Pediatric osteosarcoma: An updated review

Taran, Shachi Jain; Taran, Rakesh; Malipatil, Nagraj B

doi:10.4103/0971-5851.203513

Cited by 162 publications

(143 citation statements)

References 51 publications

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“…Osteosarcoma (OS) is the most common type of bone cancer found in children and teens [1]. The long-term survival rate for localized OS is approximately 65 percent [2] while the long-term survival rate for OS that has spread to other parts of the body is less than 30 percent [3].…”

Section: Introductionmentioning

confidence: 99%

Knock down of Fas-Associated Protein with Death Domain (FADD) Sensitizes Osteosarcoma to TNFα-induced Cell Death

et al. 2020

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Fas-associated protein with death domain (FADD) was first identified for its role in linking death receptors to the apoptotic signaling pathway with subsequent cell death. Later studies reported non-apoptotic functions for FADD in normal cells and cancer cells. Non-apoptotic functions for FADD in osteosarcoma (OS) have not been reported. In this study, FADD protein expression was knocked down in human CCHOSD, LM7, and SaOS2 OS cell lines followed by assessment of sensitivity to TNFα-or TRAIL-induced cell death. Knock down of FADD significantly increased TNFα-induced cell death in LM7 and SaOS2 cell lines. The mode of TNFα-induced cell death was apoptosis and not necroptosis. Inhibition of nuclear factor kappa B (NFκB) in wildtype cells increased TNFα-induced cell death to similar levels observed in FADD knockdown cells, suggesting a role for FADD in NFκB pro-survival cell signaling. In addition, knock down of FADD increased SMAC mimetic-mediated TNFα-induced cell death in all cell lines studied. The results of this study indicate that FADD has a pro-survival function in OS following TNFα treatment that involves NFκB signaling. The results also indicate that the pro-survival function of FADD is associated with XIAP activity.

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Section: Introductionmentioning

confidence: 99%

Knock down of Fas-Associated Protein with Death Domain (FADD) Sensitizes Osteosarcoma to TNFα-induced Cell Death

et al. 2020

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“…Osteosarcomas are the most common primary bone malignant tumors, which mainly affects children and adolescents. 1 Chemotherapy has significantly improved the 5-year overall survival of osteosarcoma patients from less than 30% to over 60%. 2 However, the long-term overall survival of patients following metastasis remains less than 20%.…”

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confidence: 99%

Targeting mutant TP53 as a potential therapeutic strategy for the treatment of osteosarcoma

Tang

Seebacher

et al. 2019

Journal Orthopaedic Research

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Mutant TP53 is a promising therapeutic target in cancers. Considering the current challenges facing the clinical treatment of cancer, as well as the urgent need to identify novel therapeutic targets in osteosarcomas, we aimed to evaluate the clinical significance of mutant TP53 in osteosarcoma patients and to explore the therapeutic effect of targeting mutant TP53 in osteosarcomas. We performed a meta‐analysis to investigate the relationship between mutant TP53 and the overall survival of patients with osteosarcoma. A CRISPR‐Cas9 system and a TP53 inhibitor, NSC59984, were also used to specifically knock‐out and inhibit mutant TP53 in the human osteosarcoma cell lines, KHOS, and KHOSR2. The meta‐analysis demonstrated that mutations in the TP53 gene could be used to predict a poor 2‐year survival in osteosarcoma patients. We also demonstrated that the expression of mutant TP53 in human osteosarcoma cell lines can be efficiently knocked‐out using CRISPR‐Cas9, and this decreased the proliferation, migration, and tumor formation activity of these osteosarcoma cells. Moreover, drug sensitivity to doxorubicin was increased in these TP53 knock‐out osteosarcoma cells. NSC59984 also showed similar anti‐tumor effects as CRISPR‐Cas9 targeted TP53 in the osteosarcoma cells in vitro. We have also demonstrated that the knock‐out or inhibition of mutant TP53 decreased the expression of the oncogene IGF‐1R, anti‐apoptotic proteins Bcl‐2, and Survivin in osteosarcoma cells. Collectively, these results suggest that mutant TP53 is a promising therapeutic target in osteosarcomas. Therefore, further studies exploring novel strategies to target mutant TP53 may help improve the treatment outcomes of osteosarcoma patients in the clinic. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

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“…OS develops rapidly and is prone to recurrence and metastasis [3]. OS takes up about 5% of pediatric tumors, and most patients die within a year of diagnosis [4,5]. Although the emergence of neoadjuvant chemotherapy greatly improves the 5-year survival rate of OS patients, the recurrence rate of OS is still high [6].…”

Section: Introductionmentioning

confidence: 99%

CA9 is an important molecular marker for the prognosis of osteosarcoma patients

Chen

Wang

et al. 2020

Preprint

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Background As a common malignant bone tumor, osteosarcoma (OS) progresses rapidly and recurs easily. This study is aimed to build a risk score system for OS patients. Methods From The Cancer Genome Atlas and Gene Expression Omnibus databases, the RNA-seq data of OS (the training set) and GSE39055 (the validation sets) separately were obtained. Combined with limma package, the differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) between recurrence and non-recurrence groups were analyzed. After the RNAs correlated with independent prognosis were screened using survival package, risk score systems were constructed and the optimal one was selected. For the independent clinical prognostic factors identified by survival package, stratification analysis was conducted. Using Gene Set Enrichment Analysis, pathways were enriched for the differentially expressed genes (DEGs) between high and low risk groups. Results For recurrence and non-recurrence groups, 319 DE-mRNAs and 14 DE-lncRNAs were identified. Subsequently, 10 DE-mRNAs (including ALDH1A1, CA9, GMDS, LCMT2, LRRC75A, METTL1, RAB29, TADA2B, TDRD7, and TIGD2) and eight DE-lncRNAs were found to be correlated with independent prognosis. From the four risk score systems, the mRNA expression status-based risk score system was selected as the optimal one. Among the three independent clinical prognostic factors, age and recurrence were significantly related to overall survival in high risk group. Additionally, vascular smooth muscle contraction, and glycine, serine and threonine metabolism were enriched for the DEGs between high and low risk groups. Conclusion The mRNA expression status-based risk score system might be devoted to predict the prognosis of OS patients.

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Pediatric osteosarcoma: An updated review

Cited by 162 publications

References 51 publications

Knock down of Fas-Associated Protein with Death Domain (FADD) Sensitizes Osteosarcoma to TNFα-induced Cell Death

Knock down of Fas-Associated Protein with Death Domain (FADD) Sensitizes Osteosarcoma to TNFα-induced Cell Death

Targeting mutant TP53 as a potential therapeutic strategy for the treatment of osteosarcoma

CA9 is an important molecular marker for the prognosis of osteosarcoma patients

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