RESUMEN
High-grade serous ovarian carcinoma presents significant clinical and therapeutic challenges. Although the traditional model of carcinogenesis has focused on the ovary as a tumor initiation site, recent studies suggest that there may be additional sites of origin outside the ovary, namely the secretory cells of the fallopian tube. Our study demonstrates that high-grade serous tumors can originate in fallopian tubal secretory epithelial cells and also establishes serous tubal intraepithelial carcinoma as the precursor lesion to high-grade serous ovarian and peritoneal carcinomas in animal models targeting the Brca, Tp53, and Pten genes. These findings offer an avenue to address clinically important questions that are critical for cancer prevention and early detection in women carrying BRCA1 and BRCA2 mutations.
Asunto(s)
Transformación Celular Neoplásica , Cistadenocarcinoma Seroso/etiología , Neoplasias de las Trompas Uterinas/patología , Genes BRCA1 , Genes BRCA2 , Neoplasias Ováricas/etiología , Lesiones Precancerosas/patología , Animales , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Epitelio/patología , Femenino , Genes p53 , Integrasas/genética , Ratones , Ratones Endogámicos C57BL , Clasificación del Tumor , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Factor de Transcripción PAX8 , Fosfohidrolasa PTEN/genética , Factores de Transcripción Paired Box/genética , Factores de Transcripción Paired Box/fisiologíaRESUMEN
Highly efficient and practical methodology for the syntheses of D- and l-4,5-O-isopropylidene-2-cyclopentenone (9 and 22), versatile intermediates for the synthesis of carbocyclic nucleosides, have been developed via a ring-closing metathesis reaction from d-ribose in eight steps. The utility of D- and l-4,5-O-isopropylidene-2-cyclopentenone is demonstrated by their application for the preparation of D-cyclopentyl-6-azauridine 12 and D-cyclopentenyl-5-halocytosine nucleosides (33-35) using Mitsunobu reaction to introduce pyrimidine bases as potential antiviral agents. Preliminary antiviral activity against orthopox viruses (smallpox, monkeypox, and cowpox virus) of the synthesized nucleosides are described.