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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 -
BioRxiv : the Preprint Server For... May 2024Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy characterized by a pathognomonic chromosomal translocation leading to the formation of the SS18::SSX...
Synovial sarcoma (SyS) is an aggressive soft-tissue malignancy characterized by a pathognomonic chromosomal translocation leading to the formation of the SS18::SSX fusion oncoprotein. SS18::SSX associates with mammalian BAF complexes suggesting deregulation of chromatin architecture as the oncogenic driver in this tumour type. To examine the epigenomic state of SyS we performed comprehensive multi-omics analysis on 52 primary pre-treatment human SyS tumours. Our analysis revealed a continuum of epigenomic states across the cohort at fusion target genes independent of rare somatic genetic lesions. We identify cell-of-origin signatures defined by enhancer states and reveal unexpected relationships between H2AK119Ub1 and active marks. The number of bivalent promoters, dually marked by the repressive H3K27me3 and activating H3K4me3 marks, has strong prognostic value and outperforms tumor grade in predicting patient outcome. Finally, we identify SyS defining epigenomic features including H3K4me3 expansion associated with striking promoter DNA hypomethylation in which SyS displays the lowest mean methylation level of any sarcoma subtype. We explore these distinctive features as potential vulnerabilities in SyS and identify H3K4me3 inhibition as a promising therapeutic strategy.
PubMed: 38798672
DOI: 10.1101/2024.05.14.594262 -
Diagnostics (Basel, Switzerland) May 2024Thank you for your comment; it adds value to the article and highlights the importance of molecular testing [...].
Thank you for your comment; it adds value to the article and highlights the importance of molecular testing [...].
PubMed: 38786311
DOI: 10.3390/diagnostics14101013 -
Diagnostics (Basel, Switzerland) May 2024With great interest, we read the article by Manole et al [...].
With great interest, we read the article by Manole et al [...].
PubMed: 38786310
DOI: 10.3390/diagnostics14101012 -
Bone Marrow Transplantation May 2024
False-positive human immunodeficiency virus nuclear acid amplification technique testing following therapy with transgenic T cell receptor cellular therapy for synovial sarcoma.
PubMed: 38760477
DOI: 10.1038/s41409-024-02307-1 -
Zhonghua Zhong Liu Za Zhi [Chinese... May 2024To investigate the proportion of different histological types and CT enhanced imaging features of primary middle mediastinal lesions in order to improve the...
To investigate the proportion of different histological types and CT enhanced imaging features of primary middle mediastinal lesions in order to improve the understanding of these tumors and the accuracy of preoperative diagnosis. Retrospective analysis was conducted on 84 patients with primary middle mediastinal lesions and clear histological classifications diagnosed and treated at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2012 to December 2022. Clinical, imaging, and pathological data were collected and classified according to tumor histological classifications. CT imaging manifestations such as tumor location, size, morphology, edge, boundary, internal components, enhancement characteristics, and surrounding tissue invasion were evaluated and recorded. The histological types of the primary middle mediastinal lesions from the 84 patients included mesenchymal tumors, anterior intestinal cysts, giant lymph node hyperplasia, substernal goiter, neuroendocrine carcinoma, lymphohematopoietic system tumors, and mesothelioma, accounting for 28.6%, 27.4%, 14.3%, 3.6%, 11.9%, 9.5%, and 4.8%, respectively. Mesenchymal tumors included peripheral nerve sheath tumors, vascular tumors, adipogenic tumors, solitary fibrous tumors, and synovial sarcoma, accounting for 54.2%, 20.8%, 12.5%, 8.3%, and 4.2%, respectively. The above tumors had diverse imaging manifestations and specific imaging features. Mature fat were found in 3 cases of liposarcoma; Calcification was observed in 2 cases of thyroid nodules and 7 cases of giant lymph node hyperplasia; Enhanced scanning showed significant enhancement in 2 cases of solitary fibrous tumors, 3 cases of thyroid nodules, and 11 cases of giant lymph node hyperplasia; Mediastinal large lymph nodes was observed in 6 cases of lymphoma and 3 cases of mesothelioma; High invasiveness was observed in 4 cases of mesothelioma and 9 cases of neuroendocrine carcinoma. Mediastinal tumors have low incidence rate and rich histological types, and their imaging manifestations are diverse. Preoperative differential diagnosis can be made according to their specific imaging characteristics.
Topics: Humans; Mediastinal Neoplasms; Retrospective Studies; Tomography, X-Ray Computed; Carcinoma, Neuroendocrine; Lymph Nodes; Mediastinum; Sarcoma, Synovial; Middle Aged; Male; Female
PubMed: 38742358
DOI: 10.3760/cma.j.cn112152-20230903-00114 -
Maedica Mar 2024Malignant solitary fibrous tumor of the breast is one of the rarest types of breast malignancy. To the best of our knowledge, only six cases have been reported so far....
Malignant solitary fibrous tumor of the breast is one of the rarest types of breast malignancy. To the best of our knowledge, only six cases have been reported so far. Here we have presented such a case from India, where a 52-year-old lady presented with a 10 cm x 8 cm breast lump. Diagnosis was achieved with the help of FDG PET, histopathology and immunohistochemistry, which showed nuclear positivity for STAT6. Fluorescent in situ hybridization (FISH) molecular study for SS18-SSX was used to rule out the differential diagnosis of synovial sarcoma. Guidelines for the management of this type of breast malignancy still do not exist. We have done a review of the literature in order to discuss which might be the best management in such cases. Evidence on this very rarest type of breast malignancy is still evolving. The interest in the case described here relies on its rarity, difficulties in achieving diagnosis and formulation of the proper management.
PubMed: 38736930
DOI: 10.26574/maedica.2024.19.11.170 -
Skeletal Radiology May 2024Synovial sarcoma (SS) is a malignant tumor comprising 5-10% of all soft tissue sarcomas. SS has distinct characteristics, such as a predilection for young adults and...
Synovial sarcoma (SS) is a malignant tumor comprising 5-10% of all soft tissue sarcomas. SS has distinct characteristics, such as a predilection for young adults and relatively slow growth compared to other soft tissue sarcomas. Some patients with SS experience long-standing pain at the tumor site before the development of a palpable mass. Herein, we report the case of a 39-year-old woman with SS in the upper arm who presented with pain for > 20 years. The tumor detected on magnetic resonance imaging at 17 years was an SS. To the best of our knowledge, no English-language reports on imaging study-based identification of SS, which was undiagnosed for > 20 years, are known in the literature. This report discusses the imaging features of this latent lesion and the volume-doubling time of this unusual tumor.
PubMed: 38727739
DOI: 10.1007/s00256-024-04701-8 -
Current Opinion in Oncology Jul 2024There are numerous sarcoma subtypes and vary widely in terms of epidemiology, clinical characteristics, genetic profiles, and pathophysiology. They also differ widely... (Review)
Review
PURPOSE OF REVIEW
There are numerous sarcoma subtypes and vary widely in terms of epidemiology, clinical characteristics, genetic profiles, and pathophysiology. They also differ widely between ethnic groups. This review focuses on the different incidence rates of sarcomas in different regions and the potential explanations for these disparities.
RECENT FINDINGS
In an intercontinental study using national cancer registry databases from France and Taiwan, the French population had a higher risk of liposarcomas, leiomyosarcomas, and synovial sarcomas, whereas the Taiwanese population had a higher incidence of angiosarcomas and malignant peripheral nerve sheath tumors. The anatomical distribution of these sarcomas also varied between these two regions. In France, most angiosarcoma cases occurred in the extremities and trunk, whereas in Taiwan, angiosarcoma cases in the abdomen and pelvis were more common. Another international study showed that in addition to the common known TP53 and NF1 germline mutations, genes involved in centromere and telomere maintenance were also involved in sarcomagenesis. We reviewed factors related to genetics, environmental effects, chemical exposure, and radiation exposure that could explain the differences in sarcoma incidence among different geographical or ethnic regions.
SUMMARY
Our understanding of the potential cause of sarcomas with different subtypes is limited. Establishing a comprehensive global database for patients with sarcomas from all ethnic groups is essential to deepen our understanding of the potential risk factors and the pathophysiology of all sarcoma subtypes.
Topics: Humans; Global Health; Incidence; Sarcoma; Taiwan; France
PubMed: 38726812
DOI: 10.1097/CCO.0000000000001046