Childhood osteosarcoma: Incidence and survival in Argentina. Report from the National Pediatric Cancer Registry, ROHA Network 2000–2013

Moreno, Florencia; Cacciavillano, Walter; Cipolla, M.; Coirini, Marcelo; Streitenberger, Patricia; Marti, Jennifer L.; Palladino, Marcela; Morici, M.; Onoratelli, Myriam; Drago, G; Schifino, A; Cores, María; Rose, Adriana; Jotomliansky, J.; Varel, M.; Lombardi, Mercedes García

doi:10.1002/pbc.26533

Cited by 34 publications

(21 citation statements)

References 21 publications

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“…In our study, survival rates in children diagnosed with osteosarcoma are low and comparable with other studies conducted in LMIC . Abandonment of treatment is a major issue in our country, as previously reported, and represents a major contributing factor of worse prognosis.…”

Section: Discussionsupporting

confidence: 88%

Prognostic impact of diagnostic and treatment delays in children with osteosarcoma

Vásquez

Silva

Chávez

et al. 2020

Pediatric Blood & Cancer

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Background The aim of this study is to evaluate the relationship between the latency to diagnosis (LD) and the time to completion of chemotherapy (TCC) with clinical outcomes in children with osteosarcoma. Methods We performed a retrospective analysis of all patients who received treatment for osteosarcoma in two tertiary centers in Peru from 2008 to 2015. All causes of delayed LD or TCC were evaluated. Overall survival (OS) and event‐free‐survival (EFS) were estimated and compared according to LD, TCC, and established clinical prognostic factors. Results One hundred and thirteen patients were included in the study. The median LD was 13.5 weeks (interquartile range, 10‐18.5 weeks). No association was observed among clinical stage, tumor size, and LD. Delayed LD was not associated with a worse clinical outcome. Multivariate analysis confirmed that OS and EFS were significantly worse in cases of a delayed TCC (≥4 weeks), with hazard ratios of 2.70 (1.11‐6.76, P = 0.003) and 1.13 (1.00‐1.26, P = 0.016), respectively. Most delays in TCC (85%) were due to extramedical reasons (e.g., lack of available hospital beds). Conclusion The LD did not seem to influence the EFS and OS in pediatric patients with osteosarcoma. However, a delay in TCC from any cause is independently associated with poor outcome in pediatric patients with osteosarcoma. Based on these results, further efforts may be needed to avoid treatment delays in patients with osteosarcoma in middle‐income countries.

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Section: Discussionsupporting

confidence: 88%

Prognostic impact of diagnostic and treatment delays in children with osteosarcoma

Vásquez

Silva

Chávez

et al. 2020

Pediatric Blood & Cancer

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“…OS is the second leading cause of cancer-associated mortality among young individuals worldwide; [3][4][5] however, the underlying mechanism that modulates its occurrence and pathophysiology remains unclear. Merlin has been identified as an anti-oncogene 31,32 and plays an essential role in OS.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3] OS primarily affects young individuals, and is the second leading cause of cancer-associated mortality in children and adolescents worldwide. 4,5 The 5-year overall survival rate of OS has increased to approximately 6070% owing to the considerable advances in surgical technologies and combined therapeutic strategies. 6 However, the survival rate remains poor in patients at advanced clinical stages and with pulmonary metastases.…”

Section: Introductionmentioning

confidence: 99%

<p>MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma</p>

Rao¹,

Wu²,

Wei³

et al. 2020

CMAR

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Moesin-ezrin-radixin-like protein (Merlin) has been identified as a tumor suppressor in several types of cancers. However, the biological function of Merlin in osteosarcoma remains unclear. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we sought to evaluate the regulation of Merlin expression by miR-25-3p and the role of the miR-25-3p/Merlin axis in osteosarcoma progression, with the aim of identifying a potential therapeutic target for osteosarcoma. Materials and Methods: TCGA (The Cancer Genome Atlas) database was used to analyze the correlation between Merlin expression and prognosis. RT-qPCR and Western blotting analyses were performed to compare Merlin expression between normal and malignant cells. A dual-luciferase reporter assay was performed to evaluate the direct targeting of Merlin by miR-25-3p. We overexpressed miR-25-3p, or/and Merlin, in U-2 OS and 143B cells, and studied their cellular functions in vitro. MTT and colony formation assays were performed to determine the effects on cell growth. EdU and cell cycle assays were performed to analyze the effects in cell replication. We used annexin V-fluorescein isothiocyanate and propidium iodide to stain apoptotic cells, and analyzed the cells using flow cytometry. The effects on cell metastasis were studied in wound healing and transwell assays. Lastly, the underlying mechanism was determined in RT-qPCR and Western blotting experiments. Results: Low Merlin expression was linked to poor prognosis. miR-25-3p was observed to directly target Merlin and downregulate its expression. miR-25-3p promoted cell growth, migration, and invasion, and inhibited apoptosis induced by cisplatin. Moreover, the overexpression of Merlin reversed the abovementioned effects of miR-25-3p. Further, the miR-25-3p/Merlin axis was observed to play an important role in the Hippo pathway, and regulated the expression of genes such as BIRC5, CTGF, and CYR61. Conclusion: miR-25-3p functions as an oncogenic microRNA in osteosarcoma by targeting Merlin, and may serve as a potential therapeutic target for osteosarcoma.

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“…Osteosarcoma is the most common tumor of the bone in adolescents [ 1 , 2 ]. The incidence of patients aged 0-24 years was between 2.0% and 7.6% depending on the regions [ 3 ]. It was reported that there were about 20% of osteosarcoma patients presenting clinical metastasis to the lungs at the time of initial examination and the 5-year survival rate was less than 20% in these patients [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

PLOD1 Is a Prognostic Biomarker and Mediator of Proliferation and Invasion in Osteosarcoma

Jiang

Guo

Yuan

et al. 2020

BioMed Research International

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Objective. Osteosarcoma is the most common primary bone tumor and most frequently develops during adolescence. PLOD family was mainly involved in lysyl hydroxylation and rarely investigated in cancers, especially in osteosarcoma. The aim of this study was to investigate the expression pattern and oncogenic role of PLODs in osteosarcoma. Methods. GEO datasets (GSE16088, GSE33382, and GSE16091) and validation cohort were used to analyze the expression pattern of PLODs in osteosarcoma. Kaplan-Meier survival analysis was used to explore the prognostic role of PLODs in patients with osteosarcoma. RNA interference of KRT19 was performed using small interfering RNA (siRNA) in MG-63 and U-2OS cells. The proliferation was detected using CCK8, clone formation assay, and EdU staining. Migration and invasion were determined using the transwell assay. Western blots and luciferase assays for β-catenin-T-cell factor protein/β-catenin-lymphoid enhancer factor- (β-catenin-TCF/LEF-) driven transcriptional activity. Results. PLOD1 was upregulated in osteosarcoma tissues compared with control tissues both in public datasets and in in-house cohort. The expression of PLOD1 in osteosarcoma tissues was significantly associated with the status of distance metastasis and Enneking stage, while PLOD2 and PLOD3 expressed no difference between osteosarcoma and benign tissues and showed no correlation with tumor malignancy. Furthermore, Kaplan-Meier survival analysis revealed that patients with a higher level of PLOD1 had worse prognosis than those with a lower level of PLOD1. Downregulation of PLOD1 dramatically inhibited proliferation, migration, and invasion of MG-63 cells and U-2OS cells in vitro. Mechanistically, PLOD1 regulated β-catenin signaling pathway in osteosarcoma. Conclusion. Our results indicated that PLOD1 promoted proliferation, migration, and invasion of osteosarcoma cells. PLOD1 was a novel prognostic marker, as well as a therapeutic target in osteosarcoma.

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Childhood osteosarcoma: Incidence and survival in Argentina. Report from the National Pediatric Cancer Registry, ROHA Network 2000–2013

Abstract: In Argentina, ASR of osteosarcoma is similar to that in high-income countries, but survival is lower in all regions. Future work will focus on identification and reduction of causes of preventable treatment failure.

Cited by 34 publications

References 21 publications

Prognostic impact of diagnostic and treatment delays in children with osteosarcoma

Prognostic impact of diagnostic and treatment delays in children with osteosarcoma

<p>MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma</p>

PLOD1 Is a Prognostic Biomarker and Mediator of Proliferation and Invasion in Osteosarcoma

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