NATALIA GARCIA
Projetos de Pesquisa
Unidades Organizacionais
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
6 resultados
Resultados de Busca
Agora exibindo 1 - 6 de 6
- Targeting Hedgehog Pathway and DNA Methyltransferases in Uterine Leiomyosarcoma Cells(2021) GARCIA, Natalia; AL-HENDY, Ayman; BARACAT, Edmund C.; CARVALHO, Katia Candido; YANG, QiweiUterine leiomyosarcoma (LMS) is an aggressive tumor that presents a poor prognosis, high rates of recurrence, and metastasis. Because of its rarity, there is no information available concerning LMS molecular mechanisms of origin and development. Here, we assessed the expression profile of Hedgehog (HH) signaling pathway markers and the effects of their pharmacological inhibition on uterine smooth muscle (UTSM), leiomyoma, and LMS cells. Additionally, we also evaluated the effects of DNMTs inhibition on LMS cell behavior. Cell proliferation, migration and apoptosis rates were evaluated by MTT, Scratch, and Annexin V assays, respectively. RNA expression and protein levels were assessed by qRT-PCR and Western blot. We found that SMO and GLIs (1, 2, and 3) expression was upregulated in LMS cells, with increased nuclear levels of GLI proteins. Treatment with LDE225 (SMOi) and Gant61 (GLIi) resulted in a significant reduction in Glis protein levels in LMS (p < 0.05). Additionally, the expression of DNMT (1, 3a, and 3b), as well as GLI1 nuclear expression, was significantly decreased after treatment with HH inhibitor in LMS cells. Our results showed that blocking of SMO, GLI, and DNMTs is able to inhibit LMS proliferation, migration, and invasion. Importantly, the combination of those treatments exhibited a potentiated effect on LMS malignant features due to HH pathway deactivation.
- SHH pathway in uterine mesenchymal tumors(2014) GARCIA, Natalia; SOUZA, Faila C.; BOZZINI, Nilo; BAIOCCHI, Glauco; CUNHA, Isabela W.; SOARES, Fernando A.; BARACAT, Edmund C.; CARVALHO, Katia C.
- Differences in neonatal exposure to estradiol or testosterone on ovarian function and hormonal levels(2015) MARCONDES, Rodrigo R.; CARVALHO, Katia C.; DUARTE, Daniele C.; GARCIA, Natalia; AMARAL, Vinicius C.; SIMOES, Manuel J.; TURCO, Edson G. Lo; SOARES JR., Jose M.; BARACAT, Edmund C.; MACIEL, Gustavo A. R.Exposure to an excess of androgen or estrogen can induce changes in reproductive function in adult animals that resemble polycystic ovary syndrome in humans. However, considerable differences exist among several types of animal models. Little is known about the molecular features of steroidogenesis and folliculogenesis in the ovaries of rats exposed to different sex steroids as neonates. Here, we evaluated the impact of androgen and estrogen exposure on the ovaries of adult female rats during their neonatal period in the gene expression of Lhr and Cyp17a1, two key players of steroidogenesis. We also assessed hormone levels, folliculogenesis and the theca-interstitial cell population. The study was performed on the second postnatal day in thirty female Wistar rats that were sorted into the following three intervention groups: testosterone, estradiol and vehicle (control group). The animals were euthanized 90 days after birth. The main outcomes were hormone serum levels, ovary histomorphometry and gene expression of Lhr and Cyp17a1 as analyzed via quantitative real-time PCR. We found that exposure to excess testosterone in early life increased the LH and testosterone serum levels, the LH/FSH ratio, ovarian theca-interstitial area and gene expression of Lhr and Cyp17a1 in adult rats. Estrogen induced an increase in the ovarian theca-interstitial area, the secondary follicle population and gene expression of Lhr and Cyp17a1. All animals exposed to the sex steroids presented with closed vaginas. Our data suggest that testosterone resulted in more pronounced reproductive changes than did estrogen exposure. Our results might provide some insight into the role of different hormones on reproductive development and on the heterogeneity of clinical manifestations of conditions such as polycystic ovary syndrome.
- Lack of expression of FOXO3 correlates with poor prognosis on uterine sarcomas(2015) ALMEIDA, Thais G.; GARCIA, Natalia; CUNHA, Isabela W.; BAIOCCHI, Glauco; SOARES, Fernando A.; MACIEL, Gustavo A.; BARACAT, Edmund C.; CARVALHO, Katia C.
- Impaired branched-chain amino acid metabolism may underlie the nonalcoholic fatty liver disease-like pathology of neonatal testosterone-treated female rats(2017) ANZAI, Alvaro; MARCONDES, Rodrigo R.; GONCALVES, Thiago H.; CARVALHO, Katia C.; SIMOES, Manuel J.; GARCIA, Natalia; SOARES JR., Jose M.; PADMANABHAN, Vasantha; BARACAT, Edmund C.; SILVA, Ismael D. C. G. da; MACIEL, Gustavo A. R.Polycystic ovary syndrome (PCOS) is frequently associated with non-alcoholic fatty liver disease (NAFLD), but the mechanisms involved in the development of NAFLD in PCOS are not well known. We investigated histological changes and metabolomic profile in the liver of rat models of PCOS phenotype induced by testosterone or estradiol. Two-day old female rats received sc injections of 1.25 mg testosterone propionate (Testos; n = 10), 0.5 mg estradiol benzoate (E2; n = 10), or vehicle (control group, CNT; n = 10). Animals were euthanized at 90-94 d of age and the liver was harvested for histological and metabolomic analyses. Findings showed only Testos group exhibited fatty liver morphology and higher levels of ketogenic and branched-chain amino acids (BCAA). Enrichment analysis showed effects of testosterone on BCAA degradation pathway and mitochondrial enzymes related to BCAA metabolism. Testos group also had a decreased liver fatty acid elongase 2 (ELOVL2) activity. E2 group had reduced lipid and acylcarnitine metabolites in the liver. Both groups had increased organic cation transporters (SLC22A4 and SLC16A9) activity. These findings indicate that neonatal testosterone treatment, but not estradiol, produces histological changes in female rat liver that mimic NAFLD with testosterone-treated rats showing impaired BCAA metabolism and dysfunctions in ELOVL2, SLC22A4 and SLC16A9 activity.
- Non canonical activation of Sonic Hedgehog pathway in uterine leiomyosarcoma(2017) GARCIA, Natalia; OLIVEIRA, Bianca C.; FERREIRA, Kelly P.; BARACAT, Edmund C.; CARVALHO, Katia C.