Osteosarcoma
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PURPOSE: Most aspects of osteosarcoma have been addressed in detail, but there is no comprehensive analysis of deceased patients and causes of death. METHODS: The database of the Cooperative Osteosarcoma Study Group COSS (1980-03/31/2021; 4475 registered high-grade central osteosarcoma patients) was searched deaths from any cause. Affected patients were analyzed for demographic and baseline variables and disease-status at the time of demise. Deaths from causes other than osteosarcoma were analyzed in detail. RESULTS: A total of 1520 deceased patients were identified (median age (range) at osteosarcoma diagnosis 16 (2-78) years; 908 (59.7%) male, 612 (40.3%) female; primary tumor: extremities 1263 (83.1%), trunk 208 (13.7%), craniofacial 47 (3.1%) (site unknown 2); metastases at registration: absent 1.051 (69.1%), present 466 (30.7%) (3 no data). The median time from diagnosis to death was 2.22 (0.08-32.02) years. 1286 (84.6%) patients succumbed to osteosarcoma (370 without achieving complete remission, 488 first, 428 more than one recurrences), 146 (9.6%) to other, 88 (5.8%) to unknown causes. Chemotherapy-related infections (40), secondary malignancies (39), and perioperative complications (19) were among the most frequent potentially treatment-related causes, and high-dose methotrexate (19), doxorubicin (17), and ifosfamide (15) were the drugs most commonly held responsible. Patients with unknown causes of death had an unusually long median follow-up. CONCLUSION: The major cause of death of patients after osteosarcoma is this malignancy, mostly from one of its multiple relapses. However, almost 10% of fatalities are due to other documented causes. Some of these deaths may be preventable with the knowledge gained from comprehensive analyses such as this.
- Klíčová slova
- Adolescent, Adult, Child, Osteosarcoma, Survival,
- MeSH
- cisplatina terapeutické užití MeSH
- doxorubicin terapeutické užití MeSH
- ifosfamid terapeutické užití MeSH
- lidé MeSH
- lokální recidiva nádoru MeSH
- methotrexát MeSH
- mladiství MeSH
- nádory kostí * farmakoterapie MeSH
- osteosarkom * farmakoterapie MeSH
- příčina smrti MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cisplatina MeSH
- doxorubicin MeSH
- ifosfamid MeSH
- methotrexát MeSH
The transcription factor c-Myb is an oncoprotein promoting cell proliferation and survival when aberrantly activated/expressed, thus contributing to malignant transformation. Overexpression of c-Myb has been found in leukemias, breast, colon and adenoid cystic carcinoma. Recent studies revealed its expression also in osteosarcoma cell lines and suggested its functional importance during bone development. However, the relevance of c-Myb in control of osteosarcoma progression remains unknown. A retrospective clinical study was carried out to assess a relationship between c-Myb expression in archival osteosarcoma tissues and prognosis in a cohort of high-grade osteosarcoma patients. In addition, MYB was depleted in metastatic osteosarcoma cell lines SAOS-2 LM5 and 143B and their growth, chemosensitivity, migration and metastatic activity were determined. Immunohistochemical analysis revealed that high c-Myb expression was significantly associated with poor overall survival in the cohort and metastatic progression in young patients. Increased level of c-Myb was detected in metastatic osteosarcoma cell lines and its depletion suppressed their growth, colony-forming capacity, migration and chemoresistance in vitro in a cell line-dependent manner. MYB knock-out resulted in reduced metastatic activity of both SAOS-2 LM5 and 143B cell lines in immunodeficient mice. Transcriptomic analysis revealed the c-Myb-driven functional programs enriched for genes involved in the regulation of cell growth, stress response, cell adhesion and cell differentiation/morphogenesis. Wnt signaling pathway was identified as c-Myb target in osteosarcoma cells. Taken together, we identified c-Myb as a negative prognostic factor in osteosarcoma and showed its involvement in the regulation of osteosarcoma cell growth, chemosensitivity, migration and metastatic activity.
- Klíčová slova
- Chemoresistance, Metastasis, Osteosarcoma, Prognosis, Proliferation, c-Myb,
- MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- nádory kostí * patologie MeSH
- osteosarkom * patologie MeSH
- pohyb buněk genetika MeSH
- prognóza MeSH
- proliferace buněk MeSH
- regulace genové exprese u nádorů MeSH
- retrospektivní studie MeSH
- signální dráha Wnt MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The reports concerns the light microscopical and ultrastructural findings obtained in three conventional osteosarcomas with an unusually high admixture of clear cells, whose presence appeared to be responsible for the marked change in the histological pattern of these tumours. In the tumours with a prevailing fibroblastic component the clear cells were either irregularly scattered throughout the tumour in the form of small groups, or they formed large groups sharply demarcated against the fusicellular areas of the tumours. In two cases it was shown that their cytoplasm contained exaggerated glycogen deposits accompanied by the formation of glycogen-containing phagolysosomes and occasional empty vacuoles. In the third case the clear cells showed vacuolar degeneration with numerous single-membrane-bound, empty vacuoles. In contrast to the clear-cell chondrosarcoma we did not find S-100 protein in clear cells of our osteosarcomas. Such findings could be particularly significant in the differential diagnosis of bone tumours.
- MeSH
- cytoplazmatická granula ultrastruktura MeSH
- elektronová mikroskopie MeSH
- glykogen analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- osteosarkom farmakoterapie patologie chirurgie ultrastruktura MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- glykogen MeSH
BACKGROUND: 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. METHODS: 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. RESULTS: For all registered patients at a median follow-up of 54 months (interquartile range: 38-73) from biopsy, 3-year and 5-year event-free survival were 59% (95% confidence interval [CI]: 57-61%) and 54% (95% CI: 52-56%), respectively. Multivariate analyses showed that the most adverse factors at diagnosis were pulmonary metastases (hazard ratio [HR] = 2.34, 95% CI: 1.95-2.81), non-pulmonary metastases (HR = 1.94, 95% CI: 1.38-2.73) or an axial skeleton tumour site (HR = 1.53, 95% CI: 1.10-2.13). The histological subtypes telangiectatic (HR = 0.52, 95% CI: 0.33-0.80) and unspecified conventional (HR = 0.67, 95% CI: 0.52-0.88) were associated with a favourable prognosis compared with chondroblastic subtype. The 3-year and 5-year overall survival from biopsy were 79% (95% CI: 77-81%) and 71% (95% CI: 68-73%), respectively. For patients with localised disease at presentation and in complete remission after surgery, having a poor histological response was associated with worse outcome after surgery (HR = 2.13, 95% CI: 1.76-2.58). In radically operated patients, there was no good evidence that axial tumour site was associated with worse outcome. CONCLUSIONS: In conclusion, data from >2000 patients registered to EURAMOS-1 demonstrated survival rates in concordance with institution- or group-level osteosarcoma trials. Further efforts are required to drive improvements for patients who can be identified to be at higher risk of adverse outcome. This trial reaffirms known prognostic factors, and owing to the large numbers of patients registered, it sheds light on some additional factors to consider.
- Klíčová slova
- Chemotherapy, Cohort, Osteosarcoma, Outcomes, Surgery,
- MeSH
- cisplatina aplikace a dávkování MeSH
- dítě MeSH
- dospělí MeSH
- doxorubicin aplikace a dávkování MeSH
- kohortové studie MeSH
- lidé MeSH
- metastázy nádorů MeSH
- methotrexát aplikace a dávkování MeSH
- míra přežití MeSH
- mladiství MeSH
- nádory kostí farmakoterapie mortalita sekundární MeSH
- následné studie MeSH
- osteosarkom farmakoterapie mortalita patologie MeSH
- prognóza MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- cisplatina MeSH
- doxorubicin MeSH
- methotrexát MeSH
Epithelioid and epithelial neoplasms of bone are rare. They include different epithelioid variants of vascular lesions, osteoblastoma, chondroblastoma and most importantly metastatic carcinoma. Up to now, only few cases of epithelioid osteosarcoma were described. In this case the authors report a 53-year-old patient presented with a medical history of chronic shoulder pain for 3 years. Magnetic resonance imaging (MRI and computed tomography (CT) showed a destructive, partially calcified osseous lesion of the scapula with expansion into the surrounding soft tissue, suggestive of a primary bone tumor. Histologically, the tumor consisted of epithelioid cells with expression of cytokeratine and the lesion was primarily diagnosed as metastatic carcinoma. With regard to the MRI morphology untypical for metastatic disease the histopathologic slides were re-evaluated and detection of tumor osteoid led to the diagnosis of epithelioid osteosarcoma. Chemotherapy was initiated, however follow-up imaging studies showed rapidly progressive disease of both primary tumor and lung metastases. In conclusion, epithelioid neoplasms of the bone are extremetumourly rare and must be distinguished from metastatic carcinoma. Despite the presence of cytokeratine positive cells a thorough histological evaluation is mandatory and osteoid detection is essential in order to establish the correct diagnosis and further treatment. Key words: osteosarcoma, epithelioid, aneurysmal bone cyst, chondrosarcoma, pathology, immunohistochemistry.
- MeSH
- aneurysmatické kostní cysty diagnóza patologie MeSH
- biopsie MeSH
- bolest ramene etiologie MeSH
- chybná diagnóza MeSH
- diferenciální diagnóza MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lopatka diagnostické zobrazování patologie MeSH
- magnetická rezonanční tomografie MeSH
- nádory kostí komplikace diagnóza patologie MeSH
- nádory páteře sekundární MeSH
- nádory plic sekundární MeSH
- osteosarkom komplikace diagnóza patologie sekundární MeSH
- poranění paže komplikace MeSH
- radiografie MeSH
- zhmoždění komplikace diagnóza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
This study was designed to investigate the association of MTHFR C677T polymorphism and the risk of two common musculoskeletal sarcomas, osteosarcoma and chondrosarcoma. MTHFR genotypes were determined in 56 patients (44 osteosarcoma, 12 chondrosarcoma) and 44 controls using the PCR-RFLP technique. In the gender subgroup analysis, wild-type A allele frequency was higher in male osteosarcoma patients than in male control subjects (P = 0.064). Mutant V allele and mutant VV genotype were similar in the control group compared to the sarcoma groups (P > 0.05). No correlation could be proved between patient tumour site, presence of metastasis, and local tumour relapse and MTHFR polymorphism. The MTHFR C677T polymorphism may not be important in an individual's susceptibility to osteosarcoma and chondrosarcoma in Turkey and may not be a useful marker for identifying patients at high risk of developing sarcomas.
- MeSH
- alely MeSH
- chondrosarkom genetika metabolismus MeSH
- dospělí MeSH
- genotyp MeSH
- lidé středního věku MeSH
- lidé MeSH
- methylentetrahydrofolátreduktasa (NADPH2) genetika metabolismus MeSH
- mladiství MeSH
- osteosarkom genetika metabolismus MeSH
- polymorfismus genetický * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- methylentetrahydrofolátreduktasa (NADPH2) MeSH
Osteosarcoma of the jaw is uncommon, occurring in about 6% to 8% of cases. The authors present the case report of a (woman 72-year-old) with osteosarcoma involving the temporomandibular joint (TMJ). Radical surgery was chosen with resection of the tumor together with the condyle, the coronoid process, the zygomatic arch and eroded bone of the skull base at the site of the joint cavity. Contact of the tumor with the dura mater was not confirmed perioperatively.Reconstruction of the TMJ was 24 months after resection. The fossa component was concurrently formed in such a way as to cover the defect in the skull base and allow the reconstruction of the fossa and resected zygomatic arch. Four years after tumor resection there are no signs of local recurrence or metastases. Two years after TMJ reconstruction, the patient is symptom-free-occlusion is satisfactory, jaw movement is within normal range.
- MeSH
- baze lební chirurgie MeSH
- lidé MeSH
- nemoci temporomandibulárního kloubu * diagnóza chirurgie MeSH
- osteosarkom * chirurgie MeSH
- protézy kloubů * MeSH
- senioři MeSH
- temporomandibulární kloub chirurgie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
The authors present five cases of periosteal osteosarcoma located in the femur (4) and tibia (1) in children and young adults (1 female and 4 males) with an age range of 9 - 23 years (mean age 15 years). Radiographs in all cases showed a broad-based soft tissue mass attached to the cortex with periosteal reaction and in two of them cortical disruption with extensive medullary involvement. Follow-ups were available in four cases (range 11 - 73 months) and revealed pelvic metastasis after 15 months with ultimately rapid dissemination and death in a 9-year-old girl and metastasis to the humerus after 13 months in a 15-year-old boy. The former tumor widely extended into the medullary cavity and an amputation was carried out, the latter had a pure juxtacortical position and an en block resection was performed; both of them were treated with chemotherapy. All the lesions displayed distinctive structural patterns combining a large island of tumorous cartilage and hypocellular, bland-looking myxoid mesenchymal stroma with abrupt transition between both components. Contrary to conventional osteosarcoma, the delicate flocculent osteoid deposits were produced by innocuous stromal cells lacking apparent atypia. They were strictly situated outside the prevailing chondroid areas and disclosed sometimes only after a meticulous search. Immunohistochemical detection of SATB2, S100protein and D2-40 assisted effectively not only in recognition of the real stromal histogenetic derivation, but also in distinction of true differentiation of a heavily mineralized extracellular matrix. Molecular analysis revealed no IDH1/2 mutation in four examined cases. Regardless of unique low-grade morphology in rare periosteal osteosarcoma, an aggressive therapeutical approach similar to conventional osteosarcoma is justified, particularly in the case of a medullary extension.
- Klíčová slova
- bone - periosteal osteosarcoma - chondroplastic osteosarcoma - SATB2 - isocitrate dehydrogenase.,
- MeSH
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- nádory kostí patologie MeSH
- okostice patologie MeSH
- osteosarkom patologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Local anesthetics are routinely used for pain management, yet their broader effects on cancer cells remain incompletely understood. Here, we investigate the impact of ropivacaine hydrochloride and lidocaine hydrochloride monohydrate on SaOS-2 human osteosarcoma cells using a series of in vitro assays. Our findings indicate that both anesthetics markedly reduce cell viability and proliferation, as measured by XTT and Colony formation assays, respectively. Mechanistic studies reveal significant disruption of mitochondrial function, evidenced by decreased membrane potential, enhanced mitochondrial superoxide production, and pronounced mitochondrial fragmentation. Concurrently, the expression of matrix metalloproteinases (MMP-2 and MMP-9) is downregulated, while pro-apoptotic markers (Caspase-3, Caspase-9, and BAX) are upregulated. Neither agent alters Vimentin or E-cadherin expression, suggesting a limited effect on epithelial-mesenchymal transition pathways. Notably, lidocaine and ropivacaine also inhibit SaOS-2 cell migration and invasion, as demonstrated by Scratch, single-cell migration, and Transwell invasion assays. Furthermore, both agents suppress alkaline phosphatase activity, a hallmark associated with osteosarcoma differentiation and metastatic potential. Taken together, these results support the conclusion that ropivacaine and lidocaine exert broad anti-tumor effects by impairing both mitochondrial homeostasis and the invasive phenotype in osteosarcoma cells. Their capacity to mitigate core hallmarks of malignancy underscores the need for further investigation into local anesthetics as potential adjuvant therapies for osteosarcoma.
- Klíčová slova
- Lidocaine, Local anesthetics, Osteosarcoma, Ropivacaine, SaOS-2,
- MeSH
- amidy * farmakologie MeSH
- anestetika lokální farmakologie MeSH
- apoptóza * účinky léků MeSH
- invazivní růst nádoru MeSH
- lidé MeSH
- lidokain * farmakologie MeSH
- mitochondrie * účinky léků metabolismus patologie MeSH
- nádorové buněčné linie MeSH
- nádory kostí * patologie farmakoterapie metabolismus MeSH
- osteosarkom * patologie farmakoterapie metabolismus MeSH
- pohyb buněk účinky léků MeSH
- proliferace buněk * účinky léků MeSH
- ropivakain * farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- amidy * MeSH
- anestetika lokální MeSH
- lidokain * MeSH
- ropivakain * MeSH
Recent studies have highlighted the significant role of 5-hydroxymethylcytosine (5hmC) in carcinogenesis. However, the specific role of 5hmC in osteosarcoma (OS) remains largely unexplored. The-re-fore, this study aimed to investigate the function of 5hmC and TET3 in OS. In this study, we found a decreased total level of 5hmC in OS tissues. The expression of the TET3 protein was also decreased in OS. Importantly, the decreased levels of TET3 were associated with a decreased disease-free survival (DFS) rate in patients. To investigate the role of TET3 and 5hmC in OS, we manipulated the levels of TET3 in MG-63 cells. Silencing TET3 in these cells resulted in a twofold increase in proliferation. Additio-nally, the level of 5hmC decreased in these cells. Con-versely, over-expression of TET3 in MG-63 cells led to the expected inhibition of proliferation and invasion, accompanied by an increase in 5hmC levels. In conclusion, both 5hmC and TET3 protein levels were decreased in OS. Additionally, the over-expression of TET3 inhibited the proliferation of MG-63 cells, while the suppression of TET3 had the opposite effect. These findings suggest that decreased levels of 5hmC and TET3 may serve as potential markers for OS.
- Klíčová slova
- 5hmC, Osteosarcoma, TET3,
- MeSH
- 5-methylcytosin * analogy a deriváty metabolismus MeSH
- demetylace DNA * MeSH
- dioxygenasy * metabolismus MeSH
- epigeneze genetická * MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádory kostí genetika metabolismus patologie MeSH
- osteosarkom genetika metabolismus patologie MeSH
- proliferace buněk * MeSH
- protoonkogenní proteiny metabolismus genetika MeSH
- regulace genové exprese u nádorů MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 5-hydroxymethylcytosine MeSH Prohlížeč
- 5-methylcytosin * MeSH
- dioxygenasy * MeSH
- protoonkogenní proteiny MeSH
- TET3 protein, human MeSH Prohlížeč