|
| ||
|
|
||
Cascade Pathway (cascade + pathway)
Selected AbstractsHomobimetallic Ruthenium Vinylidene, Allenylidene, and Indenylidene Complexes: Synthesis, Characterization, and Catalytic StudiesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 3 2009Xavier Sauvage Abstract Four homobimetallic ruthenium-(p -cymene) complexes bearing a tricyclohexylphosphine ligand and polyunsaturated carbon-rich fragments were obtained via a vinylidene-allenylidene-indenylidene cascade pathway from the ethylene complex [(p -cymene)Ru(,-Cl)3RuCl(PCy3)(,2 -C2H4)] (7a). All the products were isolated and fully characterized by IR and NMR spectroscopies. The molecular structure of the indenylidene complex 11 was determined by X-ray crystallographic analysis. The catalytic activity of the four complexes was probed in various types of olefin metathesis reactions and compared with those of a related homobimetallic ruthenium-benzylidene complex, as well as first, second, and third generation monometallic Grubbs catalysts. In the ring-closing metathesis (RCM) of diethyl diallylmalonate, the homobimetallic ruthenium-indenylidene complex 11 outperformed all the ruthenium-benzylidene complexes under investigation and was only slightly less efficient than its monometallic parent. Cross-metathesis experiments with ethylene showed that deactivation of ruthenium-benzylidene or indenylidene complexes was due to the rapid bimolecular decomposition of methylidene active species into ethylene complex 7a. Vinylidene and allenylidene complexes were far less efficient catalyst precursors for ring-opening metathesis polymerization (ROMP) or RCM and remained inert under an ethylene atmosphere. Their catalytic activity was, however, substantially enhanced upon addition of an acidic co-catalyst that most likely promoted their in situ transformation into indenylidene species. Due to its straightforward synthesis and high metathetical activity, homobimetallic ruthenium-indenylidene complex 11 is a valuable intermediate for the preparation of the Hoveyda,Grubbs catalyst [Cl2Ru(PCy3)(CH- o -O- i- PrC6H4)] via stoichiometric cross-metathesis with 2-isopropoxystyrene. The procedure did not require any sacrificial phosphine and the transition metal not incorporated into the final product was easily recovered and recycled at the end of the process. [source] Hibiscus polyphenol-rich extract induces apoptosis in human gastric carcinoma cells via p53 phosphorylation and p38 MAPK/FasL cascade pathwayMOLECULAR CARCINOGENESIS, Issue 2 2005Hui-Hsuan Lin Abstract In view of the continuing need for effective anticancer agents, and the association of diet with reduced cancer risk, edible plants are increasingly being considered as sources of anticancer drugs. Hibiscus sabdariffa Linne (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in the Sudan and Eastern Taiwan. Polyphenols had been demonstrated previously to possess antioxidative and antitumor promoting effects. In this study, investigations were conducted to examine the mechanism of the anticancer activity of H. sabdariffa L., Hibiscus polyphenol-rich extracts (HPE). Using HPLC assay, HPE was demonstrated to contain various polyphenols. HPE induced cell death of eight kinds of cell lines in a concentration-dependent manner. Among them human gastric carcinoma (AGS) cells were the most susceptible to HPE (0.95 mg/mL HPE inhibited its growth by 50%). Our results revealed that AGS cells underwent DNA fragmentation, and had an increase in the distribution of hypodiploid phase (apoptotic peak, 52.36%) after a 24-h treatment with HPE (2.0 mg/mL). This effect of HPE in AGS cells might be mediated via p53 signaling and p38 MAPK/FasL cascade pathway, as demonstrated by an increase in the phosphorylation of p53 and the usage of a specific p38 inhibitor, SB203580. Thus, our data present the first evidence of HPE as an apoptosis inducer in AGS cells and these findings may open interesting perspectives to the strategy in human gastric cancer treatment. © 2005 Wiley-Liss, Inc. [source] 16 Kallikrein 15 (KLK15) in prostate cancer: in silico analysis and single nucleotide polymorphism verificationBJU INTERNATIONAL, Issue 2006M.A. KEDDA Introduction:, Prostate cancer is the most common cancer in Caucasian men and there is strong evidence that kallikreins are part of an enzymatic cascade pathway activated in this disease. Altered KLK15 expression has been associated with cancer progression and grade and we postulate that single nucleotide polymorphisms (SNPs) in the KLK15 gene, will alter gene expression and will be associated with prostate cancer susceptibility and prognosis. Materials and Methods:, We have used in silico prediction of function of wildtype and variant promoter sequences through assessment of hormone receptor elements and transcription factor binding sites; as well as prediction of likely splice variants through genomic, splicing and EST databases and web sites, and multiple sequence alignment packages. We have also used PCR and sequence analysis to further characterise the promoter region of the gene. Results:,In silico analysis of the KLK15 gene has identified the following: two putative promoter regions, two putative androgen response elements (AREs) and four putative estrogen response elements (EREs); two clusters of cis elements; and 109 SNPs. Forty-seven SNPs alter transcription factor sites (22 gain sites), 20 gain/increase probability of an ERE and three alter nuclear hormone receptor binding sites. Three new EST clones have been identified by analysis of gene expression in CGAP databases and suggest a new KLK15 splice variant, with a different start site. Conclusion:, We have identified a number of new SNPs in the KLK15 gene, which may be functionally important and, in collaboration with the Queensland Cancer Fund (ProsCan Study), we will further investigate the association of these SNPs with prostate cancer risk and prognosis. [source] Neuron-specific phosphorylation of mitogen- and stress-activated protein kinase-1 involved in cerebral hypoxic preconditioning of miceJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2007Ping Huang Abstract Studies have demonstrated the involvement of mitogen-activated protein kinase (MAPK) cascade pathways in the development of cerebral ischemic/hypoxic preconditioning (I/HPC). However, the role of mitogen- and stress-activated protein kinase 1 (MSK1), an important downstream kinase of MAPK signaling pathways, in cerebral I/HPC is unclear. By using Western blot and immunostaining methods, we applied our unique "autohypoxia"-induced I/HPC mouse model to investigate the effects of repetitive hypoxic exposure (H0,H6, n = 6 for each group) on phosphorylation and protein expression levels of MSK1 in the brain of mice. We found that the levels of phosphorylation on threonine 645 (Thr645) and serine 375 (Ser375) of MSK1, but not the protein expression, increased significantly both in hippocampus and in cortex of mice from H1,H6 groups (P < 0.05) over that of the normoxic group (H0, n = 6). Similarly, enhanced phosphorylations on Thr645 and Ser375 of MSK1 were also observed by immunostaining in both the cortex and the hippocampus of mice following three series of hypoxic exposures (H3). In addition, we found by using double-immunofluorescence labeling that phosphorylated Thr645-MSK1 colocalized with a neuron-specific protein, neurogranin, in both cortex and hippocampus of I/HPC mice (H3). These results suggest that the increased neuron-specific phosphorylation of MSK1 on Thr645 and Ser375, not protein expression, might be involved in the development of cerebral I/HPC in mice. © 2007 Wiley-Liss, Inc. [source] | ||||||||||