Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

EGF receptors are expressed on most fetal and adult cells but their precise roles are not well known. We previously reported that, in P19 embryonal carcinoma cells, the expression of kinase-negative EGFR inhibits retinoic acid (RA)-induced differentiation to nervous tissue, suggesting that EGFR plays a role in differentiation (J.-X. Wu and E. D. Adamson (1993) Dev. Biol. 159, 208-222). Embryo stem (ES) cells differentiate into a wide range of tissue types after the removal of the cytokine LIF from the culture medium. We demonstrate here that the induction of some early markers of differentiation, tissue-type plasminogen activator (tPA), AFP and keratins 8 and 19 is inhibited, whilst brachyury and myosin are increased, in clones containing kinase-negative mutant EGFR. After an extended period of differentiation, the cell types present in mutant and control cultures differed. Mutant clones produced frequent cardiac and skeletal muscle as the predominant differentiated cell types in vitro; other cells types were sparse or absent. Teratocarcinomas formed by EGFR-deltakinase-expressing ES cells contained frequent skeletal and cardiac muscle as well as apoptotic nuclei, while normal ES cells produced no detectable muscle and less apoptoses. Since mutant differentiated cultures had slower growth rates and increased levels of cell death, we concluded that: (1) inactive EGFR does not allow some cell types to survive and/or proliferate; (2) tissues that do not require EGFR for their survival, development or function predominate in long-term mutant cultures; (3) EGFR activity is not necessary for cardiac and skeletal muscle or endoderm formation and (4) Impaired survival of EGF-dependent lineages leads to preferential selection of muscle in differentiating ES cells.
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PMID:Kinase-negative mutant epidermal growth factor receptor (EGFR) expression during embryonal stem cell differentiation favours EGFR-independent lineages. 889 44

Amphiphilic block copolymers based on PEO-PPO-PEO block copolymer (Pluronic) and poly(epsilon-caprolactone) were synthesized by bulk polymerization. The structural analysis of Pluronic/PCL block copolymer was carried out using FT-IR, 1H NMR, GPC, WAXD, DSC and TGA measurements. To prepare copolymeric nanospheres with a micellar structure, Pluronic/PCL amphiphilic block copolymers were dialyzed against water. The size and size distribution of Pluronic/PCL block copolymeric nanospheres were examined by dynamic light scattering measurement. They showed an average diameter of 116 to 196 nm depending on the type of copolymer. All the nanosphere samples exhibited a narrow size distribution. The critical micelle concentrations of Pluronic/PCL amphiphilic block copolymers determined by fluorescence spectroscopy were lower than that of common low molecular weight surfactants. We confirmed the formation of stable copolymeric nanospheres through the solution behavior of amphiphilic block copolymer in selective solvents.
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PMID:Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (Pluronic)/poly(epsilon-caprolactone) (PCL) amphiphilic block copolymeric nanospheres. I. Preparation and characterization. 1052 75

A new insertion sequence (IS) element, IS679 (2,704 bp in length), has been identified in plasmid pB171 of enteropathogenic Escherichia coli B171. IS679 has imperfect 25-bp terminal inverted repeats (IRs) and three open reading frames (ORFs) (here called tnpA, tnpB, and tnpC). A plasmid carrying a composite transposon (Tn679) with the kanamycin resistance gene flanked by an intact IS679 sequence and an IS679 fragment with only IRR (IR on the right) was constructed to clarify the transposition activity of IS679. A transposition assay done with a mating system showed that Tn679 could transpose at a high frequency to the F plasmid derivative used as the target. On transposition, Tn679 duplicated an 8-bp sequence at the target site. Tn679 derivatives with a deletion in each ORF of IS679 did not transpose, finding indicative that all three IS679 ORFs are essential for transposition. The tnpA and tnpC products appear to have the amino acid sequence motif characteristic of most transposases. A homology search of the databases found that a total of 25 elements homologous to IS679 are present in Agrobacterium, Escherichia, Rhizobium, Pseudomonas, and Vibrio spp., providing evidence that the elements are widespread in gram-negative bacteria. We found that these elements belong to the IS66 family, as do other elements, including nine not previously reported. Almost all of the elements have IRs similar to those in IS679 and, like IS679, most appear to have duplicated an 8-bp sequence at the target site on transposition. These elements have three ORFs corresponding to those in IS679, but many have a mutation(s) in an ORF(s). In almost all of the elements, tnpB is located in the -1 frame relative to tnpA, such that the initiation codon of tnpB overlaps the TGA termination codon of tnpA. In contrast, tnpC, separated from tnpB by a space of ca. 20 bp, is located in any one of three frames relative to tnpB. No common structural features were found around the intergenic regions, indicating that the three ORFs are expressed by translational coupling but not by translational frameshifting.
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PMID:Structural and functional characterization of IS679 and IS66-family elements. 1141 71

A star polymer composed of amphiphilic block copolymer arms has been synthesized and characterized. The core of the star polymer is polyamidoamine (PAMAM) dendrimer, the inner block in the arm is lipophilic poly(epsilon-caprolactone) (PCL), and the outer block in the arm is hydrophilic poly(ethylene glycol) (PEG). The star-PCL polymer was synthesized first by ring-opening polymerization of epsilon-caprolactone with a PAMAM-OH dendrimer as initiator. The PEG polymer was then attached to the PCL terminus by an ester-forming reaction. Characterization with SEC, (1)H NMR, FTIR, TGA, and DSC confirmed the star structure of the polymers. The micelle formation of the star copolymer (star-PCL-PEG) was studied by fluorescence spectroscopy. Hydrophobic dyes and drugs can be encapsulated in the micelles. A loading capacity of up to 22% (w/w) was achieved with etoposide, a hydrophobic anticancer drug. A cytotoxicity assay demonstrated that the star-PCL-PEG copolymer is nontoxic in cell culture. This type of block copolymer can be used as a drug delivery carrier.
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PMID:Synthesis and evaluation of a star amphiphilic block copolymer from poly(epsilon-caprolactone) and poly(ethylene glycol) as a potential drug delivery carrier. 1576 95

Chitosan-modified biodegradable hydrogels were prepared by UV irradiation of solutions in mild aqueous acidic media of poly(caprolactone)-co-poly(ethylene glycol)-co-poly(caprolactone) diacrylate (PCL-PEG-PCL-DA) and chitosan. Hydrogels obtained were characterized using FT-IR, DSC, TGA and XPS. FT-IR, TGA and DSC revealed the semi-interpenetrating polymer network structure formed in the hydrogel. Though the water swelling degree of these chitosan-modified hydrogels was substantial in the range of 322-539%, it was found that fibroblasts could still attach, spread and grow on them; this is in contrast to the commonly investigated PEG-diacrylate hydrogel. The MTT assay demonstrated that cells could grow better on 3 or 6% chitosan-modified hydrogel than unmodified PCL-PEG-PCL-DA hydrogels or low-content (1%) chitosan-modified PCL-PEG-PCL-DA hydrogel. Increased chitosan content resulted in increased cell interaction and also decreased water swelling, both of which results in increased cell attachment and spread.
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PMID:Cell viability of chitosan-containing semi-interpenetrated hydrogels based on PCL-PEG-PCL diacrylate macromer. 1585 Feb 86

Cell-tracing studies in the mouse indicate that the cardiac lineage arises from a population that expresses the vascular endothelial growth factor receptor 2 (VEGFR2, Flk-1), suggesting that it may develop from a progenitor with vascular potential. Using the embryonic stem (ES) cell differentiation model, we have identified a cardiovascular progenitor based on the temporal expression of the primitive streak (PS) marker brachyury and Flk-1. Comparable progenitors could also be isolated from head-fold stage embryos. When cultured with cytokines known to function during cardiogenesis, individual cardiovascular progenitors generated colonies that displayed cardiomyocyte, endothelial, and vascular smooth muscle (VSM) potential. Isolation and characterization of this previously unidentified population suggests that the mammalian cardiovascular system develops from multipotential progenitors.
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PMID:Multipotent flk-1+ cardiovascular progenitor cells give rise to the cardiomyocyte, endothelial, and vascular smooth muscle lineages. 1708 63

Thermo-responsive multiblock poly(ester urethane)s comprising poly(epsilon-caprolactone) (PCL), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments were synthesized. The copolymers were characterized by GPC, NMR, FTIR, XRD, DSC and TGA. Water-swelling analysis carried out at different temperatures revealed that the bulk hydrophilicity of the copolymers could be controlled either by adjusting the composition of the copolymer or by changing the temperature of the environment. These thermo-responsive copolymer films formed highly swollen hydrogel-like materials when soaked in cold water and shrank when soaked in warm water. The changes are reversible. The mechanical properties of the copolymer films were assessed by tensile strength measurement. These copolymers were ductile when compared to PCL homopolymers. Young's modulus and the stress at break increased with increasing PCL content, whereas the strain at break increased with increasing PEG content. The results of the cytotoxicity tests based on the ISO 10993-5 protocol demonstrated that the copolymers were non-cytotoxic and could be potentially used in biomedical applications.
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PMID:Synthesis and water-swelling of thermo-responsive poly(ester urethane)s containing poly(epsilon-caprolactone), poly(ethylene glycol) and poly(propylene glycol). 1845 19

The incidence of several extracolonic tumors, such as duodenal carcinoma, is higher in familial adenomatous polyposis (FAP) patients than in the general population, but there is little information about lung carcinoma in FAP. A 43-year-old woman presented with a lung tumor 17 years after total colectomy for FAP. Pathohistological analysis of the lung tumor demonstrated mixed adenocarcinoma consisting of a papillary adenocarcinoma component and a bronchioloalveolar carcinoma component. Sequencing analysis indicated a germline APC mutation from TCA to TGA (stop) at codon 1110, but no pathogenic germline MYH mutations. The other APC allele in the lung carcinoma was not inactivated by somatic mutations, promoter methylation, or chromosomal deletion. No somatic mutations in any of the coding regions of the p53 gene or in the mutation hot spot regions of the K-ras or EGFR genes were detected in the carcinoma. Amplification, however, of three chromosome regions, 5p, 8q, and 12q14-12q21, was identified in the carcinoma on genome-wide high-resolution single-nucleotide polymorphism (SNP) microarray. The present results suggest that the chromosomal copy number alterations detected on SNP microarray were involved in the carcinogenesis of the adenocarcinoma of the lung in the present FAP patient.
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PMID:Characterization of adenocarcinoma of the lung in a familial adenomatous polyposis patient. 1884 36

The Ras family small GTPases play a variety of essential roles in eukaryotes. Among them, classical Ras (H-Ras, K-Ras, and N-Ras) and its orthologues are conserved from yeast to human. In ascidians, which phylogenetically exist between invertebrates and vertebrates, the fibroblast growth factor (FGF)-Ras-MAP kinase signaling is required for the induction of neural system, notochord, and mesenchyme. Analyses of DNA databases revealed that no gene encoding classical Ras is present in the ascidians, Ciona intestinalis and Halocynthia roretzi, despite the presence of classical Ras-orthologous genes in nematode, fly, amphioxus, and fish. By contrast, both the ascidians contain single genes orthologous to Mras, Rras, Ral, Rap1, and Rap2. A single Mras orthologue exists from nematode to mammalian. Thus, Mras evolved in metazoans independently of other Ras family genes such as Rras. Whole-mount in situ hybridization showed that C. intestinalis Mras orthologue (Ci-Mras) was expressed in the neural complex of the ascidian juveniles after metamorphosis. Knockdown of Ci-Mras with morpholino antisense oligonucleotides in the embryos and larvae resulted in undeveloped tails and neuronal pigment cells, abrogation of the notochord marker brachyury expression, and perturbation of the neural marker Otx expression, as has been shown in the experiments of the FGF-Ras-MAP kinase signaling inhibition. Mammalian Ras and M-Ras mediate nerve growth factor-induced neuronal differentiation in rat PC12 cells by activating the ERK/MAP kinase pathway transiently and sustainedly, respectively. Activated Ci-M-Ras bound to target proteins of mammalian M-Ras and Ras. Exogenous expression of an activated Ci-M-Ras in PC12 cells caused ERK activation and induced neuritogenesis via the ERK pathway as do mammalian M-Ras and Ras. These results suggest that the ascidian M-Ras orthologue compensates for lacked classical Ras and plays essential roles in neurogenesis in the ascidian.
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PMID:M-Ras evolved independently of R-Ras and its neural function is conserved between mammalian and ascidian, which lacks classical Ras. 1897 83

In the present study, we have aimed to produce nanoparticles (NPs) possessing the capability of carrying both of the hydrophobic and hydrophilic drugs and reveal significant release for both drug types. Poly(epsilon-caprolactone) (PCL) grafted poly(vinyl alcohol) (PVA) copolymer (PCL-g-PVA) has been prepared and shaped in nano-particulate form to be adequate for carrying the drugs. Stannous octoate (Sn(II)Oct(2)) was used to catalyze PVA and epsilon-caprolactone monomer to chemically bond. Moreover, this catalyst enhanced side chain polymerization reaction for the utilized epsilon-caprolactone monomer to form poly(epsilon-caprolactone) (PCL). The formed PCL was attached as branches with PVA backbone. (1)H NMR has confirmed formation of PCL and grafting of PVA by this new polymer. Moreover, the vibration modes in the functional groups of PCL-g-PVA have been detected by FT-IR. The thermal alteration in the grafted polymer was checked by TGA analysis. The successfully synthesized grafted copolymer was able to self-aggregate into NPs by direct dialysis method. The size, morphology and charges associated with the obtained NPs were analyzed by DLS, TEM and ELS, respectively. PCL-g-PVA NPs were investigated as drug carrier models for hydrophobic and hydrophilic anti cancer drugs; paclitaxel and doxorubicin. In vitro drug release experiments were conducted; the loaded NPs reveal continuous and sustained release form for both drugs, up to 20 and 15 days for paclitaxel and doxorubicin, respectively. However, in a case of using pure drugs only, both drugs completely released within 1-2 h. The overall obtained results strongly recommend the use these novel NPs in future drug delivery systems.
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PMID:Novel self-assembled amphiphilic poly(epsilon-caprolactone)-grafted-poly(vinyl alcohol) nanoparticles: hydrophobic and hydrophilic drugs carrier nanoparticles. 1902 Sep 53


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