The In Vitro and In Vivo Antiangiogenic Effects of Flavokawain B.

Angiogenesis is implicated in the development of a variety of pathological processes, most commonly cancer. It is essential for tumor growth and metastasis, making it an important cancer therapeutic target. Naturally occurring substances have led to the discovery of anticancer agents. Flavokawain B (FKB), a chalcone isolated from the root extracts of kava-kava plant, inhibits proliferation and causes apoptosis in vitro and in vivo of various cancer cell lines. The antimetastatic potential of FKB has also been suggested. In our study, we confirm the antiangiogenic action of FKB in vitro and, for the first time, demonstrate its strong antiangiogenic activity in vivo, using a zebrafish model. Our data show that FKB inhibits human brain endothelial cell (HUVEC) migration and tube formation even at very low and non-toxic concentrations. Moreover, FKB blocks angiogenesis process in zebrafish, with a dramatic reduction of subintestinal vein formation in a dose-dependent manner. Flavokawain B at the concentration of 2.5 µg/mL did not exhibit any toxic effects in zebrafish larvae and caused a markedly or complete obliteration of subintestinal vein formation. Our findings along with previously published data confirm that FKB may form the basis for creating an additional tool in the treatment of cancer and other neovascularization-related diseases. Copyright © 2017 John Wiley & Sons, Ltd.

The rate of recurrent BRCA1, BRCA2, and TP53 mutations in the general population, and unselected ovarian cancer cases, in Belo Horizonte, Brazil.

In Brazil, several recurring mutations in BRCA1 and BRCA2 and a TP53 mutation (R337H) have been reported in high risk breast cancer cases. We hypothesized that these recurring mutations may also be detected in the general population and ovarian cancer cases in the state of Minas Gerais. To test this notion, participants were recruited from the outpatient and the Gynecological clinic in the UFMG Medical Center in Belo Horizonte, Minas Gerais, Brazil. BRCA1 (c.68_69delAG, c.5266dupC, c.181T>G, c.4034delA, c.5123C>A), BRCA2 (c.5946delT, c.8537_8538delAG, 4936_4939delGAAA), the c.156_157insAlu* BRCA2 and the c.1010G>A *TP53 mutation were genotyped using validated techniques. Overall, 513 cancer free participants (273 men) (mean age 47.7 ± 15.1 years) and 103 ovarian cancer cases (mean age at diagnosis 58.7 ± 9.6 years) were studied. None of the participants were found to carry any of the genotyped mutations. We conclude that the recurring mutations in BRCA1, BRCA2 and TP53 cannot be detected in the general population or consecutive ovarian cancer cases in this geographical region in Brazil.

Óxido nítrico e arginina di-metil assimétrica: possível via de explicação para o trabalho de parto pré-termo / Nitric oxide and asymmetric dimethyl arginine: a novel pathway to explain preterm labor

O trabalho de parto pré-termo (TPPT) assim como as outras causas de prematuridade respondem pela maior parcela da mortalidade e morbidade neonatal no mundo. Várias vias metabólicas já foram estudadas e diversas alterações já foram encontradas em pacientes que desenvolve TPPT. A via metabólica do óxido nítrico (NO) é reconhecida como um dos possíveis mecanismos de desencadeamento fisiopatológico do TPPT. Níveis elevados de dimetil-arginina assimétrica (ADMA), substância endógena inibidora da NO sintetase, estão relacionados com o desencadeamento de TPPT e com maiores taxas de complicações neonatais. O presente estudo aborda as evidências sobre a relação do TPPT e ADMA e as possíveis aplicações clínicas dessa associação.(AU)

Pre-term labor (PTL), as well as the other causes of prematurity, account for the largest portion of neonatal mortality and morbidity in the world. Several metabolic pathways were studied and a significative number of impairments have already been found in patients who develop PTL. The metabolic pathway of nitric oxide (NO) is recognized as one of the possible mechanisms of pathophysiological PTL?s trigger. High levels of asymmetric dimethyl arginine (ADMA), endogenous inhibitory substance of NO synthetase, are related to the triggering of PTL and with higher rates of neonatal complications. The present study addresses the evidence on the relationship of PTL and ADMA and possible clinical applications of this association.(AU)