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Poly(butylene succinate) (PBS)/organoclay nanocomposites were prepared by both solution blending and melt mixing methods. In addition, nanocomposites of PBS/organoclay were also prepared by a two-step process where the solution blended mixture is subsequently compounded in the melt state using a torque rheometer (SOAM method). We then investigated thermal and mechanical properties of the PBS/organoclay nanocomposite at first and determined an optimum organoclay content for the preparation of nanocomposite foams. All PBS/organoclay nanocomposite foams are found to possess closed spherical-shaped cells without any rupture when examined by an optical microscopy. The blowing ratio also increased with the increase in the blowing temperature and time, with the maximum blowing ratio of 19. Furthermore, the addition of a small amount of organoclay is found to allow the cell size to follow Gaussian distribution. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

The four overlapping cosmids from the rubradirin producer , Streptomyces achromogenes var rubradiris NRRL 3061, have 58 ORFs within a 105.6 kb fragment. These ORFs harbored essential genes responsible for the formation and attachment of four distinct moieties, along with the genes associated with regulatory, resistance, and transport functions. The PKS ( rubA) and glycosyltransferase ( rubG2) genes were disrupted in order to demonstrate a complete elimination of rubradirin production. The rubradirin biosynthetic pathway was proposed based on the putative functions of the gene products, the functional identification of sugar genes, and the mutant strains. [ABSTRACT FROM AUTHOR]

A new anthracycline ID6105 (11-hydroxyaclacinomycin X, Hyrubicin), which has potent antitumor activities against a broad range of cancer cell lines, was produced by hybrid biosynthetic approach. We investigated ID6105-induced apoptosis and in vivo efficacy on experimental tumors, and also defined its optimal dosing schedule. From PARP cleavage assay and caspase-3 activation assay, we found that ID6105 can induce apoptosis in tumor cells and its ability was superior to doxorubicin. In human tumor xenograft models, ID6105 showed greater antitumor effects on SW620 and NCI-H23 than doxorubicin. The 1 mg/kg of ID6105 treatment reduced size of tumor by 93% in NCI-H23 model whereas doxorubicin (2 mg/kg) showed only 39% inhibition rate. In SW620 model, 0.3 mg/kg of ID6105 proved to be comparable to 2 mg/kg of doxorubicin. Testing with several dosing schedule such as qd10, qd5, and q4d3, we decided intravenous qd5 treatment was an optimal schedule as a dose regimen of ID6105. In conclusion, ID6105 is a potent apoptosis-inducing anthracycline and effective in treatment of tumors with qd5 dosing schedule. [ABSTRACT FROM AUTHOR]

Hybrid biosynthetic approach produced a new anthracycline ID6105 (11-hydroxyaclacinomycin X, Hyrubicin), which has potent antitumor activities against a broad range of cancer cell lines. Like other anthracyclines, ID6105 has the inhibitory effects on DNA synthesis as well as topoisomerase II. As preclinical studies of ID6105, we investigated ID6105’s efficacy on human tumors, and cardiotoxicity. In human tumor xenografts, the ID6105’s antitumor effects were greater than other anticancer drugs. ID6105 induced tumor regression in Hep G2 human hepatoma model, and slowed down the tumor growth rates in several tumor models. Doxorubicin-refractory tumors such as PC-3, DU-145, and CX-1 were sensitive to ID6105, and the growth of EKVX, lung cancer, which did not respond to paclitaxel, was also inhibited by ID6105, but tumor mass in CFPA, MCF7, and HCT-15 was not reduced by ID6105. The cardiotoxicity of ID6105 has also been assessed in rats. ID6105 did not induce any remarkable histopathological changes in hearts, and its lipid peroxidation in rat cardiac muscles did not occur as much as doxorubicin, indicating that the cardiotoxicity of ID6105 is remarkably lower than that of doxorubicin. Taking all into account, our results suggest that ID6105 would be a promising candidate for a novel anthracycline chemotherapeutic agent. [ABSTRACT FROM AUTHOR]

An open reading frame, rub52, has been identified as a gene encoding thymidine diphospho-glucose 2,3-dehydratase by sequence analysis of the rubradirin biosynthetic gene cluster of Streptomyces achromogenes var. rubradiris NRRL3061.The gene codes for a protein consisting of 458 amino acids with calculated molecular mass of 50 862 Da. The gene was amplified and heterologously expressed in Escherichia coli as a soluble His-tagged fusion protein. C-2 deoxygenation functionality of thymidine diphospho-4-keto-6-deoxyglucose was assigned to the rub52 gene product from in vitro enzyme assay. [ABSTRACT FROM AUTHOR]

Presents a study that examined the overexpression of syntenin protein in metastatic human breast and gastric cancer cell lines. List of human breast cancer cell lines; Causes of human cancer deaths; Methods for comparing patterns of gene expression; Components of syntenin.

Macrophage inhibitory cytokine-1 (MIC-1) is a member of the transforming growth factor-β superfamily, which is overexpressed in a variety of human cancers, including breast and gastric cancer. The function of MIC-1 in cancer remains controversial and its signaling pathways remain poorly understood. In this study, we demonstrate that MIC-1 induces the transactivation of ErbB2 in SK-BR-3 breast and SNU-216 gastric cancer cells. MIC-1 induced a significant phosphorylation of Akt and ERK-1/2, and also effected an increase in the levels of tyrosine phosphorylation of ErbB1, ErbB2 and ErbB3 in SK-BR-3 and SNU-216 cells. The treatment of these cells with AG825 and AG1478, inhibitors specific for ErbB2 tyrosine kinase, resulted in the complete abolition of MIC-1-induced Akt and ERK-1/2 phosphorylation. Furthermore, the small-interfering RNA-mediated downregulation of ErbB2 significantly reduced not only the phosphorylation of Akt and ERK-1/2 but also the invasiveness of the cells induced by MIC-1. Our results show that ErbB2 activation performs a crucial function in MIC-1-induced signaling pathways. Further investigations revealed that MIC-1 induced the expression of the hypoxia inducible factor-1α protein and the expression of its target genes, including vascular endothelial growth factor, via the activation of the mammalian target of rapamycin (mTOR) signaling pathway. Stimulation of SK-BR-3 with MIC-1 profoundly induces the phosphorylation of mTOR and its downstream substrates, including p70S6K and 4E-BP1. Collectively, these results show that MIC-1 may participate in the malignant progression of certain human cancer cells that overexpress ErbB2 through the transactivation of ErbB2 tyrosine kinase. [ABSTRACT FROM AUTHOR]

Rubradirin, an ansamycin antibiotic has been purified from Streptomyces achromogenes var. rubradiris NRRL3061. It consists of four distinct structural moieties, rubransarol, 3- amino-4-hydroxy-coumarin, dihydroxydipicolinic acid, and 2,6-dideoxynitrosugar (DNS). Polymerase chain reaction (peR) primers were designed based on consensus sequences of dTDP-D-glucose 4,6-dehydratase, one of enzymes involved in the biosynthesis of 2,6-dideoxysugar. A peR product was obtained from S. achromogenes var. rubradiris. Hybridization of the peR product to a cosmid library constructed from S. achromogenes genomic DNA has led to the identification of three unlinked regions of DNA. One of three kinds of cosmid clones contains homologues of dTDP-D-glucose 4,6-dehydratase, 3-amino- 5-hydroxybenzoic acid (AHBA) synthase, and eryA genes. The size of the gene homologous to eryA is 30 kb, and the AHBA synthase gene homologue resides between the eryA homologous genes. A gene cluster of rubransarol and 2,6-dideoxynitrosugar is around 50 kb. Sequencing of the peR product from the AHBA synthase gene homologue isolated from S. achromogenes revealed 85 % amino acid sequence homology (73/86) with the AHBA synthase from a rifamycin-producer. dTDP-D-glucose 4,6-dehydratase gene homologue was sub cloned from one of the isolated cosmid clones and sequenced. It showed 65 % homology (43/66) with dTDP-D-glucose 4,6-dehydratase from a streptomycin-producer. [ABSTRACT FROM AUTHOR]