Targeting the VEGF and PDGF signaling pathway in glioblastoma treatment

Growth factor receptors dysfunction has previously been correlated with glioma cell proliferation, ability to evade apoptosis, neo-angiogenesis and resistance to therapy. Antineoplastic molecules targeting growth factor receptors are in clinical handling, however the efficacy of these compounds has often been limited by the signaling redundancy. Here, we analyzed the effect of AG1433 (a PDGFR inhibitor), SU1498 (a VEGFR inhibitor) and BEZ235 (a PI3K/Akt/mTOR signaling pathways inhibitor) on glioblastoma cells in vitro. For this study, we used a low passage glioblastoma cell line (GB9B). Assessment of cell number over 72 h showed that the growth rate was 0.3024 and the doubling time of GB9B was 2.29 days. Similar cytotoxic effects were observed by using AG1433 and SU1498 treatment, while dual PI3K/Akt/mTOR inhibition by BEZ235 was more efficient in killing glioblastoma cells than individual PDGFR or VEGFR targeting. In SU1498 treated cells, caspase 3 activity was detected 3 hours after the treatment, while activation of caspase 8 and 9 was detected 48 hours later. AG1433 treatment induced caspase 3, 8 and 9, 3 hours after the treatment. BEZ235 treatment resulted in early caspase 3 and 8 activation, 3 hours after the treatment and an activation of caspase 9, 8 hours later.     

Tissue-specific disallowance of housekeeping genes: the other face of cell differentiation

We report on a hitherto poorly characterized class of genes that are expressed in all tissues, except in one. Often, these genes have been classified as housekeeping genes, based on their nearly ubiquitous expression. However, the specific repression in one tissue defines a special class of "disallowed genes." In this paper, we used the intersection-union test to screen for such genes in a multi-tissue panel of genome-wide mRNA expression data. We propose that disallowed genes need to be repressed in the specific target tissue to ensure correct tissue function. We provide mechanistic data of repression with two metabolic examples, exercise-induced inappropriate insulin release and interference with ketogenesis in liver. Developmentally, this repression is established during tissue maturation in the early postnatal period involving epigenetic changes in histone methylation. In addition, tissue-specific expression of microRNAs can further diminish these repressed mRNAs. Together, we provide a systematic analysis of tissue-specific repression of housekeeping genes, a phenomenon that has not been studied so far on a genome-wide basis and, when perturbed, can lead to human disease.     

Helianthin induces antiproliferative effect on human glioblastoma cells in vitro

A major focus of brain cancer research today is to translate understanding of glioma biology into advances in treatment, by exploring the potential of target therapy. Here we investigated the ability of three compounds belonging to the chemical class of azo dyes (methyl red, methyl yellow, and helianthin) to inhibit glioblastoma (GB) cell growth in vitro. Our results showed that helianthin induced cytotoxicity in two GB cell cultures, cell lines 18 and 38, whereas methyl red and methyl yellow were not cytotoxic. The effect of helianthin on EGFR, IGF-1R, and their common intracellular signaling via PI3-K and ERK1/2 was also analyzed. Treatment with helianthin down-regulated EGFR and IGF-1R activity in both cell lines. Helianthin treatment blocked ERK1/2 phosphorylation without affecting PI3K activity in cell line 18 and reduced both PI3K and ERK1/2 in GB 38 cell line. The cell death was accompanied by degradation of PARP without affecting BCL2 expression in both GB cell cultures. Because of the genetic heterogeneity of malignant gliomas, we tested the effect of helianthin on other two primary GB lines (11 and 15) and two early-passage GB cultures (BT1GB and BT2GB), to assess the general nature of the anti-tumor effect of the drug in GB cells. We found that helianthin treatment induced cell death in all the GB cell cultures analyzed. To our knowledge, this is the first report indicating that helianthin can reduce GB cell growth.     

Hereditary increased muscle mechanical irritability and progressive contracture with stretch-induced electromyographic activity

A son and mother are reported with autosomal dominantly transmitted painless, increased mechanical irritability in the limb and trunk muscles and progressive finger contracture. Immediately after a tap, muscle swelling appeared. With light tapping, wavelike muscle surface movements appeared. Progressive contractures developed first in the proximal interphalangeal finger joints and subsequently involving the lower arm muscles. The contractures disappeared in the local curare test. No spontaneous activity was recorded on concentric needle recording. Serial repetitive activity was recorded with fine wire electrode recording, induced by muscle stretch, performed by percussion hammer blows or by prolonged finger grasp. A slight, irritative peripheral nervous lesion could be the cause. The chronic sensorimotor polyneuropathy may be also a part of the syndrome.     

Risk factors for partner violence among a national sample of combat veterans

In this study, the authors identified potential risk factors for partner violence perpetration among a subsample (n=109) of men who participated in a national study of Vietnam veterans. Partner violent (PV) men with posttraumatic stress disorder (PTSD) were compared with PV men without PTSD and nonviolent men with PTSD on family-of-origin variables, psychiatric problems, relationship problems, and war-zone factors. PV men with PTSD were the highest of the 3 groups on every risk factor other than childhood abuse. Group contrasts and a classification tree analysis suggest some potential markers and mechanisms for the association between PTSD and partner violence among military veterans and highlight the need for theory development in this area of inquiry.     

Economic analyses of fast-track total hip and knee arthroplasty: a systematic review

European Journal of Orthopaedic Surgery & Traumatology - The number of total hip (THA) and knee arthroplasties (TKA) grows constantly which causes enormously rising costs for healthcare...     

Investigation of Flammability of Protective Clothing System for Firefighters

The main characteristic of clothing for protection against heat and flame is the protection of users from external influences and danger in the conditions of elevated temperatures and exposure to flame, fire, smoke, and water. The paper presents research on the clothing system for protection against heat and flame using a fire manikin and systematically analyses the damage caused after testing. As part of the damage analysis, the existence of microdamage and impurities on the clothing system was determined using a USB Dino-Lite microscope. In addition, the intensities and composition of gaseous decomposition products during the thermogravimetric analysis of samples were investigated. The results of the research using a fire manikin showed that the user of the examined clothing system would not have sustained injuries dangerous to health and life, which confirmed the protective properties. The results of the TG-FTIR indicate that the decomposition of the fabric sample of the modacrylic–cotton fiber mixture takes place in three stages, and the identified gaseous degradation products were H₂O, CO₂, and CO.