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Osteosarcoma

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1. Osteosarcoma

Osteosarcoma Osteosarcoma - Symptoms, diagnosis and treatment | BMJ Best Practice You'll need a subscription to access all of BMJ Best Practice Search  Osteosarcoma Last reviewed: February 2019 Last updated: February 2019 Summary Most common non-haematological primary malignant neoplasm of bone in children and adolescents. Pain and swelling are the most common presenting symptoms. Although it can occur at any age, it usually affects patients in the second and third decade of life with a peak (...) incidence between 13 and 16 years of age. It is more common in males than females. Chemotherapy combined with surgery is the standard of care. Prognosis of patients with localised disease has improved substantially following the introduction of chemotherapy, with 75% to 80% 5-year survival rates. Definition The World Health Organization defines osteosarcoma as a primary osseous malignant neoplasm composed of mesenchymal cells producing osteoid and immature bone, even if only in small amounts. Fletcher

2019 BMJ Best Practice

3. Osteosarcoma

Osteosarcoma Osteosarcoma - Symptoms, diagnosis and treatment | BMJ Best Practice You'll need a subscription to access all of BMJ Best Practice Search  Osteosarcoma Last reviewed: February 2019 Last updated: February 2019 Summary Most common non-haematological primary malignant neoplasm of bone in children and adolescents. Pain and swelling are the most common presenting symptoms. Although it can occur at any age, it usually affects patients in the second and third decade of life with a peak (...) incidence between 13 and 16 years of age. It is more common in males than females. Chemotherapy combined with surgery is the standard of care. Prognosis of patients with localised disease has improved substantially following the introduction of chemotherapy, with 75% to 80% 5-year survival rates. Definition The World Health Organization defines osteosarcoma as a primary osseous malignant neoplasm composed of mesenchymal cells producing osteoid and immature bone, even if only in small amounts. Fletcher

2017 BMJ Best Practice

4. Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. (PubMed)

Survival and prognosis with osteosarcoma: outcomes in more than 2000 patients in the EURAMOS-1 (European and American Osteosarcoma Study) cohort. 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.Patients eligible for EURAMOS-1 were aged ≤40 years with M0 (...) or M1 skeletal high-grade osteosarcoma in which case complete surgical resection at all sites was deemed to be possible. A three-drug combination with methotrexate, doxorubicin and cisplatin was defined as standard chemotherapy, and between April 2005 and June 2011, 2260 patients were registered. We report survival outcomes and prognostic factors in the full cohort of registered patients.For all registered patients at a median follow-up of 54 months (interquartile range: 38-73) from biopsy, 3-year

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2019 European Journal of Cancer

5. Intratibial Injection Causes Direct Pulmonary Seeding of Osteosarcoma Cells and Is Not a Spontaneous Model of Metastasis: A Mouse Osteosarcoma Model. (PubMed)

Intratibial Injection Causes Direct Pulmonary Seeding of Osteosarcoma Cells and Is Not a Spontaneous Model of Metastasis: A Mouse Osteosarcoma Model. Although metastasis is the major cause of mortality in patients with osteosarcoma, little is known about how micrometastases progress to gross metastatic disease. Clinically relevant animal models are necessary to facilitate development of new therapies to target indolent pulmonary metastases. Intratibial injection of human and murine osteosarcoma (...) cell lines have been described as orthotopic models that develop spontaneous pulmonary metastasis over time. However, there is variability in reported injection techniques and metastatic efficiency.We aimed to characterize a widely used murine model of metastatic osteosarcoma, determine whether it is appropriate to study spontaneous pulmonary metastasis by establishing a reliable volume for intratibial injection, determine the incidence of primary tumor and metastatic formation, determine

2018 Clinical Orthopaedics and Related Research

6. Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability (PubMed)

Citrus aurantium Naringenin Prevents Osteosarcoma Progression and Recurrence in the Patients Who Underwent Osteosarcoma Surgery by Improving Antioxidant Capability Citrus aurantium is rich in flavonoids, which may prevent osteosarcoma progression, but its related molecular mechanism remains unclear. Flavonoids were extracted from C. aurantium and purified by reparative HPLC. Each fraction was identified by using electrospray ionisation mass spectrometry (ESI-MS). Three main components (naringin (...) , naringenin, and hesperetin) were isolated from C. aurantium. Naringenin inhibited the growth of MG-63 cells, whereas naringin and hesperetin had no inhibitory function on cell growth. ROS production was increased in naringin- and hesperetin-treated groups after one day of culture while the level was always lowest in the naringenin-treated group after three days of culture. 95 osteosarcoma patients who underwent surgery were assigned into two groups: naringenin group (NG, received 20 mg naringenin daily

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2018 Oxidative medicine and cellular longevity

7. CEACAM6 is associated with osteosarcoma metastasis and facilitates epithelial–mesenchymal transition in osteosarcoma cells (PubMed)

CEACAM6 is associated with osteosarcoma metastasis and facilitates epithelial–mesenchymal transition in osteosarcoma cells Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is a member of CEACAM family and has been reported to be upregulated in various types of human cancer and involved in tumor progression and metastasis. However, the biological roles and clinical significances of CEACAM6 in osteosarcoma still remain to be elucidated.Real-timePCR, immunohistochemistry (...) and Western blot analysis were used to determine CEACAM6 expression in osteosarcoma cell lines and clinical specimens. Then the clinical relevance of CEACAM6 was analyzed in osteosarcoma. The function of CEACAM6 in osteosarcoma was examined by wound-healing and cell invasion assays, and expression levels of epithelial-mesenchymal transition markers.In the present study, we found that CEACAM6 was markedly upregulated in metastatic osteosarcoma tissues when compared with the nonmetastatic osteosarcoma

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2018 OncoTargets and therapy

8. Hedgehog signalling in the tumourigenesis and metastasis of osteosarcoma, and its potential value in the clinical therapy of osteosarcoma (PubMed)

Hedgehog signalling in the tumourigenesis and metastasis of osteosarcoma, and its potential value in the clinical therapy of osteosarcoma The Hedgehog (Hh) signalling pathway is involved in cell differentiation, growth and tissue polarity. This pathway is also involved in the progression and invasion of various human cancers. Osteosarcoma, a subtype of bone cancer, is commonly seen in children and adolescents. Typically, pulmonary osteosarcoma metastases are especially difficult to control (...) . In the present paper, we summarise recent studies on the regulation of osteosarcoma progression and metastasis by downregulating Hh signalling. We also summarise the crosstalk between the Hh pathway and other cancer-related pathways in the tumourigenesis of various cancers. We further summarise and highlight the therapeutic value of potential inhibitors of Hh signalling in the clinical therapy of human cancers.

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2018 Cell death & disease

9. High-Grade Osteosarcoma of the Foot: Presentation, Treatment, Prognostic Factors, and Outcome of 23 Cooperative Osteosarcoma Study Group COSS Patients (PubMed)

High-Grade Osteosarcoma of the Foot: Presentation, Treatment, Prognostic Factors, and Outcome of 23 Cooperative Osteosarcoma Study Group COSS Patients Osteosarcoma of the foot is a very rare presentation of a rare tumor entity. In a retrospective analysis, we investigated tumor- and treatment-related variables and outcome of patients registered in the Cooperative Osteosarcoma Study Group (COSS) database between January 1980 and April 2016 who suffered from primary high-grade osteosarcoma (...) tumors. Median follow-up was 4.2 years (range: 0.4-18.5). At the last follow-up, 15 of the 23 patients were alive and 8 had died. Five-year overall and event-free survival estimates were 64% (standard error (SE) 12%) and 54% (SE 13%), which is similar to that observed for osteosarcoma in general. Event-free and overall survival correlated with primary metastatic status and completeness of surgery. Our findings show that high-grade osteosarcoma in the foot has a similar outcome as osteosarcoma

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2018 Sarcoma

10. Does ATRX germline variation predispose to osteosarcoma? Three additional cases of osteosarcoma in two ATR-X syndrome patients. (PubMed)

Does ATRX germline variation predispose to osteosarcoma? Three additional cases of osteosarcoma in two ATR-X syndrome patients. Osteosarcoma is the most common malignant bone tumor in adolescents and young adults. Most osteosarcomas are sporadic but the risk of osteosarcoma is also increased by germline variants in TP53, RB1 and RECQL4 genes. ATRX germline variations are responsible for the rare genetic disorder X-linked alpha-thalassemia mental retardation (ATR-X) syndrome characterized (...) by severe developmental delay and alpha-thalassemia but no obvious increased risk of cancer. Here we report two children with ATR-X syndrome who developed osteosarcoma. Notably, one of the children developed two osteosarcomas separated by 10 years. Those two cases raise the possibility that ATRX germline variant could be associated with an increased risk of osteosarcoma.

2018 European Journal of Human Genetics

11. Results of a randomized, prospective clinical trial evaluating metronomic chemotherapy in nonmetastatic patients with high-grade, operable osteosarcomas of the extremities: A report from the Latin American Group of Osteosarcoma Treatment. (PubMed)

Results of a randomized, prospective clinical trial evaluating metronomic chemotherapy in nonmetastatic patients with high-grade, operable osteosarcomas of the extremities: A report from the Latin American Group of Osteosarcoma Treatment. Metronomic chemotherapy (MC) consists of the administration of a low dose of chemotherapy on a daily or weekly basis without a long break to achieve an antitumoral effect through an antiangiogenic effect or stimulation of the immune system. The potential (...) effect of MC with continuous oral cyclophosphamide and methotrexate in patients with high-grade operable osteosarcomas (OSTs) of the extremities was investigated.Patients with high-grade OSTs who were 30 years old or younger were eligible for registration at diagnosis. Eligibility for randomization included 1) nonmetastatic disease and 2) complete resection of the primary tumor. The study design included a backbone of 10 weeks of preoperative therapy with methotrexate, adriamycin, and platinum (MAP

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2017 Cancer

12. GLP2 Promotes Directed Differentiation from Osteosarcoma Cells to Osteoblasts and Inhibits Growth of Osteosarcoma Cells (PubMed)

GLP2 Promotes Directed Differentiation from Osteosarcoma Cells to Osteoblasts and Inhibits Growth of Osteosarcoma Cells Glucagon-like peptide 2 (GLP2) is a proglucagon-derived peptide that is involved in the regulation of energy absorption and exerts beneficial effects on glucose metabolism. However, the exact mechanisms underlying the GLP2 during osteogenic differentiation has not been illustrated. Herein, we indicated that GLP2 was demonstrated to result in positive action during (...) the osteogenic differentiation of human osteosarcoma cells. Our findings demonstrate that GLP2 inhibis the growth of osteosarcoma cells in vivo and in vitro. Mechanistic investigations reveal GLP2 inhibits the expression and activity of nuclear factor κB (NF-κB), triggering the decrease of c-Myc, PKM2, and CyclinD1 in osteosarcoma cells. In particular, rescued NF-κB abrogates the functions of GLP2 in osteosarcoma cells. Strikingly, GLP2 overexpression significantly increased the expression of osteogenesis

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2017 Molecular therapy. Nucleic acids

13. STK39, overexpressed in osteosarcoma, regulates osteosarcoma cell invasion and proliferation (PubMed)

STK39, overexpressed in osteosarcoma, regulates osteosarcoma cell invasion and proliferation Serine/threonine kinase 39 (STK39) is associated with hypertension, autism, Parkinson's disease and various types of cancer in recent years. This study investigated STK39 expression and possible roles in osteosarcoma using qPCR and western blot analysis. Compared to normal bone tissues, the mRNA and protein expression of STK39 was found to be upregulated in osteosarcoma. Using small interfering RNA (...) transfection, STK39 was knocked down into two cell lines of osteosarcoma, U2OS and MG63, and the effects exerted on cell functioning were examined. The results showed that STK39 downregulation inhibited ostesarcoma cell proliferation and invasion. Moreover, STK39 knockdown in osteosarcoma cells significantly affected the expression of proteins connected to cell proliferation (proliferating cell nuclear antigen and p21) and invasion [Twist1, matrix metalloproteinase (MMP)2 and MMP9]. Phosphorylation

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2017 Oncology letters

14. Effect of entinostat on NK cell-mediated cytotoxicity against osteosarcoma cells and osteosarcoma lung metastasis (PubMed)

Effect of entinostat on NK cell-mediated cytotoxicity against osteosarcoma cells and osteosarcoma lung metastasis There is a crucial need for a new therapeutic approach for osteosarcoma (OS) lung metastasis since this disease remains the main cause of mortality in OS. We previously demonstrated that natural killer (NK) cell therapy has minimal efficacy against OS metastasis. This study determined whether the histone deacetylase inhibitor entinostat could immunosensitize OS cells to NK cell

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2017 Oncoimmunology

15. MicroRNA-567 inhibits cell proliferation, migration and invasion by targeting FGF5 in osteosarcoma (PubMed)

MicroRNA-567 inhibits cell proliferation, migration and invasion by targeting FGF5 in osteosarcoma MicroRNAs (miRNAs) have been widely reported to have important regulatory roles in various human tumors, including osteosarcoma (OS). The aim of this study was to focus on the role of less well-known miRNA-567 (miR-567) in OS. We found the expression of miR-567 was significantly reduced in OS tissues and cell lines (MG-63, U2OS and Saos-2) compared with the adjacent normal tissues and normal

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2018 EXCLI journal

16. Immunoconjugates for Osteosarcoma Therapy: Preclinical Experiences and Future Perspectives (PubMed)

Immunoconjugates for Osteosarcoma Therapy: Preclinical Experiences and Future Perspectives Osteosarcoma (OS) is an aggressive osteoid-producing tumor of mesenchymal origin, which represents the most common primary bone malignancy. It is characterized by a complex and frequently uncertain etiology. The current standard care for high-grade OS treatment is neoadjuvant chemotherapy, followed by surgery and post-operative chemotherapy. In order to ameliorate survival rates of patients, new

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2018 Biomedicines

17. Outcomes in Treatment-Naïve Patients With Metastatic Extremity Osteosarcoma Treated With OGS-12, a Novel Non–High-Dose Methotrexate–Based, Dose-Dense Combination Chemotherapy, in a Tertiary Care Cancer Center (PubMed)

Outcomes in Treatment-Naïve Patients With Metastatic Extremity Osteosarcoma Treated With OGS-12, a Novel Non–High-Dose Methotrexate–Based, Dose-Dense Combination Chemotherapy, in a Tertiary Care Cancer Center Metastatic osteosarcoma is largely treated with high-dose methotrexate (HDMTX)-based therapy, especially in the pediatric population. This mandates complex pharmacokinetic monitoring in a costly inpatient setting to mitigate unpredictable serious toxicities. Hence, a non-HDMTX-based (...) regimen is worth exploring, especially in India and low- and middle-income countries.All consecutive treatment-naïve patients with metastatic osteosarcoma were prospectively treated on the novel OGS-12 protocol consisting of sequential doublets of doxorubicin, cisplatin, and ifosfamide. Four cycles were administered as neoadjuvant therapy followed by planned curative intent surgery and metastasectomy when feasible, followed by four cycles of adjuvant chemotherapy. Baseline characteristics, histologic

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2018 Journal of global oncology

18. Optimization of the chicken chorioallantoic membrane assay as reliable in vivo model for the analysis of osteosarcoma. (PubMed)

Optimization of the chicken chorioallantoic membrane assay as reliable in vivo model for the analysis of osteosarcoma. Survival rates of osteosarcoma patients could not be significantly improved by conventional chemotherapeutic treatment regimens since the introduction of high-dose chemotherapy 35 years ago. Therefore, there is a strong clinical need for new therapeutic targets and personalized treatment strategies, requiring reliable in vivo model systems for the identification and testing (...) of potential new treatment approaches. Conventional in vivo rodent experiments face ethical issues, are time consuming and costly, being of particular relevance in orphan diseases like osteosarcoma. An attractive alternative to such animal experiments is the chicken chorioallantoic membrane (CAM) assay. The CAM is a highly vascularized, non-innervated extra-embryonic membrane that is perfectly suited for the engraftment of tumor cells. However, only few reports are available for osteosarcoma and reported

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2019 PLoS ONE

19. Viable and necrotic tumor assessment from whole slide images of osteosarcoma using machine-learning and deep-learning models. (PubMed)

Viable and necrotic tumor assessment from whole slide images of osteosarcoma using machine-learning and deep-learning models. Pathological estimation of tumor necrosis after chemotherapy is essential for patients with osteosarcoma. This study reports the first fully automated tool to assess viable and necrotic tumor in osteosarcoma, employing advances in histopathology digitization and automated learning. We selected 40 digitized whole slide images representing the heterogeneity of osteosarcoma

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2019 PLoS ONE

20. Effectiveness of mifamurtide in addition to standard chemotherapy for high-grade osteosarcoma: a systematic review. (PubMed)

Effectiveness of mifamurtide in addition to standard chemotherapy for high-grade osteosarcoma: a systematic review. Osteosarcoma mostly occurs during the period of rapid bone growth in children and adolescents as high-grade osteosarcomas. Current treatment recommended for high-grade non-metastatic and metastatic and/or relapsed osteosarcoma involves neoadjuvant multiagent conventional chemotherapy, followed by surgical resection of macroscopically detected tumor and postoperative adjuvant (...) chemotherapy. However, residual micrometastatic deposits that develop following surgery have shown resistance to postoperative/adjuvant chemotherapy. Therefore, there is a critical need for more effective and innovative therapeutic approaches such as immune stimulatory agents. The most extensively studied immune stimulatory agent in the treatment of osteosarcoma is mifamurtide. The aim of this systematic review was to identify and synthesize the evidence on the effectiveness of mifamurtide in addition

2017 JBI database of systematic reviews and implementation reports

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