Blood-based biomarkers for monitoring antiangiogenic therapy in non-small cell lung cancer

Tumor angiogenesis pathways have been identified as important therapeutic targets in non-small cell lung cancer. However, no biomarkers have been described as predictors of response to antiangiogenic therapy in these patients. In this study, plasma levels of VEGF, bFGF, E-selectin, and S-ICAM and gene expression profiles of peripheral blood mononuclear cells from non-small cell lung cancer patients treated with chemotherapy plus bevacizumab were analyzed before and after treatment. Values were correlated with clinicopathological characteristics and treatment response. Plasma factor levels were measured using commercially available ELISA kits. The TaqMan^® human angiogenesis array was used to investigate the effect of treatment on gene expression profiles. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis was performed for differentially expressed genes using WEB-based GEne SeT AnaLysis Toolkit. Our results suggest a benefit for patients with increased plasma levels of VEGF, E-selectin, and S-ICAM in the course of bevacizumab treatment. Also, we identified differentially expressed genes between paired blood samples from patients before and after treatment, and significantly perturbed pathways were predicted. These changes in gene expression and levels of plasma factors could be used to assess the effectiveness of antiangiogenic therapy, in addition to standard clinical and radiological evaluations.     

Optimization of production of chlamydospores of the nematode-trapping fungus Duddingtonia flagrans in solid culture media

The large-scale production of nematophagous fungi as agents of biological control is one of the main challenges to be commercially used. In order to improve growth of microorganism in a culture medium, the addition of growth inducer is common. At the moment, the action of their addition in the mycelia growth and sporulation rate of nematophagous fungi is not known. The purpose of this trial was to evaluate the sporulation rate of Duddingtonia flagrans by adding two growth inducers, meso-inositol and Tween 80, both at 0.5 % in a traditional culture medium Sabouraud glucose agar (SGA) and also in a traditional culture medium enriched with wheat flour and milk powder. From a traditional sterile culture of D. flagrans, four groups were made: SGA; Sabouraud glucose agar–meso-inositol 0.5 %; Sabouraud glucose agar–Tween 80 0.5 %; and Sabouraud glucose agar-enriched (SGA-E). These media were placed at a constant temperature of 27 °C for 4 weeks. Following this, chlamydospores were gently rinsed off with sterile water and counted using a Neubauer haematocytometer to estimate the number of chlamydospores per millilitre of water. The addition of meso-inositol 0.5 % to SGA promoted a significant increase (p?<?0.05) in chlamydospore production obtaining an average of 51,715,000 chlamydospores per Petri dish. The highest chlamydospore concentration was observed in the SGA-E in comparison with SGA (p?<?0.01) obtaining an average of 208,760,000 chlamydospores. The aim of this study was to obtain basic knowledge regarding the effect of enriched culture medium and growth-inducing meso-inositol and Tween 80 on mycelial growth and production of chlamydospores.     

Predictive value of combined analysis of pro‐NPY and ERG in localized prostate cancer

This study aimed to investigate if combined analysis of pro‐Neuropeptide Y (NPY) and ERG expression in tumor tissue are associated with biochemical failure (BF), castration‐based treatment, castration‐resistant prostate cancer (CRPC), and prostate cancer (PCa)‐specific death for men undergoing radical prostatectomy (RP) for PCa. This study included 315 patients, who underwent RP from 2002 to 2005. Both pro‐NPY and ERG expression were analyzed using immunohistochemistry and were scored as low or high and negative or positive, respectively. Risk of BF, castration‐based treatment, CRPC, and PCa‐specific death were analyzed with multiple cause‐specific Cox regression analyses and stratified cumulative incidences using competing risk assessment. Median follow‐up was 13.0 years (95% CI: 12.7–13.2). In total, 85.7% were pro‐NPY high and 14.3% were pro‐NPY low. The combined analyses of pro‐NPY and ERG expression was not associated with risk of BF (p = 0.7), castration‐based treatment (p = 0.8), CRPC (p = 0.4) or PCa‐specific death (p = 0.5). In the multiple cause‐specific Cox regression analysis, pro‐NPY high and ERG positivity was not associated with BF (HR: 1.02; 95% CI 0.6–1.7; p = 0.94). In conclusion the combination of pro‐NPY and ERG expression did not show association with risk of BF, castration‐based treatment, CRPC, and PCa‐specific death following RP.     

Economics of Stratified Medicine in Rheumatoid Arthritis

Calcinosis is one of the hallmark sequelae of juvenile dermatomyositis (JDM), and despite recent progress in the therapy of JDM, dystrophic calcification still occurs in approximately one third of patients. This review discusses our current, albeit limited, understanding of risk factors for the development of calcinosis in JDM, as well as approaches to assessment, and current views on its pathogenesis. Anecdotal approaches to treating calcinosis associated with JDM, including both anti-inflammatory therapies and agents aimed at inhibiting the deposition of calcium hydroxyapatite, are reviewed. An improved understanding of the pathogenesis of calcinosis, the establishment of standardized measurement tools to assess calcinosis, and randomized controlled trials employing more sensitive outcome measures are needed to develop efficacious therapies for this often disabling complication.