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Autoimmunity Dec 2024Rheumatoid arthritis (RA) is the predominant manifestation of inflammatory arthritis, distinguished by an increasing burden of morbidity and mortality. The intricate...
Rheumatoid arthritis (RA) is the predominant manifestation of inflammatory arthritis, distinguished by an increasing burden of morbidity and mortality. The intricate interplay of genes and signalling pathways involved in synovial inflammation in patients with RA remains inadequately comprehended. This study aimed to ascertain the role of necroptosis in RA, as along with their associations with immune cell infiltration. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify central genes for RA. In this study, identified total of 28 differentially expressed genes (DEGs) were identified in RA. Utilising WGCNA, two co-expression modules were generated, with one module demonstrating the strongest correlation with RA. Through the integration of differential gene expression analysis, a total of 5 intersecting genes were discovered. These 5 hub genes, namely fused in sarcoma (FUS), transformer 2 beta homolog (TRA2B), eukaryotic translation elongation factor 2 (EEF2), cleavage and polyadenylation specific factor 6 (CPSF6) and signal transducer and activator of transcription 3 (STAT3) were found to possess significant diagnostic value as determined by receiver operating characteristic (ROC) curve analysis. The close association between the concentrations of various immune cells is anticipated to contribute to the diagnosis and treatment of RA. Furthermore, the infiltration of immune cells mentioned earlier is likely to exert a substantial influence on the initiation of this disease.
Topics: Arthritis, Rheumatoid; Humans; Necroptosis; Gene Regulatory Networks; Gene Expression Profiling; Transcriptome; Computational Biology; Gene Expression Regulation; Signal Transduction; STAT3 Transcription Factor; Biomarkers; ROC Curve
PubMed: 38869013
DOI: 10.1080/08916934.2024.2358069 -
Clinical Case Reports Jun 2024Extensive studies are required to understand the behavior as well as prognosis of SS in the colorectal region. IHC staining is essential for the accurate diagnosis when...
Extensive studies are required to understand the behavior as well as prognosis of SS in the colorectal region. IHC staining is essential for the accurate diagnosis when a lesion is encountered at an unusual site.
PubMed: 38868121
DOI: 10.1002/ccr3.9062 -
Cureus May 2024Synovial sarcoma is a high-grade sarcoma. The periarticular region, deep soft tissues, and the extremities are where it is most frequently found. The head and neck...
Synovial sarcoma is a high-grade sarcoma. The periarticular region, deep soft tissues, and the extremities are where it is most frequently found. The head and neck regions are rarely affected and salivary gland localization is rather rare, especially the submaxillary gland. The process of diagnosis and therapeutic management remains challenging, particularly in cases with uncommon tumor locations where the establishment of a universal therapeutic consensus is complicated. Early diagnosis and a multidisciplinary approach can lead to success without locoregional recurrence or distant metastases.
PubMed: 38854186
DOI: 10.7759/cureus.59932 -
Asian Journal of Surgery Jun 2024
PubMed: 38853112
DOI: 10.1016/j.asjsur.2024.05.211 -
Transcriptional regulation and therapeutic potential of cyclin-dependent kinase 9 (CDK9) in sarcoma.Biochemical Pharmacology Jun 2024Sarcomas include various subtypes comprising two significant groups - soft tissue and bone sarcomas. Although the survival rate for some sarcoma subtypes has improved... (Review)
Review
Sarcomas include various subtypes comprising two significant groups - soft tissue and bone sarcomas. Although the survival rate for some sarcoma subtypes has improved over time, the current methods of treatment remain efficaciously limited, as recurrent, and metastatic diseases remain a major obstacle. There is a need for better options and therapeutic strategies in treating sarcoma. Cyclin dependent kinase 9 (CDK9) is a transcriptional kinase and has emerged as a promising target for treating various cancers. The aberrant expression and activation of CDK9 have been observed in several sarcoma subtypes, including rhabdomyosarcoma, synovial sarcoma, osteosarcoma, Ewing sarcoma, and chordoma. Enhanced CDK9 expression has also been correlated with poorer prognosis in sarcoma patients. As a master regulator of transcription, CDK9 promotes transcription elongation by phosphorylation and releasing RNA polymerase II (RNAPII) from its promoter proximal pause. Release of RNAPII from this pause induces transcription of critical genes in the tumor cell. Overexpression and activation of CDK9 have been observed to lead to the expression of oncogenes, including MYC and MCL-1, that aid sarcoma development and progression. Inhibition of CDK9 in sarcoma has been proven to reduce these oncogenes' expression and decrease proliferation and growth in different sarcoma cells. Currently, there are several CDK9 inhibitors in preclinical and clinical investigations. This review aims to highlight the recent discovery and results on the transcriptional role and therapeutic potential of CDK9 in sarcoma.
PubMed: 38848777
DOI: 10.1016/j.bcp.2024.116342 -
Pediatrics Jun 2024A 15-year-old patient with metastatic synovial sarcoma conveyed to his palliative care physician that his dying wish was to start gender-affirming hormone therapy. His...
A 15-year-old patient with metastatic synovial sarcoma conveyed to his palliative care physician that his dying wish was to start gender-affirming hormone therapy. His medical team was able to identify resources to support both him and his family as they navigated the immense difficulty of a cancer diagnosis and began to understand their child's gender identity. Literature on the care of gender diverse pediatric patients with terminal illness is minimal, but applications from adult literature, and research on supporting gender diverse adolescents more broadly, provided guidance for palliative care, oncology, and gender-affirming care teams. We believe that honoring and supporting the gender identity of adolescents with terminal illness is an essential aspect of end-of-life care. This case report outlines challenges faced by multidisciplinary pediatric team members who provided gender-affirming care for a minor under hospice care and amplifies the need for future research and guidelines pertinent to this patient population.
PubMed: 38845556
DOI: 10.1542/peds.2023-064830 -
Veterinary Research Communications Jun 2024A 12-year-old, 3 kg spayed female mixed-breed dog was evaluated to assess a 1-year history of intermittent right forelimb lameness that did not have adequate response...
A 12-year-old, 3 kg spayed female mixed-breed dog was evaluated to assess a 1-year history of intermittent right forelimb lameness that did not have adequate response to nonsteroidal anti-inflammatory drugs. The radiographic study performed under sedation showed multifocal radiolucent areas affecting both the right humerus and scapula with focal soft tissue swelling; a CT scan confirmed the existence of an aggressive and invasive soft tissue mass affecting the scapulohumeral joint. Fine needle aspiration results suggested a low-grade synovial sarcoma and therefore a scapulectomy was performed. The biopsy showed spindle to stellated cells immersed in a basophilic and mucinous (myxoid) matrix with mild to moderate anisocytosis, moderate anisokaryosis, some binucleated cells and sporadic multinucleated cells. These findings are consistent with low-grade synovial myxosarcoma, a not well described synovial neoplasm that can mimic other commonly seen joint tumors or even septic arthritis on radiographs. The purpose of this case report is to describe the first reported synovial myxosarcoma affecting the scapulohumeral joint of a small dog.
PubMed: 38833194
DOI: 10.1007/s11259-024-10430-z -
Journal of Surgical Case Reports Jun 2024A 52-year-old gentleman presented with symptoms of breathlessness and type 1 respiratory failure. His CT pulmonary angiogram showed a heterogenous, oval-shaped lesion...
A 52-year-old gentleman presented with symptoms of breathlessness and type 1 respiratory failure. His CT pulmonary angiogram showed a heterogenous, oval-shaped lesion between the heart and diaphragm with a right atrial (RA) filling defect, pericardial thickening and pulmonary metastasis. An RA debulking salvage operation confirmed this to be a pericardial tumour and further cytology and immunohistochemistry testing confirmed a primary synovial sarcoma. After 12 days in intensive care for ventilation, the patient was successfully discharged on warfarin and underwent oncology follow-up for chemotherapy. Following a 15-month follow-up, no mortality was observed despite the aggressive nature of the tumour.
PubMed: 38832058
DOI: 10.1093/jscr/rjae372 -
Anticancer Research Jun 2024Synovial sarcoma (SS) is a rare malignant tumor with a poor survival rate. We previously reported that a combination of auranofin (AUR), a thioredoxin reductase...
BACKGROUND/AIM
Synovial sarcoma (SS) is a rare malignant tumor with a poor survival rate. We previously reported that a combination of auranofin (AUR), a thioredoxin reductase inhibitor, and celecoxib (CE), an anti-inflammatory drug, significantly impedes the local progression of osteosarcoma (OS). However, the role of redox regulation in SS remains to be elucidated. This study aimed to investigate the efficacy of combined treatment of AUR and CE on the local progression of SS in vivo.
MATERIALS AND METHODS
Nu/nu mice were implanted with the human SS cell line, Aska-SS, and treated with vehicle control, AUR, or a combination of AUR and CE (AUR-CE). Primary tumor size and weight were evaluated for the study duration and upon resection, respectively. Hematoxylin and eosin (H&E) and Ki-67 staining were performed to assess the local progression of SS.
RESULTS
A statistically significant reduction in tumor size and weight was observed in the AUR- and AUR-CE-treated groups upon excision compared to that in the vehicle-treated group. The AUR-CE-treated group showed synergistic inhibition of local tumor growth. H&E staining of local SS tumors revealed decreased cell density and nuclear deformation in the AUR- and AUR-CE-treated groups compared to those in the vehicle-treated group. Immunohistochemical staining revealed a statistically significant decrease in Ki-67-positive cells in the AUR-CE-treated group compared to the vehicle-treated group.
CONCLUSION
The combination of AUR and CE showed significant potential for delaying the local progression of SS. These findings support the repurposing of AUR and CE as early treatment options for SS.
Topics: Celecoxib; Animals; Sarcoma, Synovial; Auranofin; Humans; Mice; Disease Progression; Cell Line, Tumor; Xenograft Model Antitumor Assays; Mice, Nude; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation
PubMed: 38821602
DOI: 10.21873/anticanres.17052 -
JCO Precision Oncology May 2024Sarcomas are a complex group of highly aggressive and metastatic tumors with over 100 distinct subtypes. Because of their diversity and rarity, it is challenging to...
PURPOSE
Sarcomas are a complex group of highly aggressive and metastatic tumors with over 100 distinct subtypes. Because of their diversity and rarity, it is challenging to generate multisarcoma signatures that are predictive of patient outcomes.
MATERIALS AND METHODS
Here, we identify a DNA methylation signature for progression and metastasis of numerous sarcoma subtypes using multiple epigenetic and genomic patient data sets. Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are highly metastatic sarcomas with frequent loss of the histone methyltransferase, PRC2. Loss of PRC2 is associated with MPNST metastasis and plays a critical noncanonical role in DNA methylation.
RESULTS
We found that over 900 (CpGs) were hypermethylated in MPNSTs with PRC2 loss. Furthermore, we identified eight differentially methylated CpGs in the / family that correlate with the progression and metastasis of MPNSTs in two independent patient data sets. Similar trends were identified in other sarcoma subtypes, including osteosarcoma, rhabdomyosarcoma, and synovial sarcoma. Analysis of scRNAseq data sets determined that / expression occurs in both the tumor cells and the surrounding stromal populations.
CONCLUSION
These results might have broad implications for the clinical management and surveillance of sarcoma.
Topics: Humans; DNA Methylation; Disease Progression; Interleukin-17; Neoplasm Metastasis; Gene Expression Profiling; Epigenesis, Genetic; Nerve Sheath Neoplasms; Transcriptome; Neurofibrosarcoma
PubMed: 38820476
DOI: 10.1200/PO.23.00325