NATALIA GARCIA
Projetos de Pesquisa
Unidades Organizacionais
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
11 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 11
- Involvement of miRNA expression may contribute for FoxO3a oncogenic role in uterine leiomyosarcoma(2018) GARCIA, Natalia; RICCI, Anamaria Ritti; ALMEIDA, Bruna Cristine de; ALMEIDA, Thais Gomes; CUNHA, Isabela Werneck; BARACAT, Edmund Chada; CARVALHO, Katia Candido
- Differential BMP4 and GREM1 protein expression in uterine leiomyosarcoma and leiomyoma(2013) GARCIA, Natalia; SOUZA, Faila Catarina; CUNHA, Isabela Werneck; SOARES, Fernando Augusto; MACIEL, Gustavo Arantes Rosa; BARACAT, Edmund Chada; CARVALHO, Katia Candido
- 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.
conferenceObject Hypermethylation in BMP4 and GREM1 may be associated with uterine leiomyosarcoma development.(2018) GARCIA, Natalia; OLIVEIRA, Bianca Calsolari; FERREIRA, Kelly Pedrozo; BARACAT, Edmund Chada; CARVALHO, Katia CandidoconferenceObject Metastatic vulvar squamous cell carcinoma shows rs4986938 polymorphism in estrogen receptor beta.(2018) FERREIRA, Kelly Pedrozo; NARCISO, Henderson Junior; GARCIA, Natalia; BARACAT, Edmund Chada; CARVALHO, Katia Candido- Hypothalamic transcriptional expression of the kis-speptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes(2017) MARCONDES, Rodrigo Rodrigues; CARVALHO, Katia Candido; GIANNOCCO, Gisele; DUARTE, Daniele Coelho; GARCIA, Natalia; SOARES-JUNIOR, Jose Maria; SILVA, Ismael Dale Cotrim Guerreiro da; MALIQUEO, Manuel; BARACAT, Edmund Chada; MACIEL, Gustavo Arantes RosaOBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n= 10) or estradiol benzoate (0.5 mg) (n= 10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n= 10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-b and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-a genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone-and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosteroneand estradiol-induced polycystic ovary syndrome rats.
- May Sonic Hedgehog proteins be markers for malignancy in uterine smooth muscle tumors?(2016) GARCIA, Natalia; BOZZINI, Nilo; BAIOCCHI, Glauco; CUNHA, Isabela Werneck da; MACIEL, Gustavo Arantes; SOARES JUNIOR, Jose Maria; SOARES, Fernando Augusto; BARACAT, Edmund Chada; CARVALHO, Katia CandidoSeveral studies have demonstrated that the Sonic Hedgehog signaling pathway (SHH) plays an important role in tumorigenesis and cellular differentiation. We analyzed the protein expression of SHH pathway components and evaluated whether their profile could be useful for the diagnosis, prognosis, or prediction of the risk of malignancy for uterine smooth muscle tumors (USMTs). A total of 176 samples (20 myometrium, 119 variants of leiomyoma, and 37 leiomyosarcoma) were evaluated for the protein expression of the SHH signaling components, HHIP1 (SHH inhibitor), and BMP4 (SHE target) by immunohistochemistry. Western blot analysis was performed to verify the specificity of the antibodies. We grouped leiomyoma samples into conventional leiomyomas and unusual leiomyomas that comprise atypical, cellular, mitotically active leiomyomas and uterine smooth muscle tumors of uncertain malignant potential. Immunohistochemical analysis showed that SMO, SUFU, GLIL GLI3, and BMP4 expression gradually increased depending on to the histologic tissue type. The protein expression of SMO, SUFU, and GLI1 was increased in unusual leiomyoma and leiomyosarcoma samples compared to normal myometrium. The inhibitor HHIP1 showed higher expression in myometrium, whereas only negative or basal expression of SMO, SUFU, GLIL and GLI3 was detected in these samples. Strong expression of SHE was associated with poorer overall survival. Our data suggest that the expression of SHH proteins can be useful for evaluating the potential risk of malignancy for USMTs. Moreover, GLI1 and SMO may serve as future therapeutic targets for women with USMTs.
conferenceObject CD151 gene expression in vulvar cancer cells seems to correlate to tumor progression.(2018) NARCISO, Henderson Junior; FERREIRA, Kelly Pedrozo; GARCIA, Natalia; BARACAT, Edmund Chada; CARVALHO, Katia Candido- Smoothened a new perspective for uterine leiomyoma treatment(2017) GARCIA, Natalia; ANJOS, Laura Gonzalez; MAFFAZIOLI, Giovana De Nardo; BOZZINI, Nilo; BARACAT, Edmund Chada; CARVALHO, Katia Candido
conferenceObject Oncomirs expression profiling in uterine leiomyosarcoma cells.(2018) ALMEIDA, Bruna Cristine De; GARCIA, Natalia; BARACAT, Edmund Chada; CARVALHO, Katia Candido