Lenvatinib and its use in the treatment of unresectable hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver accounting for approximately 90% of cases. Patients often present at an advanced stage when treatment options are limited. Sorafenib, a multitargeted tyrosine kinase inhibitor, has been the first-line treatment in this setting for almost a decade. Several subsequent targeted therapies have failed to demonstrate significant improvement in survival. The results of the REFLECT study suggest that lenvatinib, a multikinase inhibitor, may have promised as a first-line treatment in patients with advanced HCC. This article will review the development of lenvatinib and the evidence behind its potential use in patients with advanced HCC

Stalins særligt hemmelige verden. Om Niels Erik Rosenfeldts disputats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Lysine degradation through the saccharopine pathway has been shown only in plants and animals. Here, we show that bacteria possess the genes encoding lysine-ketoglutarate reductase (LKR) and saccharopine dehydrogenase (SDH). In Silicibacter, the contiguous lkr and sdh genes are interspersed, in another frame, by a polypeptide of unknown function. The bacterial enzyme does not contain the 110-amino-acid interdomain (ID) that intersperses the LKR and SDH domains of the plant enzyme. The ID was found in Cyanobacteria interspersing polypeptides without similarities and activities of LKR and SDH. The LKR/SDH bifunctional polypeptide of animals and plants may have arisen from a alpha-proteobacterium with a configuration similar to that of Silicibacter, whereas the ID in the plant enzyme may have been inherited from Cyanobacteria. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.5866905911Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)FAPESP [10/50114-4

Sistemas agroalimentares locais: biodiversidade conectando campo e cidade.

A abordagem dos sistemas alimentares descende do conceito de "regime alimentar" formulado inicialmente por Harriet Friedmann (1987) em sua pesquisa sobre a ordem alimentar que o mundo herdou após a segunda grande guerra, ou seja, não se trata apenas do alimento em si, mas das políticas das relações alimentares

Nivolumab versus investigator's choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck : efficacy and safety in CheckMate 141 by age

Objectives: Many patients with squamous cell carcinoma of the head and neck (SCCHN) are 6565 years old; comorbidities and other age-related factors may affect their ability to tolerate traditional chemotherapy. Nivolumab is the only immunotherapy to significantly improve overall survival (OS) versus investigator's choice (IC) of single-agent chemotherapy at primary analysis in a phase 3 trial (CheckMate 141) in patients with recurrent/metastatic SCCHN post-platinum therapy. In this post hoc analysis, we report efficacy and safety by age. Patients and methods: Eligible patients were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks (n = 240) or IC (methotrexate, docetaxel, or cetuximab n = 121). The primary endpoint of the trial was OS. For this analysis, outcomes were analyzed by age < 65 and 6565 years. The data cut-off date was September 2017 (minimum follow-up 24.2 months). Results: At baseline, 68 patients (28.3%) receiving nivolumab and 45 patients (37.2%) receiving IC were 6565 years. Baseline characteristics were generally similar across age groups. OS and tumor response benefits with nivolumab versus IC were maintained regardless of age. The 30-month OS rates of 11.2% (<65 years) and 13.0% ( 6565 years) with nivolumab were more than tripled versus corresponding IC rates of 1.4% and 3.3%, respectively. The nivolumab arm had a lower rate of treatment-related adverse events versus IC regardless of age, consistent with the overall patient population. Conclusion: In CheckMate 141, nivolumab resulted in a higher survival versus IC in patients <65 and 6565 years, with a manageable safety profile in both age groups. ClinicalTrials.gov: NCT02105636

ASASSN-15lh: A Highly Super-Luminous Supernova

We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of M_{u,AB} = -23.5+/-0.1 and bolometric luminosity L_bol = (2.2+/-0.2)x 10^45 ergs s^-1, which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-I), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-I that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (M_K ~ -25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1+/- 0.2)x10^52 ergs, challenging the magnetar model for its engine.Comment: Published in the January 15, 2016 Issue of Science Magazin

A cooperação interinstitucional e a tecnologia como fatores de desenvolvimento e superação da pobreza no meio rural amazonense.

O artigo mostra o resultado de pesquisa realizada com unidades familiares de produção da comunidade José Lindoso, localizada no km 80 do ramal ZF-9, município de Rio Preto da Eva -AM. O objetivo da pesquisa é a análise dos impactos da tecnologia, da cooperação interinstitucional e organização dos agricultores no processo de desenvolvimento local, superação da situação de pobreza das famílias e melhoria das condições de vida destas

Diagnosing the Clumpy Protoplanetary Disk of the UXor Type Young Star GM Cephei

UX Orionis stars (UXors) are Herbig Ae/Be or T Tauri stars exhibiting sporadic occultation of stellar light by circumstellar dust. GM\,Cephei is such a UXor in the young ($\sim4$~Myr) open cluster Trumpler\,37, showing prominent infrared excess, emission-line spectra, and flare activity. Our photometric monitoring (2008--2018) detects (1)~an $\sim$3.43~day period, likely arising from rotational modulation by surface starspots, (2)~sporadic brightening on time scales of days due to accretion, (3)~irregular minor flux drops due to circumstellar dust extinction, and (4)~major flux drops, each lasting for a couple of months with a recurrence time, though not exactly periodic, of about two years. The star experiences normal reddening by large grains, i.e., redder when dimmer, but exhibits an unusual "blueing" phenomenon in that the star turns blue near brightness minima. The maximum extinction during relatively short (lasting $\leq 50$~days) events, is proportional to the duration, a consequence of varying clump sizes. For longer events, the extinction is independent of duration, suggestive of a transverse string distribution of clumps. Polarization monitoring indicates an optical polarization varying $\sim3\%$--8$\%$, with the level anticorrelated with the slow brightness change. Temporal variation of the unpolarized and polarized light sets constraints on the size and orbital distance of the circumstellar clumps in the interplay with the young star and scattering envelope. These transiting clumps are edge-on manifestations of the ring- or spiral-like structures found recently in young stars with imaging in infrared of scattered light, or in submillimeter of thermalized dust emission.Comment: 20 pages, 9 figure

The Young and Bright Type Ia Supernova ASASSN-14lp: Discovery, Early-Time Observations, First-Light Time, Distance to NGC 4666, and Progenitor Constraints

On 2014 Dec. 9.61, the All-Sky Automated Survey for SuperNovae (ASAS-SN or "Assassin") discovered ASASSN-14lp just $\sim2$ days after first light using a global array of 14-cm diameter telescopes. ASASSN-14lp went on to become a bright supernova ($V = 11.94$ mag), second only to SN 2014J for the year. We present prediscovery photometry (with a detection less than a day after first light) and ultraviolet through near-infrared photometric and spectroscopic data covering the rise and fall of ASASSN-14lp for more than 100 days. We find that ASASSN-14lp had a broad light curve ($\Delta m_{15}(B) = 0.80 \pm 0.05$), a $B$-band maximum at $2457015.82 \pm 0.03$, a rise time of $16.94^{+ 0.11 }_{- 0.10 }$ days, and moderate host--galaxy extinction ($E(B-V)_{\textrm{host}} = 0.33 \pm 0.06$). Using ASASSN-14lp we derive a distance modulus for NGC 4666 of $\mu = 30.8 \pm 0.2$ corresponding to a distance of $14.7 \pm 1.5$ Mpc. However, adding ASASSN-14lp to the calibrating sample of Type Ia supernovae still requires an independent distance to the host galaxy. Finally, using our early-time photometric and spectroscopic observations, we rule out red giant secondaries and, assuming a favorable viewing angle and explosion time, any non-degenerate companion larger than $0.34 R_{\textrm{sun}}$.Comment: 12 pages, 9 figures, 4 tables. Accepted to ApJ. Photometric data presented in this submission are included as an ancillary file. For a brief video explaining this paper, see https://www.youtube.com/watch?v=1bOV-Cqs-a