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  • EXPRESSION  (6)
  • 1
    Keywords: gene expression ; HEALTH ; SIGNAL ; signal transduction ; SIGNAL-TRANSDUCTION ; EXPRESSION ; GENOME ; TRANSDUCTION ; NEW-YORK ; DISEASE ; GENE ; GENE-EXPRESSION
    Type of Publication: Book chapter
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  • 2
    Keywords: EXPRESSION ; SURVIVAL ; CELL ; Germany ; KINASE ; imaging ; NEW-YORK ; PATIENT ; ACTIVATION ; MARKER ; prognosis ; QUALITY ; TYPE-1 ; MAGNETIC-RESONANCE ; magnetic resonance imaging ; FIBER COMPOSITION ; BREAST-CANCER ; NO ; PERFORMANCE ; PLASMA ; AGE ; genetics ; FIBER ; MUSCLE ; PARAMETERS ; MORPHOLOGY ; SKELETAL-MUSCLE ; PREDICTION ; BODY ; POOR-PROGNOSIS ; heredity ; OXYGEN ; BIOPSY ; exercise ; MASSES ; BODIES ; REGRESSION ; INCREASE ; WEIGHT ; LIFE ; PHYSICAL-ACTIVITY ; HEIGHT ; QUALITY-OF-LIFE ; LEVEL ; MYOPATHY ; PLASMA-LEVELS ; technique ; USA ; LOSSES ; uptake ; correlation ; cachexia ; myopathies ; PREDICT ; BIOPSIES ; INCREASES ; - ; RESONANCE ; CANCER DIAGNOSIS ; TRACK ; FOXO TRANSCRIPTION FACTORS ; cancer cachexia ; muscle biopsy ; muscle morphology ; muscle wasting
    Abstract: Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r=0.65, p 〈 0.001) and to the CSA fraction formed by type 1 and 2a fibers (r=0.80, p 〈 0.001). However, when adjusted for body height and age by multiple regression, MG yielded a largely improved prediction of total CSA (multiple r=0.83, p 〈 0.001) and of fiber type 1 and 2a CSA (multiple r=0.89, p 〈 0.001). The correlations between CK and these muscle parameters were weaker, and elevated CK values were observed in 20% of control subjects despite a prior abstinence from exercise for 5 days. In conclusion, plasma MG, when adjusted for anthropometric parameters unaffected by weight, may be considered as a novel marker of muscle mass (CSA) indicating best the mass of MG-rich type 1 and 2a fibers as well as VO(2)max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer-related muscle wasting was not associated with increases in plasma MG or CK in this study
    Type of Publication: Journal article published
    PubMed ID: 17605115
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  • 3
    Keywords: EXPRESSION ; carcinoma ; Germany ; human ; KINASE ; MODEL ; MODELS ; PATHWAY ; PATHWAYS ; liver ; NEW-YORK ; PROTEIN ; PROTEINS ; SAMPLE ; SAMPLES ; transcription ; TISSUE ; TRANSDUCTION ; PATIENT ; ACTIVATION ; TRANSCRIPTION FACTOR ; CONTRAST ; PHOSPHORYLATION ; protein kinase ; PROTEIN-KINASE ; signal transduction ; SIGNAL ; antibodies ; antibody ; FORM ; TRANSCRIPTION FACTORS ; DECREASE ; genetics ; SIGNAL-TRANSDUCTION ; MUSCLE ; Jun ; DEGRADATION ; SKELETAL-MUSCLE ; ATROPHY ; pancreatic cancer ; heredity ; REGULATOR ; REGULATORS ; BIOPSY ; ANIMAL-MODELS ; CHAIN ; pancreas ; RE ; PANCREATIC-CANCER ; INCREASE ; TUMORIGENESIS ; HEAVY ; PROTEIN-SYNTHESIS ; WEIGHT ; LEVEL ; PHOSPHATIDYLINOSITOL 3-KINASE ; ANIMAL-MODEL ; USA ; LOSSES ; cachexia ; animal ; ACTIN ; animal model ; BIOPSIES ; comparison ; HYPERTROPHY ; FOXO TRANSCRIPTION FACTORS ; Skeletal muscle ; UBIQUITIN LIGASES
    Abstract: In animal models of cachexia, alterations in the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway have been demonstrated in atrophying skeletal muscles. Therefore, we assessed the activity of proteins in this pathway in muscle and liver biopsies from 16 patients undergoing pancreatectomy for suspect of carcinoma. Patients were divided in a non-cachectic or cachectic group according to their weight loss before operation. Extracts of skeletal muscle and liver tissue from eight cachectic patients with pancreas carcinoma and eight non-cachectic patients were analysed by Western blotting using pan- and phospho-specific antibodies directed against eight important signal transduction proteins of the PI3-K/Akt pathway. Muscle samples from cachectic patients revealed significantly decreased levels of myosin heavy chain (-45%) and actin (-18%) in comparison to non-cachectic samples. Akt protein level was decreased by -55%. The abundance and/or phosphorylation of the transcription factors Foxo1 and Foxo3a were reduced by up to fourfold in muscle biopsies from cachectic patients. Various decreases of the phosphorylated forms of the protein kinases mTOR (-82%) and p70S6K (-39%) were found. In contrast to skeletal muscle, cachexia is associated with a significant increase in phosphorylated Akt level in the liver samples with a general activation of the PI3-K/Akt cascade. Our study demonstrates a cachexia-associated loss of Akt-dependent signalling in human skeletal muscle with decreased activity of regulators of protein synthesis and a disinhibition of protein degradation
    Type of Publication: Journal article published
    PubMed ID: 17333095
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  • 4
    Keywords: CELLS ; EXPRESSION ; GROWTH ; BLOOD ; Germany ; RISK ; RNA ; RISK-FACTORS ; LESIONS ; PLASMA ; risk factors ; smoking ; LDL ; OVEREXPRESSION ; PERIPHERAL-BLOOD ; COX-2 ; LIPOPROTEINS ; N-ACETYL-CYSTEINE ; inflammation ; HYPERCHOLESTEROLEMIA ; SERUM ; ELISA ; free radicals ; MATRIX METALLOPROTEINASES ; ATHEROSCLEROTIC LESIONS ; GLUTAMATE LEVELS ; hyperlipoproteinemia ; NITRIC-OXIDE-SYNTHASE ; OXIDIZED LOW-DENSITY
    Abstract: Cyclooxygenase (COX)-2 is expressed in macrophages of arteriosclerotic lesions and promotes inflammation. We investigated whether COX-2 is already expressed in peripheral blood mononuclear cells (PBMCs) of subjects possessing risk-related factors, such as in smokers and hyperlipidemics. PBMCs were isolated from the venous blood of normolipidemic nonsmokers (NL-NSM; n = 15), normolipidemic smokers (NL-SM; n = 12), hyperlipidemic nonsmokers (HL-NSM; n = 10), and hyperlipidemic smokers (HL-SM; n = 10). RNA from PBMCs was used for RT-PCR. Plasma concentrations of oxidized low-density lipoproteins (oxLDL) were rneasured by ELISA, those of glutamate and cystine by HPLC. The results show that COX-2 expression in PBMCs was significantly increased in the groups with cardiovascular risk factors (NL-SM, HL-SM, HL-NSM) compared with NL-NSM. COX-2 expression in PBMCs was positively Correlated with concentrations of total serum cholesterol, oxLDL, glutamate, or cystine. We suggest that the elevated COX-2 expression indicates a priming of PBMCs as a response to a systemic pro-oxidative and proinflammatory shift in subjects with cardiovascular risk factors, which might also contribute to growth and instability of arteriosclerotic lesions. (C) 2004 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15607906
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  • 5
    Keywords: CANCER ; CELLS ; EXPRESSION ; tumor ; BLOOD ; Germany ; SYSTEM ; GENE-EXPRESSION ; microarray ; TUMORS ; LINES ; PATIENT ; DNA ; MECHANISM ; prognosis ; CELL-LINES ; cytokines ; antibodies ; antibody ; immunohistochemistry ; DESIGN ; OBESITY ; LINE ; SKELETAL-MUSCLE ; adenocarcinoma ; MICROARRAY ANALYSIS ; OVEREXPRESSION ; PERIPHERAL-BLOOD ; cell lines ; pancreatic cancer ; THYROID-HORMONE ; SERUM ; ELISA ; PANCREATIC-CANCER ; CAPACITY ; DUCTAL ADENOCARCINOMA ; INTERLEUKIN-6 ; INFLAMMATORY CYTOKINES ; SCREEN ; ABILITY ; DNA-MICROARRAY ; ACUTE-PHASE RESPONSE ; ANOREXIA ; cachexia ; NEUROPEPTIDE-Y ; UNCOUPLING PROTEIN-3
    Abstract: Background and Purpose: The mechanism behind aggressive development of cachexia in patients suffering from pancreatic cancer is not well understood. In this study, we investigated which factors are associated with the cachectic status of the patients and evaluated cachexia-promoting capacity of cancer and inflammatory cells. Experimental Design: DNA microarray analysis and quantitative reverse transcription-PCR were used to screen for cachexia-associated factors in pancreatic specimens obtained from non-cachectic and cachetic patients diagnosed with pancreatic ductal adenocarcinoma. The expression pattern of the most prominently altered cachexia-associated factor, interleukin-6 (IL-6), was further analyzed in patients sera by ELISA, in pancreatic specimens by immunohistochemistry, and in a coculture system by quantitative reverse transcription-PCR using pancreatic cancer cell lines T3M4 (IL-6 positive) and Panc-1 (IL-6 negative) and peripheral blood mononuclear cells (PBMC) obtained from donors and noncachectic and cachectic patients. Results: Among numerous analyzed factors, IL-6 was significantly overexpressed in pancreatic specimens and elevated in serum of cachectic patients. The coculture system revealed that pancreatic cancer T3M4 cells but not Panc-1 cells were able to stimulate IL-6 exclusively in cachectic PBMC (by 14-fold) and this triggering was reduced by half in the presence of IL-6-neutralizing antibodies. Conclusion: IL-6 represents a prominent cachexia-associated factor in pancreatic cancer. IL-6 overexpression in cachectic patients is related to the ability of certain tumors to sensitize PBMC and induce cytokine expression in cachectic PBMC
    Type of Publication: Journal article published
    PubMed ID: 16115919
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  • 6
    Keywords: CELLS ; EXPRESSION ; tumor ; BLOOD ; CELL ; Germany ; SYSTEM ; GENE ; GENE-EXPRESSION ; GENES ; DIFFERENTIATION ; TIME ; PATIENT ; TUMOR-NECROSIS-FACTOR ; RESPONSES ; MACROPHAGES ; IMMUNE-RESPONSES ; gene expression ; PLASMA ; PCR ; LYMPHOCYTES ; ADHESION ; PARAMETERS ; POLYMERASE-CHAIN-REACTION ; cholesterol ; LOW-DENSITY-LIPOPROTEIN ; immune response ; CENTRAL-NERVOUS-SYSTEM ; PERIPHERAL-BLOOD ; MONOCYTE ; CD40 LIGAND ; development ; CEREBRAL-ISCHEMIA ; ELEVATED EXPRESSION ; ONSET ; macrophage ; NECROSIS ; HUMAN ENDOTHELIAL-CELLS ; MONOCYTES ; traumatic brain injury ; POLYMERASE ; PBMC ; WELL ; MONONUCLEAR CELLS ; ACTIVATED PARENCHYMAL MICROGLIA/MACROPHAGES ; lymphopenia ; MANGANESE SUPEROXIDE-DISMUTASE ; oxLDL ; PLASMA OXIDIZED LDL
    Abstract: Peripheral blood mononuclear cells (PBMCs), i.e. lymphocytes, monocytes and macrophages are key players in the development of innate and adaptive immune responses. However, little is known about their properties in patients with acute stroke. Experimental procedures: We presently characterized the early time course of PBMC subpopulations in 19 patients with acute ischemic stroke and symptom onset below 6 h compared to 19 age-matched healthy subjects. Immediately after acute ischemic stroke, as well as 1 and 3 days thereafter, PBMC subpopulations (cluster of differentiation [CD]3+, CD14+, CD19+, CD68+) were isolated by magnetic bead system and the expression of proinflammatory (CD40, tumor necrosis factor-alpha [TNF alpha]), proapoptotic (caspase-3 [CPP32], poly(ADP-ribose) polymerase [PARP]) and adhesion relevant (CD38) genes was measured by quantitative polymerase chain reaction (PCR). Furthermore, besides routine parameters, plasma levels of oxidized low-density lipoproteins (oxLDL) were studied. Results: In comparison to healthy subjects, patients revealed (i) twofold elevated plasma oxLDL concentrations, (ii) decreased (15%) blood cholesterol levels, and (iii) a 40% decrease in total number of lymphocytes. Furthermore, the majority of PBMC subpopulations revealed an increased expression of proinflammatory, proapoptotic or adhesion-relevant genes. Significant positive correlations were observed between expression of most of these genes in PBMCs and individual plasma oxLDL concentrations. Conclusion: Elevated expression of proinflammatory, proapoptotic and adhesion genes in subsets of PBMCs after ischemic stroke may contribute to an immunodepressive syndrome, possibly due to increased plasma oxLDL levels. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19258025
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