Intracellular spread of Ewing's sarcoma within skeletal muscle fibres: is there a role for cytotoxic tumour‐infiltrating lymphocytes?

Mahjoub, Wafa Koubaa; Chrétien, Fabrice; Gherardi, R; Ortonne, Nicolas

doi:10.1111/j.1365-2559.2005.02297.x

Cited by 2 publications

(1 citation statement)

References 10 publications

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“…To our interest, the DEGs were overwhelmingly attributed to the development of muscle and bone, indicating that the disease interrupts muscle and bone growth, which is also evidenced by plain radiographs exhibiting permeative and infiltrative destruction of the affected bone (mainly in the diaphysis of the long bone) (Ozaki 2015). Similarly, intramyofiber invasion, a particular phenomenon in which malignant cells exhibit intracellular spread into skeletal muscle cells, usually occurs in ES (Mahjoub et al 2006).…”

Section: Identification Of Degs In Esmentioning

confidence: 90%

Integrative analyses of bulk microarray data to discover genes, pathways, and immune infiltration characteristics associated with targeting of Ewing sarcoma

Cao

Sun

Fan

et al. 2023

J Cancer Res Clin Oncol

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Purpose To explore transcriptome and immunological features of patients with Ewing sarcoma (ES) using all publicly available microarray data. Methods Data of 479 ES tissues were integrated and normalized. Gene expression, immune infiltration, and cancer-specific pathways were analyzed. Genes of interest were knocked down, followed by cell proliferation and colony formation assays. Results Consistent with the previous reports of differential expressed genes (DEGs) in ES, our analysis identified CCND1, HMCN1, and NKX2-2 were among the most highly expressed, while TWNC1, MYBPC1, and CKM were among the lowest expressed genes. GO, KEGG, and GSEA enrichment analysis identified that the DEGs related to bone and muscle functioning, those that contributed to crucial cellular, and metabolism pathways such as actin binding, apoptosis, TCA cycle, and cell cycle were also significantly enriched. Immune infiltration analysis discovered that many T cell subsets including CD4T, CD8 T, and Gamma delta T cells were highly infiltrated, while monocytes and B cells were less infiltrated in tumors. A total of 138 genes were both significantly up-regulated in tumors and associated with decreased survival, while 38 significantly down-regulated genes were associated with increased survival, many of which were previously reported as oncogenes and tumor suppressors in ES and other cancers. Silencing of four newly identified top ranked up-regulated genes with decreased survivals in ES inhibited proliferation and colony formation of ES cells. Conclusion This study may provide a clear representative transcriptome profile of ES, providing diagnostic biomarkers, pathways, and immune infiltrative characteristics targets for ES.

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Section: Identification Of Degs In Esmentioning

confidence: 90%

Integrative analyses of bulk microarray data to discover genes, pathways, and immune infiltration characteristics associated with targeting of Ewing sarcoma

Cao

Sun

Fan

et al. 2023

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

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Blessing or curse? Proteomics in granzyme research

Joeckel

Bird

2014

Proteomics Clinical Apps

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Granzymes (gzms) are a group of serine proteases that play an important role in innate and adaptive immunity, blood coagulation, apoptosis, and inflammation, but are also connected to atherosclerosis, diabetes, cardiovascular and inflammatory lung diseases, cancer, and sepsis. Humans have five gzms (gzms A, B, H, K, and M), which differ in their substrate specificity. It is widely accepted that they are delivered from cytotoxic lymphocytes via perforin into the cytoplasm of target cells where they initiate cell death, modulate cytokine signaling, or inactivate pathogen proteins. However, more recent evidence indicates gzms also act extracellularly in noncytotoxic processes. Proteomic approaches are directed at mapping gzm cleavage specificity, identifying substrates, and unraveling the (patho-) physiological role of these proteases. These studies have refined our understanding of gzm species specificity, and collectively uncovered an enormous number of new substrates. However, with the exception of a very few human gzmB substrates supported by independent data (Bid, DNA-PK, PARP, ICAD, and procaspase 7), it is presently unclear which are physiologically relevant. This review aims to summarize and analyze the different proteomic approaches used and discuss both their convincing and controversial outcomes.

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Intracellular spread of Ewing's sarcoma within skeletal muscle fibres: is there a role for cytotoxic tumour‐infiltrating lymphocytes?

Cited by 2 publications

References 10 publications

Integrative analyses of bulk microarray data to discover genes, pathways, and immune infiltration characteristics associated with targeting of Ewing sarcoma

Integrative analyses of bulk microarray data to discover genes, pathways, and immune infiltration characteristics associated with targeting of Ewing sarcoma

Blessing or curse? Proteomics in granzyme research

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