GLORIA

GEOMAR Library Ocean Research Information Access

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    ISSN: 1520-4804
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    ISSN: 1432-1335
    Keywords: ZD1694 ; Cellular pharmacokinetics ; Polyglutamation ; Drug sensitivity ; Acquired resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have analysed the cellular metabolism of a novel thymidylate synthase (TS) inhibitor, ZD1694, in MOLT-3 and K562 human leukaemia cell lines sensitive to or made resistant to ZD1694 by continuous exposure of the cells to ZD1694 with stepwise escalation of the drug concentration. The initial cellular uptake of [3H]ZD1694 was greater in K562 cells than in MOLT-3 cells and the drug accumulated approximately 3-fold more in the former cells following incubation with 0.1 μM ZD1694 at 37°C for 24 h. TS and dihydrofolate reductase activities were not significantly different between the two cell lines. After a 30-min incubation with the drug at 37°C, 85% of the total drug (2.3pmol/mg protein) in K562 cells was found as tri-to pentaglutamates, whereas MOLT-3 cells accumulated less drug in this time (0.83 pmol/mg protein) and polyglutamates of chain length greater than triglutamate were not found to a significant extent. When the incubation time was extended to 24 h, the polyglutamate profile in K562 cells was progressively shifted towards those of long glutamate chain length and 59% of the total cellular drug (204 pmol/mg protein) was identified as the penta form. In contrast, even distribution between tri-and pentaglutamate was observed in MOLT-3 cells. Total cellular polyglutamates were approximately 3-fold higher in K562 cells than in MOLT-3 cells, and this may explain the 2.5-fold difference in the sensitivity to ZD1694 between the two cell lines. Continuous exposure of MOLT-3 and K562 cells to ZD1694 up to 1 μM or 0.1μM resulted in 1600-and 4200-fold resistant sublines, respectively (MOLT-3/ZD1694·C and K562/ZD1694·C). The resistant MOLT-3 cells showed a markedly lower cellular accumulation and poor retention of [3H]ZD1694 with no significant change of initial drug uptake by 10 min and with a little increase of TS activity. HPLC analysis demonstrated that more than 90% of the3H co-eluted with the monoglutamate (parent drug) in the resistant MOLT-3 cells, indicating extremely diminished polyglutamation in the cells. On the other hand, cellular uptake of [3H]ZD1694 was extensively impaired in K562/ZD1694·C cells and cellular accumulation of the drug was only 2.5% of that in the parent cells following 24 h incubation with the drug. Neither an increase of TS or dihydrofolate reductase activity nor a change in the polyglutamate formation profile was observed in the resistant K562 cells. These results indicate that the cellular ability to produce the polyglutamate metabolites of ZD1694 must influence the sensitivity of the tumour cells to this drug, and development of mechanisms involved in the ZD1694 resistance may relate to the intrinsic biochemical properties of the cells.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 131 (1987), S. 393-401 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Thy-1 antigen and laminin are two components often associated with the basement membrane of the rat mammary gland and are thought to be synthesized, at least in part, by the adjacent myoepithelial cells in vivo. The relative levels of Thy-1 mRNA and laminin mRNA are compared in a rat mammary cuboidal epithelial cell line and a derivative elongated myoepithelial-like cell line by hybridizing cloned cDNAs to cellular mRNA isolated from these cell types. Although the elongated myoepithelial-like cells synthesize four times as much laminin protein as the cuboidal epithelial cells, there is only a 1.7-fold increase in laminin mRNA between the two cell types. In contrast the 17-fold increase in Thy-1 antigen between the elongated cells and the cuboidal cells can be accounted for completely by a 14-18-fold increase in Thy-1 mRNA, suggesting that changes in the steady-state levels of Thy-1 mRNA in these cell lines are modulated at either a transcriptional or a post-transcriptional level. Run-off transcription by nuclei isolated from the cell lines does not distinguish between these two possibilities. The comparative results on Thy-1 antigen and laminin show that the enhanced production of two proteins often associated with the basement membrane of the rat mammary gland can be controlled at different levels in the elongated myoepithelial-like cells.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 128 (1986), S. 76-84 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: A rat mammary myoepithelial-like cell line (Rama 401) produces 3.5 times more type IV collagen than a mammary epithelial cell line (Rama 25), as measured by the formation of protein hydroxyproline. However, using quantitative “dot” hybridization techniques, the level of poly (A)- containing mRNA hybridizing to a type IV collagen cDNA probe is only 50% higher in Rama 401 cells than in Rama 25 cells. The total amount of hydroxyproline synthesized per cell by the two cell lines is similar. However, in the Rama 25 cells approximately 70% of the hydroxyproline is found as free hydroxyproline against 13% for Rama 401 cells. When Rama 25 cells are grown on collagen gels, they accumulate 2.5-fold more type IV collagen. However, type IV collagen mRNA levels are only 30% higher in Rama 25 cells grown on collagen. The total amount of hydroxyproline synthesized is the same as cells grown on plastic, whereas the extent of collagen degradation is reduced from 70% to 30% in cells grown on collagen gels. No degradation of type IV collagen can be detected in the culture medium of Rama 25 cells. These results indicate that the increased accumulation of type IV collagen in Rama 401 cells is not due to increased synthesis but to a decreased rate of intracellular degradation, and that for Rama 25 cells, the extracellular matrix modulates type IV collagen production by regulating the rate of intracellular collagen degradation.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...