Anaplastic lymphoma kinase (ALK) inhibitor response in neuroblastoma is highly correlated with ALK mutation status, ALK mRNA and protein levels

Background In pediatric neuroblastoma (NBL), high anaplastic lymphoma kinase (ALK) levels appear to be correlated with an unfavorable prognosis, regardless of ALK mutation status. This suggests a therapeutic role for ALK inhibitors in NBL patients. We examined the correlation between levels of ALK, phosphorylated ALK (pALK) and downstream signaling proteins and response to ALK inhibition in a large panel of both ALK mutated and wild type (WT) NBL cell lines. Methods We measured protein levels by western blot and ALK inhibitor sensitivity (TAE684) by viability assays in 19 NBL cell lines of which 6 had a point mutation and 4 an amplification of the ALK gene. Results ALK 220 kDa (p=0.01) and ALK 140 kDa (p= 0.03) protein levels were higher in ALK mutant than WT cell lines. Response to ALK inhibition was significantly correlated with ALK protein levels (p<0.01). ALK mutant cell lines (n=4) were 14,9 fold (p<0,01) more sensitive to ALK inhibition than eight WT cell lines. Conclusion NBL cell lines often express ALK at high levels and are responsive to ALK inhibitors. Mutated cell lines express ALK at higher levels, which may define their superior response to ALK inhibition

Genomic Analysis Reveals a Potential Role for Cell Cycle Perturbation in HCV-Mediated Apoptosis of Cultured Hepatocytes

The mechanisms of liver injury associated with chronic HCV infection, as well as the individual roles of both viral and host factors, are not clearly defined. However, it is becoming increasingly clear that direct cytopathic effects, in addition to immune-mediated processes, play an important role in liver injury. Gene expression profiling during multiple time-points of acute HCV infection of cultured Huh-7.5 cells was performed to gain insight into the cellular mechanism of HCV-associated cytopathic effect. Maximal induction of cell-death–related genes and appearance of activated caspase-3 in HCV-infected cells coincided with peak viral replication, suggesting a link between viral load and apoptosis. Gene ontology analysis revealed that many of the cell-death genes function to induce apoptosis in response to cell cycle arrest. Labeling of dividing cells in culture followed by flow cytometry also demonstrated the presence of significantly fewer cells in S-phase in HCV-infected relative to mock cultures, suggesting HCV infection is associated with delayed cell cycle progression. Regulation of numerous genes involved in anti-oxidative stress response and TGF-β1 signaling suggest these as possible causes of delayed cell cycle progression. Significantly, a subset of cell-death genes regulated during in vitro HCV infection was similarly regulated specifically in liver tissue from a cohort of HCV-infected liver transplant patients with rapidly progressive fibrosis. Collectively, these data suggest that HCV mediates direct cytopathic effects through deregulation of the cell cycle and that this process may contribute to liver disease progression. This in vitro system could be utilized to further define the cellular mechanism of this perturbation

Hidroxiapatita: suporte para liberação de fármacos e propriedades antimicrobianas

Resumo Os fosfatos de cálcio são materiais cerâmicos que apresentam propriedades particulares como biocompatibilidade e similaridade química com os tecidos ósseos e dentários dos seres vivos. Sua morfologia porosa permite que estes se apresentem como material apropriado para a utilização em substituição de pequenas partes de tecido ósseo, já que proporciona o crescimento de canais de sistemas nervosos, suporte para vasos sanguíneos como também suporte para deposição de fármacos. Dentre os fosfatos de cálcio, a hidroxiapatita se apresenta como fosfato mais estável, o qual é encontrado em maior proporção nos tecidos ósseo e dentário no organismo. Este trabalho teve por objetivo buscar nos bancos de artigos e de patentes trabalhos que relacionem a atividade antimicrobiana da hidroxiapatita, dando suporte a pesquisadores que trabalhem com esta cerâmica para aplicações em tecido dentário, como também a utilização da hidroxiapatita focando o suporte para incorporação de fármaco. Os bancos pesquisados foram o Scopus, Scielo e Web of Science para os artigos e USPTO, EPO e INPI para os bancos de patentes. Os critérios de exclusão levaram a 19 artigos que estudaram hidroxiapatita em conjunto com a clorexidina e zero patente encontrado. Dentre os artigos encontrados, a clorexidina é o fármaco mais empregado como agente antimicrobiano, e a bactéria mais utilizada nos testes é a gram-positiva Streptococcus mutans

Desenvolvimento de biomaterial composto por hidroxiapatita e clorexidina para aplicação na cavidade oral

Resumo A hidroxiapatita (HAp) está presente no organismo humano nos tecidos ósseos e dentários, em que do total da massa de cada tecido 30 a 70% correspondem a HAp, podendo ser aplicada como revestimentos de próteses ou até substituição de pequenas partes ósseas. Assim, o objetivo foi sintetizar HAp por precipitação, incorporar clorexidina (CHX) e avaliar as propriedades microbianas. A caracterização foi realizada por DRX, FTIR, TG/DTG, MET e MEV. A CHX foi incorporada à HAp por adsorção, variando a quantidade incorporada. O difratograma apresentou picos em 25,9º, 31,5°, 32,2º e 32,7º (2θ) referentes aos planos (002), (211), (112) e (300) da HAp. O espectro de FTIR mostrou banda em 1050 cm-1 correspondente à deformação dos grupos fosfatos e deformações de grupos CH2 em 1485 e 1445 cm-1 da clorexidina, que apresentou morfologia porosa e cilíndrica. O biomaterial apresentou excelentes propriedades antimicrobianas frente a Streptococcus mutans, Staphylococcus aureus e Escherichia coli

Alkaline earth stannates applied in photocatalysis: prospection and review of literature

Abstract The ABO3 mixed oxide class known for its perovskite-like structure has aroused great scientific and technological interest in recent decades, due to its optical, magnetic and conductive properties. The objective of this work was to search the articles and patent databases for papers that relate the activity of the alkaline earth metal stannates - BaSnO3, CaSnO3 and SrSnO3 as photocatalysts for environmental application. The databases researched were the Web of Science, Scopus and Scielo for articles and USPTO, EPO and INPI for patent banks. From the exclusion criteria, 21 review articles presented different experimental parameters and conditions. Due to the excellent photocatalytic performance, the stannates presented as promising candidates in the heterogeneous photocatalysis. A description of the main papers published in literature is provided for an overview of the literature data about these materials