Cisplatin plus oral etoposide (EoP) combination is more effective than paclitaxel in patients with advanced breast cancer pretreated with anthracyclines: a randomised phase III trial of Turkish Oncology Group

Our objective was to determine whether oral etoposide and cisplatin combination (EoP) is superior to paclitaxel in the treatment of advanced breast cancer (ABC) patients pretreated with anthracyclines. From December 1997 to August 2003, 201 patients were randomised, 100 to EoP and 101 to paclitaxel arms. Four patients in each arm were ineligible. The doses of etoposide and cisplatin were 50 mg p.o. twice a day for 7 days and 70 mg m−2 intravenously (i.v.) on day 1, respectively, and it was 175 mg m−2 on day 1 for paclitaxel. Both treatments were repeated every 3 weeks. A median of four cycles of study treatment was given in both arms. The response rate obtained in the EoP arm was significantly higher (36.3 vs 22.2%; P=0.038). Median response duration was longer for the EoP arm (7 vs 4 months) (P=0.132). Also, time to progression was significantly in favour of the EoP arm (5.5 vs 3.9 months; P=0.003). Median overall survival was again significantly longer in the EoP arm (14 vs 9.5 months; P=0.039). Toxicity profile of both groups was similar. Two patients in each arm were lost due to febrile neutropenia. The observed activity and acceptable toxicity of EoP endorses the employment of this combination in the treatment of ABC following anthracyclines

A Deep Insight into the Sialotranscriptome of the Gulf Coast Tick, Amblyomma maculatum

Background: Saliva of blood sucking arthropods contains compounds that antagonize their hosts ’ hemostasis, which include platelet aggregation, vasoconstriction and blood clotting; saliva of these organisms also has anti-inflammatory and immunomodullatory properties. Perhaps because hosts mount an active immune response against these compounds, the diversity of these compounds is large even among related blood sucking species. Because of these properties, saliva helps blood feeding as well as help the establishment of pathogens that can be transmitted during blood feeding. Methodology/Principal Findings: We have obtained 1,626,969 reads by pyrosequencing a salivary gland cDNA library from adult females Amblyomma maculatum ticks at different times of feeding. Assembly of this data produced 72,441 sequences larger than 149 nucleotides from which 15,914 coding sequences were extracted. Of these, 5,353 had.75 % coverage to their best match in the non-redundant database from the National Center for Biotechnology information, allowing for the deposition of 4,850 sequences to GenBank. The annotated data sets are available as hyperlinked spreadsheets. Putative secreted proteins were classified in 133 families, most of which have no known function. Conclusions/Significance: This data set of proteins constitutes a mining platform for novel pharmacologically activ

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research

Imaging mass spectrometry of frontal white matter lipid changes in human alcoholics

BACKGROUND: Chronic alcohol use disorders (AUD) are associated with white matter (WM) degeneration with altered myelin integrity. Matrix assisted laser desorption ionization-imaging mass spectrometry (MALDI-IMS) enables high throughput analysis of myelin lipid biochemical histopathology to help characterize disease mechanisms. PURPOSE: This study utilized MALDI-IMS to investigate frontal lobe WM myelin lipid abnormalities in AUD. METHODS: Standardized cores of formalin-fixed WM from Brodmann Area 4 (BA4) and BA8/9 of 20 postmortem AUD and 19 control adult human brains were embedded in carboxymethyl-cellulose, cryo-sectioned (8 μm), thaw-mounted onto indium tin oxide (ITO) -coated glass slides, and sublimed with 2,5-dihydroxybenzxoic acid (DHB) matrix. Lipids were imaged by MALDI-time of flight in the negative ionization mode. Data were visualized with FlexImaging software v4.0 and analyzed with ClinProTools v3.0. RESULTS: Principal component analysis (PCA) and data bar plots of MALDI-IMS data differentiated AUD from control WM. The dominant effect of AUD was to broadly reduce expression of sphingolipids (sulfatides and ceramides) and phospholipids. Data bar plots demonstrated overall similar responses to AUD in BA4 and BA8/9. However, differential regional effects of AUD on WM lipid profiles were manifested by non-overlapping expression or discordant responses to AUD for a subset of lipid ions. CONCLUSIONS: Human AUD is associated with substantial inhibition of frontal lobe WM lipid expression with regional variability in these effects. MALDI-IMS can be used to characterize the nature of AUD-associated lipid biochemical abnormalities for correlation with lifetime exposures and WM degeneration, altered gene expression, and responses to abstinence or treatment

Homology modeling procedures for cytoskeletal proteins of tetrahymena and other ciliated protists

In recent years there has been an explosive increase in the number of annotated protein sequences available through genome sequencing, as well as an accumulation of published protein structural data based on crystallographic and NMR methods. When taken together with the development of computational methods for the prediction of protein structural and functional properties through homology modeling, an opportunity exists for prediction of properties of cytoskeletal proteins in a suitable model organism, such as Tetrahymena thermophila and its ciliated protist relatives. In particular, the recently sequenced genome of T. thermophila, long a model for cytoskeletal studies, provides a good starting point for undertaking such homology modeling studies. Homology modeling can produce functional predictions, for example regarding potential molecular interactions, that are of great interest to the drug industry and Tetrahymena is an attractive model system in which to follow up computational predictions with experimental analyses. We provide here procedures that can be followed to gain entry into this promising avenue of analysis

Influência dos estágios de maturação sexual no estado nutricional, antropometria e composição corporal de adolescentes Influence of the stages of sexual maturation in the nutritional status, anthropometrics and corporal composition of adolescents

Os fenômenos puberais apresentam variabilidade no que diz respeito às idades de início e término, à velocidade e magnitude com que se expressam e as suas inter-relações. Tais fenômenos influenciam as modificações antropométricas e de composição corporal que caracterizam o processo de crescimento e desenvolvimento da adolescência. O artigo tem como objetivo analisar a influência dos estágios de maturação sexual, no estado nutricional, antropometria e composição corporal de adolescentes de ambos os sexos. A revisão de literatura foi realizada utilizando-se os termos "Adolescent, Puberty and Body Composition", por meio de consulta na base de dados do HighWire Press®. Trabalhou-se com artigos publicados desde janeiro de 1995 até julho de 2006, incluindo, outros relevantes ao tema, publicados anteriormente. Na adolescência, para se avaliar o estado nutricional e as modificações antropométricas e de composição corporal, é de extrema importância a consideração não somente da idade cronológica, mas também do estágio de maturação sexual. Cabe ressaltar as consideráveis dificuldades metodológicas existentes nos estudos acerca do estadiamento pubertário. Destaca-se a importância da realização de mais estudos, no sentido de elucidar a influência dos estágios de maturação sexual na evolução dos parâmetros antropométricos e de composição corporal, possibilitando a construção e utilização sistemática de referências que considerem o desenvolvimento pubertário.<br>Puberty phenomena concerning ages of onset and ending, speed and magnitude of expression, and interrelations are variable. Such phenomena influence anthropometric and body composition changes characterizing the process of growth and development during adolescence. This article has the objective of analyzing the influence of sexual maturing status on nutritional status, anthropometry and body composition in adolescents of both sexes. Literature review was accomplished through the use of the terms "Adolescent, Puberty and Body Composition" through consultation to the HighWire Press® database. Articles published from January 1995 to July 2006 were utilized, including others previously published and relevant to the subject. To assess nutritional status, anthropometric and body composition changes, during adolescence it is extremely important that consideration is not restricted to chronological age but extended to sexual maturity as well. The considerable methodological difficulties related to puberty staging should be emphasized. There is a need to accomplish further studies to clarify sexual maturing staging in anthropometric and body composition parameters, enabling systematic building and use of references considering puberty development