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Journal of the Egyptian National Cancer... Mar 2018Osteosarcomas rarely affect jaw bones. Patients are usually older than those who suffer long bone sarcomas, with a rare incidence of metastasis. This is suggestive of a...
PURPOSE
Osteosarcomas rarely affect jaw bones. Patients are usually older than those who suffer long bone sarcomas, with a rare incidence of metastasis. This is suggestive of a different pattern of behavior compared with long bone sarcomas. This study aimed to present NCI, Cairo University experience in treating patients diagnosed with osteosarcomas of the jaw, including the diagnostic challenges and treatment outcome.
PATIENTS AND METHODS
This is a retrospective case series study of all cases of osteosarcomas of mandible and maxilla that were treated at the NCI, in the period between 2006 and 2013. Patients' data, including demographic data, various clinical presentations, results of investigations, treatment modalities performed and outcomes, were collected from hospital records kept in the Biostatistics Department at NCI.
RESULTS
Records showed 21 cases of osteosarcoma of the jaw. The mandible was affected in 15 cases, the maxilla in six. Two cases had sun-ray periosteal reactions. Erroneous biopsy results were found in 4 cases compared with final pathology reports of surgical resections. All cases underwent surgical resections, with 8 cases having positive margins. The median follow-up period was 19.3 months (range 0.3-98.0 months). The cumulative disease-free survival (DFS) was 27.5% and the median DFS was 72 months. The cumulative overall survival at end of the study was 77.4%.
CONCLUSIONS
Osteosarcoma of the jaw is challenging both to diagnose and manage. This is due to the high incidence of mistakes in biopsy results, rare specific radiological features and difficulties in proper resection due to proximity to vital structures.
Topics: Adolescent; Adult; Biopsy; Bone Neoplasms; Combined Modality Therapy; Disease Management; Female; Humans; Jaw; Magnetic Resonance Imaging; Male; Mandible; Maxilla; Middle Aged; Osteosarcoma; Recurrence; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome; Young Adult
PubMed: 29490886
DOI: 10.1016/j.jnci.2018.02.001 -
JCI Insight Jul 2023T cells recognize tumor-derived mutated peptides presented on MHC by tumors. The recognition of these neo-epitopes leads to rejection of tumors, an event that is...
T cells recognize tumor-derived mutated peptides presented on MHC by tumors. The recognition of these neo-epitopes leads to rejection of tumors, an event that is critical for successful cancer immunosurveillance. Determination of tumor-rejecting neo-epitopes in human tumors has proved difficult, though recently developed systems approaches are becoming increasingly useful at evaluating their immunogenicity. We have used the differential aggretope index to determine the neo-epitope burden of sarcomas and observed a conspicuously titrated antigenic landscape, ranging from the highly antigenic osteosarcomas to the low antigenic leiomyosarcomas and liposarcomas. We showed that the antigenic landscape of the tumors inversely reflected the historical T cell responses in the tumor-bearing patients. We predicted that highly antigenic tumors with poor antitumor T cell responses, such as osteosarcomas, would be responsive to T cell-based immunotherapy regimens and demonstrated this in a murine osteosarcoma model. Our study presents a potentially novel pipeline for determining antigenicity of human tumors, provides an accurate predictor of potential neo-epitopes, and will be an important indicator of which cancers to target with T cell-enhancing immunotherapy.
Topics: Humans; Mice; Animals; Epitopes; Monitoring, Immunologic; Sarcoma; Soft Tissue Neoplasms; Osteosarcoma; Immunotherapy
PubMed: 37427594
DOI: 10.1172/jci.insight.170324 -
Ligand-dependent hedgehog signaling maintains an undifferentiated, malignant osteosarcoma phenotype.Oncogene Nov 2023TP53 and RB1 loss-of-function mutations are common in osteosarcoma. During development, combined loss of TP53 and RB1 function leads to downregulation of autophagy and...
TP53 and RB1 loss-of-function mutations are common in osteosarcoma. During development, combined loss of TP53 and RB1 function leads to downregulation of autophagy and the aberrant formation of primary cilia, cellular organelles essential for the transmission of canonical Hedgehog (Hh) signaling. Excess cilia formation then leads to hypersensitivity to Hedgehog (Hh) ligand signaling. In mouse and human models, we now show that osteosarcomas with mutations in TP53 and RB1 exhibit enhanced ligand-dependent Hh pathway activation through Smoothened (SMO), a transmembrane signaling molecule required for activation of the canonical Hh pathway. This dependence is mediated by hypersensitivity to Hh ligand and is accompanied by impaired autophagy and increased primary cilia formation and expression of Hh ligand in vivo. Using a conditional genetic mouse model of Trp53 and Rb1 inactivation in osteoblast progenitors, we further show that deletion of Smo converts the highly malignant osteosarcoma phenotype to benign, well differentiated bone tumors. Conversely, conditional overexpression of SHH ligand, or a gain-of-function SMO mutant in committed osteoblast progenitors during development blocks terminal bone differentiation. Finally, we demonstrate that the SMO antagonist sonidegib (LDE225) induces growth arrest and terminal differentiation in vivo in osteosarcomas that express primary cilia and Hh ligand combined with mutations in TP53. These results provide a mechanistic framework for aberrant Hh signaling in osteosarcoma based on defining mutations in the tumor suppressor, TP53.
Topics: Humans; Animals; Mice; Hedgehog Proteins; Ligands; Signal Transduction; Antineoplastic Agents; Osteosarcoma; Smoothened Receptor; Cilia; Receptors, G-Protein-Coupled
PubMed: 37845394
DOI: 10.1038/s41388-023-02864-7 -
International Orthopaedics Dec 2006Bone- and cartilage-forming tumours (osteosarcomas and chondrosarcomas) are rare malignant neoplasms. These tumours are clinically aggressive and often need extensive... (Review)
Review
Bone- and cartilage-forming tumours (osteosarcomas and chondrosarcomas) are rare malignant neoplasms. These tumours are clinically aggressive and often need extensive local and/or systemic treatment. Whereas no other treatment but surgery is currently available for chondrosarcomas, osteosarcomas show an approximately 50-80% response rate to adjuvant chemotherapy. Surgical removal of these tumours is currently mostly performed with limb salvage, but amputation may be required in some cases. In addition, the tumours have a risk of local recurrences adversely affecting the prognosis compared to the primary tumour. In this report we will mainly focus on two of the most prevalent malignant bone tumours, conventional osteosarcoma and conventional chondrosarcoma, and use these to illustrate the problems with the diagnosis of bone sarcomas in general.
Topics: Bone Neoplasms; Cartilage Diseases; Chondrosarcoma; Humans; Osteosarcoma
PubMed: 16944143
DOI: 10.1007/s00264-006-0212-x -
Scientific Reports Jan 2022Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The high-throughput sequencing technology has shown potential abilities to illuminate the...
Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The high-throughput sequencing technology has shown potential abilities to illuminate the pathogenic genes in OS. This study was designed to find a powerful gene signature that can predict clinical outcomes. We selected OS cases with gene expression and survival data in the TARGET-OS dataset and GSE21257 datasets as training cohort and validation cohort, respectively. The univariate Cox regression and Kaplan-Meier analysis were conducted to determine potential prognostic genes from the training cohort. These potential prognostic genes underwent a LASSO regression, which then generated a gene signature. The harvested signature's predictive ability was further examined by the Kaplan-Meier analysis, Cox analysis, and receiver operating characteristic (ROC curve). More importantly, we listed similar studies in the most recent year and compared theirs with ours. Finally, we performed functional annotation, immune relevant signature correlation identification, and immune infiltrating analysis to better study he functional mechanism of the signature and the immune cells' roles in the gene signature's prognosis ability. A seventeen-gene signature (UBE2L3, PLD3, SLC45A4, CLTC, CTNNBIP1, FBXL5, MKL2, SELPLG, C3orf14, WDR53, ZFP90, UHRF2, ARX, CORT, DDX26B, MYC, and SLC16A3) was generated from the LASSO regression. The signature was then confirmed having strong and stable prognostic capacity in all studied cohorts by several statistical methods. We revealed the superiority of our signature after comparing it to our predecessors, and the GO and KEGG annotations uncovered the specifically mechanism of action related to the gene signature. Six immune signatures, including PRF1, CD8A, HAVCR2, LAG3, CD274, and GZMA were identified associating with our signature. The immune-infiltrating analysis recognized the vital roles of T cells CD8 and Mast cells activated, which potentially support the seventeen-gene signature's prognosis ability. We identified a robust seventeen-gene signature that can accurately predict OS prognosis. We identified potential immunotherapy targets to the gene signature. The T cells CD8 and Mast cells activated were identified linked with the seventeen-gene signature predictive power.
Topics: Adolescent; Female; Humans; Male; Osteosarcoma; Prognosis; Proportional Hazards Models
PubMed: 35075228
DOI: 10.1038/s41598-022-05341-5 -
Cell Death & Disease Jan 2019Osteosarcoma is a malignant bone sarcoma characterized by extensive genomic disruption and a propensity for metastatic spread. Osteoid production suggests a close...
Osteosarcoma is a malignant bone sarcoma characterized by extensive genomic disruption and a propensity for metastatic spread. Osteoid production suggests a close relationship with normal osteoblasts, and the latter are the presumptive cell of origin of this disease. The HACE1 gene, localized to human chromosome 6q21, encodes the HACE1 HECT E3 ligase, a tumor suppressor in diverse tumors that acts in part by targeting the activated form of RAC1 GTPase for proteasomal degradation. Disruption or loss of 6q21 is relatively common in osteosarcomas, and Hace1-/-/Tp53+/- mice frequently develop osteosarcomas, in contrast to Tp53+/- mice, which do not. This suggests an unexplored link between HACE1 loss and osteosarcoma. Here we compared HACE1 expression in normal osteoblasts and osteosarcoma cell lines in vitro by western blotting and quantitative RT-PCR, and in human osteosarcoma specimens by immunohistochemistry. Both HACE1 transcript and protein levels were reduced in osteosarcoma compared to osteoblasts in vitro. Reduced HACE1 expression in osteosarcoma tumors was observed in 76% of cases and associated with high-grade lesions. Further, clonally derived pairs of high and low metastatic osteosarcoma cell lines showed significant downregulation in the high compared to corresponding low metastatic cells. Ectopic expression of HACE1 markedly inhibited anchorage-independent growth and cell motility of HACE1 osteosarcoma cell lines, and was associated with reduced RAC1 activation and decreased reactive oxygen species (ROS). Finally, HACE1 overexpression blocked osteosarcoma xenograft growth and dramatically reduced pulmonary metastases. These findings point to a potential tumor suppressor function for HACE1 in osteosarcoma.
Topics: Animals; Biomarkers, Tumor; Bone Neoplasms; Cell Line, Tumor; Cell Movement; HEK293 Cells; Heterografts; Humans; Kaplan-Meier Estimate; Male; Mice; Mice, Nude; Osteoblasts; Osteosarcoma; Oxidative Stress; Reactive Oxygen Species; Transfection; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; rac1 GTP-Binding Protein
PubMed: 30622235
DOI: 10.1038/s41419-018-1276-4 -
Journal of Medical Case Reports Aug 2018Parosteal osteosarcomas are usually low-grade tumors, however, sometimes they transform to high-grade tumors, which is named dedifferentiation. This phenomenon has been... (Review)
Review
BACKGROUND
Parosteal osteosarcomas are usually low-grade tumors, however, sometimes they transform to high-grade tumors, which is named dedifferentiation. This phenomenon has been reported in long bones. Recently, we encountered a patient with dedifferentiated parosteal osteosarcoma occurring in the maxilla. Here, we report a first case of dedifferentiated parosteal osteosarcoma of the head and neck region.
CASE PRESENTATION
A 45-year-old Japanese woman with a refractory bone lesion in the maxilla presented to our hospital. A biopsy showed atypical spindle cell proliferation involving dedifferentiated high-grade component, which was diagnosed as dedifferentiated parosteal osteosarcoma. Three cycles of neoadjuvant chemotherapy using ifosfamide and pirarubicin were performed followed by sub-total maxillectomy. Histopathological results showed that neoadjuvant chemotherapy was effective for high-grade component. The decision to perform adjuvant chemotherapy (cisplatin and pirarubicin) was made because distant metastasis has been reported, even in cases with dedifferentiated parosteal osteosarcoma in which complete necrosis of high-grade component was achieved due to neoadjuvant chemotherapy. There was no recurrence 15 months after surgery.
CONCLUSIONS
Dedifferentiated parosteal osteosarcoma can occur in the head and neck region. Chemotherapy including anthracycline anticancer agent could be effective for high-grade component of dedifferentiated parosteal osteosarcoma.
Topics: Animals; Female; Head and Neck Neoplasms; Humans; Maxillary Neoplasms; Mice; Middle Aged; Osteosarcoma
PubMed: 30115116
DOI: 10.1186/s13256-018-1747-3 -
British Journal of Cancer May 2001
Topics: Bone Neoplasms; Follow-Up Studies; France; Humans; Incidence; Medical Oncology; Neoplasm Staging; Osteosarcoma; Quality Assurance, Health Care
PubMed: 11355976
DOI: 10.1054/bjoc.2000.1770 -
Proceedings of the Royal Society of... Sep 1976
Topics: Animals; Bone Neoplasms; Dogs; Humans; Models, Biological; Osteosarcoma
PubMed: 1068489
DOI: No ID Found -
International Journal of Molecular... Jan 2014To investigate the association of combined microRNA-340 (miR-340) and ROCK1 mRNA profiling with clinicopathologic features and prognosis in pediatric patients with...
To investigate the association of combined microRNA-340 (miR-340) and ROCK1 mRNA profiling with clinicopathologic features and prognosis in pediatric patients with osteosarcoma. Quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect expression levels of miR-340 and ROCK1 mRNA in cancerous and noncancerous bone tissues from 92 children treated for primary osteosarcomas. Compared with noncancerous bone tissues, the expression levels of miR-340 and ROCK1 mRNA were, respectively, downregulated and upregulated in osteosarcoma tissues (both p < 0.001), which was consistent with the results of in situ hybridization and immunohistochemistry analysis. The downregulation of miR-340 was negatively correlated with the upregulation of ROCK1 mRNA in osteosarcoma tissues (r = -0.78, p = 0.001). In addition, the combined miR-340 downregulation and ROCK1 upregulation (miR-340-low/ROCK1-high) occurred more frequently in osteosarcoma tissues with positive metastasis (p < 0.001) and poor response to pre-operative chemotherapy (p = 0.002). Moreover, miR-340-low/ROCK1-high expression was significantly associated with both shortest overall survival (p < 0.001) and progression-free survival (p < 0.001). Multivariate analysis further confirmed that miR-340-low/ROCK1-high expression was an independent prognostic factor of unfavorable survival in pediatric osteosarcoma (for overall survival: p = 0.006, for progression-free survival: p = 0.008). Our data offer convincing evidence, for the first time, that the combined miR-340 downregulation and ROCK1 upregulation may be linked to tumor progression and adverse prognosis in pediatric osteosarcoma.
Topics: Adolescent; Biomarkers, Tumor; Bone Neoplasms; Child; Child, Preschool; Disease Progression; Disease-Free Survival; Down-Regulation; Female; Humans; Immunohistochemistry; In Situ Hybridization; Male; MicroRNAs; Osteosarcoma; Prognosis; RNA, Messenger; Up-Regulation; Young Adult; rho-Associated Kinases
PubMed: 24398981
DOI: 10.3390/ijms15010560