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  • Biochemistry and Biotechnology  (8)
  • EXPRESSION  (3)
  • MUTATIONS  (2)
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  • 1
    Keywords: EXPRESSION ; SURVIVAL ; NETWORK ; NETWORKS ; GENE ; LINKAGE ; SUSCEPTIBILITY ; LYMPHOMA ; MALIGNANCIES ; genetics ; molecular ; FEATURES ; MALIGNANCY ; REGRESSION ; review ; FAMILIES ; CANDIDATE GENES ; CLL ; PREDISPOSITION ; leukaemia ; USA ; ENGLAND ; EXPANSION ; chronic lymphocytic leukaemia ; B-CELL LYMPHOCYTOSIS ; CHALLENGES ; family studies ; genetic association
    Abstract: Although the familial aspect of chronic lymphocytic leukaemia (CLL) has been appreciated for decades, it is only with the recent confluence of improved molecular and gene technologies and world-wide collaborative networks that accelerated progress has become apparent. In this summary we highlight selected themes in the genetics of CLL emphasizing the opportunities and challenges of this malignancy
    Type of Publication: Journal article published
    PubMed ID: 18021078
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  • 2
    Keywords: GROWTH ; CELL LUNG-CANCER ; PATHWAYS ; MUTATIONS ; sensitivity ; FUTURE ; THERAPIES
    Abstract: PURPOSE: Multiple investigational drugs are currently explored in cancer patient populations defined by specific biomarkers. This demands a new process of patient selection for clinical trials. PATIENTS AND METHODS: Starting January 1, 2012, preemptive biomarker profiling was offered at the West German Cancer Center to all patients with advanced non-small-cell lung (NSCLC) or colorectal cancer (CRC), who met generic study inclusion criteria. Tumour specimens were subjected to prespecified profiling algorithms to detect 'actionable biomarkers' by amplicon sequencing, in situ hybridisation and immunohistochemistry. The clinical course was closely monitored to offer trial participation whenever applicable. RESULTS: Within 12 months, 267 patients (188 NSCLC, 79 CRC) were profiled. Estimated additional cost for biomarker profiling was 219615.51 EUR excluding histopathology workup and administration. The most prevalent biomarkers in pulmonary adenocarcinoma were KRAS mutations (29%), loss of PTEN expression (18%), EGFR mutations (9%), HER2 amplification (5%) and BRAF mutations (3%), while the prevalence of ALK translocations and PIK3CA mutations was extremely low. In pulmonary squamous cell carcinoma FGFR1 amplifications were found in 15%, PTEN expression was lost in 20% and DDR2 was mutated in a single case. KRAS mutations (41%) predominated in CRC, followed by loss of PTEN expression (16%), PIK3CA (5%) and BRAF (5%) mutations. So far 13 patients (5%) have entered biomarker-stratified clinical trials. Therapeutic decisions for approved drugs were guided in another 45 patients (17%). CONCLUSION: Preemptive biomarker profiling can be implemented into the diagnostic algorithm of a large Comprehensive Cancer Center. Substantial investments in diagnostics and administration are required.
    Type of Publication: Journal article published
    PubMed ID: 23876834
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  • 3
    Keywords: EXPRESSION ; ACTIVATION ; mechanisms ; CELL-DEATH ; PROSTATE-CANCER ; MUTATIONS ; PET ; PHASE-II TRIAL ; IMATINIB MESYLATE ; 2-DEOXY-D-GLUCOSE
    Abstract: Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is frequently used for visualizing gastrointestinal stromal tumors (GIST), which are highly glucose-avid tumors. Dramatic metabolic responses following imatinib treatment indicate a high, KIT-dependent glucose turnover which has been particularly helpful for predicting tumor response to imatinib. The glucose analogue 2-deoxyglucose (2DG) inhibits glucose metabolism in cancer cells that depend on aerobic glycolysis for ATP production. We show that 2DG inhibits proliferation in both imatinib-sensitive and imatinib-resistant GIST cell lines at levels that can be achieved clinically. KIT-negative GIST48B have 3-14-fold higher IC50 levels than KIT-positive GIST cells indicating that oncogenic KIT may sensitize cells to 2DG. GIST sensitivity to 2DG is increased in low-glucose media (110mg/dl). 2DG leads to dose- and glucose dependent inhibition of KIT glycosylation with resultant reduction of membrane-bound KIT, inhibition of KIT-phosphorylation and inactivation of KIT-dependent signaling intermediates. In contrast to imatinib, 2DG caused ER-stress and elicited the unfolded protein response (UPR). Mannose but not pyruvate rescued GIST cells from 2DG-induced growth arrest, suggesting that loss of KIT integrity is the predominant effect of 2DG in GIST. Additive anti-tumoral effects were seen with imatinib and BH3-mimetics. Our data provide the first evidence that modulation of the glucose-metabolism by 2DG may have a disease-specific effect and may be therapeutically useful in GIST.
    Type of Publication: Journal article published
    PubMed ID: 25781619
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  • 4
    Keywords: RECEPTOR ; CELLS ; EXPRESSION ; IN-VITRO ; CELL ; Germany ; IN-VIVO ; VITRO ; VIVO ; DISEASE ; MICE ; ACTIVATION ; DNA ; INFECTION ; kidney ; MECHANISM ; murine ; SERA ; renal ; CONTRAST ; DENDRITIC CELLS ; mechanisms ; INJECTION ; antibodies ; PROGRESSION ; ESCHERICHIA-COLI ; EPITHELIAL-CELLS ; VIRAL-INFECTION ; AUTOIMMUNITY ; BACTERIAL CPG-DNA ; CHEMOKINE RECEPTOR ; chemokines,autoimmune diseases,kidney,lupus,immunity ; IMMUNE-COMPLEX GLOMERULONEPHRITIS ; IMMUNIZATION ; NZB/NZW MICE ; SYSTEMIC-LUPUS-ERYTHEMATOSUS
    Abstract: How bacterial or viral infections trigger flares of autoimmunity is poorly understood. As toll-like receptor (TLR)-9 activation by exogenous or endogenous CpG-DNA may contribute to disease activity of systemic lupus erythematosus, we examined the effects of CpG-oligodeoxynucleotides (ODN) or DNA derived from Escherichia coli (E. coli) on the course of nephritis in MRL1pr/1pr mice. In kidneys of these mice, TLR9 localized to glomerular, tubulointerstitial, and perivascular infiltrates. After intraperitoneal injection labeled CpG-ODN localized to glomerular and interstitial macrophages and dendritic cells in nephritic kidneys of MRL1pr/1pr mice but not in healthy MRL controls. Furthermore, murine J774 macrophages and splenocytes from MRL1pr/1pr mice, but not tubular epithelial cells, renal fibroblasts, or mesangial cells, expressed TLR9 and up-regulated CCL5/RANTES mRNA upon stimulation with CpG-ODN in vitro. In vivo both E. coli DNA and CpG-ODN increased serum DNA autoantibodies of the IgG(2a) isotype in MRL1pr/1pr mice. This was associated with progression of mild to crescentic glomerulonephritis, interstitial fibrosis, and heavy proteinuria. CpG-ODN increased renal CCL2/MCP-1 and CCL5/RANTES expression associated with increased glomerular and interstitial leukocyte recruitment. In contrast control GpC-ODN had no effect. We conclude that TLR9 activation triggers disease activity of systemic autoimmunity, for example, lupus nephritis, and that adaptive and innate immune mechanisms contribute to the CpG-DNA-induced progression of lupus nephritis
    Type of Publication: Journal article published
    PubMed ID: 14734643
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  • 5
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A gram scale enzymatic synthesis of eight, dinucleoside monophosphates (ApC, ApU, CpC, CpU, GpC, GpU, UpC, and UpU) is described. The synthesis involves a reaction between the appropriate ribonucleoside-2′,3′-cyclie phosphates and cytidine or uridine in the presence of ribonuelease from Aspergillus clavatus at 30°C. The enzyme is removed from the reaction mixture by chromatography on Bio-Gel P-4, and the dinucleoside monophosphate is further purified by chromatography on a DEAE-Sephadex A-25, column.A procedure for the large scale preparation of the ribonuclease from Aspergillus clavatus is also described.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 18 (1976), S. 839-846 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: An efficient method to grow Escherichia coli W to high cell concentrations on the pilot scale is described and discussed. The method involves growth linked introduction of glucose; and ammonia to the culture, sparing with oxygen, and maintenance of aerobic conditions by gradually decreasing the temperature in the culture in order to keep the oxygen demand within the limits of the capacity of supply. Under these conditions the linear rate of cell mass production is actually the result of exponential growth with a gradually decreasing growth-rate constant.About 10 kg packed cells were produced in a 50 liter working-volume fermentor in one run of 13 hr. The concentration of the cells at the end of the growth was about 47 g dry cells/liter. The expenditure for nutrients was minimal and the controls were of simple automatic nature. From the determined yield constants for glucose, nitrogen, phosphorus, and oxygen it may be inferred that the cells grown by this method are similar to those grown exponentially at constant temperature.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A substrain of Bacillus cereus 569/H produced under controlled fermentation conditions in a pilot plant fermentor phospholipase-C. A partially purified preparation showed good storage stability as a lyophylized powder and in frozen solutions. The preparation contained very small amounts of phosphomonoesterase and proteolytic activities and essentially no ribonuclease activity. The level of hemolytic activity of the preparation was much lower than that of a commercial preparation of phospholipase-C from Clostridium. Treatment of sarcoplasmic reticulum membrane with phospholipase-C from B. cereus and from Clostridium showed that the B. cereus enzyme caused hydrolysis of 96% of the membrane phospholipids whereas the enzyme from Clostridium could hydrolyze only 80% of the phospholipids.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: A procedure for the preparation of about 50 g batches of tRNA from 25 kg E. coli W is described. The method involves phenolic extraction of the cells, batch absorption of the tRNA on DEAE-cellulose, washing the DEAE-cellulose and packing it into a column, elution of the tRNA from the column and precipitation of the tRNA with ethanol. The method is less time and labor consuming than the methods described in the literature and can be carried out with relatively simple equipment.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 16 (1974), S. 933-941 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Oxygen supply is one of the main factors which influences aerobic cell growth in a fermentor. Maximal rates at which E. coli can grow on glucose as carbon source under various limiting oxygen-supply conditions were determined in a bench-scale fermentor. Culture conditions are described which gave yields of about 38 g dry cells per liter medium.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Biotechnology and Bioengineering 17 (1975), S. 227-239 
    ISSN: 0006-3592
    Keywords: Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: E. coli wax grown exponentially at different temperatures in a bench scale fermentor. pH was maintained at 6.8 by ammonia which served also as the nitrogen source. Glucose was introduced semi-continuously at a predetermined rate which ensured a glucose concentration of 25-50 g/liter during growth. The culture was sparged with pure oxygen.Yield constants for glucose, nitrogen, phosphorus, and oxygen were determined at the different temperatures of propagation.When all growth conditions, except temperature, were kept constant, the maximal possible yield of exponentially grown cell mass was found to be directly proportional to the doubling time. Concentrations of up to 55 g dry cells/liter culture were achieved.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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