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1.
Stem Cell Res ; 55: 102499, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34399164

RESUMO

Modulation of global mRNA translation, which is essential for intestinal stem cell function, is controlled by Wnt signaling. Loss of tumor supressor APC in stem cells drives adenoma formation through hyperactivion of Wnt signaling and dysregulated translational control. It is unclear whether factors that coordinate global translation in the intestinal epithelium are needed for APC-driven malignant transformation. Here we identified nucleotide exchange factor eIF2Bε as a translation initiation factor involved in Wnt-mediated intestinal epithelial stemness. Using eIF2BεArg191His mice with a homozygous point mutation that leads to dysfunction in the enzymatic activity, we demonstrate that eIF2Bε is involved in small intestinal crypt formation, stemness marker expression, and secreted Paneth cell-derived granule formation. Wnt hyperactivation in ex vivo eIF2BεArg191His organoids, using a GSK3ß inhibitor to mimic Apc driven transformation, shows that eIF2Bε is essential for Wnt-mediated clonogenicity and associated increase of the global translational capacity. Finally, we observe high eIF2Bε expression in human colonic adenoma tissues, exposing eIF2Bε as a potential target of CRC stem cells with aberrant Wnt signaling.


Assuntos
Adenoma , Células Epiteliais , Animais , Mucosa Intestinal , Intestinos , Camundongos , Fatores de Iniciação de Peptídeos , Via de Sinalização Wnt
2.
S Afr Med J ; 66(25): 961-2, 1984.
Artigo em Africano | MEDLINE | ID: mdl-6515509

RESUMO

Patients with leiomyoma and leiomyosarcoma of the vulva are described. The clinical features of these conditions are summarized and the diagnostic criteria for differentiating leiomyomas from leiomyosarcomas are mentioned. The treatment and follow-up of patients with vulval leiomyosarcomas is discussed briefly.


Assuntos
Leiomioma , Leiomiossarcoma , Recidiva Local de Neoplasia , Neoplasias Vulvares , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Leiomioma/diagnóstico , Leiomiossarcoma/diagnóstico , Pessoa de Meia-Idade , Neoplasias Vulvares/diagnóstico
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