental in the malignancy of organs like the breast, kidney, brain, ovary, lung, and endometrium. Preclinical studies have also shown some evidence of metformin’s neuroprotective role in Parkinson’s disease, Alzheimer’s disease, multiple sclerosis and Huntington’s disease. Metformin exerts its pleiotropic effects through varied pathways of intracellular signalling and exact mechanism in the majority of them remains yet to be clearly defined. This article has extensively reviewed the therapeutic benefits of metformin and the details of its mechanism for a molecule of boon in various conditions like diabetes, prediabetes, obesity, polycystic ovarian disease, metabolic derangement in HIV, various cancers and aging.
... Osteosarcoma is a tumour which is malignant in nature and affects all bones, especially the long bones in humans. It tends to mature in the later part of adulthood, showing a bimodal distribution (Moore and Luu, 2014). It is the most prevalent type of bone tumour in children and adolescents (Eaton et al., 2021). ...
Vascular endothelial growth factor (VEGF) signals cell survival, cell migration,
osteogenesis, cell proliferation, angiogenesis, and vascular permeability by
binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common
primary bone cancer, majorly affects young adults. Activation of VEGFR-2
signaling is a therapeutic target for osteosarcoma. The present study aimed to
evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway
and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study
on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of
compounds using a virtual screening, Lipinski’s rule, bioavailability graphical
RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among
the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro
studies against human MG-63 osteosarcoma cells. Various experiments such as
MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment,
transwell migration assay, gene expression analysis by a quantitative real time
polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by
immunoblotting were performed to evaluate its anti-tumour effect as
compared to standard axitinib. The MTT assay indicates that stylopine inhibits
cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane
damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the
VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The
immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-
165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has
potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug
candidate for the treatment of bone cancer in future.
... It is reported that it may cause to be metastasized to other tissue in 80% of osteosarcoma patients. In the 1970s, advances in chemotherapeutic regimens are driven a major development in the treatment rate of osteosarcoma from about 30% to 70% compared to preexisting amputation and radical removal methods (Moore and Luu, 2014). Recently, osteosarcoma is usually treated by operations with concomitant chemotherapy (Marchese et al., 2004). ...
Acetylshikonin a natural compound isolated from the root of Lithospermum erythrorhizon and one of the shikonin derivatives which possess promising anticarcinogenic ability. In this study, we attempted to investigate the anti-cancer potential of acetylshikonin towards osteosarcoma U2OS cells. The effects of acetylshikonin towards the treatment of U2OS cells showed that decreased cell proliferation and inhibited migration ability of cells which are experimentally assessed via wide range of assays including MTT, WST-1, cell counting, colony formation assays, wound healing assay and gelatin zymography assay. We also observed that early apoptosis and late apoptosis were increased through fluorescence-activated cell sorter (FACS) analysis. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay showed that acetylshikonin induced DNA fragmentation. Western blot analysis revealed the apoptotic effect of acetylshikonin by measuring of proteins such as cleaved caspase −9, −8, −3, −6, −7, and Bcl-2 family. We observed that ROS level and DNA damage were increased via DCF-DA assay and comet assay. In terms of the presence of ROS, induction of apoptosis was detected by measuring proteins such as cleaved caspase 3, PARP, Bcl-2 and Bax. We suggested that the reactions were related to the nuclear translocation of FOXO3 through western blot of cytoplasmic/nuclear protein fractionation. We finally demonstrated that the knockdown of the FOXO3 induced the decrease of the apoptosis-associated proteins via western blot of FOXO3 siRNA transfection. Taken together, these results suggested that acetylshikonin might induce ROS-mediated apoptosis in a FOXO3-dependent manner against osteosarcoma cells. Therefore, acetylshikonin may be elucidated as an effective candidate for the treatment of osteosarcoma.
... The long-term survival of OS patients was around 60% for primary tumors [176], but only a limited improvement has been made since 1980's [177]. In contrast, the 5-year survival rate of patients with metastasis is still less than 40% [178]. The emerging nucleic acid therapy may provide new hope for OS patients. ...
The overall survival, progress free survival, and life quality of cancer patients have improved due to the advance in minimally invasive surgery, precision radiotherapy, and various combined chemotherapy in the last decade. Furthermore, the discovery of new types of therapeutics, such as immune checkpoint inhibitors and immune cell therapies have facilitated both patients and doctors to fight with cancers. Moreover, in the context of the development in biocompatible and cell type targeting nano-carriers as well as nucleic acid-based drugs for initiating and enhancing the anti-tumor response have come to the age. The treatment paradigms utilization of nucleic acids, including short interfering RNA (siRNA), antisense oligonucleotides (ASO), and messenger RNA (mRNA), can target specific protein expression to achieve the therapeutic effects. Over ten nucleic acid therapeutics have been approved by the FDA and EMA in rare diseases and genetic diseases as well as dozens of registered clinical trails for varies cancers. Though generally less dangerous of pediatric cancers than adult cancers was observed during the past decades, yet pediatric cancers account for a significant proportion of child deaths which hurt those family very deeply. Therefore, it is necessary to pay more attention for improving the treatment of pediatric cancer and discovering new nucleic acid therapeutics which may help to improve the therapeutic effect and prognoses in turns to ameliorate the survival period and quality of life for children patient. In this review, we focus on the nucleic acid therapy in pediatric cancers.
... As the most prevalent original malignancy in the bone, osteosarcoma (OS), often arises in pediatric sufferers with substantial morbidity [1]. Moreover, it tends to occur in the metaphysis of long bones, accompanied by rapid infiltration and early lung metastasis [2]. ...
Background
Osteosarcoma (OS) is a serious bone malignancy that commonly occurred in humans. Recent research suggested that circular RNA (circRNA) Dedicator of cytokinesis 1 (circDOCK1, also called hsa_circ_0020378) enrolled in the tumorigenesis of osteogenic sarcoma. This subject aimed to explore the precise role and mechanism of circDOCK1 on OS progression.
Methods
CircDOCK1, microRNA-936 (miR-936), and Lymphoid enhancer binding factor 1 (LEF1) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8 (CCK-8), colony formation, 5-ethynyl-2’-deoxyuridine (EdU), transwell, wound healing, and tube formation assays were used to assess OS cell proliferation, migration, invasion, and angiogenesis. Western blot analysis of protein levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP2), MMP9, and LEF1. According to bioinformatics software (circular RNA Interactome and TargetScan) analysis, the binding between miR-936 and circDOCK1 or LEF1 was predicted, followed by verification by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays.
Results
Increased circDOCK1 and LEF1, and decreased miR-936 were found in OS tissues and cell lines. Furthermore, circDOCK1 silencing might suppress OS cell proliferation, migration, invasion, and angiogenesis in vitro. Bioinformatics analysis exhibited that circDOCK1 acted as a sponge for miR-936 and LEF1 was a downstream target of miR-936. Moreover, circDOCK1 functions through modulation of the miR-936/LEF1 axis.
Conclusion
CircDOCK1 knockdown might attenuate OS cell malignant biological behaviors by regulating the miR-936/GFRA1 axis, which may highlight the diagnostic and therapeutic potential of these molecules for OS treatment.
... In this bone portion, characterized by a high cell division rate, the incorporation of mutations leads to the growth of pleomorphic osteoblasts that overproduce osteoid tissue. The progression into metastasis is the major cause of osteosarcomarelated death, both bony and lung metastasis are associated with a drastic reduction in the patient's life expectancy [38]. ...
Bone tissue exhibits critical factors for metastatic cancer cells and represents an extremely pleasant spot for further growth of tumors. The number of metastatic bone lesions and primary tumors that arise directly from cells comprised in the bone milieu is constantly increasing. Bioceramics have recently received significant attention in bone tissue engineering and local drug delivery applications. Additionally, additive manufacturing of bioceramics offers unprecedented advantages including the possibilities to fill irregular voids after the resection and fabricate patient-specific implants. Herein, we investigated the recent advances in additively manufactured bioceramics and ceramic-based composites that were used in the local bone tumor treatment and reconstruction of bone tumor defects. Furthermore, it has been extensively explained how to bi-functionalize ceramics-based biomaterials and what current limitations impede their clinical application. We have also discussed the importance of further development into ceramic-based biomaterials and molecular biology of bone tumors to: 1) discover new potential therapeutic targets to enhance conventional therapies, 2) local delivering of bio-molecular agents in a customized and “smart” way, and 3) accomplish a complete elimination of tumor cells in order to prevent tumor recurrence formation. We emphasized that by developing the research focus on the introduction of novel 3D-printed bioceramics with unique properties such as stimuli responsiveness, it will be possible to fabricate smart bioceramics that promote bone regeneration while minimizing the side-effects and effectively eradicate bone tumors while promoting bone regeneration. In fact, by combining all these therapeutic strategies and additive manufacturing, it is likely to provide personalized tumor-targeting therapies for cancer patients in the foreseeable future.
Statement of Significance
To increase the survival rates of cancer patients, different strategies such as surgery, reconstruction, chemotherapy, radiotherapy, etc have proven to be essential. Nonetheless, these therapeutic protocols have reached a plateau in their effectiveness due to limitations including drug resistance, tumor recurrence after surgery, toxic side-effects, and impaired bone regeneration following tumor resection. Hence, novel approaches to specifically and locally attack cancer cells, while also regenerating the damaged bony tissue, have being developed in the past years. This review sheds light to the novel approaches that enhance local bone tumor therapy and reconstruction procedures by combining additive manufacturing of ceramic biomaterials and other polymers, bioactive molecules, nanoparticles to affect bone tumor functions, metabolism, and microenvironment.
