Cholesteatoma is an epidermoid cyst, which is most frequently found in the middle ear. The matrix of cholesteatoma is histologically similar to the matrix of the epidermoid cyst of the skin (atheroma); their epithelium is characterized by hyperproliferation. The c-MYC protooncogene located on chromosome 8q24 encodes a transcription factor involved in the regulation of cell proliferation and differentiation. Previous studies have found aneuploidy of chromosome 8, copy number variation of c-MYC gene, and the presence of elevated level c-MYC protein in cholesteatoma. In this study we have compared the expression of c-MYC gene in samples taken from the matrix of 26 acquired cholesteatomas (15 children and 11 adults), 15 epidermoid cysts of the skin (atheromas; head and neck region) and 5 normal skin samples (retroauricular region) using RT-qPCR, providing the first precise measurement of the expression of c-MYC gene in cholesteatoma. We have found significantly elevated c-MYC gene expression in cholesteatoma compared to atheroma and to normal skin samples. There was no significant difference, however, in c-MYC gene expression between cholesteatoma samples of children and adults. The significant difference in c-MYC gene expression level in cholesteatoma compared to that of atheroma implies a more prominent hyperproliferative phenotype which may explain the clinical behavior typical of cholesteatoma.
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January 2025
Department of Chemistry, University of Toronto, Mississauga, ON, Canada.
Protein engineering has emerged as a powerful approach toward the development of novel therapeutics targeting the MYC/MAX/E-box network, an active driver of >70% of cancers. The MYC/MAX heterodimer regulates numerous genes in our cells by binding the Enhancer box (E-box) DNA site and activating the transcription of downstream genes. Traditional small molecules that inhibit MYC face significant limitations that include toxic effects, drug delivery challenges, and resistance.
View Article and Find Full Text PDFInvest New Drugs
January 2025
UCD School of Medicine, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
Background: Since MYC is one of the most frequently altered driver genes involved in cancer formation, it is a potential target for new anti-cancer therapies. Historically, however, MYC has proved difficult to target due to the absence of a suitable crevice for binding potential low molecular weight drugs.
Objective: The aim of this study was to evaluate a novel molecular glue, dubbed GT19630, which degrades both MYC and GSPT1, for the treatment of breast cancer.
Genes Chromosomes Cancer
January 2025
Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, presenting with heterogeneous clinical and molecular subtypes. While gene fusions are predominantly associated with alveolar RMS, spindle cell RMS, especially congenital and intraosseous variants, are also linked to specific gene fusions. Furthermore, recently, FGFR1 kinase-driven RMSs were published.
View Article and Find Full Text PDFBackground: Targeting glutamine metabolism has emerged as a promising strategy in cancer therapy. However, several barriers, such as anti-tumor efficacy, drug toxicity, and safety, remain to be overcome to achieve clinical utility. Prior preclinical studies had generated encouraging data showing promises of cancer metabolism targeting drugs, although most were performed on immune-deficient murine models.
View Article and Find Full Text PDFPlants (Basel)
January 2025
State Key Laboratory of Vegetable Biobreeding, Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
The trichomes of mustard leaves have significance due to their ability to combat unfavorable external conditions and enhance disease resistance. It was demonstrated that the MYB-bHLH-WD40 (MBW) ternary complex consists of MYB, basic Helix-Loop-Helix (bHLH), and WD40-repeat (WD40) family proteins and plays a key role in regulating trichome formation and density. The bHLH gene family, particularly the Myelocytomatosis (MYC) proteins that possess the structural bHLH domain (termed bHLH-MYC), are crucial to the formation and development of leaf trichomes in plants.
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