Bevacizumab Treatment for Meningiomas in NF2: A Retrospective Analysis of 15 Patients

Bevacizumab treatment can result in tumor shrinkage of progressive vestibular schwannomas in some neurofibromatosis 2 (NF2) patients but its effect on meningiomas has not been defined.To determine the clinical activity of bevacizumab against NF2-related meningiomas, we measured changes in volume of meningiomas in NF2 patients who received bevacizumab for treatment of progressive vestibular schwannomas. A radiographic response was defined as a 20% decrease in tumor size by volumetric MRI analysis. In addition, we determined the expression pattern of growth factors associated with tumor angiogenesis in paraffin-embedded tissues from 26 unrelated meningiomas. A total of 48 meningiomas in 15 NF2 patients were included in this study with a median follow up time of 18 months. A volumetric radiographic response was seen in 29% of the meningiomas (14/48). Tumor shrinkage was not durable: the median duration of response was 3.7 months and the median time to progression was 15 months. There was no significant correlation between pre-treatment growth rate and meningioma response in regression models. Tissue analysis showed no correlation between tumor microvascular density and expression of VEGF pathway components. This data suggests that, in contrast to schwannomas, activation of VEGF pathway is not the primary driver of angiogenesis in meningiomas. Our results suggest that a minority of NF2-associated meningiomas shrink during bevacizumab therapy and that these responses were of short duration. These results are comparable to previous studies of bevacizumab in sporadic meningiomas.     

The sequence around the phosphorylation site of the porcine heart type phosphorylase isoenzyme

1. A tetradecapeptide containing the phosphorylation site was obtained from 32P-labelled pig heart phosphorylase a isoenzyme by alpha-chymotryptic digestion. 2. The peptide was purified by Mono S cation-exchange chromatography and reversed-phase HPLC. 3. The phosphorylated residue was identified as Ser and the sequence was determined: T D G E R R K Q I S V R G L. 4. The sequence was compared to the known sequences of muscle and liver type isophosphorylases and the structural consequences of the amino acid residue exchanges were predicted.     

The role of flavonoids in the establishment of plant roots endosymbioses with arbuscular mycorrhiza fungi,rhizobia and Frankia bacteria

Flavonoids are a group of secondary metabolites derived from the phenylpropanoid pathway. They are ubiquitous in the plant kingdom and have many diverse functions including key roles at different levels of root endosymbioses. While there is a lot of information on the role of particular flavonoids in the Rhizobium-legume symbiosis, yet their exact role during the establishment of arbuscular mycorrhiza and actinorhizal symbioses still remains unclear. Within the context of the latest data suggesting a common symbiotic signaling pathway for both plant-fungal and plant bacterial endosymbioses between legumes and actinorhiza-forming fagales, this mini-review highlights some of the recent studies on the three major types of root endosymbioses. Implication of the molecular knowledge of endosymbioses signaling and genetic manipulation of flavonoid biosynthetic pathway on the development of strategies for the transfer and optimization of nodulation are also discussed.     

Solid phase synthesis of a GHRP analog containing C-terminal thioamide group

[Lyst6]GHRP, the C-terminally thionated analog of the highly potent growth hormone releasing hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 was prepared by using solid support. The success of the synthesis showed that Lawesson's reagent can be used for selective thionation of an amide group not only in solution but also on the surface of a resin. The C-terminal thioamide group proved to be stable under the conditions of the solid phase synthesis.     

Intestinal-epithelial LSD1 controls goblet cell maturation and effector responses required for gut immunity to bacterial and helminth infection

Infectious and inflammatory diseases in the intestine remain a serious threat for patients world-wide. Reprogramming of the intestinal epithelium towards a protective effector state is important to manage inflammation and immunity and can be therapeutically targeted. The role of epigenetic regulatory enzymes within these processes is not yet defined. Here, we use a mouse model that has an intestinal-epithelial specific deletion of the histone demethylase Lsd1 (cKO mice), which maintains the epithelium in a fixed reparative state. Challenge of cKO mice with bacteria-induced colitis or a helminth infection model both resulted in increased pathogenesis. Mechanistically, we discovered that LSD1 is important for goblet cell maturation and goblet-cell effector molecules such as RELMß. We propose that this may be in part mediated by directly controlling genes that facilitate cytoskeletal organization, which is important in goblet cell biology. This study therefore identifies intestinal-epithelial epigenetic regulation by LSD1 as a critical element in host protection from infection.     

Recombination and mating-type switching in a ligase-defective mutant of Schizosaccharomyces pombe

Summary The ligase-defective cdc17-L16 mutant of Schizosaccharomyces pombe var. pombe was tested for genetic recombination and mating-type switching. Mitotic recombination was studied in both haploid and heteroallelic diploid cells. Cells carrying a heteroallelic ade6 duplication constructed by Schuchert and Kohli were tested for ectopic genetic recombination. We have found that cdc17-L16 is a mitotic hyper-rec mutant, as it increases the instability of the duplication by a factor of about 6 even at the permissive temperature of 23° C. In diploid cells, the enhancement of recombination rates detected was to that of cdc17 ⁺ cells. The temperature-sensitive cell cycle defect is also associated with a reduced level of mating and sporulation but does not significantly affect mating-type switching and intragenic meiotic recombination. It is supposed that the mitotic hyper-rec phenotype is a secondary result of insufficient repair of DNA breaks, while the lack of influence of the reduced ligase activity on the latter two processes might be attributed to their peculiar initiation mechanisms.     

Archenteron cells are responsible for the increase in ribosomal RNA synthesis in sea urchin gastrulae

Paracentrotus lividus embryos were continuously labeled with P32 from hatching blastula to pluteus. The archenteron cells were then separated from the rest of the embryo and the radioactivity accumulated into the ribosomal RNA of the two cell groups measured. The results clearly indicate that the bulk of ribosomal RNA is mainly if not entirely, synthesized in this time interval by the archenteron cells.     

Structural and functional properties of Drosophila melanogaster phosphorylase: comparison with the rabbit skeletal muscle enzyme

Glycogen phosphorylase isolated from Drosophila melanogaster contains one pyridoxal 5'-phosphate per subunit; the coenzyme is in a hydrophobic environment. Fruit-fly phosphorylase a has lower KM for glucose-1-phosphate and is less sensitive to allosteric inhibitors than the b form of the enzyme. The amino acid composition of Drosophila phosphorylase differs from that of rabbit skeletal muscle phosphorylase. These two enzymes give distinct one dimensional peptide maps. The distribution of reactive SH-groups is markedly different in the insect and vertebrate phosphorylase. Fruit-fly phosphorylase a is dephosphorylated by either rabbit or Drosophila protein phosphatase-1 at a slower rate than rabbit muscle phosphorylase a.