Synthesis of half-mustard combi-molecules with fluorescence properties: correlation with EGFR status

The synthesis of 6-(2-chloroethylamino)-4-anilinoquinazolines ZR2002 and ZR2003 designed to block EGFR tyrosine kinase and to damage genomic DNA is described. These compounds present fluorescence properties that permitted the quantitation of their subcellular uptake by flow cytometry. Fluorescence intensities increased with increasing levels of EGFR in a panel of isogenic and established cell lines.     

Distribution and phylogeography of Blanford’s Fox,Vulpes cana (Carnivora: Canidae), in Africa and the Middle East

The distribution of Vulpes cana in the extreme eastern Sahara is described on the basis of new photographic and sight records, as well as a recently acquired specimen from south-eastern Egypt. The proven range of this elusive fox now extends about 1000 km south into Africa along the Red Sea coastal mountains. The proven and predicted distribution ranges of this fox are discussed. Its phylogeography and evolutionary relationship to other foxes of the region are gleaned from analysis of mitochondrial cytochrome b DNA sequence and are discussed in light of climatic and paleogeographic history of the area. The results show that the species could have initially moved into Africa during the Pliocene-Pleistocene transition period when several land bridges occurred across the Gulf of Suez. More recent land bridges between the mountains of the Sinai Peninsula and the Eastern Desert of Egypt seem to have developed and disappeared several times during the Pleistocene, possibly allowing genetic exchange between V. cana populations in these two areas. The last of this population exchange and genetic flow between the two areas seems to have ended some 14,000 years ago when the present Gulf of Suez inundation took place.     

Comparison of measured and calculated doses in a Rando phantom with a realistic lung radiotherapy treatment plan including heterogeneities

In this work, dose measurements were performed to evaluate an external radiotherapy treatment plan and, particularly, to validate dose calculations for a lung lesion case. Doses were calculated by the Varian Eclipse treatment planning system using the AAA anisotropic analytical algorithm. The measurements were performed using a Rando anthropomorphic phantom and TLD700 thermoluminescent dosimeters. The comparison between doses calculated and doses measured by means of thermoluminescence (TL) shows compatibility except for a few points, due to the limitations in the heterogeneity correction used for the case studied here. The deviation between the calculated and measured doses is about 6.5% for low (<?0.5 Gy) doses and about 1% for higher doses (>?0.5 Gy).The deviation between AAA-calculated and TL-measured doses was also found to be higher in proximity to heterogeneous tissue interfaces.     

Isolation and characterization of human and canine gastric mucosal glycoproteins and their degradation by proteases and acid hydrolases

High molecular weight glycoproteins were isolated and purified from canine antral and fundic mucosal tissue by means of non-degrading techniques. The results disclosed the advantage of urea extraction technique over the culture method in isolating the native glycoproteins. The glycoproteins were susceptible to degradation by protease, thus yielding low molecular weight glycopeptides. Chemical analysis of these glycopeptides and their parent macromolecules revealed that the oligosaccharide residues are attached to threonine, serine and proline residues of the protein chains. Similarly, high molecular weight glycoproteins isolated from human gastric gel mucin showed the same characteristics of canine gastric glycoproteins. Canine fundic glycoprotein or glycopeptide released their prosthetic carbohydrate groups under the lytic effect of fundic acid hydrolases.     

Isolation and partial characterization of glycolipids and a carbohydrate from the secondary granules and plasma membrane of polymorphonuclear leukocytes

Chloroform/methanol extracts of the secondary granule and plasma membrane fractions of polymorphonuclear leukocytes have been shown to contain both non-polar and polar carbohydrate-containing materials. The ratio of the polar to the non-polar material was much higher in the plasma membrane than the secondary granule fraction. The non-polar material contains at least two ceramide-like glycolipids and accounts for most of the broad band of periodic acid/Schiff-positive material which migrates at the dye front in sodium dodecyl sulfate electrophoretic gels of granule and plasma membrane extracts. The polar material appears to be a single substance containing no fatty acids or sialic acid and is composed of glucose, hexosamine and a carboxylic acid derivative of pentose. Expressed on a per mg of protein basis, the amount of carbohydrate associated with the polar material in the plasma membrane fraction was about five times that of the secondary granule fraction.     

Interleukin-17 programs liver progenitor cell transformation into cancer stem cells through miR-122 downregulation with increased risk of primary liver cancer initiation

Chronic inflammation is a key component in the development of virtually all types of primary liver cancers. However, how chronic inflammation potentiates or even may initiate liver parenchymal cell transformation remains unclear. Cancer stem cells (CSCs) represent an exciting target for novel anticancer therapeutic strategies in several types of cancers and were also described in primary liver cancers as tumor initiating cells. Recently, we reported a key role of Interleukin (IL)-17 in Liver Progenitor Cell (LPC) accumulation in preneoplastic cirrhotic livers. In this study, we evidenced in vitro, that long-term stimulation of LPCs with IL-17 led to their transformation into CSCs. Indeed, they acquired CSC-marker expression, and self-renewal properties, showed by their increased capacity to form spheroids. The miRNome analysis revealed that long-term IL-17 treatment of LPCs led to a 90% decrease in miR-122 expression. In a model using immunodeficient mice, ectopic engraftment of LPCs in an IL-17-enriched environment led to tumor occurrence with an aggressive phenotype. Contrastingly, in a murine model of hepatocellular carcinoma induced by a unique injection of diethyl-nitrosamine associated with chronic administration of carbon tetrachloride, IL-17-deficiency or anti-IL-17 therapy protected mice from liver tumor growth. In conclusion, we showed that a chronic exposure of LPCs to IL-17 cytokine promotes their transformation into CSCs. In addition, we demonstrated that IL-17-neutralizing strategies limit CSC occurrence and liver tumor progression through miR-122 restored-expression.     

Phenylpropanoids from Thapsia transtagana

Five phenylpropanoids have been isolated from the roots of Thapsia transtagana. Their structures have been elucidated by spectroscopic means.