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Cleveland Clinic Journal of Medicine Jul 2022It is estimated that more than half of all cancers develop bony metastases, exacting a substantial cost in terms of patient quality of life and healthcare expenses.... (Review)
Review
It is estimated that more than half of all cancers develop bony metastases, exacting a substantial cost in terms of patient quality of life and healthcare expenses. Prompt diagnosis and management have been shown to reduce morbidity and costs. When a patient with a history of cancer presents with musculoskeletal pain, heightened awareness of the risk of bone metastasis should prompt immediate referral to an orthopedic specialist. A multidisciplinary approach is needed to identify an appropriate treatment plan for the patient based on the prognosis, fracture status, and extent of skeletal disease.
Topics: Bone Neoplasms; Humans; Prognosis; Quality of Life; Referral and Consultation
PubMed: 35777838
DOI: 10.3949/ccjm.89a.21062 -
Skeletal Radiology Mar 2023The role of interventional radiology (IR) is expanding. With new techniques being developed and tested, this radiology subspecialty is taking a step forward in different... (Review)
Review
The role of interventional radiology (IR) is expanding. With new techniques being developed and tested, this radiology subspecialty is taking a step forward in different clinical scenarios, especially in oncology. Musculoskeletal tumoral diseases would definitely benefit from a low-invasive approach that could reduce mortality and morbidity in particular. Thermal ablation through IR has already become important in the palliation and consolidation of bone metastases, oligometastatic disease, local recurrences, and treating specific benign tumors, with a more tailored approach, considering the characteristics of every patient. As image-guided ablation techniques lower their invasiveness and increase their efficacy while the collateral effects and complications decrease, they become more relevant and need to be considered in patient care pathways and clinical management, to improve outcomes. We present a literature review of the different percutaneous and non-invasive image-guided thermal ablation methods that are currently available and that could in the future become relevant to manage musculoskeletal oncologic diseases.
Topics: Humans; Radiology, Interventional; Bone Neoplasms; Ablation Techniques; Palliative Care; Catheter Ablation
PubMed: 36346453
DOI: 10.1007/s00256-022-04213-3 -
Cells Jul 2021Osteosarcoma (OS) is a high-grade malignant stromal tumor composed of mesenchymal cells producing osteoid and immature bone, with a peak of incidence in the second... (Review)
Review
Osteosarcoma (OS) is a high-grade malignant stromal tumor composed of mesenchymal cells producing osteoid and immature bone, with a peak of incidence in the second decade of life. Hence, although relatively rare, the social impact of this neoplasm is particularly relevant. Differently from carcinomas, molecular genetics and the role of the tumor microenvironment in the development and progression of OS are mainly unknown. Indeed, while the tumor microenvironment has been widely studied in other solid tumor types and its contribution to tumor progression has been definitely established, tumor-stroma interaction in OS has been quite neglected for years. Only recently have new insights been gained, also thanks to the availability of new technologies and bioinformatics tools. A better understanding of the cross-talk between the bone microenvironment, including immune and stromal cells, and OS will be key not only for a deeper knowledge of osteosarcoma pathophysiology, but also for the development of novel therapeutic strategies. In this review, we summarize the current knowledge about the tumor microenvironment in OS, mainly focusing on immune cells, discussing their role and implication for disease prognosis and treatment response.
Topics: Animals; Antigens, CD; Antineoplastic Agents; Bone Marrow Cells; Bone Neoplasms; Bone and Bones; Cell Communication; Cytokines; Disease Models, Animal; Gene Expression Regulation, Neoplastic; Humans; Mesenchymal Stem Cells; Neoplastic Stem Cells; Osteoclasts; Osteosarcoma; Prognosis; Signal Transduction; Tumor Microenvironment; Tumor-Associated Macrophages
PubMed: 34359840
DOI: 10.3390/cells10071668 -
AJR. American Journal of Roentgenology Nov 2021Staging of primary musculoskeletal bone and soft-tissue tumors is most commonly performed using the AJCC and the Enneking or Musculoskeletal Tumor Society (MSTS) staging...
Staging of primary musculoskeletal bone and soft-tissue tumors is most commonly performed using the AJCC and the Enneking or Musculoskeletal Tumor Society (MSTS) staging systems. Radiologic imaging is integral in achieving adequate musculoskeletal neoplastic staging by defining lesion extent and identifying regional lymph node involvement and distant metastatic disease. Additional important features in surgical planning, though not distinct components of the staging systems, include cortical involvement, joint invasion, and neurovascular encasement; these features are optimally evaluated by MRI. In 2020, the WHO updated the classification of primary musculoskeletal tumors of soft tissue and bone. The update reflects the continued explosion in identification of novel gene alterations in many bone and soft-tissue neoplasms. This growth in gene alteration identification has resulted in newly designated lesions, reclassification of lesion categories, and improved specificity of diagnosis. Although radiologists do not need to have a comprehensive knowledge of the pathologic details, a broad working understanding of the most recent update is important to aid accurate and timely diagnosis given that histologic grading is a component of all staging systems. By using a multidisciplinary approach for primary musculoskeletal neoplasms involving colleagues in pathology, orthopedic oncology, radiation oncology, and medical oncology, radiologists may promote improved diagnosis, treatment, and outcomes.
Topics: Bone Neoplasms; Humans; Lymphatic Metastasis; Neoplasm Metastasis; Neoplasm Staging; Radiography; Soft Tissue Neoplasms; World Health Organization
PubMed: 33852362
DOI: 10.2214/AJR.21.25658 -
BMC Cancer Mar 2023Osteosarcoma (OS) is the most common malignant bone tumor with a high incidence in children and adolescents. Frequent tumor metastasis and high postoperative recurrence...
BACKGROUND
Osteosarcoma (OS) is the most common malignant bone tumor with a high incidence in children and adolescents. Frequent tumor metastasis and high postoperative recurrence are the most common challenges in OS. However, detailed mechanism is largely unknown.
METHODS
We examined the expression of CD248 in OS tissue microarrays by immunohistochemistry (IHC) staining. We studied the biological function of CD248 in cell proliferation, invasion and migration of OS cells by CCK8 assay, transwell and wound healing assay. We also studied its function in the metastasis of OS in vivo. At last, we explored the potential mechanism how CD248 promotes OS metastasis by using RNA-seq, western blot, immunofluorescence staining and co-immunoprecipitation using CD248 knockdown OS cells.
RESULTS
CD248 was highly expressed in OS tissues and its high expression was correlated with pulmonary metastasis of OS. Knockdown of CD248 in OS cells significantly inhibited cell migration, invasion and metastasis, while had no obvious effect on cell proliferation. Lung metastasis in nude mice was significantly inhibited when CD248 was knocked down. Mechanistically, we found that CD248 could promote the interaction between ITGB1 and extracellular matrix (ECM) proteins like CYR61 and FN, which activated the FAK-paxillin pathway to promote the formation of focal adhesion and metastasis of OS.
CONCLUSION
Our data showed that high CD248 expression is correlated with the metastatic potential of OS. CD248 may promote migration and metastasis through enhancing the interaction between ITGB1 and certain ECM proteins. Therefore, CD248 is a potential marker for diagnosis and effective target for the treatment of metastatic OS.
Topics: Animals; Mice; Antigens, CD; Antigens, Neoplasm; Bone Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gene Expression Regulation, Neoplastic; Lung Neoplasms; Mice, Nude; Osteosarcoma; Paxillin; Integrin beta1
PubMed: 36997926
DOI: 10.1186/s12885-023-10731-7 -
The Bone & Joint Journal Jan 2024Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone...
AIMS
Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes.
METHODS
We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder's grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome.
RESULTS
Based on imaging, 35 of 49 patients (71.4%) exhibited malignant features. Overall, 40 of 49 patients (81.6%) had undergone a biopsy before en-bloc resection: 27 of 40 patients (67.5%) were diagnosed on the first biopsy, which was more accurate when carried out by open rather than needle biopsy (91.3% vs 35.3% diagnostic accuracy, respectively; p < 0.001). Of the 40 patients treated by en-bloc resection, surgical margins were wide in 38 (95.0%) and marginal in two (5.0%). Furthermore, nine of 49 patients (18.4%) underwent curettage (intralesional margin) without previous biopsy. All patients with a positive margin developed local recurrence. Distant metastases occurred in five of 49 patients (10.2%). The mean five-year overall survival (OS) and distant relapse-free survival (D-RFS) were 89.3% (SD 5.1%) and 85.7% (SD 5.5%), respectively. Univariate analysis showed that the occurrence of distant metastasis was a poor prognostic factor for OS (hazard ratio 11.54, 95% confidence interval (CI) 1.92 to 69.17; p < 0.001). Local recurrence was a poor prognostic factor for D-RFS (HR 8.72, 95% CI 1.69 to 45.0; p = 0.002).
CONCLUSION
The diagnosis of LGCOS can be challenging because it may present with non-malignant features and has a low diagnostic accuracy on biopsy. If precisely diagnosed, LGCOS can be successfully treated by surgical excision with wide margins.
Topics: Humans; Retrospective Studies; Neoplasm Recurrence, Local; Osteosarcoma; Proportional Hazards Models; Bone Neoplasms; Margins of Excision
PubMed: 38160683
DOI: 10.1302/0301-620X.106B1.BJJ-2023-0531.R1 -
Pharmacological Research Jul 2021Osteosarcoma, a highly malignant tumor, is characterized by widespread and recurrent chromosomal and genetic abnormalities. In recent years, a number of elaborated... (Review)
Review
Osteosarcoma, a highly malignant tumor, is characterized by widespread and recurrent chromosomal and genetic abnormalities. In recent years, a number of elaborated sequencing analyses have made it possible to cluster the osteosarcoma based on the identification of candidate driver genes and develop targeted therapy. Here, we reviewed recent next-generation genome sequencing studies and advances in targeted therapies for osteosarcoma based on molecular classification. First, we stratified osteosarcomas into ten molecular subtypes based on genetic changes. And we analyzed potential targeted therapies for osteosarcoma based on the identified molecular subtypes. Finally, the development of targeted therapies for osteosarcoma investigated in clinical trials were further summarized and discussed. Therefore, we indicated the importance of molecular classification on the targeted therapy for osteosarcoma. And the stratification of patients based on the genetic characteristics of osteosarcoma will help to obtain a better therapeutic response to targeted therapies, bringing us closer to the era of personalized medicine.
Topics: Animals; Antineoplastic Agents; Bone Neoplasms; Genes, Neoplasm; Humans; Molecular Targeted Therapy; Osteosarcoma
PubMed: 34022396
DOI: 10.1016/j.phrs.2021.105684 -
Cellular Signalling Jul 2021Long noncoding RNAs (lncRNAs) have been reported as essential regulators in osteosarcoma (OS), the most malignant bone tumor usually observed in children and...
Long noncoding RNAs (lncRNAs) have been reported as essential regulators in osteosarcoma (OS), the most malignant bone tumor usually observed in children and adolescents. In the present study, we detected differentially expressed lncRNAs among OS tissues through RNA-sequencing. Then through bioinformatics analysis, we constructed the aberrant lncRNAs regulatory networks, and detected the key-lncRNAs. We identified LINC01614 was most significantly up-regulated among OS tissues, which was positively correlated with the worse prognosis. Through related in vitro experiments, we confirmed that knockdown of LINC01614 could inhibit the proliferation, invasion, and metastasis activities of OS cells. Furthermore, we identified LINC01614 may promote the proliferation and invasion activities of OS cells, via binding miR-520a-3p and increase the expression of SNX3. In conclusion, we identified lncRNAs participate in various malignant behaviors in OS. We also proved that LINC01614 could function as competing endogenous RNAs and promote the proliferation, and invasion of OS cells through miR-520a-3p/SNX3 axis, and thus acts as a novel prognostic marker for OS in clinic.
Topics: Adolescent; Adult; Bone Neoplasms; Child; Female; Humans; Male; MicroRNAs; Middle Aged; Neoplasm Proteins; Osteosarcoma; RNA, Long Noncoding; RNA, Neoplasm; Sorting Nexins
PubMed: 33753211
DOI: 10.1016/j.cellsig.2021.109985 -
Scientific Reports Oct 2022Osteosarcoma is a primary malignant tumor that often metastasizes in orthopedic diseases. Although multi-drug chemotherapy and surgical treatment have significantly...
Osteosarcoma is a primary malignant tumor that often metastasizes in orthopedic diseases. Although multi-drug chemotherapy and surgical treatment have significantly improved the survival and prognosis of patients with osteosarcoma, the survival rate is still very low due to frequent metastases in patients with osteosarcoma. In-depth exploration of the relationship between various influencing factors of osteosarcoma is very important for screening promising therapeutic targets. This study used multivariate COX regression analysis to select the hypoxia genes SLC2A1 and FBP1 in patients with osteosarcoma, and used the expression of these two genes to divide the patients with osteosarcoma into high-risk and low-risk groups. Then, we first constructed a prognostic model based on the patient's risk value and compared the survival difference between the high expression group and the low expression group. Second, in the high expression group and the low expression group, compare the differences in tumor invasion and inflammatory gene expression between the two groups of immune cells. Finally, the ferroptosis-related genes with differences between the high expression group and the low expression group were screened, and the correlation between these genes was analyzed. In the high-risk group, immune cells with higher tumor invasiveness, macrophages M0 and immune cells with lower invasiveness included: mast cell resting, regulatory T cells (Tregs) and monocytes. Finally, among genes related to ferroptosis, we found AKR1C2, AKR1C1 and ALOX15 that may be related to hypoxia. These ferroptosis-related genes were discovered for the first time in osteosarcoma. Among them, the hypoxia gene FBP1 is positively correlated with the ferroptosis genes AKR1C1 and ALOX15, and the hypoxia gene SLC2A1 is negatively correlated with the ferroptosis genes AKR1C2, AKR1C1 and ALOX15. This study constructed a prognostic model based on hypoxia-related genes SLC2A1 and FBP1 in patients with osteosarcoma, and explored their correlation with immune cells, inflammatory markers and ferroptosis-related genes. This indicates that SLC2A1 and FBP1 are promising targets for osteosarcoma research.
Topics: Female; Humans; Bone Neoplasms; Osteosarcoma; Prognosis; Neoplasm Invasiveness; Hypoxia; Fetal Hypoxia
PubMed: 36316355
DOI: 10.1038/s41598-022-17622-0 -
Joint Diseases and Related Surgery 2021This study aims to investigate the characterization and follow-up results of tumors and tumor-like lesions in the talus.
OBJECTIVES
This study aims to investigate the characterization and follow-up results of tumors and tumor-like lesions in the talus.
PATIENTS AND METHODS
Twenty-one patients (15 males, 6 females; mean age: 31.6±17 years; range, 4 to 67 years) with benign and malignant tumors or tumor-like lesions in the talus region treated and followed in our clinic between January 2007 and January 2019 were evaluated retrospectively. Radiological, pathological, surgical, and demographic features were scanned from the database.
RESULTS
Patients were followed for mean 80±45.1 (range, 25 to 156) months. The most common complaint was pain and antalgic gait. Benign bone tumors were found in 15 (71%) of 21 patients, while tumor-like lesions (two intraosseous ganglia, osteomyelitis, and bone infarction) were found in four patients. The remaining two were patients with lung and bladder cancer metastasis. Lesion size was mean 2.1±0.5 (range, 1.1 to 3.3) cm. Recurrence developed in 14.3% (n=3) of the patients during follow-up.
CONCLUSION
The talus is a rare location for tumors; however, benign and malignant tumors and tumor-like lesions may be localized in the talus.
Topics: Adult; Bone Diseases; Bone Neoplasms; Female; Humans; Male; Neoplasm Recurrence, Local; Neoplasms; Orthopedic Procedures; Radiography; Retrospective Studies; Talus; Turkey
PubMed: 33463440
DOI: 10.5606/ehc.2021.78769