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  1. Article ; Online: Stathmin 1 is highly expressed and associated with survival outcome in malignant adrenocortical tumours.

    Dos Santos Passaia, Bárbara / Lima, Keli / Kremer, Jean Lucas / da Conceição, Barbara Brito / de Paula Mariani, Beatriz Marinho / da Silva, Jean Carlos Lipreri / Zerbini, Maria Claudia Nogueira / Fragoso, Maria Candida Barisson Villares / Machado-Neto, João Agostinho / Lotfi, Claudimara Ferini Pacicco

    Investigational new drugs

    2019  Volume 38, Issue 3, Page(s) 899–908

    Abstract: Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant ... ...

    Abstract Adrenocortical carcinoma (ACC) is an aggressive endocrine cancer with few molecular predictors of malignancy and survival, especially in paediatric patients. Stathmin 1 (STMN1) regulates microtubule dynamics and has been involved in the malignant phenotype of cancer cells. Recently, it was reported that STMN1 is highly expressed in ACC patients, and STMN1 silencing reduces the clonogenicity and migration of ACC cell lines. However, the prognostic significance of STMN1 and its therapeutic potential remain undefined in ACC. In the present study, STMN1 mRNA levels were significantly higher (p < 0.05) in ACC patients, especially in an advanced stage, and correlated with BUB1B and PINK1 expression, the prognostic-related genes in ACC. In paediatric tumours, high STMN1 expression was observed in both adrenocortical carcinoma and adrenocortical adenoma patients. Among the adult malignant tumours, STMN1 level was an independent predictor of survival outcomes (overall survival: hazard ratio = 6.08, p = 0.002; disease-free survival: hazard ratio = 4.65, p < 0.0001). Paclitaxel, a microtubule-stabilizing drug, reduces the activation of STMN1 and significantly decreases cell migration and invasion in ACC cell lines and ACC cells from secondary cell culture (all p < 0.0001). In summary, STMN1 expression may be of great value to clinical and pathological findings in therapeutic trials and deserves future studies in ACC.
    MeSH term(s) Adrenal Cortex Neoplasms/drug therapy ; Adrenal Cortex Neoplasms/genetics ; Adrenal Cortex Neoplasms/mortality ; Adrenocortical Carcinoma/drug therapy ; Adrenocortical Carcinoma/genetics ; Adrenocortical Carcinoma/mortality ; Adrenocortical Carcinoma/pathology ; Adult ; Biomarkers, Tumor/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Child, Preschool ; Disease-Free Survival ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Male ; Paclitaxel/therapeutic use ; Prognosis ; RNA, Messenger/genetics ; Stathmin/genetics
    Chemical Substances Biomarkers, Tumor ; RNA, Messenger ; STMN1 protein, human ; Stathmin ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2019-08-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604895-x
    ISSN 1573-0646 ; 0167-6997
    ISSN (online) 1573-0646
    ISSN 0167-6997
    DOI 10.1007/s10637-019-00846-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1823: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
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  2. Article ; Online: Cushing's disease due to somatic USP8 mutations: a systematic review and meta-analysis.

    Wanichi, Ingrid Quevedo / de Paula Mariani, Beatriz Marinho / Frassetto, Fernando Pereira / Siqueira, Sheila Aparecida Coelho / de Castro Musolino, Nina Rosa / Cunha-Neto, Malebranche Berardo Carneiro / Ochman, Gilberto / Cescato, Valter Angelo Sperling / Machado, Marcio Carlos / Trarbach, Ericka Barbosa / Bronstein, Marcello Delano / Fragoso, Maria Candida Barisson Villares

    Pituitary

    2019  Volume 22, Issue 4, Page(s) 435–442

    Abstract: Purpose: Cushing's disease (CD) is a severe illness generally caused by microcorticotropinomas (MICs) and in approximately 7-20% of patients by macrocorticotropinomas (MACs). USP8-mutations have been identified as a major genetic cause of CD (~ 50%). ... ...

    Abstract Purpose: Cushing's disease (CD) is a severe illness generally caused by microcorticotropinomas (MICs) and in approximately 7-20% of patients by macrocorticotropinomas (MACs). USP8-mutations have been identified as a major genetic cause of CD (~ 50%). Few studies have reported the distribution between MICs-MACs related to USP8-mutations and their genotype-phenotype correlations. Therefore, we aimed to evaluate USP8-mutations in a cohort of MICs-MACs from a unique center and to perform a systematic review and meta-analysis.
    Methods: DNA-tumor-tissues from 47 corticotropinomas (16 MICs and 31 MACs) were sequenced. Clinical-biochemical data, radiological imaging data and remission/recurrence rates were evaluated. In addition, we performed a meta-analysis of nine published series (n = 630).
    Results: We identified four different USP8-mutations previously described, in 11 out of 47 (23.4%) corticotropinomas; 8 out of 11 were MACs. The urinary cortisol levels of our patients with corticotrophin USP8-mutated-alleles were lower than those of patients with wild-type (WT) alleles (p ≤ 0.017). The frequency of USP8-mutated-alleles among the series was approximately 30% with a higher prevalence in female-patients (p < 0.1 × 10
    Conclusion: Our data, as well as the retrospective review of CD series associated with USP8-mutated alleles, show heterogeneous findings among the series. Several drawbacks included the lack of a systematic protocol to evaluate these patients before surgery and follow-up. Further prospective studies using a systematic protocol will provide more consistent information about the influence of the corticotropinomas with USP8-mutated alleles on the phenotype, responses to treatment and outcome of patients with CD.
    MeSH term(s) Alleles ; Endopeptidases/genetics ; Endosomal Sorting Complexes Required for Transport/genetics ; Genetic Association Studies ; Humans ; Mutation/genetics ; Pituitary ACTH Hypersecretion/epidemiology ; Pituitary ACTH Hypersecretion/etiology ; Pituitary ACTH Hypersecretion/genetics ; Ubiquitin Thiolesterase/genetics
    Chemical Substances Endosomal Sorting Complexes Required for Transport ; Endopeptidases (EC 3.4.-) ; USP8 protein, human (EC 3.4.19.12) ; Ubiquitin Thiolesterase (EC 3.4.19.12)
    Language English
    Publishing date 2019-07-04
    Publishing country United States
    Document type Journal Article ; Meta-Analysis ; Systematic Review
    ZDB-ID 1385151-2
    ISSN 1573-7403 ; 1386-341X
    ISSN (online) 1573-7403
    ISSN 1386-341X
    DOI 10.1007/s11102-019-00973-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6139: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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