Characterization of the malignant cells and microenvironment of infantile fibrosarcoma via single-cell RNA sequencing.

Background: Infantile fibrosarcoma (IFS) is the most prevalent soft tissue sarcoma in children under 1 year old and is known for its rapid growth. The tumor lacks specific immunohistochemical tumor marker and a general view of tumor microenvironment (TME). Its primary therapeutic intervention places patients at a risk of disability or mutilation. This study aimed to elucidate the universal transcriptional characteristics of IFS and explore novel targets for diagnosis and therapy using single-cell RNA sequencing (scRNA-seq). Methods: Fresh tissue samples of IFS for scRNA-seq were collected from four patients before other treatments were administered. We conducted cell clustering, inferring copy number variation from scRNA-seq (InferCNV) analysis, gene differential expression analysis, cell function evaluation, Pearson correlation analysis, and cell-cell and ligand-receptor interaction analysis to investigate the distinct ecosystem of IFS. Results: According to the single-cell resolution data, we depicted the cell atlas of IFS, which comprised 14 cell populations. Through comparison with normal cells, the malignant cells were distinguished, and potential novel markers (POSTN, IGFBP2 and CTHRC1) were identified. We also found four various functional malignant cell subtypes, three of which exhibited cancer stem cells (CSCs) phenotypes, and investigated the interplay between these subtypes and nonmalignant cells in the TME of IFS. Endothelial cells and macrophages were found to dominate the cell-cell communication landscape within the microenvironment, promoting tumorigenesis via multiple receptor-ligand interactions. Conclusions: This study provides a comprehensive characterization of the tumor transcriptome and TME of IFS at the cellular level, offering valuable insights for clinically significant advancements in the immunohistochemical diagnosis and treatment of IFS.

Single-cell landscape of undifferentiated pleomorphic sarcoma.

Undifferentiated pleomorphic sarcoma (UPS) is a highly aggressive malignant soft tissue tumor with a poor prognosis; however, the identity and heterogeneity of tumor populations remain elusive. Here, eight major cell clusters were identified through the RNA sequencing of 79,569 individual cells of UPS. UPS originates from mesenchymal stem cells (MSCs) and features undifferentiated subclusters. UPS subclusters were predicted to exist in two bulk RNA datasets, and had a prognostic value in The Cancer Genome Atlas (TCGA) dataset. The functional heterogeneity of malignant UPS cells and the immune microenvironment were characterized. Additionally, the fused cells were innovatively detected by expressing both monocyte/macrophage markers and other subcluster-associated genes. Based on the ligand-receptor interaction analysis, cellular interactions with epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) were abundant. Furthermore, 73% of patients with UPS (48/66) showed positive EGFR expression, which was associated with a poor prognosis. EGFR blockade with cetuximab inhibited tumor growth in a patient-derived xenograft model. Our transcriptomic studies delineate the landscape of UPS intratumor heterogeneity and serve as a foundational resource for further discovery and therapeutic exploration.

The potential mechanism of Aidi injection against neuroblastoma-an investigation based on network pharmacology analysis.

Background: Aidi injection, a classic traditional Chinese medicine (TCM) formula, has been used on a broader scale in treating a variety of cancers. In this study, we aimed to explore the potential anti-tumor effects of Aidi injection in the treatment of neuroblastoma (NB) using network pharmacology (NP). Methods: To elucidate the anti-NB mechanism of Aidi injection, an NP-based approach and molecular docking validation were employed. The compounds and target genes were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database. The protein-protein interaction network was constructed using the STRING database. clusterProfiler (R package) was utilized to annotate the bioinformatics of hub target genes. The gene survival analysis was performed on R2, a web-based genomic analysis application. iGEMDOCK was used for molecular docking validation, and GROMACS was utilized to validate molecular docking results. Furthermore, we investigated the anticancer effects of gomisin B and ginsenoside Rh2 on human NB cells using a cell viability assay. The Western blot assay was used to validate the protein levels of target genes in gomisin B- and ginsenoside Rh2-treated NB cells. Results: A total of 2 critical compounds with 16 hub target genes were identified for treating NB. All 16 hub genes could potentially influence the survival of NB patients. The top three genes (EGFR, ESR1, and MAPK1) were considered the central hub genes from the drug-compound-hub target gene-pathway network. The endocrine resistance and estrogen signaling pathways were identified as the therapeutic pathways using the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Gomisin B and ginsenoside Rh2 showed a good binding ability to the target protein in molecular docking. The results of cell experiments showed the anti-NB effect of gomisin B and ginsenoside Rh2. In addition, the administration of gomisin B over-regulated the expression of ESR1 protein in MYCN-amplified NB cells. Conclusion: In the present study, we investigated the potential pharmacological mechanisms of Aidi against NB and revealed the anti-NB effect of gomisin B, providing clinical evidence of Aidi in treating NB and establishing baselines for further research.

Deciphering pathological behavior of pediatric medullary thyroid cancer from single-cell perspective.

Background: Pediatric medullary thyroid cancer (MTC) is one of the rare pediatric endocrine neoplasms. Derived from C cells of thyroid glands, MTC is more aggressive and more prompt to metastasis than other types of pediatric thyroid cancer. The mechanism remains unclear. Methods: We performed single-cell transcriptome sequencing on the samples of the primary tumor and metastases lymph nodes from one patient diagnosed with MTC, and it is the first single-cell transcriptome sequencing data of pediatric MTC. In addition, whole exome sequencing was performed and peripheral blood was regarded as a normal reference. All cells that passed quality control were merged and analyzed in R to discover the association between tumor cells and their microenvironment as well as tumor pathogenesis. Results: We first described the landscape of the single-cell atlas of MTC and studied the interaction between the tumor cell and its microenvironment. C cells, identified as tumor cells, and T cells, as the dominant participant in the tumor microenvironment, were particularly discussed in their development and interactions. In addition, the WES signature of tumor cells and their microenvironment were also described. Actively immune interactions were found, indicating B cells, T cells and myeloid cells were all actively participating in immune reaction in MTC. T cells, as the major components of the tumor microenvironment, proliferated in MTC and could be divided into clusters that expressed proliferation, immune effectiveness, and naive markers separately.

Progress of oncolytic virotherapy for neuroblastoma.

As a neuroendocrine tumor derived from the neural crest, neuroblastoma (NB) is the most common extracranial solid tumor in children. The prognosis in patients with low- and intermediate-risk NB is favorable while that in high-risk patients is often detrimental. However, the management of the considerably large proportion of high-risk patients remains challenging in clinical practice. Among various new approaches, oncolytic virus (OV) therapy offers great advantages in tumor treatment, especially for high-risk NB. Genetic modified OVs can target NB specifically without affecting normal tissue and avoid the widespread drug resistance issue in anticancer monotherapy. Meanwhile, its safety profile provides great potential in combination therapy with chemo-, radio-, and immunotherapy. The therapeutic efficacy of OV for NB is impressive from bench to bedside. The effectiveness and safety of OVs have been demonstrated and reported in studies on children with NB. Furthermore, clinical trials on some OVs (Celyvir, Pexa-Vec (JX-594) and Seneca Valley Virus (NTX-010)) have reported great results. This review summarizes the latest evidence in the therapeutic application of OVs in NB, including those generated in cell lines, animal models and clinical trials.

Systematic Immune-Inflammation Index Predicts Embolic Events in Infective Endocarditis.

Infective endocarditis (IE) is a life-threatening disease with embolisms occurring in 20%-50% of cases. We aimed to evaluate the value of the systemic immune-inflammation index (SII) in predicting embolic events (EEs) in patients with infective endocarditis.A total of 186 patients diagnosed with definite IE, who admitted to the Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, were retrospectively identified from November 2011 to March 2019.The median (interquartile) age of the patients was 46 (32-57) years. Viridans group streptococci were the most common microorganism identified from blood culture (24.7%). The most frequent complication was heart failure (64.2%), followed by EEs (30.2%). Patients complicated with EEs presented a significantly higher SII than those without EEs (1605.38 versus 1039.61, P = 0.001). SII had an area under the curve (AUC) value for EEs of 0.661 (95% CI: 0.575-0.747, P = 0.001), which predicted the presence of EEs with a sensitivity of 42.6% and specificity of 86.3%. Multivariate logistic regression analysis revealed that SII (OR = 6.925; 95% CI: 1.035-46.318, P = 0.046) was an independent predictor of EEs in IE patients.We demonstrated that a high level of SII is associated with a higher likelihood of EEs. The SII may be a promising predictor for EEs in patients with IE.