All tumour cells in a patient have shared and non-shared genetic alterations, and the diversity of mutations is described as intratumoural heterogeneity (ITH). Multiregion sequencing is a genome sequencing analytical technique used for multiple, spatially-separated biopsy tissues that may further our understanding of ITH and tumour evolution. Although genetic mutations in extramammary Paget's disease (EMPD) have recently been detected by next-generation sequencing analysis, there have been no reports of ITH based on multiregion sequencing in EMPD.
View Article and Find Full Text PDFAlopecia areata (AA) is an autoimmune disease characterized by damage to hair follicles and hair loss. Cell-free DNA (cfDNA) has recently received attention as a biomarker of various disorders including inflammatory skin diseases. In this study, we aimed to investigate the clinical significance of cfDNA and the circulating DNAs of disease-associated cytokines in AA patients.
View Article and Find Full Text PDFOncogenic mutation activates phosphoinositide 3-kinase (PI3K) enzyme, and PI3K-AKT signaling activation induces several growth-regulatory transcription factors. mutations have attracted attention as biomarker in clinical trials of various inhibitors including PI3K inhibitors. About 80% of mutations in human cancers are observed in 'hot spot' regions: exon 9 (E542K and E545K) and exon 20 (H1047R).
View Article and Find Full Text PDFHypertrophic scars and keloids are fibroproliferative disorders caused by abnormal wound healing. Their exact cause has not been found, but abnormalities during the wound healing process including inflammatory, immune, genetic, and other factors are thought to predispose an individual to excessive scarring. In the present study, we performed transcriptome analysis of established keloid cell lines (KEL FIB), focusing on gene expression analysis and fusion gene detection for the first time.
View Article and Find Full Text PDFHeat shock protein 90 (HSP90) facilitates diverse cellular processes by interacting process with more than 200 client proteins. Overexpression of HSP90 contributes to the pathogenesis of various malignant tumors, and HSP90 inhibitors attenuate the progression of malignant tumors in vitro/vivo. Numerous clinical trials have used HSP90 inhibitors to treat several cancers, and pimitespib (an HSP90 inhibitor) is covered by insurance for advanced gastrointestinal stromal tumor in Japan.
View Article and Find Full Text PDFWe studied 95 patients with infantile hemangioma (IH) treated with propranolol at the Department of Dermatology, Kumamoto University Hospital, from November 2016 to January 2022, based on sex, site, clinical classification, duration of treatment, and residual lesions after treatment. Four of the 95 patients discontinued propranolol due to side effects, and 55 completed follow-ups at our hospital. We observed that 30.
View Article and Find Full Text PDFSystemic sclerosis (SSc) is characterized by excessive collagen deposition in the skin and internal organs. Activated fibroblasts are the key effector cells for the overproduction of type I collagen, which comprises the α1(I) and α2(I) chains encoded by and , respectively. In this study, we examined the expression patterns of α1(I) and α2(I) collagen in SSc fibroblasts, as well as their co-regulation with each other.
View Article and Find Full Text PDFAlthough the prognosis of patients with extramammary Paget's disease (EMPD) treated with radical resection is good, the prognosis of EMPD with distant metastasis is very poor. PIK3CA mutations predict a good response to PIK3CA inhibitors. The aim of this study was to investigate the occurrence rate of PIK3CA mutations (including multiple mutations [MM]) related to the intertumor and intratumor heterogeneity in EMPD and to evaluate the correlation between these mutations and clinical parameters of EMPD.
View Article and Find Full Text PDFDermatofibrosarcoma protuberans (DFSP) is a rare neoplasm derived from fibroblasts. Although the frequency of microsatellite instability (MSI) in skin cancer is reported to be less than 5%, there is only one report of the status of MMR in DFSP. The only analytical report of microsatellite stability in which Promega panel is not used, showed that the frequency of MSI-high, MSI-low and microsatellite stable (MSS) cases was 13.
View Article and Find Full Text PDFAlthough cancer personalized profiling by deep sequencing (CAPP-Seq) of cell-free DNA (cfDNA) has gained attention, the clinical utility of circulating tumour DNA (ctDNA) in extramammary Paget's disease (EMPD) has not been investigated. In this study, genomic alterations in the cfDNA and tumour tissue DNA were investigated in seven patients with metastatic EMPD. CAPP-Seq revealed mutations in 18 genes, 11 of which have not yet been reported in EMPD.
View Article and Find Full Text PDFTurning non-inflamed (cold) tumors into inflamed (hot) tumors is important for maximizing the effect of immune checkpoint inhibitors (ICIs) against malignancies. We showed that lactate, a product of the Warburg effect, inhibited the efficacy of ICIs and suppressed IL-12 p40 expression in dendritic cells (DCs) through reducing NF-κB p65, p50, and c-Rel DNA-binding activity to the IL-12 p40 promoter. Additionally, lactate promoted the expression of early growth response protein 1 (EGR1), whose expression was increased in human invasive melanoma compared with non-invasive melanoma.
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