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Author: search.filters.author.Alejandro Cabrera-AndradeLanguage: search.filters.language.English

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    Case Report: CYLD cutaneous syndrome with malignant transformation to spiradenocarcinoma: cooperative effects of CYLD truncation and an MSH2 clamp-domain variant in an Ecuadorian patient
    (Frontiers Media SA, 2026-02-18)
    Carlos Reyes-Silva
    ;
    Gabriela Jaramillo-Koupermann
    ;
    Maritza Quishpe
    ;
    Rosa Pacheco
    ;
    Skehirly Burgos-Tapia
    Background: CYLD cutaneous syndrome (CCS) is a rare autosomal dominant disorder caused by germline CYLD variants and characterized by multiple skin adnexal tumors. Malignant transformation is uncommon, and cooperative genetic events remain poorly defined, particularly in underrepresented populations. Case presentation: We report a 61-year-old Ecuadorian woman with multiple scalp cylindromas and spiradenomas, including one spiradenocarcinoma. Family history was notable for malignancies in first- and second-degree relatives. Whole-exome sequencing identified a heterozygous nonsense CYLD variant (c.1207C > T; p.Gln403Ter), classified as likely pathogenic, and a homozygous missense MSH2 variant (c.1609A > G; p.Lys537Glu) of uncertain significance. Histopathology confirmed malignant transformation, while immunohistochemistry showed preserved MSH2 expression with a microsatellite-stable phenotype. Nevertheless, a functional impact of the MSH2 variant cannot be excluded. Consistent with these observations, in silico modeling demonstrated that CYLD truncation eliminates the catalytic USP domain and regulatory motifs, abolishing deubiquitinase activity, whereas the MSH2 substitution affects a conserved residue in the clamp domain, likely destabilizing the MSH2–MSH6 complex despite intact nuclear localization. Conclusion: This is the first genetically confirmed case of CCS in Ecuador and among the few reported in South America. Beyond expanding the geographic spectrum, our findings highlight the value of integrating genomic and protein analyses to uncover cooperative mechanisms of malignant progression. Such integrative genomic approaches refine diagnosis, enhance genotype–phenotype interpretation, and deepen understanding of malignant transformation in CCS, particularly in underrepresented populations.
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    Gut Microbiota Disruption in Hematologic Cancer Therapy: Molecular Insights and Implications for Treatment Efficacy
    (MDPI AG, 2024-09-24)
    GUEVARA RAMIREZ, ALEXANDRA PATRICIA  
    ;
    CADENA ULLAURI, SANTIAGO ANDRE  
    ;
    PAZ CRUZ, ELUIS ANDRES  
    ;
    RUIZ POZO, VIVIANA ALEJANDRA  
    ;
    TAMAYO TRUJILLO, VICTOR RAFAEL  
    Hematologic malignancies (HMs), including leukemia, lymphoma, and multiple myeloma, involve the uncontrolled proliferation of abnormal blood cells, posing significant clinical challenges due to their heterogeneity and varied treatment responses. Despite recent advancements in therapies that have improved survival rates, particularly in chronic lymphocytic leukemia and acute lymphoblastic leukemia, treatments like chemotherapy and stem cell transplantation often disrupt gut microbiota, which can negatively impact treatment outcomes and increase infection risks. This review explores the complex, bidirectional interactions between gut microbiota and cancer treatments in patients with HMs. Gut microbiota can influence drug metabolism through mechanisms such as the production of enzymes like bacterial β-glucuronidases, which can alter drug efficacy and toxicity. Moreover, microbial metabolites like short-chain fatty acids can modulate the host immune response, enhancing treatment effectiveness. However, therapy often reduces the diversity of beneficial bacteria, such as Bifidobacterium and Faecalibacterium, while increasing pathogenic bacteria like Enterococcus and Escherichia coli. These findings highlight the critical need to preserve microbiota diversity during treatment. Future research should focus on personalized microbiome-based therapies, including probiotics, prebiotics, and fecal microbiota transplantation, to improve outcomes and quality of life for patients with hematologic malignancies.