Phase II Clinical Trial With Pegylated Liposomal Doxorubicin (CAELYX®/Doxil®) and Quality of Life Evaluation (EORTC QLQ-C30) in Adult Patients With Advanced Soft Tissue Sarcomas: A study of the Spanish Group for Research in Sarcomas (GEIS)

Background: Pegylated liposomal doxorubicin (PLD), a formulation with pharmacokinetic differences with respect to doxorubicin (DXR), might benefit patients with advanced soft tissue sarcoma (STS) pretreated with DXR

Wetland buffers are no substitute for landscape-scale conservation

Wetlands in farmland are at risk of contamination by fertilizers and pesticides. One recommendation for reducing wetland contamination is to maintain a buffer of contiguous uncropped land around the wetland (a wetland buffer). Many agricultural water protection policies around the world recommend 5 to 50-m wide uncropped buffers around water bodies, but it is unclear how large wetland buffers must be to effectively protect against these chemicals. In addition, it is unclear whether wetland buffers have similar—or stronger—effects on fertilizer and pesticide contamination than reducing the amount of cropped land within the larger landscape context around wetlands. Our study, conducted across 37 wetlands in eastern Ontario, Canada, addressed the following questions: (1) Does increasing buffer width, or increasing the amount of contiguous uncropped land within recommended buffer width guidelines, reduce nutrient and pesticide levels in agricultural wetlands? (2) Does increasing uncropped land cover in the broader landscape reduce nutrient and pesticide levels in agricultural wetlands? and (3) What is the relative importance of buffer size and landscape-scale uncropped cover for reducing nutrient and pesticide levels in agricultural wetlands? A rigorous site selection process was employed to minimize the correlation between buffer size and landscape-scale uncropped cover, minimize spatial gradients in these predictor variables, and minimize variation in potentially confounding variables. We obtained nutrient and pesticide data by collecting water samples from each wetland under similar weather conditions in June–July 2015. Nitrate concentrations were measured using ion chromatography, and atrazine and neonicotinoid (pesticide) concentrations using a combination of high-performance liquid chromatography and mass spectrometry. We found that nitrate, atrazine, and neonicotinoid concentrations in study wetlands were unaffected by wetland buffer size. However, concentrations of each chemical decreased with uncropped land cover in the surrounding 150 to 300-m radius landscapes. To effectively protect w

Liposomes in Biology and Medicine

Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS

Genetic locus (stmF) associated with cyclic GMP phosphodiesterase activity in Dictyostelium discoideum maps in linkage group II

Previous attempts to map the stmF locus in Dictyostelium discoideum, by using only clone morphology as a marker, have led to equivocal results. Since strains carrying mutations at the stmF locus possess very low cyclic GMP phosphodiesterase activity, we have remapped this locus using both morphological and biochemical markers. Our results indicate that mutations producing a stable "streamer" phenotype and reduced cyclic GMP phosphodiesterase activity are located in linkage group II, probably centromere distal to acrA.</jats:p

Relationship of the cGMP-binding activity to the cGMP-specific phosphodiesterase in <i>Dictyostelium discoideum</i>

Optimal conditions for assaying and stabilizing the soluble cGMP-binding activity in Dictyostelium discoideum were established. Using these procedures, we investigated the relationship between the cGMP-binding activity and the cGMP-specific phosphodiesterase in this organism. In wild-type strains, the binding and phosphodiesterase activities were found to be regulated differently during development. Also, stmF mutants, which possess very low levels of cGMP-specific phosphodiesterase activity, exhibited normal levels of cGMP-binding activity. Fractionation studies revealed that the binding and phosphodiesterase activities could be resolved by DEAE-cellulose chromatography. Finally, the effect of pH on cGMP binding was different from that reported for cGMP-mediated activation of the phosphodiesterase. Taken together, these results indicate that the cGMP-binding protein and the cGMP-specific phosphodiesterase are probably unrelated. In addition, the cGMP-binding activity is not associated with cGMP-stimulated kinase activity and it does not elute from DEAE-cellulose like the highly conserved cGMP-dependent protein kinases found in other systems. </jats:p

Influence of Chromosome Structure on the Frequency of <i>tonB trp</i> Deletions in <i>Escherichia coli</i>

The frequency of tonB trp deletions varies in different strains and substrains of Escherichia coli . Studies with chromosomal hybrids constructed by transducing various segments of the cysB-trp-suIII region from K-12(Ymel) into K-12(W3110) indicate that the characteristic low deletion frequency of K-12(Ymel) is determined largely by the (genetic) structure of the trp-suIII region of the chromosome. Transduction of the trp region from K-12(W3110) or K-12(Ymel) into strain B has little effect on the frequency of tonB trp deletions in that strain. When tonB trp deletions occur at 42 C rather than at 37 C, there is a significant reduction in the frequency of deletions in all strains examined except K-12(Ymel) and hybrids exhibiting a Ymel deletion pattern. The magnitude of this temperature effect in different K-12 strains increases proportionally with the frequency of tonB trp deletions at 37 C. At 42 C the frequency of tonB trp deletions in all K-12 strains approaches the low frequency observed for Ymel at 37 or 42 C. In contrast, spontaneous deletions in another region of the genome which simultaneously result in resistance to phages T7 and λ and in proline auxotrophy ( tfrA pro deletions) occur at a constant frequency regardless of growth temperature or the structure of the chromosome in the trp region. Two mutants of strain KB30 obtained after treatment with nitrosoguanidine show very low tonB trp deletion frequencies. The alterations in both mutants map in the trp region of the chromosome. These studies indicate that the structure of the cysB-trp-suIII region is responsible for many of the characteristic deletion frequencies observed. </jats:p