Glucan-immunostimulant, adjuvant, potential drug

β-glucans belong to a group of biologically active natural compounds called biological response modifiers. These substances represent highly conserved structural components of cell walls in fungi, yeast, grain and seaweed. Despite almost 160 years of intensive research, the exact mechanisms of their action remain unsolved. The significant role of glucans in cancer treatment, infection immunity, stress reduction and restoration of damaged bone marrow has already been established. The present review focuses on the various less known but potentially significant roles glucans might play in medicine. In summary, glucan might represent the most important natural immunomodulator.     

Bioactive substances with anti-neoplastic efficacy from marine invertebrates: Bryozoa, Mollusca, Echinodermata and Urochordata

The marine environment provides a rich source of natural products with potential therapeutic application. This has resulted in an increased rate of pharmaceutical agents being discovered in marine animals, particularly invertebrates. Our objective is to summarize the most promising compounds which have the best potential and may lead to use in clinical practice, show their biological activities and highlight the compounds currently being tested in clinical trials. In this paper, we focused on Bryozoa, Mollusca, Echinodermata and Urochordata.     

A quantitative evaluation of redox-active compounds in human blood lipids

Endogenous low molecular weight redox active compounds (RACs) comprise antioxidants, pro-oxidants, transition metal cations and metal chelators. Traditional electrochemical methods of measuring RACs are limited to aqueous solutions, thus providing information of only hydrophilic RAC pools. In a large number of diseases associated with oxidative stress and/or with metal toxicity, redox states of hydrophilic as well as hydrophobic compartments are modified, and therefore development of methods for their detection is both necessary and important. The pools of lipid soluble RACs in reduced and oxidized forms in n-hexane extracts obtained from blood plasma, erythrocytes and whole blood of healthy donors were determined by spectrophotometric detection of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals, which stoichiometrically interacts with hydrogen donors in non polar solutions. Measurements of RACs in extracts before and after treatment with NaBH(4) provided information about the levels of both reduced and oxidized RACs. Vitamin E was also determined using a fluorescence method. The results have shown that vitamin E is the major RAC in blood plasma lipids but not in blood cell lipids, where other phenols and quinones appear to predominate.     

Optimization of the high-shear wet granulation wetting process using fuzzy logic modeling

A fuzzy model has been developed for the optimization of high-shear wet granulation wetting on a plant scale depending on the characteristics of pharmaceutical active substance particles. The model optimized on the basis of experimental data involves a set of rules obtained from expert knowledge and full-scale process data. The skewness coefficient of particle size distribution and the tapped density of the granulated mixture were chosen as the model input variables. The output of the fuzzy ruled system is the optimal quantity of wetting liquid. In comparison to manufacturing practice, a very strong sensitivity of the optimal quantity of the added wetting liquid to the size and shape of the active substance particles has been identified by fuzzy modeling.     

Prognostic classification with laboratory parameters or imaging techniques in small-cell lung cancer

PURPOSE: Our aim in this study was to compare prognostic models based on laboratory tests with a model including imaging information in small-cell lung cancer. PATIENTS AND METHODS: A retrospective analysis was performed on 156 consecutive patients. Three existing models based on laboratory tests and performance status (PS) and a model based on disease stage assessed by imaging techniques and PS were tested with Cox regression analysis. RESULTS: The 3 laboratory-based models and the imaging-based model were significant in predicting prognosis in our patient group, with hazard ratios of 1.6-3 for medium prognosis groups and 2.6-6.1 for poor prognosis groups compared with good prognosis groups. Models based on laboratory tests appear to predict survival probabilities at least as well as a model with information from imaging techniques. CONCLUSION: Prognostic models using PS and laboratory tests provide a similar estimation of survival of patients with small-cell lung cancer as the combination of PS and disease stage assessed by imaging tests.     

Human papillomavirus DNA prevalence and type distribution in anal carcinomas worldwide

Knowledge about human papillomaviruses (HPV) types involved in anal cancers in some world regions is scanty. Here, we describe the HPV DNA prevalence and type distribution in a series of invasive anal cancers and anal intraepithelial neoplasias (AIN) grades 2/3 from 24 countries. We analyzed 43 AIN 2/3 cases and 496 anal cancers diagnosed from 1986 to 2011. After histopathological evaluation of formalin‐fixed paraffin‐embedded samples, HPV DNA detection and genotyping was performed using SPF‐10/DEIA/LiPA₂₅ system (version 1) . A subset of 116 cancers was further tested for p16^INK4a expression, a cellular surrogate marker for HPV‐associated transformation. Prevalence ratios were estimated using multivariate Poisson regression with robust variance in the anal cancer data set. HPV DNA was detected in 88.3% of anal cancers (95% confidence interval [CI]: 85.1–91.0%) and in 95.3% of AIN 2/3 (95% CI: 84.2–99.4%). Among cancers, the highest prevalence was observed in warty–basaloid subtype of squamous cell carcinomas, in younger patients and in North American geographical region. There were no statistically significant differences in prevalence by gender. HPV16 was the most frequent HPV type detected in both cancers (80.7%) and AIN 2/3 lesions (75.4%). HPV18 was the second most common type in invasive cancers (3.6%). p16^INK4a overexpression was found in 95% of HPV DNA‐positive anal cancers. In view of the results of HPV DNA and high proportion of p16^INK4a overexpression, infection by HPV is most likely to be a necessary cause for anal cancers in both men and women. The large contribution of HPV16 reinforces the potential impact of HPV vaccines in the prevention of these lesions.