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Veterinary Research Communications Mar 2015Osteosarcoma (OSA) is the most common type of bone tumors in dogs, which has high metastasis ability. 80 % of dogs with OSA die due to lung metastasis. As a result its... (Review)
Review
Osteosarcoma (OSA) is the most common type of bone tumors in dogs, which has high metastasis ability. 80 % of dogs with OSA die due to lung metastasis. As a result its treatment is a challenge for veterinary practitioners. The authors discuss the etiology, pathogenesis and the possible risk factors of OSA. The article focuses on literature review and the study of recent advances in OSA treatment. The authors describe therapies which have significantly prolonged the lives of dogs, as well as those that have proven to be ineffective. Advantages and disadvantages of limb amputation and limb-sparing surgery have been described. Authors present also the results of both single agent's therapies with the most commonly used drugs as cisplatin, carboplatin and doxorubicin and compare them to the results obtained using combined chemotherapy. The use of nanotechnology as a new approach in OSA treatment in order to avoid multidrug resistance and reduce negative side effects of cytostatic drugs is presented. The main reasons of the therapies failure are also provided in this article.
Topics: Amputation, Surgical; Animals; Antineoplastic Agents; Bone Neoplasms; Dog Diseases; Dogs; Osteosarcoma; Radiotherapy; Risk Factors
PubMed: 25422073
DOI: 10.1007/s11259-014-9623-0 -
Medicine Jun 2019The aim of this study was to develop nomograms to predict long-term overall survival and cancer-specific survival of patients with osteosarcoma.We carried out univariate...
The aim of this study was to develop nomograms to predict long-term overall survival and cancer-specific survival of patients with osteosarcoma.We carried out univariate and multivariate analyses and set up nomograms predicting survival outcome using osteosarcoma patient data collected from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute (2004-2011, n = 1426). The patients were divided into a training cohort (2004-2008, n = 863) and a validation cohort (2009-2011, n = 563), and the mean follow-up was 55 months.In the training cohort, 304 patients (35.2%) died from osteosarcoma and 91 (10.5%) died from other causes. In the validation cohort, 155 patients (27.5%) died from osteosarcoma and (12.3%) died from other causes. Nomograms predicting overall survival (OS) and cancer-specific survival (CSS) were developed according to 6 clinicopathologic factors (age, tumor site, historic grade, surgery, AJCC T/N, and M), with concordance indexes (C-index) of 0.725 (OS) and 0.718 (CSS), respectively. The validation C-indexes were 0.775 and 0.742 for OS and CSS, respectively.Our results suggest that we have successfully developed highly accurate nomograms for predicting 5-year OS and CSS for osteosarcoma patients. These nomograms will help surgeons customize treatment and monitoring strategies for osteosarcoma patients.
Topics: Adolescent; Adult; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Nomograms; Osteosarcoma; SEER Program; Survival Analysis; Young Adult
PubMed: 31261538
DOI: 10.1097/MD.0000000000016141 -
Journal of Orthopaedic Research :... Nov 2020Leucine-rich repeat containing 15 (LRRC15) is a member of the leucine-rich repeat superfamily that is overexpressed in various cancers and associated with higher tumor...
Leucine-rich repeat containing 15 (LRRC15) is a member of the leucine-rich repeat superfamily that is overexpressed in various cancers and associated with higher tumor grade and aggression. Despite its known tumorigenicity, its roles within osteosarcoma are unknown, prompting us to evaluate its expression and clinical significance within this rare yet aggressive cancer. Western blots showed differential expression of LRRC15 in the osteosarcoma cell lines MNNG/HOS, KHOS, 143B, MG63, Saos-2, and U2OS. We additionally validated this positive expression, as well as sublocalization to the cell membrane, with immunofluorescence. A tissue microarray constructed from 69 osteosarcoma patient tissues was immunohistochemically stained for LRRC15 expression, stratified, and used for clinicopathological analysis. Publicly available databases on LRRC15 expression, including RNA sequencing data from the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) and the Gene Expression database of Normal and Tumor tissues 2 (GENT2) were also analyzed. We found 63 of the 69 (91.3%) patient tissues exhibited some degree of LRRC15 immunostaining, including no staining (6 of 69, 8.7%), 1+ staining (12 of 69, 17.4%), 2+ staining (25 of 69, 36.2%), and 3+ staining (26 of 69, 37.7%). The patients with osteosarcomas having elevated LRRC15 expression demonstrated comparatively increased metastasis, chemoresistance, and shorter 5-year survival rates. Our analysis of the TARGET-OS and GENT2 databases also showed increased LRRC15 gene expression in osteosarcoma. Taken together, our study supports LRRC15 as a prognostic biomarker and emerging therapeutic target in osteosarcoma.
Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Cell Line, Tumor; Child; Female; Humans; Male; Membrane Proteins; Middle Aged; Neoplasm Metastasis; Osteosarcoma; Young Adult
PubMed: 32902907
DOI: 10.1002/jor.24848 -
The Journal of Bone and Joint Surgery.... Mar 2012There are eight reported cases in the literature of osteosarcomas secreting β-hCG. Our primary aim was to investigate the rate of β-hCG expression in osteosarcoma and... (Review)
Review
There are eight reported cases in the literature of osteosarcomas secreting β-hCG. Our primary aim was to investigate the rate of β-hCG expression in osteosarcoma and attempt to understand the characteristics of osteosarcomas that secrete β-hCG. We reviewed 37 histopathology slides (14 biopsies and 23 surgical specimens) from 32 patients with osteosarcoma. The slides were retrospectively stained for β-hCG expression. Patient and tumour characteristics, including age, gender, tumour location, subtype, proportion of necrosis, presence of metastases and recurrence were recorded. A total of five of the 32 tumours were found to be positive for β-hCG expression (one strongly and four weakly). This incidence of this expression was found in tumours with poor histological response to neoadjuvant chemotherapy. The use of β-hCG expression as a diagnostic, prognostic or follow-up marker is questionable and needs further investigation with a larger sample size.
Topics: Adolescent; Biomarkers, Tumor; Biopsy; Bone Neoplasms; Chemotherapy, Adjuvant; Child; Chorionic Gonadotropin, beta Subunit, Human; Female; Humans; Magnetic Resonance Imaging; Male; Neoadjuvant Therapy; Neoplasm Proteins; Neoplasm Recurrence, Local; Osteosarcoma; Prognosis; Retrospective Studies; Young Adult
PubMed: 22371553
DOI: 10.1302/0301-620X.94B3.27679 -
Journal of the American Academy of... Feb 2022Previous studies about osteosarcoma patient characteristics, management, and outcomes have limited patient numbers, combine varied tumor types, and/or are older studies.
INTRODUCTION
Previous studies about osteosarcoma patient characteristics, management, and outcomes have limited patient numbers, combine varied tumor types, and/or are older studies.
METHODS
Patients with osteosarcoma from the 2004 to 2015 National Cancer Database data sets were separated into axial, appendicular, and other. Demographic and treatment data as well as 1-, 5-, and 10-year survival were determined for each group. A multivariate Cox analysis of patient variables with the likelihood of death was performed, and the Kaplan Meier survival curves were generated.
RESULTS
Four thousand four hundred thirty patients with osteosarcoma (3,435 appendicular, 810 axial, and 185 other) showed survival at 1-year, 5-year, and 10-year and was highest among the appendicular cohort (91.17%, 64.43%, and 58.58%, respectively). No change in survival was seen over the periods studied. The likelihood of death was greater with increasing age category, distant metastases, and treatment with radiation alone but less with appendicular primary site, treatment with surgery alone, or surgery plus chemotherapy.
DISCUSSION
Despite advances in tumor management, surgical excision remains the best predictor of survival for osteosarcomas. No difference was observed in patient survival from 2004 to 2015 and, as would be expected, distant metastases were a poor prognostic sign, as was increasing age, male sex, and axial location.
Topics: Bone Neoplasms; Databases, Factual; Humans; Kaplan-Meier Estimate; Male; Osteosarcoma; Prognosis
PubMed: 35192571
DOI: 10.5435/JAAOSGlobal-D-22-00009 -
Canadian Journal of Veterinary Research... Jan 2016Overexpression of matrix metalloproteinases (MMPs) has been associated with increased tumor aggressiveness and metastasis dissemination. We investigated whether the...
Overexpression of matrix metalloproteinases (MMPs) has been associated with increased tumor aggressiveness and metastasis dissemination. We investigated whether the contrasting metastatic behavior of feline and canine osteosarcoma is related to levels and activities of MMP2 and MMP9. Zymography and immunohistochemistry were used to determine expression levels of MMP2 and MMP9 in canine and feline osteosarcoma. Using immunohistochemistry, increased MMP9 levels were identified in most canine osteosarcomas, whereas cat samples more often displayed moderate levels. High levels of pro-MMP9, pro-MMP2, and active MMP2 were detected by gelatin zymography in both species, with significantly higher values for active MMP2 in canine osteosarcoma. These findings indicate that MMP2 is probably involved in canine and feline osteosarcoma and their expression and activity could be associated with the different metastatic behavior of canine and feline osteosarcoma.
Topics: Animals; Bone Neoplasms; Cat Diseases; Cats; Dog Diseases; Dogs; Female; Gene Expression Regulation, Neoplastic; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Osteosarcoma
PubMed: 26733734
DOI: No ID Found -
Cancer Oct 2019Patients who are diagnosed with osteosarcoma (OS) today receive the same therapy that patients have received over the last 4 decades. Extensive efforts to identify more... (Review)
Review
Patients who are diagnosed with osteosarcoma (OS) today receive the same therapy that patients have received over the last 4 decades. Extensive efforts to identify more effective or less toxic regimens have proved disappointing. As we enter a postgenomic era in which we now recognize OS not as a cancer of mutations but as one defined by p53 loss, chromosomal complexity, copy number alteration, and profound heterogeneity, emerging threads of discovery leave many hopeful that an improving understanding of biology will drive discoveries that improve clinical care. Under the organization of the Bone Tumor Biology Committee of the Children's Oncology Group, a team of clinicians and scientists sought to define the state of the science and to identify questions that, if answered, have the greatest potential to drive fundamental clinical advances. Having discussed these questions in a series of meetings, each led by invited experts, we distilled these conversations into a series of seven Provocative Questions. These include questions about the molecular events that trigger oncogenesis, the genomic and epigenomic drivers of disease, the biology of lung metastasis, research models that best predict clinical outcomes, and processes for translating findings into clinical trials. Here, we briefly present each Provocative Question, review the current scientific evidence, note the immediate opportunities, and speculate on the impact that answered questions might have on the field. We do so with an intent to provide a framework around which investigators can build programs and collaborations to tackle the hardest problems and to establish research priorities for those developing policies and providing funding.
Topics: Child; Epigenomics; Genomics; Humans; Mutation; Osteosarcoma; Proteomics; Translational Research, Biomedical; Tumor Suppressor Protein p53
PubMed: 31355930
DOI: 10.1002/cncr.32351 -
Current Oncology (Toronto, Ont.) Jun 2023Osteosarcoma is a rare condition with a complex treatment. Most protocols include neoadjuvant chemotherapy, surgery, and consolidation chemotherapy as the standard of... (Review)
Review
Osteosarcoma is a rare condition with a complex treatment. Most protocols include neoadjuvant chemotherapy, surgery, and consolidation chemotherapy as the standard of treatment. However, the use of neoadjuvant chemotherapy lacks scientific evidence proving superiority in opposition to the use of isolated chemotherapy in an adjuvant regimen after surgery. We conducted a review for studies published in English between 1980 and 2020, using the MEDLINE/PubMed and Scopus electronic databases, to evaluate the outcomes when using neoadjuvant chemotherapy or adjuvant chemotherapy strategies in the treatment of non-metastatic appendicular osteosarcoma, as well as the toxicity associated with different chemotherapeutic regimens. Patients were divided into a neoadjuvant chemotherapy group (NAC) and adjuvant chemotherapy group (ACT), depending on the chemotherapy regimen used in association with surgery. A total of 1254 articles in English were screened by title and abstract, and 146 were pre-selected for full reading and analysis. A total of 24 assays matching the inclusion criteria were selected: 10 prospective and 14 retrospective studies. This review points to an absence of significative differences in outcomes, namely overall survival, disease-free survival/event-free survival rates, or toxicity, regarding neoadjuvant or single adjuvant chemotherapy strategies used in the treatment of appendicular non-metastatic osteosarcomas. However, there is a significative difference in population dimensions between the NAC and the ACT groups. Additionally, clinical presentation, tumor localization, tumor volume, or histological type were not considered, with these variables presenting the potential to influence these results. Despite these limitations, our findings should allow a re-thinking of our current practice and promote new opportunities to optimize treatment, always looking towards better survival and lower complications rates.
Topics: Humans; Retrospective Studies; Prospective Studies; Antineoplastic Combined Chemotherapy Protocols; Osteosarcoma; Bone Neoplasms
PubMed: 37504317
DOI: 10.3390/curroncol30070457 -
Journal of B.U.ON. : Official Journal... 2018Although osteosarcomas are rare tumors, they are the most common primary bone tumors in children and adolescents younger than 20 years with a remarkable male... (Review)
Review
Although osteosarcomas are rare tumors, they are the most common primary bone tumors in children and adolescents younger than 20 years with a remarkable male predominance. Ewing's sarcoma (ES) is the second most common primary bone tumor in children and adolescents. The preferred actual treatment modality for osteosarcoma patients is neoadjuvant chemotherapy followed by complete surgical excision and adjuvant chemotherapy including agents such as doxorubicin, cisplatin, ifosfamide, and high-dose methotrexate which are widely used and accepted as being efficacious treatment strategies in osteosarcoma patients. Conventional treatments have increased overall survival (OS) rates in osteosarcoma and ES, but not as enough as desired. High dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) may be beneficial in some subgroup of ES, including children with partial response to conventional chemotherapy and with poor-risk as well as metastatic ES. HDC and ASCT remain as a clinical option in patients with ES, but it is considered as an experimental treatment approach for patients with osteosarcoma. In this review, we discussed the current approach and role of HDC and ASCT in the treatment of osteosarcoma and ES and focused on the current literature data evaluating the treatment outcomes of some sub-groups of high risk patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Hematopoietic Stem Cell Transplantation; Humans; Osteosarcoma; Sarcoma, Ewing; Survival Rate; Transplantation, Autologous; Treatment Outcome
PubMed: 30570842
DOI: No ID Found -
Journal of Experimental & Clinical... Mar 2018Dysregulation of eukaryotic translation elongation factor 1 delta (EEF1D) in cancers has been reported; however, the role and mechanisms of EEF1D in osteosarcoma remain...
BACKGROUND
Dysregulation of eukaryotic translation elongation factor 1 delta (EEF1D) in cancers has been reported; however, the role and mechanisms of EEF1D in osteosarcoma remain poorly understood. The aim of this study is to investigate the expression and role of EEF1D in osteosarcoma and to elucidate its underlying mechanisms.
METHODS
The expression of EEF1D in osteosarcomas and cell lines was evaluated by qRT-PCR, Western blotting and immunohistochemistry. EEF1D knockdown using small interfering RNA (siRNA) was employed to analyze the role of EEF1D in osteosarcoma cell proliferation and cell cycle progression. The host signaling pathways affected by EEF1D knockdown were detected using PathScan® intracellular signaling array kit.
RESULTS
The expression of EEF1D was found to be up-regulated in human osteosarcoma tissues and cell lines. Its expression was positively correlated with Enneking stage and the tumor recurrence. EEF1D knockdown inhibited osteosarcoma cell proliferation, colony-forming ability, and cell cycle G2/M transition in vitro. In addition, EEF1D knockdown decreased the levels of phospho-Akt, phospho-mTOR, and phospho-Bad proteins.
CONCLUSIONS
EEF1D is upregulated in osteosarcoma and plays a tumor promoting role by facilitating Akt-mTOR and Akt-Bad signaling pathways. Accordingly, EEF1D is a potential target for cancer therapy.
Topics: Adolescent; Adult; Bone Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Child; Female; Gene Expression; Gene Knockdown Techniques; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Osteosarcoma; Peptide Elongation Factor 1; Proto-Oncogene Proteins c-akt; Recurrence; Signal Transduction; TOR Serine-Threonine Kinases; Young Adult
PubMed: 29510727
DOI: 10.1186/s13046-018-0715-5