Pdgfrb

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration. Methods: Immunohistochemical staining for fibroblast activation protein (FAP), platelet-derived growth factor receptor beta (PDGFRb), periostin, alpha smooth muscle actin (α-SMA) and CD8 were analyzed digitally and their association with survival, tumor- and patient characteristics was assessed...

Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro...

BACKGROUND: Pericytes are a vital component of the blood-brain barrier, and their involvement in acute inflammation was recently suggested. However, it remains unclear whether pericytes contribute to hypothalamic chronic inflammation and energy metabolism in obesity. The present study investigated the impact of pericytes on the pathophysiology of obesity by focusing on platelet-derived growth factor (PDGF) signaling, which regulates pericyte functions. METHODS: Tamoxifen-inducible systemic conditional PDGF receptor β knockout mice (Pdgfrb∆SYS -KO) and Calcium/calmodulin-dependent protein kinase type IIa (CaMKIIa)-positive neuron-specific PDGF receptor β knockout mice (Pdgfrb∆CaMKII -KO) were fed a high-fat diet, and metabolic phenotypes before and 3 to 4 weeks after dietary loading were examined...

UNLABELLED: We report a deep next-generation sequencing analysis of 13 sequentially obtained tumor samples, eight sequentially obtained circulating tumor DNA (ctDNA) samples and three germline DNA samples over the life history of 3 patients with triple-negative breast cancer (TNBC), 2 of whom had germline pathogenic BRCA1 mutation, to unravel tumor evolution. Tumor tissue from all timepoints and germline DNA was subjected to whole-exome sequencing (WES), custom amplicon deep sequencing (30,000X) of a WES-derived somatic mutation panel, and SNP arrays for copy-number variation (CNV), while whole transcriptome sequencing (RNA-seq) was performed only on somatic tumor...

Hepatocellular carcinoma (HCC) is a highly detrimental cancer type and has limited therapeutic options, posing significant threats to human health. The development of HCC has been associated with a disorder in bile acid (BA) metabolism. In this study, we employed an integrative approach, combining various datasets and omics analyses, to comprehensively characterize the tumor microenvironment in HCC based on genes related to BA metabolism. Our analysis resulted in the classification of HCC samples into four subtypes (C1, C2a, C2b, and C3)...

BACKGROUND: Radiotherapy is the main treatment modality for thoracic tumours, but it may induce pulmonary fibrosis. Currently, the pathogenesis of radiation-induced pulmonary fibrosis (RIPF) is unclear, and effective treatments are lacking. Transforming growth factor beta 1 (TGFβ1) plays a central role in RIPF. We found that activated TGFβ1 had better performance for radiation pneumonitis (RP) risk prediction by detecting activated and total TGFβ1 levels in patient serum...

Dihydromyricetin (DHM) is a bioactive flavonoid extracted from Hovenia dulcis, which has various activities. In the present study, the molecular mechanism of dihydromyricetin (DHM) in relieving liver cirrhosis was investigated through network pharmacology and experimental verification. The cell model was induced by TGF-β1 activating the human hepatic stellate cell line (HSC; LX-2). The protein levels of α-SMA, collagen I, and collagen III and pathway-related proteins within LX-2 cells were detected using Western blot...

Early identification of gastric cancer (GC) is associated with a superior survival rate compared to advanced GC. However, the poor specificity and sensitivity of traditional biomarkers suggest the importance of identifying more effective biomarkers. This study aimed to identify novel biomarkers for the prognosis of GC and construct a risk score (RS) signature based on these biomarkers, with to validation of its predictive performance. We used multi-omics data from The Cancer Genome Atlas to analyze the significance of differences in each omics data and combined the data using Fisher's method...

Non-emphysematous chronic obstructive pulmonary disease (COPD), which is defined based on chest computed tomography findings, presented different transcriptome features of peripheral blood mononuclear cells (PBMCs) compared with emphysematous COPD. Enrichment analysis of transcriptomic data in COPD demonstrated that the "Hematopoietic cell lineage" pathway in Kyoto Encyclopedia of Genes and Genomes pathway analysis was highly upregulated, suggesting that cellular dynamic dysregulation in COPD lungs is affected by pathologically modified PBMCs...

BACKGROUND AND OBJECTIVE: As a chronic inflammatory disease, periodontitis threatens oral health and is a risk factor for Alzheimer's disease (AD). There is growing evidence that these two diseases are closely related. However, current research is still incomplete in understanding the common genes and common mechanisms between periodontitis and AD. In this study, we aimed to identify common genes in periodontitis and AD and analyze the relationship between crucial genes and immune cells to provide new therapeutic targets for clinical treatment...

BACKGROUND: The current therapeutic algorithm for Advanced Stage Melanoma comprises of alternating lines of Targeted and Immuno-therapy, mostly via Immune-Checkpoint blockade. While Comprehensive Genomic Profiling of solid tumours has been approved as a companion diagnostic, still no approved predictive biomarkers are available for Melanoma aside from BRAF mutations and the controversial Tumor Mutational Burden. This study presents the results of a Multi-Centre Observational Clinical Trial of Comprehensive Genomic Profiling on Target and Immuno-therapy treated advanced Melanoma...

Myeloid and lymphoid neoplasms with eosinophilia (M/Ls-Eo) encompass heterogeneous but aggressive hematopoietic disorders triggered by fusion genes or mutations that typically lead to constitutive overexpression of tyrosine kinase. The occurrence of T-lymphoblastic lymphoma in the setting of M/Ls-Eo has been reported rarely in the literature. Herein, we present an unusual case of a 28-year-old male patient who presented with massive lymphadenopathy and T-lymphoblastic lymphoma in the lymph node occurring concurrently with myeloid hyperplasia, eosinophilia and basophilia in peripheral blood and bone marrow biopsy...

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Diabetes is a risk factor for stroke; however, its impact on stroke progression at the genomic level is not well understood. To address this gap, we used transcriptome sequencing to explore the relationship between lncRNA and mRNA expression patterns and the reperfusion duration in the cortex of diabetically induced stroke mice. First, focal ischemia was induced in adult male ob/ob mice, which were then subjected to reperfusion periods of one, three, or seven days. Total RNA was extracted from the ischemic cortical tissue for RNA sequencing, and the resulting reads were aligned to the GRCm38 murine reference genome...

BACKGROUND: Mural cells are an essential perivascular cell population that associate with blood vessels and contribute to vascular stabilization and tone. In the embryonic zebrafish vasculature, pdgfrb and tagln are commonly used as markers for identifying pericytes and vascular smooth muscle cells. However, the overlapping and distinct expression patterns of these markers in tandem have not been fully described. RESULTS: Here, we used the Tg(pdgfrb:Gal4FF; UAS:RFP) and Tg(tagln:NLS-EGFP) transgenic lines to identify single- and double-positive perivascular cell populations on the cranial, axial, and intersegmental vessels between 1 and 5 days postfertilization...

Brain arteries are wrapped by vascular smooth muscle cells (VSMCs). Fully differentiated VSMCs are important for brain artery homeostasis, and they are lost in several cerebrovascular diseases. How healthy VSMCs differentiate on different brain arteries during development is unclear. Such knowledge will help regenerate lost VSMCs in brain arteriopathy. To answer this question, we studied the developmental muscularization of the zebrafish circle of Willis (CW) arteries, the major arterial loop that supplies blood to the brain in all vertebrates...

Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL) is a subset of ALL that demonstrated a high treatment failure rate. One of the hallmarks of Ph-like ALL is PDGFRB gene fusion, with fusion partner proteins often harboring dimerization domains and enhancing the kinase activity of PDGFRB. We determined a novel oncogenic PDGFRB fusion gene, NRIP1::PDGFRB, from a pediatric patient with ALL, encoding a protein with the carboxy-terminal kinase domain of PDGFRB, without the partner peptide. We confirmed the oncogenic potential of NRIP1::PDGFRB in vitro and the efficacy of all ABL1-specific inhibitor generations, including imatinib, dasatinib, nilotinib, and ponatinib, in suppressing this potential...

PURPOSE: Uremia, which is characterized by immunodeficiency, is associated with the deterioration of kidney function. Immune-related genes (IRGs) are crucial for uremia progression. METHODS: The co-expression network was constructed to identify key modular genes associated with uremia. IRGs were intersected with differentially expressed genes (DEGs) between uremia and control groups and key modular genes to obtain differentially expressed IRGs (DEIRGs). DEIRGs were subjected to functional enrichment analysis...

Tamoxifen (TAM), a selective estrogen receptor modulator, is often used for long-term adjuvant endocrine therapy in patients with hormone receptor-positive breast cancer. TAM is known to increase the risk of endometrial cancer (EC); however, the mechanism has not yet been fully elucidated. Therefore, molecular genetic analysis of EC following TAM administration (TAM-related EC) was conducted. A total of 10 samples of TAM-related EC and 20 sporadic EC samples (as controls) were analyzed. Copy number variation analysis was conducted, microsatellite instability (MSI) status was assessed, and mismatch repair (MMR) protein expression was examined immunohistochemically...

The ETV6::PDGFRB fusion gene is commonly reported in chronic myelomonocytic leukemia with eosinophilia, yet patients with ETV6::PDGFRB presenting myeloid and lymphoid neoplasms successively have not been reported. Here, we report the first case of a 35-year-old man with myeloid and lymphoid neoplasms harboring an ETV6::PDGFRB fusion gene who demonstrated poor response to imatinib. The patient was diagnosed with an ETV6::PDGFRB fusion gene myeloid neoplasm on initial diagnosis at our hospital. After 5 months of treatment with imatinib, he was diagnosed with T-cell lymphoblastic lymphoma...