Cancer Stem Cells and Osteosarcoma: Opportunities and Limitations

Osteosarcoma (OS) is the most common primary bone malignancy and is a leading cause of cancer-related death in children and young adults. Combination chemotherapy developed 3 decades ago significantly improved long-term survival compared to surgery alone. However, despite notable tumor cytoreduction and remission, the 5-year survival rate has remained static at ∼70% since, and the surviving patients have high chemoresistance with sustained risk of recurrent OS that has propensity to metastasize. After metastasis, the 5-year survival rate is abysmally low (∼10% to 20%). Emerging new evidence has revealed that within the heterogenous OS tumor evolves a subset of cancer stem cells with progenitor abilities that contribute to chemoresistance, tumor recurrence, and metastasis. Mechanistic insight into these cells has rekindled the hope for novel agents and treatment regimens for OS patients. In this review we discuss the recent advances towards the understanding of OS with emphasis on the functions of the cancer stem cells, microenvironment niche, genetic, epigenetic factors, and signaling pathways as well as their potential for new therapeutics.
Source: Techniques in Orthopaedics - Category: Orthopaedics Tags: Symposium Source Type: research

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AbstractEwing sarcoma (ES) and Ewing-like sarcomas are highly aggressive round cell mesenchymal neoplasms, most often occurring in children and young adults. The identification of novel molecular alterations has greatly contributed to a profound reappraisal of classification, to the extent that the category of undifferentiated round cell sarcoma has significantly shrunk. In fact, in addition to Ewing sarcoma, we currently recognize three main categories: round cell sarcomas withEWSR1 gene fusion with non-ETS family members,CIC-rearranged sarcomas, andBCOR-rearranged sarcomas. Interestingly, despite significant morphologic ...
Source: Virchows Archiv - Category: Pathology Source Type: research
Authors: Gang W, Tanjun W, Yong H, Jiajun Q, Yi Z, Hao H Abstract Osteosarcoma (OS) is the most common primary bone tumor that affects adolescents and young adults. Disruption of microRNA (miRNA) regulation is well established in the pathophysiology of different cancers, including OS. Increased expression of miR-9 in OS positively correlates with the tumor size, clinical stage, and distant metastasis. In the present study, we used two different OS cell lines, MG-63 and Saos-2, as in vitro models. Small interfering RNA against miR-9 and miR-9 mimics were used to study the function of miR-9 in these two cell lines. W...
Source: Bosnian Journal of Basic Medical Sciences - Category: General Medicine Tags: Bosn J Basic Med Sci Source Type: research
Abstract Osteosarcoma (OS), the most common malignant bone tumor, is the main cause of cancer-related death in children and young adults. Despite the combination of surgery and multi-agent chemotherapy, patients with OS who develop resistance to chemotherapy or experience recurrence have a dismal prognosis. MicroRNAs (miRNAs) are a class of small noncoding RNAs that repress their targets by binding to the 3'-UTR and/or coding sequences, leading to the inhibition of gene expression. miR-221 is found to be upregulated in tumors when compared to their matched normal osteoblast tissues.   We also observed signifi...
Source: Bioscience Reports - Category: Biomedical Science Authors: Tags: Biosci Rep Source Type: research
This study is designed to evaluate the efficacy of Fur A against OS. The effect of Fur A on cell viability was assessed by Cell Counting Kit-8 (CCK-8) assay. Western blotting and quantitative real-time PCR (qRT-PCR) were performed to determine the protein and mRNA level of sphingosine kinase 1 (SphK1), respectively. To validate the role of SphK1 in the pro-apoptotic activity of Fur A, overexpressing SphK1 vector and siRNA targeting SphK1 were utilized to transfect OS cells. Moreover, a OS xenograft murine model was used to analyze the therapeutic efficacy of Fur A in vivo. Fur A treatment led to a dose-dependent decrease i...
Source: Anatomical Record - Category: Anatomy Authors: Tags: Anat Rec (Hoboken) Source Type: research
Authors: Fan H, Lu S, Wang S, Zhang S Abstract Osteosarcoma is the most common type of malignant bone cancer, which often affects teenagers and young adults. The present study aimed to screen for critical genes and microRNAs (miRNAs/miRs) involved in osteosarcoma. A total of four microarray datasets (accession numbers GSE32981, GSE21257, GSE14827 and GSE14359) were downloaded from the Gene Expression Omnibus database. Following data preprocessing, module analysis was performed to identify the stable modules using the weighted gene co‑expression network analysis (WGCNA) package. The differentially expressed g...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
CONCLUSION: Osteosarcoma and Ewing Sarcoma are the most incident bone cancers in all Brazilian regions. Bone cancers showed incidence and mortality patterns variation within the geographic regions and across age groups, although not significant. Despite limitations, it is crucial to monitor cancer epidemiology trends across geographic Brazilian regions.
Source: Clinics - Category: General Medicine Source Type: research
Conclusions: Therefore, GRP94 silencing may increase the resistance of MG63 and 143B cells to paclitaxel, gemcitabine, and epirubicin treatments by inhibiting the induction of apoptosis. Thus, GRP94 may be a key biomarker for the chemotherapeutic response of OS. PMID: 30719181 [PubMed - in process]
Source: Disease Markers - Category: Laboratory Medicine Tags: Dis Markers Source Type: research
High-grade osteosarcoma is a primary malignant bone tumour mainly affecting children and young adults. The European and American Osteosarcoma Study (EURAMOS)-1 is a collaboration of four study groups aiming to improve outcomes of this rare disease by facilitating randomised controlled trials.
Source: European Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Original Research Source Type: research
Young adults take longer to clear methotrexate and receive fewer cycles of HDMTX compared to adolescents, but do not experience increased toxicity. Patients who receive more cycles of HDMTX may have better outcomes, regardless of age. AbstractBackgroundDoxorubicin, cisplatin, and high ‐dose methotrexate (HDMTX) are the backbone of pediatric osteosarcoma treatment. However, due to toxicity concerns and the lack of data regarding efficacy in adults, high‐dose methotrexate is rarely used in the adult population.MethodsThis single ‐center retrospective study examined 33 patients who received HDMTX (12 g/m2, maximum ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Osteosarcoma (OS) is the most common bone malignancy prevalent in children and young adults. MicroRNA-133b (miR-133b), through directly targeting the fibroblast growth factor receptor 1 (FGFR1), is increasingl...
Source: Cancer Cell International - Category: Cancer & Oncology Authors: Tags: Primary research Source Type: research
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