Bloommcdermott2582

Cancer treatment represents an unmet challenge due to the development of drug resistance and severe side effects of chemotherapy. Artemisinin (ARS)-type compounds exhibit excellent antimalarial effects with few side effects and drug-resistance. ARS and its derivatives were also reported to act against various tumor types in vitro and in vivo, including acute leukemia. Therefore, ARS-type compounds may be exquisitely suitable for repurposing in leukemia treatment. To provide comprehensive clues of ARS and its derivatives for acute leukemia treatment, their molecular mechanisms are discussed in this review. Five monomeric molecules and 72 dimers, trimers and hybrids based on the ARS scaffold have been described against acute leukemia. The modes of action involve anti-angiogenic, anti-metastatic and growth inhibitory effects. These properties make ARS-type compounds as potential candidates for the treatment of acute leukemia. Still, more potent and target-selective ARS-type compounds need to be developed.The ecdysone, 20-hydroxyecdysone (20E) and ecdysone receptor (EcR), are regarded as the key regulators of development, metamorphosis, and growth in arthropods. In the present study, the role of 20E and EsEcR in regulating the expression of antimicrobial peptides (AMPs) was investigated in Chinese mitten crab, Eriocheir sinensis. The concentration of 20E in plasma was significantly (p less then 0.05) up-regulated from 3 h to 12 h after lipopolysaccharide (LPS) stimulation. The mRNA expression level of EsEcR-4 in hemocytes was significantly (p less then 0.01) up-regulated from 6 h to 24 h after LPS stimulation, while no significant changes of EsEcR-2 and EsEcR-3 transcripts were observed. After 20E injection, EsEcR-4 expression level was significantly increased from 12 h to 48 h with the highest level at 24 h (4.34-fold compared to the control group, p less then 0.01), and the mRNA expression levels of AMPs (EsALF-2, EsLYZ and EsCrus) in hemocytes were significantly increased from 6 h to 24 h with the peas of E. sinensis by regulating the mRNA expression level and phosphorylation of Dorsal and JNK.The phenomena and mechanism of electrospray modes in nanoscale are investigated from experiments and molecular dynamics simulations. It is found that the ionic concentration plays a crucial role in determining the dripping or the jetting modes in a nanoscale electrospray system. Molecular dynamics simulations uncover that the two modes are caused by the competition between the electric field stress and surface tension, which is similar to the mechanism in a macroscale electrospray system. However, in a nanoscale electrospray system, the two competing forces of the electric field stress and surface tension are more sensitive to the ion distributions than that in a macroscale electrospray system, in which the applied voltage and pressure dominate. With the decrease of the nozzle diameter to nanoscale, the ions not only affect the local electric field stress, but also destroy the hydrogen bonds among water molecules, which lead to that the ion concentration becomes a dominant factor in determining the electrospray modes in nanoscale. The discovery provides a novel method to control nanoscale electrospray modes, which may find potential applications for mass spectrometry, film deposition, and electrohydrodynamic printing.Motivation The difficulty to find new drugs and bring them to the market has led to an increased interest to find new applications for known compounds. Biological samples from many disease contexts have been extensively profiled by transcriptomics, and, intuitively, this motivates to search for compounds with a reversing effect on the expression of characteristic disease genes. However, disease effects may be cell line-specific and also depend on other factors, such as genetics and environment. Transcription profile changes between healthy and diseased cells relate in complex ways to profile changes gathered from cell lines upon stimulation with a drug. Despite these differences, we expect that there will be some similarity in the gene regulatory networks at play in both situations. The challenge is to match transcriptomes for both diseases and drugs alike, even though the exact molecular pathology/pharmacogenomics may not be known. Results We substitute the challenge to match a drug effect to a disease effecetwork-based Cellular Signatures. All source code to re-analyze and extend the CMap data, the source code of heuristics, filters and their evaluation are available to propel the development of new methods for drug repurposing. Availability https//bitbucket.org/ibima/moldrugeffectsdb. Contact steffen.moeller@uni-rostock.de. Supplementary information Supplementary data are available at Briefings in Bioinformatics online.Cancer is a genetic disease that involves the gradual accumulation of mutations. Human tumours are genetically unstable. see more However, the current knowledge about the origins and implications of genomic instability in this disease is limited. Understanding the biology of cancer requires the use of animal models. Here, we review relevant studies addressing the implications of genomic instability in cancer by using the fruit fly, Drosophila melanogaster, as a model system. We discuss how this invertebrate has helped us to expand the current knowledge about the mechanisms involved in genomic instability and how this hallmark of cancer influences disease progression.Cytokine-induced killer (CIK) cells represent an exceptional T-cell population uniting a T cell and natural killer cell-like phenotype in their terminally differentiated CD3+ CD56+ subset, which features non-MHC-restricted tumor-killing activity. CIK cells have provided encouraging results in initial clinical studies and revealed synergistic antitumor effects when combined with standard therapeutic procedures. We established the international registry on CIK cells (IRCC) to collect and evaluate clinical trials for the treatment of cancer patients in 2010. Moreover, our registry set new standards on the reporting of results from clinical trials using CIK cells. In the present update, a total of 106 clinical trials including 10,225 patients were enrolled in IRCC, of which 4,889 patients in over 30 distinct tumor entities were treated with CIK cells alone or in combination with conventional or novel therapies. Significantly improved median progression-free survival and overall survival were shown in 27 trials, and 9 trials reported a significantly increased 5-year survival rate.