Sarcoma Research Articles

Ubiquitination is one of the most prevalent and complex post-translational modifications of proteins in eukaryotes, playing a critical role in regulating various physiological and pathological processes. Targeting ubiquitination pathways, either through inhibition or activation, holds promise as a novel therapeutic approach for cancer treatment. However, the expression patterns, prognostic significance, and underlying mechanisms of ubiquitination-related genes (URGs) in sarcoma (SARC) remain unclear. We analyzed URG expression patterns and prognostic implications in TCGA-SARC using public databases, identifying DEGs related to ubiquitination among SARC molecular subtypes. Functional enrichment analysis elucidated their biological significance. Prognostic signatures were developed using LASSO-Cox regression, and a predictive nomogram was constructed. External validation was performed using GEO datasets and clinical tissue samples. The association between URG risk scores and various clinical parameters, immune response, drug sensitivity, and RNA modification regulators was investigated. Integration of data from multiple sources and RT-qPCR confirmed upregulated expression of prognostic URGs in SARC. Single-cell RNA sequencing data analyzed URG distribution across immune cell types. Prediction analysis identified potential target genes of microRNAs and long non-coding RNAs. We identified five valuable genes (CALR, CASP3, BCL10, PSMD7, PSMD10) and constructed a prognostic model, simultaneously identifying two URG-related subtypes in SARC. The UEGs between subtypes in SARC are mainly enriched in pathways such as Cell cycle, focal adhesion, and ECM-receptor interaction. Analysis of URG risk scores reveals that patients with a low-risk score have better prognoses compared to those with high-risk scores. There is a significant correlation between DRG riskscore and clinical features, immune therapy response, drug sensitivity, and genes related to pan-RNA epigenetic modifications. High-risk SARC patients were identified as potential beneficiaries of immune checkpoint inhibitor therapy. We established regulatory axes in SARC, including CALR/hsa-miR-29c-3p/LINC00943, CASP3/hsa-miR-143-3p/LINC00944, and MIR503HG. RT-qPCR data further confirmed the upregulation of prognostic URGs in SARC. Finally, we validated the prognostic model's excellent predictive performance in predicting outcomes for SARC patients. We discovered a significant correlation between aberrant expression of URGs and prognosis in SARC patients, identifying a prognostic model related to ubiquitination. This model provides a basis for individualized treatment and immunotherapy decisions for SARC patients.

BackgroundEpstein-Barr virus (EBV) infection has been closely linked to the development of various types of cancer. EB nuclear antigen 1 binding protein 2 (EBNA1BP2) is a crucial molecule for stable isolation of EBV in latent infection. However, the role of EBNA1BP2 in multiple tumor types is remains unclear. In this study, we comprehensively analyzed the functional characteristics of EBNA1BP2 and investigate its potential as a prognostic biomarker in pan-cancer.MethodsWe utilized data from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) databases and employed various bioinformatics analysis tools, including TIMER2.0, HPA, GEPIA2.0, PrognoScan, cBioPortal, CancerSEA, and BioGRID to explore the expression pattern, prognostic value, immune infiltration, and methylation level of EBNA1BP2 in pan-cancer. Additionally, we conducted enrichment analysis of genes associated with EBNA1BP2 to identify potential biological functions and pathways.ResultsOur analysis revealed that EBNA1BP2 expression was significantly higher in tumor tissues compared to tumor-adjacent tissues. We observed that lower expression of EBNA1BP2 in adrenocortical carcinoma (ACC), brain lower grade glioma (LGG), sarcoma (SARC), and uterine carcinosarcoma (UCS) was significantly associated with improved overall survival (OS) and disease-free survival (DFS). Furthermore, the promoter methylation level of EBNA1BP2 was downregulated in the majority of cancer types. At the single-cell level, EBNA1BP2 was found to be positively correlated with cell cycle and DNA repair processes, while negatively correlated with hypoxia. Additionally, EBNA1BP2 was associated with the infiltration of immune cells such as B cells, cancer-associated fibroblast cells, and CD8+ T cells. Gene enrichment analysis indicated that EBNA1BP2 was mainly involved in nucleoplasm and RNA binding pathways.ConclusionOur findings suggest that EBNA1BP2 may serve as a potential prognostic biomarker for survival in pan-cancer. Further experimental studies are needed to validate these findings and explore the underlying mechanisms by which EBNA1BP2 contributes to tumorigenesis.

Based on Type-I generalized progressive hybrid censored samples (GPHCSs), the parameter estimate for the unit-half logistic-geometry (UHLG) distribution is investigated in this work. Using maximum likelihood estimation (MLE) and Bayesian estimation, the parameters, reliability, and hazard functions of the UHLG distribution under GPHCSs have been assessed. Likewise, the computation is carried out for the asymptotic confidence intervals (ACIs). Furthermore, two bootstrap CIs, bootstrap-p and bootstrap-t, are mentioned. For symmetric loss functions, like squared error loss (SEL), and asymmetric loss functions, such as linear exponential loss (LL) and general entropy loss (GEL), there are specific Bayesian approximations. The Metropolis–Hastings samplers methodology were used to construct the credible intervals (CRIs). In conclusion, a genuine data set measuring the mortality statistics of a group of male mice with reticulum cell sarcoma is regarded as an application of the methods given.

BackgroundProstate cancer is the most common oncological disease in men and one of leading causes of death worldwide. Growing evidence has demonstrated the effectiveness of mung bean bioactive compounds in suppressing various cancer cells. However, their effects and underlying mechanisms on prostate cancer have not been verified. The present study aimed to investigate the therapeutical effects and underlying mechanisms of mung bean compounds against prostate cancer.ResultsThe results revealed that 56 proteins related to prostate cancer could be modulated by mung bean, including several vital proteins of SRC (Sarcoma), Mitogen-Activated Protein Kinase 8 (MAPK8), Heat shock protein 90 kDa alpha member A1 (HSP90AA1), and Harvey Rat sarcoma virus (HRAS). It was also found that the potential pathways associated with prostate cancer pathogenesis comprising pyrimidine metabolism, nitrogen metabolism, and prolactin signaling pathways. Of 19 mung bean compounds docked to four key proteins reveal three promising compound (dulcinoside, peonidin-3-glucoside, and chlorogenic acid) with lower binding affinity score of − 7.7, − 12.2, − 9.0, and − 6.5 kcal/mol against SRC, MAPK8, HSP90AA1, and HRAS, respectively in their site of action. Dynamic simulation results also showed values of − 36.52 ± 2.93, − 35.93 ± 1.67, and − 35.77 ± 1.17 kJ/mol for Dulcinoside-SRC, Dulcinoside-MAPK8, and P3G-HSP90AA1 complexes, respectively. The binding of the compound occur in stable and flexible with the proteins. Moreover, all mung bean compounds predicted to have good ADMET properties.ConclusionsThe study concluded that dulcinoside, peonidin-3-glucoside, and chlorogenic acid potentially exhibited anticancer activity against prostate cancer in silico. Nevertheless, further studies such as in vitro and in vivo are needed to optimize and prove the efficacy of the mung brand and its compounds against prostate cancer.Graphical abstract

A pan-cancer analysis of the association of METRN with prognosis and immune infiltration in human tumors

Bone marrow kinase, or BMX, is alternatively referred to as endothelial tyrosine kinase (Etk). It plays a vital role in the processes of cell proliferation, survival, immune activation, and the modulation of diverse signaling pathways. Since there are few direct comprehensive studies linkingBMX role with multiple cancers, this study aimed to utilize bioinformatic tools to conduct a comprehensive analysis of BMX across multiple cancers, assessing its potential role. Multiple databases including the Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), have been used to explore BMX expression across different cancers, which has been further validated by using Gene Expression Omnibus (GEO) public datasets. In addition, we used the Kaplan-Meier plotter to estimate overall survival and cBioPortal for genetic alterations analysis. This study accommodates several other analyses like clinical parameters, immune cell infiltration, and DNA promoter methylation profiles to evaluate the general role of BMXin several cancers. Results: The present investigation revealed that the BMX gene expression was significantly downregulated and could serve as an effective diagnostic biomarker in five types of cancers, namely breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and rectum adenocarcinoma (READ) (all p < 0.05). Detailed analyses revealed notable downregulation of BMX in various clinical parameters such as age, gender, race, and cancer stage (all p < 0.05). To better understand the immunotherapeutic role of BMX, this investigation further examined the immune infiltration which exhibited positive correlations between BMX expression and the infiltration of immunological cells such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, especially in COAD, LUAD, and LUSC(all p < 0.05).In addition, the present study has demonstrated that diminished BMX gene expression is correlated with an unfavorable prognosis in kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), sarcoma (SARC), and uterine corpus endometrial carcinoma (UCEC); thus BMX gene expression can be used as a prognostic target for these specific cancers. Also, the results showed that the promoter methylation level of BMX was significantly elevated in LUAD and LUSC, whereas it was significantly decreased in BRCA (all p < 0.001). Importantly, our findings of significantly low BMX expression inLUAD and LUSC, along with their methylation profiles suggest that the low expression of BMX across these cancers is due to epigenetic factors. However, genetic alteration analysis revealed that mutations existed in only approximately 2% of the TCGA samples. Our study revealed BMX as a diagnostic biomarker in BRCA, COAD, LUAD, LUSC, and READ and a prognostic biomarker in KIRC, LIHC, SARC, and UCEC. Furthermore, epigenetic variables may have a greater impact on BMX expression levels especially in LUAD and LUSC. This study also emphasized the role of BMX in the infiltration of immune cells, such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells, in certain cancers. The BMX expression level highlights the prognostic value and potential therapeutic potential of BMX.

Sarcoma (SARC) is a mesenchymal tumor which often responds poorly to systemic therapy. It is therefore important to look for possible biological markers that could tell the prognosis and the progression of SARC. A combined evaluation of the Cancer Genome Atlas (TCGA) and genotypic tissue expression (GTEx) portal was used to analyzeLMNB2 expression level in different types of cancer. Kaplan-Meier survival analysis was performed to examine LMNB2 predictive value in over-all survival rate and disease-free survival rate. The association among LMNB2 expression level and immune cell infiltration, microsatellite instability (MSI) and tumor mutational burden (TMB) were analyzed. GO and KEGG enrichment analysis were performed to predicate LMNB2 biological functions. The biological function of LMNB2 was estimated by MTT and flow cytometry assay. Additionally, western blot assay was used to examine protein expression levels. Increased LMNB2 expression was related with worsened cancer type-dependent survival. A relation between LMNB2 expression levels and immune cell infiltration was found. GO and KEGG enrichment analysis indicated that LMNB2 was involved in a series of pathways. Biology function assays revealed that down-regulation of LMNB2 impaired proliferation and cell cycle distribution. At the mechanical level, LMNB2 acts as a regulator of cyclinD1 and cyclinE1. Altogether, these data suggest that LMNB2 may serve as a tumor promoter and could be a possible target for cancer therapy.

This study focuses on the role of topoisomerases (TOPs) in sarcomas (SARCs), highlighting TOPs' influence on sarcoma prognosis through mRNA expression, genetic mutations, immune infiltration, and DNA methylation analysis using transcriptase sequencing and other techniques. The findings indicate that TOP gene mutations correlate with increased inflammation, immune cell infiltration, DNA repair abnormalities, and mitochondrial fusion genes alterations, all of which negatively affect sarcoma prognosis. Abnormal TOP expression may independently affect sarcoma patients' survival. Cutting-edge genomic tools such as Oncomine, gene expression profiling interactive analysis (GEPIA), and cBio Cancer Genomics Portal (cBioPortal) are utilizedto explore the TOP gene family (TOP1/1MT/2A/2B/3A/3B) in soft-tissue sarcomas (STSs). This in-depth analysis reveals a notable upregulation of TOP mRNA in STS patients arcoss various SARC subtypes, French Federation Nationale des Centres de Lutte Contre le Cancer classification (FNCLCC) grades, and specific molecular profiles correlating with poorer clinical outcomes. Furthermore, this investigation identifies distinct patterns of immune cell infiltration, genetic mutations, and somatic copy number variations linked to TOP genes that inversely affect patient survival rates. These findings underscore the diagnostic and therapeutic relevance of the TOP gene suite in STSs.

Aim: Pseudouridylation has demonstrated the potential to control the development of numerous malignancies. PUS7(Pseudouridine Synthase 7) is one of the pseudouridine synthases, but the literature on this enzyme is limited to several cancer types. Currently, no investigation has been performed on the systematic pan-cancer analysis concerning PUS7 role in cancer diagnosis and prognosis.Methods: Employing public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), Human Protein Atlas (HPA), UALCAN and Tumor Immune Single-cell Hub (TISCH), this work investigated the PUS7 carcinogenesis in pan-cancer. Differential expression analysis, prognostic survival analysis and biological function were systematically performed. Furthermore, PUS7 potential as an osteosarcoma biomarker for diagnosis and prognosis was assessed in this study.Results: The findings indicated that PUS7 was overexpressed in the majority of malignancies. High PUS7 expression contributed to the poor prognosis among 11 cancer types, including Adrenocortical Cancer (ACC), Bladder Cancer (BLCA), Liver Cancer (LIHC), Kidney Papillary Cell Carcinoma (KIRP), Mesothelioma (MESO), Lower Grade Glioma (LGG), Kidney Chromophobe (KICH), Sarcoma (SARC), osteosarcoma (OS), Pancreatic Cancer (PAAD), and Thyroid Cancer (THCA). In addition, elevated PUS7 expression was linked to advanced TNM across multiple malignancies, including ACC, BLCA, KIRP, LIHC and PAAD. The function enrichment analysis revealed that PUS7 participates in E2F targets, G2M checkpoint, ribosome biogenesis, and rRNA metabolic process. Moreover, PUS7 is also a reliable biomarker and a potential therapeutic target for osteosarcoma.Conclusions: In summary, PUS7 is a putative pan-cancer biomarker that reliably forecasts cancer patients’ prognosis. In addition, this enzyme regulates the cell cycle, ribosome biogenesis, and rRNA metabolism. Most importantly, PUS7 possibly regulates osteosarcoma initiation and progression.

Disulfidptosis, a newly discovered type of programmed cell death, could be a mechanism of cell death controlled by SLC7A11. This could be closely associated with tumor development and advancement. Nevertheless, the biological mechanism behind disulfidptosis-related genes (DRGs) in sarcoma (SARC) is uncertain. This study identified three valuable genes (SLC7A11, RPN1, GYS1) associated with disulfidptosis in sarcoma (SARC) and developed a prognostic model. The multiple databases and RT-qPCR data confirmed the upregulated expression of prognostic DRGs in SARC. The TCGA internal and ICGC external validation cohorts were utilized to validate the predictive model capacity. Our analysis of DRG riskscores revealed that the low-risk group exhibited a more favorable prognosis than the high-risk group. Furthermore, we observed a significant association between DRG riskscores and different clinical features, immune cell infiltration, immune therapeutic sensitivity, drug sensitivity, and RNA modification regulators. In addition, two external independent immunetherapy datasets and clinical tissue samples were collected, validating the value of the DRGs risk model in predicting immunotherapy response. Finally, the SLC7A11/hsa-miR-29c-3p/LINC00511, and RPN1/hsa-miR-143-3p/LINC00511 regulatory axes were constructed. This study provided DRG riskscore signatures to predict prognosis and response to immunotherapy in SARC, guiding personalized treatment decisions.

Liposarcoma (LPS) is the most prevalent soft-tissue sarcoma and the second most common malignant mesenchymal sarcoma. Molecular markers have proven instrumental in guiding the diagnosis, prognosis, and treatment strategies for LPS patients. Identifying potential therapeutic targets is essential for developing effective intervention strategies for LPS. LMNB2, an apoptosis-related gene, exhibits associations with various tumors. Therefore, exploring the feasibility of LMNB2 as a prognostic biomarker for LPS is crucial. After screening for differentially expressed genes (DEGs), which were analyzed by GEO2R, 14 apoptosis-related genes were obtained by overlapping DEGs from the GSE21122 and GSE159659 datasets. SPSS software was used for univariate analysis. Receiver operating characteristic curves were constructed by GraphPad software to compare the expression of LMNB2 between LPS and normal tissues. Kaplan&amp;ndash;Meier curves were generated to verify the correlation between LMNB2 expression and survival time. GeneMANIA and STRING were used to construct LMNB2-related gene-gene and protein&amp;ndash;protein interaction networks. Hiplot software facilitated function and pathway enrichment analysis to determine the potential mechanism of LMNB2-mediated LPS progression. CIBERSORT was used to evaluate the correlation between LMNB2 expression and immune cell infiltration. The expression level of LMNB2 was significantly higher in LPS, and the high expression of LMNB2 was significantly related to poor prognosis in LPS patients. Further analysis indicated that LMNB2 was mainly involved in &amp;ldquo;senescence&amp;rdquo; and &amp;ldquo;apoptosis,&amp;rdquo; further confirming its role in regulating the occurrence and development of LPS by modulating the cell cycle progression and apoptosis. This study demonstrates that the elevated expression of LMNB2 is significantly associated with poor prognostic outcomes in LPS, suggesting that LMNB2 holds high potential as a new biomarker for LPS. This study is designed to elucidate the potential mechanism of LMNB2-mediated LPS progression, with the prospect of improving therapeutic development by identifying LMNB2 as a promising prognostic biomarker for LPS.

Pan-cancer analysis predicts CANT1 as a potential prognostic, immunologic biomarker

Forkhead box J3 (FOXJ3) is a member of the forkhead box (Fox) family. Recently, increasing evidence has revealed the relationship between Fox family members and cancer. FOXJ3 is involved in various types of cancer, including lung cancer, tongue squamous carcinoma, and prostate cancer; however, a comprehensive pan-cancer analysis of FOXJ3 remains lacking. Here, we explored the function of FOXJ3 across cancers using online websites and databases including TIMER2.0, SangerBox, UALCAN, GEPIA2.0, cBioPortal, CancerSEA,STRING, BioGRID and Metascape to analyze the role of FOXJ3 in cancers. Abnormal expression of FOXJ3 was found in various tumors. The genetic alteration percentage in tumors was determined, and elevated FOXJ3 expression was found to be associated with worse overall survival in brain lower grade glioma(LGG), liver hepatocellular carcinoma (LIHC), sarcoma (SARC) and thyroid carcinoma. Elevated FOXJ3 expression was related to worse prognosis with disease-free survival in adrenocortical carcinoma, LGG and LIHC. FOXJ3 expression was related to immune infiltration in several cancers. Enrichment analysis showed that histone modification, the TGF-β signaling pathway, and chromatin organization were the top three enriched ontology clusters of the top 100 similar genes of FOXJ3. Our pan-cancer analysis provides comprehensive insights into FOXJ3 from the perspective of bioinformatics in different cancers, where it serves as a potential biomarker for prognosis, especially in LGG and LIHC. FOXJ3 is also correlated with immune infiltrates in certain human tumors.

There are more than 170 subtypes of sarcomas (SARC), which pose a challenge for diagnosis and patient management. Relatively simple or complex karyotypes play an indispensable role in the early diagnosis and effective treatment of SARC. The genes related to absorption, distribution, metabolism, and excretion (ADME) of a drug can serve as prognostic biomarkers of cancer and potential drug targets. In this study, a risk score signature was created. The SARC cohort was downloaded from The Cancer Genome Atlas (TCGA) database, and divided into high-risk group and low-risk group according to the median value of risk score. Compared with high-risk group, low-risk group has a longer survival time, which is also verified in osteosarcoma cohort from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. In addition, the relationship between the signature and immunophenotypes, including status of immune cell infiltration and immune checkpoint expression, was explored. Then, we found that high-risk group is in immunosuppressive status. Finally, we verified that PPARD played a role as a carcinogen in osteosarcoma, which provided a direction for targeted treatment of osteosarcoma in the future. Generally speaking, the signature can not only help clinicians predict the prognosis of patients with SARC, but also provide a theoretical basis for developing more effective targeted drugs in the future.

Sarcomas (SARC) are a highly heterogeneous cancer type that is prone to recurrence and metastasis. Numerous studies have confirmed that Siglecs are involved in immune signaling and play a key role in regulating immune responses in inflammatory diseases and various cancers. However, studies that systematically explore the therapeutic and prognostic value of Siglecs in SARC patients are very limited. The online databases GEPIA, UALCAN, TIMER, The Kaplan–Meier Plotter, GeneMANIA, cBioPortal, and STING were used in this study. IHC staining was performed on the collected patient tissues, and clinical data were statistically analyzed. The transcript levels of most Siglec family members showed a high expression pattern in SARC. Compared with normal tissues, Siglec-5, Siglec-10, and Siglec-12 were abnormally highly expressed in tumor tissues. Importantly, Siglec-15 was significantly associated with poor prognosis. Functional enrichment analysis showed that the Siglec family was mainly enriched in hematopoietic cell lineages. The genes associated with molecular mutations in the Siglec family were mainly TP53 and MUC16, among which Siglec-2 and Siglec-15 were significantly associated with the survival of patients. The expression levels of all Siglec family members were significantly correlated with various types of immune cells (B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils and dendritic cells). Furthermore, a significant correlation was found between the somatic copy number changes of all Siglec molecules and the abundance of immune infiltrates. Our study paints a promising vision for the development of immunotherapy drugs and the construction of prognostic stratification models by investigating the therapeutic and prognostic potential of the Siglec family for SARC.

Cancer represents a highly intricate disease, characterized by the uncontrolled proliferation and invasion of aberrant cells, leading to widespread global morbidity and mortality. This study investigates the influence of CD19, a marker specific to B-cells, within the tumor microenvironment (TME) across a spectrum of cancer types. To explore the role of CD19, we employed a wide array of bioinformatics tools and databases, including UALCAN, GEPIA2, univariate Cox regression, KM plotter, HPA, GSCA, cBioPortal, TISIDB, and DAVID. Additionally, we conducted experimental validations using cell culture, Real-time quantitative PCR (RT-qPCR), and western blot analyses. An extensive analysis of CD19 expression was performed using The Cancer Genome Atlas (TCGA) data sourced from TIMER2 and UALCAN, covering 33 different cancer types. We observed a marked variability in CD19 expression, with notable upregulation in Adrenocortical Carcinoma (ACC) and Breast Invasive Carcinoma (BRCA), contrasted by significant downregulation in Cervical Squamous Cell Carcinoma (CESC), Rectum Adenocarcinoma (READ), and Sarcoma (SARC). Prognostic assessments through univariate Cox regression and Kaplan-Meier plots revealed that lower levels of CD19 were linked to a poorer overall survival rate in CESC, READ, and SARC. These findings were reinforced by validation using GEPIA2 and GSCA, where reduced CD19 expression correlated negatively with methylation levels in the affected cancers. Furthermore, immunohistochemical staining data from the Human Protein Atlas (HPA) provided additional confirmation of these results. Mutation analysis through cBioPortal suggested that alterations in CD19 were infrequent and had a minimal impact on tumor mutation burden (TMB) and microsatellite instability (MSI). Correlation studies using TISIDB highlighted significant associations between CD19 expression and immune-related genes, emphasizing its potential role in immune regulation. Additionally, GSCA analysis demonstrated that CD19 expression was positively associated with immune cell infiltration, though no significant effect on drug sensitivity was detected. Experimental validation using RT-qPCR in READ cell lines substantiated the down-regulation of CD19. Further functional analysis revealed that reduced CD19 expression significantly influenced the cellular behavior of SW480 cells. These findings underscore the critical role of CD19 within the tumor microenvironment, suggesting its potential as a biomarker and a therapeutic target in specific types of cancer.

Rationale: Biliary complications after liver transplantation persistently affect patient prognosis and graft survival. Neutrophil-mediated immune injury is an important factor leading to biliary injury. However, the mechanism by which neutrophils reach the periphery of the bile duct and further mediate bile duct injury is not fully understood. Methods: First, we obtained hepatic tissue samples from grafted rats subjected to warm and nonwarm ischemic injury. We constructed a protein map via proteomics and analyzed the correlations between neutrophil extracellular traps (NETs) and biliary injury. HuCCT1 cells were cocultured with NETs isolated from the peripheral blood of grafted rats in vitro to evaluate the role of NETs in bile duct injury. Next, we assessed NET extravasation through the PIEZO1/SRC pathway in liver samples from rats with liver grafts via proteomic analysis, immunohistochemical staining and immunofluorescence. Finally, we evaluated the correlations between hepatic arterial blood flow and the PIEZO1/SRC pathway in a liver graft model. Results: The results revealed a close correlation between NET formation by activated neutrophils and bile duct injury. Low hepatic arterial blood flow leads to NET extravasation through the activation of the mechanosensitive ion channel PIEZO1 and its downstream signaling events, including phosphorylation of tyrosine kinases sarcoma (SRC) protein. The extravasated NETs accumulate around the bile ducts and subsequently mediate biliary cell apoptosis. Verapamil was further used to increase hepatic artery blood flow to inhibit the PIEZO1/SRC axis, which reduced bile duct injury caused by extravasated NETs. Conclusions: Suppressing NET extravasation by increasing hepatic arterial blood flow is a potential strategy for the treatment of biliary complications after liver transplantation.

Epithelioid sarcoma (ES) is a very rare and aggressive mesenchymal sarcoma subtype which represents less than 1% of soft tissue sarcomas (STS). According to the origin of the site, there are two types of ES: distal-type epithelioid sarcoma and proximal-type epithelioid sarcoma. The clinical diagnosis of ES mainly is confirmed by histopathology examination followed by immunohistochemistry. Radical excisional surgery is the best treatment option for epithelioid sarcoma. According to TNM staging, the treatment option will vary from surgery to surgery accompanied with radiotherapy and chemotherapy. Here in, we presented a 36-year-old man had non-healing ulcer in left frontotemporal scalp extending to involve left orbit. Histopathological confirmed epithelioid sarcoma. Magnetic Resonance Imaging (MRI) of Head and Neck revealed that there was mass in left frontotemporal scalp measuring 6.7 X 5.7 X 2.6 cm extending to zygomatic region and left orbit D/D malignant mass/sarcoma with bilateral (B/L) sinusitis. After that patient undergone for Wide Local excision (WLE) surgery on 11th September 2022. Adjuvant Radiation Therapy (RT) 6000 cGy radiation dose in 30 fractions (#) which was 200 cGy per fraction (#) were given during 22nd September to 10th November 2022 due to local advancement of disease. Patient was asked to follow up after 6 weeks after completion of RT. After 6 weeks of surgery, the patient was undergone for MRI and report revealed normal study.

Oval or rounded breast masses with circumscribed margins, absence of microcalcifications, and architectural distortions are usually benign. However, 10-20% of breast cancers may have circumscribed margins, which may be misdiagnosed as benign breast mass or lead to delayed diagnosis in advanced stages of cancer. Most frequently, circumscribed breast cancers are high-grade invasive ductal carcinoma of triple-negative molecular subtype. However, there are many other rare histological subtypes of cancers in the breast with circumscribed margins or less aggressive features on imaging and mimic benign breast lesions. A radiologist needs to be familiar with the imaging features of various atypical malignant breast tumors to avoid delay in diagnosis. These rare malignant breast tumors are mucinous carcinoma, papillary carcinoma, lymphoma, leukemia, myeloma, metastasis from extramammary primaries, adenoid cystic carcinoma, signet-ring carcinoma, malignant phyllodes tumor, mesenchymal sarcoma, Ewing’s sarcoma, and medullary carcinoma. This pictorial review illustrates the clinical, multimodality imaging features of rare malignant breast tumors with less aggressive features on conventional breast imaging with pathological correlation.

Follicular dendritic cell sarcoma (FDCS) is a rare mesenchymal neoplasm. It arises from not only from lymph nodes but also from extra nodal tissues, either as acquired lymphoid tissue or as part of the organized constitutive lymphoid tissue. We here report this rare entity which developed again after 7 years post tonsillectomy in a 5-year old male patient. Patient underwent radical tonsillectomy and adjuvant treatment is awaited. Differential diagnosis includes large cell lymphoma, peripheral nerve sheath tumor, extracranial meningioma, malignant melanoma, metastatic carcinoma, ectopic thymoma, malignant fibrous histiocytoma, and interstitial reticulum cell sarcoma. Currently, the management of FDCS includes the therapeutic guidelines similar to that of high-grade soft tissue sarcomas that is complete surgical resection of the lesion with possibility of adjuvant radiotherapy and/or chemotherapy. The ideal combination of management of FDCS has yet to be defined.