Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-enzymatic glycoxydation and lipoxidation of proteins continues to stimulate great interest in gerontology as both markers and promoters of aging. The first aim of the study was to determine the age-related changes in levels of Nepsilon-(carboxymethyl)lysine (CML) and 4-hydroxy-2-nonenal (HNE) present on proteins of the cardiovascular system of Fischer 344 rats and identify the particular polypeptides being modified. The second objective was to evaluate whether pharmacological administration of aminoguanidine (1g/L in the drinking water) could reverse protein glycoxidation and lipoxidation. CML content in serum, aorta, and heart proteins from 28-month-old rats was double of that found in 4-month-old animals. AG administration to old rats for 3 months from the age of 25 months lowered CML content by 15 (P=.2275), 44 (P<.0001), and 28% (P=.0072) in serum, aorta, and heart, respectively. Serum albumin, transferrin and immunoglobulins were most prominently adducted by both CML and HNE. While the extent of albumin and transferrin modification was comparable between age groups, CML and HNE bound to immunoglobulins increased in the sera of old rats as a result of the accumulation of immunoglobulin heavy and light chains. AG treatment prevented immunoglobulin accumulation in serum, suggesting a beneficial action on renal filtration. Lipoxidation of heart mitochondrial proteins was prevalent over glycoxidation, either as CML or pentosidine. Although AG prevented HNE-induced inactivation of the alpha-ketoglutarate dehydrogenase complex in vitro, it had no effect in rat hearts, suggesting AG could not reach the mitochondrial matrix.
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PMID:Reversal by aminoguanidine of the age-related increase in glycoxidation and lipoxidation in the cardiovascular system of Fischer 344 rats. 1558 11

Foods are complex mixtures of macro- and micronutrients, which interact, leading to oxidation, glycation, and hydrolysis upon heating (e.g., sterilization, cooking) and storage. Their nutritional quality and safety are consequently affected, justifying the need for accurate monitoring of the evolution of the food composition during processing and shelf life. Classical chromatographic analysis as well as newly proposed rapid methods based on fluorescence spectrometry analyses were applied on whey powder-based models and commercial samples (in powdered form and ultrahigh temperature [UHT] sterilized), some of which had been previously submitted to protein hydrolysis. These samples were incubated for 48 h at 60 degrees C to mimic accelerated storage. Fluorescence fingerprints addressing modifications in the product composition during processing were recorded and analyzed by chemometric methods. Carboxymethyllysine (Nepsilon-[carboxymethyl]lysine; CML) was measured using an ELISA method. Fluorescence, recorded in a front-face mode on intact samples, is very sensitive to pertinent physicochemical changes induced by heat treatment, formulation (the moisture level in powders, presence of vitamin C and iron), and storage. Similar trends were observed between powders' fluorescence and CML-for example, a strong effect of protein hydrolysis and increasing water content. Addition of vitamin C was associated with an antioxidant effect despite the presence of iron. Good calibration models were obtained for predicting CML from fluorescence spectra both in food models and in commercial samples, although more work is needed to obtain accurate and robust calibration models. Results show the potential of nondestructively applied fluorescence spectrometry for measuring CML in formulas, a rapid, simple, and cost-effective method to monitor formula quality.
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PMID:Evaluation of the maillard reaction in infant formulas by means of front-face fluorescence. 1603 53

Dihydroartemisinin (DHA), a more water-soluble active metabolite of artemisinin derivatives, is safe and the most effective antimalarial analog of artemisinin. In the present investigation, we assessed the effect of DHA on vascular endothelial growth factor (VEGF) expression and apoptosis in chronic myeloid leukemia (CML) K562 cells. The results demonstrated that in addition to its antiproliferation effect on CML cells, DHA was also found to induce K562 cells apoptosis. The percentage of apoptotic cells was increased to 6.9 and 15.8% after being treated with 5 and 10 micromol/l DHA for 48 h, respectively (P<0.001). In order to analyze the effect of DHA on VEGF expression in K562 cells, we assessed the level of VEGF expression by western blot; detected the form of VEGF mRNA by RT-PCR and examined the level of VEGF secreted in conditioned media (CM) by ELISA assay. All these experiments suggested that DHA could inhibit the VEGF expression and secretion effectively in K562 cells, even at a lower concentration (2 micromol/l, P<0.05). Moreover, we further assessed the stimulating angiogenic activity of CM from K562 cells on CAM model. The angiogenic activity was decreased in response to the CM from K562 cells pretreated with DHA in a dose-dependent manner. Taken together, these results from our study together with its known low toxicity make it possible that DHA might present potential antileukemia effect as a treatment for CML therapy, or as an adjunct to standard chemotherapeutic regimens.
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PMID:Dihydroartemisinin downregulates vascular endothelial growth factor expression and induces apoptosis in chronic myeloid leukemia K562 cells. 1607 80

The authors conducted a population-based case-control study of 1,068 incident leukemia cases and 5,039 controls aged 20-74 years during 1994-1997 to examine the association between exposure to drinking water chlorination disinfection by-products and adult leukemia risk in Canada. Residence and drinking water source histories and data from municipal water supplies were used to estimate individual chlorination disinfection by-product exposure according to water source, chlorination status, and chlorination disinfection by-product levels during the 40-year period before the interview. The analysis included 686 cases and 3,420 controls for whom water quality information was available for at least 30 of these years. Increased risk of chronic myeloid leukemia was associated with increasing years of exposure to different chlorination disinfection by-product indexes, with an adjusted odds ratio of 1.72 (95% confidence interval: 1.01, 3.08) for the highest exposure duration to total trihalomethanes of more than 40 microg/liter. In contrast, the risk of the other studied leukemia subtypes was found to decrease with increasing years of exposure to chlorination disinfection by-products. A protective effect was noted for chronic lymphoid leukemia (odds ratio = 0.60, 95 percent confidence interval: 0.41, 0.87) associated with the highest exposure duration to total trihalomethanes of more than 40 microg/liter. More studies with long-term exposure measures and large enough to evaluate leukemia subtypes are needed to further understanding of the issue.
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PMID:Chlorination disinfection by-products in drinking water and the risk of adult leukemia in Canada. 1631 93

Positron emission tomography (PET) with epidermal growth factor receptor (EGFR) kinase-specific radiolabeled tracers could provide the means for noninvasive and repetitive imaging of heterogeneity of EGFR expression and signaling activity in tumors in individual patients before and during therapy with EGFR signaling inhibitors. We developed the synthesis and (124)I-radiolabeling of the (E)-But-2-enedioic acid [4-(3-[(124)I]iodoanilino)-quinazolin-6-yl]-amide-(3-morpholin-4-yl-propyl)-amide (morpholino-[(124)I]-IPQA), which selectively, irreversibly, and covalently binds the adenosine-triphosphate-binding site to the activated (phosphorylated) EGFR kinase, but not to the inactive EGFR kinase. The latter was demonstrated using in silico modeling with crystal structures of the wild type and different gain-of-function mutants of EGFR kinases. Also, this was demonstrated by selective radiolabeling of the EGFR kinase domain with morpholino-[(131)I]-IPQA in A431 human epidermoid carcinoma cells and Western blot autoradiography. In vitro radiotracer accumulation and washout studies demonstrated a rapid accumulation and progressive retention postwashout of morpholino-[(131)I]-IPQA in A431 epidermoid carcinoma and in U87 human glioma cells genetically modified to express the EGFRvIII mutant receptor, but not in the wild-type U87MG glioma cells under serum-starved conditions. Using morpholino-[(124)I]-IPQA, we obtained noninvasive PET images of EGFR activity in A431 subcutaneous tumor xenografts, but not in subcutaneous tumor xenografts grown from K562 human chronic myeloid leukemia cells in immunocompromised rats and mice. Based on these observations, we suggest that PET imaging with morpholino-[(124)I]-IPQA should allow for identification of tumors with high EGFR kinase signaling activity, including brain tumors expressing EGFRvIII mutants and nonsmall-cell lung cancer expressing gain-of-function EGFR kinase mutants. Because of significant hepatobiliary clearance and intestinal reuptake of the morpholino-[(124)I]-IPQA, additional [(124)I]-IPQA derivatives with improved water solubility may be required to optimize the pharmacokinetics of this class of molecular imaging agents.
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PMID:Molecular imaging of EGFR kinase activity in tumors with 124I-labeled small molecular tracer and positron emission tomography. 1689 20

This study was purposed to investigate the effect of different heat stress conditions on expression level of heat shock protein gp96 in K562 cell line of chronic myeloid leukemia in order to provide experiment basis for seeking optimal heat stress condition increasing extraction amount of gp96 from K562 cells. The expression changes of gp96 in K562 cell line was detected by immunocytochemistry under 38, 40, 42, 44, 46 and 48 degrees C for 30 minutes in water, by flow cytometry under 40, 44, 48 and 52 degrees C for 30 minutes in water, by Western blot under 40, 44, 48 and 52 degrees C for 30 minutes in water. Immunocytochemistry assay showed that gp96 existed mainly in cytoplasm. The peak of gp96 expression was at 30 minutes after 48 degrees C in water. The result of flow cytometry was consistent to immunocytochemistry detection results under temperatures 40, 44, 48 and 52 degrees C (P < 0.01). Western blot showed that detection result was the same as the immunocytochemistry and flow cytometry detections. In conclusion, the expression of gp96 in K562 cell line reached peak at 30 minutes after 48 degrees C in water. This condition may be an effective preparative condition for extraction of gp96 from K562 cells.
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PMID:[Effect of heat stress on expression of gp96 in K562 cell line of the chronic myeloid leukemia and its significance]. 1692 96

In vitro degradation and chondrocyte-encapsulation of chitosan hydrogel made of crosslinkable and water-soluble chitosan derivative (CML) at neutral pH and body temperature were studied with respect to weight loss, cytoviability, DNA content and cell morphology. In vitro degradation of the chitosan hydrogels was sensitive to their crosslinking degree and existence of lysozyme in the solution. Chitosan hydrogel (Gel-I5) fabricated from 1% CML and 5mM ammonium persulfate (APS)/N,N,N',N'-tetramethylethylenediamine (TMEDA) displayed no degradation in phosphate buffered saline (PBS) after 18d, but degraded completely at 8d in 1mg/ml lysozyme/PBS. The chitosan hydrogel fabricated from 10mM APS/TMEDA was non-degradable even in lysozyme/PBS solution after 18d. The hydrogel loaded with chondrocytes in cell culture medium, however, was susceptible to degradation during the in vitro culture. In vitro culture of the encapsulated chondrocytes in the chitosan hydrogel demonstrated that the cells retained round shaped morphology and could survive through a 12d-culture period, although the DNA assay detected an overall reduction of the cell number. These features provide a great opportunity to use the chitosan hydrogel as an injectable scaffold in tissue engineering and orthopaedics.
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PMID:Covalently crosslinked chitosan hydrogel: properties of in vitro degradation and chondrocyte encapsulation. 1695

Advanced glycation end products (AGEs) from the Maillard reaction contribute to the pathogenesis of diabetes-associated complications such as diabetic nephropathy. In therapeutic interventions for reducing AGEs, many compounds have been reported as AGE inhibitors. The objective of the present study was to examine the effect of pyridoxamine (K-163), an AGE inhibitor, in type 2 diabetic KK-A(y)/Ta mice. KK-A(y)/Ta mice were given pyridoxamine (200 or 400 mg/kg per day) starting at 8 weeks of age for 12 weeks. They were divided into 3 groups as follows: pyridoxamine 200 mg/kg per day treatment group (n = 10), pyridoxamine 400 mg/kg per day treatment group (n = 10), and a tap water group as the control group (n = 20). The urinary albumin/creatinine ratio (ACR), body weight (BW), levels of fasting and casual blood glucose, blood glycated hemoglobin (HbA(1c)), fasting serum insulin, triglyceride (TG), total cholesterol (T-Cho), and 3-deoxyglucosone (3DG), and systemic blood pressure were measured as biochemical parameters. N(epsilon)-(Carboxymethyl)lysine (CML) and nitrotyrosine accumulations in glomeruli were evaluated by immunohistochemical analyses. Transforming growth factor beta1 (TGF-beta1) and laminin-beta1 messenger RNA expressions in the kidneys were evaluated by real-time polymerase chain reaction. Pyridoxamine, especially at 400 mg/kg per day, improved the levels of urinary ACR, fasting serum TG, and 3DG. CML and nitrotyrosine accumulations in glomeruli were decreased. Furthermore, large doses of pyridoxamine prevented not only urinary ACR but also increases of BW, casual blood glucose, and HbA(1c). TGF-beta1 and laminin-beta1 messenger RNA expressions in kidneys were significantly lower than those in the controls. There were no significant changes in the levels of fasting blood glucose, serum T-Cho, and systemic blood pressure among all groups. It appears that pyridoxamine improved urinary ACR by its anti-AGE and anti-oxidant effects in the kidneys of KK-A(y)/Ta mice.
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PMID:Effect of pyridoxamine (K-163), an inhibitor of advanced glycation end products, on type 2 diabetic nephropathy in KK-A(y)/Ta mice. 1722 27

This paper presents the life cycle impact assessment (LCIA) of four treatment technologies currently under investigation for recycling the greywater generated from households and describes the development of a new LCIA tool set produced in this study. The technologies investigated include reed beds, membrane bioreactors (MBR); membrane chemical reactors (MCR) and an innovative green roof water recycling system (GROW). The materials and energy required for the construction and operation phases of these technologies have been quantified for 20 development scales. All of the information gathered is used to prepare life cycle inventories for each technology. The inventories have been used as an input to Simapro Software for performing LCIA. Two assessment methods (CML-2 and Eco-indc-99) have been employed. For the CML method, the results were processed to express the environmental performance in ten impact categories including climate change/global warming, depletion of abiotic resources, acidification, eutrophication, and human toxicity. For the Eco-indc-99 method, results are shown in three generic environmental indicators: human health, eco system and natural resources. LCIA results obtained for 20 development scales have been used to develop a tool set using adaptive neuro-fuzzy inference system technique. The study results indicate that the technologies based on natural treatment processes (GROW and reed beds) have low environmental impact.
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PMID:Life cycle impact assessment of greywater recycling technologies for new developments. 1724 74

Betalains are water-soluble nitrogenous vacuolar pigments present in flowers and fruits of many caryophyllales with potent antioxidant properties. In the present study the antiproliferative effects of betanin, a principle betacyanin pigment, isolated from the fruits of Opuntia ficus-indica, was evaluated on human chronic myeloid leukemia cell line (K562). The results show dose and time dependent decrease in the proliferation of K562 cells treated with betanin with an IC(50) of 40 microM. Further studies involving scanning and transmission electron microscopy revealed the apoptotic characteristics such as chromatin condensation, cell shrinkage and membrane blebbing. Agarose electrophoresis of genomic DNA of cells treated with betanin showed fragmentation pattern typical for apoptotic cells. Flow cytometric analysis of cells treated with 40 microM betanin showed 28.4% of cells in sub G0/G1 phase. Betanin treatment to the cells also induced the release of cytochrome c into the cytosol, poly (ADP) ribose polymerase (PARP) cleavage, down regulation Bcl-2, and reduction in the membrane potentials. Confocal microscopic studies on the cells treated with betanin suggest the entry of betanin into the cells. These studies thus demonstrate that betanin induces apoptosis in K562 cells through the intrinsic pathway and is mediated by the release of cytochrome c from mitochondria into the cytosol, and PARP cleavage. The antiproliferative effects of betanin add further value to the nutritional characteristics of the fruits of O. ficus-indica.
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PMID:Betanin a betacyanin pigment purified from fruits of Opuntia ficus-indica induces apoptosis in human chronic myeloid leukemia Cell line-K562. 1748 44


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