KATIA CANDIDO CARVALHO
Projetos de Pesquisa
Unidades Organizacionais
LIM/58 - Laboratório de Ginecologia Estrutural e Molecular, Hospital das Clínicas, Faculdade de Medicina
77 resultados
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Agora exibindo 1 - 10 de 77
- ER PvuII and XbaI polymorphisms in postmenopausal women with posterior tibial tendon dysfunction: a case control study(2018) PONTIN, P. A.; NOGARA, P. R. B.; FONSECA, F. C. P.; NETTO, C. Cesar; CARVALHO, K. C.; SOARES JUNIOR, J. M.; BARACAT, E. C.; FERNANDES, T. D.; MAFFULLI, N.; SANTOS, M. C. L.; GODOY-SANTOS, A. L.BackgroundPosterior tibial tendon (PTT) insufficiency is considered as the main cause of adult acquired flat foot and is three times more frequent in females. High estrogen levels exert a positive effect on the overall collagen synthesis in tendons. We have previously demonstrated the association between some genetic single-nucleotide polymorphism (SNP) and tendinopathy. In the present study, we investigated the association of PvuII c454-397T>C (NCBI ID: rs2234693) and XbaI c454-351A>G (NCBI ID: rs9340799) SNPs in estrogen receptor alfa (ER-) gene with PPT dysfunction.MethodsA total of 92 female subjects with PTT dysfunction, with histopathological examination of the tendon and magnetic resonance image (MRI) evidence of tendinopathy, were compared to 92 asymptomatic females who presented an intact PPT at MRI for PvuII and XbaI SNPs in the ER- gene. Genomic DNA was extracted from saliva and genotypes were obtained by polymerase chain reaction restriction fragment length polymorphism.ResultsThe analysis of PvuII SNPs showed no significant differences in the frequency of alleles and genotypes between control and PTT dysfunction groups. The XbaI SNPs in the ER- gene showed significant differences in the frequency of genotypes between control and test groups (p=0.01; OR 95% 1.14 (0.55-2.33).ConclusionsThe XbaI SNP in the ER gene may contribute to tendinopathy, and the A/A genotype could be a risk factor for PTT tendinopathy in this population. The PvuII SNP studied was not associated with PTT tendinopathy.
- Evidence that Melatonin Increases Inhibin Beta-A and Follistatin Gene Expression in Ovaries of Pinealectomized Rats(2020) MAGANHIN, Carla C.; BARACAT, Maria Candida P.; CARVALHO, Katia C.; SEGANFREDO, Isadora Braga; LUQUETTI, Camilla Maganhin; SIMOES, Ricardo Dos Santos; CARBONEL, Adriana Aparecida Ferraz; SIMOES, Manuel de Jesus; CIPOLLA-NETO, Jose; GIRAO, Manoel Joao Batista Castello; BARACAT, Edmund C.; SOARES-JR, Jose M.Melatonin plays an important role in the regulation of ovarian function including oocyte maturation in different mammalian species. Many studies indicate that melatonin has an impact on the ovarian function of a variety of ovarian cells. However, the information on the exact mechanism and involved hormones is low. To evaluate inhibin beta-A (INHBA) and follistatin (FST) expression in the ovaries of pinealectomized rats treated with melatonin, thirty adult female Wistar rats were randomized into three groups of ten animals each: group 1 (GSh), sham-operated controls receiving vehicle; group 2 (GPx), pinealectomized animals receiving vehicle; and group 3 (GPxMe), pinealectomized animals receiving replacement melatonin (1.0 mg/kg body weight. It was assumed that each animal drank 6.5 +/- 1.2 ml per night and weighs approximately 300 g.) for 60 consecutive days. The ovaries were collected for mRNA abundance and protein of INHBA and FST by qRT-PCR and immunohistochemical analyses, respectively. Treatment with melatonin resulted in the upregulation of INHBA and FST genes in the ovarian tissue of the melatonin-treated animals (GPxMe), when compared with GPx. These findings were then confirmed by analyzing the expression of protein by immunohistochemical analyses, which revealed higher immunoreactivity of INHBA and FST in GPxMe animals in the follicular cells compared with GSh and GPx rats. Melatonin increases the expression of INHBA and FST in the ovaries of pinealectomized female rats.
- Assessment of TSPAN Expression Profile and Their Role in the VSCC Prognosis(2021) FERREIRA, Kelly Pedrozo; ALMEIDA, Bruna Cristine de; ANJOS, Laura Gonzalez dos; BAIOCCHI, Glauco; SOARES, Fernando Augusto; ROCHA, Rafael Malagoli; BARACAT, Edmund Chada; DOBROFF, Andrey Senos; CARVALHO, Katia CandidoThe role and prognostic value of tetraspanins (TSPANs) in vulvar squamous cell carcinoma (VSCC) remain poorly understood. We sought to primarily determine, at both the molecular and tissue level, the expression profile of the TSPANs CD9, CD63, CD81, and CD82 in archived VSCC samples (n = 117) and further investigate their clinical relevance as prognostic markers. Our studies led us to identify CD63 as the most highly expressed TSPAN, at the gene and protein levels. Multicomparison studies also revealed that the expression of CD9 was associated with tumor size, whereas CD63 upregulation was associated with histological diagnosis and vascular invasion. Moreover, low expression of CD81 and CD82 was associated with worse prognosis. To determine the role of TSPANs in VSCC at the cellular level, we assessed the mRNA levels of CD63 and CD82 in established metastatic (SW962) and non-metastatic (SW954) VSCC human cell lines. CD82 was found to be downregulated in SW962 cells, thus supporting its metastasis suppressor role. However, CD63 was significantly upregulated in both cell lines. Silencing of CD63 by siRNA led to a significant decrease in proliferation of both SW954 and SW962. Furthermore, in SW962 particularly, CD63-siRNA also remarkably inhibited cell migration. Altogether, our data suggest that the differential expression of TSPANs represents an important feature for prognosis of VSCC patients and indicates that CD63 and CD82 are likely potential therapeutic targets in VSCC.
- 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
conferenceObject Melatonin action on luteal - granulosa cells in women with marital infertility undergoing in vitro fertilization(2016) MAGANHIN, Carla; CARVALHO, Katia; TURCO, Edson Lo; SERAFINI, Paulo; GARCIA, Natalia; CIPOLLA-NETTO, Jose; SIMOES, Manuel; BARACAT, Edmund; SOARES-JUNIOR, Jose Maria- 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.
- 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.
- Prognostic significance of c-KIT in vulvar cancer: bringing this molecular marker from bench to bedside(2012) MAIA, Beatriz de Melo; LAVORATO-ROCHA, Andre Mourao; RODRIGUES, Iara Sant'Ana; BAIOCCHI, Glauco; CESTARI, Flavia Munhoz; STIEPCICH, Monica Maria; CHINEN, Ludmila Thome Domingues; CARVALHO, Katia C.; SOARES, Fernando Augusto; ROCHA, Rafael MalagoliBackground: Vulvar carcinomas are rare tumors, and there is limited data regarding molecular alterations. To our knowledge there are no published studies on c-KIT and squamous cell carcinomas of the vulva (VSCC). Although there are a significant number of other tumor types which express c-KIT, there remains controversy as to its relationship to patient outcome. Thus, we wished to investigate such controversial findings to determine the prognostic importance of c-KIT by evaluating its protein and mRNA expression in VSCCs, correlating these findings with clinicopathological features and Human Papillomavirus (HPV) infection. Methods: c-KIT expression was scored by immunohistochemistry (IHC) as positive or negative in 139 formalin-fixed paraffin-embedded (FFPE) cases of vulvar carcinomas arrayed in a tissue microarray (TMA) using the DAKO (R) A4502 rabbit polyclonal c-KIT antibody (diluted 1: 100). c-KIT mRNA was evaluated by qRT-PCR in 34 frozen samples from AC Camargo Hospital Biobank (17 tumoral and 17 non-tumoral samples) using TaqMan probes-Applied Biosystems [Hs00174029_m1]. HPV genotyping was assessed in 103 samples using Linear Array (R) HPV Genotyping Test kit (Roche Molecular Diagnostics, Basel, Switzerland). All results obtained were correlated with clinical and pathological data of the patients. Results: c-KIT protein was positive by immunohistochemistry in 70.5% of the cases and this was associated with a higher global survival (p = 0.007), a higher recurrence-free survival (p < 0.0001), an absence of associated lesions (p = 0.001), lymph node metastasis (p = 0.0053), and HPV infection (p = 0.034). Furthermore, c-KIT mRNA quantitation revealed higher levels of transcripts in normal samples compared to tumor samples (p = 0,0009). Conclusions: Our findings indicate that those vulvar tumors staining positively for c-KIT present better prognosis. Thus, positivity of c-KIT as evaluated by IHC may be a good predictor for use of more conservative surgery techniques and lymph node dissection in vulvar cancer. So part of the essence of our study is to see the possibility of translating our current results from the bench to the bedside. This will help provide patients a more appropriate, less mutilating treatment, in order to keep the maximum physical and psychic quality as possible to these women.
- 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.