Germline Mutations in Familial Papillary Thyroid Cancer.

Thyroid cancer, predominantly of papillary histology (PTC), is a common cancer mostly diagnosed sporadically. Hereditary PTC is encountered in ~ 5% of cases and may present at an earlier age, with greater risks of metastasis and recurrence, compared with sporadic cases. The molecular basis of hereditary PTC is unknown in most cases. In this study, the genetic basis of hereditary PTC in three Brazilian families was investigated. Whole exome sequencing (WES) was carried out for probands in each family, and validated, pathogenic/likely pathogenic sequence variants (P/LPSVs) were genotyped in additional family members to establish their putative pathogenic role. Overall, seven P/LPSVs in seven novel genes were detected: p.D283N*ANXA3, p.Y157S*NTN4, p.G172W*SERPINA1, p.G188S*FKBP10, p.R937C*PLEKHG5, p.L32Q*P2RX5, and p.Q76*SAPCD1. These results indicate that these novel genes are seemingly associated with hereditary PTC, but extension and validation in other PTC families are required.

Impact of Ethnicity on Somatic Mutation Rates of Pancreatic Adenocarcinoma.

BACKGROUND/AIM: Ethnicity has an effect on survival in patients with pancreatic adenocarcinoma (PDAC), which may be reflected in the rate of somatic driver mutations. The Brazilian population represents au extensive interethnic admixture and little is known about the spectrum and rates of somatic driver mutations in Brazilian PDAC cases. MATERIALS AND METHODS: Direct sequencing of six genes in 23 PDAC cases was performed and the ancestry of patients was determined using a validated panel of ancestry-informative insertion/deletion DNA polymorphisms. RESULTS: KRAS proto-oncogene (KRAS) was the most commonly mutated gene (60%). A novel putatively pathogenic mutation in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (c.2948T>A; p.M983K) was identified. Mutations in epidermal growth factor receptor (EGFR) (4%), PIK3CA (4%), cyclin-dependent kinase inhibitor 2A (CDKN2A) (4%) and TP53 (8%) were noted, in rates that are less frequent than those reported for other populations. Mutations of B-Raf proto-oncogene, serine/threonine kinase (BRAF) were not present. All individuals with high African ancestral component (allelic frequency, >0.45) exhibited KRAS mutations. CONCLUSION: Our results highlight the importance of the effect of ethnicity on somatic mutations in Brazilian patients with PDAC.

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.

Evaluation of the potential of microalgae Microcystis novacekii in the removal of Pb2+ from an aqueous medium.

In this study, the absorption capacity of active and inactive biomass of the microalgae Microcystis novacekii to remove Pb(2+) from aqueous solutions was investigated. This is the first reported study of biosorption by a cyanobacterium species, which is abundant and easily found in eutrophic lakes and ponds in tropical areas of the world. We also evaluated the effects of different concentrations of Pb(2+) on growth rates of M. novacekii. Inactive biomass was characterized by elemental composition, surface area, potentiometric titration, infrared spectroscopy and thermogravimetric analysis (TGA). The biosorption data of Pb(2+) by inactive biomass were analyzed using the Langmuir and Freundlich isotherms. Pb(2+) concentrations higher than 0.5 mg L(-1) inhibited species growth. Potentiometric titrations showed a significantly higher negative surface charge (1.48+/-0.22 mmol g(-1)) with two acidic groups (pKa(1)=3.74+/-0.12 and, pKa(2)=7.25+/-0.30). Analysis of inactive M. novacekii cells by infrared spectroscopy suggests that the cell wall carboxyl and amide groups participate in Pb(2+) biosorption. The maximum Pb(2+) adsorbed was found to be 70 mg g(-1), and the biosorption of Pb(2+) on inactive M. novacekii correlated well (R(2)=0.931) with the Langmuir equation compared to the Freundlich isotherm equation (R(2)=0.823) in the concentration range studied.