Recent Insights into Therapy Resistance in Osteosarcoma

Prudowsky, Zachary D.; Yustein, Jason T.

doi:10.3390/cancers13010083

Cited by 67 publications

(69 citation statements)

References 145 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Osteosarcoma is one of the common primary malignant tumors with an incidence rate of about three parts per million. The 5-year survival rate of patients with metastatic osteosarcoma is 15% to 30%, while that of localized osteosarcoma is 80% (149,150). Immune cells involved in the inflammation of osteosarcoma mainly include CD3 + T cells, CD14 + TAMs (tumor-associated macrophages), and CD68 + TAMs.…”

Section: The Macrophage-osteoclast Axis In Osteosarcomamentioning

confidence: 99%

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases

et al. 2021

View full text Add to dashboard Cite

Osteoimmunity is involved in regulating the balance of bone remodeling and resorption, and is essential for maintaining normal bone morphology. The interaction between immune cells and osteoclasts in the bone marrow or joint cavity is the basis of osteoimmunity, in which the macrophage-osteoclast axis plays a vital role. Monocytes or tissue-specific macrophages (macrophages resident in tissues) are an important origin of osteoclasts in inflammatory and immune environment. Although there are many reports on macrophages and osteoclasts, there is still a lack of systematic reviews on the macrophage-osteoclast axis in osteoimmunity. Elucidating the role of the macrophage-osteoclast axis in osteoimmunity is of great significance for the research or treatment of bone damage caused by inflammation and immune diseases. In this article, we introduced in detail the concept of osteoimmunity and the mechanism and regulators of the differentiation of macrophages into osteoclasts. Furthermore, we described the role of the macrophage-osteoclast axis in typical bone damage caused by inflammation and immune diseases. These provide a clear knowledge framework for studying macrophages and osteoclasts in inflammatory and immune environments. And targeting the macrophage-osteoclast axis may be an effective strategy to treat bone damage caused by inflammation and immune diseases.

show abstract

Section: The Macrophage-osteoclast Axis In Osteosarcomamentioning

confidence: 99%

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Dox is the anthracycline most used in OS therapy. Although Dox is one of the most active drugs for the treatment of OS, some studies have shown that a subset of OS patients are resistant or may become unresponsive to this drug during chemotherapeutic treatment [ 34 , 35 ]. In addition, despite its main mechanism of action as a DNA intercalating agent and topoisomerase II inhibitor, its use is limited by severe side effects such as cardiotoxicity [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

3′,4′-Dihydroxyflavonol Modulates the Cell Cycle in Cancer Cells: Implication as a Potential Combination Drug in Osteosarcoma

et al. 2021

View full text Add to dashboard Cite

New agents are demanded to increase the therapeutic options for osteosarcoma (OS). Although OS is the most common bone cancer in children and adolescents, it is considered a rare disorder. Therefore, finding adjuvant drugs has potential to advance therapy for this disease. In this study, 3′,4′-dihydroxyflavonol (DiOHF) was investigated to assess the effects in OS cellular models in combination with doxorubicin (Dox). MG-63 and U2OS human OS cells were exposed to DiOHF and Dox and tested for cell viability and growth. To elucidate the inhibitory effects of DiOHF, additional studies were conducted to assess apoptosis and cell cycle distribution, gene expression quantification of cell cycle regulators, and cytokinesis-block cytome assay to determine nuclear division rate. DiOHF decreased OS cell growth and viability in a concentration-dependent manner. Its combination with Dox enabled Dox dose reduction in both cell lines, with synergistic interactions in U2OS cells. Although no significant apoptotic effects were detected at low concentrations, cytostatic effects were demonstrated in both cell lines. Incubation with DiOHF altered cell cycle dynamics and resulted in differential cyclin and cyclin-dependent kinase expression. Overall, this study presents an antiproliferative action of DiOHF in OS combination therapy via modulation of the cell cycle and nuclear division.

show abstract

“…The TARGET database is focused on pediatric tumors and is designed to guide the development of effective, less toxic therapies by identifying data on molecular changes in pediatric tumors. Sarcoma patients with complete follow-up data were included in our study [19] . Clinicopathological characteristics included included age, gender, race, status of surgical margin and distant metastatic status in the study .…”

Section: Gene Expression Datasets Collectionmentioning

confidence: 99%

Development And Validation of A Novel Hypoxia- And Immune-Related Prognostic Signature For Bone And Soft Tissue Sarcoma Patients

Li¹,

Wei²,

Zheng³

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Hypoxia- and immune-status play an essential role in tumorigenesis and tumor development. This study sought to build a novel hypoxia- and immune-related signature to evaluate sarcoma patients' prognosis.Methods: Transcriptome data and clinicopathological characteristics of sarcoma patients were downloaded from the TARGET database. We grouped patients with three clusters by using t-SNE. We defined the three cluster as high-, medium-, and low-hypoxia clusters by K-M analysis and differential expression of target genes associated with the HIF-1 signaling pathway. Then we used the "limma" package to screen hypoxia-related differentially expressed genes (HRDEGs) in the high- and low-hypoxia clusters. We immediately assessed the immune status by using the single sample Gene Set Enrichment Analysis (ssGSEA) and divided the patients into high-, medium-, and low-immune clusters. Immune-related DEGs (IRDEGs) were filtered in the high- and low- immune groups. The intersection of HRDEGs and IRDEGs screened overlapping genes. We used a combination of Cox regression analysis and LASSO model to obtain prognosis-related genes and established a novel hypoxia- and immune-related prognostic signature for sarcoma patients. Combining clinicopathological characteristics of sarcoma patients, we evaluated the signature by univariate and multivariate Cox regression analysis. We further divided the patients into high- and low-risk groups based on the novel signature. Finally, we evaluated the differences in hypoxia status and the immune status in high- and low-risk groups.Results: We identified two genes associated with prognosis, CMA1 and IGDCC3. The novel Prognostic signature could be used as an independent prognostic factor for sarcoma patients. We distinguished patients more effectively by their different survival outcomes, immune cells' infiltration status, and immune-related markers.Conclusion: The hypoxia- and immune-related prognostic signature can be used to stratify the risk of sarcoma patients. Our study established a new prognostic signature and provides a potential prognostic markers for hypoxia- and immune-related therapy.

show abstract

Recent Insights into Therapy Resistance in Osteosarcoma

Cited by 67 publications

References 145 publications

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases

The Macrophage-Osteoclast Axis in Osteoimmunity and Osteo-Related Diseases

3′,4′-Dihydroxyflavonol Modulates the Cell Cycle in Cancer Cells: Implication as a Potential Combination Drug in Osteosarcoma

Development And Validation of A Novel Hypoxia- And Immune-Related Prognostic Signature For Bone And Soft Tissue Sarcoma Patients

Contact Info

Product

Resources

About