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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 97 (1980), S. 137-144 
    ISSN: 1432-1335
    Keywords: α-Ketoglutarat ; Citrat ; Succinat ; Malat Glutamat ; Yoshida Sarcom ; Tumorträger ; Leber ; Skelettmuskel ; Gastrocnemius ; Blut ; Wirt ; α-Ketoglutarate ; Citrate ; Succinate ; Malate ; Glutamate ; Yoshida sarcoma ; Tumor bearer ; Liver ; Skeletal muscle ; Gastrocnemius ; Blood ; Host
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary To elucidate the origin of increased concentrations of α-ketoglutarate (KG) in tumor bearers the tissue distribution of KG together with the related metabolites citrate, succinate, malate, and glutamate was determined in tumor, liver, gastrocnemius muscle, and blood of rats bearing the solid Yoshida sarcoma and of tumor-free rats. The sum of these metabolites was significantly increased in host liver and blood, respectively, compared with the corresponding tissues of normal rats. Among single metabolites glutamate and malate were significantly increased in host liver. The absolute concentrations were highest in host liver with the exception of KG, which was highest in the tumor. This was taken as indicative for the tumor as the prime source of increased KG in blood of tumor-bearers. No significant metabolic deviations were found in gastrocnemius muscle. The concentration of KG in this muscle of both normal and host animals correlated significantly with that of glutamate. In the tumor the concentration of KG correlated significantly with that of citrate plus succinate plus malate. This type of correlation was absent in liver and muscle of both normal and host animals. Moreover, no correlation existed between KG and glutamate either in liver or in tumor. It was suggested that the metabolic flux through the citric acid cycle determines the concentration of KG in the tumor.
    Notes: Zusammenfassung Zur Untersuchung der Ursache der erhöhten α-Ketoglutarat (KG) Konzentration in Tumorträgern wurde die Konzentration des KG sowie der Metaboliten Citrat, Succinat, Malat und Glutamat in Tumor, Leber, Gastrocnemius-Muskel und Blut von tumorfreien und Ratten, die das solide Yoshida Sarcom trugen, untersucht. Die Summe dieser Metaboliten war in der Leber und im Blut von Tumorträgern signifikant erhöht gegenüber den entsprechenden Geweben gesunder Ratten Unter den einzelnen Metaboliten waren Glutamat und Malat in der Wirtsleber signifikant erhöht. Die absoluten Konzentrationen waren jeweils in der Wirtsleber am höchsten, mit Ausnahme des KG, dessen Konzentration im Tumor am höchsten war. Es wurde geschlossen, daß die Erhöhung der KG Konzentration im Blut von Tumorträgern hauptsächlich auf den Tumor selbst zurückzuführen ist. Im Gastrocnemius-Muskel wurden keine signifikanten Stoffwechselveränderungen beobachtet. Die Konzentration des KG in diesem Muskel sowohl von gesunden als auch von Wirtstieren korrelierte signifikant mit jener des Glutamats. Im Tumor korrelierte die KG Konzentration signifikant mit der Summe der Konzentrationen von Citrat, Succinat und Malat. Diese Art der Korrelation war in der Leber und im Muskel gesunder und tumortragender Tiere nicht gegeben. Weiteres wurde weder in der Leber noch im Tumor eine Korrelation zwischen KG und Glutamat beobachtet. Diese Ergebnisse sprechen dafür, daß der metabolische Fluß durch den Citrat-Zyklus bestimmend ist für die Konzentration des KG im Tumor.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 97 (1980), S. 285-293 
    ISSN: 1432-1335
    Keywords: Yoshida sarcoma ; Tumor-bearing host ; Branched-chain amino acids ; l-leucine ; l-isoleucine ; l-valine ; Excretion of α-ketoglutarate ; Urea ; Creatinine ; Uric acid ; Nitrogen balance ; Food consumption ; Survival time ; Carcass protein ; Gastrocnemius muscle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The continuous administration of physiological doses of the branched-chain amino acids leucine, isoleucine, and valine (Leu-Ile-Val) to Yoshida sarcoma-bearing rats caused a significant increase in the survival time by 32% and a significant reduction of tumor size after 3 weeks of growth by 33%. The shift of the nitrogen balance to negative values during the cachectic stage was delayed but not prevented. On the average, less nitrogen (-47 mg/day) were lost by Leu-Ile-Val treated rats compared with untreated tumor-bearing animals (-91 mg N/day). It appeared that Leu-Ile-Val increased the synthesis of carcass proteins, while it left the proteolysis rate unchanged, since the excretion of urea and creatinine was unaffected by these amino acids. The daily excretion of α-ketoglutarate, which is correlated with tumor size during the early stage of growth, was decreased during the first 2 weeks by Leu-Ile-Val, but remained for a longer period on a high level than in untreated tumor bearers. The results point to an improvement of the metabolic resistance against carcass protein depletion of the tumor-bearing host by the administration of branched-chain amino acids.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 93 (1979), S. 293-300 
    ISSN: 1432-1335
    Keywords: α-ketoglutarate ; Blood ; Urine ; Serum albumin ; Walker carcinoma 256 ; Yoshida sarcoma ; Rhabdomyosarcoma ; Tumor bearer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Referring to the increased α-ketoglutarate (I) concentration in blood of cancer-bearing humans, the concentration of (I) in blood and of albumin (II) in serum were measured in 85 tumor-bearing and control rats by fluorimetry and cellulose acetate electrophoresis, respectively. (I) was elevated on the average by a factor of 1.82 and (II) was decreased by a factor of 0.73 in rats bearing the solid Rhabdomyosarcoma BA 1112 and the ascitic or solid forms of Walker-carcinoma 256 and Yoshida-sarcoma compared with tumor-free animals. All deviations were found to be statistically significant for the different tumor types, with the exception of the increase of (I) in Walker-ascites tumor-bearing rats. For rats bearing the ascitic and solid Yoshida-sarcoma and the ascitic Walker-carcinoma 256 and for tumor-free rats a negative correlation could be observed between increase of (I) and decrease of (II). The increase of (I) in blood was paralleled by an increased excretion rate of (I) into urine. In rats bearing the solid Yoshida-sarcoma the daily excreted amount of (I) was significantly increased by a factor of 1.86 compared with tumor-free animals. The excretion of (I) was already increased in the first week after tranplantation, remained constant for two more weeks and decreased sharply below normal values prior to death. The results suggest that rats bearing the inquested tumors are suitable models for metabolic studies on causes of pathological concentrations of (I) in blood of cancer patients.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 115 (1989), S. 79-83 
    ISSN: 1432-1335
    Keywords: Lipid peroxidation ; Lipid hydroperoxides ; 4-Hydroxynonenal ; Proliferation ; Ehrlich ascites tumor cells ; Fe(II) histidinate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of this study was to find further experimental evidence for the postulated negative association between the extent of lipid peroxidation in tumor cells and their proliferative behavior. After incubation of Ehrlich ascites tumor cells at 37°C for 30 min with increasing concentrations of Fe(II) histidinate (Fe/His) the following parameters were determined: the formation of lipid hydroperoxides was measured fluorimetrically after reaction with dichlorofluorescein; 4-hydroxynonenal was determined by reversed-phase high-pressure chromatography after derivatization with dinitrophenylhydrazine; as a third parameter of lipid peroxidation the formation of 2-thiobarbituric-acid-reactive substances was determined. The proliferative activity was determined by measuring the growth rate in vivo after reimplantation i.p. of the tumor cells into mice. Trypan-blue exclusion tests for viability were performed before reimplantation. The reliability of the trypan-blue exclusion tests was checked by comparing the results with another parameter of viability, the release of the cytosolic enzyme lactate dehydrogenase. The concentration both of lipid hydroperoxides and of 2-thiobarbituric-acid-reactive substances showed a biphasic dependence on the concentration of Fe/His with maximal increase at iron concentrations of 0.25 mM and 0.1mM respectively. 4-Hydroxynonenal, in contrast, showed a continuous increase up to 41.1 nM (corresponding to 0.58 pmol/109 cells) with increasing iron concentration in the range from 0.1 mM to 0.6 mM. The total number of tumor cells, when determined 5 days after reimplantation, continuously decreased with increasing iron concentration, showing half-maximal inhibition at about 0.22 mM Fe. The exclusion of the trypan-blue dye was unaffected by the presence of iron at any concentration used. Similarly, iron had no influence on the release of lactate dehydrogenase. The results support the hypothesis that 4-hydroxynonenal may act as an inhibiting messenger between endogenic lipid peroxidation and proliferation.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1335
    Keywords: Hepatomas ; Soluble proteins ; Thiols ; Growth rate ; Hepatome ; lösliche Proteine ; Thiole ; Wachstumsgeschwindigkeit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der SH-Gehalt der löslichen Proteine (nMole/mg Protein) von fünf transplantablen Ratten-Hepatomen und des DÄNA-Hepatoms wird mit Dithionitrobenzoat (Ellman's-Reagenz) bestimmt. Sowohl die gesamten Thiole als auch insbesondere die Zahl der SH-Gruppen, die mit Hydroxypentenal (HPE) blockiert werden, steigen mit zunehmender Wachstumsgeschwindigkeit der Tumoren an. Verglichen mit dem Thiolgehalt des am langsamsten wachsenden DÄNA-Hepatoms (Dopplungszeit ca. 100 Tage), steigen die gesamten Protein-Thiole des am schnellsten wachsenden Yoshida-Hepatoms (Dopplungszeit 2,5 Tage) um 100% an, die HPE-reaktiven Protein-Thiole dagegen um 350%. Die gesamten Protein-Thiole sind mit einer Irrtumswahrscheinlichkeit von 5% signifikant mit der Wachstumsgeschwindigkeit assoziiert, die HPE-reaktiven Thiole dagegen hochsignifikant (Irrtumswahrscheinlichkeit 〈1%). Diese Ergebnisse stehen in Übereinstimmung mit dem Konzept der molekularen Korrelationen von G. Weber und dürften danach als Folge einer “Re-Programmierung von Gen-Expressionen” zu verstehen sein.
    Notes: Summary The SH content of the soluble proteins (nanomol./mg protein) from five transplantable rat hepatomas and from the DENA-hepatoma were determined with dithionitrobenzoate (Ellman reagent). Both the total number of thiols as well as the number of SH groups that can be blocked by hydroxypentenal (HPE) increase with increasing growth rate of the tumors. In comparison with the protein thiol content of the slowest growing DENA-hepatoma (doubling time 100 days), the total protein thiols of the fastest growing Yoshida hepatoma (doubling time 2,5 days) increase by 100% and the HPE-sensitive protein thiols by 350%. The total protein thiols are significantly correlated with the growth rate (probability of error 5%), the HPE-sensitive thiols are correlated with high significance (probability of error 〈1%). These results are in accordance with the “Molecular Correlation Concept” of G. Weber and might possibly be understood as a consequence of reprogramming of gene expressions.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0263-6484
    Keywords: Enzyme mechanisms and metabolism ; DNA-polymerase ; hydroxy-nonenal ; hydroxy-alkenal ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The purpose of this study was to determine firstly whether the isolated enzyme DNA polymerase α, which functions within the DNA replicase system, exhibits different sensitivity against the thiol-blocking agent 4-hydroxy-nonenal (HNE) when adult rat liver and the rapidly dividing Yoshida ascites hepatoma were used as enzyme sources and, secondly, whether the reaction catalysed by DNA polymerase is the most sensitive step of the DNA replicase system of native cells.DNA polymerase α as well as the non-replicative DNA polymerase β, isolated from both sources, were remarkably similar with regard to their sensitivity against HNE, as indicated by the incorporation of radioactive label from [3H]deoxy-thymidine-triphosphate into DNA.The transport of [14C]thymidine through the plasma membrane and the incorporation of this precursor into DNA were studied with neonatal hepatocytes and with hepatoma cells. The incorporation of thymidine was inhibited at lower concentrations of HNE in both cell lines than the transport process and the reaction catalysed by DNA polymerase α. It was concluded that in the DNA replicase system of native liver and hepatoma cells another process different from the reaction catalysed by DNA polymerase α is more sensitive to HNE.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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