Project description:This study examines the expression profile of cells from human aggressive fibromatosis tumors. Cells from human aggressive fibromatosis tumors were manually minced, and visible clumps were removed. Enzymatic digestion using 10 mg/mL of collagenase IV, 2.4 units/mL Dispase, 0.05% trypsin, was used for 45 min at 37°C. Cells were then centrifuged at 1400 rpm for 5 min and washed thrice in PBS. RNA was extracted using RNA was extracted using Trisol as per the manufacturer's instructions, and used for gene profiling studies.
Project description:Desmoid type fibromatosis(DTF), a locally aggressive fibromatosis, lacks clear pathogenesis. RNA-seq analysis of 29 DTF cases identified hub genes like ZNF536, TWIST2, and SHOX2, indicating involvement in fibroblastic proliferation. These genes were validated in other fibrotic diseases. Immunohistochemistry revealed TWIST2 as a promising diagnostic biomarker, emphasizing its potential clinical utility.
Project description:Gingival fibromatosis (GF) is a rare oral condition characterized by proliferative fibrous overgrowth of both the attached and marginal gingiva, and the interdental papilla. But there were no papers about gene expression of gingival fibromatosis. The aim of this study was to identify the differential expression of genes in GF using cDNA microarray analysis.
Project description:The mechanism of idiopathic gingival fibromatosis is still unclear. To provide new insights into the molecular and cellular differences between idiopathic gingival fibromatosis and periodontitis, we first identified the gene TGM2, which is differentially expressed between the two. We found that the expression of TGM2 is predominantly lower in idiopathic gingival fibromatosis than in periodontitis, and that the activity of SP1 due to the decreased expression of TGM2 promotes the generation of extracellular matrix-related genes in idiopathic gingival fibromatosis. We have identified biglycan, an extracellular matrix that is specifically upregulated in idiopathic gingival fibromatosis, and highlight the effects of SP1 and TGM2 on biglycan expression.
Project description:Unsupervised clustering of desmoid tumors and normal mesenchymal tissues was performed using henes associated with HIF1 activity. This accurately distiguished neoplastic tissues from normal controls The study sought to identify genes differentially expressed in desmoid-type fibromatosis as opposed to normal mesenchymal tissues. We noted that beta-catenin, the central driver in desmoid-type fibromatosis, appeared to regulate HIF1 signaling in in vitro studies. Genes associated with HIF1 and angiogenesis pathways were then used to perform unsupervised clustering on desmoid tumors and normal mesenchymal tissues. The genes accurately differentiated neoplastic and normal samples.
Project description:BACKGROUND:Desmoid tumors (or aggressive fibromatosis) are locally infiltrative connective-tissue tumors that can arise in any anatomic location; they can be asymptomatic, or they can result in pain, deformity, swelling, and loss of mobility and/or threaten visceral organs with bowel perforation, hydronephrosis, neurovascular damage, and other complications. Existing clinical trial endpoints such as the Response Evaluation Criteria in Solid Tumors (version 1.1) and progression-free survival are inadequate in capturing treatment efficacy. This study was designed to develop a novel clinical trial endpoint by capturing patient-reported outcomes (PROs). METHODS:Following best practices in qualitative methodology, this study used concept elicitation (CE) interviews to explore desmoid patients' perspectives on key disease-related symptoms and impacts. Qualitative analysis was performed to determine the relative frequency and disturbance of symptoms and impacts as well as other characteristics of these concepts. A draft PRO scale was then developed and tested with cognitive interviewing. Information from the interviews was subsequently incorporated into the refined PRO scale. RESULTS:CE interviews with desmoid patients (n = 31) helped to identify salient concepts and led to a draft scale that included symptom and impact scales. Cognitive interviews were completed with additional patients (n = 15) across 3 phases. Patient input was used to refine instructions, revise and/or remove items, and modify the response scale. This resulted in an 11-item symptom scale and a 17-item impact scale. CONCLUSIONS:This is the first disease-specific PRO instrument developed for desmoid tumors. The instrument is available as an exploratory endpoint in clinical trials. This study highlights the feasibility and challenges of developing PRO instruments for rare diseases.
Project description:The enamel renal syndrome (ERS) is a rare disorder featured by amelogenesis imperfecta, gingival fibromatosis and nephrocalcinosis. Gingival fibromatosis is a hallmark of the disease; it is characterized by the accumulation of a collagen-rich, dense connective tissue and of mineral deposits throughout the gingiva. ERS is caused by biallelic mutations in the FAM20A gene encoding a pseudokinase, likely acting as an allosteric activator of FAM20C, the Golgi casein kinase. How mutations in FAM20A may modify the gingival connective tissue homeostasis and cause fibromatosis is currently unknown. Conditioned media of gingival fibroblasts (GF) obtained from four unrelated ERS patients carrying distinct mutations and three control subjects were used. Secretomic analysis identified 109 dysregulated proteins whose abundance had increased (69 proteins) or decreased (40 proteins) at least 1.5-fold compared to control GF. Gene Ontology (GO) analysis revealed biological processes significantly over-represented or under-represented in the ERS GF. Proteins over-represented were mainly involved in extracellular matrix organization, collagen fibril assembly, and biomineralization whereas those under-represented were extracellular matrix-associated proteins. Accordingly, GO disease analysis indicated un significant enrichment of tumoral angiogenesis and fibrosis.