Summary Chordomas are very rare bone malignant tumours that have had a shortage of effective treatments for a long time. New treatments are now available for both the local and the metastatic phase ...of the disease, but the degree of uncertainty in selecting the most appropriate treatment remains high and their adoption remains inconsistent across the world, resulting in suboptimum outcomes for many patients. In December, 2013, the European Society for Medical Oncology (ESMO) convened a consensus meeting to update its clinical practice guidelines on sarcomas. ESMO also hosted a parallel consensus meeting on chordoma that included more than 40 chordoma experts from several disciplines and from both sides of the Atlantic, with the contribution and sponsorship of the Chordoma Foundation, a global patient advocacy group. The consensus reached at that meeting is shown in this position paper.
Mesenchymal chondrosarcoma(MCS) is a rare high-grade variant of chondrosarcoma. Consensus has not been reached on its optimal management. Resection with wide margins is usually recommended, but the ...effect of margins has been demonstrated by little positive evidence. Moreover, the effectiveness of adjuvant chemo- and/or radiotherapy remains controversial.
To describe the clinical characteristics and outcomes of MCS of bone and soft tissue, to assess the efficacies of surgery, chemotherapy and radiation, and finally to deliver a more appropriate therapy.
We reviewed EMBASE-, MEDLINE-, Cochrane-, Ovid- and PubMed-based to find out all cases of MCS of bone and soft tissue described between April 1994 and April 2014. Description of treatment and regular follow-up was required for each study. Language was restricted to English and Chinese. Issues of age, gender, location, metastasis, and treatment were all evaluated for each case. Kaplan-Meier Method and Cox Proportional Hazard Regression Model were used in the survival analysis.
From the 630 identified publications, 18 meeting the inclusion criteria were selected, involving a total of 107 patients. Based on these data, the 5-, 10-and 20-year overall survival are 55.0%, 43.5% and 15.7% respectively. The 5-, 10-, 20- year event-free survival rates are 45.0%, 27.2% and 8.1%, respectively. Treatment without surgery is associated with poorer overall survival and event-free survival. Negative surgical margins could significantly bring down the local-recurrence rate and are associated with a higher event-free survival rate. Chemotherapy regime based on anthracyclines does not benefit the overall survival. The addition of radiation therapy is not significantly associated with the overall or event-free survival. However, we recommend radiation as the salvage therapy for patients with positive margin so as to achieve better local control.
This review shows that surgery is essential in the management of MCS of bone and soft tissue. Appropriate adjuvant therapy may reduce local recurrence, but cannot benefit the overall survival.
Normal skeletal development requires tight coordination of transcriptional networks, signaling pathways, and biomechanical cues, and many of these pathways are dysregulated in pathological conditions ...affecting cartilage and bone. Recently, a significant role has been identified for long noncoding RNAs (lncRNAs) in developing and maintaining cellular phenotypes, and improvements in sequencing technologies have led to the identification of thousands of lncRNAs across diverse cell types, including the cells within cartilage and bone. It is clear that lncRNAs play critical roles in regulating gene expression. For example, they can function as epigenetic regulators in the nucleus via chromatin modulation to control gene transcription, or in the cytoplasm, where they can function as scaffolds for protein-binding partners or modulate the activity of other coding and noncoding RNAs. In this review, we discuss the growing list of lncRNAs involved in normal development and/or homeostasis of the skeletal system, the potential mechanisms by which these lncRNAs might function, and recent improvements in the methodologies available to study lncRNA functions in vitro and in vivo. Finally, we address the likely utility of lncRNAs as biomarkers and therapeutic targets for diseases of the skeletal system, including osteoarthritis, osteoporosis, and in cancers of the skeletal system.
Interleukin (IL) 16 plays a key role in inflammatory diseases as well as in tumorigenesis of osteosarcoma (OS). The aim of this study was to investigate the association of IL16 polymorphisms and ...plasma IL16 level with OS risk in a Chinese population. We genotyped IL16 rs4778889, rs11556218, and rs4072111 in 358 patients with OS and 402 controls using a polymerase chain reaction-restriction fragment length polymorphism assay. Plasma IL16 level was measured by enzyme-linked immunosorbent assay. Rs11556218 was associated with an increased risk of OS in heterozygote comparison (adjusted OR = 1.65, 95% CI, 1.23-2.21, P < 0.001), dominant model (adjusted OR = 1.66, 95% CI, 1.24-2.21, P < 0.001), and allele comparison (adjusted OR = 1.44, 95% CI, 1.14-1.81, P = 0.002). Moreover, rs11556218 TG/GG genotypes were associated with higher levels of IL16 as compared to TT genotype (P = 0.03). However, no significant association of rs4778889 and rs4072111 and OS was found. These findings suggest that rs11556218 TG/GG genotypes may be associated with increased susceptibility to OS, probably by increasing the production of IL16 level.
The last report of the World Health Organization (WHO) stated that approximately four million people experience bone pain due to malignant diseases. Among them, metastatic bone pain is one of the ...most important sources of complaint. The estimated median survival in the presence of bone metastases ranks from 10 to 12 weeks. Bone represents a potential target of distant metastases for the majority of malignant tumours. However, the exact incidence of bone metastases is unknown. Bone metastases have an important socio-economic impact, and due to the enhancement of the overall survivorship, their incidence is increasing. Malignant neoplasms such as lung, thyroid, renal cancer, multiple myeloma, and melanoma often metastasize to the bone. Bone metastases commonly localize to the spinal column, pelvis, shoulder, and distal femur. The proper treatment for painful skeletal metastases is still unknown. Hence, the purpose of this review of the literature was to update current evidence concerning the aetiogenesis, biological behaviour, and treatment algorithms for painful skeletal metastases.
The progression of multiple myeloma (MM) is governed by a network of molecular signals, the majority of which remain to be identified. Recent studies suggest that Runt-related transcription factor 2 ...(Runx2), a well-known bone-specific transcription factor, is also expressed in solid tumors, where expression promotes both bone metastasis and osteolysis. However, the function of Runx2 in MM remains unknown. The current study demonstrated that (1) Runx2 expression in primary human MM cells is significantly greater than in plasma cells from healthy donors and patients with monoclonal gammopathy of undetermined significance; (2) high levels of Runx2 expression in MM cells are associated with a high-risk population of MM patients; and (3) overexpression of Runx2 in MM cells enhanced tumor growth and disease progression in vivo. Additional studies demonstrated that MM cell–derived Runx2 promotes tumor progression through a mechanism involving the upregulation of Akt/β-catenin/Survivin signaling and enhanced expression of multiple metastatic genes/proteins, as well as the induction of a bone-resident cell-like phenotype in MM cells. Thus, Runx2 expression supports the aggressive phenotype of MM and is correlated with poor prognosis. These data implicate Runx2 expression as a major regulator of MM progression in bone and myeloma bone disease.
•Myeloma cell–derived Runx2 promotes myeloma progression.•High levels of Runx2 expression are associated with a high-risk myeloma population.
Unlike other malignant bone tumors including osteosarcomas and Ewing sarcomas with a peak incidence in adolescents and young adults, conventional and dedifferentiated chondrosarcomas mainly affect ...people in the 4th to 7th decade of life. To date, the cell type of chondrosarcoma origin is not clearly defined. However, it seems that mesenchymal stem and progenitor cells (MSPC) in the bone marrow facing a pro-proliferative as well as predominantly chondrogenic differentiation milieu, as is implicated in early stage osteoarthritis (OA) at that age, are the source of chondrosarcoma genesis. But how can MSPC become malignant? Indeed, only one person in 1,000,000 will develop a chondrosarcoma, whereas the incidence of OA is a thousandfold higher. This means a rare coincidence of factors allowing escape from senescence and apoptosis together with induction of angiogenesis and migration is needed to generate a chondrosarcoma. At early stages, chondrosarcomas are still assumed to be an intermediate type of tumor which rarely metastasizes. Unfortunately, advanced stages show a pronounced resistance both against chemo- and radiation-therapy and frequently metastasize. In this review, we elucidate signaling pathways involved in the genesis and therapeutic resistance of chondrosarcomas with a focus on MSPC compared to signaling in articular cartilage (AC).
Osteosarcoma is the most common malignant bone tumor in children and adolescents with high rate of incidence, high frequency of recurrence, and high degree of metastasis. This study aimed to ...investigate the effects of long noncoding RNA antisense ncRNA in the abundant in neuroepithelium area (ANA)/B‐cell translocation gene 3 (BTG3) locus (lncRNA ASBEL) on the pathogenesis of osteosarcoma. The expression levels of ASBEL in human osteoblast cells and human osteosarcoma cells were evaluated using qRT‐PCR. Effects of ASBEL knockdown on cell viability, migration, and invasion were detected using trypan blue exclusion assay, cell migration, and cell invasion assay, respectively. The regulatory effects of ASBEL on microRNA‐21 (miR‐21) were analyzed using qRT‐PCR. The roles of miR‐21 and protein phosphatase 2A (PP2A), the possible downstream factor of miR‐21, in osteosarcoma cell proliferation, migration, and invasion were also explored. The results showed that ASBEL was highly expressed in osteosarcoma cells. Knockdown of ASBEL inhibited osteosarcoma cell viability, migration, and invasion, as well as the expression level of miR‐21. PP2A was a direct target of miR‐21, which participated in the effects of ASBEL and miR‐21 on the activation of phosphatidylinositol 3‐kinase/protein kinase 3/glycogen synthase kinase‐3β (PI3K/AKT/GSK3β) and mitogen‐activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathways as well as the enhancement of osteosarcoma cell proliferation, migration, and invasion. In conclusion, we verified that ASBEL‐miR‐21‐PP2A pathway might play critical regulatory effects on the pathogenesis of osteosarcoma and could be as the potential therapeutic target and biomarker for osteosarcoma treatment.
ASBEL was highly expressed in osteosarcoma cells. Knockdown of ASBEL inhibited osteosarcoma cell viability, migration, and invasion, as well as the expression level of miR‐21. PP2A was a direct target of miR‐21, which was participated in the effects of ASBEL and miR‐21 on the activation of phosphatidylinositol 3‐kinase/protein kinase 3/glycogen synthase kinase‐3β (PI3K/AKT/GSK3β) and mitogen‐activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathways as well as the enhancement of osteosarcoma cell proliferation, migration, and invasion.
The skeleton is the most common organ to be affected by metastatic cancer and the site of disease that produces the greatest morbidity. Skeletal morbidity includes pain that requires radiotherapy, ...hypercalcemia, pathologic fracture, and spinal cord or nerve root compression. From randomized trials in advanced cancer, it can be seen that one of these major skeletal events occurs on average every 3 to 6 months. Additionally, metastatic disease may remain confined to the skeleton with the decline in quality of life and eventual death almost entirely due to skeletal complications and their treatment. The prognosis of metastatic bone disease is dependent on the primary site, with breast and prostate cancers associated with a survival measured in years compared with lung cancer, where the average survival is only a matter of months. Additionally, the presence of extraosseous disease and the extent and tempo of the bone disease are powerful predictors of outcome. The latter is best estimated by measurement of bone-specific markers, and recent studies have shown a strong correlation between the rate of bone resorption and clinical outcome, both in terms of skeletal morbidity and progression of the underlying disease or death. Our improved understanding of prognostic and predictive factors may enable delivery of a more personalized treatment for the individual patient and a more cost-effective use of health care resources.
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